MUC5AC: A potential biomarker of severity in pediatric patients infected with influenza.

Numerous factors can increase the risk of severe influenza; however, a majority of severe cases occur in previously healthy children. Identification of high-risk children is important for targeted preventive interventions and prompt treatment. The aim of this study was to evaluate MUC5AC as a biomarker for influenza disease severity in children. For this, a prospective cohort study was conducted in 2019. Children hospitalized with acute respiratory infection (ARI) with confirmed positive influenza infection were enrolled. Influenza cases were identified by reverse transcriptase-polymerase chain reaction. Life-threatening disease (LTD) was defined by the need for intensive care and ventilatory support. MUC5AC, epidemiologic, and clinical risk factors were assessed. Three hundred and forty-two patients were hospitalized with ARI, of which 49 (14%) had confirmed influenza infection and 6 (12%) of them developed LTD. MUC5AC levels were higher in those patients with mild disease compared to cases with poorer outcomes. Our results show that the severity of influenza infection in children is significantly associated with low levels of MUC5AC. These findings suggest its potential as a suitable biomarker for predicting disease severity.

Serum Vitamin D Levels and Life-Threatening Respiratory Syncytial Virus Infection in Previously Healthy Infants.

BACKGROUND: 25-hydroxyvitamin D (VD) effects on lung function and immune-modulation might affect respiratory syncytial virus (RSV) infection outcomes. We aimed to assess VD levels on admission and their association with life-threatening RSV disease (LTD). METHODS: A prospective cohort study was conducted during 2017-2019. Previously healthy infants aged <12 months, hospitalized with a first episode of RSV infection, were enrolled. LTD was defined by need for intensive care and ventilatory support. Serum VD levels <20 ng/mL were categorized as deficient, and 20-29.9 ng/mL as insufficient. RESULTS: Of 125 patients studied, 73 (58%) were male. Median age was 4 months. Twenty-two patients developed LTD. No differences in viral load were seen between cases with LTD and controls (P = .94). Patients who developed LTD had significantly lower VD levels: median 18.4 ng/mL (IQR, 15.1-26.9 ng/mL) versus 31.7 ng/mL (IQR, 23.6-42.0 ng/mL), P < .001; 59% of infants with LTD had VD deficiency compared with 12% in those with better outcome. Multivariable regression analysis confirmed VD deficiency as a risk factor (odds ratio, 11.83; 95% confidence interval, 3.89-35.9; P < .001). CONCLUSIONS: These findings provide additional evidence for the development of strategies to prevent severe RSV infections.

Impacto clínico-epidemiológico del virus sincicial respiratorio e identificación de factores de riesgo de enfermedad grave en niños hospitalizados por infección respiratoria aguda / Clinical and epidemiological impact of respiratory syncytial virus and identification of risk factors for severe disease in children hospitalized due to acute respiratory tract infection

Introducción: La infección respiratoria aguda grave (IRA) es una causa muy frecuente de internación en pediatría; el virus sincicial respiratorio (VSR) es el principal agente etnológico. Definir en forma precisa la carga de enfermedad que compromete la vida (ECV) por este virus y los factores de riesgo es un desafío. Objetivos: Conocer el impacto del VSR en internados por IRA y describir factores de riesgo de ECV. Materiales y métodos: Estudio prospectivo en niños < 2 años internados por IRA durante 20122013 en el Hospital de Niños "R. Gutiérrez". Se definió ECV el requerimiento de ventilación no invasiva y/o asistencia respiratoria mecánica. Resultados: 622 niños estudiados, 372 VSR (+) (el 59,8 %). Tasa de hospitalización anual por VSR en < 1 año: 956 (IC 95 %: 858-1062)/10 000 internaciones. El VSR causó 56/78 (el 71,8 %) casos de ECV; 42 (el 75 %) eran previamente sanos; 32 (el 76,2 %) tenían < 6 meses de edad. En el análisis multivariado, el VSR fue un factor de riesgo de ECV (odds ratio ajustado --#91;ORa--#93; 2,04; IC 95 %: 1,15-3,63; p = 0,014). Se identificó un efecto diferencial según género en pacientes VSR (+): el hacinamiento fue un factor de riesgo de ECV en varones (ORa 2,36; IC 95 %: 1,07-5,21; p = 0,033); la lactancia materna protegió significativamente a las niñas (ORa 0,342; IC 95 %: 0,13-0,91; p = 0,032). Conclusiones: El VSR causó más de la mitad de los casos de IRA y afectó, en su mayoría, a pacientes < 1 año previamente sanos. Los varones en condiciones de hacinamiento y las niñas que no recibieron leche materna constituyeron el grupo con mayor riesgo de ECV.

Introduction: Severe acute respiratory tract infection (ARTI) is a very common cause of hospitalization in pediatrics; respiratory syncytial virus (RSV) is the major etiologic agent. Accurately defining the burden of RSV life-threatening disease (LTD) and its risk factors is a challenge. Objectives: To know the impact of RSV in children hospitalized due to ARTI and describe the risk factors for LTD. Materials and methods: Prospective study in children < 2 years old hospitalized due to ARTI during 2012-2013 at Hospital de Niños "R. Gutiérrez." LTD was defined as requiring non-invasive ventilation and/or mechanical ventilation. Results: 622 studied children, 372 were RSV(+) (59.8 %). Annual rate of hospitalization due to RSV in infants < 1 year old: 956 (95 % CI: 858-1062)/10 000hospitalizations. RSV caused 56/78 (71.8 %) cases of LTD; 42 (75 %) were previously healthy subjects; 32 (76.2 %) were < 6 months old. In the multivariate analysis, RSV was a risk factor for LTD (adjusted odds ratio --#91;aOR--#93;: 2.04; 95 % CI: 1.15-3.63; p = 0.014). A differential effect by sex was identified in RSV(+) patients: over-crowding was a risk factor for LTD in males (aOR: 2.36; 95 % CI: 1.07-5.21; p = 0.033); breastfeeding was a significant protective factor in females (aOR: 0.342; 95 % CI: 0.13-0.91; p = 0.032). Conclusions: RSV caused more than half of ARTI cases and mostly affected previously healthy patients < 1 year old. Males living in overcrowding conditions and females who were not breastfed were at the greatest risk for LTD.

Clinical and epidemiological impact of respiratory syncytial virus and identification of risk factors for severe disease in children hospitalized due to acute respiratory tract infection. / Impacto clínico-epidemiológico del virus sincicial respiratorio e identificación de factores de riesgo de enfermedad grave en niños hospitalizados por infección respiratoria aguda.

INTRODUCTION: Severe acute respiratory tract infection (ARTI) is a very common cause of hospitalization in pediatrics; respiratory syncytial virus (RSV) is the major etiologic agent. Accurately defining the burden of RSV life-threatening disease (LTD) and its risk factors is a challenge. OBJECTIVES: To know the impact of RSV in children hospitalized due to ARTI and describe the risk factors for LTD. MATERIALS AND METHODS: Prospective study in children < 2 years old hospitalized due to ARTI during 2012-2013 at Hospital de Niños "R. Gutiérrez." LTD was defined as requiring non-invasive ventilation and/or mechanical ventilation. RESULTS: 622 studied children, 372 were RSV(+) (59.8 %). Annual rate of hospitalization due to RSV in infants < 1 year old: 956 (95 % CI: 858-1062)/10 000hospitalizations. RSV caused 56/78 (71.8 %) cases of LTD; 42 (75 %) were previously healthy subjects; 32 (76.2 %) were < 6 months old. In the multivariate analysis, RSV was a risk factor for LTD (adjusted odds ratio [aOR]: 2.04; 95 % CI: 1.15-3.63; p = 0.014). A differential effect by sex was identified in RSV(+) patients: over-crowding was a risk factor for LTD in males (aOR: 2.36; 95 % CI: 1.07-5.21; p = 0.033); breastfeeding was a significant protective factor in females (aOR: 0.342; 95 % CI: 0.13-0.91; p = 0.032). CONCLUSIONS: RSV caused more than half of ARTI cases and mostly affected previously healthy patients < 1 year old. Males living in overcrowding conditions and females who were not breastfed were at the greatest risk for LTD.

Introducción: La infección respiratoria aguda grave (IRA) es una causa muy frecuente de internación en pediatría; el virus sincicial respiratorio (VSR) es el principal agente etnológico. Definir en forma precisa la carga de enfermedad que compromete la vida (ECV) por este virus y los factores de riesgo es un desafío. Objetivos: Conocer el impacto del VSR en internados por IRA y describir factores de riesgo de ECV. Materiales y métodos: Estudio prospectivo en niños < 2 años internados por IRA durante 20122013 en el Hospital de Niños "R. Gutiérrez". Se definió ECV el requerimiento de ventilación no invasiva y/o asistencia respiratoria mecánica. Resultados: 622 niños estudiados, 372 VSR (+) (el 59,8 %). Tasa de hospitalización anual por VSR en < 1 año: 956 (IC 95 %: 858-1062)/10 000 internaciones. El VSR causó 56/78 (el 71,8 %) casos de ECV; 42 (el 75 %) eran previamente sanos; 32 (el 76,2 %) tenían < 6 meses de edad. En el análisis multivariado, el VSR fue un factor de riesgo de ECV (odds ratio ajustado [ORa] 2,04; IC 95 %: 1,15-3,63; p = 0,014). Se identificó un efecto diferencial según género en pacientes VSR (+): el hacinamiento fue un factor de riesgo de ECV en varones (ORa 2,36; IC 95 %: 1,07-5,21; p = 0,033); la lactancia materna protegió significativamente a las niñas (ORa 0,342; IC 95 %: 0,13-0,91; p = 0,032). Conclusiones: El VSR causó más de la mitad de los casos de IRA y afectó, en su mayoría, a pacientes < 1 año previamente sanos. Los varones en condiciones de hacinamiento y las niñas que no recibieron leche materna constituyeron el grupo con mayor riesgo de ECV.

Brote epidémico de dengue en la Ciudad de Buenos Aires, 2016: características clínicas y hematológicas de la infección en una población pediátrica / Dengue outbreak in Buenos Aires, Argentina, 2016: Clinical and hematological features in children

El dengue es la arbovirosis humana que más morbimortalidad ocasiona mundialmente. Durante 2016, se registró, en la Ciudad de Buenos Aires, Argentina, la mayor epidemia de esta enfermedad. Objetivo: describir las características clínicas y hematológicas en una población pediátrica. Métodos: estudio de corte transversal que incluyó a pacientes atendidos del 18-1-16 al 15-4-16 en el Hospital de Niños "Dr. Ricardo Gutiérrez". Resultados: se registraron 156 casos, 82 confirmados por virología; 130 (83 %), autóctonos. Las manifestaciones clínicas más frecuentes fueron fiebre, cefalea y dolor retroocular. Las alteraciones del laboratorio significativas fueron leucopenia, plaquetopenia y aumento de transaminasas. Se internaron 35 pacientes (23 %), 25 (16 %) con signos de alarma. No se presentó ningún caso de dengue grave. Conclusiones: el reconocimiento oportuno de los signos de alarma y el control hematológico resultan fundamentales para detectar a los niños en riesgo y ofrecerles tratamiento de soporte en forma precoz.

Dengue is the human arbovirus with the highest morbidity and mortality in the world. The largest outbreak of dengue in Buenos Aires, Argentina, occurred during 2016. Objective: To describe clinical and hematological features in children with confirmed dengue infection. Methods: Cross sectional study that included children attended since January 18th to April 15th 2016 at Hospital de Niños "Dr. Ricardo Gutiérrez". Results: among 156 registered cases, 82 confirmed cases by virology test; 130 (83 %) autochthonous cases. The most frequent clinical manifestations were fever, headache and retro-ocular pain. Laboratory abnormalities were leukopenia, thrombocytopenia and increased liver enzymes. Thirty-five children were hospitalized (23 %), 25 (16 %) with warning signs. In our study, no cases of severe dengue occurred. Conclusions: early recognition of warning signs and hematological monitoring is essential in order to detect patients at risk and offer them adequate early treatment.

[Dengue outbreak in Buenos Aires, Argentina, 2016: Clinical and hematological features in children]. / Brote epidémico de dengue en la Ciudad de Buenos Aires, 2016: características clínicas y hematológicas de la infección en una población pediátrica.

Dengue is the human arbovirus with the highest morbidity and mortality in the world. The largest outbreak of dengue in Buenos Aires, Argentina, occurred during 2016. OBJECTIVE: To describe clinical and hematological features in children with confirmed dengue infection. METHODS: Cross sectional study that included children attended since January 18th to April 15th 2016 at Hospital de Niños "Dr. Ricardo Gutiérrez". RESULTS: among 156 registered cases, 82 confirmed cases by virology test; 130 (83 %) autochthonous cases. The most frequent clinical manifestations were fever, headache and retro-ocular pain. Laboratory abnormalities were leukopenia, thrombocytopenia and increased liver enzymes. Thirty-five children were hospitalized (23 %), 25 (16 %) with warning signs. In our study, no cases of severe dengue occurred. CONCLUSIONS: early recognition of warning signs and hematological monitoring is essential in order to detect patients at risk and offer them adequate early treatment.

El dengue es la arbovirosis humana que más morbimortalidad ocasiona mundialmente. Durante 2016, se registró, en la Ciudad de Buenos Aires, Argentina, la mayor epidemia de esta enfermedad. Objetivo: describir las características clínicas y hematológicas en una población pediátrica. Métodos: estudio de corte transversal que incluyó a pacientes atendidos del 18-1-16 al 15-4-16 en el Hospital de Niños "Dr. Ricardo Gutiérrez". Resultados: se registraron 156 casos, 82 confirmados por virología; 130 (83 %), autóctonos. Las manifestaciones clínicas más frecuentes fueron fiebre, cefalea y dolor retroocular. Las alteraciones del laboratorio significativas fueron leucopenia, plaquetopenia y aumento de transaminasas. Se internaron 35 pacientes (23 %), 25 (16 %) con signos de alarma. No se presentó ningún caso de dengue grave. Conclusiones: el reconocimiento oportuno de los signos de alarma y el control hematológico resultan fundamentales para detectar a los niños en riesgo y ofrecerles tratamiento de soporte en forma precoz.

Acute Flaccid Myelitis Associated with Enterovirus D68 in Children, Argentina, 2016.

After a 2014 outbreak of severe respiratory illness caused by enterovirus D68 in the United States, sporadic cases of acute flaccid myelitis have been reported worldwide. We describe a cluster of acute flaccid myelitis cases in Argentina in 2016, adding data to the evidence of association between enterovirus D68 and this polio-like illness.

Rapid Decrease in Rates of Hospitalization Resulting From Invasive Pneumococcal Disease and Community-Acquired Pneumonia in Children Aged <60 Months After 13-Valent Pneumococcal Conjugate Vaccine Introduction in Argentina.

BACKGROUND: In January 2012, Argentina included universal pneumococcal vaccination in the routine childhood vaccination program using a 13-valent pneumococcal conjugate vaccine (PCV13). A 2 + 1 schedule (2 doses in the first year of life and a booster dose at 12 months of age) in children aged <2 years and 2-dose catch-up immunization in children aged 13 to 24 months was administered during the first year of vaccine introduction. The purpose of this study was to assess the burdens of invasive pneumococcal disease (IPD) and/or community-acquired pneumonia (CAP) in hospitalized children younger than 5 years during the first 2 years of the program compared to those in the prevaccination period in our setting. METHODS: This was a multicenter, prospective, and descriptive study. Rates of hospitalization resulting from IPD and/or CAP in 5 pediatric reference centers across the country were analyzed (every 10 000 admissions). Clinical, epidemiologic, and microbiological data were recorded. Statistical analysis using Stata 8.0 was performed. RESULTS: A comparison of rates of hospitalization resulting from global IPD and/or CAP in the prevaccine (2009-2011) and postvaccine (2012-2013) periods revealed significant decreases of 50% (P = .003) and 51% (P < .0001), respectively. Significant decreases were also observed in number of hospitalizations resulting from empyema (39%; P = .03) and pneumococcal empyema (67.8%; P = .007); the reduction was not statistically significant for pneumococcal CAP (58%; P = .18). Hospital stays for IPD and/or CAP decreased by 56%. CONCLUSION: Rapid and significant decreases in the rates of hospitalization resulting from IPD and/or CAP during the first 2 years after PCV13 introduction were observed. A longer surveillance period is required to confirm these results and the effectiveness of the vaccination program.

Pandemic influenza A/H1N1 2009 antibodies in the metropolitan area of Buenos Aires in Argentina.

OBJECTIVE: To estimate the infection prevalence in Buenos Aires during the outbreak of pandemic influenza A/H1N1 2009 virus (A(H1N1)pdm09). METHODS: A(H1N1)pdm09-specific antibodies were measured by hemagglutination inhibition assay in human serum samples collected 6 months after the outbreak and before the introduction of the A(H1N1)pdm09 vaccine in Argentina. Baseline levels of cross-reactive antibodies to A(H1N1)pdm09 were determined by testing 162 serum samples collected before 2009. RESULTS: The overall seroprevalence of A(H1N1)pdm09 in 150 children and 427 adults was 28.9% (95% confidence interval (CI) 25-33%), with a 58.0% prevalence in children <19 years of age and an 18.7% prevalence in adults ≥19 years of age (p<0.001). The prevalence was 43.5% in children <5 years old and 60.6% among children aged 5-18 years. The prevalence in adults declined with increasing age: 24.9% in 19-39-year-olds, 9.7% in 40-59-year-olds, and 8.1% in those ≥60 years old. The prevalence of specific A(H1N1)pdm09 antibodies was higher compared with the baseline in children (p=0.014), adolescents (p<0.001), and adults <40 years old (p=0.017). Seroprevalence in health care workers was not different from the rest of the population (13.6% vs. 19.3%, respectively; p=0.421). CONCLUSIONS: The prevalence of specific A(H1N1)pdm09 antibodies was high at 28.9%. The highest prevalence was observed in children, adolescents, and young adults.

An epidemiologic surveillance of Shiga-like toxin-producing Escherichia coli infection in Argentinean children: risk factors and serum Shiga-like toxin 2 values.

BACKGROUND AND AIMS: Shiga-like toxin (Stx)-producing Escherichia coli (STEC) infection is an ongoing health issue that can lead to serious complications, including hemolytic uremic syndrome (HUS) and death. This study assessed demographic and epidemiologic information of STEC infection among Argentinean children. METHODS: A prospective surveillance of 2435 screened children (age, 0.5-15 years) presenting with watery diarrhea and/or bloody diarrhea was undertaken to evaluate the clinical course of STEC infection. RESULTS: Prevalence of STEC infection was 4.1% among subjects presenting with watery diarrhea for ≤ 5 days' duration, bloody diarrhea for ≤ 36 hours' duration, or both. Incidence of STEC infection was significantly higher in the subjects with bloody diarrhea. Ninety-three STEC+ children underwent further evaluation, of whom 8 (8.6%) developed HUS. White blood cells, particularly neutrophils, were abnormally elevated at screening in 5 of 8 HUS subjects. Quantifiable serum Stx-2 values were noted within 24 to 48 hours after the onset of bloody diarrhea in 3 HUS subjects using a validated chemiluminescence assay, with levels quickly dissipating by HUS onset. CONCLUSIONS: Results suggest that young STEC-positive children with bloody diarrhea and exhibiting neutrophilic leukocytosis in the early course of their diarrhea are at risk for HUS progression. The observation of measurable concentrations of Stx-2 levels in the early post-bloody-diarrhea period and rapid dissipation at the time of HUS onset requires further evaluation.

Long-term immunity after two doses of inactivated hepatitis A vaccine, in Argentinean children.

We examined long-term anti-hepatitis A virus antibody persistence in Argentinean children 10 years after the initial study in which they received 2 doses of inactivated hepatitis A vaccine (Avaxim 80U). Of the 111 children, 48 from the initial trial were enrolled. Of 48, 47 (97.9%) participants had serum anti-hepatitis A virus antibody titers > or =20 mIU/mL, with the geometric mean concentration of 390.91 (+/-370.14) mIU/mL; (95% confidence interval, 282.2-499.5 mIU/mL), range, 36 to 1860.

Safety and pharmacokinetics of urtoxazumab, a humanized monoclonal antibody, against Shiga-like toxin 2 in healthy adults and in pediatric patients infected with Shiga-like toxin-producing Escherichia coli.

Shiga-like toxin-producing Escherichia coli (STEC) infection causes diarrhea, which is often bloody and which can result in potentially life-threatening hemolytic-uremic syndrome (HUS). Urtoxazumab, a humanized monoclonal antibody directed against the Shiga-like toxin 2 (Stx2) produced by STEC, has been developed as a promising agent for the prevention of HUS. Single randomized, intravenous, double-blind, placebo-controlled doses of urtoxazumab were administered to assess its safety and pharmacokinetics in healthy adults (0.1 to 3.0 mg/kg of body weight) and STEC-infected pediatric patients (1.0 and 3.0 mg/kg). No dose-related safety trends were noted, nor were antiurtoxazumab antibodies detected. The disposition of urtoxazumab showed a biexponential decline, regardless of the dose. In healthy adults, the mean terminal elimination half-life was consistent across the dose groups and ranged from 24.6 days (3.0-mg/kg dose group) to 28.9 days (0.3-mg/kg dose group). The mean maximum serum drug concentration (C(max)) ranged from 2.6 microg/ml at 0.1 mg/kg to 71.7 microg/ml at 3.0 mg/kg. The disposition of urtoxazumab following the administration of doses of 1.0 and 3.0 mg/kg in pediatric patients showed mean C(max)s of 19.6 and 56.1 microg/ml, respectively. Urtoxazumab was well tolerated, appears to be safe at doses of up to 3.0 mg/kg, and is a potential candidate for the prevention of HUS in pediatric patients.

Perspectives on Shiga-like Toxin Infections in Argentina †.

Argentina has the highest frequency of hemolytic uremic syndrome (HUS) in the world (300 cases/year). The risk of HUS in children from 6 to 48 months old is approximately 22/100,000 in Buenos Aires. In Argentina, HUS is the most frequent cause of acute renal damage and the second cause of chronic renal injury in children. We have shown that during the spring/summer season, the incidence of Shiga-like toxin (SLT)-associated bloody diarrhea in children less than 5 years old is 30 to 39%. The risk of HUS in SLT-associated bloody diarrhea is about 4 to 5%; 14% of children with SLT diarrhea developed incomplete HUS. Household contacts of children with HUS are commonly colonized with SLT-producing Escherichia coli (39%), and seroconversion occurs in 42% of these. No evidence of free fecal SLTs was observed in healthy children. In Argentina E. coli serotype O157:H7 has been associated with only 2 to 18% of HUS patients and in 4.5 to 7% of children with bloody diarrhea. Other serotypes were also recognized. About 20% of Argentine children start to eat meat at 5 months old, and 80% of them have meat in their diets at least three times a week. Eighty percent of the meat consumed is undercooked. Few data about the incidence of SLT-producing E. coli in cows in our country are available. E. coli O157:H7 was isolated in only 7.7% of calves aged 1 to 3 weeks with E. coli bacillosis from different farms in Argentina. Preliminary data show that SLT-producing E. coli were also present in stools from healthy animals and in fresh retail ground beef, determined by polymerase chain reaction.