Bibliografía de 2020

Actualidad bibliográfica junio 2020


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.

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:

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).


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.


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:

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.


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).


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.


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.


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.


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.


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 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.


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.


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.


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,

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.

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

Top Ten

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. 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 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] 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,

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


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.


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


·         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.

·         Cryptosporidiosis. JAMA. 2020;323(3):288. doi:10.1001/jama.2019.18691.


·         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,

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.

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.


·         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 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.


·         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:

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% ( 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

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,

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:

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] 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.

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.

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 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:


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


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


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.


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.


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.