Quantifying long-term health and economic outcomes for survivors of group B Streptococcus invasive disease in infancy: protocol of a multi-country study in Argentina, India, Kenya, Mozambique and South Africa

Sepsis and meningitis due to invasive group B Streptococcus (iGBS) disease during early infancy is a leading cause of child mortality. Recent systematic estimates of the worldwide burden of GBS suggested that there are 319,000 cases of infant iGBS disease each year, and an estimated 147,000 stillbirths and young-infant deaths, with the highest burden occurring in Sub-Saharan Africa. The following priority data gaps were highlighted: (1) long-term outcome data after infant iGBS, including mild disability, to calculate quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs) and (2) economic burden for iGBS survivors and their families. Geographic data gaps were also noted with few studies from low- and middle- income countries (LMIC), where the GBS burden is estimated to be the highest. In this paper we present the protocol for a multi-country matched cohort study designed to estimate the risk of long-term neurodevelopmental impairment (NDI), socioemotional behaviors, and economic outcomes for children who survive invasive GBS disease in Argentina, India, Kenya, Mozambique, and South Africa. Children will be identified from health demographic surveillance systems, hospital records, and among participants of previous epidemiological studies. The children will be aged between 18 months to 17 years. A tablet-based custom-designed application will be used to capture data from direct assessment of the child and interviews with the main caregiver. In addition, a parallel sub-study will prospectively measure the acute costs of hospitalization due to neonatal sepsis or meningitis, irrespective of underlying etiology. In summary, these data are necessary to characterize the consequences of iGBS disease and enable the advancement of effective strategies for survivors to reach their developmental and economic potential. In particular, our study will inform the development of a full public health value proposition on maternal GBS immunization that is being coordinated by the World Health Organization

Asymptomatic COVID-19 in the elderly: dementia and viral clearance as risk factors for disease progression

Background:SARS-CoV-2 infected individuals ≥60 years old have the highest hospitalization rates and represent >80% fatalities. Within this population, those in long-term facilities represent >50% of the total COVID-19 related deaths per country. Among those without symptoms, the rate of pre-symptomatic illness is unclear, and potential predictors of progression for symptom development are unknown.Our objective was to delineate the natural evolution of asymptomatic SARS-CoV-2 infection in elders and identify determinants of progression.Methods:We established a medical surveillance team monitoring 63 geriatric institutions. When an index COVID-19 case emerged, we tested all other eligible asymptomatic elders ≥75 or >60 years old with at least 1 comorbidity. SARS-CoV-2 infected elders were followed for 28 days. Disease was diagnosed when any COVID-19 manifestation occurred. SARS-CoV-2 load at enrollment, shedding on day 15, and antibody responses were also studied.Results:After 28 days of follow-up, 74/113(65%) SARS-CoV-2-infected elders remained asymptomatic. 21/39(54%) pre-symptomatic patients developed hypoxemia and ten pre-symptomatic patients died(median day 13.5,IQR 12).Dementia was the only clinical risk factor associated with disease(OR 2.41(95%CI=1.08, 5.39). In a multivariable logistic regression model, dementia remained as a risk factor for COVID-19 severe disease. Furthermore, dementia status showed a statistically significant different trend when assessing the cumulative probability of developing COVID-19 symptoms(log-rank p=0.027).On day 15, SARS-CoV-2 was detectable in 30% of the asymptomatic group while in 61% of the pre-symptomatic(p=0.012).No differences were observed among groups in RT-PCR mean cycle threshold at enrollment(p=0.391) and in the rates of antibody seropositivity(IgM and IgG against SARS-CoV-2 nucleocapsid protein).Conclusions:In summary, 2/3 of our cohort of SARS-CoV-2 infected elders from vulnerable communities in Argentina remained asymptomatic after 28 days of follow-up with high mortality among those developing symptoms. Dementia and persistent SARS-CoV-2 shedding were associated with progression from asymptomatic to symptomatic infection.Fil: Esteban, Ignacio. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Bergero, Georgina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Alves, Camila. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Bronstein, Micaela. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Ziegler, Valeria. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Wood, Cristian. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; ArgentinaFil: Caballero, Mauricio Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Wappner, Diego. No especifíca;Fil: Libster, Romina Paula. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Perez Marc, Gonzalo. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; ArgentinaFil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentin

Respiratory failure and death in vulnerable premature children with lower respiratory tract illness

Background. Efforts to better understand the risk factors associated with respiratory failure (RF) and fatal lower respiratory tract infection (LRTI) in premature children in developing countries are necessary to elaborate evidenced-based preventive interventions. We aim to characterize the burden of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) LRTI in premature children and determine risk factors for RF and fatal illness in a vulnerable population. Methods. This is a prospective, population-based, cross-sectional study. Subjects with severe LRTI were enrolled during respiratory season. Risk factors for RF and death in premature infants were investigated. Results. A total of 664 premature children participated. Infant's hospitalization rate due to LRTI was 82.6/1000 (95% confidence interval [CI], 68.6-96.7/1000). Infant's RSV and hMPV rates were 40.9/1000 (95% CI, 36.3-45.6/1000) and 6.6/1000 (95% CI, 3.9- 9.2/1000), respectively. The RF rate was 8.2/1000 (95% CI, 4.9-11.5/1000). The LRTI mortality was 2.2/1000 (95% CI, 0.7-3.7/1000); for RSV, the rate was 0.8/1000 (95% CI, 0-1.7/1000) with a case-fatality ratio of 1.8%. Never breastfeeding, malnutrition, younger than 6 months, congenital heart disease, and lower hematocrit were risk factors for RF. Experiencing pneumonia, pneumothorax, sepsis, or apnea were clinical determinants of poor outcomes. Conclusions. Premature children under 2 years old in vulnerable environments experience RF and death more often than term counterparts. Modifiable risk factors associated with poor outcomes should prompt evidence-based interventions.Fil: Ofman, Gaston. Fundacion de Endocrinologia Infantil.; ArgentinaFil: Pradarelli, Brad. Fundacion de Endocrinologia Infantil.; ArgentinaFil: Caballero, Mauricio Tomás. Fundacion de Endocrinologia Infantil.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bianchi, Alejandra. Fundacion de Endocrinologia Infantil.; ArgentinaFil: Grimaldi, Luciano Alva. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Doctor Lucio Melendez.; ArgentinaFil: Sancilio, Andrea. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal de Agudos Evita; ArgentinaFil: Duenas, Karina. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal de Agudos Evita; ArgentinaFil: Rodriguez, Andrea. Gobierno de la Provincia de Buenos Aires. Hospital Provincial Evita Pueblo.; ArgentinaFil: Ferrero, Fernando. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Ferretti, Adrian. Fundacion de Endocrinologia Infantil.; ArgentinaFil: Coviello, Silvina Andrea. Fundacion de Endocrinologia Infantil.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ferolla, Fausto Martín. Fundacion de Endocrinologia Infantil.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Acosta, Patricio Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundacion de Endocrinologia Infantil.; ArgentinaFil: Bergel, Eduardo. Fundacion de Endocrinologia Infantil.; ArgentinaFil: Libster, Romina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundacion de Endocrinologia Infantil.; ArgentinaFil: Polack, Fernando Pedro. Fundacion de Endocrinologia Infantil.; Argentin

Quantifying long-term health and economic outcomes for survivors of group B Streptococcus invasive disease in infancy: protocol of a multi-country study in Argentina, India, Kenya, Mozambique and South Africa.

Sepsis and meningitis due to invasive group B Streptococcus (iGBS) disease during early infancy is a leading cause of child mortality. Recent systematic estimates of the worldwide burden of GBS suggested that there are 319,000 cases of infant iGBS disease each year, and an estimated 147,000 stillbirths and young-infant deaths, with the highest burden occurring in Sub-Saharan Africa.  The following priority data gaps were highlighted: (1) long-term outcome data after infant iGBS, including mild disability, to calculate quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs) and (2) economic burden for iGBS survivors and their families. Geographic data gaps were also noted with few studies from low- and middle- income countries (LMIC), where the GBS burden is estimated to be the highest. In this paper we present the protocol for a multi-country matched cohort study designed to estimate the risk of long-term neurodevelopmental impairment (NDI), socioemotional behaviors, and economic outcomes for children who survive invasive GBS disease in Argentina, India, Kenya, Mozambique, and South Africa. Children will be identified from health demographic surveillance systems, hospital records, and among participants of previous epidemiological studies. The children will be aged between 18 months to 17 years. A tablet-based custom-designed application will be used to capture data from direct assessment of the child and interviews with the main caregiver. In addition, a parallel sub-study will prospectively measure the acute costs of hospitalization due to neonatal sepsis or meningitis, irrespective of underlying etiology. In summary, these data are necessary to characterize the consequences of iGBS disease and enable the advancement of effective strategies for survivors to reach their developmental and economic potential. In particular, our study will inform the development of a full public health value proposition on maternal GBS immunization that is being coordinated by the World Health Organization

Role for Maternal Asthma in Severe Human Metapneumovirus Lung Disease Susceptibility in Children

Background: Severity of human metapneumovirus (hMPV) lower respiratory illness (LRTI) is considered similar to that observed for respiratory syncytial virus (RSV). However, differences in severity between these pathogens have been noted, suggesting the degree of illness may vary in different populations. Moreover, a potential association between hMPV and asthma also suggests that hMPV may preferentially affect asthmatic subjects. Methods: In a population-based surveillance study in children aged <2 years admitted for severe LRTI in Argentina, nasopharyngeal aspirates were tested by RT-PCR for hMPV, RSV, influenza A, and human rhinovirus. Results: Of 3947 children, 383 (10%) were infected with hMPV. The hospitalization rate for hMPV LRTI was 2.26 per 1000 children (95% confidence interval [CI], 2.04-2.49). Thirty-nine (10.2%) patients infected with hMPV experienced life-threatening disease (LTD; 0.23 per 1000 children; 95% CI,. 16-.31/1000), and 2 died (mortality rate 0.024 per 1000; 95% CI,. 003-.086). In hMPV-infected children birth to an asthmatic mother was an increased risk for LTD (odds ratio, 4.72; 95% CI, 1.39-16.01). We observed a specific interaction between maternal asthma and hMPV infection affecting risk for LTD. Conclusions: Maternal asthma increases the risk for LTD in children <2 years old hospitalized for severe hMPV LRTI.Fil: Libster, Romina Paula. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Esteban, Ignacio. Fundación para la Investigación en Infectología Infantil; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Bianchi, Alejandra Silvina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Alva Grimaldi, Luciano. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Doctor Lucio Melendez.; ArgentinaFil: Dueñas, Karina. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal de Agudos Evita.; ArgentinaFil: Sancillo, Andrea. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal de Agudos Evita.; ArgentinaFil: Rodriguez, Andrea. Gobierno de la Provincia de Buenos Aires. Hospital Provincial Evita Pueblo.; ArgentinaFil: Ferrero, Fernando. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Stein, Katherine. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Acosta, Patricio Leandro. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ferolla, Fausto Martín. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bergel, Eduardo. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Caballero, Mauricio Tomás. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Pellegrino, Gustavo. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Fernandez Gago, Guadalupe. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Pozzolo, Cecilia. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Castro, Laura. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Almeida, Rodrigo Egues. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Rebec, Beatriz. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: González, Mariela. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Calvo, Mariel. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Henrichsen, Julieta. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Nocito, Celina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Barbero, Guillermo. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Ves Losada, Juan. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Bonina, Angel. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Flamenco, Edgardo. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Rodriguez Perez, Alberto. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Kobylarz, Alicia. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Raggio, Mirta. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Schavlosky, Graciela. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Caria, Adriana. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Barboza, Edgar. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Sastre, Gustavo. Fundación para la Investigación en Infectología Infantil; Argentin

Early high-titer plasma therapy to prevent severe Covid-19 in older adults

BACKGROUND: Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness. METHODS We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible. RESULTS A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P = 0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed. CONCLUSIONS Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19. (Funded by the Bill and Melinda Gates Foundation and the Fundación INFANT Pandemic Fund; Dirección de Sangre y Medicina Transfusional del Ministerio de Salud number, PAEPCC19, Plataforma de Registro Informatizado de Investigaciones en Salud number, 1421, and ClinicalTrials.gov number, NCT04479163.).Fil: Libster, Romina Paula. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Pérez Marc, Gonzalo. Hospital Militar Central, Buenos Aires; ArgentinaFil: Wappner, Diego. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Coviello, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Bianchi, Alejandra. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Braem, Virginia. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Esteban, Ignacio. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Caballero, Mauricio Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wood, Cristian. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Berrueta, Mabel. Hospital Militar Central; ArgentinaFil: Rondan, Aníbal. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Lescano, Gabriela Mariel. Hospital Dr. Carlos Bocalandro; ArgentinaFil: Cruz, Pablo. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Ritou, Yvonne. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Fernández Viña, Valeria Silvina. Hospital Simplemente Evita; ArgentinaFil: Álvarez Paggi, Damián Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Esperante, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Ferreti, Adrián. Hospital Dr. Carlos Bocalandro; ArgentinaFil: Ofman, Gaston. University of Oklahoma; Estados UnidosFil: Ciganda, Álvaro. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal Especializado de Agudos y Cronicos San Juan de Dios.; ArgentinaFil: Rodriguez, Rocío. Hospital Simplemente Evita; ArgentinaFil: Lantos, Jorge. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Valentini, Ricardo. No especifíca;Fil: Itcovici, Nicolás. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Hintze, Alejandra. No especifíca;Fil: Oyarvide, M. Laura. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Etchegaray, Candela. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Neira, Alejandra. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Name, Ivonne. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Alfonso, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Swiss Medical Group; ArgentinaFil: López Castelo, Rocío. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Caruso, Gisela. Hospital Militar Central; ArgentinaFil: Rapelius, Sofía. Hospital Militar Central; ArgentinaFil: Alvez, Fernando. Hospital Militar Central; ArgentinaFil: Etchenique, Federico. Hospital Militar Central; ArgentinaFil: Dimase, Federico. Hospital Militar Central; ArgentinaFil: Alvarez, Darío. Hospital Militar Central; ArgentinaFil: Aranda, Sofía S.. Hospital Militar Central; ArgentinaFil: Sánchez Yanotti, Clara Inés. Hospital Militar Central; ArgentinaFil: De Luca, Julián. Hospital Militar Central; ArgentinaFil: Jares Baglivo, Sofía. Hospital Militar Central; ArgentinaFil: Laudanno, Sofía. Fundación Hematológica Sarmiento; ArgentinaFil: Nowogrodzki, Florencia. Swiss Medical Group; ArgentinaFil: Larrea, Ramiro. Hospital Municipal San Isidro; ArgentinaFil: Silveyra, María. Hospital Militar Central; ArgentinaFil: Leberzstein, Gabriel. No especifíca;Fil: Debonis, Alejandra. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Molinos, Juan. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: González, Miguel. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Perez, Eduardo. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Kreplak, Nicolás. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Pastor Argüello, Susana. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Gibbons, Luz. Hospital Municipal de San Isidro; ArgentinaFil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Bergel, Eduardo. Sanatorio Sagrado Corazón; ArgentinaFil: Polack, Fernando Pedro. Provincia de Buenos Aires. Ministerio de Salud; Argentin

Emotional and Behavioral Outcomes in Childhood for Survivors of Invasive Group B Streptococcus Disease in Infancy: Findings From 5 Low- and Middle-Income Countries.

BACKGROUND: Survivors of invasive group B Streptococcus (iGBS) disease, notably meningitis, are at increased risk of neurodevelopmental impairment. However, the limited studies to date have a median follow-up to 18 months and have mainly focused on moderate or severe neurodevelopmental impairment, with no previous studies on emotional-behavioral problems among iGBS survivors. METHODS: In this multicountry, matched cohort study, we included children aged 18 months to 17 years with infant iGBS sepsis and meningitis from health demographic surveillance systems, or hospital records in Argentina, India, Kenya, Mozambique, and South Africa. Children without an iGBS history were matched to iGBS survivors for sex and age. Our primary outcomes were emotional-behavioral problems and psychopathological conditions as measured with the Child Behavior Checklist (CBCL). The CBCL was completed by the child's primary caregiver. RESULTS: Between October 2019 and April 2021, 573 children (mean age, 7.18 years) were assessed, including 156 iGBS survivors and 417 non-iGBS comparison children. On average, we observed more total problems and more anxiety, attention, and conduct problems for school-aged iGBS survivors compared with the non-iGBS group. No differences were found in the proportion of clinically significant psychopathological conditions defined by the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). CONCLUSIONS: Our findings suggested that school-aged iGBS survivors experienced increased mild emotional behavioral problems that may affect children and families. At-risk neonates including iGBS survivors need long-term follow-up with integrated emotional-behavioral assessments and appropriate care. Scale-up will require simplified assessments that are free and culturally adapted

Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

Fil: Monsalvo, Ana Clara. Fundacion INFANT, Buenos Aires; Argentina.Fil: Batalle, Juan P. Fundacion INFANT, Buenos Aires; Argentina.Fil: Lopez, M Florencia. Fundacion INFANT, Buenos Aires; Argentina.Fil: Krause, Jens C. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Klemenc, Jennifer. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Hernandez, Johanna Zea. . Fundacion INFANT, Buenos Aires; Argentina.Fil: Maskin, Bernardo. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Bugna, Jimena. Fundacion INFANT, Buenos Aires; Argentina.Fil: Rubinstein, Carlos. Hospital Dr Federico Abete, Malvinas Argentinas, Buenos Aires; Argentina.Fil: Aguilar, Leandro. Hospital Dr Federico Abete, Malvinas Argentinas, Buenos Aires; Argentina.Fil: Dalurzo, Liliana. Hospital Italiano, Buenos Aires; Argentina.Fil: Libster, Romina. Fundacion INFANT, Buenos Aires; Argentina.Fil: Savy, Vilma. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Baumeister, Elsa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Aguilar, Liliana. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Cabral, Graciela. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Font, Julia. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Solari, Liliana. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Weller, Kevin P. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Johnson, Joyce. Department of Pathology, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Echavarria, Marcela. Department of Microbiology, CEMIC, Buenos Aires; Argentina.Fil: Edwards, Kathryn M. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Chappell, James D. Department of Pathology, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Crowe, James E. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Williams, John V. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Melendi, Guillermina A. Fundacion INFANT, Buenos Aires; Argentina.Fil: Polack, Fernando P. Fundacion INFANT, Buenos Aires; Argentina.Pandemic influenza viruses often cause severe disease in middle-aged adults without preexisting comorbidities. The mechanism of illness associated with severe disease in this age group is not well understood. Here we find preexisting serum antibodies that cross-react with, but do not protect against, 2009 H1N1 influenza virus in middle-aged adults. Nonprotective antibody is associated with immune complex-mediated disease after infection. We detected high titers of serum antibody of low avidity for H1-2009 antigen, and low-avidity pulmonary immune complexes against the same protein, in severely ill individuals. Moreover, C4d deposition--a marker of complement activation mediated by immune complexes--was present in lung sections of fatal cases. Archived lung sections from middle-aged adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a previously unknown biological mechanism for the unusual age distribution of severe cases during influenza pandemics

Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

Fil: Monsalvo, Ana Clara. Fundacion INFANT, Buenos Aires; Argentina.Fil: Batalle, Juan P. Fundacion INFANT, Buenos Aires; Argentina.Fil: Lopez, M Florencia. Fundacion INFANT, Buenos Aires; Argentina.Fil: Krause, Jens C. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Klemenc, Jennifer. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Hernandez, Johanna Zea. . Fundacion INFANT, Buenos Aires; Argentina.Fil: Maskin, Bernardo. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Bugna, Jimena. Fundacion INFANT, Buenos Aires; Argentina.Fil: Rubinstein, Carlos. Hospital Dr Federico Abete, Malvinas Argentinas, Buenos Aires; Argentina.Fil: Aguilar, Leandro. Hospital Dr Federico Abete, Malvinas Argentinas, Buenos Aires; Argentina.Fil: Dalurzo, Liliana. Hospital Italiano, Buenos Aires; Argentina.Fil: Libster, Romina. Fundacion INFANT, Buenos Aires; Argentina.Fil: Savy, Vilma. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Baumeister, Elsa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Aguilar, Liliana. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Cabral, Graciela. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Font, Julia. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Solari, Liliana. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Weller, Kevin P. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Johnson, Joyce. Department of Pathology, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Echavarria, Marcela. Department of Microbiology, CEMIC, Buenos Aires; Argentina.Fil: Edwards, Kathryn M. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Chappell, James D. Department of Pathology, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Crowe, James E. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Williams, John V. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Melendi, Guillermina A. Fundacion INFANT, Buenos Aires; Argentina.Fil: Polack, Fernando P. Fundacion INFANT, Buenos Aires; Argentina.Pandemic influenza viruses often cause severe disease in middle-aged adults without preexisting comorbidities. The mechanism of illness associated with severe disease in this age group is not well understood. Here we find preexisting serum antibodies that cross-react with, but do not protect against, 2009 H1N1 influenza virus in middle-aged adults. Nonprotective antibody is associated with immune complex-mediated disease after infection. We detected high titers of serum antibody of low avidity for H1-2009 antigen, and low-avidity pulmonary immune complexes against the same protein, in severely ill individuals. Moreover, C4d deposition--a marker of complement activation mediated by immune complexes--was present in lung sections of fatal cases. Archived lung sections from middle-aged adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a previously unknown biological mechanism for the unusual age distribution of severe cases during influenza pandemics

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09‐related pneumonia: an individual participant data meta‐analysis

BACKGROUND: The impact of neuraminidase inhibitors (NAIs) on influenza‐related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. METHODS: A worldwide meta‐analysis of individual participant data from 20 634 hospitalised patients with laboratory‐confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) ‘pandemic influenza’. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. RESULTS: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64–1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44–1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71–1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55–0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54–0·85; P = 0·001)]. CONCLUSIONS: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support