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

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

Sequencing human rhinoviruses: Direct sequencing versus plasmid cloning

Human rhinoviruses (RV) are associated with the majority of viral respiratory illnesses in infants, children and adults. Over the last several years, researchers have begun to sequence the many different species and strains of RV in order to determine if certain species were associated with increased disease severity. There are a variety of techniques employed to prepare samples for sequencing. One method utilizes plasmid-cloning, which is expensive and takes several hours to complete. Recently, some investigators have instead used direct sequencing to sequence RV strains, allowing for omission of the time- and labor-intensive cloning step. This study formally compares and contrasts the sequencing results obtained from plasmid-cloning and direct Sanger sequencing of a 500 base pair PCR product covering the VP4/VP2 region of RV. A slightly longer sequence (by 65 base pairs on average) was obtained when specimens were plasmid-cloned, and the sequences were 86% similar. After trimming the extra base pairs from the cloned sequences, the sequences were 99.7% identical. Overall success of directly sequencing samples was similar to that of cloning, 5% on average failed for each technique. Therefore, in many instances, directly sequencing samples may be considered in lieu of the more expensive and time-consuming plasmid-cloning technique.Fil: Linder, Jodell E.. Vanderbilt University; Estados UnidosFil: Plachco, Tatyana E.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital Materno Infantil “Ramón Sardá”; ArgentinaFil: Libster, Romina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Miller, E. Kathryn. Vanderbilt University; Estados Unido

Seroprevalence of Bordetella pertussis among vaccinated and unvaccinated pregnant women and newborn infants in a university hospital of Buenos Aires

INTRODUCTION:Pertussis is a highly contagious disease caused by Bordetella pertussis. It poses a high morbidity and mortality rate, especially among infants younger than 6 months old. In Argentina, pertussis incidence and mortality have increased over the past three decades.OBJETIVE:To establish Bordetella pertussisantibody titers among pregnant women in their third trimester and among newborn infants, as measured in cord blood.METHODS:This was an observational, cross-sectional study. The study started in 2011; at that time, pertussis vaccination was not mandatory for pregnant women as per the national immunization schedule, only optional. Maternal antibodies were measured in the last trimester of pregnancy for women and in cord blood for newborn infants. Antibody titers were determined using Abcam´s anti-Bordetella pertussis toxin (PT) IgG in vitro ELISA kit. The χ² test was used to compare prevalence rates.RESULTS:The study included 111 mother-newborn infant dyads; 35 infants from unvaccinated mothers (before the introduction of the vaccine) and 76 from vaccinated mothers. Positive IgG antibodies were found in 92% (70/76) of infants born from vaccinated mothers whereas 100% (35/35) of infants born from unvaccinated mothers had negative results for antibodies; p < 0.001.CONCLUSION:In the vaccinated population of this study, 92% of infants had positive IgG antibodies. This study supports the need for maternal immunization against Bordetella pertussis to provide protection to newborn infants.Fil: Bosch, Juan J.. Hospital Universitario Austral; ArgentinaFil: Fernandez, Hilario. Hospital Universitario Austral; ArgentinaFil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Musante, Gabriel. Hospital Universitario Austral; ArgentinaFil: Libster, Romina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Universitario Austral; ArgentinaFil: Rocca Rivarola, María Dolores. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Universitario Austral; Argentin

Impact of a maternal immunization program against pertussis in a developing country

Background: Pertussis disease is a growing concern for developing countries. In Argentina, rates of illness and death peaked in 2011. More than 50% of fatalities due to pertussis occurred in infants younger than two months of age, too young for vaccination. In 2012, the government offered immunization with a vaccine containing Tdap to all pregnant women after 20 weeks of gestation with the intent of reducing morbidity and mortality in young infants. Methods: Maternal acellular pertussis vaccine impact on reducing infant disease burden was estimated based on data from the Argentinean Health Surveillance System. We divided Argentinean states in two groups experiencing high (>50) and low (⩽50) Tdap vaccine coverage and compared these two groups using a Bayesian structural time-series model. Low coverage regions were used as a control group, and the time series were compared before and after the implementation of the Tdap program. Findings: We observed a relative reduction of 51% (95% CI [−67%, −35%]; p = 0.001) in pertussis cases in high coverage states in comparison with the low coverage areas. Analysis of infants between two and six months showed a 44% (95% CI [−66%, −24%]; p = 0.001) reduction in illness. Number of deaths was highest in 2011 with 76 fatalities, for an incidence rate of 2.9 per 100,000. Comparing with 2011, rates decreased by 87% to 10 subjects, or 0.9 per 100,000 in 2013. Interpretation: We show an age-dependent protective effect of maternal Tdap immunization in a developing country for infants younger than six months.Fil: Vizzotti, Carla. Ministerio de Salud de la Nación; ArgentinaFil: Juarez, Maria V.. Ministerio de Salud de la Nación; ArgentinaFil: Bergel, Eduardo. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Romanin, Viviana. Ministerio de Salud de la Nación; ArgentinaFil: Califano, Gloria. Ministerio de Salud de la Nación; ArgentinaFil: Sagradini, Sandra. Ministerio de Salud de la Nación; ArgentinaFil: Rancaño, Carolina. Ministerio de Salud de la Nación; ArgentinaFil: Aquino, Analía. Ministerio de Salud de la Nación; ArgentinaFil: Libster, Romina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina. Vanderbilt University; Estados UnidosFil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. Vanderbilt University; Estados UnidosFil: Manzur, Juan. Ministerio de Salud de la Nación; Argentin

IL-8/IL-17 gene variations and the susceptibility to severe viral bronchiolitis

Clinical manifestations of acute bronchiolitis (AB) vary from minimal disease to severe respiratory failure. The response to respiratory viral infections is possibly influenced by genetic polymorphisms linked to the regulation of the inflammatory response. In the present study, we investigated whether interleukin-8 (IL-8) and interleukin-17 (IL-17) genetic variants are associated with the severity of AB. A group of Brazilian infants hospitalized with AB and a control group (infants with no or mild AB, without hospitalization) were genotyped for four IL-8/IL-17 variations. For replication, we studied an Argentinean population sample of infants with mild and severe AB. IL-8 polymorphism (rs 2227543) and IL-17 (rs2275913) variants showed significant associations with the severity of AB. The effect of the IL-8 variation could be replicated in the Argentinean sample. This finding suggests that IL-8 variations may influence the severity of AB in young infants. Further genetic association studies in low- or middle-income populations are necessary with the aim of expanding knowledge in this area.Fil: Pinto, L.A.. Aliança INFANT; Brasil. Pontificia Universidade Católica do Rio Grande do Sul; BrasilFil: De Azeredo Leitão, L.A.. Aliança INFANT; Brasil. Pontificia Universidade Católica do Rio Grande do Sul; BrasilFil: Mocellin, M.. Aliança INFANT; Brasil. Pontificia Universidade Católica do Rio Grande do Sul; BrasilFil: Acosta, Patricio Leandro. Aliança INFANT; Brasil. Fundación INFANT; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Caballero, Mauricio Tomás. Aliança INFANT; Brasil. Fundación INFANT; ArgentinaFil: Libster, Romina Paula. Aliança INFANT; Brasil. Fundación INFANT; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vargas, J. E.. Aliança INFANT; Brasil. Pontificia Universidade Católica do Rio Grande do Sul; BrasilFil: Polack, F.. Aliança INFANT; Brasil. Fundación INFANT; ArgentinaFil: Comaru, T.. Aliança INFANT; Brasil. Pontificia Universidade Católica do Rio Grande do Sul; BrasilFil: Stein, R.T.. Aliança INFANT; Brasil. Pontificia Universidade Católica do Rio Grande do Sul; BrasilFil: De Souza, A.P.. Aliança INFANT; Brasil. Pontificia Universidade Católica do Rio Grande do Sul; Brasi

T helper type 2 bias and type 17 suppression in primary dengue virus infection in infants and young children

Background: The immune response to dengue virus (DENV) primary infection in infants and young children is not well characterized. In Northern Argentina, .90% of the population was DENV-naı¨ve before the 2009 outbreak, allowing evaluation of age-dependent primary responses to infection. Methods: We conducted a comparative study of the immune response to DENV in 27 infected infants, young children and their mothers. Lymphocyte T helper (Th) 1, Th2, Th17 and inflammatory responses were assayed in blood during the 2009 DENV-1 epidemic. Results: The immune response to DENV-1 was significantly biased to Th2 in infected infants and young children, compared to infants with other febrile illnesses (for IL-4 p,0.001) and to their infected mothers (for IL-4 p,0.01). In addition, IL-17 suppression was observed in the memory response to DENV-1 in infected infants (p,0.01 vs placebo). Conclusion: Age-related differences in the primary response to DENV, characterized by an immature Th2 polarization and Th17 suppression in infants, should be studied further in order to expand our understanding of the mechanism of dengue pathogenesis.Fil: Talarico, Laura Beatriz. Fundación para la Investigación en Infectologia Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bugna Hortoneda, Jimena. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Wimmenauer, Vera. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Espinoza, Marco A.. Hospital San Vicente de Paul; ArgentinaFil: Quipildor, Marcelo O.. Hospital San Vicente de Paul; ArgentinaFil: Hijano, Diego R.. Vanderbilt University. Department of Pediatrics; Estados Unidos. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Beccaria, Martín. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Wurster, Victoria. Vanderbilt University. Department of Pediatrics; Estados Unidos. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Cavagnaro, Luis E.. Hospital SAMIC Iguazu; ArgentinaFil: Martinez, Daniel. Hospital SAMIC Iguazu; ArgentinaFil: Fattore, Gladys. Fundación Mundo Sano; ArgentinaFil: Batalle, Juan Pio. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Acosta, Patricio Leandro. Fundación para la Investigación en Infectologia Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Reynoso, Natalia. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Melendi, Guillermina Amanda. Vanderbilt University. Department of Pediatrics; Estados Unidos. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Rey, Felix A.. Institut Pasteur. Département de Virologie. Unité de Virologie Structurale; FranciaFil: Libster, Romina Paula. Vanderbilt University. Department of Pediatrics; Estados Unidos. Fundación para la Investigación en Infectologia Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Polack, Fernando Pedro. Vanderbilt University. Department of Pediatrics; Estados Unidos. Fundación para la Investigación en Infectologia Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Fatal enhanced respiratory syncytial virus disease in toddlers

In 1967, two toddlers immunized with a formalin-inactivated vaccine against respiratory syncytial virus (FIRSV) in the United States died from enhanced RSV disease (ERD), a severe form of illness resulting from aberrant priming of the antiviral immune response during vaccination. Up to 80% of immunized children subsequently exposed to wild-type virus were hospitalized. These events hampered RSV vaccine development for decades. Here, we provide a characterization of the clinical, immunopathological, and transcriptional signature of fatal human ERD, outlining evidence for safety evaluation of RSV vaccines and a framework for understanding disease enhancement for pathogens in general.Fil: Polack, Fernando Pedro. Vanderbilt University; Estados Unidos. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Álvarez Paggi, Damián Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Libster, Romina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Caballero, Mauricio Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Blair, Robert V.. University of Tulane; Estados UnidosFil: Hijano, Diego Raúl. Fundación para la Investigación en Infectología Infantil; Argentina. St. Jude Children’s Research Hospital; Estados UnidosFil: de la Iglesia Niveyro, Paola Ximena. Hospital Italiano; ArgentinaFil: Menendez, Franco Daniel. National Institute ff Environmental Health Sciences; Estados UnidosFil: Gladwell, Wes. National Institute ff Environmental Health Sciences; Estados UnidosFil: Avendano, Luis M.. Universidad Nacional de Chile; ChileFil: Velozo, Luis. Universidad Nacional de Chile; ChileFil: Wanek, Alanna. University of Tulane; Estados UnidosFil: Bergel, Eduardo. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Prince, Gregory A.. Independent Researcher; Estados UnidosFil: Kleeberger, Steven R.. Hospital Italiano; ArgentinaFil: Johnson, Joyce. Vanderbilt University; Estados UnidosFil: Pociask, Derek. University of Tulane; Estados UnidosFil: Kolls, Jay K.. University of Tulane; Estados Unido