Bibliografía de 2020

Actualidad bibliográfica diciembre 2020

TOP TEN

  1. Helicobacter pylori infection in children. BMJ Paediatr Open. 2020; 4(1): e000679. doi: 10.1136/bmjpo-2020-000679. PMID: 32818155

Esta revisión de la infección por H pylori se centra en algunas consideraciones actuales sobre epidemiología, diagnóstico y tratamiento de la infección infantil. Las diferencias entre la infección en adultos y población pediátrica es considerable y conlleva una serie de premisas, intervenciones y decisiones de tratamiento también muy diferentes. Aunque la prevalencia de la infección es alta en niños, hay que considerar que la mayoría son asintomáticos. En la revisión se expone claramente que la enfermedad, y no la infección, está relacionada con la virulencia de la cepa, la predisposición genética, la respuesta inmune del huésped, el tiempo de exposición y factores ambientales. La decisión de investigar y tratar la infección por H. pylori en niños debe basarse en conseguir verdaderos beneficios, teniendo en cuenta la baja frecuencia de complicaciones en esta etapa, la recurrencia de la infección, las probables relaciones inversas con enfermedades alérgicas e inmunológicas (enfermedades inflamatorias intestinales), la resistencia a los antimicrobianos, así como las pocas alternativas de tratamiento disponibles para tratar la infección en niños.

  1. Tularemia in Children and Adolescents. The Pediatric Infectious Disease Journal. 39(12):e435-e438, December 2020.

Tularemia colloquially also referred to as “rabbit fever,” “wild hare disease,” or “deerfly fever” is a rare zoonotic disease caused by the Gram-negative bacterium Francisella tularensis. The wide spectrum of clinical presentations depending on the mode of acquisition and the responsible subspecies constitutes a major challenge for clinicians. This review aims to provide a summary of the current knowledge on tularemia epidemiology, clinical presentation, diagnostics, therapy, treatment, and prophylaxis in children and adolescents.

Comentario: Revisión de una patología no frecuente  pero con brotes recurrentes  en nuestro país (Especialmente dedicado  a los pediatras de Castilla y León.)

Casos clínicos

  1. Peritonsillar Abscess in an Infant. J Pediatr. 2020 Dec;227:320-321. doi: 10.1016/j.jpeds.2020.08.053

Comentario: interesante por la rareza a esta edad y por subrayar la necesidad de una exploración física cuidadosa en los lactantes con fiebre.

  1. Bronquitis bacteriana persistente, una entidad a considerar en pediatría. An Pediatr (Barc). 2020;93:413-5

.Tres casos clínicos, con la incertidumbre del diagnóstico de estos cuadros en AP.

  1. ¿Fiebre botonosa mediterránea o DEBONEL?. An Pediatr (Barc). 2020;93:429

Comentario: Es una carta al director, pero ofrece una discusión interesante.

  1. Maculopapular eruptions and vesicles on the limbs and buttocks. BMJ 2020;371:m4349. http://dx.doi.org/10.1136/bmj.m4349

Comentario: La infección por  M pneumoniae se puede asociar a distintos erupciones exantemáticas, en este caso en el mismo paciente (máculopapular, vesicular y eritema multiforme).

Para profundizar

  1. Presentation, Diagnostic Evaluation, Management, and Rates of Serious Bacterial Infection in Infants With Acute Dacryocystitis Presenting to the Emergency Department. The Pediatric Infectious Disease Journal. 39(12):1065-1068, December 2020.

Dacryocystitis is considered benign, yet infants represent a population at risk of complications. The presentation, management, and rates of serious bacterial infection in infants with dacryocystitis have not been described.

Methods: We conducted a retrospective study of infants (12 months or younger) presenting to a single urban tertiary care pediatric emergency department between January 1995 and March 2014 with concern for dacryocystitis. Exclusion criteria included immune compromise or craniofacial anomalies. Cases were identified using text search software, followed by manual chart review.

Results: We identified 333 subjects, and median age was 38 days (interquartile range, 12; 106). Fifty-three percent were female. Most were afebrile (81%, T < 38°C) at triage while 6% had fever of ≥39°C. Two of 135 blood cultures sent were positive (both Streptococcus pneumoniae). Lumbar punctures were performed on 40 patients (12%), and no cerebrospinal fluid (CSF) cultures were positive. Eye cultures were positive in 47% (N = 58) of infants cultured (N = 123); the most common pathogens were Haemophilus species (N = 17), Staphylococcus aureus (N = 13), Gram-negative rods (N = 7), and Moraxella species (N = 4). Imaging was obtained in 11 subjects (3.3%) with 3 demonstrating cellulitis and 1 a hemangioma. Ophthalmology was consulted for 21%, and an intervention/probe performed in 6%. Topical antibiotics were used in 147 subjects (44%), oral antibiotics in 100 (33%), and parenteral antibiotics in 87 (26%).

Conclusion: Infants with dacryocystitis have a variable presentation and management ranges from observation to aggressive management. The rates of serious bacterial infection were low in this sample and not associated with any presenting risk factors.

Comentario: Estudio retrospectivo  de 333 casos de dacriocistitis en menores de 12 meses  recogiendo la etiología, las complicaciones y el tratamiento realizado.

 

  1. Children and Adolescents With SARS-CoV-2 Infection: Epidemiology, Clinical Course and Viral Loads. The Pediatric Infectious Disease Journal. 39(12):e388-e392, December 2020.

Background: There is limited information on severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection in children.

Methods: We retrieved data from the national database on SARS-CoV-2 infections. We studied in-family transmission. The level of viral load was categorized as high, moderate, or low based on the cycle threshold values.

Results: We studied 203 SARS-CoV-2-infected children (median age: 11 years; range: 6 days to 18.4 years); 111 (54.7%) had an asymptomatic infection. Among the 92 children (45.3%) with coronavirus disease 2019 (COVID-19), 24 (26.1%) were hospitalized. Infants <1 year were more likely to develop COVID-19 (19.5% of all COVID-19 cases) (P-value = 0.001). There was no significant difference between viral load and age, sex, underlying condition, fever and hospitalization, as well as between type of SARS-CoV-2 infection and age, sex, underlying condition and viral load. Transmission from a household member accounted for 132 of 178 (74.2%) children for whom the source of infection was identified. An adult member with COVID-19 was the first case in 125 (66.8%) family clusters. Child-to-adult transmission was found in one occasion only.

Conclusions: SARS-CoV-2 infection is mainly asymptomatic or mild during childhood. Adults appear to play a key role in spread of the virus in families. Most children have moderate or high viral loads regardless of age, symptoms or severity of infection. Further studies are needed to elucidate the role of children in the ongoing pandemic and particularly in light of schools reopening and the need to prioritize groups for vaccination, when COVID-19 vaccines will be available.

Comentario: A partir  de 203 casos  de infección COVID en niños, los  autores concluyen que la mayoría de los niños tienen cargas virales moderadas o elevadas independientemente de la edad, los síntomas o la severidad de la infección. No hubo diferencia significativa entre la carga viral, evaluada según los valores del umbral de ciclo, y la edad, sexo, afección subyacente, fiebre y hospitalización, así como entre el tipo de infección por SARS-CoV-2 y la edad, sexo, afección subyacente y carga viral. La transmisión ocurrió a partir de un miembro de la familia en el 74% de los casos en los que se identificó la fuente del contacto. En el 66,8% de los grupos familiares el primer caso  fue un adulto de la familia con COVID19. La transmisión niño-adulto fue excepcional, solo en un caso.

 

  1. Maternal, Perinatal and Neonatal Outcomes With COVID-19: A Multicenter Study of 242 Pregnancies and Their 248 Infant Newborns During Their First Month of Life. The Pediatric Infectious Disease Journal. 39(12):e393-e397, December 2020.

Background: Our aim was to describe the clinical features of mothers with coronavirus disease 2019 (COVID-19) infection during gestation or delivery, and the potential vertical transmission. We also wish to evaluate the possible horizontal transmission after hospital discharge, by means of a follow-up of all the newborns included at 1 month of age.

Methods: This multicenter descriptive study involved 16 Spanish hospitals. We reviewed the medical records of 242 pregnant women diagnosed with COVID-19 from March 13 to May 31, 2020, when they were in their third trimester of pregnancy. They and their 248 newborn infants were monitored until the infant was 1 month old.

Results: Caesarean sections (C-sections) were performed on 63 (26%) women. The initial clinical symptoms were coughing (33%) and fever (29.7%). Mothers hospitalized due to COVID-19 pathology had a higher risk of ending their pregnancy via C-section (P = 0.027). Newborns whose mothers had been admitted due to their COVID-19 infection had a higher risk of premature delivery (P = 0.006). We admitted 115 (46.3%) newborn infants to the neonatal unit, of those, 87 (75.6%) were only admitted due to organizational circumstances. No infants died and no vertical or horizontal transmission was detected. Regarding type of feeding, 41.7% of the newborns received exclusive breast-feeding at discharge and 40.4% at 1 month.

Conclusions: We did not detect COVID-19 transmission during delivery or throughout the first month of life in the newborns included in our study. Exclusive breast-feeding rates at discharge and at 1 month of age were lower than expected.

Comentario: Estudio español que recoge 242 casos de madres diagnosticadas de COVID-19 en su tercer trimester de embarazo.  Nacen 248 niños. No detecta transmision en los  RN y observa una menor tasa de lactancia maternal al alta de la maternidad y  un mes después. Se realizó  cesárea  en 26%. Riesgo más elevado de prematuridad.

 

  1. Prospective Evaluation of Childhood Encephalitis: Predisposing Factors, Prevention and Outcome. The Pediatric Infectious Disease Journal. 39(12):e417-e422, December 2020.

Acute encephalitis in childhood is a serious condition. The severity varies between studies, partly reflecting differences in study design where only severe cases from referral centers often are reported. The aim of this study was to prospectively study the clinical picture and etiology of acute encephalitis in childhood at a primary and tertiary pediatric hospital in Sweden.

Methods: 

All children with acute encephalitis were prospectively included from 2011 to 2016. Laboratory tests, investigations and follow-up were performed according to standardized study protocols.

Results: Eighty-nine children were included (46 female and 43 male) with a median age of 53 months. An etiology was established in 61/89. Tick-borne encephalitis virus, enterovirus and rotavirus dominated and 34% were caused by a virus preventable by vaccination. Immune-mediated encephalitis was seen in 7 children. An abnormal electroencephalography picture was seen in 77/86, pathologic findings on neuroimaging in 13/49, and 38/89 children had seizures. Sequelae were reported by 49%. A high prevalence of previous contact with child and adolescent psychiatry was seen and, although not statistically significant, the need for extra support at school before encephalitis and the presence of central nervous system disease in the family seemed to predispose for a longer hospital stay.

Conclusion: Encephalitis is a condition with long-term consequences. Most children need admission to hospital, and many need surveillance in the intensive care unit. The etiology can be determined in a majority of cases, and 1/3 could have been prevented by vaccination. This study corroborates electroencephalography as a cornerstone in diagnosis.

Comentario: estudio sueco que recoge 89 casos de encefalitis registrados durante 5  años. Se logra filiar su etiología en 61 casos (69%). El 34% hubieran sido prevenibles por vacunación.

 

  1. Treatment and Outcomes of Children With Febrile Urinary Tract Infection Due to Extended Spectrum Beta-lactamase-producing Bacteria in Europe: TOO CUTE Study. The Pediatric Infectious Disease Journal. 39(12):1081-1087, December 2020.

The prevalence of extended-spectrum beta-lactamase producing Εnterobacteriaceae (ESBL-PE) is increasing globally. ESBL-PE are an important cause of urinary tract infections (UTIs) in children. We aimed to characterize the clinical presentation, treatment and outcomes of childhood UTI caused by ESBL-PE in Europe.

Methods: Multicenter retrospective cohort study. Children 0 to 18 years of age with fever, positive urinalysis and positive urine culture for an ESBL-PE uropathogen, seen in a participating hospital from January 2016 to July 2017, were included.

Main Outcome Measures: Primary outcome measure: day of defervescence was compared between (1) initial microbiologically effective treatment (IET) versus initial microbiologically ineffective treatment (IIT) and (2) single initial antibiotic treatment versus combined initial antibiotic treatment. Secondary outcome measures: Clinical and microbiologic failure of initial treatment.

Results: We included 142 children from 14 hospitals in 8 countries. Sixty-one children had IET and 77 IIT. There was no statistical difference in time to defervescence for effective/ineffective groups ( = 0.722) and single/combination therapy groups ( = 0.574). Two of 59 (3.4%) and 4/66 (6.1%) patients exhibited clinical failure during treatment ( = 0.683) when receiving IET or IIT, respectively. Eight of 51 (15.7%) receiving IET and 6/58 (10.3%) receiving IIT patients ( = 0.568) had recurring symptoms/signs suggestive of a UTI. Recurrence of a UTI occurred 15.5 days (interquartile range, 9.0–19.0) after the end of treatment.

Conclusions: Time to defervescence and clinical failure did not differ between IET/IIT groups. Non-carbapenem beta-lactam antibiotics may be used for the empiric treatment of ESBL febrile UTIs, until susceptibility testing results become available.

Comentario:  En episodios de ITU febriles producidas por bacterias con BLEE, no hubo diferencias significativas en cuanto a los signos/síntomas de ITU recurrente entre los que recibieron tratamiento microbiológicamente efectivo inicial o los que lo recibieron microbiológicamente inefectivo inicial. Tampoco hubo diferencia en el tiempo de defervescencia. Por ello concluyen que se pueden usar antibióticos beta lactámicos no carbapenémicos para el tratamiento empírico de ITUs febriles por BLEE hasta el resultado del antibiograma.  

  1. Associations of Intussusception With Adenovirus, Rotavirus, and Other Pathogens: A Review of the Literature .The Pediatric Infectious Disease Journal. 39(12):1127-1130, December 2020.

Intussusception is the leading cause of acute intestinal obstruction in infants. Intussusception is mostly idiopathic, but infectious pathogens are sometimes implicated. In addition, live oral rotavirus vaccines have been associated with intussusception.

Methods: We searched the literature published between January 1, 1990, and March 16, 2020, to describe the association between intussusception among infants and young children and various pathogens, particularly adenovirus and wild rotavirus. We tallied the number of evaluations reporting a statistically significant positive association, no association and a protective association by pathogen, using any statistical method. We also calculated the median reported odds ratios (OR) of intussusception with adenovirus and rotavirus.

Results: We identified 3793 records on intussusception from the literature; 17 evaluations from 15 countries that evaluated 52 pathogens were included in the analysis. All 14 evaluations of adenovirus reported a statistically significant positive association with intussusception; the median OR from 9 evaluations was 3.7 (interquartile range, 3.3, 8.2). Nine of 12 evaluations assessing rotavirus found no statistically significant association, 1 found a positive association and 2 reported a protective effect; the median OR from 12 evaluations was 0.9 (interquartile range, 0.2, 1.8). No consistent relationship was observed between any other pathogens and intussusception.

Conclusions: We documented a consistent association of intussusception with adenovirus, but no relationship between wild-type rotavirus and intussusception. Future research should focus on better understanding the mechanisms of intussusception with infectious pathogens, including following a rotavirus vaccination.

Comentario: A partir de 3793 registros de invaginación recogidos de la literature se documenta una asociación entre invaginación  y adenovirus. No se observa con cualquier otro patógeno.

  1. Impact of COVID-19 Quarantine and School Cancelation on Other Common Infectious Diseases. The Pediatric Infectious Disease Journal. 39(12):e449-e452, December 2020.

Coronavirus disease 2019 lead to wide-spread quarantines and cancelations. The impact of these measures on other, noncoronavirus disease 2019, infectious diseases was analyzed within Dane County, Wisconsin. The incidence of streptococcal pharyngitis and acute otitis media decreased during quarantine while gonorrhea increased. Quarantine had the expected result for infections spread via the respiratory route but a different effect from those transmitted through sexual activity.

Comentario: Artículo  de interés porque  analiza la  evolución en frecuencia  de distintas enfermedades infecciosas  en relación con la pandemia COVID. Considera datos de edad.

 

  1. Effect of Social Distancing Due to the COVID-19 Pandemic on the Incidence of Viral Respiratory Tract Infections in Children in Finland During Early 2020. The Pediatric Infectious Disease Journal. 39(12):e423-e427, December 2020.

Social distancing measures are used to reduce the spreading of infection. Our aim was to assess the immediate effects of national lockdown orders due to coronavirus disease 2019 (COVID-19) on pediatric emergency room (ER) visits and respiratory tract infections in hospitals and nationwide in Finland.

Methods: This register-based study used hospital patient information systems and the Finnish national infectious disease register. The participants were all patients visiting pediatric ER in 2 Finnish hospitals (Kuopio University Hospital, Mikkeli Central Hospital) covering 1/5th of the Finnish children population, 4 weeks before and 4 weeks after the start of the nationwide lockdown on March 16, 2020. Nationwide weekly numbers of influenza (A + B) and respiratory syncytial virus (RSV) in children were assessed from the infectious disease register from 2015 to 2020.

Results: A major decrease in the rate of daily median pediatric ER visits was detected in both hospitals in the study during the nationwide lockdown compared with the study period before the lockdown (Mikkeli, 19 vs. 7, P < 0.001; Kuopio, 9 vs. 2,5, P < 0.001). The influenza season was shorter (8 weeks from peak to no cases), and the weekly rate of new cases decreased faster compared with the previous 4 influenza seasons (previously 15–20 weeks from peak to no cases). A similar decrease was also seen in RSV cases. No pediatric cases of COVID-19 were found in participating hospitals during the study period.

Conclusion: These results strongly suggest that social distancing and other lockdown strategies are effective to slow down the spreading of common respiratory viral diseases and decreasing the need for hospitalization among children.

       Comentario: Estudio finlandés que muestra disminución de casos de infecciones respiratorias durante la época de confinamiento por COVID.

 

  1. Thoracic imaging tests for the diagnosis of COVID-19. Cochrane Database of Systematic Reviews 2020, Issue 11. Art. No.: CD013639. DOI: 10.1002/14651858.CD013639.pub3.

Se buscaron los estudios que evaluaron la precisión de las imágenes de tórax (obtenidas mediante TC, radiografía o ecografía torácica) para diagnosticar covid-19 en personas con sospecha de presentar esta enfermedad. Los estudios podían tener cualquier diseño y haberse realizado en cualquier lugar.

Los resultados agrupados mostraron que la TC de tórax diagnosticó correctamente la covid-19 en el 89,9% de las personas que presentaban covid-19. Sin embargo, identificó incorrectamente la covid-19 en el 38% de las personas que no la tenían.

El diagnóstico correcto de covid-19 con radiografías de tórax varió entre el 57% y el 89%. Sin embargo, el diagnóstico incorrecto de covid-19 en personas que no presentaban covid-19 varió entre el 11% y el 89%.

La ecografía de pulmón diagnosticó correctamente la covid-19 en el 96% de las personas con la enfermedad. Sin embargo, diagnosticó incorrectamente la covid-19 en el 38% de las personas que no presentaban covid-19.

Conclusiones de los autores:

Los hallazgos indican que la TC de tórax es sensible y moderadamente específica para el diagnóstico de covid-19 en pacientes con sospecha de la enfermedad, lo que significa que la TC puede tener una capacidad limitada para diferenciar la infección por SARS-CoV-2 de otras causas de enfermedades respiratorias. Sin embargo, la confianza en estos resultados es limitada debido a la calidad deficiente de los estudios y a la heterogeneidad de los estudios incluidos. Debido a la limitación de los datos, las estimaciones de la exactitud de la radiografía de tórax y la ecografía de pulmón para el diagnóstico de covid-19 se deben interpretar con cuidado.

  1. Delayed antibiotic prescriptions for respiratory infections. Cochrane Database of Systematic Reviews 2017, Issue 9. Art. No.: CD004417. DOI: 10.1002/14651858.CD004417.pub5.

Se investigó el efecto de la prescripción diferida de antibióticos en comparación con la prescripción inmediata o el tratamiento sin antibióticos en pacientes con infecciones respiratorias que incluyen el dolor de garganta, la infección del oído medio, la tos (bronquitis) y el resfriado común. Se incluyeron todas las IRA independientemente de si se indicaron o no antibióticos. También se evaluó el uso de los antibióticos, la satisfacción de los pacientes, la resistencia a los antibióticos, las tasas de nueva consulta y el uso de terapias suplementarias. Ésta es una actualización de una revisión publicada en 2007, 2010 y 2013.

La administración diferida de antibióticos redujo el uso de antibióticos en comparación con la administración inmediata de antibióticos, pero no mostraron ser diferentes al tratamiento sin antibióticos en cuanto al control de los síntomas ni las complicaciones de la enfermedad.

No hubo diferencias significativas en las tasas de complicaciones. Diferir la prescripción no dio lugar a niveles significativamente diferentes de satisfacción de los pacientes en comparación con la administración inmediata de los antibióticos

Es una ‘version history’ o historial de versiones donde explica lo nuevo de cada actualización. En esta, se añade un nuevo estudio de 405 pacientes.

  1. Antibiotics versus topical antiseptics for chronic suppurative otitis media. Cochrane Database of Systematic Reviews 2020, Issue 1. Art. No.: CD013056. DOI: 10.1002/14651858.CD013056.pub2.

El tratamiento de la OMSC con antibióticos tópicos (quinolonas) probablemente resulte en una mejor resolución de la secreción del oído en comparación con el ácido bórico a las dos semanas. Hubo evidencia limitada de la eficacia de otros antibióticos tópicos o antisépticos tópicos, por lo que no es posible establecer conclusiones. Los eventos adversos no se informaron de manera adecuada.

  1. Using antibiotics wisely for respiratory tract infection in the era of covid-19. BMJ 2020;371:m4125. doi: https://doi.org/10.1136/bmj.m4125 (Published 13 November 2020)

Comentario: en este artículo, a partir de un caso clínico de una  mujer adulta se hace una llamada a no sobreprescribir antibióticos y da algunas pautas.   

 

  1. Pediatric Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Clinical Presentation, Infectivity, and Immune ResponsesJ Pediatr. 2020;227:45-52.e5. doi:10.1016/j.jpeds.2020.08.037

As schools plan for re-opening, understanding the potential role children play in the coronavirus infectious disease 2019 (COVID-19) pandemic and the factors that drive severe illness in children is critical.

Study design, Children ages 0-22 years with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presenting to urgent care clinics or being hospitalized for confirmed/suspected SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) at Massachusetts General Hospital were offered enrollment in the Massachusetts General Hospital Pediatric COVID-19 Biorepository. Enrolled children provided nasopharyngeal, oropharyngeal, and/or blood specimens. SARS-CoV-2 viral load, ACE2 RNA levels, and serology for SARS-CoV-2 were quantified.

Results A total of 192 children (mean age, 10.2 ± 7.0 years) were enrolled. Forty-nine children (26%) were diagnosed with acute SARS-CoV-2 infection; an additional 18 children (9%) met the criteria for MIS-C. Only 25 children (51%) with acute SARS-CoV-2 infection presented with fever; symptoms of SARS-CoV-2 infection, if present, were nonspecific. Nasopharyngeal viral load was highest in children in the first 2 days of symptoms, significantly higher than hospitalized adults with severe disease (P = .002). Age did not impact viral load, but younger children had lower angiotensin-converting enzyme 2 expression (P = .004). Immunoglobulin M (IgM) and Immunoglobulin G (IgG) to the receptor binding domain of the SARS-CoV-2 spike protein were increased in severe MIS-C (P < .001), with dysregulated humoral responses observed.

Conclusions, This study reveals that children may be a potential source of contagion in the SARS-CoV-2 pandemic despite having milder disease or a lack of symptoms; immune dysregulation is implicated in severe postinfectious MIS-C.

Comentario: otro artículo que refiere más alta carga viral en niños que en adultos. Tiene interés un cuadro con la presencia/frecuencia de síntomas en distintas situaciones clínicas.

 

  1. Enfermedad meningocócica invasiva por serogrupo C en la era posvacunal y fallos vacunales An Pediatr (Barc). 2020;93:396-402

La incidencia de la enfermedad meningocócica invasiva (EMI) por serogrupo C ha disminuido desde la introducción de la vacunación sistemática el año 2000. El objetivo de este estudio es determinar los casos de EMI diagnosticados desde entonces y los fallos vacunales en los casos por serogrupo C.

Pacientes y métodos, Análisis retrospectivo de pacientes diagnosticados de EMI confirmada por cultivo o reacción en cadena de la polimerasa, en un hospital infantil de tercer nivel de Barcelona, entre 2001 y 2018. Se analizó el número de dosis de vacuna recibidas y la edad, recogidos de la historia clínica y del carnet de vacunaciones.

Resultados, Se confirmaron 128 casos de EMI (7,1 casos/año; 70,3% en <5 años). Se estudió el serogrupo en 125 casos (97,6%): 103 fueron B (82,4%), 10 fueron C (8%), uno fue 29E (0,8%) y uno fue Y (0,8%); solo 10 (8%) no fueron serogrupables. De los 10 pacientes con serogrupo C, 4 no estaban vacunados y en 3 la pauta fue incompleta en cuanto a número de dosis; 3 de ellos recibieron la pauta completa según la edad y el calendario vacunal vigente, por lo que se consideran fallos vacunales. Fallecieron 6 pacientes (tasa de letalidad: 4,7%): 5 por serogrupo B (letalidad: 4,8%) y uno por serogrupo C (letalidad: 10%).

Conclusiones, El serogrupo C representó solo el 8% de los casos de EMI en el periodo de estudio y los fallos vacunales de este serogrupo fueron del 30%.

 

Actualidad bibliográfica noviembre 2020

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Enferm Infecc Microbiol Clin. 2020;38:438-43 DOI: 10.1016/j.eimc.2020.07.001 Las inmunodeficiencias primarias (IDP) son unas enfermedades raras, frecuentemente infradiagnosticadas y potencialmente fatales. Las manifestaciones clínicas de las IDP pueden ser muy graves y ocasionar secuelas que empeoran la calidad de vida de los pacientes. Tradicionalmente, el tratamiento de las IDP ha sido fundamentalmente de soporte, con excepción del trasplante de progenitores hematopoyéticos y, más recientemente, la terapia génica. El descubrimiento de nuevos mecanismos patogénicos, el desarrollo de nuevas moléculas y fármacos biológicos y los avances en el conocimiento de las bases moleculares de estas enfermedades han abierto oportunidades para el tratamiento de esta afección. El objetivo de este documento es revisar el conocimiento actual y aportar recomendaciones para el diagnóstico y el tratamiento clínico de los pacientes adultos y pediátricos con IDP basado en la evidencia científica disponible y teniendo en cuenta la actual práctica y los retos futuros. Se realizó una revisión sistemática, que justifica los niveles de evidencia para cada recomendación. En el documento se responden a las siguientes cuestiones:

1-¿cuándo debería sospecharse una IDP en un niño o adultos ( habiendo descartado causas adquiridas de inmunodeficiencia?

2- ¿ Qué pruebas diagnósticas deberían realizarse si se sospecha una IDP?

3-¿ Qué otros estudios deberían realizarse en niños/adultos con IDP al diagnóstico y durante el seguimiento?

4- ¿Cómo debería hacerse el screening en neonatos?

5- ¿ Cuándo y qué tipo de profilaxis antibiótica debe ofrecerse

6- ¿Qué tipos de vacunas deben ofrecerse?

7- ¿Cuándo se recomienda el tto sustitutivo con inmunoglobulinas (Igs)? ¿Qué vía se recomienda? ¿Cómo se debe llevar a cabo la monitorización durante el seguimiento? 8- ¿ cuándo considerar un trasplante de progenitores hematopoyéticos en un niño con IDP?

9- ¿ cuándo considerar un trasplante de progenitores hematopoyéticos en un ADULTO con IDP?

10- ¿ Qué otro tto inmunomodiladores y curativos pueden emplearse?

11- ¿qué consejo genético es necesario?

To develop a more comprehensive description of multisystem inflammatory syndrome in children (MIS-C), a novel syndrome linked to severe acute respiratory syndrome coronavirus 2, by conducting a systematic analysis of studies from different settings that used various inclusion criteria.

MIS-C studies were identified by searching PubMed and Embase as well as preprint repositories and article references to identify studies of MIS-C cases published from April 25, 2020, through June 29, 2020. MIS-C study metadata were assessed and information on case demographics, clinical symptoms, laboratory measurements, treatments, and outcomes were summarized and contrasted between studies.

Eight studies were identified representing a total of 440 MIS-C cases. Inclusion criteria varied by study: 3 studies selected patients diagnosed with Kawasaki disease, 2 required cardiovascular involvement, and 3 had broader multisystem inclusion criteria. Median age of patients by study ranged from 7.3 to 10 years, and 59% of patients were male. Across all studies, the proportion of patients with positive results for severe acute respiratory syndrome coronavirus 2 reverse transcriptase-polymerase chain reaction tests ranged from 13% to 69% and for serology, from 75% to 100%. Patients with MIS-C had high prevalence of gastrointestinal (87%), dermatologic/mucocutaneous (73%), and cardiovascular (71%) symptoms. Prevalence of cardiovascular, neurologic, and respiratory system involvement significantly differed by study inclusion criteria. All studies reported elevated C-reactive protein, interleukin-6, and fibrinogen levels for at least 75% of patients in each study.

This systematic review of MIS-C studies assists with understanding this newly identified syndrome and may be useful in developing a refined, universal case definition of MIS-C.

Recently, severe manifestations associated with coronavirus disease 2019 (COVID-19) called multisystem inflammatory syndrome in children (MIS-C) have been recognized. Analysis of studies for this novel syndrome is needed for a better understanding of effective management among affected children.

An extensive search strategy was conducted by combining the terms multisystem inflammatory syndrome in children and coronavirus infection or using the term multisystem inflammatory syndrome in children in bibliographic electronic databases (PubMed, EMBASE, and CINAHL) and in preprint servers (BioRxiv.org and MedRxiv.org) following the Preferred Reporting Items for Systematic Reviews and Metaanalyses guidelines to retrieve all articles published from January 1, 2020, to July 31, 2020. Observational cross-sectional, cohort, case series, and case reports were included.

A total of 328 articles were identified. Sixteen studies with 655 participants (3 months–20 years of age) were included in the final analysis. Most of the children in reported studies presented with fever, gastrointestinal symptoms, and Kawasaki Disease-like symptoms. Sixty-eight percent of the patients required critical care; 40% needed inotropes; 34% received anticoagulation; and 15% required mechanical ventilation. More than two-thirds of the patients received intravenous immunoglobulin and 49% received corticosteroids. Remdesivir and convalescent plasma were the least commonly utilized therapies. Left ventricular dysfunction was reported in 32% of patients. Among patients presenting with KD-like symptoms, 23% developed coronary abnormalities and 26% had circulatory shock. The majority recovered; 11 (1.7%) children died.

This systematic review delineates and summarizes clinical features, management, and outcomes of MIS-C associated with SARS-CoV-2 infection. Although most children required intensive care and immunomodulatory therapies, favorable outcomes were reported in the majority with low-mortality rates.

·Clinical Manifestations and Outcomes of Critically Ill Children and Adolescents with Coronavirus Disease 2019 in New York City. J Pediatr. 2020;226:55-63.e2. doi:10.1016/j.jpeds.2020.07.039

To describe the clinical manifestations and outcomes of critically ill children with coronavirus disease-19 (COVID-19) in New York City.

Retrospective observational study of children 1 month to 21 years admitted March 14 to May 2, 2020, to 9 New York City pediatric intensive care units (PICUs) with severe acute respiratory syndrome coronavirus 2 infection.

Of 70 children admitted to PICUs, median age was 15 (IQR 9, 19) years; 61.4% male; 38.6% Hispanic; 32.9% black; and 74.3% with comorbidities. Fever (72.9%) and cough (71.4%) were the common presenting symptoms. Twelve patients (17%) met severe sepsis criteria; 14 (20%) required vasopressor support; 21 (30%) developed acute respiratory distress syndrome (ARDS); 9 (12.9%) met acute kidney injury criteria; 1 (1.4%) required renal-replacement therapy, and 2 (2.8%) had cardiac arrest. For treatment, 27 (38.6%) patients received hydroxychloroquine; 13 (18.6%) remdesivir; 23 (32.9%) corticosteroids; 3 (4.3%) tocilizumab; and 1 (1.4%) anakinra; no patient was given immunoglobulin or convalescent plasma. Forty-nine (70%) patients required respiratory support: 14 (20.0%) noninvasive mechanical ventilation, 20 (28.6%) invasive mechanical ventilation (IMV), 7 (10%) prone position, 2 (2.8%) inhaled nitric oxide, and 1 (1.4%) extracorporeal membrane oxygenation. Nine (45%) of the 20 patients requiring IMV were extubated by day 14 with median IMV duration of 218 (IQR 79, 310.4) hours. Presence of ARDS was significantly associated with duration of PICU and hospital stay, and lower probability of PICU and hospital discharge at hospital day 14 (P < .05 for all).

Critically ill children with COVID-19 predominantly are adolescents, have comorbidities, and require some form of respiratory support. The presence of ARDS is significantly associated with prolonged PICU and hospital stay.

Casos clínicos

An otherwise healthy 11-year-old Japanese boy presented with a 3-week history of a right neck mass. Except for mild fatigue, he did not display any associated general symptoms, including fever, night sweats, or weight loss. Physical examination demonstrated a prominent tender cervical lymphadenopathy in the posterior cervical triangle (Figure 1). Blood tests reported leukopenia and mildly elevated lactate dehydrogenase and aminotransferase levels. Over the following 2 weeks, his lymph nodes enlarged and his fatigue worsened; thus, we performed a cervical lymph-node excisional biopsy that revealed increased CD 68+ histiocytes, lymphocytes, and immunoblasts in the cortices with abundant karyorrhectic debris (Figure 2); these findings were compatible with Kikuchi-Fujimoto disease (KFD). At the 1-month follow-up, the patient's symptoms had improved without any intervention.

A 12-year-old girl with severe acute respiratory syndrome coronavirus 2 infection presented as phlegmasia cerulea dolens with venous gangrene. Emergent mechanical thrombectomy was complicated by a massive pulmonary embolism and cardiac arrest, for which extracorporeal cardiopulmonary resuscitation and therapeutic hypothermia were used. Staged ultrasound-assisted catheter-directed thrombolysis was used for treatment of bilateral pulmonary emboli and the extensive lower extremity deep vein thrombosis while the patient received extracorporeal membrane oxygenation support. We highlight the need for heightened suspicion for occult severe acute respiratory syndrome coronavirus 2 infection among children presenting with unusual thrombotic complications.

Phlegmasia cerulea dolens (PCD) is characterized by extensive venous thrombosis and severe venous outflow obstruction presents with painful limb swelling, cyanosis, and gangrene in extreme cases. Occurrence of PCD in healthy pediatric patients is rare.

Potential protective mechanisms cited include a decreased capacity for thrombin generation, increased alpha-2 macroglobulin inhibition of thrombin, and the antithrombotic potential of the vessel wall.

 Among adult and pediatric patients, malignancy, sepsis, surgery, hypercoagulable state, and vascular injury (indwelling central lines) predispose to PCD.

· Presentation of Severe Acute Respiratory Syndrome-Coronavirus 2 Infection as Cholestatic Jaundice in Two Healthy Adolescents J Pediatr. 2020;226:278-280. doi:10.1016/j.jpeds.2020.07.054

Liver abnormalities in severe acute respiratory syndrome-coronavirus 2 infection, including hepatitis and cholestasis, have been observed in adults and are associated with worse outcomes. We describe 2 adolescents with cholestasis and hepatitis with mild presentation of severe acute respiratory syndrome-coronavirus 2 lacking typical symptoms. Our intention is to raise index of suspicion for testing and protective equipment use. 

·Acute Meningoencephalitis as Initial Presentation of SARS-CoV-2 Infection in Pediatrics. The Pediatric Infectious Disease Journal. 39(11):e386-e387, November 2020.

Para profundizar

  • Evaluación del impacto del Documento de Consenso español sobre el abordaje de las infecciones osteoarticulares en nuestro medio a través de la Red de Infecciones Osteoarticulares Pediátricas (RIOPed) An Pediatr (Barc). 2020;93:289-96. DOI: 10.1016/j.anpedi.2019.11.008 Introducción En 2014 se publicó el Documento de Consenso desarrollado por SEIP-SERPE-SEOP para el diagnóstico y el tratamiento de las infecciones osteoarticulares (IOA). En 2015 se constituyó RIOPed como red nacional multidisciplinar para la investigación en IOA. El objetivo del estudio ha sido valorar el grado de adecuación a las recomendaciones establecidas en el consenso durante un año de seguimiento. Material y métodosEstudio prospectivo multicéntrico nacional realizado entre septiembre de 2015 y septiembre de 2016 en 37 hospitales con inclusión de pacientes menores de16años diagnosticados de IOA, confirmada mediante aislamiento microbiológico, o probable: artritis séptica (AS) con >40.000 leucocitos en líquido sinovial u osteomielitis (OM)/osteoartritis (OA)/espondilodiscitis (ED) con prueba de imagen compatible. Los resultados se compararon con los obtenidos en el estudio retrospectivo realizado entre 2008 y 2012. Resultados Se incluyeron 255 casos: 131 OM, 79 AS, 30 OA y 15 ED. Respecto a las pruebas complementarias que el consenso consideró de obligada realización, la radiografía se llevó a cabo en el 87,8% de los casos, el hemocultivo en el 91,6% y el cultivo de líquido sinovial en el 99% de AS. Se realizó RM en el 71% de las OM. La elección del tratamiento antibiótico intravenoso empírico se adecuó a las recomendaciones en el 65,1% de los casos, y en el 62,3% para el tratamiento oral. Se llevó a cabo cirugía en el 36,8% de las AS (85,7% artrotomía), con un descenso significativo respecto al estudio retrospectivo (p=0,014). Solo el 58,5% de casos se ajustaron a las recomendaciones de duración del tratamiento; sin embargo, se comprobó una menor duración del tratamiento intravenoso. Conclusiones En general, el grado de adecuación a las recomendaciones que marcaron el grupo de expertos es bueno para las pruebas complementarias y aceptable respecto a la elección del tratamiento antibiótico, aun detectándose casi un 40% de inadecuación. Se ha conseguido un descenso de la estancia hospitalaria
  •  Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS): the Evelina Experience. Archives of Disease in Childhood 2020;105:1025-1027.

Introduction

In the midst of lockdown, just as patient acuity and bed pressures eased, a number of teenagers were transferred to the paediatric intensive care unit (PICU) at Evelina London Children’s Hospital for inotropic support in the absence of respiratory involvement or any features of acute Severe acute respiratory syndrome related coronavirus 2 (SARS CoV-2) infection.1 All patients had features of toxic shock syndrome (TSS) but no pathogens were identified despite extensive microbiological investigation. Several new patients presented over the next few days; febrile with high inflammatory markers and multisystem involvement. The unusually high number of cases raised concerns, which were discussed with Public Health England regarding a possible infectious disease cluster with pathogen unknown.

Following several discussions with National Health Service England (NHSE) and pan-London tertiary paediatric services who had also seen cases, a consensus was reached that a new clinical phenomenon was being seen across London. It was sufficiently concerning to send out an NHSE alert at the end of April which triggered international discussion.2 Numerous teleconferences later, the emerging condition had a name; paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS).3 Since the alert other countries have reported similar cases (figure 1).

 Introducción En este momento existen todavía grandes interrogantes acerca de las características de enfermedad causada por el nuevo coronavirus (COVID-19) en los niños, así como acerca de los factores asociados al desarrollo de formas graves de la enfermedad. Métodos Estudio retrospectivo que incluye pacientes menores de 18 años ingresados debido a infección por SARS-CoV-2. La infección fue confirmada por la reacción en cadena de la transcriptasa inversa-polimerasa (RT-PCR) en tiempo real o por serología. Describimos los datos epidemiológicos y clínicos, los hallazgos de laboratorio y de imágenes, así como el tratamiento y la evolución de estos pacientes. Los pacientes se clasificaron en dos grupos de gravedad y luego se compararon. Resultados Se incluyeron 39 niños, con una mediana de edad de nueve años (rango 12 días-16 años); 23 eran varones. Los casos con evolución no complicada (24) se presentaron en su mayoría con fiebre y/o síntomas respiratorios sin alteraciones significativas en los hallazgos de laboratorio. De los 15 niños con enfermedad complicada, 12 desarrollaron shock. Además de la fiebre, frecuentemente presentaban alteraciones de la apariencia, taquicardia extrema, dolor abdominal, vómitos, diarrea, erupción cutánea y/o hiperemia conjuntival. También mostraron mayor linfopenia (p = 0,001), elevación de la proporción neutrófilos/linfocitos (p = 0,001), proteína C reactiva (p < 0,001), procalcitonina (p = 0,001), dímero D (p < 0,001) y ferritina (p < 0,001). Conclusiones La infección por SARS-CoV-2 en niños ingresados se presenta con una gran variabilidad clínica. Cuando se les proporciona tratamiento de soporte, los pacientes con síntomas respiratorios que no tienen alteración de las pruebas de laboratorio, generalmente tienen una enfermedad no complicada. Los pacientes con enfermedad complicada se presentan principalmente con fiebre y síntomas abdominales y/o mucocutáneos, la mayoría desarrollan un shock. La elevación de los...

Introducción SARS-CoV-2, responsable de la enfermedad por coronavirus 2019 (COVID-19), fue detectado por primera vez en España el 31 de enero de 2020. El 14 de marzo fue declarado el estado de alarma con el objetivo de controlar la pandemia. El objetivo de este estudio es analizar las consecuencias de esta crisis sanitaria sobre el patrón de demanda asistencial, así como el manejo y las características de los pacientes con sospecha de COVID-19 en el Servicio de Urgencias Pediátricas. Pacientes y métodos Estudio retrospectivo observacional en niños y adolescentes menores de 18 años, atendidos en nuestro Servicio de Urgencias Pe diátricas durante el periodo comprendido desde el 14 de marzo hasta el 17 de abril de 2020. Resultados Durante el periodo de estudio se atendieron 1.666 pacientes, un 65,4% menos que en el mismo periodo de 2019. La edad media fue de 5,4 años y el 51,2% eran varones. El 39,9% fueron clasificados con niveles de alta prioridad, un 6,5% más que en 2019. Los principales motivos de consulta fueron fiebre (26,5%), síntomas respiratorios (16,1%) y traumatismos (15,2%). Un total de 218 pacientes (13%) fueron diagnosticados de posible COVID-19, confirmándose la infección en el 18,4%. El 44% (96/218) fueron diagnosticados de infección respiratoria inferior y el 33,9% (74/218), superior. El 23,8% (52/218) fueron hospitalizados. Conclusiones Durante el brote epidémico SARS-CoV-2 disminuyó la demanda de asistencia pediátrica urgente, aumentando la proporción de casos con niveles de triaje de alta prioridad. La mayoría de los pacientes con sospecha o confirmación microbiológica de COVID-19 cursaron con clínica respiratoria leve

To assess the impact of separation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR)-positive mother–newborn dyads on breastfeeding outcomes.

This observational longitudinal cohort study of mothers with SARS-CoV-2 PCR-and their infants at 3 NYU Langone Health hospitals was conducted between March 25, 2020, and May 30, 2020. Mothers were surveyed by telephone regarding predelivery feeding plans, in-hospital feeding, and home feeding of their neonates. Any change prompted an additional question to determine whether this change was due to coronavirus disease-2019 (COVID-19).

Of the 160 mother–newborn dyads, 103 mothers were reached by telephone, and 85 consented to participate. There was no significant difference in the predelivery feeding plan between the separated and unseparated dyads (P = .268). Higher rates of breastfeeding were observed in the unseparated dyads compared with the separated dyads both in the hospital (P < .001) and at home (P = .012). Only 2 mothers in each group reported expressed breast milk as the hospital feeding source (5.6% of unseparated vs 4.1% of separated). COVID-19 was more commonly cited as the reason for change in the separated group (49.0% vs 16.7%; P < .001). When the dyads were further stratified by symptom status into 4 groups—asymptomatic separated, asymptomatic unseparated, symptomatic separated, and symptomatic unseparated—the results remained unchanged.

In the setting of COVID-19, separation of mother–newborn dyads impacts breastfeeding outcomes, with lower rates of breastfeeding both during hospitalization and at home following discharge compared with unseparated mothers and infants. No evidence of vertical transmission was observed; 1 case of postnatal transmission occurred from an unmasked symptomatic mother who held her infant at birth.

 Objective To compare cause-specific UK mortality in children and young people (CYP) with EU15+ countries (European Union countries pre-2004, Australia, Canada and Norway).

Design Mortality estimates were coded from the WHO World Mortality Database. Causes of death were mapped using the Global Burden of Disease mortality hierarchy to 22 cause groups. We compared UK mortality by cause, age group and sex with EU15+ countries in 2015 (or latest available) using Poisson regression models. We then ranked the UK compared with the EU15+ for each cause.

Setting The UK and EU15+ countries.

Participants CYP aged 1–19.

Main outcome measure Mortality rate per 100 000 and number of deaths.

Results UK mortality in 2015 was significantly higher than the EU15+ for common infections (both sexes aged 1–9, boys aged 10–14 and girls aged 15–19); chronic respiratory conditions (both sexes aged 5–14); and digestive, neurological and diabetes/urological/blood/endocrine conditions (girls aged 15–19). UK mortality was significantly lower for transport injuries (boys aged 15–19). The UK had the worst to third worst mortality rank for common infections in both sexes and all age groups, and in five out of eight non-communicable disease (NCD) causes in both sexes in at least one age group. UK mortality rank for injuries in 2015 was in the top half of countries for most causes.

Conclusions UK CYP mortality is higher than a group of comparable countries for common infections and multiple NCD causes. Excess UK CYP mortality may be amenable to health system strengthening.

Protracted bacterial bronchitis (PBB) is the leading cause of chronic wet cough in young children from developed countries. Despite its high prevalence there is a paucity of evidence to inform the optimal duration of treatment leading to variation in practice. Relapse of chronic cough is common and recurrent PBB (>3 episodes in 12 months) is associated with a future diagnosis of bronchiectasis. We investigated the factors associated with any relapse (≥1 episode in 12 months) and recurrent PBB in 66 children. No factor was significantly associated with any relapse. Duration of initial antibiotic treatment was the only factor significantly associated with recurrent PBB. Those who received antibiotics for 6 weeks antibiotics were less likely to develop recurrent PBB than those who received for 2 weeks (p=0.046). This is the first study to show an association between duration of initial antibiotic course and therefore future bronchiectasis. Prospective studies are needed to investigate this association.

Optimal dosing of antibiotics maximises efficacy while minimising toxicity and the selection of resistance. Dosing regimens of older off-patent antibiotics are long established clinically but the origins of these doses are often unclear. In 2011, we noted that dosing of the penicillins in paediatrics had remained unchanged for over 50 years and was no longer optimal due to changes in children’s weights.1 The aim of this paper is to explore further the very early origins of the dosing of oral phenoxymethylpenicillin (penicillin V), as the first oral penicillin used in children.

History of oral penicillin V use in children

Being able to administer penicillin orally was always a clear goal for children where the original doses given as high-volume intramuscular injections were particularly painful. As far as we have been able to determine, the first reported use of oral penicillin in a child was from 1940 in a 6-month-old boy with a Staphylococcus aureus urinary tract infection.2 Further studies in babies and young infants of oral benzylpenicillin (penicillin G) demonstrated good oral absorption, but that children over the age of 6–12 months rapidly degraded the drug because of high gastric acidity.3 The development of penicillin V in 1948, capable of withstanding gastric acid, was a clear step forward for paediatric use. The first large series of penicillin V being administered to children, that we can identify, was from Germany in 1953 in 106 children. The dose was based on the weight of the child (<15 kg=15 mg given four hourly, 15–30 kg=30 mg four hourly, >30 kg=30 mg three hourly).4 One of the first recorded uses of oral penicillin V in children from the UK was reported …

Enferm Infecc Microbiol Clin. 2020;38:371-4

Introducción.Se describe la distribución de serotipos de Streptococcus  neumoniae aislados en líquido cefalorraquídeo (LCR) entre los años 2007-2018 en la Comunidad de Madrid (CM) identificando aquellos con mayor tropismo meníngeo.

Métodos. Se estudiaron las cepas de episodios de enfermedad neumocócica invasora enviadas al Laboratorio Regional de Salud Pública por los servicios de microbiología de hospitales públicos y privados de la CM. La frecuencia de serotipos procedentes de LCR se comparó con la observada en otras muestras.

Resultados. Se procesaron 6.115 cepas. El 5% (n=304) se aislaron en LCR. Siete serotipos (11A, 19F, 23B, 10A, 24F, 23A y 35F) mostraron una frecuencia en LCR significativamente mayor que en otras muestras habitualmente estériles. Los serotipos 24F, 11A y 23B mostraron alta resistencia a la penicilina.

Conclusión. La frecuencia y la resistencia de determinados serotipos de neumococo con elevado tropismo meníngeo podría comprometer el tratamiento de las infecciones del sistema nervioso central.

Aim: This study was designed to assess the efficacy and safety of Saccharomyces cerevisiae variant boulardii CNCM I-3799 ( boulardii CNCM I-3799) in the management of acute diarrhea in children.

Methods: A total of 100 infants and children 3–36 months of age with acute diarrhea received medical care according to the World Health Organization guidelines on the management of acute diarrhea in children and were randomly allocated to the probiotic group ( S. boulardii CNCM I-3799 at a daily dose of 5 billion CFU twice daily) or to the placebo group. Infants and children were treated for 5 days and an extended follow-up was planned 1 and 2 months after the end of the treatment period. Primary endpoint was the time of recovery from diarrhea defined as the duration of diarrhea. Other parameters, such as frequency and consistency of stools, associated with the severity of diarrhea episodes were defined as secondary endpoints.

Results: The administration of S. boulardii CNCM I-3799 was associated with beneficial effects on duration and severity of diarrhea. The time of recovery from diarrhea was significantly shorter in the probiotic group compared with the placebo group (65.8 ± 12 hours vs. 95.3 ± 17.6 hours, = 0.0001). Faster remission in the probiotic group was also demonstrated by a shorter time before the first episode of semisolid stool [−23.5 hours, diff (95% CI): −7.99 (−31.49 to −15.51), = 0.0001] and the faster normalization of stool consistency. S. boulardii CNCM I-3799 was well tolerated.

Conclusion: S. boulardii CNCM I-3799 supplementation in children with acute diarrhea was shown effective in reducing the duration and severity of diarrhea in infants and children.

Antecedentes Para estudiar el perfil neurocognitivo de jóvenes infectados perinatalmente por VIH (PVIH+) es importante valorar tanto los factores asociados al virus como los no relacionados. El objetivo de nuestro estudio fue evaluar la cognición y la calidad de vida de una cohorte de jóvenes PVIH+ y compararlas con las de un grupo control. Métodos Treinta jóvenes PVIH+ y 30 sujetos sanos VIH− pareados por edad, sexo y nivel socioeconómico completaron un protocolo que incluía pruebas neurocognitivas, entrevista psicosocial semiestructurada y cuestionario de calidad de vida PedsQL. Se calculó el Z-score global (NPZ-5) y específico para cada dominio neurocognitivo. Adicionalmente, se consideró la categoría SIDA (PVIH+/C, PVIH+/noC). Se realizó análisis univariante y multivariante. Resultados De los 60 pacientes incluidos, el 67% eran mujeres; edad media (IQR) 19años (18-21). Respecto al grupo PVIH+, el 27% tenían categoría CDCC (ninguna encefalopatía), el 93% tomaban antirretrovirales y el 77% tenían carga viral indetectable. No hubo diferencias en cuanto a ocupación, aunque el grupo VIH− repitió menos cursos académicos (p=0,028) y tuvo mayor nivel educativo (p=0,021). No hubo diferencias entre los grupos PVIH+/noC y VIH−. El grupo PVIH+/C tuvo un rendimiento inferior al de PVIH+/noC (NPZ-5, p=0,037) y VIH− (inteligencia cristalizada, p=0,025; cociente de inteligencia, p=0,016). Mayor nadir de célulasT CD4+ se relacionó con mejor Z-score en Memoria (p=0,007) y NPZ-5 (p=0,025). La exposición temprana y prolongada a la terapia antirretroviral favoreció un mejor rendimiento en Memoria (p=0,004) y en Funciones Ejecutivas (p=0,015), respectivamente. Conclusiones No hubo diferencias significativas en el perfil neurocognitivo ni en calidad de vida entre los adolescentes PVIH+/noC y VIH−; sin embargo, los participantes PVIH+/C obtuvieron puntuaciones más bajas. La exposición temprana y prolongada a la terapia antirretroviral parece tener un efecto beneficioso.

Background: Bartonella henselae serology is commonly used to diagnose cat-scratch disease (CSD). Titers above a threshold for positivity suggest either a recent or remote infection. Recent infection can be confirmed by a 4-fold rise in the convalescent titer in some cases. Many atypical presentations attributed to CSD utilize a low threshold for positivity without supportive evidence from convalescent sera or supplemental testing, raising a concern for the overdiagnosis of CSD.

Methods: We conducted a retrospective chart review of immunocompetent pediatric patients at the Hospital for Sick Children, Toronto, spanning an 11-year period. A total of 154 cases were included with serologic titers ≥1:128. These were divided into 3 groups: group 1 = 1:128, group 2 = 1:256, and group 3 ≥ 1:512. Cases within groups were evaluated with respect to cat contact, clinical presentation, further testing, and final diagnosis.

Results:One-third of patients with a titer of 1:128 had an alternative diagnosis. Most cases with a titer of 1:128 or 1:256 did not have convalescent serologic testing performed. Within these 2 groups, only 1 case had a 4-fold rise in the convalescent titer. A trend of decreasing number of cases with alternative diagnoses ( P = 0.03) and increasing number of cases presenting with regional lymphadenopathy ( P = 0.07) was associated with higher titers in group 3 compared with group 1.

Conclusion: Concerns about the serologic diagnosis of CSD include the use of low titers for positivity, incomplete diagnostic evaluation, and the lack of convalescent serologic testing. We propose a clinical guide to assist in managing suspected cases of CSD.

Background: Acute rheumatic fever (ARF) predominantly affects indigenous Māori schoolchildren in Bay of Plenty region, and more so male Māori students, especially when socioeconomically deprived. We evaluated the effectiveness of strategies for reducing ARF with group A streptococcal pharyngitis treatment in 2011–18.

Methods: We retrospectively assessed outcomes of 3 open cohorts of Māori schoolchildren receiving different interventions: Eastern Bay rural Cohort 1, mean deprivation decile 9.80, received school-based sore-throat programs with nurse and general practice (GP) support; Eastern Whakatane township/surrounds Cohort 2, mean deprivation 7.25, GP management; Western Bay Cohort 3, mean deprivation 5.98, received predominantly GP care, but 3 highest-risk schools received school-based programs. Cases were identified from ICD10 ARF-coded hospital discharges, notifications to Ministry of Health, and a secondary-prevention penicillin database. Primary outcomes were first-presentation ARF cohorts’ incidence preintervention (2000–10) and postintervention (2011–18) with cases over annual school rolls’ Māori students-year denominators.

Results: Overall, ARF in Maori schoolchildren declined in the cohorts with school-based programs. Cohort 1 saw a postintervention (2011–18) decline of 60%, 148 to 59/100,000/year, rate ratio (RR) = 0.40(CI 0.22–0.73) P = 0.002. Males’ incidence declined 190 to 78 × 100,000/year RR = 0.41(CI 0.19–0.85) P = 0.013 and females too, narrowing gender disparities. Cohort 3 ARF incidence decreased 48%, 50 to 26/100,000/year RR = 0.52(CI 0.27–0.99) P = 0.044. In contrast, ARF doubled in Cohort 2 students with GP-only care without school-based programs increasing 30 to 69/100,000/year RR = 2.28(CI 0.99–5.27) P = 0.047, especially for males 39/100,000/year to 107/100,000/year RR = 2.71(CI 1.00–7.33) P = 0.0405.

Conclusions: School-based programs with indigenous Māori health workers’ sore-throat swabbing and GP/Nurse support reduced first-presentation ARF incidence in Māori students in highest-risk settings.

Background: In Western Europe, most pediatric tuberculosis (TB) cases occur among immigrants; however, data are rarely stratified by first/second-generation immigrants and many cases may be preventable.

Methods: This was a nationwide study of children <18 years with TB from 2009 to 2014 in Denmark. Demographic, clinical, microbiologic and treatment outcome data were obtained from registers and medical records.

Results: We identified 145 cases; 99 were immigrants (68%) of which 54 (55%) were second-generation immigrants. Most first-generation immigrants (73%) were diagnosed by passive case finding as was half the second-generation immigrants (52%), in contrast to Danish children who were mostly diagnosed by active case finding (70%). Symptoms were often nonspecific, and one-third of the children had normal blood tests at time of diagnosis. First-generation immigrants were most often infected abroad (84%) as opposed to Danish children (9%) and second-generation immigrants (30%). Approximately one-third of the children represented cases of TB disease that could possibly have been prevented by screening or rigorous contact tracing. The overall treatment success rate was 97%, and cases of unsuccessful treatment were restricted to immigrant adolescents.

Conclusions: The majority of pediatric TB in Denmark occurred among immigrant children with symptomatic TB, whereas more Danish children were diagnosed at earlier disease stages. Almost one-third of TB cases may represent missed opportunities to prevent TB disease. Improvements include enhanced adult case detection with comprehensive contact investigation among children, tailored screening and vaccination of immigrant children, and raised awareness of diagnosing and treating latent TB infection in children.

Background: Italy is classified as a low tuberculosis (TB) incidence country (rate 6.5/100,000 inhabitants). However, the Campania Region Pediatric Reference Centre (CRRC) observed an increase in TB, contemporarily with a rise in migration.

Our aim was to investigate trends in TB notification rates, association with migration, and changes in clinical outcomes of children living in Campania.

Methods: We conducted a prospective cohort study (January 1, 2009–December 31, 2018), including children <18 years who received diagnosis of TB at the CRRC. Yearly crude TB incidence rates and relative confidence interval (95% CI) were calculated. Two main outcome measures were considered: loss to follow-up and poor clinical outcome, including prolonged or second-line treatment, sequelae, or death.

Results: Overall 146 children (52.1% male; median age, 50 months; interquartile range, 96.33) received a diagnosis of TB. TB incidence rates increased from 0.44 cases (95% CI: 0.16–0.97) per 100,000 inhabitants <18 years of age in 2009 to 1.84 cases (95% CI: 1.15–2.79) in 2018 ( P < 0.05) and linearly correlated with the rate of migrants (R 2 = 0.9272; P < 0.0001). Ziehl-Neelsen-positive children had an increased likelihood of poor clinical outcomes (odds ratio, 4.83; 95% CI: 1.28–18.2; P = 0.020). Compared with Italians, foreign children showed a lower likelihood of cure without sequelae (49.3% versus 67.9%; P < 0.001; odds ratio, 0.45; 95% CI: 0.23–0.89; P = 0.02). They accounted for all fatal cases and loss to follow-up.

Conclusion: Pediatric TB rate in Campania increased in the last 10 years in association with the increase in migration. Emphasizing national TB rates may disregard important differences in local infection trends and limit medical awareness about TB. Foreign children may need tailored management programs.

Background: Children with fever and respiratory symptoms represent a large patient group at the emergency department (ED). A decision rule-based treatment strategy improved targeting of antibiotics in these children in a recent clinical trial. This study aims to evaluate the impact of the decision rule on healthcare and societal costs, and to describe costs of children with suspected lower respiratory tract infections (RTIs) in the ED in general.

Methods: In a stepped-wedge, cluster randomized trial, we collected cost data of children 1 month to 5 years of age with fever and cough/dyspnea in 8 EDs in The Netherlands (2016–2018). We calculated medical costs and societal costs per patient, during usual care (n = 597), and when antibiotic prescription was guided by the decision rule (n = 402). We calculated cost-of-illness of this patient group and estimated their annual costs at national level.

Results: The cost-of-illness of children under 5 years with suspected lower RTIs in the ED was on average €2130 per patient. At population level this is €15 million per year in The Netherlands (€1.7 million/100,000 children under 5). Mean costs per patient in usual care (€2300) were reduced to €1870 in the intervention phase ( P = 0.01). Main cost drivers were hospitalization and lost parental workdays.

Conclusions: Implementation of a decision rule-based treatment strategy in children with suspected lower RTI was cost-saving, due to a reduction in hospitalization and parental absenteeism. Given the high frequency of this disease in children, the decision rule has the potential to result in a considerable cost reduction at population level.

Background: Misuse, overuse of antimicrobials and increasing rates of antimicrobial resistance are well-recognized problems throughout Europe. The aim of this survey was to describe the current pediatric antibiotic stewardship (PAS) landscape across Europe and identify gaps, in terms of national programs, networks and guidelines.

Methods: A survey of 17 questions was circulated in July 2019 among 24 European pediatric infectious disease researchers and clinicians, professors and heads of department on the existence of PAS programs, national networks and meetings, established competencies, metrics and guidelines.

Results: We received responses from 23 countries. National guidelines on the management of children with common infections treated in hospital settings exist in 15 of 23 (70%); only 8 of 15 (53%) had been updated within the previous 4 years. Most provide guidance on antibiotic initiation and duration (14 of 15, 93%), but few on when to transition from intravenous to oral antibiotics (7 of 15, 47%). National PAS competencies have only been developed in 4 countries; only 1 addressed both community and hospital prescribing. Organized national PAS networks are only established in the United Kingdom and Germany; 21 of 23, 91% countries had no agreed metric for antibiotic prescribing in children; 2 of 23 were based on daily defined doses.

Conclusions: Fragmented implementation of PAS programs, no agreed metrics, lack of established PAS competencies and national PAS networks along with inexistent funding is alarming in view of existing high rates of antimicrobial resistance in Europe.

Background: Cytomegalovirus (CMV) is the leading cause of congenital infection worldwide. Up to 15%–20% of infected newborns will develop long-term sequelae such as hearing loss and neurologic abnormalities. The aim of this study was to investigate the prevalence of congenital CMV infection (cCMV) and associated clinical abnormalities in Spain.

Methods: A prospective screening for cCMV by viral load in saliva was performed. Saliva samples were obtained within the first 72 hours of life in a maternity ward in Madrid (Spain), during a 1-year period. All positive screening tests were confirmed with viral load in urine. Clinical, laboratory, auditory, visual and cerebral imaging assessments were performed in all children with cCMV.

Results: Of the 4097 neonates born during the study period, 3190 (78%) were included. CMV viral load in saliva was detectable in 24/3190 (0.75%) children, and congenital infection was confirmed in 15/3190 (0.47%, CI 95%: 0.29%–0.77%). Positive predictive value was 62.5% (CI 95%: 46.5%–76.1%). Two infants presented symptoms at birth. Eight (53.3%) children showed abnormalities in magnetic resonance imaging; most of them isolated white matter abnormalities. Newborns with abnormalities in magnetic resonance imaging showed higher viral loads in blood and saliva ( P = 0.04).

Conclusions: One in 200 neonates born in our hospital presented a cCMV infection. CMV viral load in saliva has been shown to be a simple and highly accepted screening method but should be confirmed by CMV detection in urine. In spite of the fact that half of infected children had abnormalities in cerebral imaging, diagnosis during the neonatal period would have been impossible without a screening program in most cases.

The clinical course of SARS-CoV-2 infection in young infants is not well understood. In this prospective cohort study, we compared the presence and duration of symptoms in febrile infants ≤60 days with (n = 7) and without (n = 16) SARS-CoV-2 infection. Overall, we observed overlapping symptoms and duration of illness, with longer length of cough and nasal congestion among the SARS-CoV-2-positive infants.

Among 439 infants presenting with symptoms of upper respiratory tract infection and temperature ≥39°C, 19 (4.3% [95% confidence interval, 2.8–6.7]) received a diagnosis of urinary tract infection (abnormal urine dipstick from a sterile urine sample and positive urine culture). Regardless of respiratory presentation, all infants presenting with a temperature of 39°C should be screened for urinary tract infection.

We conducted a descriptive time-series study of pediatric emergency healthcare use during the onset of severe acute respiratory syndrome coronavirus 2 pandemic after a state-wide stay-at-home order. Our study demonstrated decreased volume, increased acuity, and generally consistent chief complaints compared with the prior 3 years (2017 through 2019). Ingestions became a significantly more common chief complaint in 2020.

As the world waits patiently for the development of the COVID-19 vaccine, it seems to be a fertile environment for those members of society who are the anti vaccine naysayers, breeding suspicion and indeed violence and using social media to propagate their ill informed and dangerous opinions. There is growing evidence of vaccine delays or refusals due to a lack of trust in the importance, safety, or effectiveness of vaccines, alongside persisting access issues. de Figueiredo A et al [Lancet 2020;396 (10255):898–908. https://doi.org/10.1016/S0140-6736(20)31558-0] have mapped vaccine confidence across 149 countries between 2015 and 2019. Their Vaccine Confidence Project (VCP) was established in 2010 with an aim to develop …

·Macrolide and Nonmacrolide Resistance with Mass Azithromycin Distribution. N Engl J Med 2020; 383:1941-1950
DOI: 10.1056/NEJMoa2002606

BACKGROUND: Mass distribution of azithromycin to preschool children twice yearly for 2 years has been shown to reduce childhood mortality in sub-Saharan Africa but at the cost of amplifying macrolide resistance. The effects on the gut resistome, a reservoir of antimicrobial resistance genes in the body, of twice-yearly administration of azithromycin for a longer period are unclear.

METHODS: We investigated the gut resistome of children after they received twice-yearly distributions of azithromycin for 4 years. In the Niger site of the MORDOR trial, we enrolled 30 villages in a concurrent trial in which they were randomly assigned to receive mass distribution of either azithromycin or placebo, offered to all children 1 to 59 months of age every 6 months for 4 years. Rectal swabs were collected at baseline, 36 months, and 48 months for analysis of the participants’ gut resistome.

The primary outcome was the ratio of macrolide-resistance determinants in the azithromycin group to those in the placebo group at 48 months.

RESULTS: Over the entire 48-month period, the mean (+SD) coverage was 86.6+12% in the villages that received placebo and 83.2+16.4% in the villages that received azithromycin. A total of 3232 samples were collected during the entire trial period; of the samples obtained at the 48-month monitoring visit, 546 samples from 15 villages that received placebo and 504 from 14 villages that received azithromycin were

analyzed. Determinants of macrolide resistance were higher in the azithromycin group than in the placebo group: 7.4 times as high (95% confidence interval [CI], 4.0 to 16.7) at 36 months and 7.5 times as high (95% CI, 3.8 to 23.1) at 48 months. Continued mass azithromycin distributions also selected for determinants of nonmacrolide resistance, including resistance to beta-lactam antibiotics, an antibiotic class prescribed frequently in this region of Africa.

CONCLUSIONS: Among villages assigned to receive mass distributions of azithromycin or placebo twice yearly for 4 years, antibiotic resistance was more common in the villages that received azithromycin than in those that received placebo. This trial showed that mass azithromycin distributions may propagate antibiotic resistance. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02047981.)

 

Actualidad bibliográfica octubre 2020

Top ten

La Asociación Española de Pediatría de Atención Primaria (AEPap) ha elaborado un documento con propuestas para la organización de las consultas de Atención Primaria en la próxima temporada invernal, y así poder garantizar la atención a los pacientes pediátricos, con y sin sospecha de infección por SARS-CoV-2.

En dicho documento se insiste en la importancia de que la primera valoración del paciente sea telefónica para orientar a las familias sobre la idoneidad de una visita telemática o de una visita presencial y, en caso de ser así, recibir indicaciones sobre la zona del centro de salud y horario de atención en función de los síntomas, para mantener las medidas de protección y seguridad, tanto del paciente como del personal sanitario.

AEPap y SEPEAP proponen que en los centros de salud se organicen dos circuitos, uno para atender pacientes con sospecha de infección por SARS-CoV-2 y otro circuito para valorar el resto de las patologías y llevar a cabo el Programa de Salud Infantil (PSI).

Para ello, también insta a las Administraciones públicas a mejorar las herramientas de la telemedicina para garantizar el intercambio seguro de información y así poder realizar consultas no presenciales para evitar contagios en el centro sanitario, dotar a los centros de salud de personal sanitario, administrativo y de limpieza suficiente.

También es muy importante que los profesionales sanitarios dispongan de técnicas diagnósticas para descartar las infecciones pediátricas más frecuente en época invernal (rinovirus, virus respiratorio sincitial, gripe, rotavirus) y agilizar el resultado de la reacción en cadena de la polimerasa (PCR) para COVID-19 y así evitar aislamientos innecesarios.

  • Covid-19: UK studies find gastrointestinal symptoms are common in children BMJ 2020;370:m3484

Los síntomas gastrointestinales son comunes en los niños infectados con SARS-CoV-2 y deberían desencadenar la petición de pruebas para detección del virus.

Un estudio prospectivo de 992 niños sanos (edad media de 10,1 años), hijos de trabajadores de la salud de todo el Reino Unido encontró que 68 (6,9%) dieron positivo en anticuerpos contra el SARS-CoV-2.

La mitad de los niños que dieron positivo no habían informado síntomas, pero entre los que sí lo hicieron, los más comunes fueron fiebre (21 de 68, 31%); síntomas gastrointestinales, que incluyen diarrea, vómitos y calambres abdominales (13 de 68, 19%); y dolor de cabeza (12 de 68,18%).

Los últimos hallazgos de la aplicación Covid-19 Symptom Study,que se lanzó a fines de marzo para rastrear los síntomas de las personas, también muestran que los síntomas gastrointestinales ocurren con frecuencia en niños con pruebas de frotis positivas.

Los hallazgos del estudio respaldan que los síntomas gastrointestinales (diarrea y vómitos) deben agregarse a la lista actual (temperatura alta, tos y pérdida o cambio en el sentido del olfato o el gusto) que desencadenan pruebas de coronavirus.

Tim Spector, líder del estudio y profesor de epidemiología genética en el King's College de Londres, concluye que con los datos de 250 000 niños, aquellos con una prueba de frotis positiva tienen una gama de síntomas diferente a la de los adultos. La tos y la dificultad para respirar son mucho menos frecuentes y los problemas gastrointestinales, especialmente la pérdida de apetito, más frecuentes. La fiebre sigue siendo una característica, como en los adultos. El estudio confirmó la necesidad de agregar una gama más amplia de síntomas a los enumerados para el covid-19, ya que alrededor del 50% de los niños no presentaban los tres principales síntomas del adulto (temperatura alta, tos y pérdida o cambio del sentido del olfato o del gusto) y pueden presentar una amplia gama de síntomas no específicos, como malestar, pérdida de apetito, y erupción cutánea que afectó a uno de cada seis”. “La clave es que los padres mantengan a los niños en casa con estos signos inespecíficos hasta que se sientan mejor, hasta que las pruebas sean más rápidas y accesibles”.

Public health measures during the COVID-19 pandemic have potential to impact transmission of other respiratory viruses. We found 98.0% and 99.4% reductions in RSV and influenza detections respectively in Western Australian children through winter 2020; despite reopening of schools. Border closures have likely been important in limiting introductions from abroad.

We searched for studies that assessed the accuracy of chest imaging to diagnose COVID-19 disease. Studies could include people with either suspected or confirmed COVID-19, based on the results of an RT-PCR or other test. Studies could be of any design and take place anywhere.

We found 84 studies with 8279 people. Studies included either only people with confirmed COVID-19 diagnosis (71 studies, involving 6331 people) or both suspected and confirmed COVID-19 (13 studies, involving 1948 people). Infection was mainly confirmed using RT-PCR.

The majority of studies evaluated chest CT. We found studies from all over the world; 78 studies took place in Asia.

Accuracy of chest imaging for diagnosing COVID-19 in people with confirmed infection

On average, chest CT correctly identified infection in 93% of people with confirmed COVID-19 (65 studies, 5759 people). Chest X-ray correctly identified infection in 82% of people with confirmed COVID-19 (nine studies, 682 people). Lung ultrasound correctly identified infection in 100% of people with confirmed COVID-19 (2 studies, 32 people).

Accuracy of chest imaging for diagnosing COVID-19 in people with suspected or confirmed infection

On average, chest CT correctly identified infection in 86% of people who were infected with COVID-19 (13 studies, 2346 people). However, it incorrectly identified infection in 82% of people who were not infected with COVID-19. We did not find any studies that reported data on lung ultrasound.

The uncertainty resulting from the poor study quality and the heterogeneity of included studies limit our ability to confidently draw conclusions based on our results. Our findings indicate that chest CT is sensitive but not specific for the diagnosis of COVID-19 in suspected patients, meaning that CT may not be capable of differentiating SARS-CoV-2 infection from other causes of respiratory illness. This low specificity could also be the result of the poor sensitivity of the reference standard (RT-PCR), as CT could potentially be more sensitive than RT-PCR in some cases. Because of limited data, accuracy estimates of chest X-ray and ultrasound of the lungs for the diagnosis of COVID-19 should be carefully interpreted.

Future diagnostic accuracy studies should avoid cases-only studies and pre-define positive imaging findings. Planned updates of this review will aim to: increase precision around the accuracy estimates for CT (ideally with low risk of bias studies); obtain further data to inform accuracy of chest X rays and ultrasound; and continue to search for studies that fulfil secondary objectives to inform the utility of imaging along different diagnostic pathways.

Evidence is current to 25th May 2017. We included 11 trials with a total of 3555 participants evaluating prescribing strategies for people with respiratory tract infections. Ten of these studies compared strategies of delaying antibiotics with immediate antibiotics. Four studies compared delayed antibiotics with no antibiotics. Of the 11 studies, five included only children (1173 participants), two included only adults (594 participants), and four included children and adults (1761 participants). The studies investigated a variety of respiratory tract infections. One study involving 405 participants was new for this update

For many clinical outcomes, there were no differences between prescribing strategies. Symptoms for acute otitis media and sore throat were modestly improved by immediate antibiotics compared with delayed antibiotics. There were no differences in complication rates. Delaying prescribing did not result in significantly different levels of patient satisfaction compared with immediate provision of antibiotics (86% versus 91%) (moderate quality evidence). However, delay was favoured over no antibiotics (87% versus 82%). Delayed antibiotics achieved lower rates of antibiotic use compared to immediate antibiotics (31% versus 93%) (moderate quality evidence). The strategy of no antibiotics further reduced antibiotic use compared to delaying prescription for antibiotics (14% versus 28%).

Delayed antibiotics for people with acute respiratory infection reduced antibiotic use compared to immediate antibiotics, but was not shown to be different to no antibiotics in terms of symptom control and disease complications. Where clinicians feel it is safe not to prescribe antibiotics immediately for people with respiratory infections, no antibiotics with advice to return if symptoms do not resolve is likely to result in the least antibiotic use while maintaining similar patient satisfaction and clinical outcomes to delaying prescription of antibiotics. Where clinicians are not confident in using a no antibiotic strategy, a delayed antibiotics strategy may be an acceptable compromise in place of immediate prescribing to significantly reduce unnecessary antibiotic use for RTIs, and thereby reduce antibiotic resistance, while maintaining patient safety and satisfaction levels.

Introduction Invasive meningococcal disease (IMD) is a rare condition with a high case fatality rate. While most patients suffer from one single episode in life, there is anecdotal evidence for recurrent infection.

Aim, The German National Reference Laboratory for Meningococci and Haemophilus influenzae (NRZMHi) analysed IMD cases from 2002 to 2018 to retrospectively quantify the risk of recurrent infection.

Methods. Recurrent IMD was defined as detection of Neisseria meningitidis in a sample of the same patient more than 30 days after the first episode of IMD.

Results Among 5,854 patients with a median observation period of 9.4 years, 14 suffered a second IMD episode and one patient a third one. The risk of a recurrent IMD was 29.4 per 100,000 person-years for survivors of the first episode. Rare serogroups (Y, W, E and Z) were more common in patients with recurrent IMD (p < 0.0001).

Discussion Patients surviving IMD were at least at a 50-fold risk of another IMD episode compared with the general population. The study most likely underestimated the risk of recurrent infection. Increased risk may be due to undiagnosed complement deficiencies. The high risk of re-infection argues for vaccination of patients who have survived IMD.

Congenital cytomegalovirus (cCMV) infection is the most common congenital viral infection and is the leading non-genetic cause of sensorineural hearing loss (SNLH) and an important cause of neurodevelopmental disabilities. The risk of intrauterine transmission is highest when primary infection occurs during pregnancy, with a higher rate of vertical transmission in mothers with older gestational age at infection, while the risk of adverse fetal effects significantly increases if fetal infection occurs during the first half of pregnancy. Despite its prevalence and morbidity among the neonatal population, there is not yet a standardized diagnostic test and therapeutic approach for cCMV infection. This narrative review aims to explore the latest developments in the diagnosis and treatment of cCMV infection. Literature analysis shows that preventive interventions other than behavioral measures during pregnancy are still lacking, although many clinical trials are currently ongoing to formulate a vaccination for women before pregnancy. Currently, we recommend using a PCR assay in blood, urine, and saliva in neonates with suspected cCMV infection. At present, there is no evidence of the benefit of antiviral therapy in asymptomatic infants. In the case of symptomatic cCMV, we actually recommend treatment with oral valganciclovir for a duration of 12 months. The effectiveness and tolerability of this therapy option have proven effective for hearing and neurodevelopmental long-term outcomes. Valganciclovir is reserved for congenitally-infected neonates with the symptomatic disease at birth, such as microcephaly, intracranial calcifications, abnormal cerebrospinal fluid index, chorioretinitis, or sensorineural hearing loss. Treatment with antiviral drugs is not routinely recommended for neonates with the mildly symptomatic disease at birth, for neonates under 32 weeks of gestational age, or for infants more than 30 days old because of insufficient evidence from studies. However, since these populations represent the vast majority of neonates and infants with cCMV infection and they are at risk of developing late-onset sequelae, a biomarker able to predict long-term sequelae should also be found to justify starting treatment and reducing the burden of CMV-related complications.

The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the well-being of children as a result of the widespread closure of schools. Throughout the summer, states have allowed the reopening of many businesses including restaurants, bars, retail locations, and amusement parks, including in locations experiencing surges in cases. Meanwhile, many school districts across the country began the fall semester in a partially or completely virtual fashion.

A growing body of evidence suggests a return to in-person learning can be accomplished safely, particularly for young children. Throughout the pandemic, childcare centers serving school-age children have successfully operated without significant outbreaks,1 even in high prevalence areas.2 In other countries where school has been in session, reports of cases of SARS-CoV-2 infection in schools generally show little to no secondary spread.3 Initial evidence suggests that the school environment does not contribute to community transmission of the novel coronavirus in the same way that it does for other respiratory viruses such as influenza.4 When outbreaks have occurred among school-age children, these have generally reflected a lack of adherence to recommended mitigation strategies.5

National organizations have issued guidance on how to safely return to school in the fall of 2020. Key recommended elements include daily symptom screening, physical distancing, cohorting, masking for students and staff, enhanced hand hygiene, directed environmental cleaning, increased ventilation, and careful tracking of student locations and contacts to enable contact identification when an infectious case is identified. The ability of individual schools to implement these strategies is likely to vary based on school size, age of students, financial resources, community support, and access to consultation with health experts.

To provide support to our local school community, a group of pediatric infectious diseases experts and pediatric healthcare providers (MD/DO and nurse practitioners) collaborated to develop a series of algorithms addressing aspects of COVID-19 and schools (Figure and http://wupaarc.wustl.edu/COVID-19-and-Children/Algorithms-for-Clinicians-and-Schools). Included in the algorithms are a symptom decision tree for parents, students, and administrators, an algorithm for school nurses, protocols to assist in school contact tracing, and detailed algorithms for healthcare providers on how to approach students with SARS-CoV-2 symptoms or exposure. The goal of these algorithms is to provide practical guidance for children experiencing symptoms and the algorithms represent a balancing act between excluding potentially infectious students from the school environment and the educational disruption experienced by students who are kept out of the classroom.

We found 22 studies; 17 assessed people (cohort studies) and five were computer-generated models (modelling studies). Studies took place in USA, Europe, and Asia

The evidence base for the effectiveness of screening comes from two mathematical modelling studies and is limited by their assumptions. Low-certainty evidence suggests that screening at travel hubs may slightly slow the importation of infected cases. This review highlights the uncertainty and variation in accuracy of screening strategies. A high proportion of infected individuals may be missed and go on to infect others, and some healthy individuals may be falsely identified as positive, requiring confirmatory testing and potentially leading to the unnecessary isolation of these individuals. Further studies need to evaluate the utility of rapid laboratory tests, combined screening, and repeated screening. More research is also needed on reference standards with greater accuracy than RT-PCR.

Given the poor sensitivity of existing approaches, our findings point to the need for greater emphasis on other ways that may prevent transmission such as face coverings, physical distancing, quarantine, and adequate personal protective equipment for frontline workers.

We examined the usefulness of three widely available blood tests (procalcitonin, C-reactive protein, erythrocyte sedimentation rate) in differentiating upper from lower urinary tract disease. We found 34 relevant studies of which 24 provided data for our primary outcome. Twelve studies (1000 children) provided data for the procalcitonin test; 16 studies (1895 children) provided data for the C-reactive protein test, and 8 studies (1910 children) provided data for the erythrocyte sedimentation rate test.

We found all three tests to be sensitive (summary sensitivity values ranged from 81% to 93%), but not very specific (summary specificity values ranged from 37% to 76%).

Conclusions

None of the tests were accurate enough to allow clinicians to confidently differentiate upper from lower urinary tract disease.

The ESR test does not appear to be sufficiently accurate to be helpful in differentiating children with cystitis from children with pyelonephritis. A low CRP value (< 20 mg/L) appears to be somewhat useful in ruling out pyelonephritis (decreasing the probability of pyelonephritis to < 20%), but unexplained heterogeneity in the data prevents us from making recommendations at this time. The procalcitonin test seems better suited for ruling in pyelonephritis, but the limited number of studies and the marked heterogeneity between studies prevents us from reaching definitive conclusions. Thus, at present, we do not find any compelling evidence to recommend the routine use of any of these tests in clinical practice.

Introducción: el estudio de la relación entre las parasitosis intestinales y las enfermedades atópicas, como el asma o la rinoconjuntivitis, ha arrojado resultados contradictorios. El objetivo de este estudio fue evaluar la relación existente entre la parasitosis intestinal y la prevalencia de las enfermedades atópicas.

Material y métodos: se realizó un estudio observacional, transversal de campo, en niños mayores de 2 años, cuyos padres contestaron los cuestionarios para investigación de prevalencia de enfermedades atópicas. A todos los niños seleccionados les fueron realizados exámenes seriados de heces y pruebas alérgicas cutáneas. El análisis estadístico se realizó por medio de la prueba de χ2, asimismo se calcularon las razones de riesgo (odds ratio [OR]) y los intervalos de confianza del 95% (IC 95). Se consideró de significancia estadística cuando p <0,05.

Resultados: fueron evaluados 185 niños, la edad fue 6,82 ± 2,69 años, el 52% fueron masculinos, el 94% se ubicaron entre los estratos sociales III/IV. La prevalencia de cualquier enfermedad atópica fue del 41% y la reactividad en piel del 43%, la detección de cualquier parásito se hizo en el 47% de todos los niños. Se encontró relación con significación entre el cuestionario ISAAC y la prueba cutánea (p = 0,000). No se encontró asociación entre prueba cutánea y parasitosis intestinal (p = 1,29), así como tampoco entre los resultados de ISAAC y parasitosis (p = 0,447).

Conclusión: el estudio permitió considerar que la condición alérgica no guarda relación con el diagnóstico de la parasitosis.

Casos clínicos

La fascitis necrotizante (FN) es un cuadro muy grave, causado por una infección bacteriana de la piel y tejidos blandos subcutáneos, cuya evolución es hacia la destrucción y necrosis de los tejidos en un corto espacio de tiempo. Hasta en un tercio de los casos llega a ocasionar un shock séptico con fallo multiorgánico, que eleva la mortalidad de este cuadro hasta el 25%. Dependiendo del agente causante la FN se clasifica en polimicrobiana (tipo I) y estreptocócica (tipo II). Los principales microorganismos implicados son Streptococcus beta-hemolítico del grupo A, y con menor frecuencia Staphylococcus aureus [1]. Presentamos el caso de un paciente de 12 años de edad...

·Peripheral Facial Nerve Palsy in Children With Enterovirus Infection Papan, Cihan; Keeren, Kathrin; Schroten, Horst; Tenenbaum, Tobias Less The Pediatric Infectious Disease Journal. 39(10):e326-e329, October 2020.

Enteroviruses are one of the leading causes of central nervous system infections, but their causative role in peripheral facial nerve palsy is unresolved. We used data from a large national Enterovirus Surveillance Database to identify cases of facial nerve palsy, showing a rate of 3.8% of patients with facial nerve palsy to have enterovirus infection.

Clinical bottom lines

  • Otherwise well, healthy children with palpable cervical lymph nodes do not require investigation with neck ultrasound (Grade B).
  • Ultrasound should not be used as a screening tool to ‘exclude malignancy’ (Grade B).
  • Children with palpable cervical lymph nodes greater than 2 cm persisting for more than 6 weeks, or supraclavicular nodes, warrant referral for specialist assessment. An ultrasound at this stage may help direct further investigation and management (Grade B).

Clinical scenario

You are the speciality registrar seeing a 6-year-old girl in clinic who was referred by her general practitioner (GP) with a 4-week history of ‘persistent lymphadenopathy’. She is otherwise well with no fever, recent history of illness or infection. There is no medical history of note. There are palpable cervical lymph nodes on examination. There is no hepatosplenomegaly. The GP has also referred the patient for an urgent neck ultrasound in which the request states ‘persistent lymphadenopathy, otherwise well, exclude malignancy’.

Structured clinical question

Do otherwise well, healthy children (patient) with palpable cervical lymph nodes (comparison) require investigation with neck ultrasound (investigation)?

A 6-year-old girl was seen for a persistent facial rash. The rash spontaneously erupted above her upper lip as a cluster of papules and pustules that spread to the nasolabial folds and bilateral lower eyelids over the course of 3 weeks. She was systemically well and presumed to have impetigo. However, she did not improve with oral cephalexin or clindamycin. When seen by us, the clinical characteristics of the rash led us to a diagnosis of periorificial dermatitis.

This acneiform eruption is more often seen in adults but is not uncommon in young children, with a mean age of presentation of 6.6 years.1 The incidence is unknown. There is a slight female preponderance (58%).2 The diagnosis is made clinically based on the presence of erythematous to flesh-coloured papules and sometimes pustules around the mouth, nose and eyes. In general, the vermillion border of the lips is spared,1–3 but it may become involved in severe cases (figure 1).4 Comedones are also absent.1 3 The rash is often misdiagnosed as impetigo, acne vulgaris, contact dermatitis, atopic dermatitis, seborrheic dermatitis, dermatophyte infection or angiofibromas.3 Swabs and skin scrapings may help exclude bacterial and fungal infection.3 Use of corticosteroids prior to onset, whether topical, nasal or inhaled, has been associated with 58%–72% of paediatric periorificial dermatitis.1 2 While topical corticosteroids can initially improve the rash, discontinuation frequently leads to a rebound eruption. Standard treatment is with topical metronidazole and/or oral macrolides.1–3 5 Resolution may take 4–8 weeks.5

El virus del herpes simple (VHS) produce una encefalitis necrotizante aguda, afectando típicamente al lóbulo temporal. La existencia de un fármaco antiviral específico, así como el uso de medicación adyuvante como la corticoterapia, han mejorado el pronóstico de las infecciones graves. El retraso en el inicio del tratamiento con aciclovir es un factor claramente relacionado con mala evolución, así como las pautas cortas de tratamiento que se han asociado con mayor riesgo de recidivas. Se presenta el caso de una lactante de 13 meses, diagnosticada de encefalitis herpética tras un cuadro de fiebre prolongada.

·SARS-CoV-2 Encephalitis in a 20-year old Healthy Female. Babar, Aneeqa; Lewandowski, Ula; Capin, Ivana; Khariton, Megan; Venkataraman, Akila; Okolo, Nwanneka; Sharma, Dolly Less The Pediatric Infectious Disease Journal. 39(10):e320-e321, October 2020.

We report a 20-year-old female with SARS-CoV-2 encephalitis who presented with 4 days of upper respiratory symptoms, fevers and sudden acute altered mental status. An extensive work up led to the most likely cause for the neurologic decompensation to be viewed as SARS-CoV-2 symptomology.

·Multisystem Inflammatory Syndrome Associated With COVID-19 With Neurologic Manifestations in a Child: A Brief Report. De Paulis, Milena; Oliveira, Danielle Bruna Leal; Vieira, Rodolfo P.; Pinto, Isabella Coutinho; Machado, Rafael Rahal Guaragna; Cavalcanti, Mariana Pauferro; Soares, Camila Pereira; de Araujo, Ananda Medeiros Pereira; Araujo, Danielle Bastos; Bachi, Andre Luis Lacerda; Leal, Fabyano Bruno; Dorlass, Erick Gustavo; Gilio, Alfredo Elias; Durigon, Edison Luiz; Barreira, Eliane Roseli Less

The Pediatric Infectious Disease Journal. 39(10):e321-e324, October 2020

Although first considered a benign infection, recent studies have disclosed severe and potentially lethal inflammatory manifestations of COVID-19 in children. We report the case of a 4-year-old child with a post-infectious multisystem inflammatory syndrome associated with COVID-19, with a Kawasaki-like shock and prominent neurologic features, for whom a cytokine storm and reduced brain-derived neurotrophic factor were well documented.

We report dengue virus (DENV) infection in two Dutch tourists who visited Département Var, southern France, in July and August 2020. As some autochthonous dengue cases have occurred in Europe in recent years, awareness among physicians and public health experts about possible intermittent presence of DENV in southern Europe is important to minimise delay in diagnosis and treatment. Quick diagnosis can lead to timely action to contain the spread of vector-borne diseases and minimise transmission.

El episodio hipotonía-hiporrespuesta (EHH) es un tipo muy inusual de efecto adverso después de la vacunación. Se ha observado con mayor frecuencia tras las vacunas de células enteras contra la tosferina. El EHH se caracteriza por el inicio repentino de hipotonía, hiporrespuesta y el cambio de color de la piel (palidez o cianosis) en las primeras 48 horas después de la administración de una vacuna en niños. Se ha descrito que los episodios pueden durar entre 6 y 30 minutos. Se desconoce la patogénesis. Aunque se ha clasificado dentro de las reacciones adversas graves, no se han demostrado efectos a largo plazo y no se contraindica la administración de una nueva dosis de la vacuna, si así está indicado para completar el calendario de vacunación del niño. Presentamos el caso de una lactante de 5 meses de edad que presentó un EHH tres horas después de la administración de una segunda dosis de la vacuna antimeningocócica B 4CMenB (Bexsero).

La hematuria es un motivo de consulta frecuente. Una adecuada historia clínica y exploración física permiten una aproximación diagnóstica inicial en la mayoría de los casos. Lo primero es reconocer y confirmar la hematuria, descartando otras circunstancias que pueden teñir falsamente la orina. El análisis del aspecto macroscópico de la orina es clave para determinar el origen glomerular o extraglomerular de la hematuria. Presentamos el caso de una niña con falsa hematuria por agente externo (lejía), efectuándose el diagnóstico a través de una exhaustiva historia clínica.

Un nuevo coronavirus llamado coronavirus 2 del síndrome respiratorio agudo severo (SARS-CoV-2), causante de una pandemia global, afecta a la población pediátrica con unas características clínicas diferentes a las de los adultos. Las lesiones dermatológicas acroisquémicas que se pueden asociar, se manifiestan más en pacientes jóvenes sin cuadro respiratorio. Se presentan tres casos clínicos con estudios analíticos, que incluyen determinación de anticuerpos neutralizantes por inmunocromatografía. En ninguno de los casos se ha podido demostrar la participación del SARS-CoV-2 como agente implicado. El término de "acroisquemia aguda en el niño en tiempos de COVID-19” parece ser el término más adecuado hasta tener un mayor conocimiento del cuadro.

El fallo hepático agudo es un cuadro grave y poco frecuente en Pediatría. Precisa un manejo multidisplinar. Aunque en la mitad de los casos no se llega a un diagnóstico etiológico definitivo, conviene conocer sus causas según los grupos de edad, debido a su implicación pronostica y terapéutica. Se reconocen principalmente causas infecciosas, tóxicas, metabólicas y autoinmunes. Dentro de las causas infecciosas, destacan los virus de la familia herpes y los virus hepatotropos; sin embargo, también se ha relacionado con virus respiratorios y en concreto con el virus de la gripe, en cuyo caso, el pronóstico es bueno. Presentamos el caso de una niña de cuatro años que debutó con cuadro de fallo hepático agudo secundario a infección por virus influenza A con una evolución muy favorable.

La artritis séptica presenta una incidencia anual de 4 casos/100 000 niños. Es más frecuente en los miembros inferiores y suele estar provocada por Staphylococcus aureus vía hemática, por lo que la cobertura antibiótica inicial está dirigida a cubrir al menos este patógeno. Sin embargo, en algunas situaciones, como tras la manipulación periodontal o enfermedad dentaria, debemos pensar en microorganimos procedentes de la flora microbiana orofaríngea, como es Fusobacterium nucleatum, ya que el 50% de las cepas es resistente a penicilina y a algunas cefalosporinas, fármacos que forman parte del tratamiento antibiótico empírico de las infecciones osteoarticulares en la población pediátrica.

Para profundizar

OBJETIVO Revisar la evidencia disponible acerca de los riesgos infecciosos relacionados con los fármacos biológicos utilizados en las enfermedades inflamatorias de origen inmune. MATERIAL Y MÉTODOS Se seleccionaron los fármacos biológicos con indicación en enfermedades inflamatorias de origen inmune, que se dispensen desde las Unidades de Farmacia de Pacientes Externos del Servicio Navarro de Salud-Osasunbidea. Se consultaron las fichas técnicas de los medicamentos y se realizó una búsqueda en Pubmed revisando los artículos y guías más relevantes. RESULTADOS Y CONCLUSIONES El riesgo asociado a las terapias inmunosupresoras se deduce en muchas ocasiones de su mecanismo de acción y establecer una relación causal a veces es complicado. Realizar el cribado de tuberculosis se ha asociado a la reducción del riesgo de reactivación de la tuberculosis latente de hasta 7 veces y, por el momento, se recomienda mantener las recomendaciones basadas para las terapias anti-TNF-a para el resto de terapias biológicas. Aunque el herpes zoster es uno de los efectos adversos más frecuentes con las terapias anti-TNF-a, existe controversia respecto a la causalidad debido a que los pacientes con enfermedades inflamatorias autoinmunes presentan un mayor riesgo del mismo. Se recomienda realizar cribado de VHB y VHC. En pacientes con HBsAg negativo es recomendable administrar la vacuna previamente al inicio de la terapia biológica y los pacientes con HBsAg positivo deben recibir profilaxis. Las vacunas con microorganismos atenuados están contraindicadas durante el tratamiento biológico y se recomienda vacunar frente a la gripe y el neumococo a todos los pacientes que reciban estas terapias. Antes del inicio de la terapia se recomienda realizar cribado de VIH, descartar embarazo, y valorar otras patologías como insuficiencia cardíaca, citopenias, enfermedad pulmonar intersticial, enfermedad desmielinizante o enfermedad tumoral. PALABRAS CLAVE Fármacos biológicos, enfermedades inflamatorias, tuberculosis, riesgos infecciosos, vacunación.

  • Infant Respiratory Syncytial Virus Bronchiolitis and Subsequent Risk of Pneumonia, Otitis Media, and Antibiotic UtilizationClinical Infectious Diseases, Volume 71, Issue 1, 1 July 2020, Pages 211–214, https://doi.org/10.1093/cid/ciz1033

Infant respiratory syncytial virus (RSV) bronchiolitis in the first 6 months of life was associated with increased odds of pneumonia, otitis media, and antibiotic prescription fills in the second 6 months of life. These data suggest a potential value of future RSV vaccination programs on subsequent respiratory health.

Coronavirus disease 2019 (COVID-19) primarily affects adults and spares children, whereas very little is known about neonates. We tried to define the clinical characteristics, risk factors, laboratory, and imagining results of neonates with community-acquired COVID-19.

Methods: This prospective multicentered cohort study included 24 neonatal intensive care units around Turkey, wherein outpatient neonates with COVID-19 were registered in an online national database. Full-term and premature neonates diagnosed with COVID-19 were included in the study, whether hospitalized or followed up as ambulatory patients. Neonates without severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) via reverse transcriptase-polymerase chain reaction testing or whose mothers had been diagnosed with COVID-19 during pregnancy were excluded.

Results: Thirty-seven symptomatic neonates were included. The most frequent findings were fever, hypoxemia, and cough (49%, 41%, 27%, respectively). Oxygen administration (41%) and noninvasive ventilation (16%) were frequently required; however, mechanical ventilation (3%) was rarely needed. Median hospitalization was 11 days (1–35 days). One patient with Down syndrome and congenital cardiovascular disorders died in the study period. C-reactive protein (CRP) and prothrombin time (PT) levels were found to be higher in patients who needed supplemental oxygen (0.9 [0.1–8.6] vs. 5.8 [0.3–69.2] p = 0.002, 11.9 [10.1–17.2] vs. 15.2 [11.7–18.0] p = 0.01, respectively) or who were severe/critical (1.0 [0.01–8.6] vs. 4.5 [0.1–69.2] p = 0.01, 11.7 [10.1–13.9] vs. 15.0 [11.7–18.0] p = 0.001, respectively).

Conclusions: Symptomatic neonates with COVID-19 had high rates of respiratory support requirements. High CRP levels or a greater PT should alert the physician to more severe disease.

RESULTADOS: Hubo un total de 149 madres con infección por SARS-CoV-2 y 149 recién nacidos analizados (3 pares de gemelos; 3 mortinatos). El cuarenta por ciento de estas madres estaban asintomáticas. Aproximadamente el 15% de las madres sintomáticas requirió algún tipo de soporte respiratorio y el 8% requirió intubación. Se ingresaron en la UCI 18 recién nacidos (12%). Quince (10%) nacieron prematuros y 5 (3%) requirieron ventilación mecánica. Las madres sintomáticas tuvieron más partos prematuros (16% vs 3%, p = 0,02) y sus recién nacidos tenían más probabilidades de requerir cuidados intensivos (19% vs 2%, p = 0,001) que las madres asintomáticas. Un recién nacido dio positivo por SARS-CoV-2, que se consideró un caso de transmisión posnatal horizontal

CONCLUSIONES: Aunque no hubo evidencia clara de transmisión vertical de madres con SARS-CoV-2 a sus recién nacidos, sí observamos morbilidades perinatales tanto en madres como en recién nacidos. Las madres sintomáticas eran más propensas a experimentar un parto prematuro y sus recién nacidos a requerir cuidados intensivos.

The long-term prognosis of brain abscess is unclear.

Methods: Using nationwide, population-based medical registries, we included all individuals <20 years of age hospitalized with first-time diagnosis of brain abscess in Denmark from 1982 to 2016. A comparison cohort individually matched for age, sex and residence was identified, as were siblings of all study participants. Next, cumulative incidence curves of mortality and new-onset epilepsy were constructed, and Cox regression was used for analyses of hazard rate ratios (HRRs) with 95% confidence intervals.

Results: We identified 155 brain abscess patients and 1,550 population controls with median follow-up times of 15 years (interquartile range, 6–25) and 16 years (interquartile range, 11–26). Ear–nose–throat infections (22%) and congenital heart disease (13%) were the most common predisposing conditions for brain abscess. Overall mortality was 21/155 (14%) in brain abscess patients versus 20/1,550 (1%) in population controls. The corresponding HRRs were 150 (95% confidence interval: 19.8–1,116) after 1 year of observation, 24.6 (4.78–127) after 2–5 years and 0.66 (0.09–4.98) after 6–30 years. New-onset epilepsy occurred in 28% of 30-day brain abscess survivors versus 1% in population controls yielding a HRR of 29.6 (14.4–60.8) adjusted for previous head trauma, stroke and cancer. Analyses of sibling cohorts showed that family-related factors did not explain the observed increased risks of death or epilepsy among brain abscess patients.

Conclusions: Brain abscess is associated with increased risk of mortality for up to 5 years. New-onset epilepsy occurred in 28% of survivors and remained a risk for several years after infection.

The purpose of this study was to report the epidemiology, etiology, microbiologic profile and management of pediatric microbial keratitis in a quaternary and 3 tertiary ophthalmic referral centers across Sydney, New South Wales, Australia.

Methods: This is a retrospective cohort study of patients ≤ 18 years of age with a clinical diagnosis of microbial keratitis presenting between 1 January 2010 and 31 December 2016 identified from hospital coding and pathology databases. Data were extracted from the medical records. Epidemiology, predisposing factors, referral patterns, microbial profile and treatment outcomes were analyzed.

Results: Eighty eyes from 80 pediatric patients with microbial keratitis were included in the study (10% had bilateral disease). The mean age was 11 ± 5.3 years (range 0–18 years), and 44 were male (55%). Thirty-six percent of patients had ocular and 13.5% systemic comorbidities. The most common risk factor overall was contact lens wear in 26%, trauma (24%), and external lid and eye disease (20%). Overall, 74 organisms were identified, and of those, the most common isolates were Gram-positive organism. Antimicrobial resistance to common antibiotics was low across all isolates. Visual acuity following treatment was worse than 6/60 for 7 patients (11.3%%), 6/15–6/60 for 15 patients (24.2%) and better than 6/12 for 40 patients (64.5%). Preexisting corneal disease and delay of presentation were associated with worse visual prognosis. Serious complications were noted in 16 (21.3%) of patients.

Conclusions: Contact lens wear, trauma and existing ocular disease remain the most significant risk factors in the pediatric population. Preexisting corneal disease and delay in presentation were associated with poor visual acuity. The majority of patients have a good visual outcome although serious complications are not uncommon and may cause lifelong visual disability.

Bartonella henselae is the etiologic agent of cat-scratch disease, which affects the entire world population. Due to how poorly characterized the child population is, the objective was to describe the clinical behavior of this disease in children younger than 16 years of age.

Methods: This was a descriptive study with prospective follow-up of all children younger than 16 years with clinical and serologic diagnoses between 2013 and 2018.

Results: There were 142 patients; of these, 55.6% had localized disease, 34.5% disseminated with hepatosplenic involvement and 9.8% had atypical disease. The cases of atypical disease were prolonged febrile illness, Parinaud syndrome, subacute bacterial endocarditis/glomerulonephritis and aseptic meningitis. Cervical lymphadenopathy was the most frequent, followed by inguinal adenopathy. There were no differences between the type of manifestation and laboratory values except for a higher erythrocyte sedimentation rate tendency in patients with disseminated and/or atypical disease. The serologic titers throughout were distributed as follows: titer of 1/1024, 71.7%; titer of 1/512, 10.4% and titer of 1/256, 17.9%.

Conclusions: This is, to our knowledge, the largest series of cat-scratch disease published. We demonstrate that in our environment, the inguinal location is suggestive of this disease, the disseminated presentation, frequent, and that the titers are probably much higher than in other populations, which perhaps indicates the need to re-examine the cut-off point for positivity.

 Kawasaki disease (KD) is an uncommon condition occasionally reported after childhood vaccination. Admissions with a KD-compatible diagnosis identified from a national database in England were linked to immunisation records to investigate the risk after pneumococcal conjugate (PCV) or meningococcal B (MenB) vaccines. Both are given at 2/4/12 months of age but were introduced sequentially, allowing their effects to be separately assessed. A total of 553 linked admissions in 512 individuals were validated as KD. The relative incidence (RI) within 28 days of PCV doses 1 or 2 measured by the self-controlled case-series method was 0.62 (95% confidence interval (CI) 0.38–1.00) with a significantly decreased risk after dose 3 (RI 0.30 (95% CI 0.11–0.77)). For MenB vaccine, the RI after doses 1 or 2 was 1.03 (95% CI 0.51–2.05) and 0.64 (95% CI 0.08–5.26) after dose 3. This study shows no evidence of an increased risk of KD after either vaccine.

Sartoris, Giulia; Seddon, James A.; Rabie, Helena; Nel, Etienne D.; Losurdo, Giuseppe; Schaaf, H. Simon Less. The Pediatric Infectious Disease Journal. 39(10):914-919, October 2020.

Abdominal tuberculosis (TB) in children is poorly described and often poses a diagnostic challenge. We evaluated abdominal involvement in children presenting with bacteriologically confirmed TB.

Methods: We undertook a retrospective study at Tygerberg Hospital, Cape Town, from January 1, 2014, through December 31, 2018, of all children (<13 years) diagnosed with bacteriologically confirmed TB, in whom abdominal involvement was found. Demographic and clinical data were collected through folder review, laboratory records and imaging reports.

Results: Of 966 children with bacteriologically confirmed TB, 111 (11.5%) had abdominal involvement; 16 (14.4%) were excluded from further analysis because of lack of clinical data. The median age of the remaining 95 children was 43 months (interquartile range 20–94); 26 (27%) were HIV positive. The main gastrointestinal symptoms/signs were weight loss (84.2%), abdominal distention (54.7%), hepatomegaly (60.0%) and abdominal pain (26.3%). The main pathologic types were intra-abdominal lymph nodes (68.4%), solid organ involvement (54.7%), peritoneal type (23.2%) and intestinal type (10.5%). Splenic abscesses and solid organ involvement on ultrasonography were more common in HIV-positive children ( P < 0.001 and P = 0.008, respectively). Liver abscesses were associated with age less than 5 years ( P = 0.03), while abdominal lymphadenopathy on ultrasonography was more common in children older than 5 years ( P = 0.038). Abdominal specimens were collected in an attempt to identify Mycobacterium tuberculosis in 15 of 95 (15.8%) patients and were positive in 13 of 15 (86.7%).

Conclusions: Over 10% of children with confirmed TB had abdominal involvement. Abdominal TB should be considered in any pediatric TB case with abdominal symptoms, and ultrasonography should be the radiologic study of choice.

RESULTADOS: Se identificaron un total de 3371 niños menores de 5 años; la mayoría nació en países con alta incidencia de TB (> 150 casos por 100 000). La mitad recibió IGRA (n = 1878; 56%), una cuarta parte recibió TST (n = 811; 24%); El 1,4% de los niños fueron positivos para IGRA (n = 26) y el 13% fueron positivos para TST (n = 106). Veintidós resultados de IGRA fueron indeterminados (1,2%). Dieciséis niños tuvieron ambas pruebas; 9 fueron discrepantes (PT positiva con IGRA negativa). No se identificaron casos de tuberculosis durante 10 797 años-persona de seguimiento.

CONCLUSIONES: La positividad de IGRA fue menor que la de TST en niños menores de 5 años de alto riesgo. A pesar de menos diagnósticos de ITBL en la población sometida a prueba IGRA, no se identificaron casos de enfermedad de TB entre los niños que dieron negativo en la prueba, lo que sugiere que IGRA es una herramienta valiosa para identificar ITBL en esta población.

·Ebola Leggiadro, Robert J. Less . The Pediatric Infectious Disease Journal. 39(10):882, October 2020.

Background, Prescribing of systemic antibiotics in general and of cephalosporins in particular in German paediatric outpatients has previously been reported to be higher than in other European countries.

Aim Our objective was to assess recent trends in antibiotic prescribing in German children.

Methods, This study was conducted as consecutive annual cross-sectional analyses and included all children aged 0–14 years (n = 9,389,183 in 2018) covered by statutory health insurance in Germany. Annual antibiotic prescription rates from 2010 to 2018 were calculated for the age groups 0–1, 2–5, 6–9 and 10–14 years. Poisson regression was used to estimate trends of prescription rates by age group and antibiotic subgroup.

Results, Overall, the age-standardised antibiotic prescription rate decreased significantly by 43% from 746 prescriptions per 1,000 persons in 2010 to 428 per 1,000 in 2018 (p < 0.001). Reductions were most pronounced in the age groups 0–1 year (−50%) and 2–5 years (−44%). The age group 2–5 years exhibited the highest prescription rate with 683 per 1,000 in 2018 (0–1 year: 320/1,000; 6–9 years: 417/1,000; 10–14 years: 273/1,000). Cephalosporins (second and third generation) accounted for 32% of prescribed antibiotics.

Conclusions, Marked reductions in antibiotic prescribing during the last decade indicate a change towards more judicious paediatric prescribing habits. Compared with other European countries, however, prescribing of second- and third-generation cephalosporins remains high in Germany, suggesting frequent first-line use of these substances for common respiratory infections. Considerable regional variations underline the need for regionally targeted interventions.

·Impacts of Primary Care Physician System on Healthcare Utilization and Antibiotic Prescription: Difference-in-Differences and Causal Mediation Analyses. Okubo, Yusuke; Michihata, Nobuaki; Uda, Kazuhiro; Kinoshita, Noriko; Horikoshi, Yuho; Miyairi, Isao Less The Pediatric Infectious Disease Journal. 39(10):937-942, October 2020.

The overutilization of healthcare and overuse/misuse of antibiotics in Japan are responsible for the increase in healthcare expenditure and the development of antimicrobial resistance. The Japanese government started paying incentives to medical facilities for primary care physician registrations, but the impact of this new policy is still unclear.

Methods: We conducted a retrospective cohort study for all pediatric outpatients from April 2015 to December 2016 in Japan, targeting 1.4 million children under 2 years of age. We investigated the effects of primary care physician registration on physician visits, total antibiotic use and admission rates using difference-in-differences (DID) and causal mediation analyses.

Results: DID analyses showed that primary care registration policy contributed to increases in total physician visits, total and broad-spectrum antibiotic use and radiologic study utilization, but reduced out-of-hour visits and did not affect hospitalization rates. Similar results were obtained when we adjusted for and matched on potential confounders. Causal mediation analyses found that the greatest pathway was controlled by direct effects of 53.2 DOTs per 1000 person-months (95% CI: 29.1–77.2), indicating that the effect of new health policy that did not mediate increased outpatient visits mostly contributed to the excess use of antibiotics.

Conclusions: The health policy further increased antibiotic use. On April 2018, a new health policy of paying incentives for not prescribing antibiotics to children with respiratory infection or gastroenteritis was initiated. Further studies are needed whether this new health policy can mitigate the overutilization of healthcare and antibiotic use.

Pregunta clínica: ¿Cuál es el papel de las intervenciones farmacológicas en el tratamiento y la prevención del covid-19?:

Esta guía fue desarrollada por la OMS y la Fundación de Ecosistemas de Evidencia MAGIC (MAGIC), con el apoyo de The BMJ . Está impulsado por una necesidad urgente de colaboración global para brindar una guía confiable y viva, informando rápidamente de las políticas y prácticas en todo el mundo durante un brote de una enfermedad infecciosa emergente, como esta pandemia de covid-19. La OMS se ha asociado con MAGIC por su apoyo metodológico en el desarrollo y difusión de guías de vida para los tratamientos farmacológicos del covid-19, en forma de recomendaciones rápidas para proporcionar a los pacientes, médicos y responsables de la formulación de políticas información actualizada, basada en evidencia y orientación fácil de usar.

Esta es una pauta viva, por lo que las recomendaciones incluidas aquí se actualizarán y se agregarán nuevas recomendaciones sobre otras terapias para covid-19. La infografía proporciona un resumen de las recomendaciones y la evidencia de apoyo e incluye enlaces a MAGIC app para obtener más detalles sobre la evidencia y el fundamento de la recomendación, así como ayudas para la toma de decisiones del paciente. 

El panel hizo una recomendación fuerte para el uso de corticosteroides en covid-19 grave y crítico porque existe un menor riesgo de muerte entre las personas tratadas con corticosteroides sistémicos (evidencia de certeza moderada), y creen que todos o casi todos los pacientes con covid-19 grave y crítico plenamente informados elegirían este tratamiento. Por el contrario, el panel concluyó que los pacientes con covid-19 no grave rechazarían este tratamiento porque es poco probable que se beneficien y puedan resultar perjudicados. Además, teniendo en cuenta tanto la salud pública como la perspectiva del paciente, el panel advirtió que el uso indiscriminado de cualquier terapia para el covid-19 podría agotar rápidamente los recursos globales y privar a los pacientes que podrían beneficiarse más de ella como una terapia que podría salvar vidas.

·Epidemiology of Hand, Foot, and Mouth Disease Before and After the Introduction of Enterovirus 71 Vaccines in Chengdu, China, 2009–2018Han, Yutong; Chen, Zhenhua; Zheng, Ke; Li, Xianzhi; Kong, Jinwang; Duan, Xiaoxia; Xiao, Xiong; Guo, Bing; Luan, Rongsheng; Long, Lu Less . The Pediatric Infectious Disease Journal. 39(10):969-978, October 2020.

Hand, foot, and mouth disease (HFMD) has posed a serious threat to children’s health. Three inactivated monovalent enterovirus 71 (EV71) vaccines are proved to be highly efficacious in phase III clinical trials and are now available in China.

Methods: We analyzed the citywide surveillance data on HFMD cases in Chengdu during 2009–2018, and estimated cumulative first-dose EV71 vaccination coverage among children eligible to EV71 vaccination after August 2016 in Chengdu. Time series susceptible-infected-recovered model was developed to analyze basic reproduction number and herd immunity threshold of HFMD. Overall and serotype-specific HFMD incidences and severity risks were compared before and after the EV71 vaccination.

Results: Among 3 laboratory-identified serotype categories, i.e. EV71, coxsackievirus A16 (CV-A16), and other enteroviruses, the major serotype attributed to HFMD has been changing across years. The cumulative first-dose EV71 vaccination coverage rate was estimated as 60.8% during the study period in Chengdu. By contrast, herd immunity threshold for EV71-related HFMD was 94.0%. After introduction of EV71 vaccines, the overall incidence of HFMD increased 60.8%, mainly driven by 173.7% and 11.8% increased in HFMD caused by other enteroviruses and CV-A16, respectively, which offset a significant reduction in the incidence of HFMD caused by EV71. The overall case-severity risk decreased from 1.4% to 0.3%, with significantly declined presented in all serotype categories.

Conclusions: The incidence and severity of EV71-related HFMD decreased following implementation of EV71 vaccination. Developing multivalent vaccines and strengthening laboratory-based surveillance could further decline burden of HFMD.

Background: Rotavirus is a major cause of severe gastroenteritis in children worldwide. The disease burden has been substantially reduced in countries where rotavirus vaccines are used. Given the risk of vaccine-induced intussusception, the benefit–risk balance of rotavirus vaccination has been assessed in several countries, however mostly without considering indirect protection effects.

Aim: We performed a benefit–risk analysis of rotavirus vaccination accounting for indirect protection in France among the 2018 population of children under the age of 5 years.

Methods: To incorporate indirect protection effects in the benefit formula, we adopted a pseudo-vaccine approach involving mathematical approximation and used a simulation design to provide uncertainty intervals. We derived background incidence distributions from quasi-exhaustive health claim data. We examined different coverage levels and assumptions regarding the waning effects and intussusception case fatality rate.

Results: With the current vaccination coverage of < 10%, the indirect effectiveness was estimated at 6.4% (+/− 0.4). For each hospitalisation for intussusception, 277.0 (95% uncertainty interval: (165.0–462.1)) hospitalisations for rotavirus gastroenteritis were prevented. Should 90% of infants be vaccinated, indirect effectiveness would reach 57.9% (+/− 3.7) and the benefit–risk ratio would be 192.4 (95% uncertainty interval: 116.4–321.3). At a coverage level of 50%, indirect protection accounted for 27% of the prevented rotavirus gastroenteritis cases. The balance remained in favour of the vaccine even in a scenario with a high assumption for intussusception case fatality.

Conclusions: These findings contribute to a better assessment of the rotavirus vaccine benefit–risk balance

Human cases of West Nile virus (WNV) infection are recorded since 2010 in Greece, with seasonal outbreaks occurring almost annually. Enhanced surveillance has been implemented since 2010, to promptly characterise cases’ temporal and geographical distribution and inform authorities for implementation of appropriate measures (mosquito control, health education, blood safety).

Aim, We describe the epidemiology of WNV human infections in Greece focusing on the 2018 season.

Methods, The National Public Health Organization advised physicians to test all suspect WNV infection cases and refer samples to reference laboratories. Laboratories notified diagnosed cases on a daily basis. Treating physicians, patients, and infected blood donors were interviewed within 48 hours after diagnosis and the probable infection location was identified. Hospitalised cases were followed up until discharge.

Results, A total of 317 autochthonous WNV infection cases were diagnosed in 2018. Among them, 243 cases had neuroinvasive disease (WNND), representing a 23% increase of WNND cases compared with 2010, the previous most intense season. There were 51 deaths. Cases started occurring from week 22, earlier than usual. Both rural and urban areas were affected, with 86 (26% of the total) municipalities belonging to seven (54% of the total) regions recording cases. Two major epicentres were identified in Attica and Central Macedonia regions.

Conclusions, The largest number of human cases of WNV infection ever recorded in Greece occurred in 2018, with a wide geographical distribution, suggesting intense virus circulation. Enhanced surveillance is vital for the early detection of human cases and the prompt implementation of response measures.

Introducción: durante la pandemia de COVID-19, el uso de equipos y dispositivos de protección por parte de los profesionales es fundamental para evitar la transmisión de la infección en el colectivo de sanitarios.

Material y métodos: el Grupo Laboral-Profesional de la Asociación Española de Pediatría de Atención Primaria (AEPap) ha realizado una encuesta a los vocales autonómicos de la AEPap para conocer la disponibilidad que han tenido los pediatras de Atención Primaria (PAP) de sistemas de protección frente a la enfermedad, y las pruebas diagnósticas realizadas para el diagnóstico de los contagios de los PAP.

Resultados: en marzo de 2020, solo en el 32% de las comunidades autónomas (CC. AA.), los pediatras tenían sistemas de protección adecuados. En abril ascendió al 70%. En todas las CC. AA. se han registrado casos de PAP enfermos, aunque es difícil cuantificar el número de afectados. De las que tenemos datos, sumando el número de pediatras enfermos conocido, más test de reacción en cadena de la polimerasa (PCR) positivo, los que han estado en aislamiento y los ingresados, la cifra asciende al 7,65% de la cifra total de PAP. Los test rápidos serológicos o PCR o ambos se han realizado en seis comunidades los últimos días de abril y en otras seis los primeros días de mayo. Entre las CC. AA. de las que hay información, Aragón es la única comunidad en la que no se ha realizado test. Se ha correlacionado la disponibilidad de los sistemas de protección y el gasto sanitario.

Conclusiones: los sistemas de protección han sido insuficientes. Las CC. AA. con mayor gasto sanitario han contado más precozmente con sistemas de protección adecuados. Han resultado infectados PAP en todas las comunidades autónomas, especialmente en Madrid, Castilla y León y Comunidad Valenciana. La detección de profesionales afectos por la infección ha sido tardía.

CONCLUSIONES:  Entre los niños que están hospitalizados por COVID-19, la mayoría son menores de 60 días o mayores de 12 años. Los niños pueden tener una infección grave que requiera cuidados intensivos. El curso clínico de los pacientes inmunodeprimidos no fue más grave que el de otros niños. El recuento elevado de glóbulos blancos y el nivel de proteína C reactiva se asocian con una mayor gravedad de la enfermedad.

Resumen: Esta declaración actualiza las recomendaciones de la Academia Estadounidense de Pediatría para el uso rutinario de la vacuna contra la influenza y los medicamentos antivirales en la prevención y el tratamiento de la influenza en niños durante la temporada 2020-2021.

La Academia Estadounidense de Pediatría (AAP) recomienda la vacunación rutinaria contra la influenza de todos los niños sin contraindicaciones médicas, a partir de los 6 meses de edad. La vacunación contra la influenza es una intervención importante para proteger a las poblaciones vulnerables y reducir la carga de enfermedades respiratorias durante la pandemia del síndrome respiratorio agudo severo-coronavirus 2 (SARS-CoV-2). Se puede administrar cualquier vacuna autorizada, recomendada y apropiada para la edad, sin preferencia por un producto o formulación sobre otro.

Se recomienda el tratamiento antiviral de la influenza con cualquier medicamento antiviral contra la influenza autorizado, recomendado y apropiado para la edad para los niños con influenza presunta o confirmada que están hospitalizados, tienen una enfermedad grave o progresiva o padecen afecciones subyacentes que aumentan el riesgo de complicaciones de la influenza. Se puede considerar el tratamiento antiviral para cualquier paciente ambulatorio sintomático previamente sano que no tenga un alto riesgo de complicaciones de la influenza en el que se confirme o sospeche un diagnóstico de influenza, si el tratamiento puede iniciarse dentro de las 48 horas posteriores al inicio de la enfermedad, y para los niños cuyos hermanos o contactos familiares son menores de 6 meses o tienen una condición de alto riesgo que los predispone a las complicaciones de la influenza.

Objective To characterise the clinical features of children and young people admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK and explore factors associated with admission to critical care, mortality, and development of multisystem inflammatory syndrome in children and adolescents temporarily related to coronavirus disease 2019 (covid-19) (MIS-C).

Design Prospective observational cohort study with rapid data gathering and near real time analysis.

Setting 260 hospitals in England, Wales, and Scotland between 17 January and 3 July 2020, with a minimum follow-up time of two weeks (to 17 July 2020).

Participants 651 children and young people aged less than 19 years admitted to 138 hospitals and enrolled into the International Severe Acute Respiratory and emergency Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK study with laboratory confirmed SARS-CoV-2.

Main outcome measures Admission to critical care (high dependency or intensive care), in-hospital mortality, or meeting the WHO preliminary case definition for MIS-C.

Results Median age was 4.6 (interquartile range 0.3-13.7) years, 35% (225/651) were under 12 months old, and 56% (367/650) were male. 57% (330/576) were white, 12% (67/576) South Asian, and 10% (56/576) black. 42% (276/651) had at least one recorded comorbidity. A systemic mucocutaneous-enteric cluster of symptoms was identified, which encompassed the symptoms for the WHO MIS-C criteria. 18% (116/632) of children were admitted to critical care. On multivariable analysis, this was associated with age under 1 month (odds ratio 3.21, 95% confidence interval 1.36 to 7.66; P=0.008), age 10-14 years (3.23, 1.55 to 6.99; P=0.002), and black ethnicity (2.82, 1.41 to 5.57; P=0.003). Six (1%) of 627 patients died in hospital, all of whom had profound comorbidity. 11% (52/456) met the WHO MIS-C criteria, with the first patient developing symptoms in mid-March. Children meeting MIS-C criteria were older (median age 10.7 (8.3-14.1) v 1.6 (0.2-12.9) years; P<0.001) and more likely to be of non-white ethnicity (64% (29/45) v 42% (148/355); P=0.004). Children with MIS-C were five times more likely to be admitted to critical care (73% (38/52) v 15% (62/404); P<0.001). In addition to the WHO criteria, children with MIS-C were more likely to present with fatigue (51% (24/47) v 28% (86/302); P=0.004), headache (34% (16/47) v 10% (26/263); P<0.001), myalgia (34% (15/44) v 8% (21/270); P<0.001), sore throat (30% (14/47) v (12% (34/284); P=0.003), and lymphadenopathy (20% (9/46) v 3% (10/318); P<0.001) and to have a platelet count of less than 150 × 109/L (32% (16/50) v 11% (38/348); P<0.001) than children who did not have MIS-C. No deaths occurred in the MIS-C group.

Conclusions Children and young people have less severe acute covid-19 than adults. A systemic mucocutaneous-enteric symptom cluster was also identified in acute cases that shares features with MIS-C. This study provides additional evidence for refining the WHO MIS-C preliminary case definition. Children meeting the MIS-C criteria have different demographic and clinical features depending on whether they have acute SARS-CoV-2 infection (polymerase chain reaction positive) or are post-acute (antibody positive)

·Gastrointestinal Symptoms in Severe COVID-19 Children. Giacomet, Vania; Barcellini, Lucia; Stracuzzi, Marta; Longoni, Emma; Folgori, Laura; Leone, Alessandro; Zuccotti, Gian Vincenzo; on behalf of COVID-19 Pediatric network Less

The Pediatric Infectious Disease Journal. 39(10):e317-e320, October 2020.

There are growing evidence of clinical manifestations other than acute respiratory syndrome in severe acute respiratory syndrome associated with coronavirus 2-infected children. In our multicenter retrospective analysis, we observed among 127 severe acute respiratory syndrome associated with coronavirus 2 positive children that the presence of gastrointestinal symptoms was more frequently associated with severe and critical phenotype ( P = 0.029). Moreover, having gastrointestinal symptoms was more frequently reported in patients who developed cardiac impairment.

Frymoyer et al report the second, sustainability phase of a quality improvement initiative that was begun 5 years earlier at the Lucile Packard Children’s Hospital at Stanford. The initiative replaces the approach of screening laboratory tests and empiric antibiotic treatment for infants at perceived risk for early onset sepsis (EOS) with a solely clinical approach. Managing >20 000 neonates born at >35 weeks’ gestation over the intervention and sustainability phases, laboratory testing and ampicillin use declined substantially in phase 1, was sustained in phase 2, and the approach was safe. With the current extremely low incidence of EOS of 0.34 cases per 1000 live births at >35 weeks’ gestation (7 cases in the 5-year study period) it would be difficult to imagine re-instating the imperfect laboratory screening/empiric therapy approach. Weighing the downsides of screening tests and empiric therapy, the equally safe clinical approach should be considered superior.

Objectives To assess the impact of a 90-second animated video on parents' interest in receiving an antibiotic for their child.

Study design This pre-post test study enrolled English and Spanish speaking parents (n = 1051) of children ages 1-5 years presenting with acute respiratory tract infection symptoms. Before meeting with their provider, parents rated their interest in receiving an antibiotic for their child, answered 6 true/false antibiotic knowledge questions, viewed the video, and then rated their antibiotic interest again. Parents rated their interest in receiving an antibiotic using a visual analogue scale ranging from 0 to 100, with 0 being “I definitely do not want an antibiotic,” 50 “Neutral,” and 100 “I absolutely want an antibiotic.”

Results. Parents were 84% female, with a mean age of 32 ± 6.0, 26.0% had a high school education or less, 15% were black, and 19% were Hispanic. After watching the video, parents' average antibiotic interest ratings decreased by 10 points (mean, 57.0 ± 20 to M ± 21; P < .0001). Among parents with the highest initial antibiotic interest ratings (≥60), even greater decreases were observed (83.0 ± 12.0 to 63.4 ± 22; P < .0001) with more than one-half (52%) rating their interest in the low or neutral ranges after watching the video.

Conclusions A 90-second video can decrease parents' interest in receiving antibiotics, especially among those with higher baseline interest. This scalable intervention could be used in a variety of settings to reduce parents' interest in receiving antibiotics.

Objectives: To evaluate the results of the first 24 months of a postprescription review with feedback-based antimicrobial stewardship program in a European referral children's hospital. Study design. We performed a pre-post study comparing antimicrobial use between the control (2015-2016) and the intervention periods (2017-2018) expressed in days of therapy/100 days present. Quality of prescriptions was evaluated by quarterly cross-sectional point-prevalence surveys. Length of stay, readmission rates, in-hospital mortality rates, cost of systemic antimicrobial agents, and antimicrobial resistance rates were included as complementary outcomes.

Results. Total antimicrobial use and antibacterial use significantly decreased during the intervention period ( P = .002 and P = .001 respectively), and total antifungal use remained stable. A significant decline in parenteral antimicrobial use was also observed ( P < .001). In 8 quarterly point-prevalence surveys (938 prescriptions evaluated), the mean prevalence of use of any antimicrobial among inpatients was 39%. An increasing trend in the rate of optimal prescriptions was observed after the first point-prevalence survey ( P = .0898). Nonoptimal prescriptions were more common in surgical than in medical departments, in antibacterial prescriptions with prophylactic intention, and in empirical more than in targeted treatments. No significant differences were observed in terms of mortality or readmission rates. Only minor changes in antimicrobial resistance rates were noted.

Conclusions. Our antimicrobial stewardship program safely decreased antimicrobial use and expenditure, and a trend toward improvement in quality of prescription was also observed.

The early care and education of young children, more commonly known as child care, is a ubiquitous experience in the US across geographies and socioeconomic levels. Nationally, more than 12 million children—or nearly two-thirds of children under 5 years of age—regularly participate in out-of-home care, making early care and education a $47.2 billion industry with a workforce of more than 1.5 million child care providers. Early care and education involves children from birth through kindergarten entry, a time when organized, group care, including child care centers, family child care homes, preschool, and Head Start programs represent the majority of child care arrangements.

Unlike other major Western countries, the US lacks a national child care system with a comprehensive centralized mechanism for policymaking or coordinated funding.

Therefore, early care and education in the US is fragmented, leading to substantial variability in the availability, cost, and quality of child care.

This piecemeal system has been severely challenged by the global pandemic associated with the severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-2), owing to both preexisting structural and financial problems of the early care and education system, as well as the unique epidemiology of coronavirus disease 2019 (COVID-19) disease in children.

Preexisting shortcomings of the US early care and education system worsened during the pandemic, presenting novel challenges for early care and education programs related to the COVID-19 pandemic. We offer recommendations for improving health in early care and education programs at this time.

  • Rammya Mathew:: “Back to school” must be backed by a functioning covid-19 testing programme BMJ 2020;370:m3614

En este artículo de opinión acerca de la vuelta al colegio de los niños se tratan temas que son un reflejo de lo que ocurre en nuestro medio en relación a la incertidumbre sobre las consecuencias del inicio del curso escolar presencial. Estamos viendo ya, como en Inglaterra y Gales, el aumento de casos de enfermedades virales (rinovirus, parainfluenza) y la aparición de sintomatología leve respiratoria y gastrointestinal.

Se tratan tres puntos importantes: 1) Más del 50% de los niños con un test positivo presenta los síntomas clásicos que normalmente se observan en los adultos y su solapamiento de los síntomas COVID-19 con los de las enfermedades virales típicas del otoño invierno. 2) La confusión de los padres sobre si su hijo cumple los criterios de autoaislamiento y la realización de las pruebas de COVID. 3) Las escuelas a menudo tienen sus propias políticas sobre cuándo un niño puede o no puede asistir, y los foros de las redes sociales están plagados de "rumores" sobre lo que es y no es COVID.

Si los padres no pueden hacerse una prueba dentro de los primeros cinco días de la enfermedad de su hijo, toda la familia debe aislarse por sí misma durante dos semanas. No se puede subestimar la presión que esto ejerce sobre las familias. Esta presión es aún más aguda en los hogares de bajos ingresos, cuyos salarios a menudo no están protegidos si tienen que aislarse.

Cada vez que un niño da positivo, toda su burbuja (los grupos estables de convivencia en nuestro medio) debe aislarse durante dos semanas desde el inicio de los síntomas del caso índice.

Si no se reciben y asimilan nuestros mensajes de salud pública correctamente, y no se tiene la capacidad de realizar las pruebas para respaldar lo que se le pide a los padres, se verá muy rápidamente que esta situación se sale de control, con los padres forzados a enviar a sus hijos a la escuela sin estas pruebas.

RESULTADOS: Desde marzo de 2020, el 27% de los padres informaron un empeoramiento de su salud mental y el 14% informaron un empeoramiento de la salud conductual de sus hijos. La proporción de familias con inseguridad alimentaria moderada o severa aumentó del 6% antes de marzo de 2020 al 8% después de que la cobertura de seguro infantil patrocinada por el empleador disminuyó del 63% al 60%, y el 24% de los padres informaron una pérdida del cuidado infantil regular. El empeoramiento de la salud mental de los padres se produjo junto con el empeoramiento de la salud del comportamiento de los niños en casi 1 de cada 10 familias, entre las cuales el 48% informó pérdida del cuidado infantil regular, el 16% informó cambios en el estado del seguro y el 11% informó un empeoramiento de la seguridad alimentaria.

CONCLUSIONES:  La pandemia de la enfermedad del coronavirus ha tenido un impacto en tándem sustancial en padres e hijos en los Estados Unidos. A medida que los formuladores de políticas consideren medidas adicionales para mitigar los efectos económicos y de salud de la pandemia, deben considerar las necesidades únicas de las familias con niños.

  • COVID-19 and Parent-Child Psychological Well-being Pediatrics October 2020, 146 (4) e2020007294; DOI: https://doi.org/10.1542/peds.2020-007294

CONCLUSIONES:  De acuerdo con nuestras hipótesis, en familias que han experimentado múltiples dificultades relacionadas con la crisis de la enfermedad del coronavirus de 2019, la salud mental tanto de los padres como de los niños es peor. A medida que la crisis continúa desarrollándose, los pediatras deben evaluar la salud mental, con especial atención a los niños cuyas familias son especialmente vulnerables a los aspectos económicos y de enfermedad de la crisis.

Knowledge of transmission dynamics of severe acute respiratory syndrome coronavirus 2 from adults to children in household settings is limited. We found an attack rate among 213 children in 137 households to be 6.1% in households with confirmed adult 2019 novel coronavirus disease index case(s). Transmission from adult to child occurred in only 5.2% of households. Young children <5 years old were at lowest risk of infection (1.3%). Children were most likely to be infected if the household index case was the mother.

Parecía una verdad universalmente reconocida que la población no tenía inmunidad preexistente al SARS-CoV-2, pero ¿es realmente así? Peter Doshi explora las investigaciones emergentes sobre las respuestas inmunológicas.

Incluso en las áreas locales que han experimentado algunos de los mayores aumentos en el exceso de muertes durante la pandemia de covid-19, las encuestas serológicas desde el pico indican que, como máximo, solo alrededor de una quinta parte de las personas tienen anticuerpos contra el SARS-CoV-2: 23% en Nueva York, 18% en Londres, 11% en Madrid. Entre la población general, las cifras son sustancialmente más bajas, y muchas encuestas nacionales informan de un solo dígito.

Dado que las respuestas de salud pública en todo el mundo se basan en la suposición de que el virus llegó a la población sin inmunidad preexistente antes de la pandemia, los datos de encuestas serológicas llevan a muchos, como Mike Ryan, jefe de emergencias de la OMS, a concluir que el virus, tiene "un largo camino por quemar".

Sin embargo, una serie de estudios que han documentado células T reactivas al SARS-CoV-2 en personas sin exposición al virus, están planteando preguntas sobre cuán nuevo es realmente el virus pandémico, con las muchas implicaciones que esto conllevaría.

  • Covid-19: RECOVERY trial will evaluate “antiviral antibody cocktail”

BMJ 2020;370:m3584

El ensayo RECOVERY, que descubrió que la dexametasona muestra beneficios en pacientes gravemente enfermos con covid-19, investigará el impacto de un "cóctel de anticuerpos antivirales" diseñado específicamente para covid-19, conocido como REGN-COV2.

El ensayo de fase III en la Universidad de Oxford ha estado evaluando diferentes candidatos de tratamiento para el virus desde el comienzo de la pandemia. Sus investigadores han anunciado ahora que evaluarán los efectos de agregar REGN-COV2 al estándar de atención habitual, en comparación con la atención estándar sola, sobre la mortalidad por todas las causas 28 días después de la aleatorización.

La investigación, que tendrá como objetivo tener al menos 2000 pacientes asignados al azar para recibir REGN-COV2, también analizará el impacto en la estancia hospitalaria y la necesidad de ventilación.

REGN-COV2 comprende dos anticuerpos monoclonales que se unen al dominio crítico de unión al receptor de la proteína de pico del virus, disminuyendo la "capacidad de los virus mutantes para escapar del tratamiento y protegiendo contra las variantes de pico que han surgido en la población humana".

A medida que se desarrolló la pandemia de covid-19, aumentó el interés en las pruebas de anticuerpos como una forma de medir qué tan lejos se ha propagado la infección e identificar a las personas que pueden ser inmunes. 1 Las pruebas también tienen un papel clínico, dados los diferentes síntomas de covid-19 y los resultados falsos negativos de las pruebas de reacción en cadena de la polimerasa de transcripción inversa (RT-PCR), particularmente cuando las muestras se realizan con más de cinco días después del inicio de los síntomas y la sensibilidad de las pruebas RT-PCR comienzan a disminuir.  En este artículo se ofrece un enfoque para las pruebas de anticuerpos en personas con y sin síntomas que sugieran una infección por SARS-CoV-2 actual o pasada.

La interpretación de los resultados de la prueba depende no solo de la precisión de la prueba en sí, sino también de la probabilidad de infección previa a la prueba. Esto variará ampliamente dependiendo de la indicación de la prueba: cuando se evalúan individuos asintomáticos, la probabilidad previa a la prueba será relativamente baja, para aquellos con síntomas sugestivos es probable que sea mucho mayor.

 La calculadora interactiva en BMJ.com (https://sandpit.bmj.com/graphics/2020/c19testA/) permite a los médicos explorar el impacto de cambiar la probabilidad, la sensibilidad y la especificidad previas a la prueba en los resultados de la prueba. Las medidas para reducir la transmisión, como el distanciamiento social, deben mantenerse independientemente del resultado de la prueba y no recomendamos la prueba de anticuerpos para este propósito en la actualidad.

-La mayoría de los estudios sobre pruebas de anticuerpos son de pacientes hospitalizados. No sabemos qué tan bien funcionan las pruebas en pacientes con enfermedad leve que no ingresaron al hospital o en personas asintomáticas.

-Faltan datos sobre la precisión de las pruebas más allá de los 35 días; no sabemos qué tan bien funcionarán estas pruebas para las infecciones que ocurrieron hace más de cinco semanas

-La evidencia es insuficiente para saber si la presencia de anticuerpos confiere inmunidad duradera para proteger contra una futura infección por covid-19

CONCLUSIONES: En esta gran cohorte de niños a los que se les hizo la prueba del SARS-CoV-2 a través de un sitio de pruebas basado en la comunidad, las minorías raciales y / o étnicas y los niños en desventaja socioeconómica tienen la mayor carga de infección. Es necesario comprender y abordar las causas de estas diferencias para mitigar las disparidades y limitar la propagación de la infección.

CONCLUSIONES: Los datos sugieren que los casos pediátricos de COVID-19 son menos graves que los adultos; sin embargo, la edad ≤ 1 año y la presencia de condiciones subyacentes representan factores de riesgo de gravedad. Una mejor comprensión de la infección en los niños puede brindar información importante sobre la patogénesis de la enfermedad, las prácticas de atención médica y las políticas de salud pública.

Resumen Conclusiones de los autores del estudio: las dosis altas de metilprednisolona son eficaces para el tratamiento de neumonía grave por Mycoplasma pneumoniae y no aumentan la incidencia de reacciones adversas. Comentario de los revisores: las limitaciones metodológicas de los ensayos clínicos incluidos en esta revisión, su ámbito epidemiológico y la escasa información sobre las características de los pacientes hacen que los resultados de esta revisión deban ser interpretados con cautela. Aunque el uso de corticoides en pacientes con mala evolución sería razonable, es necesario un ensayo clínico multicéntrico de calidad, para comprobar el efecto, antes de incorporarlo a nuestros protocolos clínicos.

·Follow-up Study of Long-time Positive RT-PCR in Stool Specimens From Asymptomatic Children Infected With SARS-CoV-2. Xie, Jun; Long, Xiaoru; Ren, Chongsong; He, Ronghui; Yan, Xiaofeng; Li, Weiguo; Luo, Zhengxiu; Li, Qiu; Xu, Hongmei; Liu, Enmei Less

The Pediatric Infectious Disease Journal. 39(10):e315-e317, October 2020.

In the current study, we report on 4 children with confirmed SARS-CoV-2 infection, of which 3 of them were asymptomatic. These patients had both pharyngeal swabs and anal swabs testing during hospital or after discharge. All the 4 children showed long-time positive viral RNA in the stool specimens after pharyngeal swabs turned negative during the follow-up stage, especially in the asymptomatic children. The positive RNA in stool specimens of asymptomatic children last for more than 54 days after admission or 30 days after discharge.

 

Actualidad bibliográfica agosto-septiembre 2020

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El consumo total de antibióticos en el ámbito de la salud humana en España registró una bajada del 5,4 % (1,4 DHD o Dosis Diarias Definidas por cada 1.000 habitantes y día) en 2019, mientras que las ventas de antibióticos veterinarios se redujeron un 13,6 % en el mismo período. La incorporación de los datos correspondientes a 2019 al análisis desarrollado en el marco del Plan Nacional frente a la Resistencia a los Antibióticos (PRAN) del Ministerio de Sanidad confirma la tendencia decreciente registrada en ambas tasas en los últimos años.

El cálculo global del consumo en salud humana incluye los antibióticos del grupo J01 de la clasificación ATC utilizados en hospitales y ámbito comunitario. En el sector comunitario (receta oficial del Sistema Nacional de Salud, receta privada y mutuas), España ha registrado una bajada del consumo de antibióticos del 5,4 % (1,31 DHD, 2 millones de envases menos) en 2019. Los antibióticos más consumidos en este ámbito son amoxicilina/clavulánico, amoxicilina y azitromicina. Por otra parte, el consumo en hospitales bajó un 4,8 % (0,08 DHD, 2 millones de unidosis menos), con amoxicilina/clavulánico, levofloxacino y ceftriaxona como antibióticos más utilizados en esta área.

Con los últimos datos incorporados a la estadística, el consumo nacional de antibióticos en salud humana refleja una bajada del 11,8 % entre 2015 y 2019. Así, la media española de consumo total en esta área ha pasado de las 28,1 DHD de 2015 a las 24,9 DHD registradas en 2019 (1,6 DHD en hospitales y 23,3 DHD en ámbito comunitario). La media total española en humana continúa colocándose en cualquier caso por encima de la europea (20,1 DHD en 2018), aunque cabe destacar una variabilidad entre comunidades autónomas que va de 19,3 a 27,3 DHD.

En el ámbito de la sanidad animal, la reducción del 13,6 % registrada en las ventas de antibióticos veterinarios en 2019 (27,2 mg/PCU o miligramos de principio activo por Unidad de Correción de Población) engloba datos proporcionados por todos los actores involucrados en la cadena de comercialización, ya que en 2017 la recogida de datos de laboratorios farmacéuticos se amplió con los de entidades minoristas y farmacias. Con las últimas cifras añadidas a la estadística, las ventas totales de antibióticos de uso veterinario muestran una reducción del 58,8 % entre 2014 y 2019. España pasa así de los 418,8 mg/PCU contabilizados en 2014 a los 172,4 mg/PCU de 2019, más cerca de la media europea en esta área (107 mg/PCU en 2018).

There are many questions and concerns about the coronavirus disease 2019 (COVID-19), including its implications for breastfeeding.

 This commentary draws on a statement and recommendations recently issued by the Regional Office for Europe of the World Health Organization with the contribution of the European Pediatric Association-Union of National European Pediatric Societies and Associations and other main European pediatric organizations.

 Our aim is to provide pediatricians with further guidance on breastfeeding and related safety measures during COVID-19, particularly in instances where a mother has or may have COVID-19.

Children with coronavirus disease 2019 (COVID-19) are more likely to have mild or no symptoms compared with adults and may represent important vectors for transmitting the virus. Little is known about the duration of respiratory and gastrointestinal viral shedding in children with COVID-19.

Objective: To determine the average shedding times of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via the respiratory and gastrointestinal tracts in children.

Methods: We performed a systematic search of Ovid MEDLINE, Embase and Cochrane CENTRAL databases for studies reporting real-time reverse transcriptase polymerase chain reaction (rt-PCR) results in children with COVID-19, then extracted and synthesized data on duration of viral shedding from symptom onset in respiratory and gastrointestinal samples.

Results: Based on data compiled from 69 pediatric cases, the duration of viral shedding through the respiratory tract is up to 24 days from symptom onset with a mean of 11.1 ± 5.8 days. Of the children who underwent testing with stool PCR, rectal swab or anal swab, 86% returned a positive result. The mean duration of viral shedding via the gastrointestinal tract was 23.6 ± 8.8 days from symptom onset. In 89% of cases, viral shedding via the gastrointestinal tract persisted after nasopharyngeal or throat swabs became negative, for as long as 4 weeks.

Conclusions: To our knowledge, this is the first attempt to systematically review the duration of respiratory and gastrointestinal viral shedding of SARS-CoV-2 in pediatric patients. These findings may have important implications for infection control strategies during the COVID-19 pandemic.

We looked for studies that measured the accuracy of rapid point-of-care tests compared with RT-PCR tests to detect current COVID-19 infection. We were interested in two types of rapid point-of-care tests, antigen and molecular tests. Antigen tests identify proteins on the virus, often using disposable devices. Molecular tests detect the virus’s genetic material, using small portable or table-top devices. Both test the same nose or throat samples as RT-PCR tests Studies could assess any rapid antigen or molecular point-of-care test, compared with a reference standard test. The reference standard is the best available method for diagnosing the infection; we considered RT-PCR test results and clinically defined COVID-19 as reference tests. People could be tested in hospital or the community. Studies could test people with or without symptoms.

We found 18 relevant studies. Ten studies took place in North America, four in Europe, two in South America, one in China and one in multiple countries.

Nine studies deliberately included a high percentage of people with confirmed COVID-19 or included only people with COVID-19. Fourteen studies did not provide any information about the people providing the samples for testing and 12 did not provide any information about where people were tested.

None of the studies reported included samples from people without symptoms.

Main results

Five studies reported eight evaluations of five different antigen tests. Overall, there was considerable variation between the results of the antigen tests in how well they detected COVID-19 infection. Tests gave false positive results in less than 1% of samples.

Thirteen evaluations of four different molecular tests correctly detected an average of 95% of samples with COVID-19 infection. Around 1% of samples gave false positive results.

If 1000 people had molecular tests, and 100 (10%) of them really had COVID-19:

- 105 people would test positive for COVID-19. Of these, 10 people (10%) would not have COVID-19 (false positive result).

- 895 people would test negative for COVID-19. Of these, 5 people (1%) would actually have COVID-19 (false negative result).

We noted a large difference in COVID-19 detection between the two most commonly evaluated molecular tests.

How reliable were the results of the studies?

Our confidence in the evidence is limited.

What are the implications of this review?

Studies provided little information about their participants, so it is not possible to tell if the results can be applied to people with no symptoms, mild symptoms, or who were hospitalised with COVID-19. Accurate rapid tests would have the potential to select people for RT-PCR testing or to be used where RT-PCR is not available. However, the evidence currently is not strong enough and more studies are urgently needed to be able to say if these tests are good enough to be used in practice.

The individual signs and symptoms included in this review appear to have very poor diagnostic properties, although this should be interpreted in the context of selection bias and heterogeneity between studies. Based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out disease. Prospective studies in an unselected population presenting to primary care or hospital outpatient settings, examining combinations of signs and symptoms to evaluate the syndromic presentation of COVID-19 disease, are urgently needed. Results from such studies could inform subsequent management decisions such as self-isolation or selecting patients for further diagnostic testing. We also need data on potentially more specific symptoms such as loss of sense of smell. Studies in older adults are especially important.

  • Antibody tests for identification of current and past infection with SARS-CoV-2. Cochrane Database of Systematic Reviews 2020, Issue 6. Art. No.: CD013652. DOI: 10.1002/1465

The sensitivity of antibody tests is too low in the first week since symptom onset to have a primary role for the diagnosis of COVID-19, but they may still have a role complementing other testing in individuals presenting later, when RT-PCR tests are negative, or are not done. Antibody tests are likely to have a useful role for detecting previous SARS-CoV-2 infection if used 15 or more days after the onset of symptoms. However, the duration of antibody rises is currently unknown, and we found very little data beyond 35 days post-symptom onset. We are therefore uncertain about the utility of these tests for seroprevalence surveys for public health management purposes. Concerns about high risk of bias and applicability make it likely that the accuracy of tests when used in clinical care will be lower than reported in the included studies. Sensitivity has mainly been evaluated in hospitalised patients, so it is unclear whether the tests are able to detect lower antibody levels likely seen with milder and asymptomatic COVID-19 disease.

The design, execution and reporting of studies of the accuracy of COVID-19 tests requires considerable improvement. Studies must report data on sensitivity disaggregated by time since onset of symptoms. COVID-19-positive cases who are RT-PCR-negative should be included as well as those confirmed RT-PCR, in accordance with the World Health Organization (WHO) and China National Health Commission of the People's Republic of China (CDC) case definitions. We were only able to obtain data from a small proportion of available tests, and action is needed to ensure that all results of test evaluations are available in the public domain to prevent selective reporting. This is a fast-moving field and we plan ongoing updates of this living systematic review.

For many clinical outcomes, there were no differences between prescribing strategies. Symptoms for acute otitis media and sore throat were modestly improved by immediate antibiotics compared with delayed antibiotics. There were no differences in complication rates. Delaying prescribing did not result in significantly different levels of patient satisfaction compared with immediate provision of antibiotics (86% versus 91%) (moderate quality evidence). However, delay was favoured over no antibiotics (87% versus 82%). Delayed antibiotics achieved lower rates of antibiotic use compared to immediate antibiotics (31% versus 93%) (moderate quality evidence). The strategy of no antibiotics further reduced antibiotic use compared to delaying prescription for antibiotics (14% versus 28%).

Delayed antibiotics for people with acute respiratory infection reduced antibiotic use compared to immediate antibiotics, but was not shown to be different to no antibiotics in terms of symptom control and disease complications. Where clinicians feel it is safe not to prescribe antibiotics immediately for people with respiratory infections, no antibiotics with advice to return if symptoms do not resolve is likely to result in the least antibiotic use while maintaining similar patient satisfaction and clinical outcomes to delaying prescription of antibiotics. Where clinicians are not confident in using a no antibiotic strategy, a delayed antibiotics strategy may be an acceptable compromise in place of immediate prescribing to significantly reduce unnecessary antibiotic use for RTIs, and thereby reduce antibiotic resistance, while maintaining patient safety and satisfaction levels.

We found 138 studies with more than 23 million children. Fifty-one studies (10 million children) assessed how effective the vaccines were at preventing the diseases, and 87 studies (13 million children) assessed unwanted effects. In this 2020 update we have included 74 new studies published since 2012.

Conclusions:

Our review shows that MMR, MMRV and MMR+V vaccines are effective in preventing the infection of children by measles, mumps, rubella and chickenpox, with no evidence of an increased risk of autism or encephalitis and a small risk of febrile seizure. 

Background: Human coronaviruses (HCoVs) have been recognized as causative agents of respiratory tract infections.

Our aim was to describe HCoV infections in hospitalized children in a prospective surveillance study for 14 years and compare them with other respiratory viruses.

Methods: As a part of an ongoing prospective study to identify the etiology of viral respiratory infections in Spain, we performed the analysis of HCoV infections in children hospitalized in a secondary hospital in Madrid, between October 2005 and June 2018. Clinical data of HCoV patients were compared with those infected by rhinovirus, respiratory syncytial virus and influenza.

Results: The study population consisted of 5131 hospitalizations for respiratory causes in children. A total of 3901 cases (75.9%) had a positive viral identification and 205 cases (4.1%) were positive for HCoV. Only 41 cases (20%) of HCoV infection were detected as single infections. Episodes of recurrent wheezing were the most common diagnosis, and 112 children (54%) had hypoxia. Clinical data in HCoV cases were similar to those associated with rhinovirus; however, patients with HCoV were younger. Other viruses were associated with hypoxia more frequently than cases with HCoV; high fever was more common in influenza infections and bronchiolitis in respiratory syncytial virus group. Although a slight peak of circulation appears mostly in winter, HCoV has been detected throughout the year as well.

Conclusions: HCoV infections represent a small fraction of respiratory infections that require hospitalization in children and their characteristics do not differ greatly from other respiratory viral infections.

Acute rheumatic fever (ARF) is a postinfectious immune-mediated syndrome predominantly affecting children, adolescents and young adults following infection with the group A Streptococcus (Streptococcus pyogenes (Strep A). Its clinical presentation is varied, with symptoms, signs and laboratory abnormalities reflecting systemic inflammation (fever, elevated C reactive protein and erythrocyte sedimentation rate) and focal inflammation of the heart (carditis, most frequently manifest as valvulitis), joints (arthritis and arthralgia), skin (subcutaneous nodules, erythema marginatum) and brain (chorea).

Severe acute rheumatic carditis may be fatal, but mortality and morbidity due to the chronic valve lesions of rheumatic heart disease (RHD) are much greater, attributable largely to heart failure and stroke. The lesions of RHD are thought to be caused by recurrent episodes of ARF due to repeated group A streptococcal infections. In the second half of the 20th century, the global burden of ARF shifted dramatically, virtually disappearing from high-income countries to become concentrated in low- and middle-income countries and historically dispossessed and disadvantaged groups in some high-income countries, including indigenous Australians and New Zealand Māori. This epidemiological shift out of sight of wealthy populations has left ARF and RHD neglected by researchers and funders despite the persistent global burden of more than 300, 000 incident cases of ARF and more than 30 million prevalent cases of RHD.1

Prevention and control efforts for ARF and RHD are focused on primary prevention (treatment of group A streptococcal infection to prevent …

Background: Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and a well-known cause of lymphadenitis, skin and soft tissue infections. The aim of this study was to evaluate the epidemiology of extrapulmonary pediatric NTM infections occurring from 2000 to 2017 in Queensland, Australia.

Methods: All cases of NTM and TB are notifiable under the Queensland Public Health Act (2005) and associated regulations (2005). Data from 2000 to 2017 inclusive was collected from the Notifiable Conditions Database, a laboratory based notification system that covers private and public laboratory systems. Pediatric population demographic data were obtained from the Australian Bureau of Statistics by researching the number of children 0–14 years of age in Queensland from 2000 to 2017; both annual and averaged population was determined. The statistical software SPSS and Tableau was used for analysis.

Results: The mean age of diagnosis was 2.5 years with a majority of the cohort being women. Mycobacterium avium was the most commonly diagnosed pathogen. Geographic regions with the highest numbers of cases were predominantly tropical and coastal areas. M. haemophilum emerged as a more common pathogen from 2011 following a period of major flooding.

Conclusion: Characteristics of the cohort of children susceptible to NTM disease appears consistent with previous reports. However, changes in the epidemiology of NTM infection (such as incidence, species, and geographic distribution) in children may be linked to environmental and weather factors.,

The reports of Chao et al and DeBiasi et al from the Children's Hospital at Montefiore in New York City (NYC) and Children's National Hospital in Washington, DC (DC) provide their SARS-CoV-2 experience over 4- and 6-week periods, respectively, beginning on March 15, 2020. Although SARS-CoV-2 generally has been said to be a mild infection in the pediatric age group, a picture of severe COVID-19 in US children and youth emerges through these reports. Together, 91 hospitalized patients with 22 critically ill are reported, with demographic and other patient characteristics compared between groups. Hospitalized patients were representative of the Bronx, NYC, and DC communities served, with high proportion of Hispanic/Latinos in NCY and Hispanic/Latinos and African Americans in DC. Obesity (BMI >30kg/m2) was present in 26% of Bronx patients and 2% of DC patients. Although underlying medical conditions were common in hospitalized patients, 37% of hospitalized and 22% of critically ill patients in DC had no underlying condition. Of the combined studies' 22 critically ill patients, 63% were male and 82% were >10 years of age. PICU admission predominantly was due to respiratory compromise and was associated with briskly elevated inflammatory markers, lung opacities on chest radiograph, and systemic inflammatory response syndrome (SIRS). Both reports show that approximately 20% of COVID-19 hospitalizations were comprised of patients with asthma, but neither shows an excess of asthmatics among the critically ill. Because substantial SAR-CoV-2 testing of symptomatic outpatients was occurring in DC (1804 tests over 6 weeks), we also know that 21% of infected outpatients had asthma. Taken together, there likely is a signal that SARS-CoV-2 may exacerbate asthma but itself is not a major risk factor for the severe COVID-19 pulmonary syndrome. Additionally, from the DC study, we see that although children <1 year and >15 years of age were over-represented among hospitalized patients with COVID-19, only those >15 years were overrepresented among the critically ill (Figure).

Two studies totaling 66 previously unreported cases of MIS-C associated with SARS-CoV-2 infection in the US put meat on the bones of news reports and individual case notes. Several aspects of the studies make them clean and comparable, and their messages clear. Each reports 33 pediatric patients with confirmed SARS-CoV-2 infection (predominantly by antibody testing), over the same 4-week period from mid-March through mid-April, 2020 (ie, weeks following the peaks of community.

Study design Children with MIS-C admitted to pediatric intensive care units in New York City between April 23 and May 23, 2020, were included. Demographic and clinical data were collected.

Results Of 33 children with MIS-C, the median age was 10 years; 61% were male; 45% were Hispanic/Latino; and 39% were black. Comorbidities were present in 45%. Fever (93%) and vomiting (69%) were the most common presenting symptoms. Depressed left ventricular ejection fraction was found in 63% of patients with median ejection fraction of 46.6% (IQR, 39.5-52.8). C-reactive protein, procalcitonin, d-dimer, and pro-B-type natriuretic peptide levels were elevated in all patients. For treatment, intravenous immunoglobulin was used in 18 (54%), corticosteroids in 17 (51%), tocilizumab in 12 (36%), remdesivir in 7 (21%), vasopressors in 17 (51%), mechanical ventilation in 5 (15%), extracorporeal membrane oxygenation in 1 (3%), and intra-aortic balloon pump in 1 (3%). The left ventricular ejection fraction normalized in 95% of those with a depressed ejection fraction. All patients were discharged home with median duration of pediatric intensive care unit stay of 4.7 days (IQR, 4-8 days) and a hospital stay of 7.8 days (IQR, 6.0-10.1 days). One patient (3%) died after withdrawal of care secondary to stroke while on extracorporeal membrane oxygenation.

Conclusions Critically ill children with coronavirus disease-2019-associated MIS-C have a spectrum of severity broader than described previously but still require careful supportive intensive care. Rapid, complete clinical and myocardial recovery was almost universal.OK

In late April 2020, alarming news emerged from Europe that a group of children with evidence of recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection had developed a severe illness, manifesting fever, hypotension requiring inotropic support, severe abdominal pain, and myocardial dysfunction with marked elevation in cardiac damage markers. This syndrome has been named pediatric multisystem inflammatory syndrome in Europe, and multisystem inflammatory syndrome in children.

Among children with Kawasaki-like disease, what is the demographic and disease-related parameters in the COVID-19 era, compared with children diagnosed with Kawasaki disease in the pre-COVID-19 era?

Children with Kawasaki disease in the COVID-19 era, 80% of whom were antibody positive, were older and demonstrated more severe disease compared with those with Kawasaki disease prior to the COVID-19 era.

A thirty-fold increased incidence of so-called Kawasaki-like disease was reported from Italy during the SARS-CoV-2 epidemic in 2020. Eight of the 10 patients with Kawasaki disease tested positive for COVID-19 with a high incidence (6/10) of cardiac involvement. News from New York, France, and England also showed an increased incidence and severity of Kawasaki disease. Prior to COVID-19, coronavirus had been previously isolated in 7.1% of patients with Kawasaki disease.

The incidence of Kawasaki disease is not increasing in Japan, Taiwan, Korea, Hong-Kong, or China, suggesting the importance of genetic issues in the relationship between Kawasaki disease and COVID-19. In this study, the Kobayashi score, which identifies patients at high risk of IVIG resistance,revealed that of the 10 patients with Kawasaki disease, none were younger than 12 months and all had platelet counts less than 300 × 10⁹/L. Results from this study suggest that COVID-19 may be one of the triggers of Kawasaki disease. Kawasaki disease in older patients with COVID-19 is associated with an increased incidence of cardiac involvement, lower platelet counts, MAS, and Kawasaki disease shock syndrome. Early adjunctive steroid treatment to prevent coronary artery lesions should be considered in these patients with COVID-19 Kawasaki disease.

There has been a rise in the number of critically ill patients presenting with an unusual clinical picture; all have in common features of Kawasaki disease and a confirmed or suspected coronavirus disease 2019 (COVID-19) infection. According to Harahsheh et al, the diagnosis/treatment of Kawasaki disease was missed or delayed owing to the forced lockdown and doctors being focused on treating patients with COVID-19.

A similar concern was shared by adult cardiologists...

We thank Bassareo et al for their comments and agree that our community needs to come together to improve timely diagnosis and treatment of children with Kawasaki disease and Kawasaki disease-like illnesses during the 2019 novel coronavirus disease (COVID-19) pandemic to prevent the development of coronary artery aneurysms.

We would like to use this opportunity to provide context for writing our original letter and what we have learned in the interim. Between January 1, 2020, and April 1, 2020, we noted a decrease in the number of children presenting to large academic centers with Kawasaki disease.

We read with interest the article by Jiao et al discussing the behavioral and emotional impact on children and adolescents imposed by the 2019 novel coronavirus disease (COVID-19) pandemic.1 Here we intend to share our personal observations regarding the difficulties and challenges faced by the children whose parents are frontline “warriors” against COVID-19.

Apart from the effects of protracted school closure, sudden changes in their daily routine, and a sedentary lifestyle, similar to other children, children of frontline COVID-19 workers are going through unique experiences. The concept of nuclear families in recent decades already threatens the mental well-being of children, where parental duties in hospitals and subsequent quarantine of their parents make them feel deserted. Although doctors know that children are probably the least physically affected group, a fear of transmitting the virus to their children is lurking in their minds, which may prevent them from interacting with their children.2 Children less than 3 years of age who are dependent on their mothers for breast milk and other activities of daily living pass their lives in torment. Although, as a positive effect of lockdown, most children are getting more time to mingle with their parents, the story of the children of frontline COVID-19 warriors is different.3 Young children may not understand why their parents are not returning. Older children and adolescents with more mature thinking may offer respect toward their parents for being involved in the fight against the deadly COVID-19. Incidences of eviction from homes or discrimination against their medical professional parents4 creates a sense of insecurity, fear, and vulnerability among children—this may lead to long-term consequences of anger, aggressiveness, and disrespect toward society at large.

Experts have recommended strategies to combat the psychological toll of COVID-19 among children in general.5, 6, 7 In addition, we hope that government and society will be...

Dubey et al bring attention to the emotional and other difficulties of family members of the medical staff, especially those serving in the front line of the coronavirus disease-2019 battle. This demonstrates that these difficulties, if left untreated, may bring about significant stress and emotional difficulties to both medical employees and their families.

A recent survey among physicians working in coronavirus...

The first pediatric study demonstrating significantly higher positivity rate of nasal (mid-turbinate) swab testing over oropharyngeal swab testing in detecting SARS-CoV-2 (Fisher exact test 0.046, Cohen K 0.43, confidence interval 95%, 0.014–0.855). Benefits might include lower collection-related hazard for healthcare workers. We recommend it as preferred choice for swab-based SARS-CoV-2 testing in children.

Pyogenic sacroilitis is an infrequent osteoarticular infection, and its diagnosis is a challenge in young children. A series of 20 cases is described. The median age was 15 months, 75% of them being under 2 years old. Fourteen (70%) reported fever. Refusal to sit was the main reason for consultation. Final diagnosis was confirmed by bone scintigraphy. All patients achieved a complete resolution without sequelae.

Casos clínicos

A 7-year-old right-handed previously healthy boy presented with progressive clumsiness, abnormal movements of the right arm, and gait and speech abnormalities. Two weeks before his presentation, his father noted involuntary, nonrhythmic, nonsuppressible movements of his right arm that progressively developed into constant, writhing movements that did not occur during sleep. The movements had not changed in character but had progressively increased in intensity. He had decreasing dexterity at school and home and occasionally slurred words at the ends of sentences. He had no recent illnesses and no recent history of sore throat.

A 5-year-old girl presented to the dermatology clinic for evaluation of pruritic papules and blisters on the hands and forearms for three months. She was seen by her pediatrician, diagnosed with dyshidrotic eczema, and prescribed topical triamcinolone with no improvement. She reported itching everywhere, but her parents noted she most frequently scratched her hands and forearms. The itching was worse at night. No close contacts experienced pruritus. She had no history of inflammatory dermatoses or other medical problems.

A 10-month-old, fully vaccinated, infant boy was admitted to our hospital in rural Laos with respiratory distress that ultimately was diagnosed as due to beriberi.

At the time of admission, a firm mass was noted in the right axilla (Figure 1) during routine physical examination. His parents reported that the mass was first palpable at about 4 months of age, had progressively increased in size until about a month before admission, and had since stabilized. A chest radiograph demonstrated a calcified right axillary mass with the typical appearance of lymph nodes (Figure 2, arrow). A re-review of a chest radiograph obtained during a previous hospital visit at 2 months of age confirmed that this calcification was not visible at that time (Figure 3).

An 8-month-old child under tuberculosis treatment presented with multiple ecchymotic lesions. A severe coagulopathy was evidenced compatible with vitamin K deficiency [II (3%), VII (2%), IX (3%) and X (1%)]. It was reversed with vitamin K and plasma administration. Rifampicin-induced vitamin K deficiency is very rare, reported only once before, possibly related to an inhibition of vitamin K cycle.

We describe 3 cases of adolescent varicella-zoster virus reactivation, complicated by aseptic meningitis, presenting to our institution in a 3-year period. These cases highlight varicella-zoster virus reactivation as an important cause of aseptic meningitis in the differential diagnosis of healthy adolescents, even in the absence of a characteristic exanthem. Evidence-based management recommendations are needed.

We present a case of a 22-month-old girl who had 2 episodes of cutaneous larva migrans 2 months apart after returning from a tropical area, despite a single exposure period.

Since the emergence of a cluster of viral pneumonia cases in Wuhan, Hubei Province, People’s Republic of China, at the end of December 2019, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), a novel coronavirus also known as “coronavirus disease 2019 (COVID-19),” as of 7 April 2020, more than 1,214,466 cases of COVID-19 have been reported in more than 200 countries and territories, resulting in more than 67,767 deaths. The disease was recognized by World Health Organization (WHO) as a pandemic on 11 March 2020. Published reports of adult patients with COVID-19 infection described symptoms including fever, cough, fatigue, sputum production, headache, dyspnea and diarrhea. Children usually showed milder respiratory symptoms or were asymptomatic, while loss of taste or sensation of smell were seldom reported. In this paper, we report three cases of pediatric patients with COVID-19 infection who presented with anosmia and/or ageusia.

To date, although neonatal infections with severe acute respiratory syndrome coronovirus 2 (SARS-CoV-2) have been described, none of these have been proven to be the result of vertical transmission of SARS-CoV-2.

Methods: We describe the probable vertical transmission of SARS-CoV-2 in a neonate born to a mother with coronavirus disease 2019 (COVID-19).

Results: Following cesarean section, the neonate was kept in strict isolation. Molecular tests for SARS-CoV-2 on respiratory samples, blood, and meconium were initially negative, but positive on a nasopharyngeal aspirate on the third day of life. On day 5, the neonate developed fever and coryza, which spontaneously resolved. Viral genomic analysis from the mother and neonate showed identical sequences except for 1 nucleotide.

Conclusion: This report has important implications for infection control and clinical management of pregnant women with COVID-19 and their newborns.

Coronavirus disease 2019 outbreak has a growing impact on global health; vertical transmission of severe acute respiratory syndrome coronavirus 2 infection is still controversial. In this article, we describe a case of vertical transmission of severe acute respiratory syndrome coronavirus 2 in a newborn with respiratory and gastrointestinal symptoms.

Para profundizar

Nonspecific symptoms in children suspected of Lyme borreliosis (LB) are challenging for clinicians. We assessed whether nonspecific symptoms are more prevalent among children with positive immunoglobulin G (IgG) serology or a history of clinical LB.

Methods: We included children (<18 years) suspected of LB who visited the Lyme Center Apeldoorn of Gelre Hospital between 2008 and 2017. Serum samples were taken, and questionnaires on nonspecific symptoms completed. Clinical data were collected from patients’ medical records. The prevalence of nonspecific symptoms was compared between patients with positive versus negative IgG serology and between patients with versus without previous LB with the χ 2 and Fisher exact tests with Bonferroni correction. A history of LB was anamnestically determined. Patients with active Lyme manifestations were excluded.

Results: Included were 149 children (66% female; median age 13 years); 29 (19%) had positive IgG serology; 36 (24%) had previous LB; 12 (8%) had both. Common nonspecific symptoms were sleep disturbances (58%), severe fatigue (57%) and headache (42%). The prevalence of nonspecific symptoms was similar in children with positive versus negative IgG serology. None of the nonspecific symptoms occurred more frequently in children with previous LB compared with children without. More prevalent in children without previous LB were sleep disturbances (40 vs. 66%; P = 0.002) and tingling (6 vs. 34%; P < 0.001).

Conclusions: Nonspecific symptoms were not more prevalent in children with positive IgG serology nor in children with previous LB, where some were significantly less prevalent. Hence, questionnaires on nonspecific symptoms cannot be used to identify children for serologic testing in Lyme centers.

Epidemiology, Clinical and Microbiologic Profile and Risk Factors for Inpatient Mortality in Pediatric Severe Sepsis in the United States From 2003 to 2014: A Large Population Analysis The Pediatric Infectious Disease Journal. 39(9):781-788, September 2020.

To evaluate the national trends in pediatric severe sepsis in the United States from 2003 to 2014.

Study design: For this study, we included nonoverlapping years of Kids Inpatient database and National Inpatient Sample database while including hospitalizations of children between 1 and 20 years of age from more than 4200 hospitals across the United States. We identified patient hospitalizations with severe sepsis using specific ICD codes and modified Angus Criteria. Trend analysis of various factors associated with severe sepsis was calculated using the Cochrane–Armitage test. Associated foci of infection and comorbid conditions were identified using specific ICD codes, and a multivariate regression analysis with death as outcome variable was done to evaluate for in hospital predictors of mortality.

Results: Totally, 109,026 episodes of severe sepsis were identified during the study period between 2003 and 2014. Incidence of severe sepsis hospitalizations increased by 2.5 times (0.64–1.57 per 10,000 population) over the study period with notable concurrent significant decrease in mortality by more than 50%. Lower age, African American, Hispanic ethnicity, complex neurologic conditions, infective endocarditis, immunodeficient states including primary immunodeficiency disorder, HIV, burns, malignancy and transplant status are associated with mortality. There is a significant increase in use of healthcare resources ( P < 0.001) with mean charges of 94,966$ despite a notable decrease in mean length of stay (22 vs. 16 days, P < 0.001) over the study period.

Conclusion: Incidence of pediatric severe sepsis is high leading to a significant use of healthcare resources. This study provides a detailed analysis of associated inpatient factors and comorbidities associated with mortality. OK

Acute otitis media (AOM) is the most common reason for antimicrobial use, and tympanostomy tube placement (TTP) is the most common reason for surgery requiring general anesthesia in children. Ten-valent pneumococcal conjugate vaccine (PCV10) was introduced in Finland in 2010 for infants. We evaluated the indirect impact of PCV10 on these surrogate otitis outcomes in unvaccinated children.

Methods: Using before-after design, unvaccinated children ineligible for National Vaccination Program (born January 2006 to May 2010) were followed-up during 2012–2016 (target cohort, age 1.5–7 years). The target cohort was compared with an age- and season-matched unvaccinated reference cohort (born January 2000 to May 2004) during 2006–2010. Antimicrobial purchase data were obtained from the Social Insurance Institution of Finland benefits register. We assessed the relative reduction by generalized Cox regression for outpatient purchases of antibiotics recommended for treatment of AOM in the Finnish guidelines. Data on all TTP procedures were obtained from national hospital discharge register and Social Insurance Institution benefits register.

Results: The rate of outpatient purchases of antimicrobials recommended for AOM was 51 in the unvaccinated reference cohort and 44/100 person-years in the unvaccinated target cohort; relative rate reduction was 14.7% [95% confidence interval: 14.0–15.3] and absolute rate reduction 7/100 person-years. The rates of TTP in the reference and target cohorts were 1.66/100 and 1.61/100 person-years, respectively. The relative rate reduction was 3.6% (0.7–6.5).

Conclusions: Antimicrobial use and TTP procedures reduced in unvaccinated children after PCV10 introduction in infants. These indirect effects contribute to the savings in health care resource use for otitis and may also help in combating antimicrobial resistance.

Acute flaccid myelitis, defined by acute flaccid limb weakness in the setting of grey matter lesions of the spinal cord, became increasingly recognised in 2014 following outbreaks in Colorado and California, temporally associated with an outbreak of enterovirus D68 respiratory disease. Since then, there have been biennial increases in late summer/early fall. A viral infectious aetiology, most likely enteroviral, is strongly suspected, but a definitive connection has yet to be established. Patients typically present with asymmetric weakness, maximal proximally, in the setting of a febrile illness. MRI demonstrates T2/FLAIR abnormalities in the central grey matter of the spinal cord, and cerebrospinal fluid typically shows a lymphocytic pleocytosis with variable elevation in protein. The weakness may be progressive over several days and involve respiratory muscles, making early recognition and close monitoring essential. Other complications in the acute period may include autonomic instability and bowel/bladder involvement. There is no clear recommended treatment at this time, although intravenous immunoglobulin, steroids and plasma exchange have been used. Intensive therapies and rehab services have shown benefit in maximising function, and surgical interventions may be considered in cases without optimal response to therapies. Close attention should also be paid to psychosocial factors. Prognosis is generally guarded, and additional factors that predict final outcome, including host factors and treatment effects, have yet to be elucidated. Multicentre collaborative efforts will be required to provide answers about this rare but serious disorder.

Influenza infection is a common cause of respiratory disease and hospitalization in children. Neurologic manifestations of the infection have been increasingly reported and may have an impact on the severity of the disease. The aim of this study is to describe neurologic events in pediatric patients hospitalized with influenza and identify associated risk factors.

Methods: Retrospective cohort study which included all hospitalized patients with microbiologic confirmation of influenza disease over 4 epidemic seasons, focusing on neurologic complications. Demographic, laboratory and clinical data, as well as past history, were recorded. Descriptive and analytic statistical study was performed using SPSS and R statistical software.

Results: Two hundred forty-five patients were included. Median age was 21 months (interquartile range, 6–57) and 47.8% had a previous underlying condition. Oseltamivir was administered to 86% of patients, median hospitalization was 4 days (interquartile range, 3–6), and pediatric intensive care unit admission rate 8.9%. Twenty-nine patients (11.8%) developed neurologic events, febrile seizures being the most frequent, followed by nonfebrile seizures and encephalopathy. Status epilepticus occurred in 4 children, and 69.6% of seizures recurred. Patients with a previous underlying condition were at greater risk of developing a neurologic complication [odds ratio (OR), 4.55; confidence interval (CI), 95% 1.23–16.81). Male sex (OR, 3.21; CI 95%, 1.22–8.33), influenza B virus (OR, 2.82; CI 95%, 1.14–7.14) and neurologic events (OR, 3.34; CI 95%, 1.10–10.19) were found to be risk factors for pediatric intensive care unit admission.

Conclusions: A significant proportion of influenza-related hospitalized patients develop neurologic complications, especially seizures which may be prolonged or recurrent. Previous underlying conditions pose the greatest risk to neurologic events, which increase disease severity.

Streptococcus pneumoniae is the most common cause of complicated pneumonia in children, but its incidence is decreasing since the introduction of the antipneumococcal conjugated vaccines. Streptococcus pyogenes is an uncommon cause of community-acquired pleuropneumonia/empyema in children, but its relative incidence is rising.

Methods: The medical records of all children 0–18 years of age from 2004 to 2019, with discharge diagnoses of pleuropneumonia or empyema, and a positive blood and/or pleural effusion culture for group A streptococcus (GAS) ( S. pyogenes ), or S. pneumonia (SP) were reviewed. A comparison of clinical and laboratory characteristics for the 2 etiologies was performed.

Results: Ninety cases of community-acquired pleuropneumonia/empyema caused by these organisms were included: 20 GAS and 70 SP. Compared with children with SP, those with GAS were more likely to have larger pleural effusion requiring drainage and longer hospitalization, and less likely to have a positive blood culture. The relative portion of GAS empyema increased over the study period.

Conclusions: Compared with patients with SP empyema, GAS appears to cause more morbidity and a longer hospital stay. This organism is more frequently recovered from pleural fluid without bacteremia, and thus necessitates pleural fluid tap for accurate diagnosis.

A total of 714 pediatric cases of Staphylococcus aureus bacteremia were identified from 2008 to 2015 in Denmark; 98% were methicillin-susceptible S. aureus (MSSA). Fifteen isolates (2,1%) were Panton-Valentine leucocidin positive (0.17/100,000 children/year) and 87% MSSA. Eight cases (53%) were severe, including all pneumonia cases. Panton-Valentine leucocidin positive Staphylococcus aureus bacteremia is rare in our setting with high MSSA-prevalence. Half of the cases were uncomplicated.

  • The Nasopharyngeal and Gut Microbiota in Children in a Pediatric Otolaryngology Practice The Pediatric Infectious Disease Journal. 39(9):e226-e233, September 2020.

The human microbiome evolves rapidly in early life with contributions from various factors such as diet, delivery mode, medical history, antibiotics exposure, genetics, immunomodulators and the environment. A high use of antibiotics in pediatric outpatient settings has been well documented, and improvement in antibiotic selection is required to reduce the risks of antibiotic resistance and disruption of the microbiome.

Methods: We performed an exploratory study using 16S rRNA gene-based sequencing to characterize the gut and nasopharyngeal microbiome of children (n = 50) age 1–6 years of age in a pediatric otolaryngology practice.

Results: Relative abundance of Haemophilus and Moraxella were higher in nasopharyngeal swabs, while Prevotella, Bacteroides, Porphyromonas and Faecalibacterium were highly abundant in rectal swabs. The gut microbiome composition in children <2 years old was different compared with children ≥2 years age. Gut bacterial diversity increased with an increase in age of the children. Children taking probiotics had a notable increase in abundance of potentially beneficial gut bacteria such as Bacteroides and Akkermansia . The nasopharyngeal microbiome differed between children who received antibiotics in the 3 months before sample collection compared with those that did not. Haemophilus spp. was highly abundant in children who received antibiotics 3 months before sampling.

Conclusions: The pediatric nasopharyngeal and rectal microbiomes differ in bacterial composition and diversity. The increased abundance of Haemophilus spp. in the nasopharyngeal microbiome of children who received antibiotics during the 3 months before sampling suggests a potential impact of antibiotics in colonization with the otopathogen and may be relevant to clinical practice.

The outbreak of severe acute respiratory syndrome coronavirus 2 or coronavirus 2019 (COVID-19)1 in the city of Wuhan, China, in December 2019 has rapidly emerged into a pandemic affecting national communities throughout the world.2 As of May 17, 2020, more than 4.5 million people have been infected globally at a pace of 100 000/d, and 307 395 have died.3 We will briefly discuss the effects of COVID-19 on routine pediatric practice that have surfaced during the months after the onset of the pandemic and the implications for children's health. Our aim is to raise awareness about the likely need to remodel routine pediatric practice, both in hospital and ambulatory services, in light of COVID-19, and in the event of future similar infectious emergencies.

We report on the presentation and course of 33 children with multisystem inflammatory syndrome in children and confirmed severe acute respiratory syndrome coronavirus 2 infection. Hemodynamic instability and cardiac dysfunction were prominent findings, with most patients exhibiting rapid resolution following anti-inflammatory therapy.

Objective To describe the clinical profiles and risk factors for critical illness in hospitalized children and adolescents with coronavirus disease 2019 (COVID-19).

Study design Children 1 month to 21 years of age with COVID-19 from a single tertiary care children's hospital between March 15 and April 13, 2020 were included. Demographic and clinical data were collected.

Results In total, 67 children tested positive for COVID-19; 21 (31.3%) were managed as outpatients. Of 46 admitted patients, 33 (72%) were admitted to the general pediatric medical unit and 13 (28%) to the pediatric intensive care unit (PICU). Obesity and asthma were highly prevalent but not significantly associated with PICU admission (P = .99). Admission to the PICU was significantly associated with higher C-reactive protein, procalcitonin, and pro-B type natriuretic peptide levels and platelet counts (P < .05 for all). Patients in the PICU were more likely to require high-flow nasal cannula (P = .0001) and were more likely to have received Remdesivir through compassionate release (P < .05). Severe sepsis and septic shock syndromes were observed in 7 (53.8%) patients in the PICU. Acute respiratory distress syndrome was observed in 10 (77%) PICU patients, 6 of whom (46.2%) required invasive mechanical ventilation for a median of 9 days. Of the 13 patients in the PICU, 8 (61.5%) were discharged home, and 4 (30.7%) patients remain hospitalized on ventilatory support at day 14. One patient died after withdrawal of life-sustaining therapy because of metastatic cancer.

Conclusions We describe a higher than previously recognized rate of severe disease requiring PICU admission in pediatric patients admitted to the hospital with COVID-19.

Despite worldwide spread of severe acute respiratory syndrome coronavirus-2, few publications have reported the potential for severe disease in the pediatric population. We report 177 infected children and young adults, including 44 hospitalized and 9 critically ill patients, with a comparison of patient characteristics between infected hospitalized and nonhospitalized cohorts, as well as critically ill and noncritically ill cohorts. Children <1 year and adolescents and young adults >15 years of age were over-represented among hospitalized patients (P = .07). Adolescents and young adults were over-represented among the critically ill cohort (P = .02).

Objectives To compare the clinical and laboratory features of severe acute respiratory syndrome 2003 (SARS) and coronavirus disease 2019 (COVID-19) in 2 Chinese pediatric cohorts, given that the causative pathogens and are biologically similar.

Study design This is a cross-sectional study reviewing pediatric patients with SARS (n = 43) and COVID-19 (n = 244) who were admitted to the Princess Margaret Hospital in Hong Kong and Wuhan Children's Hospital in Wuhan, respectively. Demographics, hospital length of stay, and clinical and laboratory features were compared.

Results Overall, 97.7% of patients with SARS and 85.2% of patients with COVID-19 had epidemiologic associations with known cases. Significantly more patients with SARS developed fever, chills, myalgia, malaise, coryza, sore throat, sputum production, nausea, headache, and dizziness than patients with COVID-19. No patients with SARS were asymptomatic at the time of admission, whereas 29.1% and 20.9% of patients with COVID-19 were asymptomatic on admission and throughout their hospital stay, respectively. More patients with SARS required oxygen supplementation than patients with COVID-19 (18.6 vs 4.7%; P = .004). Only 1.6% of patients with COVID-19 and 2.3% of patients with SARS required mechanical ventilation. Leukopenia (37.2% vs 18.6%; P = .008), lymphopenia (95.4% vs 32.6%; P < .01), and thrombocytopenia (41.9% vs 3.8%; P < .001) were significantly more common in patients with SARS than in patients with COVID-19. The duration between positive and negative nasopharyngeal aspirate and the length in hospital stay were similar in patients with COVID-19, regardless of whether they were asymptomatic or symptomatic, suggesting a similar duration of viral shedding.

Conclusions Children with COVID-19 were less symptomatic and had more favorable hematologic findings than children with SARS.

Suspected antibiotic hypersensitivity in children is a frequent reason for consultation. Skin test performance and drug provocation test (DPT) duration are controversial issues. The objective of this study was to assess the effectiveness of diagnostic tests used in the study of antibiotic hypersensitivity and to estimate an optimal duration for DPT.

Methods: Sixty-two children with a suspected hypersensitivity reaction to antibiotics were studied. Skin tests were performed on all patients. In the case of negative results, DPTs were performed for a duration similar to the time elapsed from the start of treatment until the onset of the reaction.

Results: The frequency of antibiotic hypersensitivity in the study population was 8.1% (5 of 62). Only 1 patient showed positive skin tests. The other allergic patients were diagnosed by DPT, which reproduced the reaction within the first 6 hours in all but one of them.

Conclusions: Shortening DPT duration may decrease the sensitivity of the test for the diagnosis of non–IgE-mediated hypersensitivity; however, it should be considered as an opportunity to reduce the resulting microbial resistances.

Objective To evaluate the costs associated with evaluation of β-lactam allergy in children labeled as allergic.

Study design We performed a prospective year-long real life observational study designed to evaluate all pediatric patients with suspected β-lactam allergy who consulted for allergy evaluation. Direct and indirect costs were systematically recorded. Direct healthcare costs were calculated by taking into account the number of visits and all complementary and diagnostic tests performed. Direct nonhealthcare costs were calculated by considering the number of visits and the kilometers from their homes to the clinic. Finally, indirect costs were evaluated by considering the absenteeism of parents or other companions who took the children to the clinic.

Results A total of 40 children with suspected allergy to β-lactams were evaluated in our outpatient clinic from June 1, 2017 to May 31, 2018. Total direct healthcare costs were $5038.03, with an average cost per patient of $125.95. Direct nonhealthcare costs reached $901.87 ($22.55 per patient) and indirect nonhealthcare costs reached $6384.35 ($159.61 per patient). The total cost was $12 324.25, a cost of $308.11 per patient.

Conclusions- Elective evaluation of β-lactam allergy and delabeling children who are not allergic is not expensive. In addition, it could save future expenses because of an unnecessary lifelong use of alternative antibiotics that are usually more expensive, less effective, and more frequently associated with antimicrobial resistance and different side effects.

We used the FilmArray meningitis/encephalitis panel for evaluation of sepsis in febrile neonates. We detected human herpesvirus 6, a virus we did not routinely test for previously, in the cerebrospinal fluid of 7 neonates. In all 7 cases, detection of the virus did not warrant antiviral treatment.

In 2016, a new interferon-gamma release assay, QuantiFERON-TB Gold Plus, was introduced. We conducted a cross-sectional multicenter study, involving 158 children and adolescents with tuberculosis disease. The overall sensitivity of the assay was 82.9% (IQR 77.0%-88.8%), indicating that in children this test does not have higher sensitivity than previous generation interferon-gamma release assays.

Authors' conclusions: 

We found Xpert MTB/RIF sensitivity to vary by specimen type, with gastric aspirate specimens having the highest sensitivity followed by sputum and stool, and nasopharyngeal specimens the lowest; specificity in all specimens was > 98%. Compared with Xpert MTB/RIF, Xpert Ultra sensitivity in sputum was higher and specificity slightly lower. Xpert MTB/RIF was accurate for detection of rifampicin resistance. Xpert MTB/RIF was sensitive for diagnosing lymph node tuberculosis. For children with presumed tuberculous meningitis, treatment decisions should be based on the entirety of clinical information and treatment should not be withheld based solely on an Xpert MTB/RIF result. The small numbers of studies and participants, particularly for Xpert Ultra, limits our confidence in the precision of these estimates.

We are uncertain about the effectiveness of topical antibiotics with steroids in improving the resolution of ear discharge in patients with CSOM because of the limited amount of low-certainty evidence available. Amongst this uncertainty, we found no evidence that the addition of steroids to topical antibiotics affects the resolution of ear discharge. There is also low-certainty evidence that some types of topical antibiotics (without steroids) may be better than topical antibiotic/steroid combinations in improving resolution of discharge. There is also uncertainty about the relative effectiveness of different types of antibiotics; it is not possible to determine with any certainty whether or not quinolones are better or worse than aminoglycosides. These two groups of compounds have different adverse effect profiles, but there is insufficient evidence from the included studies to make any comment about these. In general, adverse effects were poorly reported.

After a thorough search, no RCTs which assessed the effectiveness of cranberry juice for the treatment of UTIs were found. Therefore, at the present time, there is no good quality evidence to suggest that it is effective for the treatment of UTIs. Well-designed parallel group, double blind studies comparing cranberry juice and other cranberry products versus placebo to assess the effectiveness of cranberry juice in treating UTIs are needed. Outcomes should include reduction in symptoms, sterilisation of the urine, side effects and adherence to therapy. Dosage (amount and concentration) and duration of therapy should also be assessed. Consumers and clinicians will welcome the evidence from these studies.

Objectives To determine the prevalence of vaccine hesitancy and refusal among parents of children with Down syndrome and to determine how well the Parent Attitudes about Childhood Vaccines Survey (PACV) is associated with vaccine receipt among children with Down syndrome.

Study design We mailed the PACV to parents of children with Down syndrome who attend the Down Syndrome Clinic at Akron Children's Hospital and examined associations between PACV scores and immunization status at 19 months of age.

Results Of 120 surveys sent, 63 parents completed the PACV (52% response rate) of which 60 were linked to vaccination records. Of these 60 respondents, 55 children were ≥19 months old. PACV scores were significantly correlated with days of underimmunization at 19 months of age. All parents who refused all vaccines had PACV scores of ≥50. Only 58% of children were up to date for the combined 7 vaccine series at 19 months of age.

Conclusions The PACV may be a valuable tool to identify vaccine hesitancy among parents of young children with Down syndrome. Special emphasis is needed to increase adherence with on-time vaccine recommendations for children with Down syndrome to optimize their health and to potentially avoid hospitalizations.

Vaccine refusal and hesitancy have clear adverse effects on the nonvaccinated individual as well as on the community. Related research has been performed largely in the general pediatric population. Two studies have focused their lenses on subtle forms of vaccine hesitancy, in special groups—children with Down syndrome and the general adolescent population. In this volume of The Journal Langkamp et al administered the Parental Attitudes about Childhood Vaccines Survey (PACV) (a validated tool for the general pediatric population) to 55 parents of children ≤8 years of age attending the Down Syndrome Clinic at Akron Children's Hospital and matched results with their child's immunization record to assess association with up-to-date status for standard vaccines at 19 months of age. In all, 7% of parents refused all vaccines, and 18% considered themselves as vaccine hesitant, but almost one-half reported that they were concerned that their child would have a serious side effect, thought it better to have fewer vaccines at the same time, and had decided not to have their child receive an injection for reasons other than illness or allergy. Not surprisingly at 19 months, only 58% of children with Down syndrome were up to date for all 8 vaccines and only 31% also had had no delays. The percentage of children up to date declined with higher PACV scores.

The commentary in this volume of The Journal by Williams et al validates, through evidence, the trusted role that pediatricians play in advising parents regarding administration of recommended vaccines, especially when parents are hesitant. They also provide a roadmap for forging mutually rewarding, therapeutic relationships with parents who might initially refuse vaccination. They posit proven methods of interaction based on truth, partnership, and persistence that build trust. They hope that this approach will curb the growing trend for dismissals of vaccine-hesitant families from practices, and lead to immunized, safer children and their communities.

The SARS-CoV-2 pandemic may provide a unique “teachable moment” as the tens of thousands of deaths in the US from a rampant infectious disease are an experiential reality rather than a theoretical risk. Only the development...

To evaluate a Kaiser Permanente Northern California physician training tool entitled “Effective Communication without Confrontation” aimed at improving communication with vaccine-hesitant parents, building trust, and alleviating physician stress surrounding vaccination visits.

Vaccine hesitancy is a growing public health threat. Recent data suggest that only one-half of children in the US are up-to-date for all recommended vaccines by 19-35 months, and more than one-third of children are on alternative or shot-limiting vaccine schedules.1 Measles infected 1282 Americans in 2019—the most cases since 1992—and the US nearly lost its measles elimination status.2 One in 40 kindergartners attends school with a nonmedical vaccine exemption, and many more kindergartners attend school underimmunized without plans to catch up.3 Antivaccination groups spread doubt about vaccines through film and social media outlets.4 From 2011 to 2017, elected officials introduced antivaccination bills into state legislatures more often than provaccination bills.5 Even a few physicians promote nonrecommended vaccination schedules and exempt children from vaccines without medical cause.6

In response, provaccination advocates...

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China and its rapid spread throughout the world, inflicting enormous morbidity and mortality, clearly highlights the need for safe and effective vaccines.

Many countries and pharmaceutical companies are moving rapidly to design and test such vaccines; the World Health Organization has listed more than 120 candidates in various stages of development.

 As we quickly embark on the pursuit of vaccines to prevent coronavirus disease 2019 (COVID-19), many are concerned that the rapidity with which these studies are being conducted will mean that vaccine safety will be sacrificed. However, over the past several decades...

The lower than expected rates of children affected by coronavirus disease-2019 does not mean that there was no impact on children's health. Using data on pediatric healthcare visits before and after the breakout of coronavirus disease-2019 and historical data, we identified pediatric conditions that were most affected by the pandemic and epidemic control measures during the pandemic.

This is a single-center US case series of 18 infants <90 days old who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These infants had a mild febrile illness without significant pulmonary disease. One-half of the infants were hospitalized; 1 had bacterial urinary tract co-infection. Nasopharyngeal viral loads were notably high. Latinx ethnicity was overrepresented.

Background: We investigated the association between age, duration of clinical symptoms and viral shedding in outpatient children infected with respiratory syncytial virus (RSV) in Japan.

Methods: Outpatients younger than 2 years of age, with suspected RSV infection between 2014 and 2018, were enrolled in the study. Following informed consent, nasal samples were collected at first and second clinic visits (with 0–9 days gap). RSV-A or -B infection and viral load were determined by real-time polymerase chain reaction. Clinical symptoms were recorded at first clinic visit, and fever and symptoms were recorded at home for up to 8 days. Association between clinical symptoms and patient characteristics, such as age, sex and birth weight, were analyzed using ordered logistic regression analysis. The association between viral reduction and estimated shedding period was examined using linear regression analysis.

Results: Among the 205 cases enrolled in the study, no difference was found in patient characteristics between RSV-A and -B infection. Duration of fever was prolonged with increased age. Duration of rhinorrhea and cough was shorter in females than in males and in groups with birth weight ≥3 kg than in those with <2.5 kg. Daily viral reduction increased and estimated viral elimination period decreased with age.

Conclusions: Fever duration was found to increase while viral shedding decreased with patient age.

Acute lower respiratory tract infections (ALRIs) are the most common disease for hospitalized children in Japan. The aim of this study was to identify viruses in children hospitalized for ALRIs and to demonstrate epidemiologic and clinical characteristics in Japan.

Methods: During a 2-year period from February 2013 to January 2015, we collected nasopharyngeal swab specimens from almost all hospitalized children with ALRIs in Nagasaki, a regional city of Japan, and its environs. Viruses were detected by multiplex polymerase chain reaction from these samples.

Results: We detected one or more viruses from 259 (69%) of 374 patients, 227 of whom were infected with a single virus, 30 with 2, and 2 with 3 viruses. Detected viruses in this study were rhinovirus (46.4%), respiratory syncytial virus (29.7%), human metapneumovirus (6.8%), parainfluenza virus (5.5%), enterovirus D68 (3.4%), influenza virus (2.7%), adenovirus (2.4%), bocavirus (2.0%) and Coxsackie virus (1.0%). We detected a seasonal shift in respiratory syncytial virus outbreaks from the 2013–2014 to the 2014–2015 seasons. There was no significant difference in clinical course and severity among those viruses. Patients with a history of asthma or underlying diseases were older and more frequently required oxygen therapy than previously healthy patients.

Conclusions: Viral etiology in hospitalized children with ALRIs in Nagasaki, Japan, was similar to that in many other countries. Enterovirus D68, which was recently recognized as a causative agent of severe ALRIs, was also identified in this study area. Severity of ALRIs may depend on underlying disease rather than type of etiologic virus.

Background: Estimates of the contribution of respiratory viruses to emergency department (ED) utilization remain limited.

Methods: We conducted surveillance of infants with acute respiratory infection (ARI) associated ED visits, which then resulted in either hospital admission or discharge home. Seasonal rates of specific viruses stratified by age, ethnicity, and socioeconomic status were estimated for both visits discharged directly from ED and hospitalizations using rates of positivity for each virus.

Results: During the 2014–2016 winter seasons, 3585 (66%) of the 5412 ARI ED visits were discharged home directly and 1827 (34%) were admitted to hospital. Among visits tested for all respiratory viruses, 601/1111 (54.1%) of ED-only and 639/870 (73.4%) of the hospital-admission groups were positive for at least one respiratory virus. Overall, respiratory virus-associated ED visit rates were almost twice as high as hospitalizations. Respiratory syncytial virus was associated with the highest ED (34.4 per 1000) and hospitalization rates (24.6 per 1000) among infants. ED visit and hospitalization rates varied significantly by age and virus. Māori and Pacific children had significantly higher ED visit and hospitalization rates for all viruses compared with children of other ethnicities.

Conclusions: Many infants with acute respiratory virus infections are managed in the ED rather than admitted to the hospital. Higher rates of ED-only versus admitted acute respiratory virus infections occur among infants living in lower socioeconomic households, older infants and infants of Māori or Pacific versus European ethnicity. Respiratory virus infections resulting in ED visits should be included in measurements of ARI disease burden.

Our objectives were to determine the prevalence of and to identify risk factors for coexisting bacterial meningitis (BM) in neonates with urinary tract infection (UTI).

Methods: A cross-sectional study was conducted at pediatric emergency department of a tertiary teaching hospital from 2001 to 2017. Infants <29 days of age with UTI (≥10,000 colony-forming units/mL of a single pathogen from a catheterized specimen in association with positive urinalysis) were included. Definite BM was defined as growth of a single bacterial pathogen from a cerebrospinal fluid (CSF) sample and probable BM as (1) positive blood culture with CSF pleocytosis and treatment consistent with BM or (2) antibiotic pretreatment before lumbar puncture, CSF pleocytosis and treatment consistent with BM. Univariate testing was used to identify possible risk factors associated with BM. Receiver operating characteristics curves were constructed for the laboratory markers associated with BM.

Results: Three hundred seventy-one infants were included. Five [1.3%; 95% confidence interval (CI): 0.6%–3.1%] had BM: 4 definite BM and 1 probable BM. Risk factors detected for BM were classified as not being well-appearing and a procalcitonin value ≥0.35 ng/mL [sensitivity of 100% (95% CI: 56.6%–100%) and negative predictive value of 100% (95% CI: 96.1%–100%)].

Conclusions: Coexisting BM occurs uncommonly in neonates with UTI. Well-appearing neonates with UTI and procalcitonin value <0.35 ng/mL were at very low risk for BM; avoiding routine lumbar puncture in these patients should be considered.

The Pediatric Infectious Disease Journal. 39(8):755, August 2020.

We describe 5 children with severe SARS-CoV-2 infection, hemodynamic instability and suspected acute abdomen. This form of the disease has not been previously documented. Four of the cases were confirmed SARS-CoV-2 infection and 1 probable. All of them were previously healthy and needed a pediatric critical care unit admission. The respiratory symptoms were not dominant or were absent. Also, fever was observed. Laboratory testing revealed lymphopenia and high levels of C-reactive protein and procalcitonin with d -dimer, ferritin and interleukin-6 usually elevated. Respiratory support and inotropic support were almost always necessary. In all of them, deterioration occurred on the day of admission.

We examined the dynamics of coronavirus 2019 (COVID-19) transmission within families. Our investigation demonstrated significantly lower rates of COVID-19 positivity in children compared with adults residing in the same household. Children of 5–17 years of age were 61% and children of 0–4 years of age were 47% less likely to have positive polymerase chain reaction results compared with adults residing in the same household.

In the US, 40% of families have school-aged children and in more than 90% of these households, at least 1 parent is employed outside the home. Schools play an important role in these working families.

Yet, schools have been closed for approximately 2 months in an effort to curb the coronavirus 2019 (COVID-19) pandemic, and closing has had a profound influence on family health and well-being. When and how should they reopen? We approach these questions with limited data, and past epidemics provide little guidance for COVID-19.

However, we know this: schools will reopen. Their closure is too burdensome on parents, communities, and the economy. Simply put, we cannot fully reopen society without reopening schools. This requires that children will be part of the first wave to re-emerge from shelter-in-place policies. With fast-approaching preparations required for a new school year, a collaborative team of clinicians, scientists, and educators developed this commentary to begin to highlight issues that must be considered to ensure a safe and strategically planned reopening of schools. The American Academy of Pediatrics also has recently posted considerations important to the reopening of schools.

In the US, in an urgent attempt to curb spread of severe acute respiratory syndrome coronavirus 2 and save lives, the nationwide closure of K-12 schools occurred rapidly. Planning for school reopenings must be more deliberate, delineating precisely how, when, under what conditions, and base the reopening on available data. School reopening can mitigate risks to children, families, and school personnel only if it is sensitive to community needs. Models such as the Center for Disease Control and Prevention's Whole School, Whole Community, Whole Child and the School Health Index can provide a helpful framework.

Systematic review of the early Chinese experience reveals that patients younger than 19 years accounted for only 2.2% of 44 672 confirmed cases. Although severe COVID-19 is uncommon in children, a picture of critically ill children in the US is emerging, with up to 22% having no underlying medical condition and the medical conditions of others seemingly varying by communities served.

Furthermore, without more community-based data, we don't know whether most children actually evade infection or, if infected, largely are asymptomatic. This uncertainty is dangerous. In children, who frequently require hands-on care, asymptomatic infection may pose a greater risk to susceptible individuals than might exposure to an asymptomatic adult.

In addition, current data indicate that children and adults have different infection outcomes. Possible mechanisms include changes in innate and adaptive immune responses with maturation, pediatric vaccinations or common infections that stimulate protective innate responses in children or, conversely, previous infections with common upper respiratory infection coronaviruses that stimulate deleterious acquired responses in adults, and differences in virus binding and infectivity of host epithelial cells.

Although severe acute respiratory syndrome coronavirus 2 community surveillance testing has yet to be standardized, large-scale viral nucleic acid and serologic testing in children is needed to guide safe school reopening. This testing approach will require activation of nontraditional testing sites, such as homes and schools, and “child-friendly” self-collection methods. Testing capability is only the first step. The second is understanding the test results in the appropriate context. As large-scale testing is implemented, care must be taken to ensure that these test results are interpreted and communicated appropriately so as to inform, empower, and protect families, school personnel, and communities.

I n just a matter of weeks, the coronavirus disease-2019 (COVID-19) pandemic has led to huge societal public health and economic challenges worldwide. The clinical effects of COVID-19 on young children are uncertain when compared with older age groups, with lower morbidity and mortality rates and no conclusive evidence supporting transmission during pregnancy; however, there is emerging evidence of increasing rates of child hyperinflammatory shock.1-3 Research on the effects of prior pandemics and disasters clearly indicates that there will be both immediate and long-term adverse consequences for many children, with particular risks faced during early childhood, when brain architecture is still rapidly developing and highly sensitive to environmental adversity.4 Estimates predict an increase in maternal and child mortality in low- and middle-income countries as health services for non-COVID-related issues become scarce. For example, a conservative scenario of 15% decrease in coverage of life-saving essential health interventions for 6 months in low- and middle-income countries is associated with a 9.8% increase in mortality among children less than 5 years of age and an 8.3% increase in maternal mortality.5 Before the pandemic, 43% of all children less than 5 years of age in the world were estimated to be at risk of not achieving their developmental potential.

Coronavirus diease-2019 has disrupted pediatric healthcare. Observation of public health principles are vital. However, coronavirus diease-2019 has had unintended consequences on standard pediatric care. We describe cases of delayed diagnosis of diabetes leading to severe diabetic ketoacidosis; our aim is to highlight the need to apply basic pediatric principles for optimal care.

Raba, Ali Ahmed; Abobaker, Anis Less

The Pediatric Infectious Disease Journal. 39(8):e213, August 2020.

Drug-induced liver injury (DILI) is a rare but known adverse event associated with trimethoprim-sulfamethoxazole (TMP-SMX) in adults. No studies to date have looked at the risk of this association in children. We systematically reviewed the evidence for a potential association between TMP-SMX and DILI in the pediatric population.

Methods: PubMed, Medline, Embase, Cochrane Database of Systematic Reviews, Scopus and Web of Science was searched using a combination of terms to identify reports of TMP-SMX exposure, liver injury and pediatrics (≤18 years old). We included any studies with hepatic adverse events occurring after exposure to TMP-SMX. Bibliographies were reviewed for additional relevant references. The Narajno scale was used to assess causality in case studies.

Results: A total of 22 studies were identified: 3 randomized trials, 1 prospective observational study, 8 retrospective observational studies and 10 case reports. Among the randomized trials and prospective studies, only mild, transient hepatic function abnormalities were reported. Retrospective observational studies reported 1 fatal DILI and statistically significant increased odds of DILI with TMP-SMX use compared with nonuse. Among the 10 case reports, severe liver outcomes and mild hepatic function abnormalities were both reported. Naranjo scores suggested reported hepatic adverse events were probably because of exposure in 5, possible in 4, and doubtful in 1 case report.

Conclusions: Evidence regarding DILI associated with TMP-SMX exposure in pediatrics is limited. Observational population studies show mild hepatic abnormalities. Case reports suggest more severe manifestations of DILI. Additional studies may reveal the association between TMP-SMX and DILI in pediatrics.

The Pediatric Infectious Disease Journal. 39(8):e215-e216, August 2020.

Cohen, Robert; Madhi, Fouad; Levy, Corinne; Bonacorsi, Stéphane Less

The Pediatric Infectious Disease Journal. 39(8):e216-e217, August 2020.

Ozkaya-Parlakay, Aslinur; Polat, Meltem Less

The Pediatric Infectious Disease Journal. 39(8):e218-e219, August 2020.

Diabetes Care 2020;43:991-9.

Estudio restrospectivo de cohortes en niños de 2-12 meses. Miden indicación de los tests y tratamiento antibiótico

Conclusiones: La tasa de uso de antibióticos en la bronquiolitis fue baja en todas las redes y se asoció con CXR, fiebre y apnea. Las pruebas no indicadas eran comunes fuera del Reino Unido e Irlanda y variaban a través de las redes, independientemente de las características del paciente. (Ponen en resultados que en España y Portugal se realizaron pruebas no indicadas en alrededor del 50% de los niños testados)

Se valora el efecto que la ITU durante la infancia puede tener en complicaciones renales posteriores durante el embarazo

Conclusiones: las infecciones urinarias infantiles no aumentaron el riesgo de complicaciones relacionadas con el embarazo en este estudio poblacional controlado. Por tanto, las infecciones urinarias en la infancia sin anomalías graves del tracto urinario parecen tener un efecto mínimo sobre la salud renal en la edad adulta temprana.

Artículo comentario:

Casi 6 meses después de la pandemia, la evidencia acumulada y la experiencia colectiva argumentan que los niños, particularmente los niños en edad escolar, son impulsores de la transmisión del SARS-CoV-2 mucho menos importantes que los adultos. Por lo tanto, se debe considerar seriamente las estrategias que permiten que las escuelas permanezcan abiertas, incluso durante los períodos de propagación de COVID-19. Al hacerlo, podríamos minimizar los costos sociales, de desarrollo y de salud potencialmente profundos y adversos que nuestros hijos seguirán sufriendo hasta que se pueda desarrollar y distribuir un tratamiento o vacuna eficaz o, en su defecto, hasta que alcancemos la inmunidad colectiva.

While the FilmArray Respiratory Panel EZ has been proven to reduce inappropriate antibiotic use in the outpatient pediatric setting, it is unclear whether its implementation will also reduce downstream health costs such as provider visits and telephone calls. This analysis will help pediatricians make more informed decisions on the implementation and judicious use of the Respiratory Panel EZ in their clinical practice.

 

Actualidad bibliográfica julio 2020

Top Ten

·The Role of Human Coronavirus Infection in Pediatric Acute Gastroenteritis The Pediatric Infectious Disease Journal. 39(7):645-649, July 2020.

Since human coronavirus (HCoV)–like particles were detected in the stool specimens of acute gastroenteritis and necrotizing enterocolitis children with electron microscopy, the relationship between HCoV and the pediatric gastrointestinal illness had been recognized. In recent years, the overall detection rates have been low and have varied by region. HCoVs have not been considered as the major pathogens in pediatric acute gastroenteritis. HCoVs detected in children with acute gastroenteritis have included 229E, OC43, HKU1, NL63, and severe acute respiratory syndrome coronavirus, Middle East Respiratory Syndrome Coronavirus and severe acute respiratory syndrome coronavirus-2 have also been associated with gastrointestinal symptoms in children. Although digestive tract has been recognized as an infection route, it has not been possible to fully investigate the association between HCoVs infection and the gastrointestinal symptoms because of the limited number of pediatric cases. Furthermore, pathologic features have not been clear. Till now, our knowledge of severe acute respiratory syndrome coronavirus-2 is limited. However, diarrhea and vomiting have been seen in pediatric cases, particularly in newborns and infants. It has been necessary to pay more attention on gastrointestinal transmission to identify the infected children early and avoid the children without apparent or mild symptoms becoming the sources of infection.

  • Prevalence of Gastrointestinal Symptoms and Fecal Viral Shedding in Patients With Coronavirus Disease 2019: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020;3(6):e2011335. doi:10.1001/jamanetworkopen.2020.11335

Importance:  Coronavirus disease 2019 (COVID-19) is a global pandemic and can involve the gastrointestinal (GI) tract, including symptoms like diarrhea and shedding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in feces.

Objective:  To provide a pooled estimate of GI symptoms, liver enzyme levels outside reference ranges, and fecal tests positive for SARS-CoV-2 among patients with COVID-19.

Data Sources:  An electronic literature search was performed for published (using MEDLINE/PubMed and Embase) and preprint (using bioRxiv and medRxiv) studies of interest conducted from November 1, 2019, to March 30, 2020. Search terms included “COVID-19,” “SARS-Cov-2,” and/or “novel coronavirus.”

Study Selection:  Eligible studies were those including patients with SARS-CoV-2 infection who reported GI symptoms.

Data Extraction and Synthesis:  Data on patients with GI symptoms (ie, diarrhea, nausea, or vomiting), liver enzyme level changes, and fecal shedding of virus were extracted. Quality of studies was examined using methodological index for nonrandomized studies. Pooled estimates (%) were reported with 95% CIs with level of heterogeneity (I2).

Main Outcomes and Measures:  Study and patient characteristics with pooled detection rates for diarrhea, nausea or vomiting, liver enzyme levels outside reference ranges, and SARS-CoV-2 positivity in feces tests were analyzed.

Results:  Of 1484 records reviewed, 23 published and 6 preprint studies were included in the analysis, with a total of 4805 patients (mean [SD] age, 52.2 [14.8] years; 1598 [33.2%] women) with COVID-19. The pooled rates were 7.4% (95% CI, 4.3%-12.2%) of patients reporting diarrhea and 4.6% (95% CI, 2.6%-8.0%) of patients reporting nausea or vomiting. The pooled rate for aspartate aminotransferase levels outside reference ranges was 20% (95% CI, 15.3%-25.6%) of patients, and the pooled rate for alanine aminotransferase levels outside reference ranges was 14.6% (95% CI, 12.8%-16.6%) of patients. Fecal tests that were positive for SARS-CoV-2 were reported in 8 studies, and viral RNA shedding was detected in feces in 40.5% (95% CI, 27.4%-55.1%) of patients. There was high level of heterogeneity (I2 = 94%), but no statistically significant publication bias noted.

Conclusions and Relevance:  These findings suggest that 12% of patients with COVID-19 will manifest GI symptoms; however, SAR-CoV-2 shedding was observed in 40.5% of patients with confirmed SARS-CoV-2 infection. This highlights the need to better understand what measures are needed to prevent further spread of this highly contagious pathogen.

Desde la aparición de los primeros casos en diciembre de 2019 hasta el momento actual, más de tres millones de personas se han infectado por SARS-CoV-2 en el mundo. Los síntomas más frecuentes son fiebre, tos, mialgias y dificultad respiratoria. No obstante, al progresar la pandemia, se ha prestado una atención creciente a los síntomas gastrointestinales. Entre ellos, destacan hiporexia, náuseas, vómitos y diarrea. También puede haber hipertransaminasemia. Desde el punto de vista digestivo, cabe tener en cuenta que ciertas patologías crónicas, como la enfermedad inflamatoria intestinal, pueden beneficiarse de ciertas modificaciones en cuanto a tratamiento se refiere. Por último, cabe reflejar que ha de extremarse la precaución durante la realización de endoscopias. En esta revisión se ahonda en todos estos aspectos.

Inmunidad innata frente a SARS-CoV-2. La activación de la vía del IFN limita la replicación viral e induce la posterior respuesta inmune adaptativa.  El SARS-CoV y el SARS-CoV-2 parecen compartir como receptor la ACE2, que se expresa principalmente en las células alveolares tipo 2 del pulmón  y  también se encuentran en monocitos, macrófagos o células endoteliales habiéndose descrito también neurotropismo . Los macrófagos, tras verse infectados, realizan presentación de antígenos a las células T. Este proceso, en el que se añade la presencia de PAMP (patrones moleculares asociados a patógenos) derivados de viru ( y que reconocen las células de la inmunidad innata) , conduce a la activación y diferenciación de células T, incluida la producción de citocinas asociadas con los diferentes subconjuntos de células T-

Se especuló que en la infección por SARS-CoV o MERS-CoV, el retraso en la respuesta IFN tipo 1 comprometía el control de la replicación viral. Esto provocaba la citada afluencia de neutrófilos y monocitos-macrófagos9. El aumento y activación persistente de estas células derivaría en daño pulmonar, incluida la neumonía o el síndrome de dificultad respiratoria aguda. En la infección por SARS-CoV-2, sería esperable un escenario similar.

Papel de linfocitos T en la inflamación por coronavirus

En la respuesta inmune a coronavirus, el papel de los linfocitos T es predominante. En el caso de MERS CoV  los linfocitos CD4+ eran más susceptibles a la infección y su daño condicionaba una peor evolución. Dicha susceptibilidad se observó también en el caso de SARS-CoV9. En este caso la depleción de CD4+ se traducía en un menor reclutamiento de linfocitos en territorio pulmonar, lo que condicionaba una importante neumonitis intersticial con un menor aclaramiento del viru. A consecuencia de esta disregulación, los linfocitos T CD4+ presentes generaban un aumento de citocinas que se traducía en un cúmulo de monocitos y neutrófilos que activaban a su vez otras cascadas inflamatorias mediante la síntesis de citocinas (IL-1, LL-6, IL-8, IL-21, TNF-β y MCP-1).

Mecanismos de evasión inmunitaria

Los coronavirus están particularmente adaptados para evadir la detección inmune en el reconocimiento de interferón, el cross-talking intercelular y la señalización intracelular suponen los 3 modos fundamentales para lograr evadir la actividad inmunitaria.

 Los coronavirus infectan de forma primaria a macrófagos. Estos presentan los antígenos sobre las células T, lo que provoca su activación y la producción de citocinas asociadas a los diferentes subtipos de estos (destacando Th17). Posteriormente estas citocinas amplificarán la respuesta inmune9.

La producción de IFN tipo 1 es de gran importancia c para optimizar la liberación de proteínas antivirales, promover la fagocitosis por macrófagos y facilitar la protección de células no infectadas. Las proteínas accesorias de los coronavirus pueden interferir la señalización vía PAMP de los receptores de tipo toll (toll-like receptors o TLR) durante la replicación para evitar así la activación. Con ello, Por un lado, se facilita la persistencia viral. Por otro, se genera un efecto negativo en células natural killer (NK) o macrófagos y se altera la activación de las células T CD8+.

 Ambos fenómenos se pueden acompañar de una producción inadecuada de citocinas ( IL-1, IL-6, IL-8, IL-21, factor de necrosis tumoral beta (TNF-β) y proteína quimioatrayente de monocitos 1 (MCP-1)  que provoca el reclutamiento de linfocitos y leucocitos en el lugar de infección

Patrón de respuesta inmune a coronavirus SARS-CoV-2

La mayoría de pacientes con COVID-19 y necesidad de ingreso hospitalario mostraron linfopenia. Esto se justificaría, como se ha explicado, por la migración a territorio pulmonar de linfocitos T, que se apreciaría como . neumonías bilaterales con imágenes en vidrio esmerilado constituirían   ( en RxT y Tc Tórax). 

En relación con las poblaciones leucocitarias, y dada la linfopenia, se ha propuesto el ratio neutrófilo-linfocito como un posible marcador de evolución. El descenso relativo de linfocitos sería un marcador indirecto de la inflamación pulmonar subyacente.

En pacientes COVID-19 hospitalizados con mala evolución, se han descrito niveles de citocinas aumentados (IL-2, IL-7, IL-10, G-CSF, IP-10, MCP-1, MIP-1A y TNFα28)

 También se ha descrito un aumento de dímero D, troponina I, IL-6 en suero y de proteína C reactiva3. En relación con la IL-6, esta es producida por macrófagos, células T, células endoteliales y fibroblastos y su expresión exacerbada no solo condiciona un estado proinflamatorio , sino también fenómenos de activación macrofágica

Tratamientos

Lopinavir/ritonavir: El uso de ambos antivirales se plantea en COVID-19 como resultado de su anterior utilidad frente a SARS-CoV y MERS-CoV. No existe evidencia actual que sustente su uso y los primeros trabajos realizados indican que puede no tener influencia sobre la mortalidad de estos pacientes.

Remdesivir: posee actividad antiviral frente a un número amplio de virus ARN. Su efecto y utilidad frente a SARS-CoV-2 se encuentra en estudio.

Hidroxicloroquina: alcaliniza el medio dificultando la acción del fagolisosoma viral y, por lo tanto, enlentece o dificulta la replicación de coronavirus. Recientemente se ha demostrado su utilidad in vitro contra el SARS-CoV-2. Dicha utilidad aún no dispone de evidencia clínica siendo por lo tanto su uso empírico. Se debe prestar atención a los posibles efectos secundarios.

Macrólidos: Se atribuye a este grupo de antibióticos cierto perfil inmunomodulador (sobre la acción de neutrófilos o la liberación de citocinas como IL-8) . No existe aún evidencia que confirme que su uso individual o en combinación con HQ permita una mejor evolución35.

Interferón alfa y beta: objetivo mitigar la posible disrupción que en esta vía de respuesta innata produce el virus. En  anteriores epidemias por coronavirus ofreció resultados controvertidos.

Corticoides: su  uso en COVID-19 resulta discutido. Por un lado,  tiene  efecto inmunosupresor que ante una disregulación inmune proinflamatoria pudiera ser útil. Por otro lado, incrementan y perpetúan la linfopenia pudiendo interferir en una respuesta dirigida a aclarar la presencia viral. Las recomendaciones realizadas por los clínicos que atendieron COVID-19 en Wuhan pivotan sobre 5 claves: (1) Se debe valorar cuidadosamente el beneficio/riesgo de su uso. (2) Se deben considerar sobre todo en pacientes críticos. (3) En pacientes con hipoxemia debida a enfermedades subyacentes o con tratamiento con corticoides de forma regular debe considerarse su uso. (4) Las dosis deben ser bajas o moderadas (≤0,5-1mg/kg por día de metilprednisolona o equivalente), y (5) la duración debe ser corta (≤7días)37.

Tocilizumab: anticuerpo monoclonal humanizado dirigido contra el receptor de la IL-6. Su uso podría frenar la activación inmunitaria subyacente siendo por lo tanto una opción terapéutica en pacientes con crítica o mala evolución. En el caso de no disponer de la determinación de esta molécula, se puede utilizar como biomarcador la ferritina.

Suero de convaleciente: Planteado su uso en epidemias previas por SARS-CoV y MERS-CoV, en el momento actual existen pocos datos acerca de su beneficio. Solo un trabajo sobre 5 pacientes parece ofrecer resultados. Debe ser valorado su uso con precaución .

Schistosomiasis, also known as Bilharzia, is a waterborne parasitic disease that affects over 230 million people worldwide, accounting for 1.44 million disability-adjusted life years lost.1,2 It is caused by trematode parasites of the genus Schistosoma, (S.) which have intricate life cycles requiring human freshwater contact and the presence of a suitable snail vector. Transmission occurs during freshwater contact, as cercariae penetrate human skin and migrate via major blood vessels to final venous plexuses. The lifespan of a schistosome ranges between 3 and 10 years but can live up to 40 years

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2763176

https://jamanetwork.com/journals/jama/fullarticle/2767634

·Symptomatic Infection is Associated with Prolonged Duration of Viral Shedding in Mild Coronavirus Disease 2019: A Retrospective Study of 110 Children in Wuhan The Pediatric Infectious Disease Journal. 39(7):e95-e99, July 2020.

Information regarding viral shedding in children with coronavirus disease 2019 (COVID-19) was limited. This study aims to investigate the clinical and laboratory characteristics associated with viral shedding in children with mild COVID-19.

Methods: The clinical and laboratory information of 110 children with COVID-19 at Wuhan Children’s Hospital, Wuhan, China, from January 30 to March 10, 2020, were analyzed retrospectively.

Results: The median age was 6 years old. The median period of viral shedding of COVID-19 was 15 days (interquartile range [IQR], 11–20 days) as measured from illness onset to discharge. This period was shorter in asymptomatic patients (26.4%) compared with symptomatic patients (73.6%) (11 days vs. 17 days). Multivariable regression analysis showed increased odds of symptomatic infection was associated with age <6 years (odds ratio [OR] 8.94, 95% confidence interval [CI]: 2.55–31.35; P = 0.001), hypersensitive C-reactive protein >3.0 mg/L (OR 4.89; 95% CI: 1.10–21.75; P = 0.037) and presenting pneumonia in chest radiologic findings (OR 8.45; 95% CI: 2.69–26.61; P < 0.001). Kaplan-Meier analysis displayed symptomatic infection ( P < 0.001), fever ( P = 0.006), pneumonia ( P = 0.003) and lymphocyte counts <2.0 × 10 9 /L ( P = 0.008) in children with COVID-19 were associated with prolonged duration of viral shedding in children with COVID-19.

Conclusion: Prolonged duration of viral shedding in children with COVID-19 was associated with symptomatic infection, fever, pneumonia and lymphocyte count less than 2.0 × 10 9 /L. Monitoring of symptoms could help to know the viral shedding in children with COVID-19.

·Mycoplasma pneumoniae in Children With and Without Community-acquired Pneumonia. What do PCR and Serology Say? The Pediatric Infectious Disease Journal: July 2020 - Volume 39 - Issue 7 - p e104-e108 doi: 10.1097/INF.0000000000002636

Background: IgM titers of Mycoplasma pneumoniae can remain high for months or years, and specific DNA can be detected in asymptomatic people.

Methods: We compared the performance of serology and PCR in children with and without community-acquired pneumonia (CAP) for the diagnosis of M. pneumoniae.

Results: In children with CAP, a positive test by M. pneumoniae (PCR and/or paired serology or both) were found in 13.9%. Of these, 10.3% were positive by multiplex PCR (Seeplex-Seegen), and 6.7% exhibited quadrupled titers (22 for IgG, 6 for IgM and 5 for both). Both tests were positive in 2.8% of cases. In the group without CAP, 3.3% were positive by PCR. Thirty-two percent of children with CAP and 38.3% of healthy children had IgM titers >11 in the acute phase.

Conclusions: The detection of IgM is not useful for diagnosing acute M. pneumoniae infection, and a positive PCR result can be due to colonization and not infection. New and better diagnostic techniques are required.

The clinical spectrum of Mycoplasma pneumoniae pneumonia is widely variable. This study evaluated the clinical manifestations of M. pneumoniae pneumonia in children of different age groups and by the presence of co-detected respiratory virus.

Methods: This study included children hospitalized with M. pneumoniae pneumonia between 2010 and 2015. At the time of pneumonia diagnosis, a nasopharyngeal aspirate was analyzed for respiratory viruses by reverse transcription-polymerase chain reaction (RT-PCR). The clinical manifestations and laboratory findings were reviewed from medical records.

Results: Of the 286 children with M. pneumoniae pneumonia, 84 (29.4%) had a co-detected respiratory virus, with the highest co-detection rate in young children (51.9% of children <2 years; P = 0.002). In children <2 years, with and without co-detected virus, wheezing occurred in 35.7% and 15.4%, respectively. Among the 202 children without any virus detected, only 6.4% were <2 years. These young children showed fewer median days of fever than the children ≥2 years (8 vs. 11 days; P = 0.022). Children ≥2 years tended to have accompanying skin rashes (21.7% vs.7.7%; P = 0.310) and elevated liver enzymes (21.7% vs. 0%; P = 0.075) more frequently than children <2 years. Only 53.8% of the patients <2 years were treated with macrolide compared with 94.1% of the patients ≥2 years (P < 0.001).

Conclusions: The clinical manifestations of M. pneumoniae pneumonia in young children are milder than those in older children. A high prevalence of co-detected respiratory virus in young children suggests that virus might play a role in making pneumonia clinically apparent in this age group.

Objetivos: analizar el empleo de los test de detección rápida de antígeno estreptocócico en Pediatría de Atención Primaria (AP), su impacto en la prescripción de antibióticos y la reducción de costes del tratamiento antibiótico. Material y métodos: estudio descriptivo transversal, en menores de 15 años atendidos en AP, en 24 centros de salud, desde abril de 2017 hasta febrero de 2018. Se elaboró un protocolo de utilización del test de detección rápida de antígeno estreptocócico (TDRS). Se incluyeron pacientes con escala Centor mayor o igual a 2 puntos. Se extrajeron del sistema de facturación de recetas datos del número de dosis diaria definida (DDD) e importe de antibióticos en dicha temporada, comparándose con el gasto en los 12 meses previos. Resultados: se realizaron 819 TDRS. Resultaron positivos 250 (30,5%), negativos 557 (68%) y 12 no valorables (1,5%). Se prescribió antibiótico al 33% de los pacientes (todos los positivos, 18 negativos, 3 no valorables). En 539 pacientes (97%) con resultado negativo no se instauró antibiótico. El número de DDD total disminuyó en 21 960 (12%), de las cuales 19 023 (86,6%) corresponden a los antibióticos más utilizados (penicilinas, amoxicilina, amoxicilina-clavulánico y azitromicina). La reducción económica fue de 11 320 € (12,5%) y el gasto en TDRS fue de 991 €, lo que supone un ahorro de 10 329€. Conclusiones: la introducción del TDRS en consultas de Pediatría de AP ha permitido que se eviten un elevado número de tratamientos antibióticos. Su utilización ha demostrado ser eficiente en la optimización del consumo de antibióticos, consiguiendo reducir su utilización, evitar efectos adversos y reducir el gasto farmacéutico innecesario.

Casos clínicos

An otherwise healthy 8-year-old girl presented with a 2-month history of mildly pruritic, area of alopecia on her scalp. Examination revealed a well-circumscribed, annular (4 × 3 cm), slight scaly, noninflammed, grayish-white patch of hair loss (Figure, A ). Marked hair fragility was elicited on hair pull; no cervical lymphadenopathy was noted. Other mucocutaneous sites were uninvolved. Dermoscopic (Dermlite, DL4, polarized/contact mode, 10×, San Juan Capistrano, California) evaluation of the alopecic patch showed multiple black dots, comma hair, and corkscrew hair along with peripilar scales (Figure, B). Wet mount with 10% potassium hydroxide of skin scraping and pulled hair revealed branched, septate hyphae and spores within the hair shaft. Based on the clinicodermoscopic and microbiologic findings, a diagnosis of tinea capitis was established. The lesion healed with a 4-week course of systemic and topical antifungals without any residual scarring.

A 2-year-old girl is admitted to the paediatric critical care unit following a traumatic pneumothorax as a result of a road traffic collision. After a few days, the chest drain is removed, and she is transferred to the ward for further observation. You clerk the patient on admission to the paediatric ward and are pleased to note that she is well, with no signs of respiratory distress and all observations within normal limits for her age. A senior colleague requests that you arrange a chest X-ray (CXR) to ensure that the pneumothorax has resolved. You question the importance of this investigation in an asymptomatic child.

Structured clinical question

Following chest drain removal in children (patient), does routine chest radiography (intervention) assist in monitoring or change the management of asymptomatic patients (outcome)?

Search

In December 2019, we searched Embase (1946–present) and MEDLINE (1946–present) databases using the OVID search interface. Our search terms included: (chest x-ray OR chest radiograph) AND (chest drain OR chest tube OR thoracostomy tube) AND (removal OR withdrawal) AND (children OR paediatrics OR adolescents OR infants). We identified 98 articles, written in English language, which were reviewed further; case reports and conference abstracts were excluded. A further search of the Cochrane Library was performed using the same search terms, which identified 14 clinical trials; however, none of these trials were appropriate for our clinical question. A total of 6 relevant studies were identified as described in table 1. The level of evidence was classified according to Oxford Centre for Evidence-Based Medicine 2009.1

A 6-month-old infant and her family presented with a 5-month relapsing scabies at a post-therapy visit. Topical 5% permethrin treatment was administered to all members, and repeated five times at a once every week regimen.

The examination was negative for active skin burrows, though an elongated, scaling lesion around the infant’s second right fingernail lateral folds and an analogous lesion on the elder brother’s hallux nail folds were detected. Dermoscopy showed intact burrows and subsequent scraping confirmed the presence of Sarcoptes mites (figure 1). Topical treatment with 5% permethrin under occlusion led to the definitive resolution of the scabies. …

·Mycobacterium abscessus Soft Tissue Infection: Review of Published Cases and Challenges in Treatment. The Pediatric Infectious Disease Journal. 39(7):e130-e132, July 2020

We report the first case of Mycobacterium abscessus soft tissue infection following a firearm injury. We summarize previous published cases of M. abscessus soft tissue infection and review the current evidence on management.

 la sintomatología gastrointestinal está presente de forma relevante, según un metaanálisis, con una incidencia acumulada del 17,6% y en el subgrupo de población pediátrica del 24,8%. Posible fisiopatogenia : elevada expresión del receptor de la enzima convertidora de angiotensina 2 en las células intestinales, el cual modula la inflamación gastrointestinal.

Niño de 11 años, sin antecedentes , con dolor abdominal en FII, fiebre, vómitos y diarrea de 5 días, sin otra sintomatología y sin ambiente epidémico familiar.EF: REG, sin aspecto séptico, normotenso, sin signos de distrés, auscultación cardiopulmonar normal, abdomen distendido, blando, depresible con dolor a la palpación en hemiabdomen izquierdo y defensa abdominal. PPCC: hemograma con linfopenia (590/mcl). Bioquímica normal excepto ferritina 463ng/ml e IL-6 65,9pg/ml. Coagulación: AP 61%, dímero D 1.062μg/l, fibrinógeno >500s. Proteína C reactiva (PCR) 416,4mg/l y procalcitonina (PCT) 1,34ng/ml; hemocultivos, coprocultivo y toxina de Clostridium difficile negativos; test de detección de anticuerpos para SARS-CoV-2 y PCR-SARS-CoV-2 nasofaríngea positivos. Rx Tórax normal y ecografía abdominal con engrosamiento parietal difuso de colon descendente e hiperecogenicidad de la grasa adyacente. Con diagnóstico de infección por SARS-CoV-2 con afectación gastrointestinal se inicia tto con hidroxicloroquina, lopinavir/ritonavir y metilprednisolona intravenosa. Ante la sospecha de sobreinfección bacteriana abdominal, por elevación PCR y PCT, se asocia amoxicilina-clavulánico iv.Tras 24 h, mejoría clínica y descenso de los marcadores inflamatorios hasta su normalización al alta, completando 7 días de tto, momento en el que se repite PCR-SARS-CoV-2 nasofaríngea siendo negativa.

Se ha descrito la posibilidad de su transmisión por la excreción fecal, por la detección del ARN viral en las heces de pacientes infectados, incluso varias semanas tras su negativización en muestras respiratorias

·Erupción purpúrica petequial, ni en guantes, ni en calcetines. Rev Pediatr Aten Primaria. 2020;22:e55-e59.

El parvovirus B19 generalmente infecta a niños y adultos jóvenes, presentando cuadros exantemáticos característicos, como el eritema infeccioso. Dentro de las manifestaciones hemorrágicas con erupción purpúrica-petequial, está el síndrome papular-purpúrico en guantes y calcetines. En ocasiones, distribuciones atípicas con erupciones petequiales asimétricas podrían complicar el diagnóstico, llevando a plantear diagnósticos diferenciales y a realizar pruebas de laboratorio. Se describe un caso inusual de parvovirus B19 con erupción petequial atípica, y se hace una revisión de la literatura médica reciente.

·Tumoración cervical como única manifestación de fístula de seno piriforme. Rev Pediatr Aten Primaria. 2020;22:169-73.

Las adenopatías son la tumoración cervical benigna más frecuente en los niños, pero se deben sospechar otras patologías en caso de localización atípica, crecimiento rápido, consistencia pétrea, signos inflamatorios o supuración espontánea. La fístula del seno piriforme es una malformación congénita infrecuente de los arcos branquiales. Tras una infección, da lugar a una pseudotumoración que normalmente cursa con signos inflamatorios locales, fiebre y odinofagia, por lo que el tratamiento del proceso agudo es la antibioterapia sistémica de amplio espectro asociada en ocasiones a drenaje. El estudio de toda masa cervical debe iniciarse con una ecografía, a completar con una tomografía computarizada con contraste en caso de hallazgos sugestivos de absceso adyacente al tiroides o inflamación del mismo, que pueden orientar hacia fístula del seno piriforme. El método diagnóstico de confirmación es el examen endoscópico en el quirófano bajo anestesia general, que permite además realizar el tratamiento quirúrgico definitivo. Presentamos el caso clínico de una paciente que acude remitida desde Atención Primaria tras detectársele una tumoración indurada a nivel paramedial izquierda como única manifestación, consecuencia de una fístula de seno piriforme. 

·Rigidez de nuca, ¿siempre neurológico? Pensemos algo más. Rev Pediatr Aten Primaria. 2020;22:175-80.

Las complicaciones supurativas de la faringoamigdalitis aguda no tratada o inadecuadamente tratada son infrecuentes. Destacan, por su potencial gravedad, el absceso retrofaríngeo y parafaríngeo. Por su presentación clínica como limitación de movilidad cervical o rigidez de nuca en contexto infeccioso, pueden plantear la sospecha inicial de meningitis aguda. Por ello, es necesario que los profesionales sanitarios conozcan las características clínicas y la evolución de estas complicaciones, para así actuar de manera correcta, precoz y eficaz, debido a su potencial gravedad. A continuación, se presentan dos casos de complicaciones supurativas del área otorrinolaringológica que debutaron con clínica cervical: rigidez de nuca o limitación de la movilidad, y que suponen un reto diagnóstico

La infección por el nuevo coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2 [SARS-CoV-2]), identificado en 2019 en Wuhan (China), es el causante de la denominada enfermedad por coronavirus 2019 (COVID-19)1. Actualmente se ha extendido provocando una pandemia mundial que, según la Organización Mundial de la Salud, afecta a más de un millón y medio de personas en el mundo2. Al inicio del brote de COVID-19, la afectación en pacientes pediátricos fue descrita solo excepcionalmente, pero con la extensión progresiva del brote, cada vez se han comunicado más casos en niños, siendo la mayor parte de ellos leves o asintomáticos3.

Las manifestaciones clínicas comunes incluyen fiebre, tos seca, odinofagia, cefalea, astenia, mialgias y dificultad respiratoria. Hasta el momento, las manifestaciones cutáneas relacionadas con la COVID-19 han sido descritas solamente en la población adulta3,4. Dada la escasa información sobre esta clínica en pediatría se presentan 2 casos de pacientes pediátricos con infección por SARS-CoV-2 y afectación cutánea.

El primer caso es el de...

Desde la descripción de lesiones acroisquémicas asociadas a COVID-19 en la población pediátrica1 y su extensa difusión a través de medios de comunicación y redes sociales, son numerosas las asistencias diarias en consultas de pediatría y dermatología por estas lesiones.

La paciente 1...

·The Treatment of Acute Rheumatic Fever: Novel Use of Hydroxychloroquine The Pediatric Infectious Disease Journal. 39(7):e120-e122, July 2020.

Hydroxychloroquine (HCQ) suppresses an interleukin-1β-granulocyte-macrophage colony-stimulating factor cytokine axis, reported to be dysregulated in peripheral blood mononuclear cells of acute rheumatic fever patients ex vivo . We describe HCQ treatment for 2 patients with rheumatic carditis and a protracted inflammatory course. HCQ was associated with control of inflammatory markers, control of pericarditis in first patient and stabilization of progressive carditis in the second patient

Para profundizar

·The Association of Antibiotic Duration With Successful Treatment of Community-Acquired Pneumonia in Children. Journal of the Pediatric Infectious Diseases Society, piaa055, https://doi.org/10.1093/jpids/piaa055

National guidelines recommend 10 days of antibiotics for children with community-acquired pneumonia (CAP), acknowledging that the outcomes of children hospitalized with CAP who receive shorter durations of therapy have not been evaluated.

Methods

We conducted a comparative effectiveness study of children aged ≥6 months hospitalized at The Johns Hopkins Hospital who received short-course (5–7 days) vs prolonged-course (8–14 days) antibiotic therapy for uncomplicated CAP between 2012 and 2018 using an inverse probability of treatment weighted propensity score analysis. Inclusion was limited to children with clinical and radiographic criteria consistent with CAP, as adjudicated by 2 infectious diseases physicians. Children with tracheostomies; healthcare-associated, hospital-acquired, or ventilator-associated pneumonia; loculated or moderate to large pleural effusion or pulmonary abscess; intensive care unit stay >48 hours; cystic fibrosis/bronchiectasis; severe immunosuppression; or unusual pathogens were excluded. The primary outcome was treatment failure, a composite of unanticipated emergency department visits, outpatient visits, hospital readmissions, or death (all determined to be likely attributable to bacterial pneumonia) within 30 days after completing antibiotic therapy.

Results

Four hundred and thirty-nine patients met eligibility criteria; 168 (38%) patients received short-course therapy (median, 6 days) and 271 (62%) received prolonged-course therapy (median, 10 days). Four percent of children experienced treatment failure, with no differences observed between patients who received short-course vs prolonged-course antibiotic therapy (odds ratio, 0.48; 95% confidence interval, .18–1.30).

Conclusions

A short course of antibiotic therapy (approximately 5 days) does not increase the odds of 30-day treatment failure compared with longer courses for hospitalized children with uncomplicated CAP.

Starting from 2 pediatric cases of COVID-19, with confirmation at nasopharyngeal and rectal swabs, we considered the lesson learnt from previous Coronavirus epidemics and reviewed evidence on the current outbreak. Surveillance with rectal swabs might be extended to infants and children, for the implications for household contacts and isolation timing.

·Children’s Healthcare During Corona Virus Disease 19 Pandemic: the Italian Experience. The Pediatric Infectious Disease Journal. 39(7):e137-e140, July 2020.

The unexpected outbreak of Corona Virus Disease 19 had several consequences worldwide and on the Italian Health System. We report our experience in the reorganization of our Pediatric Department to prevent the risk of infection for both children and staff. We strongly believe that the need to face an unpredictable emergency situation should not affect the quality of the assistance to the non–Corona Virus Disease patients.

La pandemia de COVID-19 ha planteado a nivel epidemiológico, clínico y preventivo incógnitas aún no resueltas por la comunidad científica. El impacto directo de la infección en los niños es muy bajo en comparación con el que ha supuesto en población adulta. A fecha de 31 de mayo de 2020, los menores de 14 años suponen el 0,6% de los pacientes totales confirmados en España, la afectación que han presentado ha sido más leve y mejor el pronóstico de la enfermedad, registrándose hasta la fecha tres fallecimientos1.

Sabemos que, durante el momento más duro de la pandemia, muchos pediatras, tanto de hospital como de Atención Primaria, colaboraron activamente en la atención a adultos enfermos de COVID-19, pero a continuación voy a referirme exclusivamente a las condiciones de atención a los pacientes pediátricos y a los condicionantes que, derivados de esta situación, pueden influir en la salud de los niños.

·Unique Features of Hospitalized Children with Alveolar Pneumonia Suggest Frequent Viral-Bacterial Coinfections The Pediatric Infectious Disease Journal. 39(7):586-590, July 2020.

The World Health Organization Pneumonia Expert Group (WHO-PEG) defined a standardized radiologic endpoint for childhood community-acquired alveolar pneumonia (RD-CAAP), as the most likely to be pneumococcal, not ruling out other bacteria or coinfecting viruses. We aimed to determine the characteristics associated with hospitalization among children <5 years old presenting to the pediatric emergency room (PER) with RD-CAAP.

Methods: This study was a part of an ongoing prospective population-based surveillance on hospital visits for RD-CAAP. RD-CAAP was determined according to the WHO-PEG. The study was conducted in the prepneumococcal conjugate vaccine era (2004–2008).

Results: Of 24,432 episodes with chest radiographs, 3871)15.8%) were RD-CAAP: 2319 required hospitalization and 1552 were discharged (outpatients). Compared with outpatients, hospitalized children had lower temperature, peripheral white cell and absolute neutrophil counts and C reactive protein serum levels, but higher rates of hypoxemia, rhinorrhea, cough and respiratory virus detection. PER visits during the respiratory virus season presented a 1.83 times higher risk of hospitalization than visits during nonrespiratory season.

Conclusions: Although RD-CAAP is most often a bacterial infection, the unique characteristics of those visiting the PER and subsequently hospitalized suggest a frequent involvement of respiratory viruses, potentially as viral-bacterial coinfections, compared with outpatients.

Question: In the era of the pneumococcal vaccine, what is the evidence for adjusting high-dose beta-lactam antibiotic recommendations for acute otitis media (AOM)?

Relative presence of nasopharyngeal-cultured respiratory bacterial organisms.

There has been an increase in recovery of Haemophilus influenzae and a decrease in recovery of penicillin-resistant Streptococcus pneumoniae from nasopharyngeal specimens.

Conclusions: Recent microbiologic data suggest a treatment recommendation of regular dose amoxicillin-clavulanate.

Commentary: Pneumococcal conjugate vaccination has impacted the proportion of AOM infections, and presumably acute bacterial sinusitis infections caused by pneumococci. Based on our publication in 2017  and other sources, I agree that use of amoxicillin-clavulantate in preference to amoxicillin would be appropriate because about 50% of Haemophilus influenzae and all Moraxella catarrhalis isolated from middle ear fluid are resistant to amoxicillin.

 However, as the paper by Wald and DeMuri point out the situation is dynamic. Since publication of our paper, we have observed a dramatic increase in pneumococcal AOM,  returning to an incidence similar to pre-pneumococcal vaccine (PCV)13 (Kaur et al, manuscript submitted) and rising. In particular, we found that serotypes 35B and 35F are increasing in frequency and these strains are penicillin and multi-antibiotic resistant.

 Neither serotype will be included in forthcoming PCVs from Merck (PCV15) or Pfizer (PCV20). Also, we and others have found that H. influenzae is the most important pathogen causing recurrent AOM, chronic AOM, otitis media with effusion, and otitis media-associated hearing loss. The bacteria often form biofilms in the nasopharynx and middle ear, leading to the false impression of a “spontaneous cure” rate, often quoted to be 50%. Thirdly, disturbance of the resident, commensal microbiome in the nasopharynx and gut by antibiotic use can be harmful, with adverse effects on innate and adaptive immunity, autoimmunity, etc. Broader spectrum antibiotics, especially those that have activity against anaerobes such as amoxicillin-clavulanate, disturb the microbiome more than narrow spectrum antibiotics such as amoxicillin. Therefore, antibiotic treatment decisions are complicated by the need to weigh benefits and risks. My treatment of choice in today’s practices would be high-dose amoxicillin-clavulanate for a shortened 5-days treatment to optimize cure and reduce microbiome-disturbing adverse effects.

Question, Among children treated with antibiotics for acute otitis media (AOM), what is the incidence of common antibiotic-attributable adverse events (AEs)?

Design, Systematic review, meta-analysis.

Setting, Presumably outpatient and presumably in developed countries.

Participants: Children, 0-19 years old, treated with antibiotics for otitis media.

Intervention: Antibiotic (amoxicillin, amoxicillin/clavulanate, azithromycin, and cefdinir) treatment of AOM.

Outcomes: Incidences of diarrhea, generalized rash, diaper rash, and candidal diaper dermatitis.

Main Results: The meta-analysis included 82 articles. The incidences were of diarrhea: azithromycin (2.2%), placebo (6.9%), low-dose amoxicillin (8.7%), cefdinir (13.0%), high-dose amoxicillin (13.8%), and high-dose amoxicillin/clavulanate (18.9%); of generalized rash: azithromycin (1.4%), placebo (2.3%), low-dose amoxicillin (2.9%), high-dose amoxicillin/clavulanate (4.9%), and high-dose amoxicillin (6.5%); of diaper rash: placebo (4.6%), low-dose amoxicillin (6.4%), cefdinir (10.1%), and high-dose amoxicillin/clavulanate (14.8%); of candidal diaper rash: high-dose amoxicillin/clavulanate (3.3%), low-dose amoxicillin (5.8%).

Conclusions: The incidence of common AEs varied widely among commonly employed antibiotics.

Commentary: Antibiotics are the most commonly prescribed drug class for children,  as well as the leading cause of emergency department visits for adverse drug events in children.

 Knowledge of antibiotic AEs is therefore important for pediatric providers. The results of this meta-analysis should be interpreted with some caution, due to significant heterogeneity of included studies and a high risk of bias related to AE reporting. Still, the pooled AE rates provide useful insight into the frequency of common AEs observed with antibiotic therapy for AOM. The authors suggest that these AE rates may be helpful to clinicians when selecting antibiotics for AOM. Indeed, the highest rate of diarrhea (18.9%) occurred with high-dose amoxicillin/clavulanate, the recommended second-line agent for AOM.

 This underscores limiting its use to children who recently received amoxicillin, have otitis-conjunctivitis syndrome, or are failing high-dose amoxicillin. However, high-dose amoxicillin, the recommended first-line agent, had the second-highest rate of diarrhea (13.8%) and the highest rate of generalized rash (6.5%). Does this mean we should abandon high-dose amoxicillin in favor of other agents? High-dose amoxicillin has the highest activity of the commonly prescribed oral agents against the most common bacterial AOM pathogen, Streptococcus pneumoniae, and it retains activity against more than half of Haemophilus influenzae strains. It is also the most narrow-spectrum drug of these agents and is well tolerated. Thus, for children who truly need antibiotics, high-dose amoxicillin is still the best choice. A better question, then, may be whether antibiotics are warranted at all. Observation is a guideline-recommended option for select groups of children with AOM, and it is also the best way to avoid antibiotic AEs. This study is an important reminder that even the “best” antibiotics carry risk, and the need for judicious antibiotic prescribing is paramount.

Introducción y objetivos: analizar las características clínico-epidemiológicas de la dermatitis perianal por estreptococo betahemolítico del grupo A (SBHGA). Material y métodos: serie de casos con recogida prospectiva de datos durante un periodo de ocho años en una consulta de Pediatría. Resultados: se diagnosticaron 95 episodios (1/298 consultas) en 76 niños (varones/mujeres: 1,6/1). Edad media 4,5 años. Padecieron más de un episodio 13 pacientes con un total de 19 episodios sucesivos: 10 de ellos en un periodo inferior a 6 meses respecto al anterior (11% del total de episodios). Los motivos de consulta más frecuentes fueron: prurito, sangrado, dolor, estreñimiento y eritema perianal. El tratamiento se realizó por vía tópica en el 70% de los primeros episodios y combinado (tópico y sistémico) en el 68% de los sucesivos. Se constató un fracaso terapéutico inicial en tres episodios. La distribución estacional fue similar a la de faringoamigdalitis y escarlatinas por SBHGA diagnosticadas en el mismo periodo. Conclusiones: cinco motivos de consulta (prurito, sangrado, dolor, estreñimiento y eritema perianal), solos o combinados, estuvieron presentes en el 92% de los episodios. En solo el 17% de los primeros episodios el eritema perianal fue motivo de consulta. Puede ser tenue, sus bordes no siempre son nítidos y en ocasiones asocia lesiones satélites.

Streptococcus pyogenes (S. pyogenes) es un importante patógeno humano responsable de una gran diversidad de infecciones, algunas de las cuales presentan un carácter severo con elevada morbimortalidad asociada. La proteína M es un determinante de virulencia crítico de este microorganismo. Diferentes estudios comunican un incremento de enfermedad invasora por S. pyogenes (EISP) relacionado con un aumento de serotipos M1 y M3, de reconocida virulencia. El objetivo del trabajo es confirmar el incremento observado de las enfermedades invasoras por S. pyogenes durante 2011-2018, y conocer qué serotipos pudieran estar implicados.

Material y métodos: La identificación de los aislados se realizó mediante pruebas fenotípicas convencionales: morfología de las colonias, β-hemólisis, pruebas bioquímicas y detección de antígeno A de Lancefield (DiaMondiaL Strep Kit, DiaMondiaL, Langenhagen, Alemania). La sensibilidad antibiótica se determinó mediante microdilución (Vitek®2 Compact, bioMeriéux, Inc., Durham, NC). La caracterización genotípica incluyó el gen emm y el perfil de superantígenos.

Resultados: Entre 2011-2018 se recuperaron 29 S. pyogenes invasores de sangre (16), líquido pleural (9), líquido sinovial (3) y líquido cefalorraquídeo (1). Entre 2011 y 2013, se cuantificó una cepa por año. Entre 2014 y 2018 se aislaron 2, 5, 4, 6 y 9 cepas, respectivamente. Las entidades clínicas más frecuentes fueron bacteriemia y neumonía (10 y 9 casos). Los serotipos mayoritarios fueron M1 (11) y M3 (3), asociados predominantemente a neumonía (6/7 casos) e infección profunda de partes blandas (3/3 casos).

Conclusiones: Se constata un incremento de las enfermedad invasora por S. pyogenes en el periodo estudiado resultando mayoritarios, conforme a la bibliografía, los serotipos M1 y M3, los cuales se asocian con neumonía e infección profunda de partes blandas.

·Asymptomatic bacteriuria prevalence Prevalence of Asymptomatic Bacteriuria in Children: A Meta-Analysis. J Pediatr 2020;217:110-7.e4.

Question: Among well children, what is the prevalence of asymptomatic bacteriuria (AB)?

Design: Systematic review and meta-analysis of studies measuring prevalence of AB.

Setting: International.

Participants: Asymptomatic children, 0-19 years of age.

Intervention: Bladder catheterization, suprapubic aspiration, or 3 consecutive clean catch urine samples.

Outcomes: >1 organism with 100 000 colony forming units per milliliter (CFU/mL) for samples obtained by catheterization and 10 000 CFU/mL for samples obtained using suprapubic aspiration, with and without pyuria.

Main Results: 14 studies (49 806 children) demonstrated an overall AB prevalence of 0.37% (95% CI, 0.09-0.82) and 0.47% (95% CI, 0.36-0.59), and and AB prevalence without pyuria of 0.18% (95% CI, 0.02-0.51) and 0.38% (95% CI, 0.22-0.58), in boys and girls, respectively. Median AB duration from one study was 1.5 – 2 months.

Conclusions: AB prevalence is notably lower than that of urinary tract infection (UTI) in most subgroups, and therefore, a negative urinalysis (UA) with growth on urine culture should not be assumed to exclude a UTI.

Commentary: Historically, many clinicians have treated a positive urine culture with a negative UA as a true UTI, though these findings could also represent a false positive urine culture from either contamination or AB. Shaikh et al conclude that the prevalence of AB is too low to use it as an explanation for positive urine cultures without pyuria. However, although the absolute prevalence of AB may be low, the proportion of positive urine cultures caused by AB is still relatively high. For example, if 3.1% of patients with bronchiolitis have positive urine cultures,  and the prevalence of AB is 0.4-0.5%, then AB would account for over 10% of these cultures: [(0.4-0.5%)/3.1% >10%]. Additionally, in 13/14 studies in the meta-analysis by Shaikh et al, the method of collection was either suprapubic aspirate or “‘clean catch” (with 3 successive positive cultures required to be considered AB). As such, the pooled prevalence in their study does not factor in contamination, an important cause of false positive urine cultures in the real world. Shaikh et al suggest reconsidering the AAP guideline  recommendation to incorporate pyuria in the definition of UTI. We worry that treating all positive urine cultures without pyuria as true UTI will drive excessive antibiotic use, hospitalization, and imaging.

This study reports on the prevalence, intensity, and timing of an altered sense of smell or taste in patients with SARS-CoV-2 infections....

Importance:  An altered sense of smell and taste has been reported to be associated with coronavirus disease 2019 (COVID-19). To understand the evolution of these symptoms during the course of the disease is important to identify patients with persistent loss of smell or taste and estimate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the burden of olfactory and gustative dysfunctions.

Objective:  To evaluate the evolution of the loss of sense of smell and taste in a case series of mildly symptomatic patients with SARS-CoV-2 infection.

Design, Setting, and Participants:  This cross-sectional survey-based study included 202 mildly symptomatic adults (≥18 years) consecutively assessed at Treviso Regional Hospital, Italy, between March 19 and March 22, 2020, who tested positive for SARS-CoV-2 RNA by polymerase chain reaction on nasopharyngeal and throat swabs.

Main Outcomes and Measures:  Prevalence of altered sense of smell and taste at follow-up and their variation from baseline.

Results:  Of 202 patients completing the survey at baseline, 187 (92.6%) also completed the follow-up survey (103 [55.1%] women; median age, 56 years). The evaluation of the evolution of altered sense of smell or taste in the 113 patients reporting sudden onset of these symptoms at baseline showed that 55 patients (48.7%; 95% CI, 39.2-58.3) reported complete resolution of smell or taste impairment, 46 (40.7%; 95% CI, 31.6-50.4) reported an improvement in the severity, and only 12 (10.6%; 95% CI, 5.6-17.8) reported the symptom was unchanged or worse. Persistent loss of smell or taste was not associated with persistent SARS-CoV-2 infection.

Conclusions and Relevance:  At 4 weeks from the onset, 89% of the SARS-CoV-2–positive mildly symptomatic patients who had had a sudden onset of altered sense of smell or taste experienced a complete resolution or improvement of these symptoms. Persistent loss of smell or taste was not associated with persistent SARS-CoV-2 infection.

Importance: The epidemiologic and clinical characteristics of pediatric patients with coronavirus disease 2019 (COVID-19) have been reported, but information on immune features associated with disease severity is scarce.

Objective:  To delineate and compare the immunologic features of mild and moderate COVID-19 in pediatric patients.

Design, Setting, and Participants:  This single-center case series included 157 pediatric patients admitted to Wuhan Children’s Hospital with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data were collected from January 25 to April 18, 2020.

Exposures:  Documented SARS-CoV-2 infection.

Main Outcomes and Measures:  Clinical and immunologic characteristics were collected and analyzed. Outcomes were observed until April 18, 2020.

Results:  Of the 157 pediatric patients with COVID-19, 60 (38.2%) had mild clinical type with pneumonia, 88 (56.1%) had moderate cases, 6 (3.8%) had severe cases, and 3 (1.9%) were critically ill. The 148 children with mild or moderate disease had a median (interquartile range [IQR]) age of 84 (18-123) months, and 88 (59.5%) were girls. The most common laboratory abnormalities were increased levels of alanine aminotransferase (ALT) (median [IQR], 16.0 [12.0-26.0] U/L), aspartate aminotransferase (AST) (median [IQR], 30.0 [23.0-41.8] U/L), creatine kinase MB (CK-MB) activity (median [IQR], 24.0 [18.0-34.0] U/L), and lactate dehydrogenase (LDH) (median [IQR], 243.0 [203.0-297.0] U/L), which are associated with liver and myocardial injury. Compared with mild cases, levels of inflammatory cytokines including interleukin 6, tumor necrosis factor α, and interferon γ were unchanged, whereas the level of immune suppressive interleukin 10 was markedly increased in moderate cases compared with mild cases (median [IQR], 3.96 [3.34-5.29] pg/mL vs 3.58 [3.10-4.36] pg/mL; P = .048). There was no statistically significant difference in absolute number of lymphocytes (including T cells and B cells) between mild and moderate cases, but moderate cases were associated with a decrease in neutrophil levels compared with mild cases (median [IQR], 2310/μL [1680/μL-3510/μL] vs 3120/μL [2040/μL-4170/μL]; P = .01). Immunoglobin G and the neutrophil to lymphocyte ratio were negatively associated with biochemical indices related to liver and myocardial injury (immunoglobulin G, ALT: r, −0.3579; AST: r, −0.5280; CK-MB activity: r, −0.4786; LDH: r, −0.4984; and neutrophil to lymphocyte ratio, ALT: r, −0.1893; AST: r, −0.3912; CK-MB activity: r, −0.3428; LDH: r, −0.3234), while counts of lymphocytes, CD4+ T cells, and interleukin 10 showed positive associations (lymphocytes, ALT: r, 0.2055; AST: r, 0.3615; CK-MB activity: r, 0.338; LDH: r, 0.3309; CD4+ T cells, AST: r, 0.4701; CK-MB activity: r, 0.4151; LDH: r, 0.4418; interleukin 10, ALT: r, 0.2595; AST: r, 0.3386; CK-MB activity: r, 0.3948; LDH: r, 0.3794).

Conclusions and Relevance:  In this case series, systemic inflammation rarely occurred in pediatric patients with COVID-19, in contrast with the lymphopenia and aggravated inflammatory responses frequently observed in adults with COVID-19. Gaining a deeper understanding of the role of neutrophils, CD4+ T cells, and B cells in the pathogenesis of SARS-CoV-2 infection could be important for the clinical management of COVID-19.

Hemos leído con atención el artículo de Rey Galán et al. expresando la necesidad de comunicar experiencias clínicas con respecto a la población pediátrica en relación al virus SARS-CoV-2 (COVID-19)1. El actual estado de urgencia sanitaria y social, entre otros aspectos, ha desembocado en un aumento de la investigación sobre el virus. En este contexto se han ido reportando nuevas manifestaciones clínicas ligadas al COVID-19, algunas como la anosmia, parecen ser distintivas, permitiendo el diagnóstico aun en individuos asintomáticos2. Entre ellas se han descrito lesiones cutáneas

Hemos leído con interés el artículo «Abscesos cervicales profundos infantiles: experiencia de una unidad de ORL infantil de referencia durante 15 años», publicado recientemente en su revista1.

Los autores refieren que el 88,9% de los niños (64/72) requirieron cirugía como parte del tratamiento. Los únicos casos que no precisaron tratamiento quirúrgico fueron las adenopatías abscesificadas menores de 1,5cm. El artículo concluye que la realización de cirugía precoz en abscesos grandes o profundos disminuye el número de complicaciones graves y recidivas. Un dato muy llamativo en la serie mencionada es que la totalidad de los niños con abscesos periamigdalinos y para/retrofaríngeos se intervinieron1, situación que dista mucho de nuestra práctica habitual.

Routine rotavirus (RV)-vaccination is recommended in Germany since August 2013. Five years later, we evaluated the recommendation by examining vaccine uptake and the impact on RV-gastroenteritis (RVGE) burden in all age groups and on intussusceptions in infants.

Methods: We estimated RV-vaccine uptake in the 2014–2018 birth cohorts using statutory health insurance prescription data. For impact assessment, we analyzed RVGE-surveillance data of the German infectious diseases notification system. We compared age-specific RVGE-incidences of different severity between pre-vaccination (2005/06–2007/08) and routine vaccination period (2013/14–2017/18) calculating incidence rate ratios (IRR) using Poisson regression. To determine the effect on intussusception, we used hospital discharge data (2006–2017) and compared incidences between pre-vaccination and routine vaccination period using Poisson regression.

Results: Vaccination coverage increased from 59% (2014) to 80% (2018). Incidences of RVGE-outpatient cases, RVGE-hospitalization and nosocomial RVGE among <5-year-olds decreased by 74% (IRR = 0.26; 95% CI: 0.26–0.27), 70% (IRR = 0.30; 95% CI: 0.30–0.31) and 70% (IRR = 0.30; 95% CI: 0.30–0.31), respectively. Incidence of RVGE-outpatient cases in age groups ineligible for RV-vaccination decreased by 38% (IRR 0.62; 95% CI: 0.61–0.63). Compared with the pre-vaccination period, incidence of intussusception in the first year of life decreased by 28% (IRR = 0.73; 95% CI: 0.68–0.79) while at age of the first vaccine-dose (7th–12th week of age) increase in incidence of intussusception was non-significant (IRR = 1.29; 95% CI: 0.93–1.78).

Conclusions: Routine RV-vaccination is well accepted in Germany. Since implementation of routine RV-vaccination, RVGE significantly decreased in <5-year-olds and in non-vaccinated older age groups through herd protection. The decline of intussusceptions in the first life year suggests a potential vaccination-associated protection against gastrointestinal infections that might trigger intussusceptions. These encouraging results should be communicated to doctors and parents for further improvement of vaccine uptake and protection of more infants.

·Mandatory vaccine policies associated with increased vaccination rates and decreased measles incidence. Mandatory Vaccination in Europe. Pediatrics 2020;145: pii e20190620.

Question: Among children living in Europe, what is the association between mandatory vaccination and vaccine-preventable disease reduction?

Design: Data analysis from the data banks of the European Centre for Disease Prevention and Control and the World Health Organization.

Setting: 29 European countries.

Participants: Children vaccinated.

Intervention: Vaccination rates from 2006 to 2015 for measles, 2006 to 2016 for pertussis, and mandatory vaccination policies.

Outcomes: Measles and pertussis vaccine coverage and the annual incidence of these diseases.

Main Results: Mandatory vaccine policies were associated with higher vaccination prevalence, 3.71% (95% CI, 1.68 - 5.74) and 2.14% (95% CI, 0.13 to 4.15) for measles and pertussis, respectively. Some countries imposed a monetary penalty for non-compliance. Every €500 increase in the maximum penalty demonstrated an increase of 0.8% and 1.1% for measles pertussis vaccination prevalence, respectively (P < .0001 for both). Only countries without non-medical exemptions demonstrated an association with a lower measles rate compared with countries without a mandatory vaccine policy, adjusted incidence rate ratio, 0.14 (95% CI, 0.05 to 0.36). Pertussis rates were not statistically different.

Conclusions: Mandatory vaccination policies were associated with higher vaccination rates and a decreased measles incidence.

Commentary: High rates of vaccination coverage are important in preventing infectious diseases. Strategies adopted by European Union countries to achieve and maintain high immunization rates in target populations include compulsory and recommended vaccinations, free of charge and co-payment.

In Europe, mandatory vaccination policies vary not only in the presence or absence of a mandate but also in the implementation and enforcement of the mandates as well as in the consequences faced by individuals who fail to comply with their country’s policy. This study found that mandatory vaccination against both measles and pertussis was associated with a higher prevalence of vaccination when compared with countries that did not have mandatory vaccination. Moreover, the magnitude of fines (in those European countries which imposed them) was associated with higher vaccination coverage. Currently, within the scientific community, there is an ongoing debate concerning compulsory vaccination.

2The findings from Vaz et al suggest mandatory immunization programs increase measles and pertussis coverage. Health care policy makers may find these results useful in identifying effective immunization rate-enhancing strategies.

·COVID-19 in Neonates and Infants: Progression and Recovery. The Pediatric Infectious Disease Journal. 39(7):e140-e142, July 2020.

Between March 10, 2020 and April 17, 2020, of 8/70 (11.4%) SARS-CoV-2 positive infants that presented, 5/8 (63%) developed fever, 4/8 (50%) had lower respiratory tract involvement, 2/8 (25%) had neutropenia and thrombocytosis, and 4/8 infants (50%) were treated for suspected sepsis with broad-spectrum antibiotics. Only 1/8 (13%) required pediatric intensive care. All patients were eventually discharged home well.

As many countries begin to lift some of the restrictions to contain COVID-19 spread, lack of evidence of transmission in the school setting remains. We examined Irish notifications of SARS-CoV2 in the school setting before school closures on 12 March 2020 and identified no paediatric transmission. This adds to current evidence that children do not appear to be drivers of transmission, and we argue that reopening schools should be considered safe accompanied by certain measures.

·Three Hypotheses About Children COVID19. The Pediatric Infectious Disease Journal. 39(7):e157, July 2020.

·Comparison of the Clinical Features of SARS-CoV-2, Other Coronavirus and Influenza Infections in Infants Less Than 1-Year-Old. The Pediatric Infectious Disease Journal. 39(7):e157-e158, July 2020.

·COVID-19 in the Pediatric Population Admitted to a Tertiary Referral Hospital in Northern Italy: Preliminary Clinical Data. The Pediatric Infectious Disease Journal. 39(7):e160, July 2020.

·False-positive Results of Quantiferon-Tb-Gold Assay in Children. The Pediatric Infectious Disease Journal. 39(7):620-623, July 2020.

We present a pediatric case series describing false-positive QuantiFERON-TB Gold In-tube (QFT-GIT) assay (QIAGEN, Germany) results observed in a tertiary hospital in Spain (2013–2018). During the study period, 7 of 737 test results were considered false-positives: 4 children with chronic medical conditions, 1 Mycobacterium lentiflavum lymphadenitis, 1 infant born to a mother with pulmonary tuberculosis, and 1 child exposed to a noninfectious tuberculosis patient. Data regarding interferon-gamma release assays false-positive results in children are scarce, and more studies are necessary to determine the rates of false-positive results in low-prevalence settings.

·Probiotic Use and Safety in the Neonatal Intensive Care Unit: A Matched Cohort Study.  J Pediatr. 2020;222:59-64.e1. doi:10.1016/j.jpeds.2020.03.051.

To determine the prevalence of probiotic administration in infants born preterm over time, as well as the association between probiotic administration and select adverse outcomes.

Study design We performed a multicenter cohort study of infants 23-29 weeks of gestational age admitted to 289 neonatal intensive care units from 1997 to 2016. We evaluated the type of probiotics given and prevalence of exposure to probiotics over time and by site. We matched infants exposed to probiotics by several factors to unexposed infants receiving enteral feeds on the same postnatal day. We performed conditional logistic regression to evaluate the association between probiotics exposure and adverse outcomes, including necrotizing enterocolitis (NEC), bloodstream infections, meningitis, and death.

Results Of 78 076 infants, 3626 (4.6%) received probiotics. Probiotic use increased over the study period and varied among neonatal intensive care units. We matched 2178 infants exposed to probiotics to 33 807 without exposure. Probiotic administration was associated with a decrease in NEC (OR 0.62, 95% CI 0.48-0.80) and death (OR 0.52, 95% CI 0.39-0.70), an increase in Candida infection (OR 2.23, 95% CI 1.29-3.85), but no increase in bloodstream infection (OR 0.86, 95% CI 0.70-1.05) or meningitis (OR 1.18, 95% CI 0.40-3.46).

Conclusions Probiotic use increased over time and was associated with decreased odds of NEC and death. Prospective, randomized-controlled studies of specific probiotic products are needed to further investigate the safety and efficacy of probiotics in preterm infants.

·Etiology of Microcephaly and Central Nervous System Defects during the Zika Epidemic in Colombia.  J Pediatr. 2020;222:112-119.e3. doi:10.1016/j.jpeds.2020.02.023

To estimate the prevalence of microcephaly and central nervous system (CNS) defects during the Zika virus (ZIKV) epidemic in Colombia and proportion attributable to congenital ZIKV infection.

Study design

Clinical and laboratory data for cases of microcephaly and/or CNS defects reported to national surveillance between 2015 and 2017 were reviewed and classified by a panel of clinical subject matter experts. Maternal and fetal/infant biologic specimens were tested for congenital infection and chromosomal abnormalities. Infants/fetuses with microcephaly and/or CNS defects (cases) were classified into broad etiologic categories (teratogenic, genetic, multifactorial, and unknown). Cases classified as potentially attributable to congenital ZIKV infection were stratified by strength of evidence for ZIKV etiology (strong, moderate, or limited) using a novel strategy considering birth defects unique or specific to ZIKV or other infections and laboratory evidence.

Results Among 858 reported cases with sufficient information supporting a diagnosis of microcephaly or CNS defects, 503 were classified as potentially attributable to congenital ZIKV infection. Of these, the strength of evidence was considered strong in 124 (24.7%) cases; moderate in 232 (46.1%) cases; and limited in 147 (29.2%). Of the remaining, 355 (41.4%) were attributed to etiologies other than ZIKV infection (syphilis, toxoplasmosis, rubella, cytomegalovirus, herpes 1 and herpes 2 viruses only, n = 32 [3.7%]; genetic, n = 16 [1.9%]; multifactorial, n = 42 [4.9%]; unknown, n = 265 [30.9%]).

Conclusions Fifty-eight percent of cases of microcephaly and/or CNS defects were potentially attributable to congenital ZIKV infection; however, the strength of evidence varied considerably. This surveillance protocol might serve as a model approach for investigation and etiologic classification of complex congenital conditions.

Parechovirus A Infections in Healthy Australian Children During the First 2 Years of Life: A Community-based Longitudinal Birth Cohort StudyClinical Infectious Diseases, Volume 71, Issue 1, 1 July 2020, Pages 116–127, https://doi.org/10.1093/cid/ciz761

Background

Hospital-based studies identify parechovirus (PeV), primarily PeV-A3, as an important cause of severe infections in young children. However, few community-based studies have been published and the true PeV infection burden is unknown. We investigated PeV epidemiology in healthy children participating in a community-based, longitudinal birth cohort study.

Methods

Australian children (n = 158) enrolled in the Observational Research in Childhood Infectious Diseases (ORChID) study were followed from birth until their second birthday. Weekly stool and nasal swabs and daily symptom diaries were collected. Swabs were tested for PeV by reverse-transcription polymerase chain reaction and genotypes determined by subgenomic sequencing. Incidence rate, infection characteristics, clinical associations, and virus codetections were investigated.

Results

PeV was detected in 1423 of 11 124 (12.8%) and 17 of 8100 (0.2%) stool and nasal swabs, respectively. Major genotypes among the 306 infection episodes identified were PeV-A1 (47.9%), PeV-A6 (20.1%), and PeV-A3 (18.3%). The incidence rate was 144 episodes (95% confidence interval, 128–160) per 100 child-years. First infections appeared at a median age of 8 (interquartile range, 6.0–11.7) months. Annual seasonal peaks changing from PeV-A1 to PeV-A3 were observed. Infection was positively associated with age ≥6 months, summer season, nonexclusive breastfeeding at age <3 months, and formal childcare attendance before age 12 months. Sole PeV infections were either asymptomatic (38.4%) or mild (32.7%), while codetection with other viruses in stool swabs was common (64.4%).

Conclusions

In contrast with hospital-based studies, this study showed that diverse and dynamically changing PeV genotypes circulate in the community causing mild or subclinical infections in children.

Parechovirus can cause severe illnesses in children. However, studies focus mainly on hospitalized populations. True disease burden in the community remains largely unknown. From our community-based cohort, we found diverse parechovirus genotypes in the community, causing mild or subclinical infections in children.

El molusco contagioso (MC) es una enfermedad cutánea común con una prevalencia que oscila entre el 5,1 y el 11,5% en niños de 0 a 6 años de edad. Los niños con enfermedades cutáneas crónicas, como la dermatitis atópica, son más propensos a desarrollarlo.

Serie de 5 casos en niños de 4 a 10 años de edad, 3 de ellos diagnosticados previamente de dermatitis atópica. Acudieron S, Urgencias con lesiones inflamatorias muy pruriginosas en los codos y las rodillas de inicio abrupto en las últimas 48-72 h. No tenían fiebre ni otros síntomas generales, y no habían tomado medicación con anterioridad a la aparición de las lesiones. Todos habían consultado previamente a su médico por motivo de MC (2 no recibieron tto, 2 fueron tratados con hidróxido de potasio al 10% y uno con cantaridina. EF  pápulas edematosas de color rojizo/rosáceo localizadas en los aspectos extensores de las extremidades, en 3 casos restringidos a las rodillas y los codos. La erupción apareció al inflamarse el MC, lo que sugería una posible asociación.  TTO: corticoterapia tópica u oral, dependiendo de la extensión y el grado de inflamación de las lesiones. Las lesiones desaparecieron entre los días 7 y 15 del tratamiento, al igual que el MC.

Las reacciones inflamatorias secundarias a MC no están bien estudiadas, pero son comunes y causa frecuente de dolor y prurito. En muchos casos hay inflamación local que puede malinterpretarse como sobreinfección bacteriana. En pacientes con dermatitis atópica, las lesiones de MC tienden a aparecer en zonas de dermatitis eccematosa. Con menor frecuencia, los pacientes afectados desarrollan una reacción inflamatoria grave consistente en un exantema papular pruriginoso en los codos y las rodillas conocido como reacción al síndrome de Gianotti-Crosti-like (RSGC-L).  Un estudio retrospectivo reciente en 696 pacientes con MC encontró RSGC-L en 35 pacientes (4,9% de los casos): en 23 (67,6%) localizadas exclusivamente en los aspectos extensores de las extremidades, y en los 12 restantes (35,3%) restringidas a las rodillas y/o los codos.

Las RSGC-L se caracterizan por pápulas liquenoides alrededor de los codos, las rodillas y las nalgas. La aparición de estas reacciones no está relacionada con el número de lesiones de MC.Esta reacción puede estar presente en la visita inicial (50%) o desarrollarse uno o 2 meses después de iniciarse el tratamiento de MC (38%), independientemente del tratamiento recibido. En niños, las RSGC suelen asociarse a infecciones virales (virus de Epstein-Barr o hepatitis), en las que el desarrollo de lesiones cutáneas asintomáticas suele ir precedido de febrícula, dolor de garganta o malestar general. Estos pacientes sufren una respuesta inflamatoria seria y muy pruriginosa al MC, con desarrollo de estas lesiones típicas y en la mayoría de los casos con resolución espontánea del MC en pocos días o semanas.

·Managing Asthma during Coronavirus Disease-2019: An Example for Other Chronic Conditions in Children and Adolescents. J Pediatr. 2020;222:221-226. doi:10.1016/j.jpeds.2020.04.049

CDC (Centers for Disease Control and Prevention), COVID-19 (Novel coronavirus disease-2019), OCS (Oral corticosteroids), SARS-CoV-2 (Severe acute respiratory syndrome corona virus)

The novel coronavirus disease-2019 (COVID-19), caused by the pathogen severe acute respiratory syndrome corona virus (SARS-CoV-2), has now spread around the globe with more than 1.8 million individuals affected and more than 110 000 deaths internationally.1,  2,  3,  4 As of April 12, 2020, there are 530 830 cases in the US with more than 20 000 deaths.2,3 The Institute for Health Metrics and Evaluation has predicted that this pandemic could exceed current healthcare capacity in the US with a total of 81 114 deaths (95% CI, 38 242-162 106) through August 2020.5

Asthma is one of the most common chronic diseases of childhood in the US. Data from the US Department of Health and Human Services notes that asthma prevalence increased between 2001 and 2010 and is now at its highest prevalence ever (overall 8.4% in 2010).6 In the US, approximately 7 million children have asthma.6 The morbidity of asthma in the US is high, and is higher in children than adults. Children missed 10.5 million school days owing to asthma in 2008; there were 6.7 million primary care visits related to asthma and 600 000 asthma-related emergency department visits for children in 2007.7

Multiple guidelines have emerged from international societies on the management of medical care during the COVID-19 pandemic, which include a section on pediatric asthma, including a North American guideline on contingency planning for allergy and immunology clinics during a pandemic and a Canadian Pediatric Society statement on asthma management during the COVID-19 pandemic.8,9 Owing to the high prevalence of asthma in the US, which is at the current epicenter of a global pandemic, the goal of this commentary is to provide an overview of what is known, and what is yet to be learned, about COVID-19 and pediatric asthma.

Differentiating Asthma from COVID-19

Symptoms of COVID-19 can be similar to those of worsening asthma, or an asthma exacerbation. Dry cough and shortness of breath, commonly seen in asthma, are among the most common presenting symptoms of COVID-19 in case series of children admitted to the hospital in China, as well as in available data from the Centers for Disease Control and Prevention (CDC) in the US.10,  11,  12

Fever, a common presenting symptom of COVID-19, may help to differentiate COVID-19 from an asthma exacerbation, although fever can be present in other virus-triggered asthma exacerbations as well.3,10,  11,

Importance:  Children of all ages appear susceptible to severe acute respiratory syndrome coronavirus 2 infection. To support pediatric clinical studies for investigational treatments of coronavirus disease 2019 (COVID-19), pediatric-specific dosing is required.

Objective:  To define pediatric-specific dosing regimens for hydroxychloroquine and remdesivir for COVID-19 treatment.

Design, Setting, and Participants:  Pharmacokinetic modeling and simulation were used to extrapolate investigated adult dosages toward children (March 2020-April 2020). Physiologically based pharmacokinetic modeling was used to inform pediatric dosing for hydroxychloroquine. For remdesivir, pediatric dosages were derived using allometric-scaling with age-dependent exponents. Dosing simulations were conducted using simulated pediatric and adult participants based on the demographics of a white US population.

Interventions:  Simulated drug exposures following a 5-day course of hydroxychloroquine (400 mg every 12 hours × 2 doses followed by 200 mg every 12 hours × 8 doses) and a single 200-mg intravenous dose of remdesivir were computed for simulated adult participants. A simulation-based dose-ranging study was conducted in simulated children exploring different absolute and weight-normalized dosing strategies.

Main Outcomes and Measures:  The primary outcome for hydroxychloroquine was average unbound plasma concentrations for 5 treatment days. Additionally, unbound interstitial lung concentrations were simulated. For remdesivir, the primary outcome was plasma exposure (area under the curve, 0 to infinity) following single-dose administration.

Results:  For hydroxychloroquine, the physiologically based pharmacokinetic model analysis included 500 and 600 simulated white adult and pediatric participants, respectively, and supported weight-normalized dosing for children weighing less than 50 kg. Geometric mean-simulated average unbound plasma concentration values among children within different developmental age groups (32-35 ng/mL) were congruent to adults (32 ng/mL). Simulated unbound hydroxychloroquine concentrations in lung interstitial fluid mirrored those in unbound plasma and were notably lower than in vitro concentrations needed to mediate antiviral activity. For remdesivir, the analysis included 1000 and 6000 simulated adult and pediatric participants, respectively. The proposed pediatric dosing strategy supported weight-normalized dosing for participants weighing less than 60 kg. Geometric mean-simulated plasma area under the time curve 0 to infinity values among children within different developmental age-groups (4315-5027 ng × h/mL) were similar to adults (4398 ng × h/mL).

Conclusions and Relevance:  This analysis provides pediatric-specific dosing suggestions for hydroxychloroquine and remdesivir and raises concerns regarding hydroxychloroquine use for COVID-19 treatment because concentrations were less than those needed to mediate an antiviral effect.

 

Actualidad bibliográfica junio 2020

TOP TEN

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has spread rapidly across the globe. In contrast to initial reports, recent studies suggest that children are just as likely as adults to become infected with the virus but have fewer symptoms and less severe disease. In this review, we summarize the epidemiologic and clinical features of children infected with SARS-CoV-2 reported in pediatric case series to date. We also summarize the perinatal outcomes of neonates born to women infected with SARS-CoV-2 in pregnancy. We found 11 case series including a total of 333 infants and children. Overall, 83% of the children had a positive contact history, mostly with family members. The incubation period varied between 2 and 25 days with a mean of 7 days. The virus could be isolated from nasopharyngeal secretions for up to 22 days and from stool for more than 30 days. Co-infections were reported in up to 79% of children (mainly mycoplasma and influenza). Up to 35% of children were asymptomatic. The most common symptoms were cough (48%; range 19%–100%), fever (42%; 11%–100%) and pharyngitis (30%; 11%–100%). Further symptoms were nasal congestion, rhinorrhea, tachypnoea, wheezing, diarrhea, vomiting, headache and fatigue. Laboratory test parameters were only minimally altered. Radiologic findings were unspecific and included unilateral or bilateral infiltrates with, in some cases, ground-glass opacities or consolidation with a surrounding halo sign. Children rarely needed admission to intensive care units (3%), and to date, only a small number of deaths have been reported in children globally. Nine case series and 2 case reports described outcomes of maternal SARS-CoV-2 infection during pregnancy in 65 women and 67 neonates. Two mothers (3%) were admitted to intensive care unit. Fetal distress was reported in 30% of pregnancies. Thirty-seven percent of women delivered preterm. Neonatal complications included respiratory distress or pneumonia (18%), disseminated intravascular coagulation (3%), asphyxia (2%) and 2 perinatal deaths. Four neonates (3 with pneumonia) have been reported to be SARS-CoV-2 positive despite strict infection control and prevention procedures during delivery and separation of mother and neonates, meaning vertical transmission could not be excluded.

https://www.ecdc.europa.eu/sites/default/files/documents/covid-19-risk-assessment-paediatric-inflammatory-multisystem-syndrome-15-May-2020.pdf

Yellow fever vaccine contains ovalbumin, and guidelines for vaccination of egg allergic patients vary widely. We present our experience of administering yellow fever vaccine to 11 egg-allergic children, including 3 with anaphylaxis to egg, in 2 Australian tertiary pediatric hospitals. There was variation in the vaccination protocols used; however, all patients were successfully vaccinated and no serious adverse events were reported.

We included five trials (2891 children and adult participants in total; 2545 participants after adjusting for clustering). Management in the intervention group was as follows: in three trials rapid tests were used in combination with a clinical scoring system; in one trial, some physicians were asked to use rapid tests alone, while others were asked to use rapid tests in combination with a clinical scoring system; in one trial, rapid tests were used alone

Participants in the rapid test group were less likely to be prescribed antibiotics than participants managed based on clinical grounds (481/1197 versus 865/1348). A 25% reduction (i.e., a decrease of 25 percentage points) in antibiotic prescription rates is likely to be achieved by using rapid testing in people with sore throat in primary care. However, there may be little or no reduction between groups in dispensed antibiotic treatments. Antibiotic prescriptions refer to medicines prescribed by healthcare providers. Antibiotic dispensing refers to medicines accessed in pharmacies. In some cases, patients may not present to the pharmacy to get their prescription filled. Four trials reported data on the number of participants with a complication attributed to the initial infection (e.g., tonsil abscess): complications were rare (0 to 3 per trial), and there may be little or no difference between people managed on clinical grounds alone and those managed with rapid testing but the evidence is very uncertain.

Among children with pharyngitis who test positive for group A Streptococcus (GAS), 10%–25% are GAS carriers. Current laboratory methods cannot distinguish acute infection from colonization.

Methods: We examined 2 separate longitudinal studies of children with symptomatic pharyngitis associated with a positive GAS throat culture (illness culture). In cohort 1, children presented with pharyngitis symptoms to a clinician, then had follow-up cultures at regular intervals. In cohort 2, throat cultures were performed at regular intervals and with pharyngitis symptoms. Illness cultures were categorized as acute infection or carrier based on follow-up culture results. In cohort 2, carriers were further categorized as a GAS carrier with a new emm-type or a GAS carrier with a previous emm-type based on typing data from prior culture results. For each cohort, symptoms were compared at the time of illness culture between carriers and those with acute infection.

Results: Cohort 1 (N = 75 illness cultures): 87% of the children were classified as acutely infected versus 13% carriers. Carriers were more likely to have upper respiratory (URI) symptoms [odds ratio (OR): 5.5; 95% confidence interval (CI): 1.4–22.1], headache (OR: 6.0; 95% CI: 1.2–40.5) or vomiting (OR: 5.5; 95% CI: 1.2–24.5). Cohort 2 (N = 122 illness cultures): 79% were acutely infected and 21% were carriers. Children determined to be carriers with a previous detected emm-type were more likely to have URI symptoms compared with those with acquisition of a new emm-type.

Conclusions: Children with symptomatic pharyngitis and GAS on throat culture identified as carriers were more likely to present with URI and atypical symptoms than children who were acutely infected.

1. What serological methods are available and how accurate are they in the diagnosis of CE? Re

• conventional and rapid diagnostic tests have a low sensitivity in the case of inactive cysts (A-I).
• Classical techniques are being replaced with purified, recombinant antigens and/or peptides (derived mostly from E. granulosus Ag5 and AgB ) (A-I).
• Most recombinant antigen and purified antigen techniques are highly specific. However, they can show cross-reactivity with alveolar echinococcosis and cysticercosis. They are usually more sensitive in multiple CE (A-I).

2. Are molecular methods useful in the diagnosis of CE? Do the new parasitological tools help in the diagnosis?
Molecular techniques may be helpful in the future for the diagnosis ofCE, but they are still in the process of optimisation
3. What is the best follow-up schedule for CE?
The optimal follow-up schedule for CE has not yet been established (C-III). Theoretically, follow-up should be long: at least 3–5 years,
4. Surgical indications in hepatic CE: when and how?
Surgical is generally the treatment of choice and should be assessed on an individual basis (A-II). Open surgery is the most accepted procedure for the treatment of hepatic CE, especially in complicated cases (B-II
• The relative contraindications for surgery are (i) patients who are unsuitable for surgery due to their general status or associated comorbidities, (ii) multiple cysts, (iii) very small, difficult-to-access cysts that are partially or completely calcified (B-II).
5. What are the best and most frequently used techniques in hepatic CE? Are classical surgical techniques still the techniques of choice? What is the preferred strategy in hepatic CE: radical surgery or conservative treatment?
Wherever possible, radical techniques are preferable to conservative techniques (B-II). • Anatomical liver resection, total cystopericystectomy and open or partial cystectomy with or without omentoplasty are the most frequently used surgical techniques (B-II). • The ideal approach should be simple, with complete resection of the cyst without rupture. All efforts should be made to protect the peritoneal cavity and avoid intraoperative cyst leakage (B-II). • Conservative procedures: risk of morbidity and recurrence may be higher (B-II).
6. In hepatic CE, how effective ar e surgical techniques and what are their complications? Does laparoscopic surgery have any benefit over traditional surgical techniques? Are there any differences between urgent surgery and elective surgery in terms of complications or recurrence rate?). • Laparoscopic surgery can be used in selected cases of hepatic CE (C-III). • Patients with deep cysts, cysts in posterior lobes, near the vena cava, multiple (>3) cysts or calcified cysts may not be candidates for laparoscopic surgery (C-III).
7. What are the most frequently used surgical techniques in pulmonary CE? Cystopericystectomy is the surgical technique of choice in pulmonary CE (C-II). the minimum pulmonary resection necessary should be performed (C-II). • Surgical approaches via thoracotomy and VATS have comparable outcomes, although VATS has a lower morbidity, and is therefore the recommended technique (B-II). • Percutaneous techniques are not recommended in pulmonary CE due to the high risk of cyst rupture and secondary dissemination (B-II).
8. In pulmonary CE, how effective are surgical techniques and what are the possible complications? s • Surgery is one of the best treatment options for pulmonary CE. It has a low rate of associated morbidity and mortality (C-II). • Patients who undergo surgery for complicated cysts have a higher incidence of postoperative complications (C-II).

9. What is the best approach for difficult-to-access hepatic and pulmonary sites?
• Most cases of cardiac CE are treated surgically via a midline sternotomy and using extracorporeal circulation (C-III).
10. What is the management of patients with multi-organ CE?
Patients with hepatic CE should have a simple chest X-ray or a chest CT, and patients with pulmonary CE should have an abdominal ultrasound or CT (B-II).
• A standardised medical treatment regimen has not yet fully established. When medical treatment is the only option, it should be prolonged, or even indefinite (avoiding stopping treatment) (B-III).).
• In patients with multiple bilateral cysts, a sequential bilateral approach or a midline sternotomy may be used (D-III).
• If the upper hepatic segments and right pulmonary lobes are affected, the surgical team may consider thoracophrenolaparotomy, or a sequential independent approach via thoracotomy or VATS and laparotomy or laparoscopy (C-II). OK

11. How should patients with atypical location CE be managed? Recommendations
• All patients with suspicion of extrahepatic CE should have a CT of the chest and abdomen (A-III).
• Wherever surgical techniques allow it, the treatment of choice for atypical location CE is surgery (B-I).
• In splenic CE, conservative surgery is preferable; splenectomy should be reserved for patients with large cysts in the centre or close to the splenic hilum (A-II).
• Anthelminthic treatment must be given for at least 2 weeks before and for up to 3 months after surgery (B-III).
• In renal CE, laparoscopic surgery can be a safe and effective option (B-III). • If nephrectomy is performed, the largest possible amount of parenchyma should be preserved; total nephrectomy should be reserved for cysts on non-functioning kidneys, large cysts (occupying the entire parenchyma) or those with signs of infection (B-II).
• Echocardiography is the technique of choice for the diagnosis of cardiac CE, (B-II). In cardiac CE, antiparasitic treatment prior to surgery can increase the risk of damage to the cyst wall and of cyst rupture (B-I).
• The treatment of choice in cerebral CE is excision of the cyst intact, using the Dowling technique (B-I).
• In CE of the bone, surgery should remove the affected bone and at least 1–2 cm of surrounding healthy bone; intraoperative irrigation should be performed with a scolicidal solution of hypertonic saline (B-I).
12. What type of image-guided interventional techniques are currently used?
• PAIR is a safe and effective technique in selected patients (CE1 and CE3a) (B-II).
13. What is the usual procedure for image-guided interventional techniques? Recommendations • To avoid complications, communication between the cysts and the biliary, renal, or bronchial tree must be excluded (CIII).
14. What is the best scolicidal solution?
• Currently there is no perfect scolicidal agent. Ethanol (95%) and hypertonic saline solution (minimum 20% concentration) are the scolicidal agents of choiceTheir use is limited by their side effects such as chemical sclerosing cholangitis and anaphylactic reactions (B-III). • Before using,the presence of cysto-biliary fistulas must be ruled out (B-III).
15. What are the indications for each of the image-guided interventional techniques? How effective is percutaneous interventional treatment?
• PAIR is indicated for cysts between 5 and 10 cm that are stage CL, CE1 or CE3a, and for accessible multiple cysts, infected cysts, postsurgical recurrence or after failed medical treatment (B-III).). • Percutaneous techniques can be used in pregnant women and in children older than 3 years (B-III).

16. What factors influence the choice of antiparasitic treatment? Which, when, how and for how long?
• Pharmacological treatment is recommended for inoperable or multi-organ CE and as an adjunct to percutaneous treatment or surgery (B-II).
• Benzimidazoles are useful drugs in CE, albendazole being the drug of choice (A-I). • Better results are achieved when surgery or PAIR are combined with anthelminthics given before and/or after the procedure (A-I).
• Recommendations on duration of treatment prior to intervention range from 1 day to 3 months, and for after the intervention, from 1 to 3 months (B-II).
. 17. Is combined anthelminthic treatment with albendazole and praziquantel better than treatment with albendazole alone?
Combined treatment with albendazole and praziquantel before an interventional procedure reduces the viability of the cysts. The sterilising effect of the combination may be superior to that of monotherapy (C-II). • A longer duration of combined treatment appears to be associated with a greater reduction in the viability of the cysts (C-II). • Treatment dose and duration are not well defined, but it is recommended to give atleast 4 weeks of combined treatment prior to intervention (C-II).
• The use of combined medical treatment may have some benefit in patients with (i) disseminated disease, (ii) previous treatment failure, (iii) poor disease control on monotherapy, or (iv) whensurgery is contraindicated. Thedose andduration of combination therapy are not well established (C-II).
18. Are there any other safe and effective anthelminthic treatments?
• Drugs such as nitazoxanide and thiabendazole may have some efficacy in CE (B-III).

19. In which patients is a watch and wait strategy recommended?
• The W&W strategy is suggested for the management of patients with asymptomatic uncomplicated hepatic cysts in stages CE4 and CE5 (B-III). • The follow-up of these patients is important and should be long-term, for at least 3–5 years (C-III).

20. What follow-up is needed after a therapeutic procedure: which patients, how, and for how long? What are the most useful tools? • Initial follow-up should assess early complications of surgery or percutaneous intervention; late complications and recurrence should be assessed at a later date (B-II).. It should last at least 3 years, although in certain patients is may be extended indefinitely (B-II).
• In hepatic CE, follow-up should routinely involve ultrasound (B-II). In other locations, CT and/or MR may be used depending on availability (B-II).

21. Is serology useful in post-treatment follow-up?

. Occasionally, a reduction in the titres can be associated with cure, and an increase can be associated with a recurrence (B-III). • In patients who have undergone intervention, complete antigen detection techniques are not useful for follow-up (C-II).
• In patients with stage CE1–CE3a cysts who have undergone intervention with curative intent, detection of antibodies against AgB2t and Ag2B2t can be useful for follow-up, as it can differentiate active infection from cure (B-II).

22. Are radiological methods useful in post-treatment follow-up?

• Ultrasound is the technique of choice for the follow-up of disease in the liver, abdomen, soft-tissues, and lungs with cysts in contact with the pleura, and any location that is accessible with ultrasound (B-II). If there are limitations to ultrasound, CT and MR can be used for follow-up, (CIII).
• When it is difficultto determine the activity ofthe cyst, imaging techniques should be complemented with blood tests (C-III).

23. What measures can be taken to prevent CE?
• Interventions aimed atthe definitive host are essential, as the main risk factors in acquiring CE are linked to dogs, which represent the most common primary source of infection in humans (A-III).

En los últimos años, la resistencia a los antibióticos se ha intensificado, y se ha convertido en una amenaza para la salud pública.

El consumo de antibióticos está directamente relacionado con el desarrollo de resistencias.

La presión selectiva de los antibióticos sobre las bacterias se incrementa a medida que se alarga la duración del tratamiento.

La duración de los tratamientos es uno de los aspectos que hay que tener en cuenta en la valoración de la idoneidad de la antibioticoterapia.

La disminución de la duración del tratamiento antibiótico es una de las estrategias clave de los programas de optimización del uso de antibióticos.

Los tratamientos cortos han demostrado ser eficaces, con menos efectos adversos y riesgo de selección de resistencias, además de ser más económicos y favorecer la adherencia al tratamiento.

El elevado consumo de antibióticos y el importante porcentaje de tratamientos inapropiados en la atención primaria ofrece una gran oportunidad para su optimización.

Gran parte de las infecciones atendidas a nivel de la atención primaria pueden ser tratadas con cursos de tratamientos antibióticos iguales o inferiores a 7 días.

Es necesario promover el cambio hacia la optimización de las duraciones de los tratamientos antibióticos lo más cortas posible, según la evidencia disponible.

Actualmente, no hay evidencia para indicar tratamientos cortos en pacientes con inmunosupresión, infecciones graves, infecciones quirúrgicas con mal control del foco o infecciones protésicas.

Background Most effective strategies designed to improve antimicrobial prescribing have multiple approaches. We assessed the impact of the implementation of a rigorous antimicrobial guide and subsequent multifaceted interventions aimed at improving antimicrobial use in Primary Care.

Methods A quasi-experimental study was designed. Interventions aimed at achieving a good implementation of the guide consisted of the development of electronic decision support tools, local training meetings, regional workshops, conferences, targets for rates of antibiotic prescribing linked to financial incentives, feedback on antibiotic prescribing, and the implementation of a structured educational antimicrobial stewardship program. Interventions started in 2011, and continued until 2018.

Outcomes: rates of antibiotics use, calculated into defined daily doses per 1,000 inhabitants-day (DID). An interrupted time-series analysis was conducted. The study ran from January 2004 until December 2018.

Results Overall annual antibiotic prescribing rates showed increasing trends in the pre-intervention period. Interventions were followed by significant changes on trends with a decline over time in antibiotic prescribing. Overall antibiotic rates dropped by 28% in the Aljarafe Area and 22% in Andalusia between 2011 and 2018, at rates of -0.90 DID per year (95%CI:-1.05 to -0.75) in Aljarafe, and -0.78 DID (95%CI:-0.95 to -0.60) in Andalusia. Reductions occurred at the expense of the strong decline of penicillins use (33% in Aljarafe, 25% in Andalusia), and more precisely, amoxicillin clavulanate, whose prescription plummeted by around 50%. Quinolones rates decreased before interventions, and continued to decline following interventions with more pronounced downward trends. Decreasing cephalosporins trends continued to decline, at a lesser extent, following interventions in Andalusia. Trends of macrolides rates went from a downward trend to an upward trend from 2011 to 2018.

Conclusions Multifaceted interventions following the delivering of a rigorous antimicrobial guide, maintained in long-term, with strong institutional support, could led to sustained reductions in antibiotic prescribing in Primary Care.

In the late 1970s and early 1980s, an epidemic of silent, post-transfusion hepatitis directly led to the discovery of a novel, hepatotropic agent of the flavivirus family aptly named the hepatitis C virus (HCV, formerly known as the non-A, non-B hepatitis virus). Less than 30 years later, through advancements in viral sequencing and 3-dimensional determination of the nonstructural proteins that direct RNA polymerases required for HCV replication, a new class of medications, known as direct-acting antivirals (DAAs), were introduced to treat HCV. DAAs have demonstrated virologic response rates exceeding 95% across all genotypes after short durations of oral administration. These highly effective antiviral agents are now approved for use in children as young as 3 years of age. No virus to date has been globally eradicated without the development of a prophylactic vaccine; however, the efficacy and safety profile of DAAs enable a unique prospect—offering pediatric primary and subspecialty care providers an opportunity to cure hepatitis C.

To analyze host and pathogen factors related to disease severity of community-acquired bone and joint infections in children, a cohort of pediatric patients was prospectively recruited from 13 centers in 7 European countries. A total of 85 children were included, 11 (13%) had a severe infection. Panton-Valentine leukocidin–positive isolates were 17%, and 6% of the isolates were methicillin-resistant Staphylococcus aureus. Multivariate analysis identified Panton-Valentine leukocidin presence (adjusted odds ratio, 12.6; P = 0.01) as the only factor independently associated with severe outcome, regardless of methicillin resistance.

Casos clínicos

A 6-year-old boy living in a farming household presented to dermatology clinic for evaluation of worsening rash on the right eyelid. He had developed an erythematous plaque with a peripheral scale on the right lower eyelid 2 months prior (Figure 1, A ). He was initially diagnosed with eyelid eczema and treated with hydrocortisone and moisturizer. The rash worsened and he was subsequently treated with topical erythromycin and systemic cephalexin, amoxicillin-clavulanic acid, clindamycin, and valacyclovir without improvement. At presentation, physical examination was significant for an erythematous plaque with numerous superficial pustules involving the right upper and lower eyelids and loss of eyelashes (Figure 1, B). The constellation of physical examination findings and prior failed therapies was suggestive of a tinea faciei. Fungal cultures were collected which subsequently grew Trichophyton verrucosum. The patient was treated with a 2-month course of itraconazole 5 mg/kg/day, which resulted in resolution of the eruption (Figure 2). OK

Niña angolana 16 años, remitida a Portugal con hinchazón progresiva de la cadera derecha y pérdida de 30kg de peso en 18 meses. No síntomas respiratorios. Al ingreso presentó con delgadez extrema y deshidratación; estaba febril, con múltiples úlceras de decúbito y una masa ilíaca dura de 30cm que se extendía al abdomen. La auscultación pulmonar fue anodina. Las pruebas de sangre revelaron anemia grave (6g/dl) y un índice de parasitemia (Plasmodium falciparum) del 0,5%. El cribado del VIH fue negativo. La tomografía computarizada (TC) abdominal reveló una masa ilíaca de 30cm con fragmentación cortical (fig. 1) invadiendo la aorta, la vena cava, el colon y la vejiga. El examen histológico de una muestra obtenida por biopsia identificó un condrosarcoma de grado 1. Por añadidura, la TC torácica reveló cavitación extensa apical en ambos pulmones adyacente a los bronquios de drenaje (signo de la raqueta de tenis [fig. 2]). El examen microscópico de un frotis teñido de aspirado gástrico objetivó una alta concentración de bacilos ácido-alcohol resistentes, aislándose Mycobacterium tuberculosis en cultivo. La paciente desarrolló vómitos fecaloideos. Al ser imposible la cura, se iniciaron cuidados paliativos y la paciente murió el octavo día.

SARS-CoV-2, the RNA coronavirus etiologic agent of pneumonias that appeared in December 2019 was sequenced and confirmed in January 2020 by the Chinese Center for Disease Control and Prevention.1 The World Health Organization on March 11 officially designated COVID-19 a pandemic as it spread rapidly to 196 countries with over 54,000 confirmed cases in the United States alone.2

While reports about the virus have focused on the adult population, the largest study on children to date has been reported from China by Dong et al. Their clinical severity analysis, which included both COVID-19-positive patients and those with a high index of suspicion, revealed that severe (ie, respiratory distress) and critical (ie, ARDS or shock) occurred in 5.9% of children compared with 18.5% in adults, with infants below age one comprising the highest proportion.3

We report a previously healthy, fully vaccinated, late preterm, 58-day-old male who presented with fever. On the day of admission, he was sleeping longer than normal, had watery eye discharge with periorbital erythema and a rectal temperature of 101.2F. Stools were softer and greener for the past 2 days. There was no respiratory distress, cough, decreased intake, decreased frequency of wet diapers, sick contacts, or travel.

Since December 2019, novel coronavirus-infected pneumonia (coronavirus disease 19) occurred in Wuhan and rapidly spread throughout China and beyond. During this period, increasing of reports found that several recovered patients from different hospitals showed positive results of nucleic acid test again soon after discharge. However, little attention has been paid to recovered children. Herein, we reported a case of 8-year-old recovered child, who was rehospitalized again because of unexplained fever.

Para profundizar

Importance: The longitudinal association among persistent Staphylococcus aureus colonization, household environmental contamination, and recurrent skin and soft tissue infection (SSTI) is largely unexplored to date.

Objectives: To identify factors associated with persistent S aureus colonization and recurrent SSTI in households with children with community-associated methicillin-resistant S aureus (MRSA) SSTI.

Design, Setting, and Participants: This 12-month prospective cohort study included 150 children with community-associated MRSA SSTI, 542 household contacts, and 154 pets enrolled from January 3, 2012, through October 20, 2015. A total of 5 quarterly home visits were made to 150 households in the St Louis, Missouri, region. Statistical analysis was performed from September 18, 2018, to January 7, 2020.

Exposures: Covariates used in S aureus strain persistence and interval SSTI models included S aureus colonization and contamination measures, personal hygiene and sharing habits, health history, activities external to the home, and household characteristics (eg, cleanliness, crowding, home ownership, and pets). Serial samples to detect S aureus were collected from household members at 3 anatomic sites, from pets at 2 anatomic sites, and from environmental surfaces at 21 sites.

Main Outcomes and Measures: Molecular epidemiologic findings of S aureus isolates were assessed via repetitive-sequence polymerase chain reaction. Individual persistent colonization was defined as colonization by an identical strain for 2 consecutive samplings. Longitudinal, multivariable generalized mixed-effects logistic regression models were used to assess factors associated with persistent S aureus personal colonization, environmental contamination, and interval SSTI.

Results: Among 692 household members in 150 households, 326 (47%) were male and 366 (53%) were female, with a median age of 14.82 years (range, 0.05-82.25 years). Of 540 participants completing all 5 samplings, 213 (39%) were persistently colonized with S aureus, most often in the nares and with the strain infecting the index patient at enrollment. Nine pets (8%) were persistently colonized with S aureus. Participants reporting interval intranasal mupirocin application were less likely to experience persistent colonization (odds ratio [OR], 0.44; 95% credible interval [CrI], 0.30-0.66), whereas increasing strain-specific environmental contamination pressure was associated with increased individual persistent colonization (OR, 1.17; 95% CrI, 1.06-1.30). Strains with higher colonization pressure (OR, 1.47; 95% CrI, 1.25-1.71) and MRSA strains (OR, 1.57; 95% CrI, 1.16-2.19) were more likely to persist. Seventy-six index patients (53%) and 101 household contacts (19%) reported interval SSTIs. Individuals persistently colonized with MRSA (OR, 1.56; 95% CrI, 1.17-2.11), those with a history of SSTI (OR, 2.55; 95% CrI, 1.88-3.47), and index patients (OR, 1.54; 95% CrI, 1.07-2.23) were more likely to report an interval SSTI.

Conclusions and Relevance: The study findings suggest that recurrent SSTI is associated with persistent MRSA colonization of household members and contamination of environmental surfaces. Future studies may elucidate the effectiveness of specific combinations of personal decolonization and environmental decontamination efforts in eradicating persistent strains and mitigating recurrent SSTIs.

Scenario. A healthy 8-year-old boy presents with recurrent staphylococcal skin infections, frequently requiring surgical drainage. Decolonisation of the patient and whole family with nasal mupirocin and chlorhexidine washes has been suggested. His parents ask how effective this or other interventions are likely to be (or not to be).

Structured clinical question. In an otherwise healthy child with recurrent community-acquired staphylococcal skin and soft tissue infections (SSTI) (patient), are decolonisation measures (intervention) over and above standard hygiene measures (comparator) effective in preventing recurrences (outcome)?

Importance:  Descriptions of the coronavirus disease 2019 (COVID-19) experience in pediatrics will help inform clinical practices and infection prevention and control for pediatric facilities.

Objective:  To describe the epidemiology, clinical, and laboratory features of patients with COVID-19 hospitalized at a children’s hospital and to compare these parameters between patients hospitalized with and without severe disease.

Design, Setting, and Participants  This retrospective review of electronic medical records from a tertiary care academically affiliated children’s hospital in New York City, New York, included hospitalized children and adolescents (≤21 years) who were tested based on suspicion for COVID-19 between March 1 to April 15, 2020, and had positive results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Exposures  Detection of SARS-CoV-2 from a nasopharyngeal specimen using a reverse transcription–polymerase chain reaction assay.

Main Outcomes and Measures:  Severe disease as defined by the requirement for mechanical ventilation.

Results:  Among 50 patients, 27 (54%) were boys and 25 (50%) were Hispanic. The median days from onset of symptoms to admission was 2 days (interquartile range, 1-5 days). Most patients (40 [80%]) had fever or respiratory symptoms (32 [64%]), but 3 patients (6%) with only gastrointestinal tract presentations were identified. Obesity (11 [22%]) was the most prevalent comorbidity. Respiratory support was required for 16 patients (32%), including 9 patients (18%) who required mechanical ventilation. One patient (2%) died. None of 14 infants and 1 of 8 immunocompromised patients had severe disease. Obesity was significantly associated with mechanical ventilation in children 2 years or older (6 of 9 [67%] vs 5 of 25 [20%]; P = .03). Lymphopenia was commonly observed at admission (36 [72%]) but did not differ significantly between those with and without severe disease. Those with severe disease had significantly higher C-reactive protein (median, 8.978 mg/dL [to convert to milligrams per liter, multiply by 10] vs 0.64 mg/dL) and procalcitonin levels (median, 0.31 ng/mL vs 0.17 ng/mL) at admission (P < .001), as well as elevated peak interleukin 6, ferritin, and D-dimer levels during hospitalization. Hydroxychloroquine was administered to 15 patients (30%) but could not be completed for 3. Prolonged test positivity (maximum of 27 days) was observed in 4 patients (8%).

Conclusions and Relevance:  In this case series study of children and adolescents hospitalized with COVID-19, the disease had diverse manifestations. Infants and immunocompromised patients were not at increased risk of severe disease. Obesity was significantly associated with disease severity. Elevated inflammatory markers were seen in those with severe disease.

Resultados: Hubo 728 (34,1%) casos confirmados por laboratorio y 1407 (65,9%) casos sospechosos. La mediana de edad de todos los pacientes fue de 7 años (rango intercuartil: 2-13 años), y 1208 pacientes de casos (56,6%) eran niños. Más del 90% de todos los pacientes eran casos asintomáticos, leves o moderados. La mediana del tiempo desde el inicio de la enfermedad hasta el diagnóstico fue de 2 días (rango: 0-42 días). Hubo un rápido aumento de la enfermedad en la etapa temprana de la epidemia, y luego hubo una disminución gradual y constante. La enfermedad se propagó rápidamente de la provincia de Hubei a las provincias  circundantes con el tiempo. Se infectaron más niños en la provincia de Hubei que en cualquier otra provincia. 

CONCLUSIONES: Los niños de todas las edades fueron susceptibles a COVID-19, y no hubo diferencias significativas de sexo. Aunque las manifestaciones clínicas de los casos de COVID-19 de los niños fueron generalmente menos graves que las de los pacientes adultos, los niños pequeños, especialmente los lactantes, fueron vulnerables a la infección. La distribución de los casos de COVID-19 de los niños varió con el tiempo y el espacio, y la mayoría de los casos se concentraron en la provincia de Hubei y sus alrededores. Además, este estudio proporciona una fuerte evidencia de transmisión de persona a persona.

Pediatrics June 2020, 145 (6) e20200834; DOI: https://doi.org/10.1542/peds.2020-0834

COMENTARIO FINAL: Aunque el foco de las pandemias a menudo está en el impacto en las personas que usan los recursos más altos o en los grupos de edad económicamente favorecidos, habrá que ser rigurosos en medir el impacto de COVID-19 en los niños para modelar/evaluar con precisión la pandemia y asegurar que los recursos apropiados son asignados a niños que requieren determinados cuidados. Muchas enfermedades infecciosas afectan a los niños de manera diferente a los adultos, y comprender estas diferencias puede proporcionar información importante sobre la patogénesis de la enfermedad, el manejo y el desarrollo de la terapéutica. Esto probablemente será cierto para COVID-19, tal como lo fue para las enfermedades infecciosas más antiguas.

Importance: The recent and ongoing coronavirus disease 2019 (COVID-19) pandemic has taken an unprecedented toll on adults critically ill with COVID-19 infection. While there is evidence that the burden of COVID-19 infection in hospitalized children is lesser than in their adult counterparts, to date, there are only limited reports describing COVID-19 in pediatric intensive care units (PICUs).

Objective: To provide an early description and characterization of COVID-19 infection in North American PICUs, focusing on mode of presentation, presence of comorbidities, severity of disease, therapeutic interventions, clinical trajectory, and early outcomes.

Design, Setting, and Participants:  This cross-sectional study included children positive for COVID-19 admitted to 46 North American PICUs between March 14 and April 3, 2020. with follow-up to April 10, 2020.

Main Outcomes and Measures: Prehospital characteristics, clinical trajectory, and hospital outcomes of children admitted to PICUs with confirmed COVID-19 infection.

Results:  Of the 48 children with COVID-19 admitted to participating PICUs, 25 (52%) were male, and the median (range) age was 13 (4.2-16.6) years. Forty patients (83%) had significant preexisting comorbidities; 35 (73%) presented with respiratory symptoms and 18 (38%) required invasive ventilation. Eleven patients (23%) had failure of 2 or more organ systems. Extracorporeal membrane oxygenation was required for 1 patient (2%). Targeted therapies were used in 28 patients (61%), with hydroxychloroquine being the most commonly used agent either alone (11 patients) or in combination (10 patients). At the completion of the follow-up period, 2 patients (4%) had died and 15 (31%) were still hospitalized, with 3 still requiring ventilatory support and 1 receiving extracorporeal membrane oxygenation. The median (range) PICU and hospital lengths of stay for those who had been discharged were 5 (3-9) days and 7 (4-13) days, respectively.

Conclusions and Relevance:  This early report describes the burden of COVID-19 infection in North American PICUs and confirms that severe illness in children is significant but far less frequent than in adults. Prehospital comorbidities appear to be an important factor in children. These preliminary observations provide an important platform for larger and more extensive studies of children with COVID-19 infection.

We studied 1217 specimens tested for SARS-CoV-2 and other respiratory pathogens, from 1206 unique patients; 116 of the 1217 specimens (9.5%) were positive for SARS-CoV-2 and 318 (26.1%) were positive for 1 or more non–SARS-CoV-2 pathogens. Table 1 reports patient demographics and location of testing, stratified by presence of SARS-CoV-2 and non–SARS-CoV-2 pathogens.

Of the 116 specimens positive for SARS-CoV-2, 24 (20.7%) were positive for 1 or more additional pathogens, compared with 294 of the 1101 specimens (26.7%) negative for SARS-CoV-2 (Table 1) (difference, 6.0% [95% CI, –2.3% to 14.3%]). The most common co-infections were rhinovirus/enterovirus (6.9%), respiratory syncytial virus (5.2%), and non–SARS-CoV-2 Coronaviridae (4.3%) (Table 2). None of the differences in rates of non–SARS-CoV-2 pathogens between specimens positive and negative for SARS-CoV-2 were statistically significant at P < .05.

Of 318 specimens positive for 1 or more non–SARS-CoV-2 pathogens, 24 (7.5%) were also positive for SARS-CoV-2. Among 899 specimens negative for other pathogens, 92 (10.2%) were positive for SARS-CoV-2 (difference, 2.7% [95% CI, –1.0% to 6.4%]).

Results were not substantially changed by restricting the analysis to 1 specimen per patient (defaulting to the second specimen when results conflicted): of 115 patients positive for SARS-CoV-2, 23 (20.0%) were positive for other pathogens, compared with 292 of 1091 patients (26.8%) negative for SARS-CoV-2 (difference, 6.8% [95% CI, –1.5% to 15.0%]). Of 315 patients positive for other pathogens, 23 (7.3%) were positive for SARS-CoV-2, compared with 92 of 891 patients (10.3%) negative for other pathogens (difference, 3.0% [95% CI, –0.7% to 6.7%]).

Patients with co-infections did not differ significantly in age (mean, 46.9 years) from those infected with SARS-CoV-2 only (mean, 51.1 years) (difference, 4.2 [95% CI, –4.8 to 13.2] years).

Discussion: These results suggest higher rates of co-infection between SARS-CoV-2 and other respiratory pathogens than previously reported, with no significant difference in rates of SARS-CoV-2 infection in patients with and without other pathogens. The presence of a non–SARS-CoV-2 pathogen may not provide reassurance that a patient does not also have SARS-CoV-2.

The study is limited to a single region. Given limited sample size, restriction to multiply tested specimens, and spatiotemporal variation in viral epidemiology, the analysis is limited in the detection of specific co-infection patterns potentially predictive of SARS-CoV-2. Nonetheless, these results suggest that routine testing for non–SARS-CoV-2 respiratory pathogens during the COVID-19 pandemic is unlikely to provide clinical benefit unless a positive result would change disease management (eg, neuraminidase inhibitors for influenza in appropriate patients).

Results

There were 1070 specimens collected from 205 patients with COVID-19 who were a mean age of 44 years (range, 5-67 years) and 68% male. Most of the patients presented with fever, dry cough, and fatigue; 19% of patients had severe illness. Bronchoalveolar lavage fluid specimens showed the highest positive rates (14 of 15; 93%), followed by sputum (72 of 104; 72%), nasal swabs (5 of 8; 63%), fibrobronchoscope brush biopsy (6 of 13; 46%), pharyngeal swabs (126 of 398; 32%), feces (44 of 153; 29%), and blood (3 of 307; 1%). None of the 72 urine specimens tested positive (Table).

The mean cycle threshold values of all specimen types were more than 30 (<2.6 × 104 copies/mL) except for nasal swabs with a mean cycle threshold value of 24.3 (1.4 × 106 copies/mL), indicating higher viral loads (Table).

Twenty patients had 2 to 6 specimens collected simultaneously (Figure). Viral RNA was detected in single specimens from 6 patients (respiratory specimens, feces, or blood), while 7 patients excreted virus in respiratory tract specimens and in feces (n = 5) or blood (n = 2). Live SARS-CoV-2 was observed in the stool sample from 2 patients who did not have diarrhea.

Discussion

In this study, SARS-CoV-2 was detected in specimens from multiple sites of 205 patients with COVID-19, with lower respiratory tract samples most often testing positive for the virus. Importantly, the live virus was detected in feces, implying that SARS-CoV-2 may be transmitted by the fecal route. A small percentage of blood samples had positive PCR test results, suggesting that infection sometimes may be systemic. Transmission of the virus by respiratory and extrarespiratory routes may help explain the rapid spread of disease. In addition, testing of specimens from multiple sites may improve the sensitivity and reduce false-negative test results. Two smaller studies reported the presence of SARS-CoV-2 in anal or oral swabs and blood from 16 patients in Hubei Province,3 and viral load in throat swabs and sputum from 17 confirmed cases.4

The limitations of this study include that some patients did not have detailed clinical information available, so the data could not be correlated with symptoms or disease course and that the number of some types of samples was small. Further investigation of patients with detailed temporal and symptom data and consecutively collected specimens from different sites is warranted.

To the Editor:

Fabi et al present 98 consecutive cases of acute rheumatic fever (ARF) observed in a single hospital in the Emilia-Romagna Region of Italy.1 They concluded that 49% of the patients developed ARF despite having received antibiotic treatment for pharyngitis and that a 10-day course of antibiotics is needed to prevent ARF.

The design of the study, a case series, does not allow an inference to be drawn about the association between the duration of antibiotic treatment and the development of ARF. The number of patients treated for pharyngitis who have not developed ARF is unknown in this type of study. In addition, the study design does not allow an evaluation of whether the observed cases of ARF are above the expected number or the direction of the temporal trend. There is a lack of description of the review methods for data extraction from medical records and there is a risk of misclassification, because the presence of symptoms related to pharyngitis is known only for 71 patients whereas antibiotic treatment is reported for all 98 cases without specifying the timing of antibiotic treatment: patients may have been treated for other causes and/or at other times and may have been incorrectly classified as being treated for pharyngitis.

To the Editor:

Di Mario et al raised concerns about our finding showing that acute rheumatic fever (ARF) develops in 49% of patients despite the antibiotic treatment and debate 1 potential explanation of these results. Because we documented that the mean duration of antibiotic treatment for primary prophylaxis was 5.9 ± 3.1 days, we speculated that the duration could partially explain the fact that ARF develops despite antibiotic treatment and, considering the incidence of ARF in our area, we suggested 10 days of antibiotic treatment, according to American Academy of Pediatrics1 and Infectious Disease Society of America.2 We underlined that the duration of treatment can depend on several factors, such as child's and parental adherence.

Pneumonia. Pediatrics June 2020, 145 (6) e20193728; DOI: https://doi.org/10.1542/peds.2019-3728

Los biomarcadores del huésped predicen la gravedad de la enfermedad en adultos con neumonía adquirida en la comunidad (NAC). Evaluamos la asociación del recuento de glóbulos blancos (WBC), el recuento absoluto de neutrófilos (NT)), la proteína C reactiva (PCR) y la procalcitonina con el desarrollo de resultados graves en niños con NAC.

CONCLUSIONES: El recuento de leucocitos, NT, PCR y procalcitonina generalmente no son útiles para discriminar la enfermedad severa y no severa en niños con NAC, aunque la PCR y la procalcitonina podrían tener alguna utilidad para predecir los resultados más severos.

Resultados. Evaluamos a 231 pacientes que cumplían con la definición de caso de encefalitis, entre los cuales el 42% no tenía una etiología reconocida. Entre aquellos con una etiología identificada, los más comunes fueron infecciosos (73; 31%), incluyendo virales (n = 51; 22%), siendo los más frecuentes el virus del Nilo Occidental (VNO; n = 12) y bacterianos (n = 19; 8%), siendo los más frecuentes Bartonella henselae (n = 7). Entre los casos de encefalitis autoinmune (n = 60; 26%), la causa más frecuente fue la encefalitis anti-N-metil-D-aspartato (NMDAR) (n = 31). Las causas autoinmunes se observaron con mayor frecuencia en pacientes de sexo femenino (P &lt;.01). Las pruebas para detectar el virus del herpes simple y el enterovirus fueron casi universales; las pruebas de encefalitis anti-NMDAR, VNO y Bartonella fueron menos comunes.

CONCLUSIONES: El VNO fue la causa infecciosa más común de encefalitis en nuestra población pediátrica a pesar de la menor frecuencia de pruebas de VNO que el virus del herpes simple o el enterovirus. El aumento de las pruebas de encefalitis anti- NMDAR resultó en la identificación frecuente de casos de este tipo autoinmune. El aumento de la sensibilización a esta causa y las pruebas para detectar el VNO y Bartonella probablemente resulten en un aumento de causas identificadas de encefalitis pediátrica. El diagnóstico etiológico más precoz de encefalitis puede conducir a mejorar los resultados clínicos.

Coronavirus disease 2019 (CoVID-19) is a new infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated from Wuhan in China and has now spread globally. However, despite the concern focused on SARS-CoV-2, influenza virus continues to circulate and cause disease. Here we report a mixed infection. Physicians should be alert that a positive test for influenza does not rule out the possibility of COVID-19 disease.

The number of subjects infected with SARS-Cov-2 is dramatically increasing in Lombardy, Northern Italy, since February 21, 2020, leading to an infection chain that represents the largest coronavirus disease 2019 (CoVID-19) outbreak in Europe to date. Nowadays, few SARS-Cov-2–positive children have been admitted to pediatric departments. In winter season, a huge number of children with acute respiratory failure needs to be hospitalized in pediatric ward/pediatric intensive care units if ventilated. This setting could be very difficult to have clinical criteria aiming to isolate suspected SARS-CoVID-2 children to avoid spreading of infection among health care professionals, other patients and visitors. The aim of this report is to document our experience in facing pediatric CoVID-19 emergency in Milan.

 

We performed a cohort study to investigate whether children hospitalized with measles (cases) between 2000 and 2015 in Switzerland would have a higher frequency of hospital admissions due to other infectious diseases thereafter than children who did not have measles (controls). Cases were identified by ICD-10 discharge diagnoses for measles and/or keyword search and matched to 2 controls by time of hospitalization, age and sex. All hospitalizations ≤3 years after original admission, infectious or noninfectious in origin, were identified in cases and controls.

Results: One hundred thirteen cases (56% males), mean age 9.0 years (range 2 weeks–17.8 years), and 196 controls were identified. Twelve rehospitalizations due to an infectious disease occurred in 11 cases and 6 in 6 controls (episode rates 0.106 versus 0.031 per person; ratio 3.47; 95% CI: 1.20–11.3; P = 0.012) in 3 years of follow-up. Of these, 9 and 3 occurred in cases and controls, respectively, during year 1 [ratio 5.20 (95% CI: 1.30–29.88; P = 0.012)]. Infectious diseases following measles affected various organ systems, were neither particularly severe nor fatal and revealed no specific pattern.

Conclusions: The increased risk for nonspecific infectious disease hospitalizations supports the concept of immunologic amnesia after measles. Universal immunization against measles provides additional benefit beyond protection against measles itself.

Influenza A viruses are conventionally thought to cause more severe illnesses than B viruses, but few studies with long observation periods have compared the clinical severity of A and B infections in hospitalized children.

Methods: We analyzed the clinical presentation, outcomes and management of all children <16 years of age admitted to Turku University Hospital, Finland, with virologically confirmed influenza A or B infection during the 14-year period of 1 July 2004 to 30 June 2018. All comparisons between influenza A and B were performed both within predefined age groups (0–2, 3–9 and 10–15 years) and in all age groups combined.

Results: Among 391 children hospitalized with influenza A or B infection, influenza A was diagnosed in 279 (71.4%) and influenza B in 112 (28.6%) children. Overall, there were no significant differences in any clinical features or outcomes, management, treatment at intensive care unit or length of stay between children with influenza A and B, whether analyzed by age group or among all children. As indicators of the most severe clinical presentations, blood cultures were obtained from 101 (36.2%) children with influenza A and 39 (34.8%) with influenza B (P = 0.80), and lumbar puncture was performed to 16 (5.7%) children with influenza A and 11 (9.8%) children with influenza B (P = 0.15).

Conclusions: The clinical severity of influenza A and B infections is similar in children. For optimal protection against severe influenza illnesses, the use of quadrivalent vaccines containing both lineages of B viruses seems warranted in children. OK

When faced with an infant between the ages of 29 and 60 days presenting with a fever, there are various prediction rules or risk assessment tools that can be used to identify those at low risk of serious bacterial infection (SBI). The Boston and Philadelphia criteria were developed over twenty years ago to identify young, febrile infants at low risk for SBI who may be safely discharged from emergency departments and children’s assessment units. The Archivist continues to see these criteria included in some hospital guidelines. The epidemiology of SBI has changed since the development of conjugate vaccines. How useful are these criteria … OK

  • C difficile 2020. J Pediatrics 2020; 221: 1-3. The study by Miranda-Katz et al from Kaiser Permanente Northern California approximates the true incidence of community-associated Clostridioides difficile diarrheal disease—13.7 cases per 100 000 per year for the population aged 1 to 17 years.

Compared with previous studies, this study has several strengths of broad geographic range, large number of subjects, and optimal testing methods for C difficile and toxin. Equally important, the investigators used rigorous methods to minimize inclusion of colonized but unaffected patients: 1) limiting cases to ages 1 year and older and to those with diarrhea and 2) excluding patients with hospital-acquired infection and those in whom another pathogen also is detected in stool specimen. Using a case-control study format, they also identified the usual risk factors for C difficile as healthcare visits in the preceding year and receipt of certain antimicrobial agents in the preceding three months. This said, the highest case incidence (70 cases/100 000/year) occurred in children in the community between 1 and 2 years of age without remarkable healthcare-related risk factors. This epidemiology has not been widely recognized previously or definitively shown.

Here is an alert to the up-to-date consumer of the medical literature. The gurus of medical microbiology have decided that the genus Clostridioides should replace the genus Clostridium for the species difficile. Thankfully, the designation as C difficile or “C diff” still works.

To assess which risk factors are associated with community-associated Clostridioides difficile infection (CDI) in children.

Study design. This case control study was a retrospective review of all children 1-17 years of age with stool specimens sent for C difficile testing from January 1, 2012, to December 31, 2016. Cases and controls were children who had C difficile testing performed in the community or first 48 hours of hospital admission and >12 weeks after hospital discharge, with no prior positive C difficile testing in last 8 weeks, without other identified causes of diarrhea, and with clinical symptoms. Cases had positive confirmatory testing for C difficile. Controls had negative testing for C difficile and were matched to cases 1:1 by age and year of specimen collection.

Results. The overall incidence rate of community-acquired CDI in this cohort was 13.7 per 100 000 children per year. There was a substantial increase in community-acquired CDI from 9.6 per 100 000 children per year in 2012 to a peak of 16.9 per 100 000 children per year in 2015 (Cochran-Armitage test for trend P = .002). The risk factors for community-acquired CDI included non-Hispanic ethnicity; amoxicillin-clavulanate, cephalosporin, and clindamycin use within the previous 12 weeks; a previous positive C difficile test within 6 months; and increased health care visits in the last year.

Conclusions. As rates of community-acquired CDI are increasing, enhanced antibiotic stewardship and recognition of health care disparities may ease the burden of community-acquired CDI.

Chagas disease has become a global health problem, with the pediatric population being especially vulnerable. Our aim was to describe the clinical-epidemiologic aspects of disease in this population, as well as tolerance and adherence to treatment and the subsequent evolution of the disease.

Methods: A prospective study involving 949 children 0–14 years of age screened from 2007 to 2018. Diagnosis was performed by polymerase chain reaction and/or microhematocrit in <1-year-old children or serology in those ≥1 year of age. After diagnosis, children were examined for the clinical manifestation of Chagas disease and were treated with benznidazole. Treatment response was monitored by polymerase chain reaction and serology.

Results: Forty children were infected (4.2% of the population screened). Twelve children were diagnosed during the acute phase (≤1-year-old), 3 of whom were symptomatic, and 28 (4- to 14-year-olds) were in the chronic phase: 18 in the indeterminate phase and 10 presented cardiac and/or digestive involvement. Regarding treatment, 10 (25.6%) children had side effects (6 mild, 2 moderate and 2 severe reactions), leading to treatment interruption in 3 of them. No side effects were detected in ≤1-year-old children (P < 0.05). Cure was confirmed in 29.4% of the children during follow-up, and the age of the children at treatment (≤1 year) was clearly associated with the effectiveness of treatment (P < 0.05).

Conclusions: Effectiveness and safety of treatment were optimum in ≤1-year-old children. Increased side effects, cardiac and/or digestive disorder incidence and lower treatment effectiveness were detected in older children, highlighting the need for early screening.

Cephalexin is used for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) infections in children. Although 4 times daily dosing is recommended, less frequent dosing regimens are often prescribed to improve treatment acceptability and adherence. We developed a population pharmacokinetic model of cephalexin in children to determine a twice-daily (BID) and thrice-daily (TID) cephalexin dosing regimen for MSSA infections.

Methods: A population pharmacokinetic model was developed using a nonlinear mixed effects modeling approach. The dataset used was from a prospective open-label pharmacokinetic study of orally administered cephalexin in 12 children 1–16 years of age with bone and joint infections. Simulations were performed to determine a BID and TID dosing regimen so that ≥90% of children in this age group would achieve the pharmacodynamic target for MSSA (ie, time that the free drug concentration exceeds the minimum inhibitory concentration of the bacteria for at least 40% of the dosing interval).

Results: The final model was 1 compartment with a transit compartment model to account for delay in oral absorption. For BID dosing, doses of 22–45 and 80 mg/kg were required for MSSA with minimum inhibitory concentrations of 1–2 and 4 mg/L, respectively. For TID dosing, the respective required doses were 15–25 and 45 mg/kg.

Conclusions: Our study proposes a BID and TID cephalexin dosing regimen that can be prospectively evaluated. Through reducing the dose frequency of this widely prescribed antibiotic, we can reduce the medication burden for children and improve treatment compliance for MSSA infections.

Osteoarticular infections are one of the more common invasive bacterial infections encountered in children. There exist significant practice variations in both the diagnosis and treatment of such infections. However, the practice of transitioning from parenteral therapy to oral antibiotics has been well validated by several studies. For methicillin-sensitive Staphylococcus aureus (MSSA), cephalexin is often recommended. Prospective, controlled data regarding optimal dosing of cephalexin in pediatric osteomyelitis are not available. We sought to review our retrospective, uncontrolled data on four times daily (QID) versus three times daily (TID) dosing of cephalexin for pediatric osteoarticular infections. Children ≥1 month to <18 years of age admitted to Rady Children’s Hospital-San Diego with a diagnosis of osteomyelitis or septic arthritis between January 1, 2002, and November 30, 2007, were identified and previously reported. Only patients with culture-positive MSSA infections are included in this report. Demographic and clinical data were manually extracted from the electronic medical record. Fifty-nine patients were treated with cephalexin and had records available for review through our electronic medical record. Thirty-eight patients (64.4%) were treated QID, and 21 patients (35.6%) were treated TID. Clinical cure was achieved in all patients with only one adverse event occurring in the QID group. In this retrospective chart review of children with osteoarticular infections caused by MSSA treated with cephalexin, similar clinical outcomes were found with QID versus TID dosing.

Several evidence-based guidelines for the management of children with febrile neutropenia (FN) have been published, with special focus in bacterial and fungal infections. However, the role of acute respiratory infections caused by respiratory viruses (RV) has not been clearly established. The aim of this study was to evaluate the epidemiology, clinical presentation and outcome of acute respiratory infections in children with FN.

Methods: Patients, <18 years of age admitted to the Pediatric Oncology-Hematology Unit after developing FN between November 2010 and December 2013, were prospectively included in the study. Children were evaluated by clinical examination and laboratory tests. Nasopharyngeal sample was obtained for detection of RV.

Results: There was a total of 112 episodes of FN in 73 children admitted to the hospital during a 32-month period. According to disease severity, 33% of the episodes were considered moderate or severe. Rhinovirus was the most frequently detected RV (66.6%; 24/36), followed by parainfluenza. On regard to clinical outcome, RV-infected children developed fewer episodes of moderate or severe FN compared with non-RV infected children (16.7% vs. 33.3%; P = 0.08).

Conclusions: A great proportion of children with FN admitted to a tertiary hospital had a RV isolation. The rate of this RV isolation was significantly higher when a rapid molecular test was used compared with conventional microbiologic methods. Rhinovirus was the most frequently isolated, although its role as an active agent of acute infection was not clear. Children with FN and a RV isolate had a lower rate of severe disease.

Objective To describe infants with acute gastroenteritis symptoms in primary and secondary care who have the Rotarix vaccine-derived G1P[8] rotavirus strain identified in their stools.

Design This is a prospective national surveillance conducted by Public Health England (PHE). Rotavirus-positive samples from vaccine-eligible children are routinely submitted to PHE for confirmation, and general practitioners are requested to complete a surveillance questionnaire for all cases. The modified Vesikari Score was used to assess severity of gastroenteritis.

Setting England, July 2013–September 2016.

Results 2637 rotavirus strains were genotyped and 215 (8%) identified as the Rotarix vaccine-derived G1P[8] strain. There were no Rotarix vaccine-derived G1P[8] strains detected in unimmunised infants. Rotarix vaccine-derived G1P[8] strains clustered around the time of rotavirus vaccination and were responsible for 82% (107 of 130) of rotavirus-positive samples in 2-month-old infants and 68% (36 of 53) in 3-month-old infants. However, 13 samples were obtained more than 7 weeks after the last vaccination date; 10 of these specimens were from six children who were subsequently diagnosed with severe combined immunodeficiency (SCID). Diarrhoea was the single most common presenting symptom (83.0%) in infants with Rotarix vaccine-derived G1P[8] strains, who were less likely to present with fever, vomiting, dehydration or severe gastroenteritis than infants with wild-type rotavirus infection.

Conclusions Rotavirus identified in stools of infants around the time of their routine immunisations is most likely the Rotarix vaccine-derived G1P[8] strain. Infants with undiagnosed SCID at the time of rotavirus immunisation may experience prolonged gastroenteritis symptoms. Most infants with vaccine strains in their stools more than 7 weeks after immunisation had SCID.

Objective. To evaluate the hypothesis that early-onset sepsis increases risk of death or neurodevelopmental impairment (NDI) among preterm infants; and that among infants without early-onset sepsis, prolonged early antibiotics alters risk of death/NDI.

Study design. Retrospective cohort study of infants born at the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers (2006-2014) at 22-26 weeks of gestation and birth weight 401-1000 g. Early-onset sepsis defined as growth of a pathogen from blood or cerebrospinal fluid culture ≤72 hours after birth. Prolonged early antibiotics was defined as antibiotics initiated ≤72 hours and continued ≥5 days without culture-confirmed infection, necrotizing enterocolitis, or spontaneous perforation. Primary outcome was death before follow-up or NDI assessed at 18-26 months corrected age. Poisson regression was used to estimate adjusted relative risk (aRR) and CI for early-onset sepsis outcomes. A propensity score for receiving prolonged antibiotics was derived from early clinical factors and used to match infants (1:1) with and without prolonged antibiotic exposure. Log binomial models were used to estimate aRR for outcomes in matched infants.

Results. Among 6565 infants, those with early-onset sepsis had higher aRR (95% CI) for death/NDI compared with infants managed with prolonged antibiotics (1.18 [1.06-1.32]) and to infants without prolonged antibiotics (1.23 [1.10-1.37]). Propensity score matching was achieved for 4362 infants. No significant difference in death/NDI (1.04 [0.98-1.11]) was observed with or without prolonged antibiotics among the matched cohort.

Conclusions. Early-onset sepsis was associated with increased risk of death/NDI among extremely preterm infants. Among matched infants without culture-confirmed infection, prolonged early antibiotic administration was not associated with death/NDI. 

To evaluate the effect of different modalities of centralized reminder/recall (autodialer, text, mailed reminders) on increasing childhood influenza vaccination.

Study design. Two simultaneous randomized clinical trials conducted from October 2017 to April 1, 2018, in New York State and Colorado. There were 61 931 children in New York (136 practices) and 23 845 children in Colorado (42 practices) who were randomized to different centralized reminder/recall modalities—4 arms in New York (autodialer, text, mailed, and no reminder control) and 3 arms in Colorado (autodialer, mailed, and no reminder control). The message content was similar across modalities. Up to 3 reminders were sent for intervention arms. The main outcome measure was receipt of ≥1 influenza vaccine.

Results. In New York, compared with the control arm (26.6%), postintervention influenza vaccination rates in the autodialer arm (28.0%) were 1.4 percentage points higher (adjusted risk ratio, 1.06; 95% CI, 1.02-1.10), but the rates for text (27.6%) and mail (26.8%) arms were not different from controls. In Colorado, compared with the control arm (29.9%), postintervention influenza vaccination rates for the autodialer (32.9%) and mail (31.5%) arms were 3.0 percentage points (adjusted risk ratio, 1.08; 95% CI, 1.03-1.12) and 1.6 percentage points (adjusted risk ratio, 1.06; 95% CI, 1.02-1.10) higher, respectively. Compared with the control arm, the incremental cost per additional vaccine delivered was $20 (New York) and $16 (Colorado) for autodialer messages.

Conclusions. Centralized reminder/recall for childhood influenza vaccine was most effective via autodialer, less effective via mail, and not effective via text messages. The impact of each modality was modest. Compared with no reminders, the incremental cost per additional vaccine delivered was also modest for autodialer messages.

We conducted a secondary analysis of a prospective study of infants ≤60 days of age who were febrile to assess the diagnostic accuracy of automated vs manual immature neutrophils for invasive bacterial infections. Although manual counts were superior compared with automated counts, bands had suboptimal accuracy overall and had significant variability in test characteristics based on methodology.

Congenital toxoplasmosis (CT) can cause significant neurologic manifestations and other untoward sequelae. Neither the current epidemiology nor the disease severity of CT in Israel is known.

Methods: Records of CT were collected from the National Toxoplasmosis Reference Laboratory and from 15 medical centers across Israel between 2001 and 2017. Eligible case-patients were fetuses or infants <12 months of age at the time of diagnosis.

Results: Of the 43 CT cases identified, 24 (55%) were in Jews and the remaining 19 cases were in patients of Arab (non-Bedouin) origin. The overall annual estimated rate of symptomatic CT was calculated as 0.55 per 100,000 live births. One or more severe clinical manifestations were reported in 12 (46%) of the 28 live-born infants and included cerebral calcifications (7 cases), chorioretinitis (4 cases), hydrocephalus (2 cases) and 1 case of death. Sensitivities of blood polymerase chain reaction (PCR), cerebrospinal fluid PCR and IgM antibody tests were 50% each. However, analyzing PCR samples from both sites, together with IgM testing, increased the sensitivity to 93%.

Conclusions: The relative rate of severe manifestations was higher than in previous European reports. It is possible that the greater disease severity observed in Israel is in part due to the lack of systematic antenatal treatment and screening. Arab (non-Bedouin) infants are at higher risk for contracting CT. Performing serologic and PCR tests simultaneously is essential to improve CT diagnosis. This study demonstrates a need for an educational program to target high-risk populations.

Serratia can cause serious bloodstream infections (BSIs). This retrospective cohort study identified 5,312 pediatric inpatient encounters with BSIs from 2009 to 2016, of which 82 (0.01%) had Serratia BSIs. The rate among hospitalized patients increased significantly from 0.4 in 2009 to 1.0 in 2016 per 10,000 admissions. Risk factors differed and outcomes were worse for Serratia BSIs compared with non-Serratia BSIs.

Results

The cohort of 305 individuals aged 4 to 60 years was balanced with regard to sex (48.9% male). Because the cohort had been recruited to study biomarkers of asthma, 49.8% had asthma.

We found age-dependent ACE2 gene expression in nasal epithelium (Figure). ACE2 gene expression was lowest (mean log2 counts per million, 2.40; 95% CI, 2.07-2.72) in younger children (n = 45) and increased with age, with mean log2 counts per million of 2.77 (95% CI, 2.64-2.90) for older children (n = 185), 3.02 (95% CI, 2.78-3.26) for young adults (n = 46), and 3.09 (95% CI, 2.83-3.35) for adults (n = 29).

Linear regression with ACE2 gene expression as the dependent variable and age group as the independent variable showed that compared with younger children, ACE2 gene expression was significantly higher in older children (P = .01), young adults (P < .001), and adults (P = .001) (Figure). As the distributions of sex and asthma varied among the age groups, a linear regression model adjusted for sex and asthma was built that also showed significant adjusted associations (P ≤ .05) between ACE2 expression and age group. Regression (β) coefficients for age groups from the unadjusted and adjusted models are shown in the Table. These regression coefficients indicate the difference in ACE2 expression (in log2 counts per million) between a given age group and the group of children younger than 10 years. Tests for trend using polynomial orthogonal contrasts indicated a significant linear trend for change in ACE2 expression with advancing age group (P ≤ .05).

Discussion

The results from this study show age-dependent expression of ACE2 in nasal epithelium, the first point of contact for SARS-CoV-2 and the human body. Covariate-adjusted models showed that the positive association between ACE2 gene expression and age was independent of sex and asthma. Lower ACE2 expression in children relative to adults may help explain why COVID-19 is less prevalent in children.3 A limitation of this study is that the sample did not include individuals older than 60 years.

Few studies have examined the relationship between ACE2 in the airway and age. A study of bronchoalveolar lavage fluid from 92 patients with acute respiratory distress syndrome reported no association between ACE2 protein activity and age,5 but epithelial gene expression was not examined, and ACE2 protein may be variably shed into bronchoalveolar lavage fluid. Furthermore, the lung and nasal environments are distinct, with known differences in gene expression.6 This study provides novel results on ACE2 gene expression in nasal epithelium and its relationship with age.

We identified eight studies (seven case-series and one prospectively planned single-arm intervention study) with a total of 32 participants (range 1 to 10). Most studies assessed the risks of the intervention; reporting two adverse events (potentially grade 3 or 4), one of which was a serious adverse event. We are very uncertain whether convalescent plasma is effective for people admitted to hospital with COVID-19 as studies reported results inconsistently, making it difficult to compare results and to draw conclusions. We identified very low-certainty evidence on the effectiveness and safety of convalescent plasma therapy for people with COVID-19; all studies were at high risk of bias and reporting quality was low.

No RCTs or controlled non-randomised studies evaluating benefits and harms of convalescent plasma have been completed. There are 47 ongoing studies evaluating convalescent plasma, of which 22 are RCTs, and one trial evaluating hyperimmune immunoglobulin. We will update this review as a living systematic review, based on monthly searches in the above mentioned databases and registries. These updates are likely to show different results to those reported here.

Introducción Evaluamos la presencia de inmunoglobulina secretoria A (sIgA) frente a proteínas secretadas por E. coli (Esp) relacionadas con el sistema de secreción tipo III (T3SS) en saliva, y su concentración semicuantitativa en niños menores de 2 años (no lactantes) colonizados o infectados previamente con E. coli enteropatógena (EPEC).

Métodos. Analizamos la presencia de sIgA en 40 niños con cultivos positivos previos para EPEC asociados (n=17) o no (n=23) con diarrea, mediante la técnica de Western-blot frente a las proteínas secretadas por E. coli (EspABCD), realizando mediciones semicuantitativas de la reacción de cada proteína mediante sus picos de densidad (OD).

Resultados. Ambos grupos presentaron sIgA frente a las proteínas EspABCD, aunque los pacientes enfermos presentaron mayores concentraciones de estos anticuerpos que los colonizados

 

Actualidad bibliográfica mayo 2020

Top ten

Importance The current rapid worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection justifies the global effort to identify effective preventive strategies and optimal medical management. While data are available for adult patients with coronavirus disease 2019 (COVID-19), limited reports have analyzed pediatric patients infected with SARS-CoV-2.

Objective To evaluate currently reported pediatric cases of SARS-CoV-2 infection.

Evidence Review An extensive search strategy was designed to retrieve all articles published from December 1, 2019, to March 3, 2020, by combining the terms coronavirus and coronavirus infection in several electronic databases (PubMed, Cochrane Library, and CINAHL), and following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Retrospective cross-sectional and case-control studies, case series and case reports, bulletins, and national reports about the pediatric SARS-CoV-2 infection were included. The risk of bias for eligible observational studies was assessed according to the Strengthening the Reporting of Observational Studies in Epidemiology reporting guideline.

Findings A total of 815 articles were identified. Eighteen studies with 1065 participants (444 patients were younger than 10 years, and 553 were aged 10 to 19 years) with confirmed SARS-CoV-2 infection were included in the final analysis. All articles reflected research performed in China, except for 1 clinical case in Singapore. Children at any age were mostly reported to have mild respiratory symptoms, namely fever, dry cough, and fatigue, or were asymptomatic. Bronchial thickening and ground-glass opacities were the main radiologic features, and these findings were also reported in asymptomatic patients. Among the included articles, there was only 1 case of severe COVID-19 infection, which occurred in a 13-month-old infant. No deaths were reported in children aged 0 to 9 years. Available data about therapies were limited.

Conclusions and Relevance  To our knowledge, this is the first systematic review that assesses and summarizes clinical features and management of children with SARS-CoV-2 infection. The rapid spread of COVID-19 across the globe and the lack of European and US data on pediatric patients require further epidemiologic and clinical studies to identify possible preventive and therapeutic strategies.

A fecha 10 de marzo de 2020, el nuevo coronavirus 2019 (SARS-CoV-2) ha sido responsable de más de 110,000 infecciones y 4000 muertes en todo el mundo. Hasta el momento, los datos sobre epidemiologia y clínica de los niños infectados son limitados. Una revisión reciente de 72,314 casos realizada por el Centro Chino para el Control y la Prevención de Enfermedades mostró que menos del 1% de los casos correspondía a niños menores de 10 años. Para determinar el espectro de la enfermedad en niños, este artículo evalúa características de la infección  niños tratados en el Hospital de Infantil de Wuhan.

Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day–17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered. 

 

 

·Risk Factors for Carriage of Antibiotic-resistant Bacteria in Healthy Children in the Community: A Systematic Review. The Pediatric Infectious Disease Journal. 39(5):397-405, May 2020.

Background: In addition to health care settings, antibiotic resistance has also been increasing in the community. Healthy children represent an important potential reservoir of antibiotic-resistant (AR) bacteria. However, strategies to reduce the spread of AR bacteria often fail to specifically address the factors that promote the carriage of AR bacteria in this population.

The objective of this review was to Identify risk factors for carriage of AR bacteria by healthy children.

Methods: We did a systematic search of MEDLINE, Embase and PubMed for studies in developed (OECD) countries that assessed risk factors for carriage of AR bacteria in healthy children in the community. We excluded studies done before 1998 and studies of AR Streptococcus pneumoniae carriage in the absence of pneumococcal conjugate vaccination.

Results: Of 1234 studies identified, 30 were eligible for inclusion. These studies assessed the impact of 49 risk factors on AR strains of S. pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Streptococcus pyogenes and Escherichia coli. The majority of these risk factors were assessed in 2 or fewer studies per bacteria. Recent antibiotic consumption was associated with carriage of resistant respiratory bacteria (S. pneumoniae, H. influenzae); however, it was not consistently associated with carriage of AR bacteria in skin or stool (S. aureus and E. coli). For AR S. aureus, transmission within households appeared to have a greater impact than individual antibiotic use.

Conclusions: The factors that promote carriage of AR bacteria by healthy children differed between bacterial species. To reduce reservoirs of AR bacteria in the community, it is essential for intervention strategies to target the specific risk factors for different bacteria.

Background. An increase in invasive meningococcal disease (IMD) serogroup W (IMD-W) cases caused by sequence type-11 clonal complex (cc11) was observed from October 2015 in the Netherlands. We compared the clinical picture and disease outcome of IMD-W cases with other serogroups, adjusting for host characteristics.

Methods. We included IMD cases reported from January 2015 to June 2018 in the Netherlands and assessed clinical manifestation and symptoms at disease onset and calculated case fatality rates (CFRs). We used logistic regression to compare clinical manifestations and mortality of IMD-W with IMD caused by meningococci serogroup B, Y, or C, adjusting for age, gender, and comorbidities.

Results. A total of 565 IMD cases were reported, of which 204 were IMD-W, 270 IMD-B, 63 IMD-Y, and 26 IMD-C. Most IMD-W isolates belonged to cc11 (93%; 175/188). Compared with other serogroups, IMD-W patients were diagnosed more often with septicemia (46%) or pneumonia (12%) and less often with meningitis (17%, P < .001). IMD-W cases presented more often with respiratory symptoms (45%, P < .001); 16% of IMD-W patients presented with diarrhea without IMD-specific symptoms (P = .061). The CFR for IMD-W was 16% (32/199, P < .001). The differences between IMD-W and other serogroups remained after adjusting for age, gender, and comorbidities.

Conclusions. The atypical presentation and severe outcome among IMD-W cases could not be explained by age, gender, and comorbidities. Almost all our IMD-W cases were caused by cc11. More research is needed to identify the bacterial factors involved in clinical presentation and severity of IMD-W cc11.

We wanted to find out how effectively MMR, MMR+V and MMRV vaccines stop children (up to 15 years old) from catching measles, mumps, rubella and chickenpox. We also wanted to know if the vaccines cause unwanted effects

We found 138 studies with more than 23 million children. Fifty-one studies (10 million children) assessed how effective the vaccines were at preventing the diseases, and 87 studies (13 million children) assessed unwanted effects. In this 2020 update we have included 74 new studies published since 2012. Measles: results from seven studies (12,000 children) showed that one dose of vaccine was 95% effective in preventing measles. Seven per cent of unvaccinated children would catch measles and this number would fall to less than 0.5% of children who receive one dose of vaccine. Mumps: results from six studies (9915 children) showed that one dose of vaccine was 72% effective in preventing mumps. This rose to 86% after two doses, (3 studies, 7792 children). In unvaccinated children, 7.4% would catch mumps and this would fall to 1% if children were vaccinated with two doses. The results for rubella (1 study, 1621 children) and chickenpox (one study, 2279 children) also showed that vaccines are effective. After one dose, vaccination was 89% effective in preventing rubella, and after 10 years the MMRV vaccine was 95% effective at preventing chickenpox infection. Unwanted effects Overall, the studies found that MMR, MMRV and MMR+V vaccines did not cause autism (2 studies 1,194,764 children), encephalitis (2 studies 1,071,088 children) or any other suspected unwanted effect. Our analyses showed very small risks of fits due to high temperature or fever (febrile seizures) around two weeks after vaccination, and of a condition where blood does not clot normally (idiopathic thrombocytopenic purpura) in vaccinated children.

Existing evidence on the safety and effectiveness of MMR/MMRV vaccines support their use for mass immunisation. Campaigns aimed at global eradication should assess epidemiological and socioeconomic situations of the countries as well as the capacity to achieve high vaccination coverage. More evidence is needed to assess whether the protective effect of MMR/MMRV could wane with time since immunisation.

 El vínculo epidemiológico más importante en este momento es el contacto con personas con infección confirmada sin menospreciar la importancia de haber viajado a una zona considerada de alto riesgo como es en este momento el norte de Italia,

Se han publicado varias series pediátricas en China confirmándose que los casos pediátricos oscilan entre el 0,8 y el 2% de los contabilizados. Los cuadros clínicos son leves en la mayoría de los niños, incluso en lactantes, con fiebre de corta duración y síntomas catarrales3–6. No se refiere en los artículos publicados que se asocie a sibilancia.s La analítica de los niños es generalmente anodina y en la tomografía computarizada (TC) se observan infiltrados parcheados (no siempre en la radiografía de tórax). Se ha documentado que los niños, aun siendo casos leves, pueden ser una importante fuente de transmisión del virus con una tasa de infección entre sus contactos de un 7,4% en los niños menores de 10 años, similar a la media de la población adulta con un 7,9%. Se ha detectado, además, que pueden excretar virus fundamentalmente en heces durante un tiempo prolongado, incluso un mes, y que los niños pueden tener altas cargas virales en secreciones respiratorias. No se ha descrito mortalidad en menores de 10 años, y la recuperación es la norma entre 14 y 30 días. No hay datos de la infección en niños inmunodeprimidos.

Respecto al tratamiento, algunos de los pacientes publicados han sido tratados con lopinavir/ritonavir a pesar de tener cuadros leves. Se esperan los resultados de un ensayo clínico con este fármaco que arrojará luz a la posibilidad de emplear este antirretroviral como tratamiento, pues actualmente hay dudas de su posible eficacia. Numerosos estudios en adultos están comparando tratamientos combinados con los antipalúdicos cloroquina e hidroxicloroquina, junto a otros antivirales, si bien no hay ningún dato en niños. Remdesivir, el antiviral análogo de nucleótido desarrollado para el virus del Ebola, continúa siendo en el momento actual el fármaco que se posiciona con mayores posibilidades de eficacia, teniendo dosis pediátricas establecidas. Su uso para esta indicación es compasivo, a través de (AEMPS).

En el momento de redactar esta carta se han detectado 6 casos de infección COVID-19 en niños, 2 en la Comunidad de Castilla-La Mancha y 5 en la Comunidad de Madrid, de un total de más de 500 casos, lo que supone alrededor de un 1%

A fecha de 7 de marzo de 2020, menos de 10 días después de que se hiciera público el primer caso de COVID-19 en Madrid, se ha realizado reacción en cadena de polimerasa (PCR) de SARS-CoV-2 al menos a 63 pacientes menores de 14 años (54% varones). La media de edad ha sido de 4,5 años, y 10 de ellos (16%) tenían enfermedad previa. De los 63 pacientes a los que conocemos que se ha hecho el análisis, 13 (20%) eran contactos de casos confirmados de COVID-19, 15 (28%) eran pacientes con síntomas compatibles y datos de riesgo (viaje a zona de riesgo o contacto estrecho con adultos con clínica compatible y viaje a zona de riesgo) y 35 (63%) eran pacientes ingresados con un cuadro respiratorio grave sin datos epidemiológicos de riesgo. El cuadro clínico más frecuente entre estos pacientes fue la neumonía (n=32/35, 91%), con o sin sibilancias asociadas (tabla 1). Se ha confirmado presencia de SARS-CoV-2 en el aspirado nasofaríngeo en 5 pacientes (8%). De ellos, 2 eran contactos de casos confirmados, 2 pacientes eran familiar en primer grado de un contacto de caso confirmado, y en un caso no había un contacto epidemiológico.

Se confirma por el momento con estos resultados que alrededor de un 1% de los casos de infección COVID-19 son niños, tal y como se describe en otros países. Sin embargo, las cifras deben ser interpretadas con precaución, dado que la incidencia varía en función del número de casos analizados, y por ahora se ha realizado cribado en un pequeño porcentaje de pacientes pediátricos. Esto podría enmascarar un porcentaje superior de casos que pueden pasar desapercibidos por ser cuadros leves, con el consiguiente riesgo de transmisión comunitaria.

Pneumonia is considered as the single largest cause of death in children under the age of five years, causing more than 800,000 deaths every year worldwide. In Spain, the incidence rates of community-acquired pneumonia (CAP) hospitalizations decreased among children from 2001 to 2014, mainly in those younger than 2 years old. Overall crude in-hospital mortality fell from 4.1‰ to 2.8‰. Once again, improvement in PCV vaccination coverage seems to have an effect on hospitalizations and outcomes for CAP in children.

The PERCH study was an impressive effort of collaboration that enrolled more than 1700 children with severe or very severe pneumonia according to WHO classification with a positive chest-X-ray in seven countries of Africa and Asia from 2011 to 2014. Viruses caused most of the severe pneumonia cases (61%), and RSV was the leading pathogen (31%) at all sites. Streptococcus pneumoniae represented 6.7% of all cases globally.4 The EPIC study was a multicenter, prospective, population-based study of community-acquired pneumonia requiring hospitalization among children in the United States of America from 2010 to 2012. Among 2222 children with radiographic evidence of pneumonia, a viral or bacterial pathogen was detected in 1802 (81%), one or more viruses in 1472 (66%), bacteria in 175 (8%), and both bacterial and viral pathogens in 155 (7%). The most commonly detected pathogen was RSV (in 28% of the children). S. pneumoniae, S. aureus, and S. pyogenes were detected in 4%,1% and 1% respectively.5 The main result of these studies is that respiratory viruses, mainly RSV, are currently the most common causes of pneumonia in any child who requires admission to a hospital worldwide.

The rapid identification of respiratory viruses in children with pneumonia presenting for hospital care may result in favorable interventions, such as a prescription of an early and appropriate antiviral, -when indicated-, aiding on decisions on hospital admissions, but also optimizing infection-control practices. Rapid antigen-based tests are not adequately accurate. However, there are also commercially multiplex molecular diagnostics for respiratory viruses with rapid turn-around time . These rapid diagnostic testing (RDT) provide accurate results for respiratory viruses when compared to the best available reference standard. Although most respiratory infections are caused by viruses, antibiotics are frequently overprescribed in this setting. The most common antibiotic prescribed in children with a respiratory infection is a β lactam antibiotic. Nasrint et al. observed in a prospective cohort of 461 children that the carriage of penicillin-resistant pneumococci was significantly associated with the use of β lactam antibiotics in the previous two months.

Several studies have given insights into the use of RDT to achieve stewardship principles in children. A Cochrane review published in 2014 and based on four studies involving 759 previously healthy children coming to the Emergency Department with fever and respiratory symptoms, observed that the use of rapid viral tests showed fewer antibiotic prescriptions trend, but this finding was not statistically significant.9 More recently, a controlled clinical trial in 583 children admitted to hospital with suspected acute respiratory infections (mainly RSV) in the Netherlands, could not show either a benefit in antibiotic use when RDT results were rapidly communicated to the clinicians. However, other observational studies have reported significant reductions on the use of antibiotic and finally, there are also favorable international recommendations for the use of RDT; the guidelines of the Infectious Diseases Society of America for the management of CAP in children stated that testing for respiratory viruses can modify clinical decision making including the prescription of antibacterial therapy.

In this issue of Enfermedades Infecciosas y Microbiología Clínica, Aguilera Alonso et al.13 described the experience of early identification of respiratory viruses in 100 children (median age of 21 months) with 105 episodes of CAP in a tertiary hospital in Madrid. This was an observational, retrospective study of children admitted to care management from 2014 to 2018. In a step-by-step approach, a rapid antigen-based test, for RSV and influenza A and B, and a multiplex molecular diagnostics respiratory viruses were used. All children included had x-ray findings of pneumonia. S. pneumoniae was isolated in blood culture of one child. There was an identification of a respiratory virus in 93 (88%) cases, mainly RSV in 37 (35%) cases, and influenza in 21 (20%) cases. Patients with RSV detection had a lower onset of empirical antibiotic therapy (35.1% vs 55.9%, p = 0.042). The duration of antibiotic therapy in cases with no viral identification was higher than in those with RSV or influenza identification (68.8% received antibiotics more than 2 days vs 45.6%, respectively, p = 0.017).

Prescriptions of antibiotics to children in Spain remains also high and antibiotics for respiratory infections are of the most prescribed.  Aguilera Alonso et al reported that empiric antibiotics were used in 51 cases (48.6%). Interestingly, viral tests were done in the first 48 h after admission and the testing TAT had a maximum time of 24 h. Shorter TATs have been related to decreased antibiotic use, early antibiotic discontinuations, decreased length of stay, and also decreased costs in randomized controlled trials in adults.16, 17

In addition, about 15% of the cases with RSV or influenza identification were admitted without antibiotic therapy but started on antibiotics later. This result may illustrate the concerns of clinicians about a possible bacterial-viral co-infection in a patient with a severe respiratory infection. Viral co-detection was observed in half of the patients with bacterial pneumonia in EPIC study, and specifically, in 82% of the cases of pneumococcal pneumonia a virus was also identified.

The main limitation of etiologic pneumonia studies is that it is very hard to identify the final cause of pneumonia in children. Only in a minority of cases, we can isolate or identify the pathogen in the lung, lower respiratory tract or blood. The detection of pathogens in nasopharyngeal or oropharyngeal swabs with the use of a molecular method could represent infection limited to the upper respiratory tract or convalescent-phase shedding, and thus detection may not denote causation. No current diagnostic test is adequately sensitive to exclude bacterial–viral coinfection when a virus is detected. In clinical practice, biomarkers such as procalcitonin or C-reactive protein may help in ruling out bacterial infection when the levels are low.

 It is also important to consider that the impact of influenza vaccination in disease prevention may be higher with the administration of inactivated quadrivalent influenza vaccine IIV4 provides a broader protection against influenza. In a phase III, observer-blind trial, including more than 12,000 children from 6 to 35 months of age, IIV4 was related to the reduction of antibiotic use associated with influenza illness by 71% in the group of European children. The impact of PCV in pneumonia, previously commented, maybe notorious in Spain with the recent inclusion of PCV13 in the National Immunization Program. There are also an urgent need and an important pipeline of development with RSV vaccine candidates that are been evaluated in children but also in pregnant women, which could lead to safeguarding their infants in the first few vulnerable months of life.

Introducción. Los virus son una de las causas más frecuentes de neumonía adquirida en la comunidad (NAC) en niños. La identificación precoz de virus respiratorios podría suponer una disminución en el consumo de antibióticos.
Métodos. Estudio observacional, retrospectivo, desde enero del 2014 hasta junio del 2018, que incluyó a los pacientes pediátricos ingresados en un hospital terciario con diagnóstico de NAC, a los que se realizó test antigénico o PCR viral en muestra respiratoria.
Resultados. Se incluyeron 105 episodios de NAC, identificándose algún virus respiratorio en 93 (88,6%) casos. Los pacientes con detección de virus respiratorio sincitial (VRS) presentaron menor inicio de antibioterapia empírica (35,1% vs. 55,9%, p valor: 0,042). Además, los casos con identificación de VRS o influenza precisaron menor duración de antibioterapia (recibiendo el 45,6% ≥ 2 días frente al 68,8% de los que no se identificó, p = 0,017).
Conclusión El uso de técnicas diagnósticas de virus respiratorios en nuestro medio puede optimizar el consumo de antibióticos en niños ingresados con NAC.

Casos clínicos

·Slowly Progressive Elbow Swelling. J Pediatr. 2020 May;220:262-263. doi: 10.1016/j.jpeds.2019.12.043.

A 9-year-old boy was brought to us with the complaint of a lump over the lateral side of the right elbow for the past 1 month. The swelling was slowly progressive and tender to touch, accompanied by a low-grade fever. There was no history of trauma, weight loss, cough, or dyspnea. Contact history with tuberculosis was negative. Examination revealed a 9 × 8 × 8 cm swelling over the proximal and lateral aspect of the right forearm without any obvious joint involvement, slightly tender on palpation with no other signs of inflammation. A clinical possibility of extrapulmonary tuberculosis or chronic bacterial infection was considered. His routine blood investigations were normal. Tuberculin skin test was positive and HIV serology was negative. An anteroposterior and lateral radiograph of the right elbow showed a large osteolytic lesion of the proximal end of the ulna (Figure 1). 

  • Manifestaciones cutáneas en contexto del brote actual de enfermedad por coronavirus 2019

DOI: 10.1016/j.anpedi.2020.04.013

CASO 1:  niño de 6 años ingresado para estudio de una hepatopatía colestásica no filiada. A las 2 semanas de su ingreso, en contexto de febrícula y un empeoramiento de los marcadores hepáticos de colestasis y citolisis, se le realizó estudio de SARS-CoV-2 que resultó positivo. A las 48h, inició un exantema maculopapular eritematoso, confluente y no pruriginoso, en el tronco y el cuello, que progresivamente se extendió a mejillas y extremidades superiores e inferiores, con afectación palmar . La duración total de la clínica cutánea fue de 5 días, y se resolvió sin otras complicaciones y sin necesidad de tratamiento específico. Se acompañó de mejoría analítica (bilirrubina, transaminasas y parámetros de coagulación). Dado el empeoramiento de la afectación hepática coincidiendo con la obtención del resultado positivo de la PCR para SARS-CoV-2 en aspirado nasofaríngeo, se realizó PCR al virus en el tejido hepático obtenido por biopsia en el estudio inicial del paciente, que resultó negativa. Durante su evolución no presentó otra clínica asociada a la infección por coronavirus

CASO 2: lactante de 2 meses que acudió a urgencias por febrícula y un cuadro de urticaria aguda, aparentemente pruriginoso, de 4 días de evolución. Inicialmente afectaba la cara y las extremidades superiores, extendiéndose en pocas horas al tronco y las extremidades inferiores. No había afectación palmoplantar. Estas manifestaciones no se acompañaban de angioedema acral, labial ni lingual.

La paciente convivía con 2 personas con COVID-19 demostrada, por lo que se realizó PCR a SARS-CoV-2 en aspirado nasofaríngeo, que fue positiva. Se pautó tratamiento sintomático vía oral con buena respuesta. La duración de la mayoría de las lesiones fue inferior a 24h, resolviéndose la clínica cutánea en 5 días, sin otras manifestaciones asociadas.

Según lo descrito en la literatura, hasta el momento, las manifestaciones cutáneas del nuevo coronavirus son similares a las producidas por otras infecciones virales comunes. No se ha observado relación entre la magnitud de la clínica cutánea y la gravedad de la enfermedad. Debemos tener presente que, además de los exantemas propios de la fase aguda de la infección descritos en este artículo, recientemente se han descrito lesiones acrales y/o perniosiformes en niños y jóvenes, por lo demás asintomáticos, que podrían ser una manifestación tardía reflejo de fenómenos inflamatorios o microtrombóticos en la fase de respuesta inmunológica.

A diferencia de nuestros casos, todos los pacientes adultos descritos desarrollaron sintomatología respiratoria durante la evolución de su enfermedad y podrían haber recibido tratamiento para la misma. En este contexto, hay que valorar también la posibilidad de manifestaciones cutáneas por reacción adversa a fármacos.

  • Primer caso de infección neonatal por SARS-CoV-2 en España
    Madre de 41años , cesárea urgente por preeclampsia grave a la semana 38+4.  Gestación por FIV e hipotiridismo en tto.

Rn bajo peso (2.500g) y APGAR 7/9requiriendo una reanimación con aspiración de secreciones en orofaringe. Fue trasladada a la unidad neonatal por dificultad respiratoria inmediata con un dispositivo de presión continua nasal (CPAP). La asistencia respiratoria se retiró a las 2horas de vida, siendo la exploración física a las 9horas normal. Este cuadro se interpretó como un distrés de adaptación a la vida extrauterina, trasladándose posteriormente a las plantas de maternidad con su madre.

Al tercer día del ingreso, la madre comenzó con febrícula descartándose complicaciones obstétricas. Dos días después presentó picos febriles y clínica respiratoria, objetivándose en la radiografía de tórax una neumonía bilateral grave. NO refería viajes a zonas de riesgo de Coronavirus ni contacto con personas infectadas, aunque su pareja presentaba desde el día de la cesárea un cuadro febril con gastroenteritis asociada. Tras descartarse infecciones víricas habituales se solicitó RT-PCR COVID-19 que fue positiva. El test de su pareja también fue positivo posteriormente.

Hasta ese momento la niña permaneció asintomática con su madre en las plantas de maternidad alimentada con lactancia mixta. Debido a la situación clínica de la madre, que requirió asistencia en una unidad especial, se procedió a la separación y se realizó a la recién nacida una RT-PCR COVID-19 de una muestra extraída por aspirado nasofaríngeo que fue negativa (6.o día de vida).

A pesar de la negatividad del test de la niña, se mantuvo en aislamiento en planta de maternidad bajo los cuidados del personal sanitario hasta la obtención de una segunda muestra a las 36horas (mediante exudado nasofaríngeo) que resultó positiva (8.o día de vida). En ese momento se trasladó a la unidad neonatal sin realizarse pruebas complementarias por permanecer asintomática. Se mantuvo una vigilancia estrecha y al noveno día de vida se observó polipnea intermitente con leve tiraje intercostal y 2 desaturaciones de oxígeno autolimitadas con el sueño profundo y durante la alimentación. Se realizó una gasometría capilar con leve acidosis transitoria (pH 7,27, pCO2 49, bicarbonato 22, EB −4, láctico normal), una radiografía de tórax con tenue opacidad en vidrio deslustrado de predominio perihiliar derecho y una proteína C reactiva negativa (0,06mg/dl). Transcurridas 24horas la clínica desapareció manteniéndose asintomática hasta el momento actual (día 13 de vida) en el que se ha repetido la RT-PCR COVID-19 que sigue positiva. La madre está en cuidados intensivos con ventilación mecánica.

En este caso sospechamos que la transmisión ha sido horizontal, ya que el primer test realizado fue negativo.

Para profundizar

Según el último informe de la Red Nacional de Vigilancia Epidemiológica4, la tasa de incidencia total de tuberculosis en España en 2016 fue de 10,38 casos/100.000 habitantes (4,10 en menores de 15 años de edad). La tasa de incidencia en menores de 15 años en España de los años 2013, 2014 y 2015 fue de 5,33; 4,35 y 5,05 casos/100.000 habitantes, respectivamente. A pesar de que la tendencia de la tasa de incidencia total nacional de tuberculosis es descendente en los últimos años, su ritmo de descenso es inferior al 11% anual (objetivo marcado por la OMS).

Con el objetivo de analizar la distribución de los casos de tuberculosis de la población menor de 15 años residente en la ciudad de Sevilla en función del NSE de las áreas de residencia, se calcularon las tasas de incidencia anuales de los casos de tuberculosis en niñas y niños declarados al Servicio de Epidemiología del Distrito Sevilla del Servicio Andaluz de Salud durante los años 2013, 2014 y 2015 - Las tasas de incidencia anuales de tuberculosis de la población menor de 15 años de la ciudad de Sevilla para los 3 años estudiados superan la media nacional para este grupo de edad: 6,61 casos por 100.000 habitantes menores de 15 años en el 2013, 14,71 en el 2014 y 8,54 en el 2015 . Las diferencias máximas en el cálculo de tasa de incidencia por subdistritos del año 2014 tomando la población por subdistritos del año 2013 y la del 2015 fueron de+/− 3 casos por 100.000 habitantes, sin cambios en las tasas de incidencia por subdistritos con y sin ZNTS (Zonas de Necesidad de Transformación Social)  de ese año. Las RI(razón incidencia) anuales entre los subdistritos de Sevilla con zonas estructurales de pobreza y los que no las contienen muestra diferencias importantes de hasta casi 9 veces superior en las zonas más desfavorecidas (RI-2013=8,73; RI-2014=3,13; RI-2015=4,47)

Objective To determine the frequency that non-first-line antibiotics, safety-net antibiotic prescriptions (SNAPS), and longer than recommended durations of antibiotics were prescribed for children ≥2 years of age with acute otitis media and examine patient and system level factors that contributed to these outcomes.Study design. Children age ≥2 years with acute otitis media seen at Denver Health Medical Center outpatient locations from January to December 2018 were included. The percentages of patients who received first-line antibiotics, SNAPs, and recommended durations of antibiotics were determined. Factors associated with non-first-line and longer than recommended antibiotic durations were evaluated using multivariate logistic regression modeling.

Results. Of the 1025 visits evaluated, 98.0% were prescribed an antibiotic; only 4.5% of antibiotics were SNAPs. Non-first-line antibiotics were prescribed to 18.8% of patients. Most antibiotic durations (94.1%) were longer than the institution recommended 5 days and 54.3% were ≥10 days. Private insurance was associated with non-first-line antibiotics (aOR, 1.89; 95% CI, 1; 14-3.14, P = .01). Patients who were younger (2-5 years; aOR 2.01; 95% CI, 1.32-3.05; P < .001) or seen in emergency/urgent care sites (aOR, 1.73; 95% CI, 1.26-2.38; P < .001) were more likely to receive ≥10 days of antibiotic compared with those in pediatric clinics.

Conclusions: Antibiotic stewardship interventions that emphasize the duration of antibiotic therapy as well as the use of SNAPs or observation may be higher yield than those focusing on first-line therapy alone. Numerous system and patient level factors are associated with off-guideline prescribing.

·Clinical Characteristics of Pediatric Pyelonephritis Without Pyuria or Bacteriuria. The Pediatric Infectious Disease Journal. 39(5):385-388, May 2020.

Background: The gold standard for the diagnosis of acute pyelonephritis (APN) in children is the finding of both pyuria (P) and bacteriuria (B); however, some APN patients have neither of these findings [APN(P(−);B(−))].

Methods: In this study, we investigated APN patients who visited our hospital over 14 years to identify specific clinical characteristics of APN(P(−);B(−)).

Results: A total of 171 APN patients were included in the study, and of these 29 were APN(P(−);B(−)). Of the APN(P(−);B(−)) patients, 25.9% had vesicoureteral reflux (VUR), the same percentage as the APN(P(+);B(+)) patients, and 69.0% of APN(P(−);B(−)) patients had already taken antibiotics before diagnosis. APN(P(−);B(−)) patients were older and had a longer duration between onset of fever and diagnosis than the patients with pyuria and/or bacteriuria. In addition, they showed higher C-reactive protein levels. APN(P(−);B(−)) patients had high levels of urinary α-1 microglobulin and urinary β-2 microglobulin.

Conclusions: APN is difficult to diagnose in febrile patients who display neither pyuria nor bacteriuria, but as these patients have the same risk for VUR as APN patients with pyuria and bacteriuria, a detailed history establishing the clinical course as well as urinary chemistry investigations, may assist in diagnosis.

·Identifying Patients at Lowest Risk for Streptococcal Pharyngitis: A National Validation Study. J Pediatr. 2020 May;220:132-138.e2. doi: 10.1016/j.jpeds.2020.01.030

OBJECTIVES: To determine the prevalence of features of viral illness in a national sample of visits involving children tested for group A Streptococcus pharyngitis. Additionally, we sought to derive a decision rule to identify patients with features of viral illness who were at low risk of having group A Streptococcus and for whom laboratory testing might be avoided.

STUDY DESIGN: Retrospective validation study using data from electronic health records of patients 3-21 years old evaluated for sore throat in a national network of retail health clinics (n = 67 127). We determined the prevalence of features of viral illness in patients tested for group A Streptococcus and developed a decision tree algorithm to identify patients with features of viral illness at low risk (<15%) of having group A Streptococcus.

RESULTS: Overall, 54% of patients had features of viral illness. Among patients with features of viral illness, those without tonsillar exudates who were 11 years or older and either lacked cervical adenopathy or had cervical adenopathy and lacked fever were identified as at low risk for group A Streptococcus according to the decision rule. This group comprised 34% of patients with features of viral illness, or 19% of all patients tested for group A Streptococcus infection.

CONCLUSIONS: Our findings provide an objective way to identify patients with features of viral illness who are at low risk of having group A Streptococcus. Improved identification such patients at low risk of group A Streptococcus could improve appropriate testing and antibiotic prescribing for pharyngitis.

·Clinical Description and Outcomes of Australian Children With Invasive Group A Streptococcal Disease. The Pediatric Infectious Disease Journal. 39(5):379-384, May 2020

Background: Invasive group A streptococcal disease is a severe infection with a high case fatality rate, estimated to cause more than 150,000 deaths per year worldwide. The clinical presentation of this infection is variable, and early diagnosis can be challenging. There are few data on its short- and longer-term outcomes, especially in children. The aim of this study was to assess the clinical presentation, management and short- and longer-term outcomes of invasive group A streptococcal disease in children in Australia.

Methods: We undertook a prospective surveillance study of children with laboratory-confirmed invasive group A streptococcus disease admitted to 7 sentinel tertiary and quaternary pediatric hospitals in Australia between July 2016 and June 2018. We collected demographic and clinical data and contacted patients 6 months after discharge to assess longer-term outcomes.

Results: We enrolled 181 children, 7 days to 16 years of age. The principal site of invasive infection was blood (126 children, 69.6%), and the most frequent clinical presentation was pneumonia in 46 children (25.4%). Twenty-six children developed streptococcal toxic shock syndrome (14.4%), and 74 had severe disease (40.9%), including 71 admitted to the intensive care unit. Five children died (2.8%). At discharge and 6 months, 29.3% and 15.2% of the children had persisting health problems, respectively.

Conclusions: Invasive group A streptococcal infection in Australian children is frequently severe and has a high long-term morbidity burden, highlighting the need for strengthened clinical care pathways, epidemiologic surveillance and prevention strategies.

·User-friendly smartphone detection of middle ear fluid. Sci Transl Med 2019;11: pii: eaav1102.

Question: Among children with middle ear fluid, what is the diagnostic accuracy of a smartphone-based, machine-learning-trained fluid detector, compared with surgical and tympanometry findings, in diagnosing middle ear  18 months to 17 years old undergoing ear, nose, and throat surgery for those with and without middle-ear-related diagnoses. The smartphone system was also tested on a smaller cohort of children <18 months of age.

Smartphone-based middle ear fluid detection using smartphone-based speakers and microphones compared with surgery findings and/or tympanometry.

Main Results: The smartphone-based-fluid-detector demonstrated sensitivity and specificity of 84.6% (95%CI, 65.1% - 95.6%) and 81.9% (95% CI, 71.1% - 90.0%), respectively. Area under the curve (AUC) was 0.898 for middle ear fluid. This compares favorably with an AUC of 0.776 for commercial acoustic reflectometry (EarCheck Middle Ear Monitor, Innovia Medical). Parents demonstrated similar results as researchers with the smartphone detector.

Conclusions : A smartphone-based middle ear fluid detector may be an effective screening tool.

Commentary : Acute otitis media (AOM) is one of the leading causes of urgent care visits and the most common reason for administration of antibiotics in children.1 Detecting middle ear fluid is critical for accurately diagnosing acute otitis media, persistent middle ear effusion, and other ear conditions in children.2 Visual assessment is the current standard diagnostic method, but it is more accurate when pneumatic otoscopy is used to assess mobility and it is observer dependent. Diagnosis of otitis media with effusion or AOM currently requires detecting middle ear fluid using either pneumatic otoscopy (which can be extremely painful in children with AOM) or tympanometry, which is more accurate but technically difficult, and not as accurate in infants less than 6 months of age.3 In this report, researchers evaluated a new technology that will permit both physicians and parents to detect and monitor middle ear fluid in children with nothing more than a smartphone and a piece of paper. Their results are encouraging and demonstrate the potential for standard smartphones (using standard speakers and microphones) to be an effective tool for detecting the presence of middle ear fluid. Further testing, especially in infants less than 1 year of age, is necessary to confirm the sensitivity and specificity as it is most challenging to make the diagnosis at this age.

April 30,2020 N Engl J Med 2020; 382:e40 DOI: 10.1056/NEJMp2005638

Carta al editor. Resultados de un ensayo clinico: La vacuna tetravalente contra el dengue (TAK-003, Takeda) en el ensayo de Biswal et al. (Número del 21 de noviembre) 1 parece prometedor y tiene una mejor eficacia general que CYD-TDV (Dengvaxia, Sanofi Pasteur) .2 Dos mejoras importantes en este ensayo son que todos los participantes se sometieron a pruebas serológicas antes de la aleatorización y no hubo necesidad de hacer un Análisis post hoc según grupos de edad. Sin embargo, es demasiado pronto para concluir que TAK-003 será mejor que CYD-TDV.

·Oseltamivir provides up to 3 days earlier time to recovery over usual care. Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial. Lancet 2020;395:42-52.

Question: Among patients with influenza, what is the therapeutic efficacy of oseltamivir, compared with usual care, in time to recovery?

Compared with usual care, the time to recovery with oseltamivir was 0·70 days earlier (95% Bayesian Credible Interval, 0.30–1.20) in patients younger than 12 years and/or with milder illness to 3.20 days (95% BCrI 1·00–5·50) in patients aged 65 years or older and/or with more severe illness.

Oseltamivir provided an overall time to recovery benefit of 1 day, with older/sicker patients deriving more benefit.

Commentary: Prompt antiviral treatment of influenza is recommended for all hospitalized patients and outpatients at increased risk of complications, including children <2 years.1 Early oseltamivir treatment of previously healthy children with uncomplicated influenza is supported by randomized trials. A meta-analysis of randomized placebo-controlled trials reported that oseltamivir treatment within 48 hours of symptom onset significantly reduced duration of influenza illness in children by about one day and lowered risk of otitis media by a third.2 A meta-analysis of observational data reported that neuraminidase inhibitor antiviral treatment reduced the likelihood of hospital admission by 75% in children <16 years.3 The trial by Butler et al showed benefit of oseltamivir treatment compared with usual care in a “real-world” primary care setting, in adults and children (14% [448] were children <12 years). It utilized patient-reported time to recovery as the primary outcome, a composite of return to usual activities and symptom resolution, which differs from trials that have generally used one or the other. Unexpectedly, benefit from oseltamivir was similar in participants with and without RT-PCR-confirmed influenza, which has not been shown previously. However, this study lacked a placebo group, raising questions about a placebo effect and other unknown factors that require further study. New or worsening nausea or vomiting was increased slightly in oseltamivir recipients (21% vs 16% in usual care group); few serious adverse events were reported (similar to previous findings2). Although the pediatric population was small, this study provides additional evidence of the clinical benefit of oseltamivir treatment for uncomplicated influenza.

The conclusions in this commentary are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Background: Viral acute respiratory tract infections (vARTI) are a frequent source of inappropriate antibiotic prescribing. We describe the prevalence of antibiotic prescribing for vARTI in the pediatric emergency department (ED) and urgent care (UC) within a health system, and identify factors associated with overall and broad-spectrum antibiotic prescribing.

Methods: Retrospective chart review within a single pediatric referral health system. Visits of patients, 3 months– 17 years old, with a discharge diagnosis of a vARTI from 2010 to 2015. Data collected included specific vARTI diagnosis, site type (ED or UC), provider type [pediatric emergency medicine subspecialist or physicians, nurse practitioners, physician assistants (non-PEM)] and discharge antibiotics. Odds ratios and 95% confidence intervals (CI) were calculated where appropriate.

Results: There were 132,458 eligible visits, mean age 4.1 ± 4.3 years. Fifty-three percent were treated in an ED. Advanced practice providers, a term encompassing nurse practitioners and physician assistants, were the most common provider type (47.7%); 16.5% of patients were treated by a pediatric emergency medicine subspecialist. Antibiotics were prescribed for 3.8% (95% CI: 3.72–3.92) of children with vARTI; 25.4% (95% CI: 24.2–26.6) of these were broad-spectrum, most commonly first-generation cephalosporins (11%; 95% CI 10.2–11.9). Patients treated in an ED or by a non-PEM and those receiving chest radiograph (CXR) received antibiotics most frequently. Prescribing rates varied by specific vARTI diagnosis.

Conclusions: Patients discharged from the pediatric ED or UC with vARTI receive inappropriate antibiotics at a lower rate than reported in other community settings; however, they frequently receive broad-spectrum agents.

·Pediatric Antibiotic Prescribing in China According to the 2019 World Health Organization Access, Watch, and Reserve (AWaRe) Antibiotic Categories. J Pediatr. 2020 May;220:125-131.e5. doi: 10.1016/j.jpeds.2020.01.044

Objectives To assess clinical indication-specific antibiotic prescribing in pediatric practice in China based on the World Health Organization (WHO) Access, Watch, and Reserve (AWaRe) metrics and to detect potential problem areas.

Study design Pediatric prescription records on the 16th of each month during 2018 were sampled for all encounters at outpatient and emergency departments of 16 tertiary care hospitals via hospital information systems. Antibiotic prescribing patterns were analyzed across and within diagnostic conditions according to WHO AWaRe metrics and Anatomical Therapeutic Chemical (ATC) classification.

Results A total of 260 001 pediatric encounters were assessed, and antibiotics were prescribed in 94 453 (36.3%). In 35 167 encounters (37.2%), at least 1 intravenous antibiotic was administered. WHO Watch group antibiotics accounted for 82.2% (n = 84 176) of all antibiotic therapies. Azithromycin (n = 15 791; 15.4%) was the most commonly prescribed antibiotic, and third-generation cephalosporins (n = 44 387; 43.3%) were the most commonly prescribed antibiotic class. In at least 66 098 encounters (70.0%), antibiotics were prescribed for respiratory tract conditions, mainly for bronchitis/bronchiolitis (n = 25 815; 27.3%), upper respiratory tract infection (n = 25 184; 26.7%), and pneumonia (n = 13 392; 14.2%).

Conclusions Overuse and misuse of WHO Watch group antibiotics for respiratory tract conditions and viral infectious diseases is common in pediatric outpatients in China. Pediatric antimicrobial stewardship should be strengthened using WHO AWaRe metrics. 

Importance  The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection.

Observations  No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19.

Conclusions and Relevance  The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.

Lifecycle and Potential Drug Targets. Schematic represents virus-induced host immune system response and viral processing within target cells. Proposed targets of select repurposed and investigational products are noted. ACE2, angiotensin-converting enzyme 2; S protein, spike protein; and TMPRSS2, type 2 transmembrane serine protease.

Since December 8, 2019, an epidemic of coronavirus disease 2019 (COVID-19) has spread rapidly.1 As of February 6, 2020, China reported 31 211 confirmed cases of COVID-19 and 637 fatalities.

Previous studies suggest that COVID-19 is more likely to infect older adult men, particularly those with chronic comorbidities.2-4 Few infections in children have been reported. We identified all infected infants in China and described demographic, epidemiologic, and clinical features.

Methods

For this retrospective study, we identified all hospitalized infants diagnosed with COVID-19 infection between December 8, 2019, and February 6, 2020, in China. The summary number and geographic location of new COVID-19 infections, released daily by the central government, were screened to identify infants (aged 28 days to 1 year). Demographic information, including age, sex, and geographic location, released anonymously by local health departments, were then retrieved and local hospitals and the Centers for Disease Control and Prevention were contacted for demographic data, family clustering (≥1 infected family member residing with the infant), linkage to Wuhan (residing in or visiting Wuhan or contact with visitors from Wuhan ≤2 weeks before the onset of infection), clinical features (symptoms at admission, dates of admission and diagnosis), treatment (intensive care unit or mechanical ventilation), prognosis (any severe complications, including death), and discharge date. Efforts were made to reach families of patients to confirm the information.

Nasopharyngeal swabs were collected during hospitalization. Real-time polymerase chain reaction testing was used to detect COVID-19 according to the recommended protocol. Infection was defined as at least 2 positive test results.

This study was approved by the institutional review board of Wuhan University School of Health Sciences. Informed consent was waived as part of a public health outbreak investigation.

Results: Nine infected infants were identified between December 8, 2019, and February 6, 2020 (Table). All patients were hospitalized. Seven patients were female. The youngest was aged 1 month and the oldest was 11 months. There were 2 patients from Beijing, 2 from Hainan, and 1 each from Guangdong, Anhui, Shanghai, Zhejiang, and Guizhou.

Four patients were reported to have fever, 2 had mild upper respiratory tract symptoms, 1 had no symptoms but tested positive for COVID-19 in a designated screening because of exposure to infected family members, and 2 had no information on symptoms available. The time between admission and diagnosis was 1 to 3 days.

Families of all 9 infants had at least 1 infected family member, with the infant’s infection occurring after the family members’ infection. Seven infants were reported to be either living in Wuhan or having family members who visited Wuhan, 1 had no direct linkage to Wuhan, and 1 had no information available. None of the 9 infants required intensive care or mechanical ventilation or had any severe complications.

Discussion: Based on the sources of data used in this study, 9 infants were infected with COVID-19 and were hospitalized in China between December 2019 and February 6, 2020. Given the number of infections reported, the number of infected infants identified was small. This may be due to a lower risk of exposure or incomplete identification due to mild or asymptomatic disease, rather than resistance to infection.1,5 However, this study showed that infants can be infected by COVID-19; the earlier stage of the COVID-19 epidemic primarily involved adults older than 15 years.2-4

Family clustering occurred for all infected infants. Infants who have infected family members should be monitored or evaluated and family clustering should be reported to ensure a timely diagnosis.

Seven of the 9 infant patients were female. Previous studies found higher percentages of infection in men than women.2-4 Whether female infants may be more susceptible to COVID-19 infection than male infants requires further study.

The study was limited by small sample size, inclusion only of infants who were hospitalized, and lack of inclusion of asymptomatic patients. Although a systematic and comprehensive search was made for relevant infections in infants, the epidemic is spreading rapidly and incomplete identification of cases is possible.

Because infants younger than 1 year cannot wear masks, they require specific protective measures. Adult caretakers should wear masks, wash hands before close contact with infants, and sterilize the infants’ toys and tableware regularly.

Methods: One hospitalized patient and 3 patients (all medical personnel) quarantined at home with COVID-19 were treated at Zhongnan Hospital of Wuhan University, Wuhan, China, from January 1, 2020, to February 15, 2020, and evaluated with real-time reverse transcriptase-polymerase chain reaction (RT-PCR) tests for COVID-19 nucleic acid to determine if they could return to work. All the following criteria had to be met for hospital discharge or discontinuation of quarantine: (1) normal temperature lasting longer than 3 days, (2) resolved respiratory symptoms, (3) substantially improved acute exudative lesions on chest computed tomography (CT) images, and (4) 2 consecutively negative RT-PCR test results separated by at least 1 day.

The RT-PCR tests were performed on throat swabs following a previously described method. The RT-PCR test kits (BioGerm) were recommended by the Chinese Center for Disease Control and Prevention. The same technician and brand of test kit was used for all RT-PCR testing reported; both internal controls and negative controls were routinely performed with each batch of tests.

Demographic information, laboratory findings, and radiological features were collected from electronic medical records. After recovery, patients and their families were contacted directly, and patients were asked to visit the hospital to collect throat swabs for the RT-PCR tests.

This study was approved by the Zhongnan Hospital of Wuhan University institutional review board and the need for informed consent was waived.

Results

All 4 patients were exposed to the novel 2019 coronavirus through work as medical professionals. Two were male and the age range was 30 to 36 years. Among 3 of the patients, fever, cough, or both occurred at onset. One patient was initially asymptomatic and underwent thin-section CT due to exposure to infected patients. All patients had positive RT-PCR test results and CT imaging showed ground-glass opacification or mixed ground-glass opacification and consolidation. The severity of disease was mild to moderate.

Antiviral treatment (75 mg of oseltamivir taken orally every 12 hours) was provided for the 4 patients. For 3 of the patients, all clinical symptoms and CT imaging abnormalities had resolved. The CT imaging for the fourth patient showed delicate patches of ground-glass opacity. All 4 patients had 2 consecutive negative RT-PCR test results. The time from symptom onset to recovery ranged from 12 to 32 days.

After hospital discharge or discontinuation of quarantine, the patients were asked to continue the quarantine protocol at home for 5 days. The RT-PCR tests were repeated 5 to 13 days later and all were positive. All patients had 3 repeat RT-PCR tests performed over the next 4 to 5 days and all were positive. An additional RT-PCR test was performed using a kit from a different manufacturer and the results were also positive for all patients. The patients continued to be asymptomatic by clinician examination and chest CT findings showed no change from previous images. They did not report contact with any person with respiratory symptoms. No family member was infected.

Discussion

Four patients with COVID-19 who met criteria for hospital discharge or discontinuation of quarantine in China (absence of clinical symptoms and radiological abnormalities and 2 negative RT-PCR test results) had positive RT-PCR test results 5 to 13 days later. These findings suggest that at least a proportion of recovered patients still may be virus carriers. Although no family members were infected, all reported patients were medical professionals and took special care during home quarantine. Current criteria for hospital discharge or discontinuation of quarantine and continued patient management may need to be reevaluated. Although false-negative RT-PCR test results could have occurred as suggested by a previous study, 2 consecutively negative RT-PCR test results plus evidence from clinical characteristics and chest CT findings suggested that the 4 patients qualified for hospital discharge or discontinuation of quarantine.

The study was limited to a small number of patients with mild or moderate infection. Further studies should follow up patients who are not health care professionals and who have more severe infection after hospital discharge or discontinuation of quarantine. Longitudinal studies on a larger cohort would help to understand the prognosis of the disease.

Más información COVID-19 en JAMA: Coronavirus (COVID19)

 Una revisión sistemática reciente confirma la asociación entre la exposición a contaminantes atmosféricos (partículas en suspensión <2,5μ [PM2,5] y <10μ [PM10], dióxido de nitrógeno [NO2] y dióxido de sulfuro [SO2]), y el riesgo de ingreso por bronquiolitis2. Un estudio realizado en centros de atención primaria en Madrid concluyó que los niveles de NO2 (especialmente aquellos mayores de 40μg/m3) se asociaban a un aumento en la incidencia de problemas respiratorios en (valoren sustituir la edad pediátrica por niños, el texto quedaría...respiratorios en, probable errata) niños3. Hasta donde nosotros sabemos, no se han llevado a cabo estudios similares en Barcelona.

A modo de estudio piloto, se examinó a 391 pacientes del área metropolitana de Barcelona ingresados con bronquiolitis en la unidad de cuidados intensivos del Hospital Sant Joan de Déu (Esplugues de Llobregat, Barcelona), desde 2011 hasta 2016. El código postal de cada paciente nos permitió añadir promedios mensuales de temperatura y humedad a la base de datos. También se registró el valor del índice catalán de calidad del aire (Índex Català de Qualitat de l’Aire [ICQA]) 10 días antes de la fecha del ingreso del paciente

Ni la temperatura ni los contaminantes parecen haber influenciado la incidencia de bronquiolitis en el área metropolitana de Barcelona entre 2011 y 2016. Aunque no se detectaron diferencias en la distribución de los principales contaminantes entre los días en los que hubo casos de bronquiolitis y el resto del mes, cabe resaltar que el NO2 es el principal contaminante presente durante todo el año en el área metropolitana de Barcelona. 

Introduction: Septic arthritis (SA) and osteomyelitis (OM) can present as medical emergencies in children. Typically, antimicrobial treatment for bone and joint infections is between 1 and 2 weeks of intravenous treatment followed by an oral antibiotic course of 2–4 weeks.1 2 However, recent data from a large randomised controlled trial in adults3 show that oral therapy is non-inferior to intravenous therapy. Short intravenous courses reduce length of hospital stay, support antimicrobial stewardship and improve patient quality of life. We describe the epidemiology of bone and joint infections at the John Radcliffe Hospital, Oxford, over the last decade in order to inform improved management.

Methods_We identified cases of SA and OM from September 2009 to February 2019 using hospital discharge clinical coding data. Inclusion criteria were (1) children <16 years of age (2) with clinical or radiological features typical of SA or OM …

·Osteoarticular Infections of the Chest Wall Due to Kingella Kingae: A Series of 8 Cases. The Pediatric Infectious Disease Journal. 39(5):e54-e56, May 2020.

Osteoarticular infections of the chest wall are relatively uncommon in pediatric patients and affect primarily infants and toddlers. Clinical presentation is often vague and nonspecific. Laboratory findings may be unremarkable in osteoarticular chest wall infections and not suggestive of an osteoarticular infection. Causative microbes are frequently identified if specific nucleic acid amplification assays are carried out. In the young pediatric population, there is evidence that Kingella kingae is 1 of the main the main causative pathogens of osteoarticular infections of the chest wall.

·Should We Investigate Osteoarticular Infections for Kingella kingae in Older-than-expected Immunocompetent Children? The Pediatric Infectious Disease Journal. 39(5):e57-e58, May 202

Since the 1980s, the reported number of cases of osteoarticular infections due to Kingella kingae has increased markedly owing to the widespread use of nucleic acid amplification assays. These advances have resulted in the recognition of K. kingae as the predominant germ of hematogenous infections of bones, joints, intervertebral discs and tendon sheaths in children 6–48 months of age, indicating that its role in osteoarticular infection has probably been underestimated in the past.1 Current evidence indicates that nearly all invasive K. kingae infections occur in children <4 years of age, corresponding to the period of maximal oropharyngeal colonization. In fact, the main risk factor for invasive infections due to K. kingae is close, intimate contact among infants and preschool-age children as it is found in settings such as group childcare.2 In addition, the maternal immunity that is conveyed to the fetus during pregnancy diminishes gradually between 6 and 24 months. Longitudinal investigations have revealed that the average IgG levels against K. kingae are high at birth and slowly decrease thereafter reaching the lowest point at 6–7 months postnatally.3 However, the IgG persists at low levels until the age of 18–24 months, at which point a progressive increase of the serum levels of the immunoglobulin has been reported.3 Therefore, in the period between 6 and 48 months, a child is more susceptible to invasive infections.

We read with interest the case report by Fremlin and colleagues1 on non-sexually acquired genital ulceration (NSAGU), also termed Lipschütz ulcers. NSAGU is characterised by acute painful genital ulcerations in girls and young women and has been associated with a large spectrum of acute infections, for example, Epstein-Barr virus (EBV), cytomegalovirus (CMV) and parvovirus.2 3 We would like to draw attention to the possibility of another important cause of this condition. …

Methods: Data for January 2006 through December 2017 were analyzed from the IBM MarketScan Commercial Database (formerly known as the Truven Health MarketScan Commercial Claims and Encounters database), which contains deidentified data from more than 20 million individuals in employer-sponsored commercial health insurance plans. Because all data were fully deidentified and no interaction occurred with humans, this analysis was deemed exempt from review and informed consent by the US Centers for Disease Control and Prevention institutional review board.

Children were included if they were age eligible to receive rotavirus vaccine (with a birthdate of January 1, 2006, or later) and continuously enrolled in their insurance plan from birth. Current Procedural Terminology codes (90680 [for RotaTeq vaccine (Merck Sharp & Dohme Corporation)] and 90681 [for Rotarix vaccine (GlaxoSmithKline)]) were used to determine rotavirus vaccination status and age at each dose, as previously described. To increase specificity, T1D was defined as 2 or more separate claims listing International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 250.X1 or 250.X3 or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes E10.X in any care setting. Children with a single T1D claim were excluded, as were those diagnosed those diagnosed before 27 weeks of age (survival curve) or before 12 months of age (measures of association).

For the survival curve, follow-up began at 27 weeks of age. For measures of association, follow-up began at 12 months of age. Crude rate ratios were calculated using person-time accumulated in each stratum of rotavirus vaccination status. Extended Cox regression models with age in weeks as the time scale included rotavirus vaccination status as the time-varying exposure and were controlled for birth year. To mitigate exposure misclassification from missing vaccination claims and control for confounding by medical conditions possibly associated with missed vaccinations and risk of T1D, only children who received at least 1 dose of diphtheria-tetanus-pertussis-containing vaccine were included. This restriction was lifted in a sensitivity analysis. In a second sensitivity analysis, children in states with universal vaccine purchase programs were excluded, since they could have been vaccinated without a vaccination-associated insurance claim. Results were stratified by birth year, since loss to follow-up increased with increasing age. Data were censored at the end of continuous enrollment, the end of the study period (December 31, 2017), or diagnosis of T1D, whichever came first.

Analyses used SAS version 9.4 (SAS Institute) and R version 3.4.2 (the R Foundation for Statistical Computing). Data analysis occurred from January 2019 to April 2019; [alpha] was set to .05.

Results

Overall, 843 of 2 854 571 eligible children were diagnosed with T1D; the 10-year cumulative incidence was 0.25% (95% CI, 0.22%-0.28%). Among 1 563 540 children followed up until age 12 months or older, 1 035 198 (66.2%) were fully vaccinated (2 doses of Rotarix or 3 doses of RotaTeq), 210 057 (13.4%) were partially vaccinated, and 318 285 (20.4%) were unvaccinated against rotavirus.

Unadjusted T1D-free survival curves were stratified by rotavirus vaccination status (Figure). Adjusted hazard ratios comparing fully and partially vaccinated children with unvaccinated children were nonsignificant in primary and sensitivity analyses (Table).

Discussion: We found no association between rotavirus vaccination and T1D among US children with commercial insurance who were followed up until a maximum of 12 years of age. This is consistent with results from 2 Finnish cohorts. 

Importance  Chikungunya virus (CHIKV) is a mosquito-borne Alphavirus prevalent worldwide. There are currently no licensed vaccines or therapies.

Objective  To evaluate the safety and tolerability of an investigational CHIKV virus–like particle (VLP) vaccine in endemic regions.

Design, Setting, and Participants  This was a randomized, placebo-controlled, double-blind, phase 2 clinical trial to assess the vaccine VRC-CHKVLP059-00-VP (CHIKV VLP). The trial was conducted at 6 outpatient clinical research sites located in Haiti, Dominican Republic, Martinique, Guadeloupe, and Puerto Rico. A total of 400 healthy adults aged 18 through 60 years were enrolled after meeting eligibility criteria. The first study enrollment occurred on November 18, 2015; the final study visit, March 6, 2018.

Interventions  Participants were randomized 1:1 to receive 2 intramuscular injections 28 days apart (20 µg, n = 201) or placebo (n = 199) and were followed up for 72 weeks.

Main Outcomes and Measures  The primary outcome was the safety (laboratory parameters, adverse events, and CHIKV infection) and tolerability (local and systemic reactogenicity) of the vaccine, and the secondary outcome was immune response by neutralization assay 4 weeks after second vaccination.

Results  Of the 400 randomized participants (mean age, 35 years; 199 [50%] women), 393 (98%) completed the primary safety analysis. All injections were well tolerated. Of the 16 serious adverse events unrelated to the study drugs, 4 (25%) occurred among 4 patients in the vaccine group and 12 (75%) occurred among 11 patients in the placebo group. Of the 16 mild to moderate unsolicited adverse events that were potentially related to the drug, 12 (75%) occurred among 8 patients in the vaccine group and 4 (25%) occurred among 3 patients in the placebo group. All potentially related adverse events resolved without clinical sequelae. At baseline, there was no significant difference between the effective concentration (EC50)—which is the dilution of sera that inhibits 50% infection in viral neutralization assay—geometric mean titers (GMTs) of neutralizing antibodies of the vaccine group (46; 95% CI, 34-63) and the placebo group (43; 95% CI, 32-57). Eight weeks following the first administration, the EC50 GMT in the vaccine group was 2005 (95% CI, 1680-2392) vs 43 (95% CI, 32-58; P < .001) in the placebo group. Durability of the immune response was demonstrated through 72 weeks after vaccination.

Conclusions and Relevance  Among healthy adults in a chikungunya endemic population, a virus-like particle vaccine compared with placebo demonstrated safety and tolerability. Phase 3 trials are needed to assess clinical efficacy.

Trial Registration  ClinicalTrials.gov Identifier: NCT02562482

·Description of Eschar-associated Rickettsial Diseases Using Passive Surveillance Data—United States, 2010–2016. The Pediatric Infectious Disease Journal. 39(5):405, May 2020.

What is already known about this topic? Eschars are a clinical sign used to differentiate less severe rickettsioses from potentially deadly Rocky Mountain spotted fever.

What is added by this report? Eschars are infrequently reported in tickborne rickettsial disease (TBRD) surveillance data and represent an underutilized resource to aid in distinguishing the various spotted fever group Rickettsia. Although 1% of total TBRD case reports during 2010–2016 documented the presence of an eschar, 81% of cases lacked information on eschars altogether.

What are the implications for public health practice? Systematic reporting of the presence or absence of eschars on the TBRD case report form can improve the quality of surveillance data and enhance understanding of the impact of spotted fever rickettsioses in the United States. OK

Background: In children with epilepsy, fever and illness are known triggers for seizure; therefore, clinicians and parents could be concerned that immunization-induced inflammation and fever could also trigger seizures. We sought to estimate the risk of emergency department (ED) visit or hospitalization for epilepsy/seizure and all causes after immunization in children younger than 7 years of age with epilepsy.

Methods: We conducted a self-controlled case series of children diagnosed with epilepsy before their 7th birthday and immunized from 2005 to 2015 in Ontario (population 14.2 million) and Manitoba (population 1.3 million), Canada, using administrative healthcare data. We estimated the age- and season-adjusted relative incidence (aRI) of epilepsy/seizure-related and all-cause ED visits/hospitalizations during various risk periods 0–28 days after inactivated and live immunizations versus a control period 35–83 days postimmunization. Estimates from each province were analyzed separately and then combined in a random-effects meta-analysis.

Results: The combined risk of epilepsy/seizure-related hospitalization/ED visit was increased 0–2 days after inactivated vaccines (aRI = 1.5, 95% confidence interval: 1.1–1.9) and 7–10 days after live vaccines (aRI = 1.9, 1.4–2.7). For all-cause ED visit/hospitalization, the combined aRI estimate was 0.9 (0.8–1.2) 0–2 days after inactivated vaccines and 1.3 (1.1–1.5) 7–10 days after live vaccines.

Conclusions: The risk of epilepsy/seizure-related ED visit/hospitalization was modestly increased among children with epilepsy during peak periods of fever and inflammation following inactivated and live vaccines. These risks must be balanced against the risk of complications from vaccine-preventable diseases. OK

Background and objective The Zika virus outbreak has drawn attention to microcephaly, whose definition is based on head circumference measuring below a percentile or number of SDs below the mean. The objective of this analysis was to assess how differences in measurement precision might affect prevalence and trends of microcephaly.

Methods Data from all births in Uruguay during 2010–2015 were obtained from the Perinatal Information System. The prevalence of births with microcephaly was calculated based on head circumference measurement at birth applying the INTERGROWTH-21st standards for sex and gestational age, and compared by method of ascertaining gestational age.

Results Rounding and digit preference was observed: 74% of head circumference measurements were reported as a whole centimetre value. The prevalence of births varied substantially by the criterion used to define microcephaly (<3 SD, <2 SD, <3rd percentile for gestational age) and could be halved or doubled based on adding or subtracting a half-centimetre from all reported head circumference measurements. If 4 days were added to gestational age calculations, rather than using completed gestational weeks (without days) for gestational age reporting, the prevalence was 1.7–2 times higher.

Discussion Rounding in measurement of head circumference and reporting preferences of gestational age may have contributed to a lower prevalence of microcephaly than expected in this population. Differences in head circumference measurement protocols and gestational age dating have the potential to affect the prevalence of babies reported with microcephaly, and this limitation should be acknowledged when interpreting head circumference data collected for surveillance.OK

We included nine studies, of which two were classified as ongoing studies. The seven included studies involved a total of 2774 participants and were conducted in high-income countries (UK, USA and Chile) and lower-middle-income countries (Bangladesh and Pakistan). Four studies were conducted in hospital settings, two in schools, and one at a military training centre. Three studies included children under five years of age, two school-aged children, one adult participants, and one older participants aged 60 to 90 years. Two studies assessed the effect of vitamin C supplementation for pneumonia prevention; four studies assessed the effect of vitamin C supplementation in pneumonia treatment; and one study assessed the role of vitamin C for both prevention and treatment of pneumonia. The doses of vitamin C supplementation used were 125 mg, 200 mg, 500 mg, and 2 g

We assessed the rate of pneumonia (incidence), how common pneumonia is (prevalence), numbers of deaths from pneumonia (mortality), and unintended and harmful outcomes (adverse effects) associated with vitamin C for preventing pneumonia. Only two studies (736 people) reported incidence, and one study reported one adverse effect (hives) associated with vitamin C for preventing pneumonia. No study reported on prevalence or mortality. Evidence was insufficient to determine the effect of vitamin C for preventing pneumonia.

We also assessed how long people were ill (duration of illness), how many people were cured, mortality, and adverse effects associated with the use of vitamin C as a treatment for pneumonia. Although two studies reported duration of illness, results could not be combined for analysis. One study reported mortality. No studies reported cure rates or adverse effects. Evidence was insufficient to determine the effect of vitamin C for treating pneumonia.

Quality of the evidence

We judged the included studies to be at overall high or unclear risk of bias. We rated the quality of the evidence as very low due to study limitations, variations amongst the studies, small sample sizes and uncertainty of estimates.

Authors' conclusions:

Due to the small number of included studies and very low quality of the existing evidence, we are uncertain of the effect of vitamin C supplementation for the prevention and treatment of pneumonia. Further good-quality studies are required to assess the role of vitamin C supplementation in the prevention and treatment of pneumonia.

We found 24 relevant studies with 2278 participants that evaluated types of PPE, modified PPE, procedures for putting on and removing PPE, and types of training. Eighteen of the studies did not assess healthcare workers who were treating infected patients but simulated the effect of exposure to infection using fluorescent markers or harmless viruses or bacteria. Most of the studies were small, and only one or two studies addressed each of our questions.

We found low- to very low-certainty evidence that covering more parts of the body leads to better protection but usually comes at the cost of more difficult donning or doffing and less user comfort, and may therefore even lead to more contamination. More breathable types of PPE may lead to similar contamination but may have greater user satisfaction. Modifications to PPE design, such as tabs to grab, may decrease the risk of contamination. For donning and doffing procedures, following CDC doffing guidance, a one-step glove and gown removal, double-gloving, spoken instructions during doffing, and using glove disinfection may reduce contamination and increase compliance. Face-to-face training in PPE use may reduce errors more than folder-based training.

We still need RCTs of training with long-term follow-up. We need simulation studies with more participants to find out which combinations of PPE and which doffing procedure protects best. Consensus on simulation of exposure and assessment of outcome is urgently needed. We also need more real-life evidence. Therefore, the use of PPE of HCW exposed to highly infectious diseases should be registered and the HCW should be prospectively followed for their risk of infection.

Objective To understand the impact of the National Institute for Health and Care Excellence (NICE) bronchiolitis guidelines on the management of children referred to paediatric intensive care unit (PICU) with bronchiolitis.

Design and setting Data were collected on all children referred to a regional PICU transport service with the clinical diagnosis of bronchiolitis during the winter prior to the NICE consultation period (2011–2012) and during the winter after publication (2015–2016). Management initiated by the referring hospital was assessed.

Results There were 165 infants referred with bronchiolitis in epoch 1 and 187 in epoch 2. Nebuliser use increased from 28% in epoch 1 to 53% in epoch 2. Increased use of high-flow nasal cannula oxygen and reduction in continuous positive airway pressure use were observed. The use of antibiotics did not change between epochs.

 

Conclusion The use of nebulised therapies has increased in the management of severe bronchiolitis despite national guidance to the contrary.

 

Actualidad bibliográfica abril 2020

Top Ten

COVID-19 is a pandemic with a rapidly increasing incidence of infections and deaths. Many pharmacologic therapies are being used or considered for treatment. Given the rapidity of emerging literature, IDSA identified the need to develop living, frequently updated evidencebased guidelines to support patients, clinicians and other health-care professionals in their decisions about treatment and management of patients with COVID-19.

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/APA.15270

AIM: The coronavirus disease 2019 (COVID-19) pandemic has affected hundreds of thousands of people. Data on symptoms and prognosis in children are rare.

METHODS: A systematic literature review was carried out to identify papers on COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using the MEDLINE and Embase databases between January 1 and March 18, 2020.

RESULTS: The search identified 45 relevant scientific papers and letters. The review showed that children have so far accounted for 1%-5% of diagnosed COVID-19 cases, they often have milder disease than adults and deaths have been extremely rare. Diagnostic findings have been similar to adults, with fever and respiratory symptoms being prevalent, but fewer children seem to have developed severe pneumonia. Elevated inflammatory markers were less common in children, and lymphocytopenia seemed rare. Newborn infants have developed symptomatic COVID-19, but evidence of vertical intrauterine transmission was scarce. Suggested treatment included providing oxygen, inhalations, nutritional support and maintaining fluids and electrolyte balances.

CONCLUSIONS: The coronavirus disease 2019 has occurred in children, but they seemed to have a milder disease course and better prognosis than adults. Deaths were extremely rare.

Objetivos. En 1998 la Región de Europa de la Organización Mundial de la Salud fijó el objetivo de eliminar el sarampión. En este estudio se analizó la prevalencia de la inmunidad frente al virus del sarampión en la población del área sanitaria de Santiago de Compostela a partir de los datos obtenidos entre 2008-2018.
Pacientes y métodos. Se estudiaron 7.150 pacientes diferentes que se dividieron en grupos según su año de nacimiento: 2010-2017, 2000-2009, 1990-1999, 1980-1989, 1953-1979 y <1953. La determinación en suero de IgG frente al virus del sarampión se realizó mediante un inmunoensayo quimioluminiscente comercializado.
Resultados. Se observó un mínimo (76%) para las tasas de protección frente al virus del sarampión en los nacidos entre 1990-1999. Por grupo de edad se vio que en todos los grupos las mujeres presentaron un porcentaje superior de anticuerpos frente al sarampión. En un modelo de regresión logística con año de nacimiento y sexo se obtuvo una odds ratio para el año de nacimiento (p<0,001) de 1,06 y para el sexo (p=0,0013) de 0,82.
Conclusiones. Se observaron seroprevalencias inferiores a partir de la implantación de la vacuna, un cambio más acusado durante el periodo de implantación y desde el plan de vacunación para el sarampión del año 2000 en Galicia, las tasas de protección frente al virus del sarampión han ido aumentado en nuestra área. Aunque se observó una mayor proporción de mujeres protegidas frente a la de hombres, estas diferencias fueron escasas.

Polysaccharide conjugate vaccines (PCVs) target the pneumococcal capsular types that most commonly cause fatal pneumonia and sepsis. Because these types were eliminated by the vaccines, it became apparent that in immunized populations, most invasive pneumococcal diseases, including bacteremia, sepsis and complicated pneumonia, were greatly reduced. However, the protective effects of PCVs against another invasive disease, meningitis, has shown much less or no decrease in disease incidence.

Methods:

References were identified through searches of PubMed for articles published from January 1930 to the present by use of specific search terms. Relevant articles were also identified through searches in Google and Google Scholar. Relevant references cited in those articles were also reviewed.

Results:

Even in the presence of the PCVs, meningitis rates in children have been reported globally to be as high as 13 per 100,000 annually. Widespread use of vaccines resulted in the emergence of a broad diversity of replacement non-PCV type strains. These strains generally failed to cause sepsis, but caused meningitis of comparable severity and levels similar to, or in excess of, prior pneumococcal meningitis rates. This is probably because these non-PCV type strains do not survive well in the blood, therefore possibly entering the brain through nonhematogenous routes.

Conclusions:

Because virtually all cases of pneumococcal meningitis lead to either permanent neurologic sequelae or death, it would be well worth the effort to develop a new vaccine capable of preventing pneumococcal meningitis regardless of capsular type. Such a vaccine would need to protect against colonization with most, if not all, pneumococci.

Introducción: la neumonía adquirida en la comunidad (NAC) sigue siendo una enfermedad frecuente en la edad pediátrica, encontrándose entre las primeras causas de mortalidad. El objetivo del estudio fue conocer la incidencia de las neumonías ingresadas y describir sus características.

Material y métodos: estudio descriptivo y retrospectivo que incluyó a los pacientes ingresados en el Servicio de Pediatría del Hospital Universitario Miguel Servet de Zaragoza (España), con el diagnóstico de NAC durante dos años para describir sus características clínicas, radiológicas, analíticas, demográficas y complicaciones.

Resultados: se registraron 248 casos de neumonía, con una media de edad de 37,60 ± 2,20 meses, siendo significativamente mayor en neumonías bacterianas típicas (41,98 ± 37,46) y atípicas (73,43 ± 41,28) frente a las víricas (23,30 ± 19,07) (p <0,0001 y p = 0,0004 respectivamente). La neumonía más frecuente fue la de probable origen neumocócico (47,6%; intervalo de confianza del 95% [IC 95]: 41,84 a 54,18) mientras que el agente identificado con más frecuencia el virus respiratorio sincitial (34,65%; IC 95: 26,93 a 43,26). La odds ratio de presentar patrón radiológico alveolar en neumonías bacterianas frente a víricas fue de 2,98 (IC 95: 1,50 a 5,91; p = 0,0013). El antibiótico más utilizado fue ampicilina intravenosa (62,87%), siendo la duración mayor en las neumonías típicas bacterianas.

Conclusión: la NAC que precisa ingreso hospitalario es más prevalente en niños menores de cuatro años; con una incidencia y complicaciones similares a las descritas en otras series. El diagnóstico etiológico y el consiguiente tratamiento antibiótico continúa siendo un reto difícil de alcanzar.

Resumen: revisión sistemática y metaanálisis, que investiga el desarrollo de la tuberculosis en niños con contacto estrecho con enfermos de tuberculosis. 137 647 niños expuestos a tuberculosis fueron evaluados al inicio del estudio y 130 512 niños fueron seguidos durante 429 538 años-persona, durante los cuales se diagnosticaron 1299 casos de tuberculosis prevalentes y 999 incidentes. Los niños que no recibieron terapia preventiva con un resultado positivo para la infección de tuberculosis tuvieron una incidencia de tuberculosis acumulativa a 2 años significativamente más alta que los niños con un resultado negativo para la infección de tuberculosis, y esta incidencia fue mayor entre los niños menores de 5 años. La efectividad de la profilaxis con isoniacida fue del 63% entre todos los niños expuestos, y del 91% entre aquellos con un resultado positivo para la infección tuberculosa. Entre todos los niños <5 años que desarrollaron tuberculosis, el 83% fueron diagnosticados dentro de los 90 días de la visita inicial. El riesgo de desarrollar tuberculosis entre los bebés expuestos y los niños pequeños es muy alto. La mayoría de los casos ocurrieron dentro de las semanas posteriores al inicio de la investigación de contacto y podrían no prevenirse mediante profilaxis. Esto sugiere que se necesitan estrategias alternativas para la prevención, como el inicio temprano de la terapia preventiva a través del diagnóstico rápido de casos de adultos con búsqueda activa en la comunidad.

Objetivo. Los patógenos se pueden transmitir a los billetes debido a los hábitos antihigiénicos personales. El objetivo del estudio fue buscar los posibles patógenos en los billetes que circulan en el mercado y también observar su resistencia antibacteriana así como sus diversos factores de virulencia utilizando métodos genotípicos y fenotípicos. Material y métodos. Se recogieron al azar un total de 150 muestras de billetes entre agosto de 2017 y marzo de 2018. Se utilizaron los sistemas VITEK para la identificación y las pruebas de sensibilidad a los antimicrobianos, respectivamente. Los genes de resistencia a los antimicrobianos (mecA, van, betalactamasas de espectro ampliado [BLEA] y carbapenemasas) y los genes de virulencia estafilocócica (SE, pvl y tsst -1) se determinaron mediante PCR a tiempo real. Resultados. Se detectó la presencia de cepas de Staphylococcus aureus, Staphylococcus coagulasa negativos (SCN), Enterococcus spp, bacterias gramnegativas, bacterias gramnegativas no fermentativas y Candida spp en un 48%, 54,7%, 56%, 21,3%, 18,7% y 4% de los billetes, respectivamente. Se observó la presencia de S. aureus resistente a meticilina, Enterococcus resistentes a vancomicina y gramnegativos productores de BLEA en un 46,8%, 1,3% y 28,7%, respectivamente. Los genes Pvl, tsst-1 y SE se encontraron en un 2,8/4,9%; 1,4/1,2% y 100/87,8% de las cepas de S. aureus/SCN, respectivamente. El gen sea fue el gen enterotoxigénico más frecuente. Los genes blaTEM, blaSHV, blaCTX-M-2, blaCTX-M-1, blaKPC, y blaOXA-48 se encontraron 55,8%, 46,5%, 41,2%, 18,6%, 18,6%, y 18,6%, respectivamente en cepas gramnegativas. Conclusión. Estos resultados son muy importantes para resaltar el estado higiénico de los billetes. De este modo, los billetes pueden contribuir a la propagación de patógenos y de la resistencia a los antimicrobianos. Por lo tanto, es posible que debamos comenzar a utilizar productos alternativos a los billetes.

Streptococcus pyogenes (SGA) es el agente bacteriano más común de faringoamigdalitis agudas (FAA) en niños (30-40% entre los 3-13 años) y susceptible de tratamiento antibiótico. El tratamiento precoz reduce la severidad y duración de los síntomas, disminuye la transmisión y previene las complicaciones supurativas y no supurativas como la fiebre reumática y las infecciones invasivas [1]. El cultivo es el gold-standard para el diagnóstico de SGA pero la obtención de un resultado requiere un mínimo de 18- 24 horas. Los test de detección de antígeno (TRDA) aportan rapidez al resultado y aunque no existe un criterio unánime se han incluido en diversas guías de práctica clínica por su utilidad para guiar las decisiones terapéuticas en las FAA [1-3]. Entre los TRDA destacan los inmunocromatográficos que por sus características pueden usarse como “pruebas en el punto de atención al paciente” [4]. El objetivo del estudio fue evaluar en nuestro medio el test AlereTMTestPack+Plus with OBC Strep A (Alere-StrepA) para detección de SGA en niños con sospecha de FAA. El cultivo fue el método de referencia.

Because of the limited number of subjects in prelicensure studies, autoimmune diseases and other rare adverse effects of vaccines may go undetected. Since 2006, millions of human papillomavirus (HPV) vaccine doses have been distributed and a considerable amount of postlicensure safety data has been generated. The objective of this study was to review available HPV postlicensure safety studies and to summarize risk estimates of autoimmune and other rare diseases.

Methods: For this systematic review and meta-analysis, we searched literature databases to identify any postlicensure safety studies related to HPV vaccination and autoimmune adverse events from inception to April 16, 2019. Pooled risk estimates were computed using fixed- or random-effects models if at least 2 estimates per disease and per HPV vaccine were available.

Results: Twenty-two studies met our inclusion criteria. The studies applied various methodologies and used different types of data sources and outcome definitions. Quadrivalent HPV vaccine (4vHPV) was most commonly assessed. Type 1 diabetes mellitus, immune thrombocytopenia purpura and thyroiditis diseases were most frequently reported. The meta-analysis was conducted on 35 diseases corresponding to 48 pooled risk estimates. Majority of the pooled estimates showed no significant effect (n = 43). Three negative (paralysis, immune thrombocytopenia purpura and chronic fatigue syndrome) and 2 positive (Hashimoto and Raynaud diseases) associations were detected.

Background: Universal childhood vaccination against varicella began in the United States as a 1-dose schedule in 1996, changing to a 2-dose schedule in 2006. The exogenous boosting hypothesis, which postulates that reexposure to circulating wild-type varicella delays the onset of herpes zoster, predicts a transient increase in the incidence of herpes zoster, peaking in adults 15–35 years after the start of varicella vaccination.

Methods: This was a retrospective study of administrative claims data from the MarketScan Commercial and Medicare databases between 1991–2016. Outcome measures were the incidences of herpes zoster per 100 000 person-years, by calendar year and age category, and the annual rates of change in herpes zoster by age category, in an interrupted time series regression analysis, for the periods of 1991–1995 (prevaccine), 1996–2006 (1-dose vaccination period), and 2007–2016 (2-dose vaccination period).

Results: The annual incidences of herpes zoster increased throughout the period of 1991–2012 in all adult age categories, with a plateau in 2013–2016 that was most evident in the ≥65 age group. In 1991–1995, the herpes zoster incidences increased at annual rates of 4–6% in age categories 18–34, 35–44, 45–54, and 55–64 years. In the same age categories during 1996–2006 and 2007–2016, the herpes zoster incidences increased at annual rates of 1–5%.

Conclusions: Although the annual incidence of herpes zoster in adults has continued to increase, the rates of change decreased during both the 1- and 2-dose vaccination periods. The hypothesized increase in herpes zoster predicted from modelling of the exogenous boosting hypothesis was not observed.

·Dose, Timing, and Type of Infant Antibiotic Use and the Risk of Childhood Asthma, Clinical Infectious Diseases, , ciz448, https://doi.org/10.1093/cid/ciz448

Aspects of infant antibiotic exposure and its association with asthma development have been variably explored. We aimed to evaluate comprehensively and simultaneously the impact of dose, timing, and type of infant antibiotic use on the risk of childhood asthma.

Methods: Singleton, term-birth, non–low-birth-weight, and otherwise healthy children enrolled in the Tennessee Medicaid Program were included. Infant antibiotic use and childhood asthma diagnosis were ascertained from prescription fills and healthcare encounter claims. We examined the association using multivariable logistic regression models.

Results: Among 152 622 children, 79% had at least 1 antibiotic prescription fill during infancy. Infant antibiotic use was associated with increased odds of childhood asthma in a dose-dependent manner, with a 20% increase in odds (adjusted odds ratio [aOR], 1.20 [95% confidence interval {CI}, 1.19–1.20]) for each additional antibiotic prescription filled. This significant dose-dependent relationship persisted after additionally controlling for timing and type of the antibiotics. Infants who had broad-spectrum-only antibiotic fills had increased odds of developing asthma compared with infants who had narrow-spectrum-only fills (aOR, 1.10 [95% CI, 1.05–1.19]). There was no significant association between timing, formulation, anaerobic coverage, and class of antibiotics and childhood asthma.

Conclusions: We found a consistent dose-dependent association between antibiotic prescription fills during infancy and subsequent development of childhood asthma. Our study adds important insights into specific aspects of infant antibiotic exposure. Clinical decision making regarding antibiotic stewardship and prevention of adverse effects should be critically assessed prior to use during infancy.

https://services.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/

Casos clínicos

You are the paediatric registrar on night shift in a busy district general hospital. Earlier in the day, a 2-year-old boy with symptoms and signs of lower respiratory tract infection (LRTI) was admitted to the ward. He is now febrile, and the nurse in charge contacts you to ask if she can give him a dose of ibuprofen to control his temperature. You recall a teaching session in the hospital about the association between non-steroidal anti-inflammatory drug (NSAID) use and invasive bacterial infection. You wonder if giving ibuprofen in the context of LRTI is not without risk.

Structured clinical question

In children with symptoms and signs of LRTI (population), does exposure to ibuprofen (intervention) compared with no exposure to ibuprofen (control) have any association with complicated respiratory disease (outcome)?

En los últimos 25 años se ha producido un aumento global de casos de leishmaniasis. Se postula que el cambio climático, el aumento global de la temperatura, las migraciones masivas del campo a la ciudad y los proyectos agroindustriales (creación de pantanos, sistemas de riego, formación de pozos...) potencian la aparición de reservorios de mosquitos flebotomos, que son los vectores de esta enfermedad. Cabe destacar que en la Comunidad Valenciana, zona endémica, la tasa de incidencia ha sufrido un aumento considerable en los últimos años. Describimos a un paciente de dos años que presenta cuadro clínico y analítico compatible con leishmaniasis visceral (fiebre, esplenomegalia y pancitopenia) con el antecedente, varios meses antes, de leishmaniasis cutánea. Existen pocos casos en la literatura médica que describan una afectación cutánea y visceral concomitante, hecho que otorga importancia a nuestro caso. La inmadurez de la respuesta inmune celular a esa edad podría ser la causa de esta forma de presentación atípica.

El exantema periflexural asimétrico de la infancia es una entidad benigna y autolimitada que se manifiesta típicamente en lactantes y preescolares con predominio del sexo femenino. La etiología es desconocida, aunque se ha relacionado con infecciones virales principalmente, y también bacterianas. El diagnóstico es clínico y el tratamiento sintomático. A pesar de ser una enfermedad común, es infradiagnosticada debido en parte al desconocimiento de esta. Nuestro objetivo es contribuir para mejorar el conocimiento de este trastorno. Se presenta el caso clínico de una paciente diagnosticada de exantema periflexural asimétrico con el antecedente de pielonefritis aguda la semana anterior a la aparición de las lesiones cutáneas.

El síndrome de shock tóxico estreptocócico (SSTS) es un cuadro grave e infrecuente en Pediatría. Sin embargo, en las últimas décadas está aumentando la incidencia de infecciones invasivas por Streptococcus pyogenes o estreptococo del grupo A. Aparece más frecuentemente en niños preescolares, ya que el diagnóstico de enfermedad estreptocócica es más complicado a esta edad. Es fundamental el diagnóstico y tratamiento precoz debido a su potencial gravedad, precisando en algunas ocasiones medidas intensivas de soporte vital y prevención del fallo multiorgánico.

 

Para ampliar

Atopic dermatitis (AD) predisposes to viral skin infections, such as eczema herpeticum (EH), and to bacterial skin infections, such as those caused by Staphylococcus aureus (SA) and group A streptococcus (GAS). This study evaluated clinical features of EH and its frequency of codetection with SA or GAS in children hospitalized for presumed AD skin infection.

Methods: We retrospectively reviewed clinical data for children ≤18 years of age admitted to a large hospital system for AD with presumed skin infection from January 2004 to December 2018. Those with an alternate primary diagnosis or missing microbiologic data were excluded. Encounters with herpes simplex virus testing were identified as AD with EH (ADEH+) or without (ADEH−). Encounters with bacterial skin culture growth were identified as SA or GAS.

Results: Among 180 AD encounters with suspected skin infection, 133 (74%) were tested for herpes simplex virus. Clinical findings associated with ADEH+ status (n = 61) included fever on admission (59% vs. 32% in ADEH−; P = 0.002), rash on the neck (30% vs. 13%; P = 0.015) and vesicular rash (70% vs. 49%; P = 0.011). Encounters in the ADEH+ group had a longer hospital length of stay compared with encounters in the ADEH− group [median 4 days (interquartile range 3–5 days) vs. 3 days (interquartile range 2–3 days); P < 0.001]. GAS was identified in only 1 ADEH+ encounter (2%) versus 15 ADEH− encounters (26%), P < 0.001.

Conclusions: Providers should maintain a high index of suspicion for EH in children admitted for presumed AD skin infection. GAS was more commonly associated with ADEH− encounters.

  • Quarantine alone or in combination with other public health measures to control COVID-19: a rapid review. Cochrane Database of Systematic Reviews 2020, Issue 4. Art. No.: CD013574. DOI: 10.1002/14651858.CD013574

COVID-19 is spreading rapidly, so we needed to answer this question as quickly as possible. This meant we shortened some steps of the normal Cochrane Review process. Nevertheless, we are confident that these changes do not affect our overall conclusions.

We looked for studies that assessed the effect of any type of quarantine, anywhere, on the spread and severity of COVID-19. We also looked for studies that assessed quarantine alongside other measures, such as isolation, social distancing, school closures and hand hygiene. COVID-19 is a new disease, so, to find as much evidence as possible, we also looked for studies on similar viruses, such as SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome).

Studies measured the number of COVID-19, SARS or MERS cases, how many people were infected, how quickly the virus spread, how many people died, and the costs of quarantine.

Key results: We included 29 studies. Ten studies focused on COVID-19, 15 on SARS, two on SARS plus other viruses, and two on MERS. Most of the studies combined existing data to create a model (a simulation) for predicting how events might occur over time, for people in different situations (called modelling studies). The COVID-19 studies simulated outbreaks in China, UK, South Korea, and on the cruise ship Diamond Princess. Four studies looked back on the effect of quarantine on 178,122 people involved in SARS and MERS outbreaks (called ‘cohort’ studies). The remaining studies modelled SARS and MERS outbreaks.

The modelling studies all found that simulated quarantine measures reduce the number of people with the disease by 44% to 81%, and the number of deaths by 31% to 63%. Combining quarantine with other measures, such as closing schools or social distancing, is more effective at reducing the spread of COVID-19 than quarantine alone. The SARS and MERS studies agreed with the studies on COVID-19.

Two SARS modelling studies assessed costs. They found that the costs were lower when quarantine measures started earlier.

We cannot be completely certain about the evidence we found for several reasons. The COVID-19 studies based their models on limited data and made different assumptions about the virus (e.g. how quickly it would spread). The other studies investigated SARS and MERS so we could not assume the results would be the same for COVID-19.

Conclusion: Despite limited evidence, all the studies found quarantine to be important in reducing the number of people infected and the number of deaths. Results showed that quarantine was most effective, and cost less, when it was started earlier. Combining quarantine with other prevention and control measures had a greater effect than quarantine alone.

This review includes evidence published up to 12 March 2020.

·Letter: Cellulitis: oral versus intravenous and home versus hospital—what makes clinicians decide? Arch Dis Child. 2020 Apr;105(4):413-415

There is a lack of evidence-based guidance for management of cellulitis and use of outpatient parenteral antimicrobial therapy (OPAT) in children. The only published guidelines for skin infections are for adults.1 Lack of standardised guidelines for children can result in variation in paediatricians’ practice, with implications on care and resources.2 Our aim was to understand hospital paediatricians’ opinions about cellulitis management, important in reducing variation in care, regarding: (1) indications for using intravenous antibiotics, (2) indications for hospitalisation and (3) barriers to OPAT.

This web-based anonymous survey was undertaken over 4 weeks at The Royal Children’s Hospital in Melbourne. Acute care paediatricians who diagnose and manage cellulitis were surveyed. Questions related to a clinical scenario (box 1), and none were mandatory.

Resumen: estudia exhaustivamente la dinámica de transmisión en domicilio de S.aureus resitente a meticilina en niños con infección de piel y partes blandas. El entorno doméstico desempeña un papel clave en la transmisión. Las futuras intervenciones deberían centrarse en los miembros del hogar y el ambiente domiciliario, enfocándose en las estrategias de mejora en la higiene de las manos y los comportamientos higiénicos en los convivientes.

·Syphilis screening in pregnant women: Discordant results require careful confirmation. J Pediatr. 2020 Apr;219:1-3

In the past 15 years, many high volume clinical laboratories implemented reverse sequence syphilis screening. Reverse sequence screening uses an automated treponemal immunoassay as the initial screening step, instead of the traditional rapid plasma reagin. Reverse sequence screening is economical for high volume laboratories but has led to diagnostic difficulties when the testing algorithm yields discordant results, particularly for pregnant women. In this volume of The Journal, Williams et al evaluated 35 108 reverse sequence syphilis screening events among pregnant women in Ohio from 2011-2018. Overall, 127 women had discordant screening results, of which 85 (65%) were ultimately found to have a false positive treponemal immunoassay. These results suggest that for pregnant women in this cohort, discordant screening results were often secondary to false positive screening and were not indicative of syphilis infection.

Interpretation of reverse sequence syphilis screening results is challenging in pregnant women, as the stakes are high for early diagnosis and treatment to prevent congenital syphilis. From 2013-2017, the CDC reported that the national rate of reported primary and secondary syphilis in women rose by 156%. In 2016, 628 cases of congenital syphilis were reported by CDC, with 41 cases of syphilis-related stillbirth. Congenital syphilis cases were concentrated in 9 regions across the US (Ohio was one of these areas), and the rise in syphilis in women has been linked to the amphetamine and opioid epidemics. Thus, the results reported by Williams et al require careful interpretation in the context of local epidemiology. Nevertheless, this study highlights the challenges of interpreting screening assays that may offer convenience over specificity and underscores the need to perform confirmatory testing for pregnant women with discordant syphilis screening results.

Rhinovirus is the most common virus causing respiratory tract illnesses in children. Rhinoviruses are classified into species A, B and C. We examined the associations between different rhinovirus species and respiratory illness severity.

Methods: This is a retrospective observational cohort study on confirmed rhinovirus infections in 134 children 3–23 months of age, who were enrolled in 2 prospective studies on bronchiolitis and acute otitis media, respectively, conducted simultaneously in Turku University Hospital, Turku, Finland, between September 2007 and December 2008.

Results: Rhinovirus C is the most prevalent species in our study, and it was associated with severe wheezing and febrile illness. We also noted that history of atopic eczema was associated with wheezing.

Conclusions: Our understanding of rhinovirus C as the most pathogenic rhinovirus species was fortified. Existing research supports the idea that atopic characteristics are associated with the severity of the rhinovirus C-induced illness.

Resumen: los tres modelos de predicción fueron consistentes y sugieren que la alta cobertura de vacunación contra el VPH de las niñas puede conducir a la eliminación del cáncer de cuello uterino en la mayoría de los países en vías de desarrollo para fines de siglo. El mantenimiento del cribado de cáncer de cuello a amplios secotres de la población femenina acelerará las reducciones y será necesario para eliminar el cáncer de cuello uterino en los países con mayor carga de la enfermedad.

Conclusion: Our study demonstrated an absence of clear association between HPV vaccines and autoimmune and other rare diseases. The review also highlights the need for more systematic collaborations to monitor rare safety adverse events.

La terapia con antibióticos a menudo se prescribe para la sospecha de neumonía adquirida en la comunidad (NAC) en niños a pesar de la falta de conocimiento del patógeno causante. Nuestro objetivo en este estudio fue investigar la asociación entre la prescripción de antibióticos y el fracaso del tratamiento en niños con sospecha de NAC que son dados de alta del servicio de urgencias (DE) del hospital.

Conclusiones: Entre los niños con sospecha de NAC, los resultados no fueron estadísticamente diferentes entre los que recibieron y no recibieron una receta de antibióticos.

Invasive pneumococcal disease (IPD) causes life-threatening illnesses including meningitis and bloodstream infection. Here, we report the impact of 7- and 13-valent pneumococcal conjugate vaccines (PCV7/PCV13) after introduction into the Irish pediatric immunization schedule in 2008 and 2010, respectively, and the clinical details surrounding suspected PCV vaccine failures.

Methods: Serotyping and antimicrobial susceptibility testing of all culture-confirmed cases referred from children <16 years of age from July 2007 to June 2018 were assessed. Surveillance data were assessed to identify any potential vaccine failures.

Results: The number of IPD cases has decreased by >50% since the introduction of PCVs. The most significant decline PCV serotypes in children <2 years of age, with a 97% decline in PCV7 serotypes, incidence rate ratio (IRR) 0.03, 95% confidence interval (CI): 0.00–0.21; and a 78% decline PCV13-only (PCV13-7) serotypes, IRR 0.22, 95% CI: 0.05–1.04, respectively. However, there has been an increase in non-PCV13 serotypes in children <2 years during the same period (IRR: 2.82, 95% CI: 1.02–7.84; P = 0.0463), with similar serotype trends observed for those 2–4 and 5–15 years of age. There were no clear vaccine replacement serotypes, instead a number of different serotypes emerged. Sixteen vaccine failures were identified, 10 of which were postbooster vaccine failures. Most failures were serotype 19A and resistant to antimicrobials.

Conclusions: Further reducing the incidence of IPD is more challenging as the number of non-PCV13 serotypes has expanded and is now less susceptible to antimicrobials. Consequently, higher valency or broader target vaccines are now required to further prevent IPD in children.

Determinar la efectividad de la vacuna (VE) de PCV-13 y PCV-10 en la prevención de la enfermedad neumocócica invasiva (IPD) y la otitis media aguda (OMA) en niños <5 años.

Resultados: Se informó una eficacia significativa contra la ENI según el  tipo de vacuna en niños ≤5 años para ≥1 dosis de PCV-13 en el esquema 3 + 1 (86% –96%) y 2 + 1 (67.2% –86%) y para PCV- 10 para los programas 3 + 1 (72.8% –100%) y 2 + 1 (92% –97%). En niños <12 meses de edad, la eficacia vacunal PCV-13 VE contra la serie post-primaria del serotipo 19A fue significativa para el esquema 3 + 1 pero no para el esquema 2 + 1. La protección cruzada de PCV-10 contra 19A fue significativa en niños ≤5 años con ≥1 dosis (82.2% y 71%). Ninguno de los PCV resultó efectivo contra el serotipo 3. PCV-13 fue efectivo contra la OMA (86%; intervalo de confianza [IC] del 95%: 61 a 94). PCV-10 fue eficaz contra la OMA clínicamente definida (26.9%; IC 95%: 5.9 a 43.3) y OMA bacteriológicamente confirmada (43.3%; IC 95%: 1.7 a 67.3).

Conclusiones: Ambas vacunas PCV ofrecen protección contra infecciones neumocócicas, con PCV-10 protegiendo contra 19A IPD, pero esta eficacia vacunal no se ha verificado en los grupos de edad más jóvenes.

·Invasive Haemophilus influenzae Type b Disease in the Post Hexavalent Era: Ten Years of Molecular Surveillance in Tuscany The Pediatric Infectious Disease Journal. 39(4):294-297, April 2020.

The epidemiologic characteristics of invasive Haemophilus influenzae type b disease (HIBD) have markedly changed since the introduction of the Haemophilus influenzae type b (Hib) conjugate vaccine worldwide. The immunization schedule against Haemophilus influenzae type b differs in Europe.

Methods: This is a retrospective observational study which evaluates all the data included in the molecular surveillance register for invasive infectious diseases at the Laboratory of Molecular Diagnosis at Meyer Children’s University Hospital from December 2008 to December 2018 with a diagnosis of invasive HIBD in children <5 years of age.

Results: We identified 4 cases of HIBD: all the cases presented signs or symptoms of invasive infection and the H. influenzae type b was identified in cerebrospinal fluid, or blood or bronchoalveolar lavage by molecular test. The crude incidence for Hib invasive disease in Tuscany is 0.26/100,000 p-y in children younger than 5 years, significantly different from the incidence rate before the introduction of the Hib vaccination. Vaccination effectiveness can be estimated at 97.9% and the impact of hexavalent (2p+1) vaccine at 99.6%.

Conclusions: This work confirms the high impact of the hexavalent vaccine 2p+1 schedule for HIBD in children <5 years, emphasizing the role of molecular test for HIBD diagnosis and surveillance.

Resumen: la mortalidad por diarrea ha disminuido sustancialmente desde 1990, aunque hay variaciones según el país. Las mejoras en los indicadores sociodemográficos podrían explicar algunas de estas tendencias, pero los cambios en la exposición a los factores de riesgo, particularmente mal saneamiento, el fallo de medro infantil y el bajo uso de la solución de rehidratación oral, parecen estar relacionados con las tasas relativas y absolutas de menor disminución de la mortalidad por diarrea. Aunque las intervenciones más efectivas pueden variar según el país o la región, identificar y ampliar las intervenciones destinadas a prevenir y proteger contra la diarrea que ya han mostrado reducir la mortalidad por diarrea, podrían evitar aún más miles de muertes debido a esta enfermedad.

Resumen: nuestros resultados muestran que ha habido disminuciones sustanciales pero desiguales en la mortalidad por infecciones respiratorias bajas entre los países entre 1990 y 2017. Aunque las mejoras en los indicadores de desarrollo sociodemográfico podrían explicar algunas de estas tendencias, los cambios en la exposición a factores de riesgo modificables (por ejemplo vacunaciones) están relacionados con las tasas de disminución en esta mortalidad. Ninguna intervención individual aceleraría universalmente las reducciones en la pérdida de salud asociada con estas infecciones en todos los entornos, pero enfatizar los factores de riesgo más dominantes, particularmente en países con alta letalidad, puede contribuir a la reducción de muertes prevenibles.

Resumen: Los pacientes de atención primaria con síndrome gripal (n=1629, la mitad confirmados con PCR como positivos a influenza) tratados con oseltamivir, se recuperaron en promedio un día antes (HR: 1.02 días; ICrB 95%: 0,74 a 1,31) que los manejados solo con atención habitual. Los pacientes más mayores, con comorbilidades y una mayor duración de estas se recuperaron 2-3 días antes. En menores de 12 años el efecto fue menor (HR: 0,70 días, ICrB 95%: 0,30 a 1,20).

En el contexto generalizado de recursos limitados para financiar las intervenciones sanitarias disponibles para una población, se requieren criterios explícitos que permitan seleccionar el conjunto de prestaciones que aporten el mayor beneficio en salud posible con los recursos existentes. La evaluación económica de intervenciones sanitarias es una herramienta de análisis que compara los costes y los resultados en salud de programas sanitarios alternativos con el fin de informar sobre su eficiencia. El marco tradicional de la evaluación económica presenta algunas limitaciones para la evaluación específica de intervenciones de salud pública, como son los programas de vacunación, especialmente los destinados a la población pediátrica. Entre ellos se destacan los desafíos que presenta evaluar intervenciones donde los efectos en salud ocurren en el largo plazo, sobre poblaciones diferentes a las que se aplica la intervención, con posibles efectos adversos en población sana, con efectos intangibles considerables, con implicaciones relevantes sobre la desigualdad, y que requieren de la medición de resultados en salud en niños y niñas, así como en sus entornos. Entre las principales vías de avance para que las evaluaciones económicas sean capaces de abordar las problemáticas inherentes a los programas de vacunación en población pediátrica destacamos la posibilidad de emplear medidas de resultados capaces de captar beneficios de bienestar social más allá de las mejoras en salud individuales, así como la aplicación de los métodos que caractericen los efectos dinámicos y los altos niveles de incertidumbre cuando estos sean necesarios.

El artículo “Evaluación económica de la inclusión en el calendario vacunal de 4CMenB (Bexsero) en España”1 concluye que, con la información disponible y el precio de la vacuna actual, un programa de vacunación universal en lactantes con la vacuna 4CMenB no es una medida coste-efectiva para el Sistema Nacional de Salud (SNS). Estos resultados están en línea con la amplia mayoría de evaluaciones internacionales realizadas en otros países. En la actualidad, la vacuna no se incluye en el calendario común de vacunación establecido por el Consejo Interterritorial del Sistema Nacional de Salud (CISNS) de España y su uso se limita a grupos de riesgo establecidos. Sin embargo, algunas comunidades autónomas (CC. AA.) han aprobado y administran de forma sistemática la vacuna en la población infantil.

He leído con interés el artículo publicado recientemente en Gaceta Sanitaria “Evaluación económica de la inclusión en el calendario vacunal de 4CMenB (Bexsero) en España”, firmado por los autores Rafael Ruiz-Montero et al.1, donde hacen un excelente análisis de coste-utilidad, siguiendo procedimientos clásicos y modelos estandarizados en el campo de la farmacoeconomía aplicada a vacunas2, pero al que, a mi juicio, cabe hacer algunos comentarios.

OBJECTIVES: To determine if a multicomponent intervention was associated with increased use of first-line antibiotics (cephalexin or sulfamethoxazole and trimethoprim) among children with uncomplicated urinary tract infections (UTIs) in outpatient settings.

METHODS: The study was conducted at Kaiser Permanente Colorado, a large health care organization with ∼127 000 members <18 years of age. After conducting a gap analysis, an intervention was developed to target key drivers of antibiotic prescribing for pediatric UTIs. Intervention activities included development of new local clinical guidelines, a live case-based educational session, pre- and postsession e-mailed knowledge assessments, and a new UTI-specific order set within the electronic health record. Most activities were implemented on April 26, 2017. The study design was an interrupted time series comparing antibiotic prescribing for UTIs before versus after the implementation date. Infants <60 days old and children with complex urologic or neurologic conditions were excluded.

RESULTS: During January 2014 to September 2018, 2142 incident outpatient UTIs were identified (1636 preintervention and 506 postintervention). Pyelonephritis was diagnosed for 7.6% of cases. Adjusted for clustering of UTIs within clinicians, the proportion of UTIs treated with first-line antibiotics increased from 43.4% preintervention to 62.4% postintervention (P < .0001). The use of cephalexin (first-line, narrow spectrum) increased from 28.9% preintervention to 53.0% postintervention (P < .0001). The use of cefixime (second-line, broad spectrum) decreased from 17.3% preintervention to 2.6% postintervention (P < .0001). Changes in prescribing practices persisted through the end of the study period.

CONCLUSIONS: A multicomponent intervention with educational and process-improvement elements was associated with a sustained change in antibiotic prescribing for uncomplicated pediatric UTIs.

BACKGROUND AND OBJECTIVES: Antibiotic therapy is often prescribed for suspected community-acquired pneumonia (CAP) in children despite a lack of knowledge of causative pathogen. Our objective in this study was to investigate the association between antibiotic prescription and treatment failure in children with suspected CAP who are discharged from the hospital emergency department (ED).

METHODS: We performed a prospective cohort study of children (ages 3 months–18 years) who were discharged from the ED with suspected CAP. The primary exposure was antibiotic receipt or prescription. The primary outcome was treatment failure (ie, hospitalization after being discharged from the ED, return visit with antibiotic initiation or change, or antibiotic change within 7–15 days from the ED visit). The secondary outcomes included parent-reported quality-of-life measures. Propensity score matching was used to limit potential bias attributable to treatment selection between children who did and did not receive an antibiotic prescription.

RESULTS: Of 337 eligible children, 294 were matched on the basis of propensity score. There was no statistical difference in treatment failure between children who received antibiotics and those who did not (odds ratio 1.0; 95% confidence interval 0.45–2.2). There was no difference in the proportion of children with return visits with hospitalization (3.4% with antibiotics versus 3.4% without), initiation and/or change of antibiotics (4.8% vs 6.1%), or parent-reported quality-of-life measures.

CONCLUSIONS: Among children with suspected CAP, the outcomes were not statistically different between those who did and did not receive an antibiotic prescription.

BACKGROUND: The ability of the decades-old Boston and Philadelphia criteria to accurately identify infants at low risk for serious bacterial infections has not been recently reevaluated.

METHODS: We assembled a multicenter cohort of infants 29 to 60 days of age who had cerebrospinal fluid (CSF) and blood cultures obtained. We report the performance of the modified Boston criteria (peripheral white blood cell count [WBC] ≥20 000 cells per mm3, CSF WBC ≥10 cells per mm3, and urinalysis with >10 WBC per high-power field or positive urine dip result) and modified Philadelphia criteria (peripheral WBC ≥15 000 cells per mm3, CSF WBC ≥8 cells per mm3, positive CSF Gram-stain result, and urinalysis with >10 WBC per high-power field or positive urine dip result) for the identification of invasive bacterial infections (IBIs). We defined IBI as bacterial meningitis (growth of pathogenic bacteria from CSF culture) or bacteremia (growth from blood culture).

RESULTS: We applied the modified Boston criteria to 8344 infants and the modified Philadelphia criteria to 8131 infants. The modified Boston criteria identified 133 of the 212 infants with IBI (sensitivity 62.7% [95% confidence interval (CI) 55.9% to 69.3%] and specificity 59.2% [95% CI 58.1% to 60.2%]), and the modified Philadelphia criteria identified 157 of the 219 infants with IBI (sensitivity 71.7% [95% CI 65.2% to 77.6%] and specificity 46.1% [95% CI 45.0% to 47.2%]). The modified Boston and Philadelphia criteria misclassified 17 of 53 (32.1%) and 13 of 56 (23.3%) infants with bacterial meningitis, respectively.

CONCLUSIONS: The modified Boston and Philadelphia criteria misclassified a substantial number of infants 29 to 60 days old with IBI, including those with bacterial meningitis.

Background: Limited data are available on childhood encephalitis. Our study aimed to increase insight on clinical presentation, etiology, and clinical outcome of children with severe encephalitis in the Netherlands.

Methods: We identified patients through the Dutch Pediatric Intensive Care Evaluation database and included children diagnosed with encephalitis <18 years of age admitted to 1 of the 8 pediatric intensive care units (PICU) in the Netherlands between January 2003 and December 2013. We analyzed demographic characteristics, clinical symptoms, neurologic imaging, etiology, treatment and mortality.

Results: We included 121 children with a median age of 4.6 years (IQR 1.3–9.8). The most frequently described clinical features were headache (82.1%), decreased consciousness (79.8%) and seizures (69.8%). In 44.6% of the children, no causative agent was identified. Viral- and immune-mediated encephalitis were diagnosed in 33.1% and 10.7% of the patients. A herpes simplex virus infection (13.2%) was mainly seen in children <5 years of age, median age, 1.73 years (IQR 0.77–5.01), while immune-mediated encephalitis mostly affected older children, median age of 10.4 years (IQR, 3.72–14.18). An age of ≥ 5 years at initial presentation was associated with a lower mortality (OR 0.2 [CI 0.08–0.78]). The detection of a bacterial (OR 9.4 [CI 2.18–40.46]) or viral (OR 3.7 [CI 1.16–11.73]) pathogen was associated with a higher mortality.

Conclusions: In almost half of the Dutch children presenting with severe encephalitis, a causative pathogen could not be identified, underlining the need for enhancement of microbiologic diagnostics. The detection of a bacterial or viral pathogen was associated with a higher mortality.

The Pediatric Infectious Disease Journal. 39(4):273-276, April 2020.

Background: Sensorineural hearing loss (SNHL) is well described in children with congenital cytomegalovirus (CMV) infection, but limited data are available on middle ear effusion (MEE) occurrence in this population. We assessed the prevalence of MEE and the degree of transient hearing change associated with MEE among children with congenital CMV infection.

Methods: Children with congenital CMV infection enrolled in a longitudinal study received hearing and tympanometric testing during scheduled follow-up visits annually up to 6 years of age. We used a generalized linear mixed-effect logistic regression model to compare the odds of MEE, defined as type B tympanogram (normal ear canal volume with little tympanic membrane movement) among patients categorized as symptomatic or asymptomatic based on the presence of congenital CMV-associated signs in the newborn period.

Results: Forty-four (61%) of 72 symptomatic and 24 (28%) of 87 asymptomatic patients had ≥1 visit with MEE. After controlling for the number of visits, symptomatic patients had significantly higher odds of MEE (odds ratio: 2.09; 95% confidence interval: 1.39–3.14) than asymptomatic patients. Transient hearing decrease associated with a type B tympanogram ranged from 10 to 40 dB, as measured by audiometric air-bone gap in 11 patients.

Conclusions: Among children with congenital CMV, MEE can result in transient hearing decrease, which can reduce the efficacy of a hearing aid in those with SNHL. It is warranted that children with congenital CMV infection and SNHL receive routine audiologic and tympanometric testing to better manage hearing aid amplification levels.

Background: Congenital cytomegalovirus (CCMV) accounts for high rates of infant morbidity and mortality. Neutropenia is a common finding in CCMV infection, of which the age of presentation overlaps with autoimmune neutropenia (AIN). AIN represents one of the most common forms of chronic neutropenia in childhood.

Methods: A literature search exploring biologic associations between CCMV and AIN was conducted: PubMed (MEDLINE), Ovid and Web of Science. We further describe 2 cases of concurrent CCMV and AIN. Both cases were confirmed with the indirect granulocyte immunofluorescence test and alternative etiologies for neutropenia excluded.

Results: Our 2 patients represent confirmed cases of AIN in infants with CCMV. One patient demonstrated neutropenia while undergoing treatment with Valganciclovir, while the other was never treated. With interruption of Valganciclovir in infant A, neutrophil counts (ANC) did not improve and upon resumption of treatment ANC remained static.

Conclusions: Further studies examining a possible biologic link between CCMV and AIN are advocated for. We encourage clinicians to actively consider AIN in the differential diagnosis of all infants with CCMV presenting with neutropenia.

·Early Life Parechovirus Infection Neurodevelopmental Outcomes at 3 Years: A Cohort Study J Pediatr. 2020 Apr;219:111-117.e1.

Objective To investigate the long-term developmental and behavioral outcomes in an established cohort of children hospitalized as infants with human parechovirus (HPeV) infection and sepsis-like illness.

Study designThe HPeV cohort was composed of children 3 years of age after HPeV infection and hospitalization in early infancy that occurred during a well-documented HPeV genotype 3 outbreak in Australia. We assessed neurodevelopmental and behavioral outcomes using the Bayley Scales of Infant and Toddler Development-III and the Child Behavior Checklist. We compared their outcomes with a subsample of healthy control infants drawn from the independently sampled Triple B Pregnancy Cohort Study.

Results Fifty children, with a mean age of 41 months, were followed for 3 years after hospital admission with HPeV infection. There were 47 children whose original illness was fever without source or sepsis-like illness and 3 who had encephalitis. All children in the HPeV cohort showed age-specific development within the population normal range on the Bayley Scales of Infant and Toddler Development-III. There was no difference in developmental attainment compared with 107 healthy control infants after adjusting for measured confounders. The HPeV cohort showed higher average scores on the Child Behavior Checklist and a higher frequency of clinical range scores compared with healthy controls.

Conclusions Although HPeV sepsis-like illness did not result in neurodevelopmental delay at 3 years of age, it was associated with increased behavioral problems compared with healthy controls. The behavioral problems reached a clinical threshold in a minority of children. Results inform clinical management and planning for children after severe HPeV infection in infancy.

Resumen: 74 niños atendidos en el Children's Hospital de Colorado con enfermedad neurológica por enterovirus. EV-A71 fue identificado en 43 (58%) de estos niños. La mediana de edad de los niños con enfermedad neurológica EV-A71 fue de 22,7 meses (RIQ: 4,0-31,9), y la mayoría de estos niños eran varones (79%). 93% de niños con enfermedad neurológica por EV-A71 tenían hallazgos sugestivos de meningitis, 72% mostraron evidencia de encefalitis y 23% de niños cumplieron con la definición de caso de mielitis flácida aguda. Todos los niños con la enfermedad EV-A71 tenían fiebre y el 42% tenían lesiones en manos, pies o boca al inicio neurológico o antes. Los niños con enfermedad EV-A71 se diferenciaron mejor de aquellos con otros enterovirus (n = 31) por los hallazgos neurológicos de mioclonus, ataxia, debilidad e inestabilidad. De las muestras recolectadas de niños con EV-A71, este enterovirus se detectó en el 94% de las muestras rectales, el 79% de las orofaríngeas, el 56% de las nasofaríngeas y el 20% de las muestras de líquido cefalorraquídeo.  El 93% de niños con enfermedad neurológica EV-A71 que pudieron ser seguidos mostraron una recuperación completa en 1-2 meses. En comparación con los niños con mielitis flácida aguda asociada con EV-D68, los niños con mielitis flácida aguda asociada con EV-A71 eran más jóvenes, mostraban un inicio neurológico antes del inicio de los síntomas prodrómicos, tenían una debilidad más leve, mostraban una mejoría más rápida y eran más propensos a la recuperación completa.

Resumen: analizan 556 casos de Zika confirmados por laboratorio y 548 casos no relacionados con zika. La definición de caso de la OMS hubiera detectado 176 casos confirmados de zika, y la definición de la OPS 109, la mayoría de los cuales presentaron un perfil clínico similar al dengue. Los dos tercios restantes de los casos de zika, caracterizados por fiebre indiferenciada o erupción cutánea afebril, se hubieran quedado sin diagnóstico. Entre los casos de zika, la erupción cutánea (n = 440), especialmente la erupción eritematosa generalizada (n = 334), la fiebre (n = 333), la leucopenia (n = 217) y el dolor de cabeza (n = 203) fueron más comunes y alcanzaron su punto máximo a los 3 días de inicio de enfermedad. La presentación más común de zika durante la primera semana de enfermedad fue solo erupción (n = 80). Además, el zika se manifestó de manera diferente en la edad pediátrica: los niños más mayores con zika se presentaron con un perfil clínico similar al dengue, mientras que los casos más jóvenes de zika se presentaron con fiebre indiferenciada o erupción cutánea afebril. La mayoría de los casos pediátricos de zika no se detectan según las definiciones de casos de la OMS y la OPS, lo que sugiere que las normas actuales para la determinación de casos de zika deben de ser revisadas.

 

 

Actualidad bibliográfica marzo 2020

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Abstract: Coronaviruses (CoVs) are a large family of enveloped, singlestranded, zoonotic RNA viruses. Four CoVs commonly circulate among humans: HCoV2-229E, -HKU1, -NL63 and -OC43. However, CoVs can rapidly mutate and recombine leading to novel CoVs that can spread from animals to humans. The novel CoVs severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. The 2019 novel coronavirus (SARS-CoV-2) is currently causing a severe outbreak of disease (termed COVID-19) in China and multiple other countries, threatening to cause a global pandemic. In humans, CoVs mostly cause respiratory and gastrointestinal symptoms. Clinical manifestations range from a common cold to more severe disease such as bronchitis, pneumonia, severe acute respiratory distress syndrome, multiorgan failure and even death. SARS-CoV, MERS-CoV and SARS-CoV-2 seem to less commonly affect children and to cause fewer symptoms and less severe disease in this age group compared with adults, and are associated with much lower case-fatality rates. Preliminary evidence suggests children are just as likely as adults to become infected with SARS-CoV-2 but are less likely to be symptomatic or develop severe symptoms. However, the importance of children in transmitting the virus remains uncertain. Children more often have gastrointestinal symptoms compared with adults. Most children with SARSCoV present with fever, but this is not the case for the other novel CoVs. Many children affected by MERS-CoV are asymptomatic. The majority of children infected by novel CoVs have a documented household contact, often showing symptoms before them. In contrast, adults more often have a nosocomial exposure. In this review, we summarize epidemiologic, clinical and diagnostic findings, as well as treatment and prevention options for common circulating and novel CoVs infections in humans with a focus on infections in children.

 

·A Case Series of children with 2019 novel coronavirus infection.  Clin Infect Dis. 2020 Feb 28. pii: ciaa198.  https://doi.org/10.1093/ cid/ciaa198

We first described the 2019 novel coronavirus infection in 10 children occurring in areas other than Wuhan. The coronavirus diseases in children are usually mild and epidemiological exposure is a key clue to recognize pediatric case. Prolonged virus shedding is observed in respiratory tract and feces at the convalescent stage.

A small number of cases of coronavirus disease 2019 (Covid-19) have been described in children,1,2 and our understanding of the spectrum of illness is limited.3 We conducted a retrospective analysis involving hospitalized children in Wuhan, China. From January 7 to January 15, 2020, a total of 366 hospitalized children (≤16 years of age) were enrolled in a retrospective study of respiratory infections at three branches of…

Since early January 2020, after the outbreak of 2019 novel coronavirus infection in Wuhan, China, ≈365 confirmed cases have been reported in Shenzhen, China. The mode of community and intrafamily transmission is threatening residents in Shenzhen. Strategies to strengthen prevention and interruption of these transmissions should be urgently addressed.

Based on the sources of data used in this study, 9 infants were infected with COVID-19 and were hospitalized in China between December 2019 and February 6, 2020. Given the number of infections reported, the number of infected infants identified was small. This may be due to a lower risk of exposure or incomplete identification due to mild or asymptomatic disease, rather than resistance to infection.1,5 However, this study showed that infants can be infected by COVID-19; the earlier stage of the COVID-19 epidemic primarily involved adults older than 15 years.2-4Family clustering occurred for all infected infants. Infants who have infected family members should be monitored or evaluated and family clustering should be reported to ensure a timely diagnosis. Seven of the 9 infant patients were female. Previous studies found higher percentages of infection in men than women.2-4 Whether female infants may be more susceptible to COVID-19 infection than male infants requires further study. The study was limited by small sample size, inclusion only of infants who were hospitalized, and lack of inclusion of asymptomatic patients. Although a systematic and comprehensive search was made for relevant infections in infants, the epidemic is spreading rapidly and incomplete identification of cases is possible. Because infants younger than 1 year cannot wear masks, they require specific protective measures. Adult caretakers should wear masks, wash hands before close contact with infants, and sterilize the infants’ toys and tableware regularly

To determine the epidemiology of 2019 novel coronavirus disease (COVID-19) in a remote region of China, far from Wuhan, we analyzed the epidemiology of COVID-19 in Gansu Province. From January 23 through February 3, 2020, a total of 35 (64.8%) of 54 reported cases were imported from COVID-19–epidemic areas. Characteristics that differed significantly during the first and second waves of illness in Gansu Province were mean patient age, occupation, having visited epidemic areas, and mode of transportation. Time from infection to illness onset for family clusters was shorter in Gansu Province than in Wuhan, consistent with shortened durations from onset to first medical visit or hospitalization. Spatial distribution pattern analysis indicated hot spots and spatial outliers in Gansu Province. As a result of adequate interventions, transmission of the COVID-19 virus in Gansu Province is decreasing.

We report an asymptomatic child who was positive for a 2019 novel coronavirus by reverse transcription PCR in a stool specimen 17 days after the last virus exposure. The child was virus positive in stool specimens for at least an additional 9 days. Respiratory tract specimens were negative by reverse transcription PCR.

To determine possible modes of virus transmission, we investigated a cluster of COVID-19 cases associated with a shopping mall in Wenzhou, China. Data indicated that indirect transmission of the causative virus occurred, perhaps resulting from virus contamination of common objects, virus aerosolization in a confined space, or spread from asymptomatic infected persons.

Human coronaviruses (HCoVs) have long been considered inconsequential pathogens, causing the “common cold” in otherwise healthy people. However, in the 21st century, 2 highly pathogenic HCoVs—severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)—emerged from animal reservoirs to cause global epidemics with alarming morbidity and mortality. In December 2019, yet another pathogenic HCoV, 2019 novel coronavirus (2019-nCoV), was recognized in Wuhan, China, and has caused serious illness and death. The ultimate scope and effect of this outbreak is unclear at present as the situation is rapidly evolving. 

Background Neonates with congenital urinary tract dilatation (UTD) may have an increased risk of urinary tract infections (UTI). At present, the management of these patients is controversial and the utility of continuous antibiotic prophylaxis (CAP) remains uncertain as the literature presents contradicting evidence. The aim of this observational study was to assess UTI occurrence in children with prenatal diagnosis of urinary collecting system dilatation without antibiotic prophylaxis.

Methods Between June 2012 and August 2016, we evaluated the incidence of UTI and the clinical and ultrasonography evolution in 407 children with a prenatally diagnosed UTD. All subjects underwent two prenatal ultrasounds scans (USs) at 20 weeks and 30 weeks of gestation and within 1 month of birth. Patients with a confirmed diagnosis of UTD underwent US follow-up at 6, 12 and 24 months of life. According to the UTD classification system stratify risk, after birth UTD were classified into three groups: UTD-P1 (low risk group), UTD-P2 (intermediate risk group), and UTD-P3 (high risk group). Voiding cystourethrogram was performed in all patients who presented a UTI and in those with UTD-P3. No patient underwent CAP.

Results Postnatal US confirmed UTD in 278 out of 428 patients with the following rates: UTD-P1 (126), UTD-P2 (95) and UTD-P3 (57). During postnatal follow-up, 6.83% patients presented a UTI (19 out of 278). Eleven out of 19 had vesicoureteral reflux (VUR), and other four were diagnosed with obstructive uropathy and underwent surgical correction. Five patients presented a UTI reinfection.

Conclusion The occurrence of UTI in patients with urinary collecting system dilatation was low. The recent literature reports an increased selection of multirestistant germs in patients with VUR exposed to CAP. This study constitutes a strong hint that routine continuous antibiotic prophylaxis could be avoided in patients with UTD.

Casos clínicos

·Strongyloides stercoralis Hyperinfection and Intractable Pulmonary Hemorrhage. J Pediatr. 2020 Mar;218:258

A 10-year-old previously healthy boy, hailing from an Indian village had a history of hematuria, proteinuria, and generalized swelling for 3 months. This was diagnosed as crescentic glomerulonephritis on renal biopsy, and the patient was started on steroids. He presented with hypotensive shock and respiratory distress after a massive episode of hemoptysis following recurrent episodes of hemoptysis of small amounts for a month prior to this episode. Evaluation for causes of recurrent hemoptysis such as tuberculosis and pulmonary vasculitis were inconclusive. Computed tomography of the chest revealed diffuse infiltrates suggestive of recurrent pulmonary hemorrhage (Figure) for which he underwent plasmapheresis and pulse steroid therapy. There was no improvement in his symptoms, and he showed progressive worsening with involvement of kidneys, brain, and refractory shock requiring supportive care and peritoneal dialysis. The peritoneal fluid sent for microscopy incidentally revealed freely moving larvae of Strongyloides stercoralis (Video; available at www.jpeds.com). Samples of bronchoalveolar lavage and gastric aspirate confirmed Strongyloides hyperinfection. He was treated with oral albendazole 400 mg once a day and oral ivermectin (200 mcg/kg/day) initially for 4 days followed by subcutaneous Ivermectin 5 mg subcutaneously because of nonresponse to oral treatment. Despite clearing of the parasites in the peritoneal fluid within 3 days of subcutaneous Ivermectin, the child succumbed to multiorgan failure.

·Successful Resolution of Recurrent Vaginal Pinworm Infection With Intermittent Albendazole Administration The Pediatric Infectious Disease Journal. 39(3):254-255, March 2020.

We describe the case of a 7-year-old girl with repeated vaginal Enterobius vermicularis infection, never detected as a digestive tract infection. Two-dose pyrantel pamoate or 2-dose albendazole could not suppress recurrence. Finally, 3-dose albendazole after 2-week intervals was successful in preventing relapse.

A 6-year-old boy presented with a 2-year history of recurrent episodes of painful, haemorrhagic vesicles and erythema affecting the face, ears and neck, 2 hours after sun exposure (figures 1 and 2). He had severe ulceration and crusting affecting the helix of his ear (figure 3). Healing was accompanied by residual varioliform, atrophic scarring (figure 4). His rash occurred during spring and summer months and only affected sun-exposed sites.

·Noma Neonatorum: A Unique Presentation of Sepsis in Neonates The Pediatric Infectious Disease Journal. 39(3):260, March 2020.

A 14-day-old female infant presented to the hospital with cough for 4 days, black discoloration of her lips and tongue, lethargy, decreased feeding for 1 day and 1 episode of blood-tinged emesis. She was born full term via normal vaginal delivery with a birth weight of 2.5 kg. Antenatal period was uneventful, and there was no maternal history of antibiotic use during pregnancy or of prolonged vaginal leakage. She was exclusively breast-fed, and there was no history of local trauma. On examination, the baby was toxic appearing with a temperature of 38.9°C, heart rate of 180 beats/min, respiratory rate of 68 breaths/min, oxygen saturation of 94% in ambient air and capillary refill time of <3 seconds. The baby had respiratory distress with subcostal and intercostal retractions, and on chest auscultation, bilateral crackles were heard.

El artesunato iv se recomienda actualmente como fármaco de elección en casos de malaria grave, con una disminución de mortalidad del 23% en ninos ˜ comparado con quinina. SE ha descrito la posibilidad de anemia hemolítica asociada a su uso.

Los  tres pacientes habían nacido en España,  sin antecedentes personales de malaria previa. Dos hermanas de 6 y 4 anos ˜ fueron diagnosticadas en nuestro centro de malaria grave por P. falciparum. Estancia reciente en Senegal sin profilaxis. Recibieron artesunato iv (2,4 mg/kg/dosis, cada 12 horas las dos primeras dosis, y cada 24 horas con posterioridad), con un número acumulado de 5 dosis la hermana mayor y 4 dosis en la menor, seguidos de piperaquina-artenimol durante 3 días. Ambas quedaron afebriles y con desaparición de la parasitemia en las primeras 48 horas. En controles analíticos, se objetivaron parámetros compatibles con anemia hemolítica a los 10 días del inicio del tto: descenso de hemoglobina hasta 7,4 mg/dl  en la hermana mayor y 6,3 mg/dl (en control de 5 días previos, hemoglobina 8,8 g/dL) en la menor, incremento de LDH hasta 751 U/L  y 1831U/L  respectivamente, niveles de haptoglobina indetectables y  Coombs negativo en los 2. Ante la sospecha de anemia hemolítica secundaria a artemisininas, y una vez descartadas hemoglobinopatías, se inició  prednisolona a 1 mg/kg/día durante 3 días con buena evolución

10-year-old previously healthy female admitted to our PICU due to an acute kidney injury (AKI) (creatinine clearance < 30 ml/min/1.73 m2), anemia (7.9 g/dl) with schistocytosis of 3.5% and thrombocytopenia (29,000/mm3). She was conscious and did not require respiratory or hemodynamical support (SpO2 100%, blood pressure 107/68 mmHg and heart rate (HR) 110 bpm). She was diagnosed as hemolytic-uremic syndrome (HUS), and supportive treatment with intravenous fluid therapy, bloodproducts, omeprazole and acetaminophen was started. The patient presented flu-like symptoms from the previous 48 h, and  H1N1 Influenza A  was detectedas the trigger agent.

 Treatment with oral Oseltamivir 30 mg od. (adjusted for AKI) was initiated. Twelve hours after the first dose we noticed a severe bradycardia on the cardiacmonitor, with a normal blood pressure …..

La ingesta de cuerpos extraños es un accidente frecuente en niños, representando el 70% de todos los casos de perforación, siendo el esófago la localización más frecuente 1. Las complicaciones derivadas de la perforación son raras. La perforación con migración del cuerpo extraño asociada, es aún más rara, pudiendo ocasionar complicaciones cervicales2.

Niña de 3 años que acude a urgencias por fiebre, sialorrea y lateralización del cuello. Antecedente de ingesta de pescado, seguido de dolor retroesternal y salivación. De forma urgente se realiza fibrobroncoscopia y gastroscopia, objetivando edema epiglótico, sin lograr identificar ningún cuerpo extraño.

Dada la persistencia de la clínica se completa el estudio con ecografía (fig. 1) y TC cervical (fig. 2) donde se observa flemón retrotraqueal y retrofaríngeo con formación de absceso tiroideo derecho secundario a perforación esofágica por espina de pescado migrada. Se realiza cervicotomía exploradora y faringoscopia rígida donde se identifica la espina de pescado a nivel cervical y perforación de la pared esofágica posterior, a la altura del esfínter esofágico superior.

La no detección del cuerpo extraño en la endoscopia, no descarta su presencia, por lo que, ante una clínica persistente es necesario llevar a cabo pruebas diagnósticas de imagen, para valorar su posible migración3.

Para profundizar

Importance  Studies suggest that postnatal cytomegalovirus (CMV) infection can lead to long-term morbidity in infants with very low birth weight (VLBW; <1500 g), including bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and neurodevelopmental impairment. However, to date, the association of postnatal CMV with hearing, growth, and length of stay among VLBW infants is unknown. Objectives  To determine the risk for failed hearing screen, increased postnatal age at discharge, or decreased growth at discharge in VLBW infants with postnatal CMV infection compared with CMV-uninfected infants and to compare the risk for other major outcomes of prematurity, including BPD and NEC, in infants with and without postnatal CMV infection. Participants  This multicenter retrospective cohort study included VLBW infants from 302 neonatal intensive care units managed by the Pediatrix Medical Group from January 1, 2002, through December 31, 2016. Infants hospitalized on postnatal day 21 with a diagnosis of postnatal CMV and hearing screen results after a postmenstrual age of 34 weeks were included in the study population. Data were analyzed from December 11, 2017, to June 14, 2019. Main Outcomes and Measures  Infants with and without postnatal CMV infection were matched using propensity scores. Poisson and linear regression were used to examine the association between postnatal CMV and the risk of failed hearing screen, postnatal age at discharge, growth, BPD, and NEC. Results  A total of 304 infants with postnatal CMV were identified, and 273 of these infants (89.8%; 155 boys [56.8%]) were matched with 273 infants without postnatal CMV (148 boys [54.2%]). Hearing screen failure occurred in 45 of 273 infants (16.5%) with postnatal CMV compared with 25 of 273 infants (9.2%) without postnatal CMV (risk ratio [RR], 1.80; 95% CI, 1.14 to 2.85; P = .01). Postnatal CMV was also associated with an increased postnatal age at discharge of 11.89 days (95% CI, 6.72 to 17.06 days; P < .001) and lower weight-for-age z score (−0.23; 95% CI, −0.39 to −0.07; P = .005). Analysis confirmed an increased risk of BPD (RR, 1.30; 95% CI, 1.17 to 1.44; P < .001), previously reported on infants from this cohort from 1997 to 2012, but not an increased risk of NEC after postnatal day 21 (RR, 2.00; 95% CI, 0.18 to 22.06; P = .57). Conclusions and Relevance  These data suggest that postnatal CMV infection is associated with lasting sequelae in the hearing and growth status of VLBW infants and with prolonged hospitalization. Prospective studies are needed to determine the full effects of postnatal CMV infection and whether antiviral treatment reduces the associated morbidity.

Infection with human cytomegalovirus (CMV) is ubiquitous, with a global seroprevalence of approximately 85%.1 In all human history, most CMV infections have probably been acquired from breastfeeding. Hayes et al2 in 1972 demonstrated that CMV could be cultured in breast milk, and breastfeeding was proposed as a mechanism by which the virus could be transmitted to the neonate. Subsequent work showed that such postnatal infections are generally innocuous in full-term infants,3 in contrast to the potentially devastating neurodevelopmental and audiological consequences of CMV infections acquired in utero.

·Meta-analysis of the Clinical Efficacy and Safety of High- and Low-dose Methylprednisolone in the Treatment of Children With Severe Mycoplasma Pneumoniae Pneumonia. The Pediatric Infectious Disease Journal. 39(3):177-183, March 2020.

Mycoplasma pneumoniae pneumonia is generally a self-limiting disease, but it can develop into severe Mycoplasma pneumoniae pneumonia (SMPP). Immunologic mechanisms are thought to play an important role in the pathogenesis of SMPP. Therefore, the use of systemic glucocorticoids may have beneficial effects. However, to date, the use of glucocorticoid therapy in SMPP is limited to small case series, and the glucocorticoid dosage for children with SMPP has not been established.

Methods: Here, we used a meta-analysis method to collect data from randomized control trials of different doses of methylprednisolone in SMPP to assess the safety and efficacy of treatment with low- versus high-dose methylprednisolone in children with SMPP.

Results: We included 13 Chinese randomized control trials that included 1049 children. The high- and low-dose groups were comprised of 524 and 525 children, respectively. The high-dose group was significantly more effective than the low-dose group in clinical efficacy [risk ratio = 1.30, 95% confidence interval (CI) (1.23, 1.38), P < 0.05]. In addition, compared with low-dose methylprednisolone, high-dose methylprednisolone significantly shortened hospital stays and antipyretic therapy, pulmonary rales disappearance, cough disappearance and pulmonary shadow absorption times. There was no significant difference in adverse events between the high- and low-dose groups: risk ratio= 0.85, 95% CI (0.53, 1.36), P > 0.05.

Conclusions: We conclude that high-dose methylprednisolone is effective in the treatment of SMPP without increasing the incidence of adverse reactions.

Introducción  La neumonía por Pneumocystis jirovecii (PJP) es una enfermedad potencialmente letal en niños inmunocomprometidos. Nuestro objetivo es analizar las características epidemiológicas y clínicas de la PJP, describiendo el pronóstico y los factores de riesgo.

Métodos  Estudio retrospectivo (enero 1989-diciembre 2016) de pacientes pediátricos (≤18 años) con PJP. Definición de caso: paciente con neumonitis aguda y detección de P. jirovecii en lavado broncolaveolar o aspirado traqueal usando tinción con plata-metenamina o inmunofluorescencia directa, o reacción en cadena de polimerasa en tiempo real.

Resultados. Se identificaron veinticinco casos (0,9 casos/año); edad mediana: 2,2 años (rango intercuartílico: 0,5-12,3), 64% de sexo masculino, y 12% bajo profilaxis anti-PJP. La coinfección por citomegalovirus se demostró en el 26%. Las enfermedades subyacentes más frecuentes fueron las inmunodeficiencias primarias (36%) y el 16% estaban infectados por el VIH. Dieciocho ingresaron en Cuidados Intensivos Pediátricos (UCIP) y la mortalidad global a los 30 días fue del 20% (31,25% en VIH- vs 0% VIH+; OR: 0,33 95%CI 0,02-7,24 p=0,55). El pronóstico fue peor en niñas y en aquellos que recibieron tratamiento adyuvante con corticoides. Se identificaron como factores de riesgo para ingreso en UCIP la ausencia de infección por VIH, valores iniciales elevados de LDH, menor edad y un período más corto entre el diagnóstico de PJP y la enfermedad subyacente (p=0,05, p=0,026, p=0,04 y p=0,001, respectivamente).

Conclusiones.  Tras la aplicación generalizada de la terapia antirretroviral, la PJP se diagnostica casi exclusivamente en niños no infectados por el VIH en los que, además, se identificó una mayor morbilidad.

Background Urinary tract infection (UTI) is a common childhood infection. Many febrile children require a urine sample to diagnose or exclude UTI. Collecting urine from young children can be time-consuming, unsuccessful or contaminated. Cost-effectiveness of each collection method in the emergency department is unknown.

Objective To determine the cost-effectiveness of urine collection methods for precontinent children.

Methods A cost-effectiveness analysis was conducted comparing non-invasive (urine bag, clean catch and 5 min voiding stimulation for clean catch) and invasive (catheterisation and suprapubic aspirate (SPA)) collection methods, for children aged 0–24 months in the emergency department. Costs included equipment, staff time and hospital bed occupancy. If initial collection attempts were unsuccessful subsequent collection using catheterisation was assumed. The final outcome was a definitive sample incorporating progressive dipstick, culture and contamination results. Average costs and outcomes were calculated for initial collection attempts and obtaining a definitive sample. One-way and probabilistic sensitivity analyses were performed.

Results For initial collection attempts, catheterisation had the lowest cost per successful collection (GBP£25.98) compared with SPA (£37.80), voiding stimulation (£41.32), clean catch (£52.84) and urine bag (£92.60). For definitive collection, catheterisation had the lowest cost per definitive sample (£49.39) compared with SPA (£51.84), voiding stimulation (£52.25), clean catch (£64.82) and urine bag (£112.28). Time occupying a hospital bed was the most significant determinant of cost.

Conclusion Catheterisation is the most cost-effective urine collection method, and voiding stimulation is the most cost-effective non-invasive method. Urine bags are the most expensive method. Although clinical factors influence choice of method, considering cost-effectiveness for this common procedure has potential for significant aggregate savings.

Background Neonates with congenital urinary tract dilatation (UTD) may have an increased risk of urinary tract infections (UTI). At present, the management of these patients is controversial and the utility of continuous antibiotic prophylaxis (CAP) remains uncertain as the literature presents contradicting evidence. The aim of this observational study was to assess UTI occurrence in children with prenatal diagnosis of urinary collecting system dilatation without antibiotic prophylaxis.

Methods Between June 2012 and August 2016, we evaluated the incidence of UTI and the clinical and ultrasonography evolution in 407 children with a prenatally diagnosed UTD. All subjects underwent two prenatal ultrasounds scans (USs) at 20 weeks and 30 weeks of gestation and within 1 month of birth. Patients with a confirmed diagnosis of UTD underwent US follow-up at 6, 12 and 24 months of life. According to the UTD classification system stratify risk, after birth UTD were classified into three groups: UTD-P1 (low risk group), UTD-P2 (intermediate risk group), and UTD-P3 (high risk group). Voiding cystourethrogram was performed in all patients who presented a UTI and in those with UTD-P3. No patient underwent CAP.

Results Postnatal US confirmed UTD in 278 out of 428 patients with the following rates: UTD-P1 (126), UTD-P2 (95) and UTD-P3 (57). During postnatal follow-up, 6.83% patients presented a UTI (19 out of 278). Eleven out of 19 had vesicoureteral reflux (VUR), and other four were diagnosed with obstructive uropathy and underwent surgical correction. Five patients presented a UTI reinfection.

Conclusion The occurrence of UTI in patients with urinary collecting system dilatation was low. The recent literature reports an increased selection of multirestistant germs in patients with VUR exposed to CAP. This study constitutes a strong hint that routine continuous antibiotic prophylaxis could be avoided in patients with UTD.

Urinary tract infections (UTI) are the most common bacterial infections among infants and young children with fever without a source. Extended-spectrum β-lactamases (ESBLs) have emerged as emerging cause of UTI globally; however, data about risk factors and clinical features of children with ESBL-UTI have been scarce.

Objective: To describe the predisposing risk factors, clinical and microbiologic features associated with pediatric UTIs caused by ESBL-producing bacteria (ESBL-PB).

Methods: Our nested case-control study ran from January 1, 2012 to December 31, 2016. Pediatric patients with ESBL-PB UTI were compared with patients with non-ESBL-PB UTI matched for age and year of diagnosis.

Results: A total of 720 children were enrolled (240 cases and 480 controls). Patients with ESBL-PB UTI were more likely to have a history of prior intensive care unit (ICU) admission (22.5% vs. 12.3%, P < 0.001), at least one underlying comorbidity (19.2% vs. 5.8%, P < 0.001), prior hospitalization (47.1% vs. 32.9%, P < 0.001), exposure to a cephalosporin antibiotic within 30 days before culture (7.5% vs. 4.2%, P = 0.035), and to have cystostomy (7.9% vs. 1.5%, P < 0.001) compared with those with non-ESBL-PB UTI. Patients with ESBL-PB UTI were more likely to present with hypothermia (48.8% vs. 38.5%, P = 0.009); had significantly longer average hospital stays {8.7 days [95% confidence interval (CI): 3.2–14.3] vs. 4.0 days (95% CI: 2.5–5.5)} and were more likely to be admitted to the ICU [odds ratio (OR) 1.8; 95% CI: 1.1-2.9). Multivariate analysis determined that only having cystostomy (OR 3.7; 95% CI: 1.4–9.4] and at least one underlying comorbidity (OR 2.4; 95% CI: 1.3–4.3) were the independent risk factors for ESBL-PB UTI. All ESBL-PB isolates tested against meropenem were susceptible, majority were resistant to multiple non-beta-lactam antibiotics.

Conclusions: Children with underlying comorbidities and cystostomy are at higher risk for ESBL-PB UTI, but majority of ESBL cases were patients without any known risk factors. Clinical signs/symptoms and commonly used biochemical markers were unreliable to differentiate cases caused by ESBL-PB from those caused by non-ESBL-PB. Further research is needed to elucidate the conditions most associated with ESBL-PB UTIs among children to properly guide empirical therapy in patients at-risk for these infections, to improve the outcomes, and finally, to determine strategies for rational antimicrobial use.

  • Selección del tratamiento antibiótico empírico en pielonefritis según el perfil del paciente. An Pediatr (Barc). 2020;92:181-2
     En nuestra opinión, existe una diferencia significativa en cuanto a microorganismos aislados y resistencias entre los lactantes con su primera ITU alta, y aquellos que la presentan teniendo antecedentes de uropatía conocida, ya estén intervenidos o instrumentalizados en el entorno sanitario, con o sin profilaxis previa, siendo un porcentaje importante de los episodios, de repetición.
    Presentamos nuestra experiencia de microorganismos aislados en pielonefritis entre 2013-2017 .Se observa una diferencia claramente significativa en los aislamientos microbiológicos de ambos grupos . Un análisis bayesiano tipos (WISCA)2–4sobre la sensibilidad a los distintos antibióticos generalmente indicados empíricamente, así como a combinaciones de biterapia, muestra como en el grupo de primera infección urinaria febril sin antecedentes conocidos de uropatía se mantiene una aceptable sensibilidad a amoxicilina-clavulánico (87%) en nuestro medio, lo que nos permite su uso empírico con seguridad, tanto oral como intravenosa. En cambio, en el grupo con uropatía conocida, las resistencias en monoterapia de amoxicilina-clavulánico, cefotaxima, ceftazidima y gentamicina superan el umbral de seguridad (38,5, 38,8, 25 y 18%, respectivamente) probablemente con relación a que aproximadamente la mitad de los aislamientos se trataba de enterobacterias no coliPseudomonas aeruginosa y Enterococcus, añadido a un porcentaje del 17% de productores de betalactamasas de espectro extendido. A la vista de los resultados, nosotros optamos por una terapia empírica con amoxicilina-clavulánico tanto oral sin ingreso hospitalario, como intravenosa con ingreso, en el primer grupo, con buenos resultados validados en el último año y que obviaría los problemas de desabastecimiento temporales de cefalosporinas (cefuroxima axetilo y cefixima). En cuanto al segundo grupo, la biterapia con ampicilina o amoxicilina-clavulánico en combinación con gentamicina o amikacina alcanza sensibilidades de hasta el 99% permitiendo el ahorro de otras opciones empíricas de mayor espectro e inducción de resistencias, como cefalosporinas de tercera generación, quinolonas y carbapenémicos. Su empleo estaría, no obstante, condicionado a un filtrado glomerular normal, monitorización de niveles y sustitución por alternativa según antibiograma cuanto antes.
     Nuestra propuesta es que se distingan, al menos, estos 2 grupos diferenciados en los futuros estudios epidemiológicos de resistencias, tratamientos empíricos y recomendaciones de consenso.
  • Ecografía clínica en la infección del trato urinario. An Pediatr (Barc). 2020;92:182-3
     Igual que se proponen una serie de signos y síntomas clínicos compatibles con la infección urinaria, creemos que deberían considerarse también los criterios ecográficos característicos de la misma.

En el caso de infección urinaria baja las características ecográficas de la vejiga pueden ser determinantes para su diagnóstico topográfico. La pared vesical engrosada en vejiga distendida (>3mm), su espesor disuniforme a modo de «mamelones» y/o la presencia de contenido hiperecogénico y móvil, en un contexto clínico compatible, son muy sugerentes de cistitis infecciosa.

Si bien es cierto que ante una pielonefritis aguda no complicada podemos tener una ecografía del aparato excretor normal, hay signos característicos de un mayor grado de afectación como son el aumento del tamaño renal (global o focal), alteraciones de ecogenicidad (aumentada o disminuida) con respecto al resto del parénquima renal, pérdida de diferenciación córtico-medular y engrosamiento de las paredes de la pelvis renal o de los uréteres.

Es admitido que la ecografía es la prueba diagnóstica de elección para el estudio inicial del tracto urinario en pediatría (tabla 1).

  • Respuesta a las recomendaciones sobre el diagnóstico y tratamiento de la infección urinaria. An Pediatr (Barc). 2020;92:183-4

    Las recientes recomendaciones publicadas por Piñeiro et al.1 consideran, si se realiza sondaje vesical, bacteriuria significativa>10.000UFC/ml. Sin embargo, en la Guía de práctica clínica de infección del tracto urinario de la Academia Americana de Pediatría (AAP), publicada en 20112 y revisada en 2016, se define infección del tracto urinario (ITU) en los pacientes de 2 a 24 meses como la presencia de piuria y>50.000UFC/ml de un único patógeno.    Las guías europeas publicadas recientemente. Wolf et al.4 y otros autores definen ITU como la presencia de piuria y>10.000UFC/ml o>50.000UFC/ml de un único patógeno de orina obtenida por sondaje vesical. La bibliografía publicada hace pensar que el diagnóstico de ITU podría definirse como la presencia de>50.000UFC/ml de un único patógeno, o 10.000-50.000UFC y piuria asociada.
           En cuanto al tratamiento ambulatorio recomiendan cefixima con En la bibliografía médica reciente no existen estudios en los que se compare la pauta vía oral de cefixima de doble dosis el primer día con la dosis estándar. Tanto en la Guía de práctica clínica de infección del tracto urinario de la AAP publicada en 20112, como en el protocolo de infección urinaria de la Asociación Española de Pediatría6, se indica la pauta de cefixima 8mg/kg/día.El hecho de que no existan estudios comparativos de ambas posologías vía oral, el que haya discrepancias en cuanto a la pauta más adecuada para el tratamiento de la ITU en diversas publicaciones y que el pautar doble dosis el primer día sea una pauta diferente a la establecida en la ficha técnica, pudiendo inducir errores en la dosificación del fármaco, hace pensar que la pauta más adecuada para el tratamiento ambulatorio sea cefixima 8mg/kg/día.
  • «Recomendaciones sobre el diagnóstico y tratamiento de la infección urinaria», respuesta de los autores. An Pediatr (Barc). 2020;92:184-6
    Con respecto a la réplica de Lorente y Vázquez2, aunque la American Academy of Pediatrics mantiene el punto de corte en ≥ 50.000UFC/ml para considerar bacteriuria significativa en orinas recogidas mediante sondaje vesical, existen otros estudios3 que recomiendan bajar el límite a ≥ 10.000UFC/ml. Igualmente, hay publicaciones4 que consideran que el diagnóstico de ITU. puede establecerse si hay fiebre, piuria y un recuento ≥ 10.000UFC/ml, sin afectar la especificidad y aumentando la sensibilidad. Recientemente, una amplia revisión5 concluye que establecer el diagnóstico con ≥ 10.000UFC/ml aumenta la sensibilidad sin disminuir la especificidad, por lo que ayudaría a evitar el infradiagnóstico. Sin embargo, un metaanálisis6 publicado también en 2019 resume que el punto de corte más idóneo sea ≥ 100.000UFC/ml, con independencia del método de recogida . Es decir, la evidencia es insuficiente en la actualidad. En el documento de recomendaciones1 se ha optado por la opción con mayor sensibilidad.
                 En relación con la dosificación doble de cefixima el primer día de tratamiento, la recomendación se basa en el clásico estudio de Hoberman et al.7, si bien debería ajustarse a los menores de 2 años tal y como se detalla en el artículo  y en el Pediamécum8.
             Con respecto a la réplica de Oltra-Benavent et al.9, en el documento de recomendaciones se realizan propuestas basadas en los patrones de susceptibilidad descritos en la literatura revisada1. De forma paralela al desarrollo de dicho documento, el Grupo de Trabajo coordinó un estudio nacional de susceptibilidad en 1.200 ITU pediátricas. El microrganismo predominante fue Escherichia coli (E. coli) (> 80%). Un 19% de los niños presentaron malformación urinaria, un 6,7% recibía profilaxis antibiótica y un 8,5% había recibido antibióticos el mes anterior. En la tabla 1 se muestra un extracto de la sensibilidad frente a diferentes antimicrobianos. Mediante análisis de regresión logística, el único factor de riesgo asociado con la presencia de bacterias productoras de betalactamasas de espectro extendido (BLEE) fue la profilaxis antimicrobiana11.
  • Timing of voiding cystourethrography after febrile urinary tract infection in children: a systematic review Arch Dis Child. 2020 Mar;105(3):264-269

Background Despite a trend towards early voiding cystourethrography (VCUG) after febrile urinary tract infection (fUTI) in children, clinical guidelines do not comment on the optimal timing and current practice varies considerably.

Objective To assess whether the detection rate of vesicoureteric reflux (VUR) in children depends on the time period of VCUG procedure after onset of antibiotic therapy.

Methods MEDLINE, EMBASE and Cochrane Controlled Trials Register electronic databases were searched for eligible studies without language or time restriction (19 November 2018). Inclusion criteria were (1) patients <18 years of age; (2) VCUG performed in patients with fUTI after onset of antibiotic therapy either in the same patient population or in two or more different patient populations within one study at different time periods; and (3) with reported detection rate of VUR. The systematic review was carried out following the recommendations of the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Results Of 4175 records, nine studies were included (number of patients, n=1745) for the main outcome prevalence of VUR by VCUG <8 days compared with VCUG ≥8 days after onset of antibiotic therapy. Pooled overall prevalence of VUR was not significantly different between the early and the late VCUG groups (risk ratio 0.98, 95% CI 0.81 to 1.19). Prevalence of VUR stratified by grade was not significantly different between the two groups.

Conclusion Early VCUG within 8 days after onset of antibiotic therapy does not affect the prevalence of VUR.

·A Pharmacoepidemiologic Study of the Safety and Effectiveness of Clindamycin in Infants. The Pediatric Infectious Disease Journal. 39(3):204-210, March 2020.

Despite the absence of adequate safety or efficacy data, clindamycin is widely prescribed in the neonatal intensive care unit. We evaluated the association between clindamycin exposure and adverse events, as well as antibiotic effectiveness in infants.

Methods: This was a retrospective cohort study of infants receiving clindamycin before postnatal day 121 who were discharged from a Pediatrix Medical Group neonatal intensive care unit (1997–2015). Using a previously developed pharmacokinetic model, we performed simulations to predict clindamycin exposure based on available dosing data. We used multivariable logistic regression to evaluate the association between clindamycin exposure and safety outcomes during and after clindamycin therapy. We reported the proportion of infants with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and clearance of MRSA bacteremia.

Results: A total of 4089 infants received clindamycin at a median (25th–75th percentile) dose of 15 mg/kg/d (12–16). Clearance increased with older gestational age. Infants with the highest total clindamycin exposure had marginally increased odds of necrotizing enterocolitis within 7 days (adjusted odds ratio = 1.95 [1.04–3.63]), but exposure was not associated with death, sepsis, seizures, intestinal perforation or intestinal strictures. Of 25 infants who had MRSA bacteremia, 19 (76%) cleared the infection by the end of the clindamycin course.

Conclusions: Higher clindamycin exposure was not associated with increased odds of death or nonlaboratory adverse events. The use of pharmacokinetic models combined with available electronic health record data offers a valuable, cost-effective approach to analyzing the safety and effectiveness of drugs in infants when large-scale trials are not feasible.

An 8-year-old boy with poorly controlled asthma presents to respiratory clinic. Two months ago, he had an asthma exacerbation while outside the UK and was prescribed azithromycin. His mother has continued giving it to him, as she feels it improves his respiratory symptoms.

Structured clinical question In children with asthma (population), is adjunctive macrolide therapy (intervention) beneficial in treating exacerbations and/or persistent uncontrolled symptoms (outcomes)?

As the technology has arrived to test newborns' urine or saliva samples by polymerase chain reaction (PCR) for congenital infection due to cytomegalovirus (cCMV), the “who” of screening is as yet unsettled. The “why” of screening would be to detect infants with extant or risk to develop hearing loss as a sequelae of cCMV infection. Should screening be universal, ie, to include all healthy newborns and all potential infections? Or should it be targeted, eg, to infants who fail the newborn screening test for hearing (NBHS), which would miss some infected infants who could lose hearing over time? With the additional lack of understanding of the “what to do” with a positive PCR test result, or knowledge of potential unintended consequences of labeling for parents their infants as cCMV-infected, 11 state legislatures (starting with Utah in 2013) have enacted laws to mandate targeted screening for cCMV of infants failing NBHS, or educational programs about cCMV, or both.

Objectives To understand caregiver knowledge of and attitudes toward congenital cytomegalovirus (cCMV) testing in Utah.

Study design We surveyed 365 caregivers whose children were being seen in an otolaryngology clinic at a tertiary pediatric hospital about their knowledge of and attitudes toward cCMV and cCMV screening. Descriptive statistics and cluster analysis were used to examine their responses.

Results The majority of caregivers were unsure how cCMV was spread, the symptoms of cCMV, and why cCMV screening of infants was important. Most caregivers did not know that cCMV screening was required by law in Utah if an infant is referred after newborn hearing screening. A majority wanted to know if their child had cCMV even if asymptomatic and were willing to pay $20 for cCMV screening. Caregivers of children who had been tested for cCMV were significantly more likely to be strongly in favor of cCMV screening than expected by chance. Caregivers in the highly knowledgeable cluster were more likely to be strongly in favor of cCMV screening.

Conclusions Caregivers frequently were unaware of cCMV and its implications. Attitudes toward cCMV screening generally were positive. Education on epidemiology and impact of cCMV may benefit both prevention of infection and attitudes toward screening.

Two months after the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the possibility of established and widespread community transmission in the European Union and European Economic Area (EU/EEA) is becoming more likely. We provide scenarios for use in preparedness for a possible widespread epidemic. The EU/EEA is moving towards the ‘limited sustained transmission’ phase. We propose actions to prepare for potential mitigation phases and coordinate efforts to protect the health of citizens.

The centrally coordinated response that controlled the polio epidemics of the 1950s through immunisation led to the development of a national immunisation strategy in the UK and the formation of the Joint Committee on Vaccination and Immunisation (JCVI) in 1963, which oversees the immunisation programme and advises the UK Department of Health on new vaccine introductions. As a result of technological advances in vaccine development and scientific advances in immunology and microbiology over the 56 years since then, and the formation of a comprehensive public health surveillance system for vaccine-preventable disease, the National Health Service immunisation programme now covers 18 serious diseases of childhood, with an astonishing impact on child health. Here we consider the formation of the JCVI and the development of the national immunisation programme and review the introduction of vaccines over the past half century to defend public health.

·The Importance of Echocardiogram during the Second Week of Illness in Children with Kawasaki Disease. J Pediatr. 2020 Mar;218:72-77.e1.

Objective To determine the timing of peak coronary artery dilation and the characteristics of patients who present with new-onset coronary artery dilation during the acute phase of Kawasaki disease with an initial normal echocardiogram.

Study design This retrospective study analyzed 231 children hospitalized for Kawasaki disease in Hawai'i over a period of 7 years. Clinical and echocardiographic data were collected to calculate the timing of peak z score, and study subjects were compared based on the timing of coronary dilation.

Results Peak coronary artery dilation was observed on average at 11.5 days from the onset of fever (median 8, IQR 7-13 days). Among study subjects with normal z scores in both coronary arteries during the initial encounter and echocardiogram (n = 164), 16 (10%) developed coronary artery dilation or aneurysm at the second echocardiogram, and 5 (3%) continued to have coronary artery dilation or aneurysm at the convalescent phase.

Conclusions A repeat echocardiogram during the second week of illness (day 7-14 from fever onset) in patients with normal initial echocardiogram could identify new-onset coronary artery dilation or aneurysm and could be useful in the timely adjustment of antithrombotic or anti-inflammatory therapies.

Among unimmunized children who contract measles, what is the subsequent effect on the humoral immune system?

·Sepsis prediction model derived from hospital-arrival clinical data. J Pediatr. 2020 Mar;218:259-262

Among children presenting to emergency departments (EDs) or urgent care sites, what is the diagnostic accuracy of clinical criteria at the time of arrival, compared with a septic shock definition, in detecting septic shock within the first 24 hours?

The Archivist has seen the impact of Sepsis six and now, Sepsis three with concern about the over use of antibiotics and antimicrobial resistance. Rudd KE et al (Lancet 2020;395(10219):200–211 https://doi.org/10.1016/S0140-6736(19)32989-7] gives us an important reminder about the worldwide seriousness and impact of this devastating disease. The Global Burden of Disease (GBD) is a group of more than 3600 researchers examining health issues from around the world. GBD 2017 reports on 282 underlying causes of death in 195 countries. This group has estimated the global, regional, and national incidence …

Introducción. Las infecciones son una causa importante de morbimortalidad en los pacientes con cáncer (mortalidad estimada en 3%). La neutropenia febril conlleva con frecuencia el ingreso hospitalario de los pacientes oncológicos, incrementando el riesgo de infección nosocomial así como los costes sanitarios por ingresos.

Métodos. Estudio observacional ambispectivo (01/07/2015 - 31/12/2018) de los episodios de neutropenia febril posquimioterapia en población pediátrica. Se recogieron edad, sexo, percentil de peso (OMS), estancia hospitalaria (días), temperatura (oC), aislamiento de germen, foco infeccioso, profilaxis o no antibiótica y antifúngica, cifras de hemoglobina (g/dl), plaquetas (/mm3), neutrófilos (/mm3), linfocitos (/mm3), monocitos (/mm3), proteína C reactiva (PCR) (mg/L) y procalcitonina (PCT) (ng/ml) al ingreso y días con neutropenia<500/mm3. El análisis estadístico se realizó con el programa SPSSv.23.

Resultados. De 69 pacientes, se registraron 101 episodios. La estancia media fue de 7,43 días (mediana 6 días). Se aisló germen en un 44,6% de los episodios, no identificándose foco infeccioso en un 36% de los mismos. Se halló correlación inversa entre hemoglobina, plaquetas y linfocitos al ingreso con la estancia hospitalaria (-0,356 (p 0,001); -0,216 (p 0,042) y -0,216 (p 0,042) respectivamente). La estancia media fue mayor si al ingreso presentaron PCR>90mg/L (10,94 vs. 6,66 días p 0,017), si PCT>1ng/ml (16,50 vs. 6,77 días p 0,0002), si ≤100 neutrófilos (8,27 vs. 5,04 días p 0,039) y si hubo aislamiento microbiológico (9,54 vs. 5,78 días p 0,006).

Conclusión La relación entre hemoglobina, plaquetas y linfocitos al ingreso con la estancia media es inversamente proporcional. Además, aquellos pacientes con ≤100 neutrófilos al ingreso, PCR>90mg/L y PCT>1ng/ml presentaron mayor estancia media. Estos factores podrían ser importantes en el manejo de la neutropenia febril en el paciente con cáncer infantil.

·COVID-19 in 2 Persons with Mild Upper Respiratory Tract Symptoms on a Cruise Ship, Japan. CDC Volume 26, Number 6—June 2020

  • A case of 2019 Novel Coronavirus in a pregnant woman with preterm delivery, Clinical Infectious Diseases, , ciaa200, https://doi.org/10.1093/cid/ciaa200

We presented a case of a 30-week pregnant woman with COVID-19 delivering a healthy baby with no evidence of COVID-19. 

 


·Co-infection with SARS-CoV-2 and Influenza A Virus in Patient with Pneumonia, China CDC  Volume 26, Number 6—June 2020

·Severe Acute Respiratory Syndrome Coronavirus 2 from Patient with 2019 Novel Coronavirus Disease, United States. CDC Volume 26, Number 6—June 2020

TOP TEN:

Novel Coronavirus Infection in Hospitalized Infants Under 1 Year of Age in ChinaJAMA. Published online February 14, 2020. doi:10.1001/jama.2020.2131

Based on the sources of data used in this study, 9 infants were infected with COVID-19 and were hospitalized in China between December 2019 and February 6, 2020. Given the number of infections reported, the number of infected infants identified was small. This may be due to a lower risk of exposure or incomplete identification due to mild or asymptomatic disease, rather than resistance to infection.1,5 However, this study showed that infants can be infected by COVID-19; the earlier stage of the COVID-19 epidemic primarily involved adults older than 15 years.2-4Family clustering occurred for all infected infants. Infants who have infected family members should be monitored or evaluated and family clustering should be reported to ensure a timely diagnosis. Seven of the 9 infant patients were female. Previous studies found higher percentages of infection in men than women.2-4 Whether female infants may be more susceptible to COVID-19 infection than male infants requires further study. The study was limited by small sample size, inclusion only of infants who were hospitalized, and lack of inclusion of asymptomatic patients. Although a systematic and comprehensive search was made for relevant infections in infants, the epidemic is spreading rapidly and incomplete identification of cases is possible. Because infants younger than 1 year cannot wear masks, they require specific protective measures. Adult caretakers should wear masks, wash hands before close contact with infants, and sterilize the infants’ toys and tableware regularly.

PARA PROFUNDIZAR

Coronavirus Infections—More Than Just the Common ColdJAMA. 2020;323(8):707–708. doi:10.1001/jama.2020.0757

Human coronaviruses (HCoVs) have long been considered inconsequential pathogens, causing the “common cold” in otherwise healthy people. However, in the 21st century, 2 highly pathogenic HCoVs—severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)—emerged from animal reservoirs to cause global epidemics with alarming morbidity and mortality. In December 2019, yet another pathogenic HCoV, 2019 novel coronavirus (2019-nCoV), was recognized in Wuhan, China, and has caused serious illness and death. The ultimate scope and effect of this outbreak is unclear at present as the situation is rapidly evolving. 

Association of Adverse Hearing, Growth, and Discharge Age Outcomes With Postnatal Cytomegalovirus Infection in Infants With Very Low Birth Weight. JAMA Pediatr. 2020;174(2):133–140. doi:10.1001/jamapediatrics.2019.4532

Importance  Studies suggest that postnatal cytomegalovirus (CMV) infection can lead to long-term morbidity in infants with very low birth weight (VLBW; <1500 g), including bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and neurodevelopmental impairment. However, to date, the association of postnatal CMV with hearing, growth, and length of stay among VLBW infants is unknown. Objectives  To determine the risk for failed hearing screen, increased postnatal age at discharge, or decreased growth at discharge in VLBW infants with postnatal CMV infection compared with CMV-uninfected infants and to compare the risk for other major outcomes of prematurity, including BPD and NEC, in infants with and without postnatal CMV infection. Participants  This multicenter retrospective cohort study included VLBW infants from 302 neonatal intensive care units managed by the Pediatrix Medical Group from January 1, 2002, through December 31, 2016. Infants hospitalized on postnatal day 21 with a diagnosis of postnatal CMV and hearing screen results after a postmenstrual age of 34 weeks were included in the study population. Data were analyzed from December 11, 2017, to June 14, 2019. Main Outcomes and Measures  Infants with and without postnatal CMV infection were matched using propensity scores. Poisson and linear regression were used to examine the association between postnatal CMV and the risk of failed hearing screen, postnatal age at discharge, growth, BPD, and NEC. Results  A total of 304 infants with postnatal CMV were identified, and 273 of these infants (89.8%; 155 boys [56.8%]) were matched with 273 infants without postnatal CMV (148 boys [54.2%]). Hearing screen failure occurred in 45 of 273 infants (16.5%) with postnatal CMV compared with 25 of 273 infants (9.2%) without postnatal CMV (risk ratio [RR], 1.80; 95% CI, 1.14 to 2.85; P = .01). Postnatal CMV was also associated with an increased postnatal age at discharge of 11.89 days (95% CI, 6.72 to 17.06 days; P < .001) and lower weight-for-age z score (−0.23; 95% CI, −0.39 to −0.07; P = .005). Analysis confirmed an increased risk of BPD (RR, 1.30; 95% CI, 1.17 to 1.44; P < .001), previously reported on infants from this cohort from 1997 to 2012, but not an increased risk of NEC after postnatal day 21 (RR, 2.00; 95% CI, 0.18 to 22.06; P = .57). Conclusions and Relevance  These data suggest that postnatal CMV infection is associated with lasting sequelae in the hearing and growth status of VLBW infants and with prolonged hospitalization. Prospective studies are needed to determine the full effects of postnatal CMV infection and whether antiviral treatment reduces the associated morbidity.

 

También dedican una editorial a ello: Breast Milk–Acquired Cytomegalovirus in Premature Infants: Uncertain Consequences and Unsolved Biological Questions. JAMA Pediatr. 2020;174(2):121–123. doi:10.1001/jamapediatrics.2019.4538

Bibliografía febrero 2020

TOP TEN

·         Prevalence of Asymptomatic Bacteriuria in Children: A Meta-Analysis. J Pediatr. 2019 Nov 28. pii: S0022-3476(19)31343-5

To determine the point prevalence of bacteriuria and bacteriuria without pyuria in asymptomatic children by a systematic review of the literature.

We searched MEDLINE and EMBASE for English-, French-, German-, Italian-, and Spanish-language articles. We included articles reporting data on bacteriuria in asymptomatic children up to 19 years of age who had urine collected by suprapubic bladder aspiration, bladder catheterization, or by 3 consecutive clean catch samples. Two independent reviewers assessed studies for inclusion and abstracted data.

Fourteen studies (49 806 children) were included. The prevalence of asymptomatic bacteriuria was 0.37% (95% CI, 0.09-0.82) in boys and 0.47% (95% CI, 0.36-0.59) in girls. The corresponding values for asymptomatic bacteriuria without pyuria were 0.18% (95% CI, 0.02-0.51) and 0.38% (95% CI, 0.22-0.58), respectively. The subgroups with the highest prevalence of asymptomatic bacteriuria were uncircumcised males <1 year of age and females >2 years of age. In males, the prevalence of asymptomatic bacteriuria after infancy was 0.08% (95% CI, 0.01-0.37). The median duration of asymptomatic bacteriuria in untreated boys and girls, from the one study reporting this outcome, was 1.5 and 2 months, respectively.

Some clinicians are concerned that when a preverbal child with asymptomatic bacteriuria develops a nonlocalizing febrile illness and presents for evaluation, they may be mistakenly diagnosed as having a urinary tract infection (UTI). Given that the prevalence of asymptomatic bacteriuria is considerably lower than the prevalence of UTI in most subgroups examined, this will occur extremely rarely. These data suggest that the current definition of UTI should be revisited.

·         Tratamiento del acné: actualización, CADIME

El acné es una dermatosis crónica de presentación clínica variable y con frecuencia mixta, que requiere tratamiento farmacológico hasta en un 30% de los casos. - La selección del tratamiento debe ser individualizada, en función de la gravedad, la presentación clínica, las posibles secuelas psicológicas y la afectación de la calidad de vida. - En general se recomienda un tratamiento escalonado y progresivo, siendo la primera opción -para los casos leves- el tratamiento tópico (en monoterapia o asociación), en segundo lugar, la asociación de fármacos tópicos con antibióticos orales y finalmente los retinoides sistémicos (isotretinoína oral) o los anticonceptivos orales (en mujeres). - Para reducir el riesgo de resistencias, se recomienda que los antibióticos no se utilicen nunca como tratamiento de primera línea, de mantenimiento, ni en monoterapia, limitar su administración (≤ 3-4 meses) y no asociar antibióticos tópicos y orales. - El tratamiento debe evaluarse a los 2-3 meses (1-2 meses los antibióticos) y si la respuesta es inadecuada, antes de pasar al siguiente escalón, probar todas las opciones posibles y descartar otras posibles causas de ineficacia. - Los retinoides (tópicos y sistémicos) están contraindicados en embarazadas; y las mujeres tratadas con isotretinoína oral con capacidad de gestación, deben seguir el “Plan de prevención de embarazos”. - Los pacientes que precisen tratamiento con isotretinoína oral requieren un seguimiento especial y deben derivarse a dermatología. También deben derivarse: los pacientes con acné cicatrizante; efectos adversos graves; intolerancia a los tratamientos habituales; recidiva tras tratamiento sistémico; o, alteraciones endocrinas. - Tras finalizar un tratamiento de choque, se recomienda tratamiento de mantenimiento tópico para prevenir las recaídas en todos los pacientes, excepto en los tratados con isotretinoína oral. - Independientemente del tratamiento farmacológico, todos los pacientes con acné deberían seguir las medidas complementarias, pero no parece necesario modificar la dieta.

·         Acute Otitis MediaJAMA Pediatr. Published online January 27, 2020. doi:10.1001/jamapediatrics.2019.5664

 

·         Periorbital and Orbital Cellulitis. JAMA. 2020;323(2):196. doi:10.1001/jama.2019.18211. https://bit.ly/2UadMnv

·         Cryptosporidiosis. JAMA. 2020;323(3):288. doi:10.1001/jama.2019.18691. https://bit.ly/37NhK9I

 

·         Bacterial Reservoirs in the Middle Ear of Otitis-prone Children Are Associated With Repeat Ventilation Tube Insertion The Pediatric Infectious Disease Journal. 39(2):91-96, February 2020.

Repeat ventilation tube insertion (VTI) is common in children with recurrent acute otitis media (rAOM). Identifying risk factors associated with repeat surgery will improve clinical management and prevent repeat VTI.

Surgical records were assessed at 8 years following VTI surgery for rAOM in children 6–36 months of age. Children were grouped according to detection of bacterial otopathogen in their middle ear effusion (MEE) at the time of VTI, and outcomes for future otorhinolaryngology surgery compared.

Age, gender, pneumococcal vaccination status, antibiotic usage, day-care attendance, number of siblings and number of AOM episodes were similar between groups. Of the 63 children who had PCR +ve MEE, 58.7% required repeat VTI compared with 31.4% of the 51 children with no otopathogen detected in their MEE (odds ratio = 3.1, 95% confidence interval [1.4–6.8]; P = 0.004). Nontypeable Haemophilus influenzae (NTHi) was the predominant otopathogen in MEE (79% of all PCR +ve MEE). Respiratory virus detection was not associated with repeat VTI.

Presence of bacterial otopathogen, specifically nontypeable H. influenzae, in the middle ear during VTI was a predictor of children at-risk of repeat VTI. Here, we identify a modifiable microbiologic factor for repeat VTI that can be targeted to improve clinical management of rAOM.

·         Changes in Otitis Media Episodes and Pressure Equalization Tube Insertions Among Young Children Following Introduction of the 13-Valent Pneumococcal Conjugate Vaccine: A Birth Cohort–based Study, Clinical Infectious Diseases, Volume 69, Issue 12, 15 December 2019, Pages 2162–2169, https://doi.org/10.1093/cid/ciz142

Background. The impact of 13-valent pneumococcal conjugate vaccine (PCV13) introduction on the occurrence of first and subsequent otitis media (OM) episodes in early childhood is unclear. We compared the risk of OM episodes among children age <2 years before and after PCV13 introduction, accounting for the dependence between OM episodes.

Methods. We identified consecutive annual (July–June) cohorts of Tennessee Medicaid–enrolled children (2006–2014) from birth through age 2 years. We identified OM episodes using coded diagnoses (we classified diagnoses <21 days apart as the same episode). We modeled adjusted hazard ratios (aHRs) for OM comparing 7-valent pneumococcal conjugate vaccine (PCV7)–era (2006–2010) and PCV13-era (2011–2014) birth cohorts, accounting for risk factors and dependence between first and subsequent episodes. Secondary analyses examined pressure equalization tube (PET) insertions and compared the risk of recurrent OM (≥3 episodes in 6 months or ≥4 episodes in 12 months) between PCV7- and PCV13-era birth cohorts.

Results. We observed 618 968 OM episodes and 24 875 PET insertions among 368 063 children. OM and PET insertion rates increased during the PCV7 years and declined after PCV13 introduction. OM and PET insertion risks were lower in the 2013–2014 cohort compared with the 2009–2010 cohort (aHRs [95% confidence interval], 0.92 [.91–.93] and 0.76 [.72–.80], respectively). PCV13 introduction was associated with declines in the risk of first, subsequent, and recurrent OM.

Conclusions. The transition from PCV7 to PCV13 was associated with a decline of OM among children aged <2 years due to a reduction in the risk of both the first and subsequent OM episodes.

·         Studies Support HPV Safety. JAMA. 2020;323(4):302. doi:10.1001/jama.2019.21289. https://bit.ly/2S8VRLr

With more than 28 million doses administered since 2014, the CDC hasn't identified any new or unexpected safety concerns with the human papillomavirus vaccine, according to a pair of CDC studies published in Pediatrics.

The first study mined data from 7244 reports of adverse events after administration of the 9-valent human papillomavirus vaccine (9vHPV) submitted to the Vaccine Adverse Event Reporting System (VAERS) between December 2014 and December 2017. About 97% of the reports weren't serious. The most commonly reported adverse events were dizziness, syncope, headache, and injection site reactions. The authors reported 2 verified deaths after use of the vaccine but found no evidence that the vaccine caused the deaths. The overall rate of adverse event reports was 259 per million doses of 9vHPV and 7 serious adverse event reports per million doses.

"No new or unexpected safety concerns or reporting patterns of 9vHPV with clinically important [adverse events] were detected," the authors concluded. They note that their data were consistent with prelicensure safety data and with safety data from the previous quadrivalent HPV vaccine.

The second study provided near real-time surveillance of 9vHPV-associated adverse events using electronic records from Vaccine Safety Datalink sites from October 2015 to October 2017. During the 105 weeks of surveillance, 838 991 doses of the vaccine were given. Unexpected signals for a statistical relationship between vaccination and appendicitis among boys aged 9 to 17 years after the third dose, pancreatitis among men aged 18 to 26 years, and allergic reactions in girls and women after the second dose were identified. However, further analysis didn't confirm any safety signals for those events.

"With this large observational study, we contribute reassuring postlicensure data that will help bolster the safety profile of 9vHPV," the second study's authors wrote.

·         Tonsillectomy for periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA). Cochrane Database of Systematic Reviews 2019, Issue 12. Art. No.: CD008669. DOI: 10.1002/14651858.CD008669.pub3

The evidence for the effectiveness of tonsillectomy in children with PFAPA syndrome is derived from two small randomised controlled trials. These trials reported significant beneficial effects of surgery compared to no surgery on immediate and complete symptom resolution (NNTB = 2) and a substantial reduction in the frequency and severity (length of episode) of any further symptoms experienced. However, the evidence is of moderate certainty (further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate) due to the relatively small sample sizes of the studies and some concerns about the applicability of the results. Therefore, the parents and carers of children with PFAPA syndrome must weigh the risks and consequences of surgery against the alternative of using medications. It is well established that children with PFAPA syndrome recover spontaneously and medication can be administered to try and reduce the severity of individual episodes. It is uncertain whether adenoidectomy combined with tonsillectomy adds any additional benefit to tonsillectomy alone.

·         Racecadotril for acute diarrhoea in children. Cochrane Database of Systematic Reviews 2019, Issue 12. Art. No.: CD009359. DOI: 10.1002/14651858.CD009359.pub2

The review authors searched for available trials and included seven trials. The trials were conducted in a total of 1140 children aged from 3 months to 5 years. Children who were given racecadotril were compared to a control group (children who, instead of racecadotril, received a placebo (a dummy drug that contains no racecadotril) or no drug). The review shows that when children with diarrhoea were given racecadotril, compared to placebo or no drug:

• racecadotril may reduce the risk of rehydration failure (low-certainty evidence); • we are uncertain whether or not racecadotril shortens duration of diarrhoea (very low-certainty evidence); • we are uncertain whether racecadotril influences the number of stools (very low-certainty evidence); • racecadotril may reduce weight of stool output (low-certainty evidence); • racecadotril may make little or no difference to length of hospital stay for inpatients (low-certainty evidence); • racecadotril may make little or no difference to rates of side-effect events (low-certainty evidence)

·         Sequential inactivated (IPV) and live oral (OPV) poliovirus vaccines for preventing poliomyelitis. Cochrane Database of Systematic Reviews 2019, Issue 12. Art. No.: CD011260. DOI: 10.1002/14651858.CD011260.pub2

IPV-OPV compared to OPV may reduce VAPPs (vaccine-associated paralytic polio) without affecting vaccination coverage, safety or humoral response, except P2 with sequential schemes without P2 components, but increase poliovirus faecal excretion after OPV challenge for some polio serotypes. Compared to IPV-only schedules, IPV-OPV may have little or no difference on SAEs (serious adverse events), probably has little or no effect on persons with protective humoral response, may increase neutralising antibodies, and probably reduces faecal excretion after OPV challenge of certain polio serotypes.

Using three IPV doses as part of a IPV-OPV schedule does not appear to be better than two IPV doses for protective humoral response.

Sequential schedules during the transition from OPV to IPV-only immunisation schedules seems a reasonable option aligned with current WHO recommendations. Findings could help decision-makers to optimise polio vaccination policies, reducing inequities between countries.

CASOS CLÍNICOS

·         Episodio de hipotonía e hiporrespuesta en el lactante. Rev Pediatr Aten Primaria. 2019;21:379-81.

Se conoce como episodio de hipotonía-hiporrespuesta a un evento adverso de baja frecuencia de la vacunación infantil predominantemente del componente antitosferina. Es caracterizado por una pérdida súbita del tono muscular asociada a hiporreactividad a estímulos y a cambios en la coloración de la piel (palidez cutánea o cianosis). Debido a que es una entidad poco conocida, secundaria a mecanismos fisiopatológicos desconocidos y con diagnóstico por exclusión, adquiere una mayor importancia el conocimiento por el profesional sanitario de este evento, para elaborar un adecuado diagnóstico diferencial de episodios colapsiformes, evitar pruebas o medidas innecesarias y prevenir el miedo poblacional a las vacunas. Se presenta el caso de un lactante de 2 meses que acude a su centro de salud para iniciar el calendario vacunal sistemático. Aproximadamente un minuto tras la administración de las vacunas correspondientes a su edad (vacuna hexavalente [difteria, tétanos y tosferina acelular, Haemophilus influenzae tipo b, vacuna antipolio inactivada, hepatitis B] y vacuna antineumocócica conjugada de 13 valencias) presenta un episodio brusco de palidez cutánea, hipotonía e hiporreactividad, manteniendo respiración espontánea y conexión con el presented with a newly developed, nontender subtle medio, de apariencia colapsiforme, con recuperación espontánea y progresiva en los siguientes dos minutos.

·         A 6-Year-Old Boy with a Frontal Mass: Pott Puffy Tumor. J Pediatr. 2019 Oct 31. pii: S0022-3476(19)31213-2.

A 6-year-old boy was treated with sultamicillin for 6 days for frontal sinusitis. Upon clinical improvement, he was discharged with oral antibiotics to be continued for another week. Within 24 hours, he frontal swelling. His general condition was not compromised, and there were no signs of local inflammation or a history of recent trauma.

A cranial computed tomography scan demonstrated osteomyelitis of the right frontal bone with subdural abscess formation (Figure, C and D); magnetic resonance imaging revealed perifocal edema (Figure, B). The patient underwent immediate surgery with abscess drainage (Video; available at www.jpeds.com). Microbiological cultures grew Streptococcus intermedius, and the antibiotic treatment was switched to cefotaxime and clindamycin for 14 days. The patient was discharged home in good condition without neurologic sequelae.

·         Acute Periorbital Rash. J Pediatr. 2019 Nov 1. pii: S0022-3476(19)31318-6.

A 7-year-old girl presented with a sudden onset, asymptomatic rash around the eyes for the past 3 days. She was receiving treatment for an upper respiratory tract infection, characterized by severe paroxysms of nonproductive cough. The lesions had appeared spontaneously and was not associated with any prior trauma. Physical examination revealed bilaterally symmetrical, erythematous, nonblanchable macules distributed over both the upper and lower eyelids (Figure). There were no similar lesions and the systemic examination was unremarkable. Facial localization of purpuric lesions in the presence of severe bouts of coughing suggested cough purpura.

·         Infección del tracto urinario por Pantoea agglomerans: ¿un patógeno de pacientes inmunodeprimidos? Rev Pediatr Aten Primaria. 2019;21:e201-e203.

La infección por Pantoea agglomerans es muy rara de forma global y particularmente en Pediatría. La mayoría de las infecciones que causa son nosocomiales en pacientes inmunodeprimidos. Se han descrito infecciones articulares tras punción con espinas vegetales dando lugar a artritis, sinovitis u osteítis; meningitis o septicemia neonatal tras la contaminación de la nutrición parenteral o transfusiones de hematíes; infecciones de orina o respiratorias y peritonitis. En inmunocompetentes las infecciones son excepcionales, por lo que se aconseja realizar estudio de inmunidad, como en nuestro caso. El germen es muy resistente a antibióticos betalactámicos y para erradicarlo suele ser necesario tratar según antibiograma.

·         Edema agudo hemorrágico del lactante. Rev Pediatr Aten Primaria. 2019;21:397-9.

El edema agudo hemorrágico del lactante (EAHL) es una vasculitis de pequeño vaso que afecta característicamente a los lactantes, con predominio en varones. Su etiología es desconocida pero con frecuencia se asocia a infecciones o fármacos. Las lesiones cutáneas que provoca son purpúricas y asocian edema y febrícula. Su evolución es favorable y sin secuelas, se resuelve en pocas semanas y el tratamiento es sintomático. El caso clínico que presentamos trata de un lactante varón de 15 meses atendido en nuestro centro de salud con episodio de otitis media aguda y posterior aparición de edema agudo hemorrágico.

·         Urticaria multiforme, una entidad infradiagnosticada. Rev Pediatr Aten Primaria. 2019;21:401-3.

La urticaria multiforme es un trastorno cutáneo, propio de lactantes y niños pequeños, caracterizado por lesiones habonosas de centro violáceo y morfología anular. Presenta similitud con el eritema multiforme, pero a diferencia de este, tiene un carácter benigno y autolimitado. Su etiología es desconocida y el tratamiento, sintomático. Su conocimiento y diagnóstico diferencial es importante para evitar pruebas diagnósticas innecesarias, realizar un manejo correcto y proporcionar información adecuada a los padres. Caso clínico de lactante de 4 meses con urticaria multiforme.

·         Disseminated Cysticercosis—A Tropical Curse. J Pediatr. 2019 Oct 24. pii: S0022-3476(19)31155-2

A 7-year-old boy from rural northern India presented with complaints of fever, headache, and vomiting for the last 4 months. His headache was moderate to severe in intensity and associated with nonprojectile vomiting. There was no history of seizures, altered sensorium, or blurring of vision. Examination revealed pallor, bilateral proptosis, normal fundoscopy, and multiple palpable, nontender, pinhead-sized, subcutaneous nodules over extremities. There were no signs of meningeal irritation. The remainder of the systemic examination was unremarkable.

The child was investigated for disseminated tuberculosis, cysticercosis, Langerhans cell histiocytosis, and malignancy. Whole-body magnetic resonance imaging (MRI) including MRI of the brain supported the diagnosis of cysticercosis (Figure). Serology for cysticercus was also positive (IgG titers 1:1600). Hence, a diagnosis of disseminated cysticercosis was made.

·         Vaccine-Strain Herpes Zoster Ophthalmicus in a 14-month-old Boy Prompting an Immunodeficiency Workup: Case Report and Review of Vaccine-strain Herpes Zoster. The Pediatric Infectious Disease Journal. 39(2):e25-e27, February 2020.

We present a case of herpes zoster ophthalmicus in an otherwise healthy 14-month-old male associated with vaccine-strain varicella-zoster virus 11 weeks after monovalent varicella vaccine administration. Herpes zoster ophthalmicus, especially in the setting of familial immunoglobulin A deficiency, prompted further immunologic workup. A high index of suspicion is necessary for timely diagnosis and treatment of vaccine-strain herpes zoster.

PARA AMPLIAR

·         Predicting septic shock upon arrival to the emergency department

Sepsis continues to kill children around the world. The death of a child with sepsis in New York State resulted in a state-wide mandate for sepsis care in 2013 (JAMA 2018;320:358-67). This mandate was later found to be associated with lower risk of mortality from pediatric sepsis. Since then, other states have promulgated similar mandates.

Survival from sepsis depends on early diagnosis and timely intervention, preferably before septic shock occurs. Yet, clinicians often fail to recognize sepsis in time to prevent deterioration to septic shock. In this volume of The Journal, Scott et al derived and validated the first prediction model for pediatric septic shock. They used variables that are easily available from the electronic health records and are known upon arrival to the emergency department, including the initial vital signs. The model, which was developed using a modern predictive algorithm, strongly discriminated the risk of septic shock and added predictive value to initial clinician suspicion of sepsis. The model can be incorporated in the electronic health records to automate the stratification of the risk of pediatric shock.

Stratification of the risk of pediatric shock will allow for timely intervention before deterioration occurs. It is a critical step toward the prevention of death from pediatric sepsis. The prediction model by Scott et al is a positive step toward this direction.

·         Every Minute Counts: The Urgency of Identifying Infants with Sepsis

The need for immediate recognition and treatment of sepsis has been a major focus of quality improvement efforts in medicine over the past decade, exemplified by national efforts to raise awareness and identify and implement process improvement measures to increase survival, as in the Surviving Sepsis Campaign.1 Multiple studies in adults and mixed adult/pediatric populations have demonstrated that delayed time to administration of antibiotics adversely affects outcome in the setting of sepsis. However, to date there have not been published studies focusing solely on infants less than 1 year of age, with inclusion of both preterm and term gestational age infants.

In this volume of The Journal, Schmatz et al demonstrate that among preterm and term gestational age infants less than 1 year of age (median 35 days, IQR 18-114 days) hospitalized in a neonatal intensive care unit, prolonged time to antibiotic administration was associated with increased rates of mortality at 14 and 30 days, with fewer inotrope-free days.2 In this single-center prospective observational study at a large academic referral center, the authors defined suspected sepsis as any clinical concern prompting blood culture sampling and initiation of intravenous antibiotics. 

·         Impact of Baseline Tuberculin Skin Test and Isoniazid Chemoprophylaxis on Subsequent Quantiferon-TB Gold In-Tube Performance in Young Children Assessed After Tuberculosis Contact in Catalonia. The Pediatric Infectious Disease Journal. 39(2):e22-e25, February 2020.

We investigated the impact of baseline tuberculin skin tests (TSTs) and preventive isoniazid chemoprophylaxis on subsequent QuantiFERON-TB Gold In-Tube (QFT-GIT) assays performed after a 10- to 12-week window period in 114 children <5 years of age. Previous TSTs and chemoprophylaxis had no impact on the magnitude of subsequent antigen-induced responses in QFT-GIT. Furthermore, previous TSTs did not induce conversion from a negative to a positive QFT-GIT result.

·         Surviving Sepsis in a Referral Neonatal Intensive Care Unit: Association between Time to Antibiotic Administration and In-Hospital Outcomes. J Pediatr. 2019 Oct 8. pii: S0022-3476(19)31081-9

To determine if time to antibiotic administration is associated with mortality and in-hospital outcomes in a neonatal intensive care unit (NICU) population.

We conducted a prospective evaluation of infants with suspected sepsis between September 2014 and February 2018; sepsis was defined as clinical concern prompting blood culture collection and antibiotic administration. Time to antibiotic administration was calculated from time of sepsis identification, defined as the order time of either blood culture or an antibiotic, to time of first antibiotic administration. We used linear models with generalized estimating equations to determine the association between time to antibiotic administration and mortality, ventilator-free and inotrope-free days, and NICU length of stay in patients with culture-proven sepsis.

Among 1946 sepsis evaluations, we identified 128 episodes of culture-proven sepsis in 113 infants. Among them, prolonged time to antibiotic administration was associated with significantly increased risk of mortality at 14 days (OR, 1.47; 95% CI, 1.15-1.87) and 30 days (OR, 1.47; 95% CI, 1.11-1.94) as well as fewer inotrope-free days (incidence rate ratio, 0.91; 95% CI, 0.84-0.98). No significant associations with ventilator-free days or NICU length of stay were demonstrated.

Among infants with sepsis, delayed time to antibiotic administration was an independent risk factor for death and prolonged cardiovascular dysfunction. Further study is needed to define optimal timing of antimicrobial administration in high-risk NICU populations.

·         Análisis de la cobertura vacunal frente a tétanos en adolescentes: evolución y situación actual en Extremadura (España). Rev Pediatr Aten Primaria. 2019;21:e193-e200.

Introducción: el tétanos es una enfermedad aguda grave cuyo tratamiento es difícil y, por tanto, es fundamental su prevención. La administración de cinco dosis de vacuna antitetánica es suficiente para conferir una protección a largo plazo. En los últimos años se ha observado cierta disminución en las coberturas, lo que supone la existencia de población no suficientemente inmunizada. El objetivo de este estudio es analizar la cobertura vacunal de la dosis de recuerdo frente al tétanos en adolescentes en la localidad de Santa Amalia, provincia de Badajoz (España), durante los últimos 20 años (1996-2016).

Material y métodos: estudio observacional transversal. Se revisaron las tarjetas de vacunación y los registros de las dosis administradas en los documentos manuscritos y registro informático en el entorno JARA Atención Sanitaria (JARA-AS). Entre 1996 y 2001, la vacunación se hacía en el centro escolar, con registro manual. Desde 2002, se administró la vacuna en el centro de salud, con registro manual (2002-2007) e informático (2008-2016).

Resultados: analizada la cobertura de forma agrupada, los peores resultados de vacunación se apreciaron en centro de salud utilizando registro manual (35,6%), mientras que las mejores cifras de vacunación se encontraron en centro de salud con registro informático (100%), seguido por el grupo de centro escolar (83,0%).

Conclusiones: este estudio pone de manifiesto una alta cobertura de vacunación frente a tétanos en la dosis de recuerdo en adolescentes de 14 años en Santa Amalia, similar a la cobertura nacional, a diferencia de la baja cobertura existente en el resto de resExtremadura.

·         Mandatory Vaccination in Europe. Pediatrics February 2020, 145 (2) e20190620; DOI: https://doi.org/10.1542/peds.2019-0620

CONCLUSIONES: La vacunación obligatoria y la magnitud de las multas se asociaron con una mayor cobertura de vacunación. Además, la vacunación obligatoria se asoció con una menor incidencia de sarampión en los países con vacunación obligatoria sin exenciones no médicas. Estos hallazgos pueden informar las políticas legislativas destinadas a aumentar la cobertura de vacunación.

·         Outcomes of Empirical Antimicrobial Therapy for Pediatric Community-onset Febrile Urinary Tract Infection in the Era of Increasing Antimicrobial Resistance. The Pediatric Infectious Disease Journal. 39(2):121-126, February 2020.

Urinary tract infection (UTI) is a common cause of fever in children. Despite the increasing numbers of extended-spectrum beta-lactamase-producing organisms in the community, the empirical therapy of choice is still third-generation cephalosporins. This study was performed to investigate whether inappropriate empirical therapy (IAT) of community-onset UTI results in adverse clinical outcomes.

Methods: We retrospectively studied a cohort of pediatric patients with first-episode community-onset UTI caused by Escherichia coli, Klebsiella pneumoniae and Proteus spp. at Ramathibodi Hospital from 2011 to 2017. The patients were classified into IAT and appropriate empirical therapy (AT) groups. Medical records were reviewed to assess clinical outcomes.

Results: One hundred fifty-one eligible patients were enrolled in this study. The most common causative organism was E. coli (88.8% and 96.2% in the AT and IAT groups, respectively). Among the causative organisms, 19.8% were extended-spectrum beta-lactamase-producing organisms. There was no significant difference in clinical failure, microbiologic failure, relapse or time to defervescence between the 2 groups. No patients in either group developed sepsis after receiving empirical therapy. However, the length of hospital stay was significantly longer in the IAT than AT group [4.00 (4.50–6.00) vs. 7.00 (5.00–11.25) days, respectively; P = 0.000].

Conclusions: No significant difference in treatment outcomes was found between pediatric patients receiving AT and IAT for the treatment of UTI. In the era of increasing antimicrobial resistance, third-generation cephalosporins may still be a good choice as an empirical antimicrobial for children diagnosed with community-onset UTI.

·         The Novel Coronavirus Originating in Wuhan, China: Challenges for Global Health Governance. JAMA. Published online January 30, 2020. doi:10.1001/jama.2020.1097. 

On December 31, 2019, China reported to the World Health Organization (WHO) cases of pneumonia in Wuhan, Hubei Province, China, caused by a novel coronavirus, currently designated 2019-nCoV. Mounting cases and deaths pose major public health and governance challenges. China’s imposition of an unprecedented cordon sanitaire (a guarded area preventing anyone from leaving) in Hubei Province has also sparked controversy concerning its implementation and effectiveness. Cases have now spread to at least 4 continents. As of January 28, there are more than 4500 confirmed cases (98% in China) and more than 100 deaths.1 In this Viewpoint, we describe the current status of 2019-nCoV, assess the response, and offer proposals for strategies to bring the outbreak under control.

·         Another Decade, Another Coronavirus N Engl J Med. 2020 Jan 24. doi: 10.1056/NEJMe2001126

For the third time in as many decades, a zoonotic coronavirus has crossed species to infect human populations. This virus, provisionally called 2019-nCoV, was first identified in Wuhan, China, in persons exposed to a seafood or wet market. The rapid response of the Chinese public health, clinical, and scientific communities facilitated recognition of the clinical disease and initial understanding of the epidemiology of the infection. First reports indicated that human-to-human transmission was limited or nonexistent, but we now know that such transmission occurs, although to what extent remains unknown. Like outbreaks caused by two other pathogenic human respiratory coronaviruses (severe acute respiratory syndrome coronavirus [SARS-CoV] and Middle East respiratory syndrome coronavirus [MERS-CoV]), 2019-nCoV causes respiratory disease that is often severe.1 As of January 24, 2020, there were more than 800 reported cases, with a mortality rate of 3% (https://promedmail.org/. opens in new tab).

·         A Novel Coronavirus from Patients with Pneumonia in China, 2019 N Engl J Med. 2020 Jan 24. doi: 10.1056/NEJMoa2001017

 https://www.nejm.org/doi/full/10.1056/NEJMoa2001017?

In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed another clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).

·         First Case of 2019 Novel Coronavirus in the United States. N Engl J Med. 2020 Jan 31. doi: 10.1056/NEJMoa2001191

An outbreak of novel coronavirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient's initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.

·         Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany. N Engl J Med. 2020 Jan 30. doi: 10.1056/NEJMc2001468

·         Complications of Otitis Media and Sinusitis Caused by Streptococcus anginosus Group Organisms in Children. The Pediatric Infectious Disease Journal. 39(2):108-113, February 2020

The Streptococcus anginosus group (SAG, S. anginosus , S. intermedius and S. constellatus ) are often associated with severe disease and abscess formation. In our institution, we observed an apparent increase in frequency of intraorbital and intracranial infections resulting from SAG at Texas Children’s Hospital. We undertook a retrospective review to describe the frequency and clinical features of these infections.

Methods: We reviewed the database of the microbiology laboratory at Texas Children’s Hospital from 2011 to 2018 for SAG-positive cultures. Cases included were those associated with (1) either otitis media or sinusitis and (2) Pott’s puffy tumor, orbital abscesses, mastoiditis, epidural abscesses, subdural empyema, brain parenchymal abscesses or dural enhancement by imaging. The number of overall diagnoses were determined using diagnostic codes and used to estimate the proportion of disease caused by SAG.

Results: Ninety-five cases were identified meeting inclusion criteria. The median age of patients was 11.4 years, and 75.8% were previously healthy. S. intermedius was most commonly isolated (80%) followed by S. constellatus (12.6%) and S. anginosus (7.4%); 50.5% of cases were polymicrobial. Among polymicrobial cases, Staphylococcus aureus was most frequently isolated. All patients underwent surgical intervention. 8.4% of patients experienced persistent neurologic deficits. We observed a significant increase in disease incidence during the study period; in addition, the overall proportion of all intracranial infections caused by SAG increased.

Conclusions: Complications of otitis media and sinusitis caused by SAG are associated with substantial morbidity. These infections are becoming increasingly common at our center although the precise reason for this temporal trend is unclear.

·         Changes in US Outpatient Antibiotic Prescriptions From 2011–2016, Clinical Infectious Diseases, Volume 70, Issue 3, 1 February 2020, Pages 370–377, https://doi.org/10.1093/cid/ciz225

While antibiotics are life-saving drugs, their use is not without risk, including adverse events and antibiotic resistance. The majority of US antibiotic prescriptions are prescribed in outpatient settings, making outpatient antibiotic prescribing an important antibiotic stewardship target. The primary objective of this study was to describe trends in US outpatient oral antibiotic prescriptions from 2011–2016.

Methods. We estimated annual oral antibiotic prescription rates using national prescription dispensing count data from IQVIA Xponent, divided by census estimates for 2011–2016. We calculated the ratio of broad- to narrow-spectrum prescriptions by dividing broad-spectrum prescription

rates by narrow-spectrum prescription rates. We used Poisson models to estimate prevalence rate ratios, comparing 2011 and 2016 antibiotic prescription rates, and linear models to evaluate temporal trends throughout the study period.

Results. Oral antibiotic prescription rates decreased 5%, from 877 prescriptions per 1000 persons in 2011 to 836 per 1000 persons in 2016. During this period, rates of prescriptions dispensed to children decreased 13%, while adult rates increased 2%. The ratio of broad- to narrow-spectrum antibiotics decreased from 1.62 in 2011 to 1.49 in 2016, driven by decreases in macrolides and fluoroquinolones. The proportion of prescriptions written by nurse practitioners and physician assistants increased during the study period; in 2016, these providers prescribed over one-quarter of all antibiotic prescriptions.

Conclusions. Outpatient antibiotic prescription rates, especially of broad-spectrum agents, have decreased in recent years. Clinicians who prescribe to adults, including nurse practitioners and physician assistants, are important targets for antibiotic stewardship.

·         Enterovirus, parechovirus, adenovirus and herpes virus type 6 viraemia in fever without source. Archives of Disease in Childhood 2020;105:180-186.

Objectives To evaluate the potential associations between fever without a source (FWS) in children and detection of human enterovirus (HEV), human parechovirus (HPeV), adenovirus (AdV) and human herpesvirus type 6 (HHV-6) in the plasma; and to assess whether the detection of viruses in the plasma is associated with a reduced risk of serious bacterial infection (SBI) and antibiotic use.

Design and setting Between November 2015 and December 2017, this prospective, single-centre, diagnostic study tested the plasma of children <3 years old with FWS. Real-time (reverse-transcription) PCR for HEV, HPeV, AdV and HHV-6 was used in addition to the standardised institutional work-up. A control cohort was also tested for the presence of viruses in their blood.

Results HEV, HPeV, AdV and HHV-6 were tested for in the plasma of 135 patients of median age 2.4 months old. At least one virus was detected in 47 of 135 (34.8%): HEV in 14.1%, HHV-6 in 11.1%, HPeV in 5.9% and AdV in 5.2%. There was no difference in antibiotic use between patients with or without virus detected, despite a relative risk of 0.2 for an SBI among patients with viraemia. Controls were less frequently viraemic than children with FWS (6.0% vs 34.8%; p<0.001).

Conclusions HEV, HPeV, AdV and HHV-6 are frequently detected in the plasma of children with FWS. Antibiotic use was similar between viraemic and non-viraemic patients despite a lower risk of SBI among patients with viraemia. Point-of-care viral PCR testing of plasma might reduce antibiotic use and possibly investigations and admission rates in patients with FWS.

·         Zika Virus Infection—After the Pandemic. The Pediatric Infectious Disease Journal. 39(2):136, February 2020.

·         Provider Experience Recommending HPV Vaccination Before Age 11 Years. J Pediatr. 2019 Nov 19. pii: S0022-3476(19)31354-X

Objectives. To describe health care providers' experiences recommending human papillomavirus (HPV) vaccination before age 11 years as part of a multisession intervention to improve HPV vaccination coverage.

Study design. Between 2016 and 2018, we conducted 30-minute qualitative interviews with intervention participants approximately 1 month after intervention completion. Interviews explored participants' experiences with new strategies, including changing the age of routine recommendation. Thematic analysis of interview transcripts involved both deductive and inductive approaches.

Results Twenty-six participants at 5 clinical sites were interviewed. Most were female (88%) primary care providers (46%), and worked 1.5-3.0 clinical days weekly. Many providers described initial skepticism about recommending vaccination before age 11 years, fearing that removing the HPV vaccine from the adolescent bundle with tetanus and meningitis vaccines would decrease parental acceptance. However, providers uniformly reported high parental acceptance owing to reduced stigma relating to sexual activity and the opportunity to administer fewer shots at each visit. Providers also noted that initiating vaccination earlier increased opportunities to complete the series and decreased the need for resource-intensive vaccine recall programs.

Conclusions. Providers had positive experiences recommending HPV vaccination before age 11 years. Routine recommendation before age 11 years may offer advantages related to fewer shots per visit, fewer missed opportunities, and reduction of parental concerns related to sexual activity.

·         Maternal Vaccination in Argentina: Tetanus, Diphtheria, and Acellular Pertussis Vaccine Effectiveness During Pregnancy in Preventing Pertussis in Infants <2 Months of Age. Clin Infect Dis. 2020 Jan 16;70(3):380-387. doi: 10.1093/cid/ciz217.

BACKGROUND: In 2011, Argentina experienced its highest pertussis incidence and mortality rates of the last decade; 60% of deaths were among infants aged <2 months. In response, a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine was recommended for all pregnant women at ≥20 weeks of gestation. Although recent studies suggest that maternal Tdap vaccination is effective at preventing infant disease, no data have come from low- or middle-income countries, nor from ones using whole-cell pertussis vaccines for primary immunization.

METHODS: We conducted a matched case-control evaluation to assess the effectiveness of maternal Tdap vaccination in preventing pertussis among infants aged <2 months in Argentina. Pertussis case patients identified from September 2012 to March 2016 at 6 hospital sites and confirmed by polymerase chain reaction testing were included. Five randomly selected controls were matched to each case patient by hospital site and mother's health district. We used multivariable conditional logistic regression to calculate odds ratios (ORs). Vaccine effectiveness (VE) was estimated as (1 - OR) × 100%.

RESULTS: Seventy-one case patients and 300 controls were included in the analysis. Forty-nine percent of case patients and 78% of controls had mothers who were vaccinated during pregnancy. Overall Tdap VE was estimated at 80.7% (95% confidence interval, 52.1%-92.2%). We found similar VE whether Tdap was administered during the second or third trimester.

CONCLUSIONS: Tdap vaccination during pregnancy is effective in preventing pertussis in infants aged <2 months in Argentina, with similar effectiveness whether administered during the second or third trimester of pregnancy.

·         Clinical Response to Discordant Therapy in Third-Generation Cephalosporin-Resistant UTIs. Pediatrics February 2020, 145 (2) e20191608; DOI: https://doi.org/10.1542/peds.2019-1608

CONCLUSIONES: La mayoría de los niños con infecciones urinarias resistentes a  cefalosporinas de tercera generación que comenzaron con antibióticos discordantes experimentaron una mejoría clínica inicial y pocos requirieron una intensificación de la atención. Nuestros hallazgos sugieren que la terapia empírica de espectro bajo es apropiada mientras se esperan los resultados finales del cultivo de orina.

·         What Matters to Parents Regarding Immunization of Their Children: Systematic Analysis of Expert Advice to Parents in an Internet Forum. The Pediatric Infectious Disease Journal. 39(2):157-163, February 2020.

World Health Organization announced vaccine hesitancy among the top 10 threats to global health in 2019. While the number of persons looking for information on health topics on the internet is increasing, information regarding immunization on the internet is often inaccurate and misleading. We aimed to determine the kind of information parents seek on the internet for decision-making regarding immunizations for their children.

Methods:  We investigated threads of an internet vaccine forum, where parents can get personalized advice from a vaccine expert, with regard to the types of vaccines and content of the questions. One thousand six hundred twenty consultations (4896 questions) between September 2001 and December 2018 were examined. Of these, 1386, including 4000 questions, were related to immunizations of the user’s child. Date of consultation, user gender and country of residence, age of the child; kind of vaccine(s), and topic of the question according to the following categories were analyzed: Vaccination schedule, safety, effectiveness, necessity, vaccine application, serology, exchangeability of different vaccine types and brands, maternally acquired immunity, reimbursement, and vaccine product related.

Results: Most questions concerned infants (47.7%) and regarded measles-component (28.9%) and diphtheria-tetanus-pertussis combination vaccines (25.3%). Parents were mainly interested in vaccination schedule (33.8%), safety (26.6%), and effectiveness (17.8%) of vaccines. Over time, safety-related questions decreased, and effectiveness related questions increased. Disease outbreaks or newly introduced vaccines and vaccinations temporarily raised interest. From 2011 onwards, most questions regarded measles-component vaccines.

Conclusions: Our findings will assist health care professionals and policy makers in preparing targeted information campaigns to address questions and counteract vaccine hesitancy.

·         Archivist: Simple strategies for methicillin resistant Staphlococcus aureus (MRSA) infection Archives of Disease in Childhood 2020;105:186.

The Archivist is currently working in an environment where there is a high prevalence of methicillin resistant Staphlococcus aureus (MRSA) skin and soft tissue infections. Management of this remains a major challenge to the paediatric and adult antibiotic stewardship world. When we identify this infection what should we do? If we are to target the approaches to prevent these infections, we need to understand the factors predisposing to acquisition. Mark RL et al [Lancet Infectious Disease 2019 https://doi.org/10.1016/S1473-3099(19)30570-5] have comprehensively defined household longitudinal, strain-level S aureus transmission dynamics in households of children …

·         Dengue Vaccine Protects Youth. JAMA. 2020;323(3):209. doi:10.1001/jama.2019.21234. https://bit.ly/36JEUwe

Researchers have reported that a new vaccine against the dengue virus protected children and adolescents in a phase 3 trial conducted in Asia and Latin America.

The most recent trial results of the new vaccine candidate, TAK-003, in about 20 000 young study participants suggest that its overall efficacy against infection is about 80%. Twelve months after the second dose, the vaccine was 95.4% effective against dengue infection requiring hospitalization. Among those who tested seronegative for a previous dengue infection, the vaccine's efficacy was 74.9%.

At the American Society of Tropical Medicine and Hygiene's recent annual meeting, researchers reported that the vaccine's overall efficacy was 73.3% at 18 months.

·         Rapid point of care test for detecting urogenital infection in nonpregnant women and men at reproductive age. Cochrane Database of Systematic Reviews 2020, Issue 1. Art. No.: CD011708. DOI: 10.1002/14651858.CD011708.pub2

Based on the results of this systematic review, the POC test based on antigen detection has suboptimal sensitivity but good specificity. Performance of this test translates, on average, to a 52% chance of mistakenly indicating absence of infection and a 2% chance of mistakenly pointing to the presence of this condition. Because of its deleterious consequences for reproductive health, and considering the current availability of safe and effective interventions to treat C trachomatis infection, the POC screening strategy should not be based on a rapid diagnostic test for antigen detection. Research in this topic should focus on different technologies.

·         Topical antiseptics for chronic suppurative otitis media. Cochrane Database of Systematic Reviews 2020, Issue 1. Art. No.: CD013055. DOI: 10.1002/14651858.CD013055.pub2

We found five studies but it was not possible to tell how many participants were included as two studies only reported how many ears were treated. Different types of antiseptics were used: some used ear drops and some used powders.

Topical antiseptic (boric acid) versus no treatment (with a background treatment of ear cleaning)

One study (254 children) compared using boric acid in alcohol ear drops with no topical antiseptic treatment. All children had their ears cleaned daily using cotton wool sticks (dry mopping). The very low certainty of the evidence means that it is unclear whether or not treatment with an antiseptic leads to an increase in resolution of ear discharge at four weeks or at three to four months compared with the group who did not receive any topical

antiseptic. The study reported that there was no difference between the two treatment groups in hearing or suspected ototoxicity. There was no information for any of the other outcomes.

Comparison of topical antiseptic agents: One study (93 participants) compared a single dose of boric acid powder with daily acetic acid ear drops. The very low certainty of the evidence means that it is unclear if boric acid leads to an increase in resolution of ear discharge compared to daily acetic acid drops at four weeks. It was uncertain if one group had more ear discomfort than the other group. There was no information for any of the other outcomes.

Authors' conclusions: Due to paucity of the evidence and the very low certainty of that which is available the effectiveness and safety profile of antiseptics in the treatment of CSOM is uncertain.

·         Equivalent schedules of intradermal fractional dose versus intramuscular full dose of inactivated polio vaccine for prevention of poliomyelitis. Cochrane Database of Systematic Reviews 2019, Issue 12. Art. No.: CD011780. DOI: 10.1002/14651858.CD011780.pub2

There is low- and very low-certainty evidence that intramuscular full-dose IPV may result in a slight increase in seroconversion rates for all three types of wild poliovirus, compared with intradermal fractional-dose IPV. We are uncertain whether intradermal fractional-dose (one-fifth) IPV has better protective effects and causes fewer adverse events in children than intramuscular full-dose IPV.

·         Original research: Gelatin tannate for acute diarrhoea and gastroenteritis in children: a systematic review and meta-analysis. Archives of Disease in Childhood 2020;105:141-146.

Objective To determine the effectiveness and safety of gelatin tannate (GT) for reducing the duration of the acute diarrhoea and gastroenteritis (ADG) in children.

Design Systematic review and meta-analysis.

Data sources MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials, LILACS and grey literature, published from inception to October 2018. No language restrictions.

Eligibility criteria for selecting studies Randomised controlled trials in children with ADG, comparing GT with placebo.

Results Of 797 titles identified, we included three studies (276 children). We performed a random effects model meta-analysis for the main outcome (diarrhoea duration). We did not find significant differences between GT and placebo for diarrhoea duration (mean difference (MD)=−15.85 hours; 95% CI −42.24 to 14.82, I2=92%; three studies), stool frequency at day 2 (MD=0.11 stools/day; 95% CI −0.39 to 0.62: I2=26%; two studies), diarrhoea at day 3 (risk ratio [RR]=0.46; 95% CI 0.06 to 3.47: I2=73%; two studies), vomiting (RR=1.31; 95% CI 0.95 to 1.80: I2=0%; two studies) or adverse events (RR=0.86; 95% CI 0.27 to 2.66: I2=0%; two studies). Most common adverse events included abdominal pain and nausea.

Conclusion The effect of GT was no different to placebo for mean diarrhoea duration (low certainty on the evidence) and stool frequency at day 2 (high certainty) and for the presence of diarrhoea at day 3 (very low certainty) of vomiting (moderate certainty) and of adverse events (low certainty).

·         El nuevo escenario de las inmunodeficiencias primarias y el rol del inmunólogo clínico en la consulta especializada. An Pediatr (Barc). 2020;92:117-8

En segundo lugar, como mencionan Millán-Longo et al.1, cada vez es más conocida la base genética de muchas IDP, gracias a los avances en técnicas de secuenciación masiva disponibles en muchos centros que permiten un diagnóstico preciso con un mayor conocimiento de la historia natural de la enfermedad, una oportunidad de manejo más específico, así como consejo genético.

·         ¿Es la transmisión vertical de Chlamydia trachomatis un problema en nuestro país? An Pediatr (Barc). 2020;92:119

Hemos leído con interés el artículo publicado por Piñeiro et al. «¿Es la transmisión vertical de Chlamydia trachomatis un problema poco reconocido en España?»1, publicado en el número de junio.

En el citado trabajo, los autores hacen referencia a la transmisión perinatal de la infección por Chlamydia trachomatis, y estiman una transmisión al recién nacido del 10,7% partiendo de una muestra de 103 mujeres infectadas en el puerperio. Los recién nacidos fueron analizados entre 7 y 10 días después del parto mediante exudado faríngeo y conjuntival, este último en la parte final del estudio y en los casos que presentaron conjuntivitis.

·         App Enables Sharing Off-label Treatments for Infectious DiseasesJAMA. 2020;323(3):210. doi:10.1001/jama.2019.21735. https://bit.ly/2OeUVnv

A new app will allow health professionals to share how they’ve used FDA-approved drugs for off-label indications with patients who have difficult-to-treat infectious diseases. The internet-based repository, called CURE ID, is a collaboration between the FDA and the National Center for Advancing Translational Sciences, which is part of the National Institutes of Health (NIH).

In addition, the app will offer a treatment discussion forum for clinicians to discuss treatments with other health professionals around the world. The FDA and NIH will remove posts that users flag as suspicious, inappropriate, or offensive. Nearly 1500 initial cases from clinicians and the published literature as well as 18 000 clinical trials were added in a recent update. The app is available at https://cure.ncats.io or from the App Store or Google Play.

·         Immunization Against Hepatitis A in Migrant Children: Three Vaccination Strategies, A Retrospective Study. The Pediatric Infectious Disease Journal. 39(2):164-169

Hepatitis A is endemic in many countries. Swiss guidelines recommend vaccinating patients native from endemic areas. In Geneva’s Children’s hospital, migrant children are screened and vaccinated if seronegative. Because hepatitis A’s prevalence is decreasing worldwide, more children are seronegative at arrival, highlighting the need for immunization in medical centers and refugee camps and questioning the benefits of systematic serology. Other Swiss hospitals vaccinate regardless of serostatus. This study’s aim is to assess migrant children’s immunity according to origin and age, and the cost-effectiveness of different immunization strategies.

We retrospectively analyzed 329 children’s serostatus (1–16 years of age) between 2012 and 2015, using enzyme-linked fluorescent assay method. Serology and vaccine costs were based on local prices. Groups were compared with χ 2 test and the age-seropositivity relationship was studied with linear regression.

The predominant regions were the Eastern Mediterranean and European Regions with mostly negative serologies (71% and 83%) and the African Region with mostly positive serologies (79%). Immunity varied depending on birth country. Regardless of region, seropositivity increased with age ( P < 0.001). The most cost-effective vaccination strategy was an individualized approach based on age and origin, reducing costs by 2% compared with serology-guided immunization and by 17% compared with systematic vaccination.

Many migrant children >5 years old are seronegative and at risk of clinical infection. They need to be immunized. New guidelines according to age and origin should be defined to reduce immunization costs. We recommend systematic vaccination for patients <5 years old or native from low endemicity areas (≤25.7% of seropositivity). For the others, we propose serology-based vaccination.

 

 

Actualidad bibliográfica enero 2020

Top ten

El CAV-AEP publica anualmente el calendario de vacunaciones que estima idóneo para los niños residentes en España, teniendo en cuenta la evidencia científica disponible.

Se mantiene el esquema 2+1 (2, 4 y 11 meses) con vacunas hexavalentes (DTPa-VPI-Hib-HB) y con antineumocócica conjugada 13-valente.

Se aconseja un refuerzo a los 6 años, preferentemente con DTPa (si está disponible), junto a una dosis de polio para aquellos que recibieron esquemas 2+1, así como vacunación con Tdpa en adolescentes y en cada embarazo, preferentemente entre las 27 y las 32 semanas.

La vacuna del rotavirus debería ser sistemática para todos los lactantes.

Se sigue proponiendo la incorporación en el calendario de la vacuna antimeningocócica B, con esquema 2+1 en lactantes.

Además de la inclusión de la vacuna antimeningocócica conjugada tetravalente (MenACWY) a los 12 años con rescate hasta los 18 años, inclusive, el CAV recomienda que esta vacuna sea introducida también a los 12 meses de edad, sustituyendo a MenC. Igualmente, se recomienda en los mayores de 6 semanas de edad con factores de riesgo o que viajen a países de elevada incidencia de estos serogrupos.

Se emplearán esquemas de 2dosis para triple vírica (12 meses y 3-4 años) y varicela (15 meses y 3-4 años). La segunda dosis se podría aplicar como vacuna tetravírica.

Se recomienda la vacunación sistemática universal frente al VPH, tanto a chicas como a chicos, preferentemente a los 12 años, debiendo realizar un mayor esfuerzo para mejorar las coberturas. La de 9 genotipos amplía la cobertura para ambos sexos.

Controversy has arisen during the past decade or so regarding the medical and public health management of acute group A streptococcal pharyngitis (GAS) in children and adolescents. In particular, as the incidence of acute rheumatic fever (ARF) in many developed countries has declined, the need for testing throat swabs for GAS as an essential part of the routine evaluation of acute pharyngitis in childhood has been called into question.1 In a recent “Perspective” published in Circulation, Berkley argued that the currently recommended approach in the US of “extensive throat swabbing and antibiotic administration” for streptococcal pharyngitis to reduce the risk of ARF “can hardly be justified.”2 Berkley presented 5 arguments to support his contention: (1) the decline of ARF in developed countries preceded the widespread use of antibiotics and is likely related to changes in the prevalence of GAS M protein types historically associated with ARF; (2) the military-based treatment studies have never been replicated and did not demonstrate 100% efficacy in preventing ARF, GAS is still endemic in developed countries despite widespread use of antibiotics, and there has not been a resurgence of ARF in developed countries that advocate withholding antibiotics; (3) the outbreak of ARF in Utah in the 1980s occurred due to the presence of a GAS M type (M18) previously associated with ARF, and some patients with ARF did not have a history of sore throat; (4) ARF is so rare in the US that “any possible benefit [of antibiotic treatment of GAS pharyngitis] is likely dwarfed by the potential for harm, including drug-related reactions, increased antibiotic resistance, medicalization of a simple illness, and the huge burden on medical resources”; and (5) ARF is rarely a severe disease and only infrequently progresses to rheumatic heart disease (RHD).

American guidelines for the management of pharyngitis advocate extensive throat swabbing and antibiotic administration when group A streptococcus (GAS) is identified, with the stated aim of preventing acute rheumatic fever (ARF).1 Conversely, guidelines from Australia and several European countries, claiming a lack of evidence that antibiotic treatment is beneficial in ARF prevention, recommend the general avoidance of throat swabs and antibiotics in low-risk populations.2

In the evaluation of the relative merits of these 2 conflicting approaches, the following points should be considered:

Conclusions

Prednisone treated croup equally effectively compared with dexamethasone.

OBJECTIVES:The use of either prednisolone or low-dose dexamethasone in the treatment of childhood croup lacks a rigorous evidence base despite widespread use. In this study, we compare dexamethasone at 0.6 mg/kg with both low-dose dexamethasone at 0.15 mg/kg and prednisolone at 1 mg/kg.

METHODS:Prospective, double-blind, noninferiority randomized controlled trial based in 1 tertiary pediatric emergency department and 1 urban district emergency department in Perth, Western Australia. Inclusions were age >6 months, maximum weight 20 kg, contactable by telephone, and English-speaking caregivers. Exclusion criteria were known prednisolone or dexamethasone allergy, immunosuppressive disease or treatment, steroid therapy or enrollment in the study within the previous 14 days, and a high clinical suspicion of an alternative diagnosis. A total of 1252 participants were enrolled and randomly assigned to receive dexamethasone (0.6 mg/kg; n = 410), low-dose dexamethasone (0.15 mg/kg; n = 410), or prednisolone (1 mg/kg; n = 411). Primary outcome measures included Westley Croup Score 1-hour after treatment and unscheduled medical re-attendance during the 7 days after treatment.

RESULTS: Mean Westley Croup Score at baseline was 1.4 for dexamethasone, 1.5 for low-dose dexamethasone, and 1.5 for prednisolone. Adjusted difference in scores at 1 hour, compared with dexamethasone, was 0.03 (95% confidence interval -0.09 to 0.15) for low-dose dexamethasone and 0.05 (95% confidence interval -0.07 to 0.17) for prednisolone. Re-attendance rates were 17.8% for dexamethasone, 19.5% for low-dose dexamethasone, and 21.7% for prednisolone (not significant [P = .59 and .19]).

CONCLUSIONS: Noninferiority was demonstrated for both low-dose dexamethasone and prednisolone. The type of oral steroid seems to have no clinically significant impact on efficacy, both acutely and during the week after treatment.

Global public health authorities have celebrated the eradication of wild poliovirus type 3, the second wild poliovirus strain to have been eliminated. The last type 3 case was detected in Nigeria in 2012. Now only a single strain remains: wild poliovirus type 1.

In 2015, wild poliovirus type 2 was the first strain to be declared eradicated. Although vaccine-derived strains remain a concern in the countries with endemic polio, the latest victory suggests worldwide polio eradication is within reach.

“Global wild poliovirus type 3 eradication is a tremendous achievement and is an important milestone on the road to eradicate all poliovirus strains,” Tedros Ghebreyesus, PhD, MSc, director-general of the World Health Organization (WHO) and chair of the Global Polio Eradication Initiative Polio Oversight Board, said in a statement. “This shows us that the tactics are working, as individual family lines of the virus are being successfully knocked out. But the job is not finished until ALL strains of poliovirus are fully eradicated—and stay eradicated.”

Wild poliovirus type 1 continues to circulate in Afghanistan and Pakistan, according to the WHO. No wild type viruses have been detected on the African continent since 2016, David Salisbury, CB, chair of the independent Global Commission for the Certification of Poliomyelitis Eradication, said at the WHO celebration. However, Salisbury noted that vaccine–derived poliovirus strains continue to circulate in Africa. Ghebreyesus said that vaccines now in development might help reduce the risk of infections linked to vaccine-derived strains.

Las recomendaciones NO HACER son todas aquellas que no han demostrado eficacia, tienen escasa o dudosa efectividad, o no son coste-efectivas. Esta iniciativa parte de la National Physicians Alliance de Estados Unidos con el proyecto “Choosing Wisely” (Elegir con Prudencia), elaborando en cada sociedad científica un listado de cinco recomendaciones dirigidas a promover la mejora en la calidad de la atención sanitaria. De forma simultánea, la National Institute for Health and Care Excellence (NICE) ha venido elaborando las recomendaciones “Do not do” para las prácticas clínicas que no aportan beneficio o en las que la relación entre riesgos y beneficios no es razonable o bien no existe suficiente evidencia para aconsejar su uso sistemático.

La Sociedad Española de Infectología Pediátrica (SEIP) propuso a cada uno de sus grupos de trabajo la elaboración de 5 recomendaciones NO HACER, centradas en la optimización del uso de antimicrobianos, en abandonar prácticas establecidas pero no respaldadas por la evidencia científica, en la utilización racional de las pruebas diagnósticas y, en definitiva, en mejorar la calidad de la asistencia sanitaria en la patología infecciosa de la infancia.

Acute otitis media (AOM) is one of the most common diseases in children: at least 60% of children under the age of 3 years have experienced at least one AOM episode and approximately 24% display 3 or more episodes.1,2 Moreover, AOM is one of the most frequent reasons for antibiotic prescription in children, accounting for up to 25% of the total number. Therefore, the appropriateness of antibiotic therapy in children with AOM is an extremely relevant problem. In some countries guidelines have been issued and, in some instances, their implementation has contributed to reduce the unnecessary prescription of antibiotics by up to 12% with a 58% increase in antibiotics correctly prescribed in terms of the molecule and dose used.3 Italian guidelines were published in 2010,4 but in recent years there have been advances in terms of the diagnosis, therapy and prevention of this disease. 

In recent years, new progress has been made regarding the diagnosis, treatment and prevention of acute otitis media (AOM). The Italian Pediatric Society therefore decided to issue an update to the previous guidelines published in 2010.

Methods: Literature searches were conducted on MEDLINE by Pubmed, including studies in children, in English or Italian, published between January 1, 2010, and December 31, 2018. The quality of the included studies was assessed using the grading of recommendations, assessment, development and evaluations (GRADE) methodology. In particular, the quality of the systematic reviews was evaluated using the AMSTAR 2 appraisal tool. The guidelines were formulated using the GRADE methodology by a multidisciplinary panel of experts.

Results: The diagnosis of AOM is based on acute clinical symptoms and otoscopic evidence; alternatively, the presence of otorrhea associated with spontaneous tympanic membrane perforation allows the AOM diagnosis. The diagnosis of AOM must be certain and the use of a pneumatic otoscope is of fundamental importance. As an alternative to the pneumatic otoscope, pediatricians can use a static otoscope and a tympanometer. To objectively establish the severity of the episode for the formulation of a correct treatment program, an AOM severity scoring system taking into account clinical signs and otoscopic findings was developed.

Conclusions: The diagnosis of AOM is clinical and requires the introduction of specific medical training programs. The use of pneumatic otoscopes must be promoted, as they are not sufficiently commonly used in routine practice in Italy.

New insights into the diagnosis, treatment and prevention of acute otitis media (AOM) have been gained in recent years. For this reason, the Italian Paediatric Society has updated its 2010 guidelines.

Methods: A literature search was carried out on PubMed. Only pediatric studies published between January 1, 2010 and December 31, 2018 in English or Italian were included. Each included study was assessed according to the GRADE methodology. The quality of the systematic reviews was assessed using AMSTAR 2. The recommendations were formulated by a multidisciplinary panel of experts.

Results: Prompt antibiotic treatment is recommended for children with otorrhea, intracranial complications and/or a history of recurrence and for children under the age of 6 months. For children 6 months to 2 years of age, prompt antibiotic treatment is recommended for all forms of unilateral and bilateral AOM, whether mild or severe. Prompt antibiotic treatment is also recommended for children over 2 years with severe bilateral AOM. A watchful-waiting approach can be applied to children over 2 years with mild or severe unilateral AOM or mild bilateral AOM. High doses of amoxicillin, or amoxicillin-clavulanic acid for patients with a high risk of infection by Beta-lactamase producing strains, remain the first-line antibiotics.

Conclusions: AOM should be managed on a case-by-case basis that takes account of the child’s age, the severity of the episode and whether it is unilateral or bilateral. In patients under 2 years, prompt antibiotic treatment is always recommended.

In recent years, new information has been acquired regarding the diagnosis, treatment and prevention of acute otitis media (AOM). The Italian Pediatric Society, therefore, decided to issue an update to the Italian Pediatric Society guidelines published in 2010.

Methods: The search was conducted on Pubmed, and only those studies regarding the pediatric age alone, in English or Italian, published between January 1, 2010 and December 31, 2018, were included. Each study included in the review was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. The quality of the systematic reviews was evaluated using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2 appraisal tool. The guidelines were formulated using the GRADE methodology by a multidisciplinary panel of experts.

Results: The importance of eliminating risk factors (passive smoking, environmental pollution, use of pacifier, obesity, limitation of day-care center attendance) and the promotion of breastfeeding and hygiene practices (nasal lavages) was confirmed. The importance of pneumococcal vaccination in the prevention of AOM was reiterated with regard to the prevention of both the first episode of AOM and recurrences. Grommets can be inserted in selected cases of recurrent AOM that did not respond to all other prevention strategies. Antibiotic prophylaxis is not recommended for the prevention of recurrent AOM, except in certain carefully selected cases. The use of complementary therapies, probiotics, xylitol and vitamin D is not recommended.

Conclusions: The prevention of episodes of AOM requires the elimination of risk factors and pneumococcal and influenza vaccination. The use of other products such as probiotics and vitamin D is not supported by adequate evidence.

Kawasaki disease (KD), a systemic vasculitis, is the leading cause of acquired heart disease in industrialised countries. Despite decades of research, the aetiology and pathogenesis remain unclear. Prompt diagnosis and management of KD are essential to reduce the risk of coronary artery damage that may cause significant morbidity, including risk of myocardial ischaemia or infarction, and occasional mortality. In practice, this is often difficult due to a lack of a diagnostic test and relies on the recognition of a constellation of clinical features.

Since the American Heart Association (AHA) guideline in 2004,1 there have been over 2000 scientific and clinical publications on KD. The recently published 2017 AHA guideline, a scientific statement, provides detailed updated recommendations on the diagnosis, management and treatment of KD.2 Here we highlight and summarise the key updates of particular relevance to paediatricians and discuss other recent advances.

Key points from the 2017 AHA Kawasaki disease guideline

Diagnosis

La infección por el virus de la hepatitis E (VHE) es una de las principales causas de hepatitis aguda tanto en países desarrollados como en vías de desarrollo, situándose como una enfermedad infecciosa de alta prevalencia e incidencia en Europa. La infección por el VHE tiene mayor impacto clínico en poblaciones especialmente vulnerables, como pacientes inmunodeprimidos, mujeres embarazadas y pacientes con hepatopatía base. Por todo ello, desde el Grupo de Estudio de las Hepatitis Víricas (GeHEP) de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) se considera de gran relevancia la elaboración de un Documento de Consenso que sirva de ayuda en la toma de decisiones sobre el diagnóstico, manejo clínico-terapéutico y la prevención de la infección por el VHE.

Casos clínicos

El flujo vaginal es uno de los motivos de consulta ginecológica más frecuentes en niñas prepuberales, y a menudo se debe a la presencia de vulvovaginitis1,2. La mayoría de los casos son de etiología inespecífica y se resuelven con medidas higiénicas1,2. No obstante, cuando los síntomas persisten o recurren han de considerarse otras posibles causas, tales como procesos infecciosos, anomalías congénitas, trauma, reacciones alérgicas, entidades dermatológicas o la presencia de cuerpos extraños1,2. Presentamos el caso de una niña de 5 años sana…

Los senos dérmicos congénitos corresponden a una pequeña proporción de defectos de línea media con una indicencia de 1-2.500/3.000 recién nacidos vivos. Normalmente se acompañan de estigmas cutáneos en línea media, especialmente en región lumbosacra, y pueden asociar espina bífida oculta, siendo las infecciones y el déficit neurológico frecuentes1. Las lesiones cutáneas paramediales son extremadamente raras con tan solo 7 casos publicados2,3. Niña de 8 años con absceso glúteo derecho recurrente con celulitis local y drenaje purulento

resistente a tto local y antibioterapia iv . No alteraciones neurológicas. Estudio de EII negativo. Como antecedente personal destaca la presencia de un orificio en la misma localización desde época neonatal. Radiológicamente se muestra un trayecto fistuloso glúteo que termina en fondo de saco por encima de la fosa isquiorrectal, sin comunicación con el recto ni intraespinal , una malformación sacrocoxígea compleja con adelgazamiento del elevador del ano derecho y del músculo isquiocoxígeo, y una estructura osificada anómala localizada entre los músculos glúteos y la fascia endopélvica , con ausencia de alteraciones del sistema nervioso central y cono medular. Se realizó exéresis completa del trayecto fistuloso cuya histología correspondió a seno dérmico. Tras 2 años de seguimiento, la paciente se encuentra asintomática.


 

  • Pneumococcal Pneumonia Resembling Acute Myocardial Infarction in an Adolescent Male. The Pediatric Infectious Disease Journal. 39(1):81-84, January 2020.

Myocarditis is commonly associated with viruses. However, we present a novel case of a teenager with pneumococcal pneumonia and bacteremia complicated by myocarditis and rhabdomyolysis, presenting with features of acute ST-elevation myocardial infarction and cardiogenic shock. Physicians should be aware that Streptococcus pneumonia e infection, like Group A Streptococcus , can mimic acute myocardial infarction in young males without cardiovascular risk factors.

  • Concurrent Bacteremia Due to Non-vaccine Serotype 24F Pneumococcus in Twins: A Rapid Increase in Serotype 24F-invasive Pneumococcal Disease and its High Invasive Potential. The Pediatric Infectious Disease Journal. 39(1):85-87, January 2020.

Although concurrent bacteremia in siblings is rare, serotype 24F Streptococcus pneumoniae was isolated from the blood of twin 1-year-old girls within a 3-day interval, supporting the high invasive potential of this serotype. As the prevalence of childhood serotype 24F-invasive pneumococcal diseases increases in Europe and the Western Pacific Region, investigation and surveillance of this serotype are necessary.

La infección por Pantoea agglomerans es muy rara de forma global y particularmente en Pediatría. La mayoría de las infecciones que causa son nosocomiales en pacientes inmunodeprimidos. Se han descrito infecciones articulares tras punción con espinas vegetales dando lugar a artritis, sinovitis u osteítis; meningitis o septicemia neonatal tras la contaminación de la nutrición parenteral o transfusiones de hematíes; infecciones de orina o respiratorias y peritonitis. En inmunocompetentes las infecciones son excepcionales, por lo que se aconseja realizar estudio de inmunidad, como en nuestro caso. El germen es muy resistente a antibióticos betalactámicos y para erradicarlo suele ser necesario tratar según antibiograma.

Niño de 2 años ingresado de urgencia con fiebre, adenopatía cervical y crisis generalizadas tónico-clónicas. Examen neurológico y analítica anodinos. Se dio de alta al paciente con diagnóstico de crisis febril simple secundaria a infección respiratoria viral. Al día siguiente, el paciente reingresó con estado epiléptico febril. Los hallazgos de la TC cerebral fueron normales y el análisis del líquido cefalorraquídeo (LCR) mostró pleocitosis (74 células/mm3) y niveles normales de proteínas y glucosa. El paciente presentaba adenopatía cervical y hepatoesplenomegalia. Se hizo un diagnóstico presuntivo de encefalitis…

Para profundizar

Introducción

La malaria es considerada la cuarta causa de mortalidad infantil después de la neumonía, las complicaciones por parto prematuro y la asfixia perinatal.

Material y métodos

Estudio retrospectivo y descriptivo de los casos de paludismo confirmados y tratados en la Unidad de Enfermedades Infecciosas Pediátricas (edad inferior a 15 años) del Hospital La Fe (Valencia) en el período comprendido entre 1993 y 2015.

Resultados

Durante el período 1993-2015 se diagnosticaron 54 casos de malaria infantil, el 51,8% en varones. El 46,2% eran menores de 5 años. La mayoría de los niños procedían de Guinea Ecuatorial (68,5%). Solo en el 5,6% de los pacientes se pudo constatar que recibieran profilaxis antimalárica. Se evidenció que Plasmodium falciparum fue la especie causal del 81,4% de los episodios. Siete casos (13%) presentaron malaria complicada. El tratamiento más empleado fue la quinina, sola o en combinación con otros fármacos: atovacuona-proguanil fue empleada a partir del año 2010 y estuvo indicada en el 20,3% de los pacientes. A partir del año 2013 se inició la utilización de: artesunato, piperaquina y dihidroartemisina. No hubo mortalidad ni efectos adversos relevantes, siendo la respuesta clínica favorable en el 100% de los niños.

Conclusiones

La malaria sigue siendo una enfermedad vigente en nuestra población, consecuencia de la inmigración y del turismo a países endémicos. Debe ser considerada como diagnóstico probable ante un niño febril que procede o ha viajado a un área endémica en el último año.

DOI: 10.1016/j.anpedi.2019.01.027

Introducción: No existen datos actuales de prevalencia de (ITU) en niños menores de 2 años con fiebre elevada en nuestro medio.

Método: Estudio prospectivo, multicéntrico, observacional incluyendo niños con fiebre a los que se realizó análisis de orina para descartar ITU en un periodo de un año en siete servicios de urgencia pediátricos españoles. Se incluyeron niños menores de un año y niñas menores de 2 años con fiebre sin focalidad > 39°C y sin antibioterapia previa. El diagnóstico de ITU se basó en la presencia de leucocituria y urocultivo positivo.

Resultados: Un total de 1675 pacientes fueron incluidos. Doscientos sesenta niños (15,5%, 95% IC 13,8-17,3) fueron diagnosticados de ITU. La prevalencia puntual de ITU fue 32,9% (95% IC 26,6-39,9) en lactantes febriles menores de 6 meses y 19,3% (95% IC 16,1-22,9) en lactantes febriles menores de 12 meses. La prevalencia puntual de ITU fue 13% (95% IC 10,8-15,6) en niños menores de 2 años con fiebre de menos de 24 horas de evolución versus 17,5% (95% IC 15,2-20,1) en aquellos con más horas de evolución de fiebre (p = 0,014).

Conclusiones: La prevalencia puntual de ITU en niños con fiebre sin focalidad > 39°C en nuestro medio es superior a la referida previamente, especialmente en lactantes varones <6 meses y lactantes mujeres <12 meses. Nuestros resultados sugieren que los pediatras deben buscar de forma estrecha ITU en niños menores de 2 años con fiebre sin causa >39°C

Pertussis infection can cause serious complications, particularly among infants younger than 2 months, who are too young to be vaccinated.1 To reduce pertussis morbidity and mortality among young infants, the Advisory Committee on Immunization Practices (ACIP) issued a series of recommendation changes regarding antenatal administration of the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine, the most recent of which was issued in 2012 and recommends administration in every pregnant woman, regardless of prior receipt.2 Pertussis incidence among US infants younger than 1 year decreased after 20123; however, data on trends in young infants are scarce. We examined trends in pertussis hospitalizations among infants younger than 2 months before and after the changes to the ACIP recommendations in 2012.

Invasive pneumococcal disease (IPD) is associated with significant morbidity and mortality in children. Universal pneumococcal conjugate vaccination has changed the epidemiology of IPD. In vaccinated children, IPD can be a marker of an underlying immunodeficiency.

Methods: This is a retrospective audit of children younger than 18 years with IPD admitted to 2 tertiary pediatric hospitals in Australia between 2011 and 2017. Data on predisposing conditions, immunologic evaluation, pneumococcal serotype, antibiotic susceptibility and treatment were collected.

Results: During the 7-year period, there were 131 presentations with IPD in 127 children; 3 children had recurrent IPD. Patients presented with sepsis (41%), empyema (29%), meningitis (18%), mastoiditis (12%), pneumonia (10%) and septic arthritis (4%). In 19 (15%) presentations, risk factors for IPD were present, including malignancy, hematologic disorder, chronic liver disease, chronic kidney disease and cochlear implant. Pneumococcal serotypes were determined in 78/131 (60%) of presentations: the most frequent serotypes were 19A (19%), 3 (13%), 7F (10%) and 19F (8%) and non-vaccine serotypes 22F (8%), 35B (6%), 15A (4%) and 38 (4%). Overall, 11% of isolates were non-susceptible to ceftriaxone. Only 36 patients (32%) had an immunologic evaluation, and 4 patients had proven or probable immunodeficiency.

Conclusion: Although pneumococcal conjugate vaccine serotypes 19A, 3, 19F and 7F remain frequent causes of IPD, non-vaccine serotypes are emerging. Our data support vancomycin treatment for children with pneumococcal meningitis given 11% of our isolates were not susceptible to ceftriaxone. It is important to consider underlying conditions predisposing to IPD in a population with high rates of pneumococcal vaccination.

  • Birth Season and Infection Risk Among Children Under 5 Years Old: A Study of Hospital Admissions and Short Message Service-reported Symptoms at Home The Pediatric Infectious Disease Journal. 39(1):23-29, January 2020.

Background: The season in which a child is born may affect the immune system development and thereby influence the risk of infections. In this study, we examined the associations between birth season and the risk of hospital admission or symptoms associated with a wide range of infections.

Methods: This study is a prospective cohort study of 2434 children with an average follow-up of 3.5 years. Admission data were obtained from the Danish National Patient Registry. Via short message service (SMS) questionnaires, 1279 families reported symptoms of infections in a 1-year period.

Results: Of the 2434 children, 639 (26.3%) were admitted to the hospital, and the children experienced on average 64.4 days with symptoms of infection within 1 year. There was no association between birth season and hospital admissions due to all infectious causes [incidence rate ratio (IRR) = 0.89; 95% confidence interval (CI), 0.65–1.22; P = 0.471]. However, children born in the fall had a higher IRR for admission due to all infectious causes when excluding admissions within the first year of life. Winter- and spring-born children had lower IRRs for admission due to gastrointestinal infections than summer-born children, but this association was alone present when admissions within the first year of life were included. The short message service-survey showed significantly lower IRRs for any symptom of infection among winter-born (IRR = 0.85; 95% CI, 0.75–0.96; P = 0.009) and fall-born children (IRR = 0.88; 95% CI, 0.78–0.99; P = 0.033) in comparison with summer-born children.

Conclusions: Birth season was not associated with hospital admission due to all infectious causes within the first 5 years of age; however, fall-birth was associated with a higher IRR for admissions due to all infectious causes after the first year of life. The association between birth season and admissions due to gastrointestinal infections was only seen when including children admitted under the age of one. Being born in fall or winter was associated with a decreased IRR for number of days with any symptom of infection registered at home.

Objective: To test whether updated clinical practice guidelines for managing upper respiratory tract infections released in France in November 2011 were associated with changes in national outpatient pediatric antibiotic use.

Study design: We performed an interrupted time–series analysis using national antibiotic dispensation data in French children from January 2009 to December 2017 (IQVIA Suivi de la Dispensation Médicale database). We described the overall evolution of antibiotic prescription rates and modeled the changes in the proportion of amoxicillin and the proportion of broad-spectrum antibiotics following the guidelines in 2 age groups (0-5 and 6-14 years old).

Results: We analyzed 123 million pediatric antibiotic prescriptions. The most commonly prescribed individual antibiotic agent was amoxicillin (37.7%). Over the study period, the annual antibiotic prescription rate decreased by 33.1% (from 1387 to 928 per 1000 pediatric inhabitants per year), consistently across age groups and major antibiotic agents except for amoxicillin (+14.4%). After the release of the guidelines, we observed a gradual increase in the proportion of amoxicillin (relative change 5 years postintervention of +64.3% [95% CI 51.6-80.1] and +28.4% [21.1-36.2] for children 0-5 and 6-14 years, respectively) concomitantly with a gradual decrease in the proportion of broad-spectrum antibiotics (relative change 5 years postintervention of −26.1% [–29.3, −23.7] and −19.8% [–22.1, −16.0] for children 0-5 and 6-14 years old, respectively).

Conclusions: The 2011 guidelines for upper respiratory tract infections preceded changes in outpatient pediatric antibiotic use at the national level, with a replacement of broad-spectrum antibiotics by amoxicillin.

Yellow fever is an endemic disease in tropical areas in America and Africa. We report a case where the wild-type yellow fever virus was detected in a breast milk sample of a 33-year-old woman, from a rural area in the municipality of São Paulo, thus highlighting a potential risk for transmission of yellow fever virus through breast-feeding.

OBJECTIVE: To estimate the cost-effectiveness of routine, screening renal bladder ultrasound (RBUS) for children age 2-24 months after a first febrile urinary tract infection (UTI), as recommended by the American Academy of Pediatrics.

STUDY DESIGN: We developed a decision analytic model that simulates a population of children after a first febrile UTI. The model incorporates the diagnostic utility of RBUS to detect vesicoureteral reflux and genitourinary anomalies. We adopted a health-system perspective, 5-year horizon, and included 1-way and 2-way sensitivity analyses. Costs were inflated to 2018 US dollars, and our model incorporated a 3% discounting rate. We compared routine RBUS after first, febrile UTI compared with routine RBUS after second UTI (ie, control arm). Our main outcomes were recurrent UTI rate and incremental cost per quality-adjusted life-year (QALY).

RESULTS: Among children 2-24 months after a first febrile UTI, RBUS had an overall accuracy (true positives + true negatives) of 64.4%. The recurrent UTI rate in the intervention arm was 19.9% compared with 21.0% in the control arm. Thus, 91 patients would need to be screened with RBUS to prevent 1 recurrent UTI. RBUS increases QALYs by +0.0002 per patient screened, corresponding to an incremental cost-effectiveness ratio of $803 000/QALY gained. In the RBUS arm, 20.6% of children would receive unnecessary voiding cystourethrograms compared with 12.2% of children in the control group.

CONCLUSIONS: Screening RBUS after a first, febrile UTI in children age 2-24 months does not meet cost-effectiveness guidelines. Our findings support deferred screening until a second UTI.

The problems of antimicrobial resistance (AMR) are global and enormous. Like other global, enormous problems it is often difficult to know where to start—and it is easy to doubt that individual efforts will have meaningful impact. With all such problems, accurate data are important but are hard to come by. Li et al 1 from 39 hospitals in 12 countries provide revealing insights into the extent of AMR and antibiotic prescribing practices in neonatal units through a Neonatal AMR network (NeoAMR) of tertiary units in Asia, Africa and South America. The study proves that global-scale AMR surveillance networks can be established and yield useful information for clinicians and policy makers.

In this study, AMR in neonatal infections (both early and late onset) was widespread. More than 50% of enteric Gram-negative bacilli isolated from blood cultures were resistant to third-generation cephalosporins in 8 of the 10 countries where hospitals reported this. Further, carbapenem resistance was a significant problem in Gram-negative isolates from at least half the countries. Resistance among Gram-positive bacteria was less common, but vancomycin-resistant enterococci were emerging as a problem in two countries (Nigeria and India). There are limitations in this early report from the NeoAMR in their method and in the data reported. The results do not tell us about population-based prevalence of AMR in newborn sepsis, nor about AMR in health facilities outside tertiary hospitals. No attempt is made to distinguish community-acquired from hospital-acquired infections, and aminoglycoside resistance rates are not reported.

AMR drives poor prescribing, and poor prescribing drives AMR: it is a vicious cycle. The study is most revealing in the reported first-line antibiotic therapies for neonatal infections. Only 16 of 39 (41%) hospitals used antibiotic therapy for early-onset neonatal sepsis (EOS) that is consistent with that recommended by the WHO: ampicillin (or benzylpenicillin) plus …

Objective: Data from rigorous evaluations of the impact of interventions on improving surgical antibiotic prophylaxis (SAP) compliance in pediatrics are lacking. Our objective was to assess the impact of a multifaceted intervention on improving pediatric SAP compliance in a hospital without an ongoing antimicrobial stewardship program.

Study Design: A multidisciplinary team at the Montreal Children’s Hospital performed a series of interventions designed to improve pediatric SAP compliance in June 2015. A retrospective, quasi-experimental study was performed to assess SAP compliance before and following the interventions. Our study included patients under 18 years old undergoing surgery between April and September in 2013 (preintervention) and in 2016 (postintervention). A 10-week washout period was included to rigorously assess the persistence of compliance without ongoing interventions. SAP, when indicated, was qualified as noncompliant, partially compliant (adequate agent and timing) or totally compliant (adequate agent, dose, timing, readministration, duration).

Results: A total of 982 surgical cases requiring SAP were included in our primary analysis. The composite partial and total compliance increased from 51.4% to 55.8% [adjusted odds ratio 1.3; 95% confidence interval: 1.0–1.8; P = 0.06]. Although improvements in correct dose and readministration were significant, there was no significant improvement in correct timing, agent selection or duration.

Conclusion: Our study demonstrated that overall SAP compliance did not significantly improve following a washout period, illustrating the importance of ongoing surveillance and feedback from an antimicrobial stewardship program. Our strict approach in evaluating the timing criterion may also explain the lack of a significant impact on SAP compliance.

Background: Following the introduction of the 4CMenB (Bexsero, GlaxoSmithKline, Rixensart, Belgium) vaccine against Meningococcal B into the UK vaccination schedule, Public Health England advised paracetamol to be given prophylactically with the vaccine. This was based on observations of increased postvaccination febrile reactions in term infants. Evidence in preterm infants was lacking. We aimed to evaluate whether (i) 4CmenB is associated with an increase in adverse events (AEs) in the 48 hours after vaccination in preterm infants and (ii) the impact of prophylactic paracetamol on AEs.

Methods: Retrospective case-note review of preterm infants, within a UK level 3 neonatal unit, receiving first or second 4CMenB vaccination, within 3 periods; (i) period 1 (pre-4CMenB): September 2014–September 2015; (ii) period 2 (4CMenB without prophylactic paracetamol): September 2015–March 2016 and (iii) period 3 (4CMenB with prophylactic paracetamol): June 2016–May 2018. Data were collected on a predefined list of postvaccination AEs within 48 hours of vaccination: (i) number (%) of infants with temperature >37.5°C; (ii) highest temperature (°C); (iii) number (%) of infants receiving evaluation for sepsis and (iv) number (%) of infants receiving intravenous antibiotics.

Results: Ninety-five vaccination episodes were included. Compared with the pre-4CMenB (period 1), more infants developed temperature >37.5°C, needed partial septic screens and had intravenous antibiotics when 4CMenB was introduced without paracetamol prophylaxis (period 2). Paracetamol prophylaxis (period 3) with 4CMenB resulted in fewer infants experiencing postvaccination fever and antibiotic administration comparable to period 1.

Conclusions: 4CMenB is associated with AEs in hospitalized preterm infants. Prophylactic paracetamol administration attenuates this.

Conclusions Positive urinalysis in young (especially 31 to 60 days old), febrile, well-appearing infants may not require routine CSF testing.

To estimate birth prevalence of congenital cytomegalovirus (cCMV) in HIV-exposed uninfected children born in the current era of combination antiretroviral therapy and describe cCMV-related neurodevelopmental and hearing outcomes.

STUDY DESIGN: The Surveillance Monitoring for ART Toxicities cohort study follows HIV-exposed uninfected children at 22 sites in the US and Puerto Rico. Birth cCMV prevalence was estimated in a subset of participants who had blood pellets collected within three weeks of birth and underwent ≥1 of 6 assessments evaluating cognitive and language development including an audiologic examination between 1 and 5 years of age. Detection of CMV DNA by polymerase chain reaction testing of peripheral blood mononuclear cells was used to diagnose cCMV. Proportions of suboptimal assessment scores were compared by cCMV status using Fisher exact test.

RESULTS: Mothers of 895 eligible HIV-exposed uninfected children delivered between 2007 and 2015. Most (90%) were on combination antiretroviral therapy, 88% had an HIV viral load of ≤400 copies/mL, and 93% had CD4 cell counts of ≥200 cells/μL. Eight infants were diagnosed with cCMV, yielding an estimated prevalence of 0.89% (95% CI, 0.39%-1.75%). After adjusting for a sensitivity of 70%-75% for the testing method, projected prevalence was 1.2%-1.3%. No differences were observed in cognitive, language and hearing assessments by cCMV status.

CONCLUSIONS: Although birth cCMV prevalence in HIV-exposed uninfected children born to women with well-controlled HIV is trending down compared with earlier combination antiretroviral therapy-era estimates, it is above the 0.4% reported for the general US population. HIV-exposed uninfected children remain at increased risk for cCMV

La exacerbación de la enfermedad pulmonar obstructiva crónica y la neumonía adquirida en la comunidad son las infecciones del tracto respiratorio inferior más frecuentes en la práctica clínica diaria. La selección del antibiótico es un componente crucial en su tratamiento y, en la mayoría de las ocasiones, se realiza de forma empírica. Las sociedades científicas elaboran recomendaciones terapéuticas basadas en la evidencia científica y/o recomendaciones de expertos que son de gran ayuda para los clínicos. Los betalactámicos, las fluoroquinolonas y los macrólidos son los fármacos más utilizados por vía oral. Desde un punto de vista práctico, existen tres claves para la adecuada elección del tratamiento antibiótico oral, que son la efectividad, la seguridad y el impacto ecológico en la microbiota del paciente, incluyendo el desarrollo de resistencias, que van a ser valoradas en profundidad en esta revisión. 

El Virus Linfotrópico Humano T tipo 1 (HTLV-1) afecta hasta a 10 millones de personas en todo el mundo. Está directamente asociado a una de las neoplasias malignas de células T más agresivas: Leucemia-Linfoma de células T del Adulto (LLTA) y a un trastorno neurológico progresivo: Paraparesia Espástica Tropical / Mielopatía Asociada a HTLV-1 (PET/MAH). Además, los pacientes infectados tienden a tener formas más graves de enfermedades infecciosas como la Estrongiloidiasis y Tuberculosis. El HTLV se propaga a través de las siguientes vías: parenteral, sexual y vertical. La transmisión viral efectiva se produce principalmente por el mecanismo de contacto directo de célula a célula, a diferencia de otros retrovirus como el VIH, que generalmente se propaga infectando a las células mediante partículas virales libres. El HTLV-1 tiene una distribución peculiar, con grupos de alta endemicidad en áreas cercanas de muy baja prevalencia o ausencia del virus. Esto podría explicarse por factores que incluyen un posible efecto fundador, el predominio de la transmisión vertical (leche materna) y los mecanismos de transmisión por contacto célula a célula. Hoy en día se necesitan más datos epidemiológicos para desarrollar estrategias en áreas endémicas, destinadas a reducir la diseminación viral. En esta revisión, se analiza la patogénesis, la epidemiología, el diagnóstico, las enfermedades asociadas, las estrategias preventivas y los tratamientos del HTLV-1, con énfasis en el riesgo emergente para Europa y particularmente España, centrándonos en los métodos de prevención para evitar la transmisión viral y las enfermedades asociadas.