Factores de riesgo asociados a las secuelas neurológicas y auditivas en la cohorte nacional de niños con infección congénita por citomegalovirus

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Pediatría, leída el 14-01-2016El citomegalovirus humano (CMV) es la primera causa de infección congénita a nivel mundial. En la unión europea nacen anualmente 40000 niños con esta infección y hasta un 15‐20% van a desarrollar secuelas a largo plazo, principalmente hipoacusia y alteraciones neurológicas. Los factores de riesgo asociados a las secuelas a largo plazo no han sido determinados con exactitud y es difícil predecir qué niños van a desarrollar secuelas. Objetivos: Estudiar los factores de riesgo que se asocian al desarrollo de hipoacusia y de alteraciones neurológicas en la cohorte estatal de niños con infección congénita por CMV y desarrollar un modelo predictivo de secuelas. Material y métodos: Estudio longitudinal prospectivo multicéntrico que se desarrolla en una cohorte nacional de niños con infección congénita por citomegalovirus. Se incluyeron aquellos niños con un aislamiento para CMV positivo (cultivo viral o PCR) en fluidos corporales durante los primeros 14 días de vida y nacidos entre 2011 y 2015. Participaron 34 hospitales de toda España. Se realizó un seguimiento longitudinal de estos pacientes, con una evaluación auditiva (PEATC) y neurológica a los 6 y 12 meses de edad. Se definió hipoacusia como la presencia en al menos un oído de un umbral de respuesta ≥ 25 dB en los PEATC. Se definió la alteración neurológica a los 6 y 12 meses como la presencia de alteraciones motoras (espasticidad o paresias), epilepsia, coriorretinitis, retraso madurativo para su edad objetivado por un neurólogo infantil y la incapacidad para mantener la sedestación sin ayuda a los 12 meses. Se construyeron modelos de regresión logística multivariantes para describir la asociación de los factores de riesgo con el desarrollo de hipoacusia y/o alteraciones neurológicas. Se realizaron dos modelos pronósticos de hipoacusia y de alteraciones neurológicas a los 12 meses de edad...Depto. de Salud Pública y Materno - InfantilFac. de MedicinaTRUEunpu

Interferon-Gamma Release Assays Differentiate between Mycobacterium avium Complex and Tuberculous Lymphadenitis in Children

Spanish Pediatric TB Research Network (pTBred) and the European NontuberculouS MycoBacterial Lymphadenitis in childrEn (ENSeMBLE) Study.[Objectives] To assess the performance of interferon-gamma release assays (IGRAs) in the differential diagnosis between Mycobacterium avium complex (MAC) and tuberculosis (TB) in children affected with subacute/chronic submandibular/cervical lymphadenitis.[Study design] Multicenter observational study comparing children with microbiologically confirmed MAC lymphadenitis from the European NontuberculouS MycoBacterial Lymphadenitis in childrEn study with children with TB lymphadenitis from the Spanish Network for the Study of Pediatric TB database.[Results] Overall, 78 patients with MAC and 34 with TB lymphadenitis were included. Among MAC cases, 44 out of 74 (59.5%) had positive tuberculin skin test (TST) results at the 5-mm cut-off, compared with 32 out of 33 (97%) TB cases (P < .001); at the 10-mm cut-off TST results were positive in 23 out of 74 (31.1%) vs 26 out of 31 (83.9%), respectively (P < .001). IGRA results were positive in only 1 out of 32 (3.1%) patients with MAC who had undergone IGRA testing, compared with 21 out of 23 (91.3%) TB cases (P < .001). Agreement between TST and IGRA results was poor in MAC (23.3%; κ = 0.017), but good in TB cases (95.6%; κ = 0.646). IGRAs had a specificity of 96.9% (95% CI 84.3%-99.8%), positive predictive value of 95.4% (95% CI 78.2%-99.8%), and negative predictive value of 93.9% (95% CI 80.4%-98.9%) for TB lymphadenitis.[Conclusions] In contrast to TST, IGRAs have high specificity, negative predictive value, and positive predictive value for TB lymphadenitis in children with subacute/chronic lymphadenopathy, and consequently can help to discriminate between TB and MAC disease. Therefore, IGRAs are useful tools in the diagnostic work-up of children with lymphadenopathy, particularly when culture and polymerase chain reaction results are negative.Peer reviewe

Differences in saliva ACE2 activity among infected and non-infected adult and pediatric population exposed to SARS-CoV-2

Background Variations in the ACE2 activity in saliva could explain the striking differences of susceptibility to infection and risk of severe disease. Methods We analyze the activity of ACE2 in saliva in different population groups across a wide age range and disease status during April to June 2020, before SARS-CoV-2 vaccine implementation, and we establish differences between infected people and participants considered resistant (highly exposed healthcare workers and children who cohabited with parents with COVID-19 without isolation and remain IgG negative). Results We included 74 adults, of which 47 (64%) were susceptible and 27 (36%) were resistant, and 79 children, of which 41 (52%) were susceptible and 38 (48%) were resistant. Resistant adults have significantly lower ACE2 activity in saliva than susceptible adults and non-significant higher values than susceptible and resistant children. ACE2 activity is similar in the susceptible and resistant pediatric population (p = 0.527). In contrast, we observe an increase in activity as the disease's severity increases among the adult population (mild disease vs. severe disease, 39 vs. 105 FU, p = 0.039; severe disease vs. resistant, 105 vs. 31 FU, p < 0.001). Conclusions using an enzymatic test, we show that ACE2 activity in saliva correlates with the susceptibility to SARS-Cov-2 infection and disease severity. Children and adults with low-susceptibility to SARS-Cov-2 infection showed the lowest ACE2 activity. These findings could inform future strategies to identify at-risk individuals.This work was supported by Instituto de Salud Carlos III (AC17/00019, PI18/00154, COV20/00349, ICI20/00058), CRUE-Supera COVID, cofinanced by the European Development Regional Fund ‘‘A way to achieve Europe’’ (ERDF), Merck, Sharp & Dohme Investigator Studies Program (code MISP# IIS 60257), Fondo Supera COVID-19 (2020-001), and SEIMC (becas SEIMC).Peer reviewe

Accuracy of Xpert Ultra for the diagnosis of paediatric tuberculosis in a low TB burden country: a prospective multicentre study

[Introduction] Childhood pulmonary tuberculosis (TB) remains a diagnostic challenge. This study aimed to evaluate the performance of Xpert Ultra for the diagnosis of pulmonary TB in children in a low TB prevalence setting.[Methods] Prospective, multicentre, diagnostic accuracy study. Children with clinical or radiological suspicion of pulmonary TB were recruited at 11 paediatric units in Spain. Up to three gastric or sputum specimens were taken on 3 consecutive days, and analysed by Xpert MTB/RIF, Xpert Ultra and culture in parallel.[Results] 86 children were included (median age 4.9 years, IQR 2.0–10.0; 51.2% male). The final diagnosis was pulmonary TB in 75 patients (87.2%); 33 (44.0%) were microbiologically confirmed. A total of 219 specimens, comprising gastric aspirates (n=194; 88.6%) and sputum specimens (n=25; 11.4%), were analysed. Using culture as reference standard and comparing individual specimens, the sensitivity was 37.8% (14/37) for Xpert MTB/RIF and 81.1% (30/37) for Xpert Ultra (p<0.001); specificity was 98.4% (179/182) and 93.4% (170/182), respectively (p=0.02). In the per-patient analysis, considering positive results on any specimen, the sensitivity was 42.9% (9/21) for Xpert MTB/RIF and 81.0% for Xpert Ultra (17/21, p=0.01); specificity was 96.9% (63/65) and 87.7% (57/65, p=0.07), respectively.[Conclusions] In children with pulmonary TB in a low burden setting, Xpert Ultra has significantly higher sensitivity than the previous generation of Xpert assay and only marginally lower specificity. Therefore, in children undergoing evaluation for suspected pulmonary TB, Xpert Ultra should be used in preference to Xpert MTB/RIF whenever possible.This study did not receive any project-specific funding. DA-A was supported by the Spanish Ministry of Health – Instituto de Salud Carlos III (ISCIII) and cofunded by the European Union (FEDER) (Contrato Río Hortega CM18/00100). AN-J was supported by 'Subvencions per a la Intensificació de Facultatius Especialistes' (Departament de Salut de la Generalitat de Catalunya, Programa PERIS 2016-2020) (SLT008/18/00193). DBG was supported by the Spanish Ministry of Science and Innovation – Instituto de Salud Carlos III and Fondos FEDER by 'Contratos para la intensificación de la actividad investigadora en el Sistema Nacional de Salud, 2020 (INT20/00086)'. BS-G was supported by the Spanish Ministry of Health – Instituto de Salud Carlos III (ISCIII) and cofunded by the European Union (FEDER) (Contrato Juan Rodés JR16/00036).Peer reviewe

Oral saliva swab reverse transcription PCR for Covid-19 in the paediatric population

8Pág. Centro de Investigación en Sanidad Animal (CISA)To evaluate the performance of oral saliva swab (OSS) reverse transcription PCR (RT-PCR) compared with RT-PCR and antigen rapid diagnostic test (Ag-RDT) on nasopharyngeal swabs (NPS) for SARS-CoV-2 in children.The study was funded by: Project PI20/00095, from the Instituto de Salud Carlos III (Ministry of Economy, Industry and Competitiveness) and cofounded by the European Regional Development Fund, by Infanta Sofia University Hospital and Henares University Hospital Foundation for Biomedical Research and Innovation (FIIB HUIS HHEN), and by SERMAS-Fundación para la Investigación Biomédica del Hospital 12 de Octubre. EC-C is supported by the Spanish Society of Paediatrics (Asociación Española de Pediatría); Grant COVID-19 EPICO-AEP 2020. JMM is funded by SERMAS-Fundación para la Investigación Biomédica del Hospital Infanta Sofía y del Henares and by Universidad Europea de Madrid, Spain. MdlS is funded by Grant Cantera de Investigación Santander, Fundación Universidad Europea de Madrid, Spain. ED is funded by the Juan de la Cierva–Incorporación granted by the Spanish Ministry of Science and Innovation. DB-G is funded by the Spanish Ministry of Science and Innovation—Instituto de Salud Carlos III and Fondos FEDER by ’Contratos para la intensificación de la actividad investigadora en el Sistema Nacional de Salud, 2020 (INT20/00086)’.Peer reviewe

Fever without source as the first manifestation of SARS-CoV-2 infection in infants less than 90 days old

Fever without source (FWS) in infants is a frequent cause of consultation at the emergency department, and the emergence of SARS-CoV-2 could affect the approach to those infants. The aim of this study is to define the clinical characteristics and rates of bacterial coinfections of infants < 90 days with FWS as the first manifestation of SARS-CoV-2 infection. This is a cross-sectional study of infants under 90 days of age with FWS and positive SARS-CoV2 PCR in nasopharyngeal swab/aspirate, attended at the emergency departments of 49 Spanish hospitals (EPICO-AEP cohort) from March 1 to June 26, 2020. Three hundred and thirty-three children with COVID-19 were included in EPICO-AEP. A total of 67/336 (20%) were infants less than 90 days old, and 27/67(40%) presented with FWS. Blood cultures were performed in 24/27(89%) and were negative in all but one (4%) who presented a Streptococcus mitis bacteremia. Urine culture was performed in 26/27(97%) children and was negative in all, except in two (7%) patients. Lumbar puncture was performed in 6/27(22%) cases, with no growth of bacteria. Two children had bacterial coinfections: 1 had UTI and bacteremia, and 1 had UTI. C-reactive was protein over 20 mg/L in two children (one with bacterial coinfection), and procalcitonin was normal in all. One child was admitted to the pediatric intensive care unit because of apnea episodes. No patients died.Conclusion: FWS was frequent in infants under 90 days of age with SARS-CoV-2 infection. Standardized markers to rule out bacterial infections remain useful in this population, and the outcome is generally good. What is Known: • Fever without source (FWS) in infants is a common cause of consultation at the emergency department, and young infants have a higher risk of serious bacterial infections (SBI). • The emergence of the new coronavirus SARS-CoV-2 could affect the approach to young infants with FWS in the emergency department. management of those children is a challenge because information about bacterial coinfection and prognosis is scarce. What is New: • SARS-CoV-2 infection should be ruled out in young infants (< 90 days of age) with FWS in areas with community transmission. • Bacterial coinfection rarely coexists in those infants. • Inflammatory markers were not increased in children without bacterial coinfection. • Outcome is good in most patients.Sin financiación3.860 JCR (2021) Q1, 28/130 Pediatrics0.806 SJR (2021) Q1, 65/320 Pediatrics, Perinatology and Child HealthNo data IDR 2020UE

Growth Patterns in Children with Congenital Cytomegalovirus Infection

Background: Congenital cytomegalovirus infection (CMVc) affects 0.7%-6% of recent births. Among its clinical manifestations are low weight and length at birth. Objective: Describe the growth patterns of children with CMVc in their early years. Methods: Observational, multicenter study of patients with CMVc. Anthropometric data were collected during the first 2 years of life and compared with World Health Organization standards. Results: Anthropometric characteristics of 383 children with CMVc were studied, of which 198 (51%) were symptomatic at birth. At birth, 9% were small for gestational age (SGA) in terms of their weight and length and 17% had microcephaly. At 24 ± 3 months, 10% had a weight and length ≤2 SD, and 13% a head circumference ≤2 SD. Of those who were SGA at birth, at 24 ± 3 months >20% remained at ≤2 SD of their weight and length. Conversely, 75% of children with low weight or length at 24 ± 3 had not been SGA at birth. 20% of infants with microcephaly at birth remained with microcephaly, and 10% of those without microcephaly developed it at 24 ± 3 months. The average growth rate in length and weight was normal. Patients who were symptomatic at birth, premature and with motor and neurocognitive impairment had a significantly higher risk of low weight and length at 24 ± 3 months. Conclusion: Around 10% of children with CMVc are at ≤2 SD in weight, length and head circumference at 24 ± 3 months. The lack of adequate growth is associated with symptoms at birth, prematurity and motor and neurocognitive impairment. Growth impairment could be incorporated into the symptomatic spectrum of CMVc.Sin financiación3.164 JCR (2020) Q3, 56/92 Infectious Diseases1.269 SJR (2020) Q1, 69/292 Infectious DiseasesNo data IDR 2019UE

Role of Magnetic Resonance Imaging and Cranial Ultrasonography in Congenital Cytomegalovirus Infection

Sin financiación2.126 JCR (2019) Q4, 123/159 Immunology1.139 SJR (2019) Q1, 39/311 Pediatrics, Perinatology and Child HealthNo data IDR 2019UE

Hand Hygiene Compliance Rates in 9 Pediatric Intensive Care Units Across Europe: Results from the Reducing Antimicrobial use and Nosocomial Infections in Kids Network.

A unified surveillance mechanism for hand hygiene and hospital-acquired infections for pediatric wards is lacking in Europe. We managed to setup such a mechanism in 9 pediatric intensive care units in 7 European countries, using World Health Organization's definitions and common methodology which allows for benchmarking among units and countries. Median hand hygiene compliance was found high 82.3% (interquartile range 71.6-94.5%), but gaps in practices were identified

Treatment and outcome in children with tuberculous meningitis - a multi-centre Paediatric Tuberculosis Network European Trials Group study.

INTRODUCTION: Currently, data on treatment, outcome, and prognostic factors in children with tuberculous meningitis (TBM) in Europe are limited. To date, most existing data on TBM originate from adult studies, or studies conducted in low-resource settings. METHODS: Multicentre, retrospective study involving 27 paediatric healthcare institutions in nine European countries via an established paediatric TB research network, before and after the 2014 revision of WHO dosing recommendations. RESULTS: Of 118 children, 39 (33.1%) had TBM grade 1, 68 (57.6%) grade 2 and 11 (9.3%) grade 3. Fifty-eight (49.1%) children received a standard four-drug treatment regimen; other commonly used drugs included streptomycin, prothionamide, and amikacin. Almost half of the patients (48.3%; 56/116) were admitted to intensive care unit, with a median stay of 10 (IQR 4.5-21.0) days. Of 104 children with complete outcome data, 9.6% (10/104) died, and only 47.1% (49/104) recovered fully. Main long-term sequelae included spasticity of one or more limbs and developmental delay both in 19.2% (20/104), and seizure disorder in 17.3% (18/104). Multivariate regression analyses identified microbiological confirmation of TBM, the need for neurosurgical intervention and mechanical ventilation as risk factors for unfavourable outcome. DISCUSSION: There was considerable heterogeneity in the use of TB drugs in this cohort. Despite few children presenting with advanced disease and the study being conducted in a high-resource setting, morbidity and mortality were high. Several risk factors for poor outcome were identified, which may aid prognostic predictions in children with TBM in the future