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Background BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine encoding a prefusion-stabilized, membrane-anchored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) full-length spike protein. BNT162b2 is highly efficacious against coronavirus disease 2019 (Covid-19) and is currently approved, conditionally approved, or authorized for emergency use worldwide. At the time of initial authorization, data beyond 2 months after vaccination were unavailable. Methods In an ongoing, placebo-controlled, observer-blinded, multinational, pivotal efficacy trial, we randomly assigned 44,165 participants 16 years of age or older and 2264 participants 12 to 15 years of age to receive two 30-μg doses, at 21 days apart, of BNT162b2 or placebo. The trial end points were vaccine efficacy against laboratory-confirmed Covid-19 and safety, which were both evaluated through 6 months after vaccination. Results BNT162b2 continued to be safe and have an acceptable adverse-event profile. Few participants had adverse events leading to withdrawal from the trial. Vaccine efficacy against Covid-19 was 91.3% (95% confidence interval [CI], 89.0 to 93.2) through 6 months of follow-up among the participants without evidence of previous SARS-CoV-2 infection who could be evaluated. There was a gradual decline in vaccine efficacy. Vaccine efficacy of 86 to 100% was seen across countries and in populations with diverse ages, sexes, race or ethnic groups, and risk factors for Covid-19 among participants without evidence of previous infection with SARS-CoV-2. Vaccine efficacy against severe disease was 96.7% (95% CI, 80.3 to 99.9). In South Africa, where the SARS-CoV-2 variant of concern B.1.351 (or beta) was predominant, a vaccine efficacy of 100% (95% CI, 53.5 to 100) was observed. Conclusions Through 6 months of follow-up and despite a gradual decline in vaccine efficacy, BNT162b2 had a favorable safety profile and was highly efficacious in preventing Covid-19. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

Background Many deaths in infants from low-middle income countries (LMICs) occur at home or upon arrival to health facilities. Although acute lower respiratory tract illness plays an important role in community mortality, the accuracy of mortality rates due to respiratory syncytial virus (RSV) remains unknown. Methods An active surveillance study among children aged under 5 years old (U5) was performed in Buenos Aires, Argentina, between January and December 2019, to define the burden and role of RSV in childhood community mortality. Results A total of 63 families of children U5 participated in the study. Based on a combined approach of tissue sampling, verbal autopsies, and expert’s analysis, RSV infection was found in the causal chain of 11 from 12 cases with positive molecular biology results in respiratory samples. The estimated mortality rate due to RSV among infants was 0.27 deaths/1000 live births. The mean age of RSV-related household deaths was 2.8 months of age (standard deviation [SD] 1.7), and 8/12 were male infants (66.7%). Dying at home from RSV was associated with Streptococcus pneumoniae and/or Moraxella catarrhalis lung coinfection (75%), living in slums and settlement (odds ratio [OR], 17.09; 95% confidence interval [CI], 1.3–219.2), and other underlying comorbidities (OR, 14.87; 95% CI, 1.3–164.6). Conclusions Infant community mortality rates due to RSV are higher than those reported in industrialized countries and similar to those reported in hospital-based studies in the same catchment population.

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; Argentina Fil: Pérez Marc, Gonzalo. Hospital Militar Central, Buenos Aires; Argentina Fil: Wappner, Diego. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Coviello, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Bianchi, Alejandra. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Braem, Virginia. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Esteban, Ignacio. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Caballero, Mauricio Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Wood, Cristian. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Berrueta, Mabel. Hospital Militar Central; Argentina Fil: Rondan, Aníbal. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Lescano, Gabriela Mariel. Hospital Dr. Carlos Bocalandro; Argentina Fil: Cruz, Pablo. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Ritou, Yvonne. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Fernández Viña, Valeria Silvina. Hospital Simplemente Evita; Argentina Fil: Álvarez Paggi, Damián Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: 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; Argentina Fil: Ferreti, Adrián. Hospital Dr. Carlos Bocalandro; Argentina Fil: Ofman, Gaston. University of Oklahoma; Estados Unidos Fil: Ciganda, Álvaro. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal Especializado de Agudos y Cronicos San Juan de Dios.; Argentina Fil: Rodriguez, Rocío. Hospital Simplemente Evita; Argentina Fil: Lantos, Jorge. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Valentini, Ricardo. No especifíca; Fil: Itcovici, Nicolás. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Hintze, Alejandra. No especifíca; Fil: Oyarvide, M. Laura. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Etchegaray, Candela. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Neira, Alejandra. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Name, Ivonne. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Alfonso, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Swiss Medical Group; Argentina Fil: López Castelo, Rocío. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina Fil: Caruso, Gisela. Hospital Militar Central; Argentina Fil: Rapelius, Sofía. Hospital Militar Central; Argentina Fil: Alvez, Fernando. Hospital Militar Central; Argentina Fil: Etchenique, Federico. Hospital Militar Central; Argentina Fil: Dimase, Federico. Hospital Militar Central; Argentina Fil: Alvarez, Darío. Hospital Militar Central; Argentina Fil: Aranda, Sofía S.. Hospital Militar Central; Argentina Fil: Sánchez Yanotti, Clara Inés. Hospital Militar Central; Argentina Fil: De Luca, Julián. Hospital Militar Central; Argentina Fil: Jares Baglivo, Sofía. Hospital Militar Central; Argentina Fil: Laudanno, Sofía. Fundación Hematológica Sarmiento; Argentina Fil: Nowogrodzki, Florencia. Swiss Medical Group; Argentina Fil: Larrea, Ramiro. Hospital Municipal San Isidro; Argentina Fil: Silveyra, María. Hospital Militar Central; Argentina Fil: Leberzstein, Gabriel. No especifíca; Fil: Debonis, Alejandra. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Molinos, Juan. Fundación para la Investigación en Infectología Infantil; Argentina Fil: González, Miguel. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Perez, Eduardo. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Kreplak, Nicolás. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Pastor Argüello, Susana. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Gibbons, Luz. Hospital Municipal de San Isidro; Argentina Fil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Bergel, Eduardo. Sanatorio Sagrado Corazón; Argentina Fil: Polack, Fernando Pedro. Provincia de Buenos Aires. Ministerio de Salud; Argentina

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., This prospective, population-based, cross-sectional studied factors associated with respiratory failure and fatal LRTI in premature infants in developing countries. Six hundred sixty-four premature children participated, 60 developed respiratory failure, and 15 died. Several risk factors were identified for future interventions.

BackgroundBNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine encoding a prefusion-stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. BNT162b2 is highly efficacious against COVID-19 and is currently authorized for emergency use or conditional approval worldwide. At the time of authorization, data beyond 2 months post-vaccination were unavailable.MethodsIn an ongoing, placebo-controlled, observer-blinded, multinational, pivotal efficacy study, 44,165 ≥16-year-old participants and 2,264 12-15-year-old participants were randomized to receive 2 doses, 21 days apart, of 30 µg BNT162b2 or placebo. Study endpoints reported here are vaccine efficacy (VE) against laboratory-confirmed COVID-19 and safety data, both up to 6 months post-vaccination.ResultsBNT162b2 continued to be safe and well tolerated. Few participants had adverse events leading to study withdrawal. VE against COVID-19 was 91% (95% CI 89.0-93.2) through up to 6 months of follow-up, among evaluable participants and irrespective of previous SARS-CoV-2 infection. VE of 86%-100% was seen across countries and in populations with diverse characteristics of age, sex, race/ethnicity, and COVID-19 risk factors in participants without evidence of previous SARS-CoV-2 infection. VE against severe disease was 97% (95% CI 80.3−99.9). In South Africa, where the SARS-CoV-2 variant of concern, B.1.351 (beta), was predominant, 100% (95% CI 53.5, 100.0) VE was observed.ConclusionWith up to 6 months of follow-up and despite a gradually declining trend in vaccine efficacy, BNT162b2 had a favorable safety profile and was highly efficacious in preventing COVID-19. (ClinicalTrials.govnumber,NCT04368728)

Background An unusual feature of SARS-Cov-2 infection and the COVID-19 pandemic is that children are less severely affected than adults. This is especially paradoxical given the epidemiological links between poor air quality and increased COVID-19 severity in adults and that children are generally more vulnerable than adults to the adverse consequences of air pollution. Objectives To identify gaps in knowledge about the factors that protect children from severe SARS-Cov-2 infection even in the face of air pollution, and to develop a transdisciplinary research strategy to address these gaps. Methods An international group of researchers interested in children’s environmental health was invited to identify knowledge gaps and to develop research questions to close these gaps. Discussion Key research questions identified include: what are the effects of SAR-Cov-2 infection during pregnancy on the developing fetus and child; what is the impact of age at infection and genetic susceptibility on disease severity; why do some children with COVID-19 infection develop toxic shock and Kawasaki-like symptoms; what are the impacts of toxic environmental exposures including poor air quality, chemical and metal exposures on innate immunity, especially in the respiratory epithelium; what is the possible role of a “dirty” environment in conveying protection – an example of the “hygiene hypothesis”; and what are the long term health effects of SARS-Cov-2 infection in early life. Conclusion A concerted research effort by a multidisciplinary team of scientists is needed to understand the links between environmental exposures, especially air pollution and COVID-19. We call for specific research funding to encourage basic and clinical research to understand if/why exposure to environmental factors is associated with more severe disease, why children appear to be protected, and how innate immune responses may be involved. Lessons learned about SARS-Cov-2 infection in our children will help us to understand and reduce disease severity in adults, the opposite of the usual scenario.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently.In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety.A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups.A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.).

The Covid-19 death rate increases exponentially with age, and the main risk factors are having underlying conditions such as hypertension, diabetes, cardiovascular disease, severe chronic respiratory disease and cancer. These characteristics are consistent with the multi-step model of disease. We applied this model to Covid-19 case fatality rates (CFRs) from China, South Korea, Italy, Spain and Japan. In all countries we found that a plot of log(CFR) against log(age) was approximately linear with a slope of about 5. We also conducted similar analyses for selected other respiratory diseases. SARS showed a similar log–log age-pattern to that of Covid-19, albeit with a lower slope, whereas seasonal and pandemic influenza showed quite different age-patterns. Thus, death from Covid-19 and SARS appears to follow a distinct age-pattern, consistent with a multi-step model of disease that in the case of Covid-19 is probably defined by comorbidities and age producing immune-related susceptibility. Supplementary Information The online version of this article (10.1007/s10654-020-00711-7).

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; Argentina Fil: Bergero, Georgina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Alves, Camila. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Bronstein, Micaela. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Ziegler, Valeria. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Wood, Cristian. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina Fil: Caballero, Mauricio Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Wappner, Diego. No especifíca; Fil: Libster, Romina Paula. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Perez Marc, Gonzalo. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina

BackgroundTherapies to interrupt progression of early COVID-19 remain elusive. Among them, convalescent plasma in hospitalized patients was unsuccessful, perhaps because antibody should be administered earlier. We advanced plasma infusions to the first 72 hours of symptoms to arrest COVID-19 progression.MethodsA randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against SARS-CoV2 in elderly subjects within 72 hours of mild COVID-19 symptoms. The primary endpoint was severe respiratory disease defined as a respiratory rate ≥30 and/or an O2satResults160 patients underwent randomization. In the intention-to-treat analysis (ITT), 13/80(16.2%) patients receiving plasma vs. 25/80(31.2%) receiving placebo experienced severe respiratory disease [RR(95%CI)= 0.52(0.29,0.94); p=0.026)] with an RRR=48%.A modified ITT analysis, excluding six subjects who experienced the primary endpoint before infusion, showed a larger effect size [RR(95%CI) = 0.40(0.20, 0.81), p=0.007]. High- and low-titer donor analyses, based on a median IgG titer=1:3,200, evidenced a dose-dependent response with an RRR=73.3% for recipients of high-titer plasma (p=0.016) and a number needed to treat (NNT)=4.4. All secondary endpoints exhibited trends towards protection. No solicited adverse events were observed.ConclusionsEarly administration of high-titer convalescent plasma against SARS-CoV2 to mildly ill infected seniors reduced COVID-19 progression. This safe, inexpensive, outpatient intervention facilitates access to treatment from industrialized to LMIC, can decompress demands on hospitals, and may contribute to save lives.Funded by The Bill & Melinda Gates Foundation and The Fundación INFANT Pandemic Fund. Registered in the Dirección de Sangre y Medicina Transfusional del Ministerio de Salud (PAEPCC19), Plataforma PRIISA (1421), and clinicaltrials.gov (NCT04479163).All authors have completed the ICMJE uniform disclosure form atwww.icmje.org/coi_disclosure.pdfand declare: no support from any organization for the submitted work; RL, GPM, DW and FPP are investigators in a phase 3 SARS CoV2 trial from Pfizer; no other relationships or activities that could appear to have influenced the submitted work.

Background Respiratory syncytial virus infection is the leading cause of bronchiolitis in Colombia. There is growing evidence about the impact of Respiratory syncytial virus on society in terms of years of life lost due to this condition. The objective of the present study is to determine the Disability-Adjusted Life Years for respiratory syncytial virus in children under 2 years in Colombia. Methods Data from the national epidemiological surveillance system were used to estimate DALYs, calculated from the sum of years of life lost and years lived with disability due to RSV infection in Colombia. A bootstrapped method with 10,000 iterations was used to estimate each statistical parameter using the package DALY calculator in R. Results In 2019, 260,873 years of life (CI95% 208,180–347,023) were lost due to RSV bronchiolitis in Colombian children under 2 years. The estimated rate was 20 DALYs / 1000 person-year (95% CI 16–27). Conclusion This is the first report estimating the impact of RSV bronchiolitis morbidity and mortality in Colombia. The findings of the present study suggest that the actual burden and cost of bronchiolitis due to RSV is high. Prevention strategies, such as RSV vaccination, to reduce morbidity associated with RSV infection should be encouraged in our country.

Summary of study A multi-country randomized, placebo-controlled trial of the safety, immunogenicity and efficacy of respiratory syncytial virus (RSV) F-protein nanoparticle vaccine was undertaken in 4,636 pregnant women and their infants. RSV F-protein vaccine was safe and immunogenic in the pregnant women inducing anti-F IgG, palivizumab-competing antibodies and RSV neutralizing antibodies that were transferred to the fetus. Although the primary endpoint of prevention of RSV-specific medically-significant lower respiratory tract infection (MS-LRTI) was not met per protocol criteria for efficacy (i.e. 97.52% lower bound >30%), vaccine efficacy was 39.4% (97.52% CI: -1.0, 63.7%; p=0.0278) in infants 0-90 days age. Furthermore, there was a 58.8% (95% CI 31.9, 75.0%) lower rate of RSV LRTI with severe hypoxemia (secondary endpoint) through to 90 days of age in the expanded intent-to-treat analysis. The number of women needed to be vaccinated to prevent RSV-specific MS-LRTI or LRTI with severe hypoxemia in their infants through to 180 days of life were 88 and 82, respectively. Background RSV is the dominant cause of severe lower respiratory tract infection (LRTI) in infants, with most severe disease concentrated in younger-age infants. Methods Healthy, pregnant women between 28 and 36 weeks gestation, with expected delivery near the start of the RSV season, were randomized to a single intramuscular dose of nanoparticle RSV F-protein vaccine, or placebo in a 2:1 ratio. Their infants were followed for 180 days for medically-significant LRTI (MS-LRTI), LRTI with severe hypoxemia and/or LRTI- hospitalization. RSV detection was performed centrally by PCR. Safety evaluation continued until 364 days age. Results 4,636 women were randomized, with 4,579 live births. Over the first 90 days of life, efficacy against RSV-MS-LRTI was 39.4% (97.52%CI: -1.0, 63.7%; p=0.0278) and 41.4% (95%CI: 5.3, 61.2%) in the per protocol and expanded intent-to-treat (eITT) analyses, respectively. There was a lower rate (efficacy 58.8%; 95%CI 31.9, 75.0% in eITT analysis; not adjusted for multiplicity) of RSV-LRTI with severe hypoxemia in infants of vaccinees through 90 days age. Pneumonia reported as a serious adverse events was 49.4% less common in infants of vaccinees (2.6%) than placebo-recipients through 364 days age. Conclusions Maternal vaccination with RSV F-nanoparticle vaccine was safe and immunogenic. The prespecified primary endpoint success criterion (efficacy 97.5% lower bound ≥30%) was not achieved. However, maternal immunization was associated with reduced risk of RSV-confirmed MS-LRTI and LRTI with severe hypoxemia in early infancy. Trial Registration Number ClinicalTrials.Gov: NCT02624947. Funding statement Funded by Novavax, with supporting grant from the Bill and Melinda Gates Foundation.

Covid-19 death has a different relationship with age than is the case for other severe respiratory pathogens. The Covid-19 death rate increases exponentially with age, and the main risk factors are age itself, as well as having underlying conditions such as hypertension, diabetes, cardiovascular disease, severe chronic respiratory disease and cancer. Furthermore, the almost complete lack of deaths in children suggests that infection alone is not sufficient to cause death; rather, one must have gone through a number of changes, either as a result of undefined aspects of aging, or as a result of chronic disease. These characteristics of Covid-19 death are consistent with the multistep model of disease, a model which has primarily been used for cancer, and more recently for amyotrophic lateral sclerosis (ALS). We applied the multi-step model to data on Covid-19 case fatality rates (CFRs) from China, South Korea, Italy, Spain and Japan. In all countries we found that a plot of ln (CFR) against ln (age) was approximately linear with a slope of about 5. As a comparison, we also conducted similar analyses for selected other respiratory diseases. SARS showed a similar log-log age-pattern to that of Covid-19, albeit with a lower slope, whereas seasonal and pandemic influenza showed quite different age-patterns. Thus, death from Covid-19 and SARS appears to follow a distinct age-pattern, consistent with a multistep model of disease that in the case of Covid-19 is probably defined by comorbidities and age producing immune-related susceptibility. Identification of these steps would be potentially important for prevention and therapy for SARS-COV-2 infection.

Numerous preventive strategies against respiratory syncytial virus (RSV) are undergoing late stage evaluation in humans and, in addition to their intended benefit for acute illness, may impact long term consequences of infection in infants. Severe RSV infection has been repeatedly associated in the literature with long term complications, including impaired lung function, recurrent wheezing, and asthma. However, whether RSV lower respiratory tract infection (LRTI) causally affects the odds for developing wheezing and/or asthma during childhood requires further study, and the biological mechanisms underlying this hypothetical progression from viral illness to chronic lung disease are poorly characterized. In this review, we summarize the literature exploring the association between RSV LRTI in infancy and subsequent recurrent wheezing and pediatric asthma.

This review addresses differences in respiratory syncytial virus (RSV) lower respiratory tract illness (LRTI) between industrial- ized and developing countries and provides observations associated with the dissimilar consequences of viral infection in both environments. RSV LRTI is an important cause of morbidity and mortality in infants worldwide. Its burden is highest in de- veloping countries, where most hospitalizations and mortality occur. Palivizumab has been approved for disease prevention in premature infants in numerous countries but its cost and requirement for several doses hampers its routine use. The significant gap between low- and high-income countries in mortality rates stresses the need to identify specific risk factors for RSV LRTI prevention in different populations.Conclusion. RSV LTRI continues to be a serious problem for industrialised and developing countries, although mortality occurs preferentially in the latter. Several vaccines and monoclonal antibodies to prevent severe disease are advancing steadily in late phase trials. The next decade may witness a change in the landscape of RSV infections in young infants.

Nothing essential has changed in the definition of bronchiolitis since itsdescription nearly eighty years ago [1,2]. The syndrome affects infants and youngchildren at different ages, presents with a few overlapping symptoms of varying intensityand other manifestations often associated with specific pathogens (e.g.: fever andpharyngitis in influenza or wheezing with respiratory syncytial virus), and is caused byinfection with one or a combination of half a dozen viruses with different inflammatory,antiviral and/or atopic phenotypes [3]. Conceived as a single entity, a number ofcandidate drugs failed as therapeutics against it in randomized trials [4]. To date,management recommendations for hospitalized patients are based on supportive therapy[2]. Etiologic testing is discouraged [2]. Fil: Álvarez Paggi, Damián Jorge. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina

We are ignoring evidence suggesting that the diagnosis of bronchiolitis encompasses several diseases with distinct underlying mechanisms, considerable heterogeneity in treatment responses, and ultimately different therapeutic targets. Understanding this heterogeneity may be the only way to deliver appropriate, stratified treatments.

Infection by any of the four dengue virus (DENV) serotypes produces a wide spectrum of clinical illness in humans. Differences in clinical manifestation and severity have been associated with secondary heterologous infection, patient age, and virus serotype. In this context, this retrospective study sought to analyze the presentation of dengue in patients during the 2014 DENV-4 outbreak affecting the City of Orán, Salta Province, Argentina. Demographic data, clinical manifestations, and laboratory abnormalities of laboratory-confirmed dengue patients were compared between age groups and between patients with and without warning signs. Of 301 patients with laboratory-confirmed dengue, 37.9% presented dengue with warning signs. Although nearly half of all patients had secondary DENV infections, no severe dengue cases, or deaths were reported. Furthermore, no association was found between incidence of warning signs and pre-existing immunity to DENV. Pediatric patients were least likely to present warning signs and showed significantly decreased risk of fever, retro-orbital pain, arthalgia, diarrhea and thrombocytopenia, and higher risk of rash compared to older patients. Female patients of all ages were also at higher risk of developing several symptoms. The characterization of DENV-4 infection in humans, a DENV serotype recently reported in Argentina, revealed differences in clinical manifestations, laboratory parameters and the presence/absence of warning signs based on age group. Further investigation of these age-related differences should contribute to better assessment of dengue disease in at risk populations. Fil: Byrne, Alana Brooke. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gutierrez, Francisco Guillermo. Hospital San Vicente de Paul; Argentina. Universidad Nacional de Tucumán. Facultad de Medicina; Argentina Fil: Bruno, Agostina Alejandra. Hospital San Vicente de Paul; Argentina Fil: Cordoba, María Teresa. Hospital San Vicente de Paul; Argentina Fil: Bono, María M.. Hospital San Vicente de Paul; Argentina Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Talarico, Laura Beatriz. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Quipildor, Marcelo Omar. Hospital San Vicente de Paul; Argentina

Background: Premature birth is a growing and serious public health problem affecting more than one of every ten infants worldwide. Bronchopulmonary dysplasia (BPD) is the most common neonatal morbidity associated with prematurity and infants with BPD suffer from increased incidence of respiratory infections, asthma, other forms of chronic lung illness, and death (Day and Ryan, Pediatr Res 81: 210-213, 2017; Isayama et la., JAMA Pediatr 171:271-279, 2017). BPD is now understood as a longitudinal disease process influenced by the intrauterine environment during gestation and modulated by gene-environment interactions throughout the neonatal and early childhood periods. Despite of this concept, there remains a paucity of multidisciplinary team-based approaches dedicated to the comprehensive study of this complex disease. Methods: The Discovery BPD (D-BPD) Program involves a cohort of infants < 1,250 g at birth prospectively followed until 6 years of age. The program integrates analysis of detailed clinical data by machine learning, genetic susceptibility and molecular translation studies. Discussion: The current gap in understanding BPD as a complex multi-trait spectrum of different disease endotypes will be addressed by a bedside-to-bench and bench-to-bedside approach in the D-BPD program. The D-BPD will provide enhanced understanding of mechanisms, evolution and consequences of lung diseases in preterm infants. The D-BPD program represents a unique opportunity to combine the expertise of biologists, neonatologists, pulmonologists, geneticists and biostatisticians to examine the disease process from multiple perspectives with a singular goal of improving outcomes of premature infants. Trial registration: Does not apply for this study. Fil: Ofman, Gaston. University of Alabama at Birmingahm; Estados Unidos Fil: Caballero, Mauricio Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Álvarez Paggi, Damián Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Marzec, Jacqui. National Institute of Environmental Health Sciences; Estados Unidos Fil: Nowogrodzki, Florencia. No especifíca; Fil: Cho, Hye Youn. National Institute of Environmental Health Sciences; Estados Unidos Fil: Sorgetti, Mariana. No especifíca; Fil: Colantonio, Guillermo. No especifíca; Fil: Bianchi, Alejandra. No especifíca; Fil: Prudent, Luis M.. Fundación para la Salud Materno Infantil; Argentina Fil: Vain, Néstor Eduardo. Fundación para la Salud Materno Infantil; Argentina. Sanatorio de la Trinidad Palermo.; Argentina Fil: Mariani, Gonzalo Luis. Hospital Italiano; Argentina Fil: Digregorio, Jorge. Sanatorio de la Trinidad Palermo.; Argentina Fil: Lopez Turconi, Elba. No especifíca; Fil: Osio, Cristina. Sanatorio "Otamendi y Miroli S. A."; Argentina Fil: Galletti, Maria Fernanda. Hospital Italiano; Argentina Fil: Quiros, Mariangeles. Clinica y Maternidad Suizo Argentina; Argentina Fil: Brum, Andrea. Sanatorio de la Trinidad Palermo.; Argentina Fil: Lopez Garcia, Santiago. No especifíca; Fil: Garcia, Silvia. Sanatorio "Otamendi y Miroli S. A."; Argentina Fil: Bell, Douglas. National Institute of Environmental Health Sciences; Estados Unidos Fil: Jones, Marcus H.. Pontificia Universidade Católica do Rio Grande do Sul; Brasil Fil: Tipple, Trent E.. University of Alabama at Birmingahm; Estados Unidos Fil: Kleeberger, Steven R.. National Institute of Environmental Health Sciences; Estados Unidos Fil: Polack, Fernando Pedro. University of Alabama at Birmingahm; Estados Unidos

The landscape of infant bronchiolitis and viral pneumonia may be altered by preventive interventions against respiratory syncytial virus under evaluation today. Pediatric wards in 2018 in developing countries may differ from those attended by future generation pediatricians who may not witness the packed emergency rooms, lack of available beds, or emergency situations that all physicians caring for children with RSV experience every year. In this review, we describe and discuss different prevention strategies under evaluation to protect pediatric patients. Then, we outline a number of potential challenges, benefits, and concerns that may result from successful interventions after licensure.

Experimental data show that type I interferon has a key role in innate immune response against influenza infection.We compared nasal levels of interferon-α2 and β among inpatients and outpatients with influenza.Children younger than 5 years of age with influenza-like illness seeking care at the emergency department within the first 72 h of disease onset were prospectively included. Clinical and demographic data and secretions through nasal wash were obtained. Influenza infection was assessed through reverse-transcription polymerase chain reaction and nasal levels of interferon-α2 and β were measured by enzyme-linked immunosorbent assay. All patients followed until the end of the disease.One hundred patients were included, of which 24 had confirmed influenza infection, and 5 of them were hospitalized. Subtypes A (H3N2) and B were confirmed in 10 and 14 patients, respectively. Seventy-six patients without influenza, including 48% of outpatients, were recruited as controls. All hospitalized patients were significantly younger regardless of influenza status (age6 months in 59% vs. 23.2%, p 0.001). All other data were similar among the groups. Comparing median levels of interferon-α2 among children with influenza, levels were significantly higher in outpatients than in hospitalized patients and were 263.2 pg/mL (25-75 interquartile range: 58.3-634) and detectable in only one patient (90 pg/mL), respectively. The levels of interferon-α2 in controls and those of interferon-β in all groups were not detected.Higher levels of interferon-α2 in patients with less severe influenza reinforce experimental evidence about the protective role of interferon-α2 against influenza infection.

Background Numerous deaths in children aged, Specific subgroups of children in socioeconomically vulnerable communities are at higher risk for dying at home from acute respiratory tract infection. This is the first study to provide at-home mortality rates due to respiratory syncytial virus and influenza A virus infection among infants.

Objective: Delineate risk factors associated with severe hypoxemia (O2 sat ≤87%) in infants and children younger than 2 years hospitalized with single pathogen HRV infection. Study Design: Prospective study in a yearly catchment population of 56 560 children 10 pg/mL) predisposed to life-threatening disease. Conclusions: Targeted interventions against IL-13 should be evaluated to decrease severity of HRV illness in infancy and early childhood. Fil: Caballero, Mauricio Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Hijano, Diego Raúl. Fundación para la Investigación en Infectología Infantil; Argentina. St. Jude Children's Research Hospital; Estados Unidos Fil: Acosta, Patricio Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Mateu, Cecilia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Marcone, Débora Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina Fil: Linder, Jodell E.. Vanderbilt University; Estados Unidos Fil: Talarico, Laura Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Elder, John M.. Vanderbilt University; Estados Unidos Fil: Echavarría, Marcela Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina Fil: Miller, Eva Kathryn. Vanderbilt University; Estados Unidos Fil: Polack, Fernando Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina

Recognition of the acute and chronic burden of respiratory syncytial virus (RSV) lower respiratory tract infections (LRTI) sparked a wave of initiatives to develop preventive and therapeutic products against the pathogen in recent years. RSV is a leading cause of hospitalization in infants in industrialized and developing countries, has been causally linked to recurrent wheezing during childhood, associated with pediatric asthma, and is an important cause of mortality in the first months of life in the developing world. Significant changes in the epidemiology, clinical manifestations, and severe consequences of LRTI may emerge in the next decade with the advent of novel preventive strategies against RSV. This manuscript outlines some of these changes and discusses potential scenarios based on the current literature and experiences with other pathogens.

Objective: The aim of this review was to address advances in management and treatment of acute viral bronchiolitis in infants. Sources: A systematic review search was made including all articles published in English between 2010 and 2017, and available in the electronic databases PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) and specialized register of the Acute Respiratory Infections Group (Cochrane review group). The following MESH terms in English were included, using different Boolean operators for the search strategy: “bronchiolitis, viral,” “diagnosis,” “epidemiology,” “etiology,” “therapy,” “virology,” “prevention and control,” “respiratory syncytial virus, human.” Additional filters were used. Summary of findings: Few effective interventions are recommended for the management of RSV bronchiolitis in young infants. The main goal is to ensure an adequate oxygen supplementation and fluid balance whenever deemed necessary. Hypertonic saline nebulization is helpful only for hospitalized infants. Numerous antiviral drugs and specific vaccines for RSV are under evaluation and foretell advances in disease management in the near future. Conclusion: A number of promising new technologies are advancing in the field. Until new interventions became feasible, early detection and modification of preventable risk factors is essential to improve outcomes. Resumo: Objetivo: O objetivo desta análise é abordar avanços no manejo e no tratamento de bronquiolite viral aguda em neonatos. Fontes: Uma pesquisa de análise sistemática foi realizada e incluiu todos os artigos publicados em inglês entre 2010 e 2017 e disponíveis nas bases de dados eletrônicas PubMed, no Registro Central de Ensaios Controlados (CENTRAL) da Cochrane e no registro especializado do Grupo de Infecções Respiratórias Agudas (grupo de revisão Cochrane). Os seguintes termos MESH em inglês foram incluídos na abordagem utilizando diferentes operadores booleanos para a estratégia de pesquisa: “bronquiolite, viral”, “diagnóstico”, “epidemiologia”, “etiologia”, “terapia”, “virologia”, “prevenção e controle”, “vírus sincicial respiratório, humano”. Foram utilizados filtros adicionais. Resumo dos achados: Poucas intervenções efetivas são recomendadas para o manejo da bronquiolite por VSR em neonatos jovens. O principal objetivo é garantir uma suplementação de oxigênio adequada e equilíbrio de fluidos sempre que considerado necessário. A nebulização de solução salina hipertônica ajuda apenas em casos de neonatos hospitalizados. Vários medicamentos antivirais e vacinas específicas contra VSR estão em fase de avaliação e predizem avanços no manejo da doença no futuro próximo. Conclusão: Várias novas tecnologias promissoras estão avançando no campo. Até que as novas intervenções se tornem viáveis, a detecção precoce e a modificação de fatores de risco de prevenção são fundamentais para melhorar os resultados. Keywords: Viral bronchiolitis, Infants, Respiratory syncytial virus, Palavras-chave: Bronquiolite viral, Neonatos, Vírus sincicial respiratório

Summary Background: Respiratory syncytial virus (RSV) is a major public health burden worldwide. We aimed to review the current literature on the incidence and mortality of severe RSV in children globally. Methods: Systematic literature review and meta‐analysis of published data from 2000 onwards, reporting on burden of acute respiratory infection (ARI) due to RSV in children. Main outcomes were hospitalization for severe RSV‐ARI and death. Results: Five thousand two hundred and seventy‐four references were identified. Fifty‐five studies were included from 32 countries. The global RSV‐ARI hospitalization estimates, reported per 1,000 children per year (95% Credible Interval (CrI), were 4.37 (2.98, 6.42) among children

Rationale: Respiratory syncytial virus (RSV) is the most frequent cause of hospitalization and an important cause of death in infants in the developing world. The relative contribution of social, biologic, and clinical risk factors to RSV mortality in low-income regions is unclear. Objectives: To determine the burden and risk factors for mortality due to RSV in a low-income population of 84,840 infants. Methods: This was a prospective, population-based, crosssectional, multicenter study conducted between 2011 and 2013. Hospitalizations and deaths due to severe lower respiratory tract illness (LRTI) were recorded during the RSV season. All-cause hospital deaths and community deaths were monitored. Risk factors for respiratory failure (RF) and mortality due to RSV were assessed using a hierarchical, logistic regression model. Measurements and Main Results: A total of 2,588 (65.5%) infants with severe LRTI were infected with RSV. A total of 157 infants (148 postneonatal) experienced RF or died with RSV. RSV LRTI accounted for 57% fatal LRTI tested for the virus. A diagnosis of sepsis (odds ratio [OR], 17.03; 95% confidence interval [CI], 13.14-21.16 for RF) (OR, 119.39; 95% CI, 50.98-273.34 for death) and pneumothorax (OR, 17.15; 95% CI, 13.07-21.01 for RF) (OR, 65.49; 95% CI, 28.90-139.17 for death) were the main determinants of poor outcomes. Conclusions: RSV was the most frequent cause of mortality in lowincome postneonatal infants. RF and death due to RSV LRTI, almost exclusively associated with prematurity and cardiopulmonary diseases in industrialized countries, primarily affect term infants in a developing world environment. Poor outcomes at hospitals are frequent and associated with the cooccurrence of bacterial sepsis and clinically significant pneumothoraxes. Fil: Geoghegan, Sarah. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Erviti, Anabella. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Caballero, Mauricio Tomás. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Vallone, Fernando Daniel. Región Sanitaria I. - Gobierno de la Provincia de Buenos Aires. Ministerio de Salud. Region Sanitaria I.; Argentina Fil: Zanone, Stella M.. Fundacion de Endocrinologia Infantil.; Argentina Fil: Ves Losada, Juan. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina Fil: Bianchi, Alejandra. Fundacion de Endocrinologia Infantil.; Argentina Fil: Acosta, Patricio Leandro. Fundacion de Endocrinologia Infantil.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Talarico, Laura Beatriz. Fundacion de Endocrinologia Infantil.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Ferretti, Adrian. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Grimaldi, Luciano Alva. Hospital Melendez; Argentina Fil: Sancilio, Andrea. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina Fil: Dueñas, Karina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina Fil: Sastre, Gustavo. Hospital Zonal General de Agudos Descentralizado Evita; Argentina Fil: Rodriguez, Andrea. Hospital Zonal General de Agudos Descentralizado Evita; Argentina Fil: Ferrero, Fernando. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina Fil: Barboza, Edgar. Hospital Zonal General de Agudos Dr. Narciso Lopez; Argentina Fil: Gago, Guadalupe Fernández. Hospital de Niños de la Plata; Argentina Fil: Nocito, Celina. Hospital Interzonal General de Agudos “Dr. Pedro Fiorito"; Argentina Fil: Flamenco, Edgardo. Hospital Zonal General de Agudos Dr. Arturo Onativia; Argentina Fil: Perez, Alberto Rodriguez. Hospital Zonal General de Agudos Dr. Alberto Eurnekian; Argentina Fil: Rebec, Beatriz. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal General de Agudos Presidente Peron; Argentina Fil: Ferolla, Fausto Martín. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Libster, Romina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Karron, Ruth A.. No especifíca; Fil: Bergel, Eduardo. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. Vanderbilt University; Estados Unidos

Pneumococcal disease is a major public health problem worldwide. From March to September of 2010, 10-valent pneumococcal non-typeable Haemophilus influenzae protein conjugate vaccine (PHiD-CV) was introduced in the Brazilian childhood National Immunization Program (NIP) in all 27 Brazilian states. The aim of the present study is to report national time-trends in incidence of hospital admissions for childhood pneumonia in Brazil before and after two years of introduction of this new pneumococcal conjugate vaccine.Analysis of hospitalization data of children aged 0-4 years in Brazilian public health system with an admission diagnosis of pneumonia from 2002 to 2012 was performed comparing pre (2002-2009) and post-vaccination periods (2011-2012). Hospital number of admission due to pneumonia and all non-respiratory diseases were obtained from DATASUS, the Brazilian government open-access public health database system. Incidence of pneumonia hospitalization was compared to incidence of all non-respiratory admissions.Admission rates for pneumonia decreased steadily from 2010 to 2012. In children aged less than four years, incidence of pneumonia hospitalizations decreased 12.65% when pre (2002-2009) and post-vaccination introduction periods (2011-2012) were compared and adjusted for seasonality and secular-trend (p0.001). On the other hand, non-respiratory admission rates remained stable comparing both periods (p=0.39).Childhood pneumonia hospitalization rates were fluctuating prior to 2010 and decreased significantly in the two years after PHiD-CV introduction. Conversely, rate of non-respiratory admissions has shown no decrease. These data are an evidence of the effectiveness and public health impact of this new pneumococcal vaccine.

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; Argentina Fil: Juarez, Maria V.. Ministerio de Salud de la Nación; Argentina Fil: Bergel, Eduardo. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Romanin, Viviana. Ministerio de Salud de la Nación; Argentina Fil: Califano, Gloria. Ministerio de Salud de la Nación; Argentina Fil: Sagradini, Sandra. Ministerio de Salud de la Nación; Argentina Fil: Rancaño, Carolina. Ministerio de Salud de la Nación; Argentina Fil: Aquino, Analía. Ministerio de Salud de la Nación; Argentina Fil: Libster, Romina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina. Vanderbilt University; Estados Unidos Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. Vanderbilt University; Estados Unidos Fil: Manzur, Juan. Ministerio de Salud de la Nación; Argentina

We analyzed data from 524 Argentinean infants hospitalized with lower respiratory tract illness (LRTI) due to respiratory syncytial virus (RSV) to inform selection of clinical end points for RSV vaccine efficacy trials. Cases of LRTI due to RSV that required a mask, continuous or bilevel positive airway pressure, or mechanical ventilation were classified as critical. Oxygen saturation of ≤90%, tachypnea, and tachycardia were each associated with an increased odds of critical LRTI due to RSV (adjusted odds ratios [ORs], 2.30 [95% confidence interval {CI}, 1.26-4.24; P = .007], 2.22 [95% CI, 1.19-4.16; P = .012], and 2.35 [95% CI, 1.22-4.50; P = .010], respectively). The odds of critical LRTI due to RSV increased substantially (OR, 8.57; 95% CI, 2.19-73.5; P = .001) among individuals with ≥2 indicators. Lower chest wall indrawing was not associated with critical disease.

RSV is a major cause of morbidity and mortality worldwide. Although no treatment or vaccine currently exists, RSV therapeutics and preventative strategies are being evaluated in clinical trials, including phase 3 trials. Despite great prospects, the regulatory pathways of novel RSV therapeutics have been defined insufficiently. Here we report the results from the ReSViNET 2nd High–level expert meeting 2016 on RSV therapeutics, which was held in Zeist, the Netherlands on March 2nd and 3rd. This meeting was organized to advance discussion on regulatory pathways, clinical development, clinical trials, and health technology models in the RSV therapeutics field. During this meeting regulators, public health specialists, academia, non–governmental organizations and pharmaceutical companies openly discussed and addressed the needs for the successful development of RSV therapeutics and prophylaxis.

Objectives: To assess incidence, burden of illness, and risk factors for human rhinoviruses (HRVs) in a cohort of very low birth weight (VLBW) infants. Methods: A 2-year prospective cohort study was conducted among VLBW premature infants in Buenos Aires, Argentina. Infants were enrolled in the NICU from June 1, 2003, to May 31, 2005, and managed monthly and with every acute respiratory illness (ARI) during the first year of life. Nasal wash samples were obtained during every respiratory episode and tested for HRV, respiratory syncytial virus (RSV), human parainfluenza viruses, influenza viruses, and human metapneumovirus using reverse transcriptase-polymerase chain reaction. Results: Of 119 patients, 66 (55%) had HRV-associated ARIs. The incidence of HRV-associated ARI was 123 events per 100 child-years of follow-up. Of those infants experiencing an episode of bronchiolitis, 40% had HRV versus 7% with RSV. The incidence of HRV-associated bronchiolitis was 75 per 100 infant-years of follow-up. HRV was associated with 12 of 36 hospitalizations (33%), and RSV was associated with 9 of 36 hospitalizations (25%). The incidence of HRV-associated hospitalization was 12 per 100 infant-years of follow-up. The risk of HRV-associated hospitalization was higher for infants with bronchopulmonary dysplasia and those who were not breastfed. Conclusions: HRV is an important and frequent pathogen associated with severe respiratory infections in VLBW infants. Bronchopulmonary dysplasia and the absence of breastfeeding are risk factors for hospitalization. The results of our study reveal that HRV is the predominant pathogen of respiratory infections in premature infants.

Breastfeeding is a well-known protective factor against severe respiratory tract infections. Recently, a gender specific role for human milk has been described in very low birth weight infants and neonates: breast milk protected girls but not boys.To determine whether the protective effect of breastfeeding on the severity of acute respiratory infections in full term infants is different for girls and boys.A prospective cross-sectional study of infants seeking medical care for acute respiratory infection. The protective role of breastfeeding against viral pneumonia and hospitalization were assessed by univariate and multivariate analyses. Analyses were adjusted for important confounders.A total of 323 patients were enrolled in this study. Breastfeeding protected girls against pneumonia and hospitalization, but did not protect boys. Nonbreastfeeding females were particularly susceptible to severe acute respiratory infections.Breastfeeding had a protective effect against severe disease in infant girls experiencing their first symptomatic respiratory infection. Nonbreastfeeding females are at significant risk for severe acute lung disease and should be targeted intensively by breastfeeding campaigns.

Aim: This study explored whether alcohol consumption during pregnancy increased the risk of life-threatening respiratory infections in children.Methods: We prospectively evaluated children under the age of two years admitted to hospitals in Buenos Aires, Argentina, with severe acute respiratory infections during the winters of 2011 and 2012. Information on maternal alcohol consumption during the third trimester of pregnancy was collected using standardised questionnaires and categorised as never, low if it was once a week and high if it was equal or more than once a week.Results: Of the 3423 children hospitalised with acute respiratory infection, 2089 (63.7%) had respiratory syncytial virus (RSV). Alcohol consumption during the last trimester was reported by 398 mothers (12.4%) and categorised as low (n = 210, 6.5%) or high (n = 188, 5.9%). A greater effect on life-threatening respiratory infection, defined as oxygen saturation of or up to 87%, was observed with higher alcohol intake due to all viruses and specifically RSV in the logistic regression analyses. Alcohol consumption was strongly associated with life-threatening disease, particularly in boys whose adjusted odds ratio rose from 3.67 to 13.52 when their mothers drank alcohol.Conclusion: Alcohol consumption during pregnancy was associated with life-threatening respiratory infections in boys. Fil: Libster, Romina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina. Vanderbilt University; Estados Unidos Fil: Ferolla, Fausto M.. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Hijano, Diego R.. Fundación para la Investigación en Infectología Infantil; Argentina. Vanderbilt University; Estados Unidos Fil: Acosta, Patricio Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Erviti, Anabella. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. Vanderbilt University; Estados Unidos

Background Respiratory syncytial virus (RSV) lower respiratory tract infection (LRI) during infancy has been consistently associated with an increased risk of childhood asthma. In addition, evidence supports that this relationship is causal. However, the mechanisms through which RSV contributes to asthma development are not understood. The INSPIRE (Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure) study objectives are to: 1) characterize the host phenotypic response to RSV infection in infancy and the risk of recurrent wheeze and asthma, 2) identify the immune response and lung injury patterns of RSV infection that are associated with the development of early childhood wheezing illness and asthma, and 3) determine the contribution of specific RSV strains to early childhood wheezing and asthma development. This article describes the INSPIRE study, including study aims, design, recruitment results, and enrolled population characteristics. Methods/design The cohort is a population based longitudinal birth cohort of term healthy infants enrolled during the first months of life over a two year period. Respiratory infection surveillance was conducted from November to March of the first year of life, through surveys administered every two weeks. In-person illness visits were conducted if infants met pre-specified criteria for a respiratory illness visit. Infants will be followed annually to ages 3-4 years for assessment of the primary endpoint: wheezing illness. Nasal, urine, stool and blood samples were collected at various time points throughout the study for measurements of host and viral factors that predict wheezing illness. Nested case-control studies will additionally be used to address other primary and secondary hypotheses. Discussion In the INSPIRE study, 1952 infants (48% female) were enrolled during the two enrollment years and follow-up will continue through 2016. The mean age of enrollment was 60 days. During winter viral season, more than 14,000 surveillance surveys were carried out resulting in 2,103 respiratory illness visits on 1189 infants. First year follow-up has been completed on over 95% percent of participants from the first year of enrollment. With ongoing follow-up for wheezing and childhood asthma outcomes, the INSPIRE study will advance our understanding of the complex causal relationship between RSV infection and early childhood wheezing and asthma.

Respiratory syncytial virus (RSV) is a major worldwide cause of morbidity and mortality in children under five years of age. Evidence-based management guidelines suggest that there is no effective treatment for RSV lower respiratory tract infection (LRTI) and that supportive care, ie, hydration and oxygenation, remains the cornerstone of clinical management. However, RSV treatments in development in the past decade include 10 vaccines and 11 therapeutic agents in active clinical trials. Maternal vaccination is particularly relevant because the most severe disease occurs within the first 6 months of life, when children are unlikely to benefit from active immunisation. We must optimise the implementation of novel RSV therapeutics by understanding the target populations, showing safety, and striving for acceptable pricing in the context of this worldwide health problem. In this Review, we outline the limitations of RSV LRTI management, the drugs in development, and the remaining challenges related to study design, regulatory approval, and implementation.

Atopic asthma is a chronic allergic disease that involves T-helper type 2 (Th2)-inflammation and airway remodeling. Bronchiolar club cells (CC) and alveolar macrophages (AM) are sentinel cells of airway barrier against inhaled injuries, where allergy induces mucous metaplasia of CC and the alternative activation of AM, which compromise host defense mechanisms and amplify Th2-inflammation. As there is evidence that high levels of environmental endotoxin modulates asthma, the goal of this study was to evaluate if the activation of local host defenses by Lipopolysaccharide (LPS) previous to allergy development can contribute to preserving CC and AM protective phenotypes. Endotoxin stimulus before allergen exposition reduced hallmarks of allergic inflammation including eosinophil influx, Interleukin-4 and airway hyperreactivity, while the T-helper type 1 related cytokines IL-12 and Interferon-γ were enhanced. This response was accompanied by the preservation of the normal CC phenotype and the anti-allergic proteins Club Cell Secretory Protein (CCSP) and Surfactant-D, thereby leading to lower levels of CC metaplasia and preventing the increase of the pro-Th2 cytokine Thymic stromal lymphopoietin. In addition, classically activated alveolar macrophages expressing nitric oxide were promoted over the alternatively activated ones that expressed arginase-1. We verified that LPS induced a long-term overexpression of CCSP and the innate immune markers Toll-like receptor 4, and Tumor Necrosis Factor-α, changes that were preserved in spite of the allergen challenge. These results demonstrate that LPS pre-exposition modifies the local bronchioalveolar microenvironment by inducing natural anti-allergic mechanisms while reducing local factors that drive Th2 type responses, thus modulating allergic inflammation. Fil: García, Luciana Noemí. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina Fil: Leimgruber, Carolina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina Fil: Uribe Echevarría, E. M.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina Fil: Acosta, Patricio Leandro. Fundación para la Investigación en Infectologia Infantil; Argentina Fil: Brahamian, Jorge M.. Fundación para la Investigación en Infectologia Infantil; Argentina Fil: Polack, Fernando P.. Fundación para la Investigación en Infectologia Infantil; Argentina. Vanderbilt University; Estados Unidos Fil: Miró, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Quintar, Amado Alfredo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina Fil: Sotomayor, Claudia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Maldonado, Cristina Alicia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina

Background: Asthma and wheezing account for a substantial disease burden around the world. Very low birth weight (VLBW

Rationale: Respiratory syncytial virus (RSV) is an important cause of hospitalization and death in infants worldwide. Most RSV deaths occur in developing countries, where burden and risk factors for life-threatening illness are unclear. Objectives: We defined the burden of life-threatening (O2 saturation [O2 sat] ≤ 87%) and fatal RSV infection, and characterized risk factors for life-threatening disease in hospitalized children. Special emphasis was placed on studying the impact of dietary habits during pregnancy. We hypothesized that dietary preferences, differing from those of our remote ancestors, would negatively impact children’s pulmonary health. For instance, a diet rich in carbohydrates is a signature of recent millennia and typical of low-income populations, heavily burdened by life-threatening RSV disease. Methods: Prospective study in a catchment population of 56,560 children under 2 years of age during the RSV season in Argentina. All children with respiratory signs and O2 sat less than 93% on admission were included. Measurements and Main Results: Among 1,293 children with respiratory infections, 797(61.6%) were infected with RSV: 106 of these had life-threatening disease; 1.9 per 1,000 children (95% confidence interval [CI], 1.5–2.2/1,000) under 24 months. A total of 22 hospitalized children died (9 RSV+), 26 died at home due to acute respiratory infection (14 attributed to RSV); all were under 12 months old. The annual attributable mortality rate for RSV was 0.7 per 1,000 infants (95% CI, 0.4–1.1/1,000). Life-threatening disease was dose-dependently associated with carbohydrate ingestion during pregnancy (adjusted odds ratio from 3.29 [95% CI, 1.15–9.44] to 7.36 [95% CI, 2.41–22.5] versus the lowest quartile). Conclusions: Life-threatening and fatal RSV infections are a heavy burden on infants in the developing world. Diets rich in carbohydrates during pregnancy are associated with these severe outcomes. Fil: Ferolla, Fausto Martín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Hijano, Diego Raúl. Fundación para la Investigación en Infectologia Infantil; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Acosta, Patricio Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Rodríguez, Andrea. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos Descentralizado “Evita Pueblo"; Argentina Fil: Dueñas, Karina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina Fil: Sancilio, Andrea. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina Fil: Barboza, Edgar. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos “Dr. Narciso López"; Argentina Fil: Caría, Adriana. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos “Dr. Narciso López"; Argentina Fil: Fernández Gago, Guadalupe. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; Argentina Fil: Egües Almeida, Rodrigo. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; Argentina Fil: Castro, Laura. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina Fil: Pozzolo, Cecilia. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal de Agudos "Dr. Arturo Oñativia"; Argentina Fil: Martínez, María V.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos “Dr. Lucio Meléndez”; Argentina Fil: Grimaldi Alva, Luciano. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos “Dr. Lucio Meléndez”; Argentina Fil: Rebec, Beatriz. Provinicia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos “Presidente Perón”; Argentina Fil: Calvo, Mariel. Provinicia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos “Presidente Perón"; Argentina Fil: Henrichsen, Julieta. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos “Dr. Pedro Fiorito”; Argentina Fil: Nocito, Celina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos “Dr. Pedro Fiorito”; Argentina Fil: González, Mariela. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos “Dr. Alberto Eurnekián"; Argentina Fil: Barbero, Guillermo. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina Fil: Ves Losada, Juan. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina Fil: Caballero, Mauricio Tomás. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Zurankovas, Valeria. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Raggio, Mirta. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina Fil: Schavlovsky, Graciela. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina Fil: Kobylarz, Alicia. Provincia de Buenos Aires. Ministerio de Salud. Hospital Materno Infantil “Ana Goitia”; Argentina Fil: Wimmenauer, Vera. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Bugna, Jimena. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Williams, John V.. Vanderbilt University; Estados Unidos Fil: Sastre, Gustavo. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina Fil: Flamenco, Edgardo. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal de Agudos "Dr. Arturo Oñativia"; Argentina Fil: Rodríguez Pérez, Alberto. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos “Dr. Alberto Eurnekián"; Argentina Fil: Ferrero, Fernando. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina Fil: Libster, Romina Paula. Vanderbilt University; Estados Unidos. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Grijalva, Carlos G.. Vanderbilt University; Estados Unidos Fil: Polack, Fernando Pedro. Vanderbilt University; Estados Unidos. Fundación para la Investigación en Infectología Infantil; Argentina

BACKGROUND While the Northern Hemisphere experiences the effects of the 2009 pandemic influenza A (H1N1) virus, data from the recent influenza season in the Southern Hemisphere can provide important information on the burden of disease in children. METHODS We conducted a retrospective case series involving children with acute infection of the lower respiratory tract or fever in whom 2009 H1N1 influenza was diagnosed on reverse-transcriptase polymerase-chain-reaction assay and who were admitted to one of six pediatric hospitals serving a catchment area of 1.2 million children. We compared rates of admission and death with those among age-matched children who had been infected with seasonal influenza strains in previous years. RESULTS Between May and July 2009, a total of 251 children were hospitalized with 2009 H1N1 influenza. Rates of hospitalization were double those for seasonal influenza in 2008. Of the children who were hospitalized, 47 (19%) were admitted to an intensive care unit, 42 (17%) required mechanical ventilation, and 13 (5%) died. The overall rate of death was 1.1 per 100,000 children, as compared with 0.1 per 100,000 children for seasonal influenza in 2007. (No pediatric deaths associated with seasonal influenza were reported in 2008.) Most deaths were caused by refractory hypoxemia in infants under 1 year of age (death rate, 7.6 per 100,000). CONCLUSIONS Pandemic 2009 H1N1 influenza was associated with pediatric death rates that were 10 times the rates for seasonal influenza in previous years.

Viral respiratory infections are the main pediatric cause of hospitalization in infants and young children during the winter worldwide.1 In particular, very low birth weight (VLBW) infants are at high risk for severe viral lung disease.2–4 Although respiratory infections are a serious threat to VLBW infants everywhere, the rate of severe presentations is higher in infants who live in developing countries.4,5 Unlike in industrialized nations,2–4 preterm infants in developing countries often lack access to prophylaxis against respiratory syncytial virus (RSV)5 and have low immunization rates against influenza virus.6 Virus-specific preventive interventions against other agents are not available. Hospitalization rates for VLBW infants in developing countries can exceed 25% during the first year of life.5,7 The protective role of breastfeeding against severe respiratory infections in healthy term infants is well established.8,9 In VLBW infants, a similar beneficial effect has been described.10 For all of these populations, the mechanism of breast milk–mediated protection is unclear. A widely accepted hypothesis attributes the effect of breast milk to neutralization of infectious agents by passively transferred secretory immunoglobulin A in the respiratory tract of exposed infants.9,11–13 Alternative theories attribute protection to the passive transfer of other molecules with anti-infective activity.14–16 All of these hypotheses assume that breastfeeding confers similar passive protection to each and every infant; however, a few observations in recent years suggested that the benefits of breast milk against acute lung disease may differ according to gender.17,18 If confirmed, then these gender differences could challenge the current theories that postulate a passive mechanism of breast milk–mediated protection and identify certain subgroups of infants who are at higher risk for severe disease (ie, those not protected by breast milk). We present the results of a prospective cohort study designed to determine the role of gender and breastfeeding on susceptibility to severe acute lung disease among intensively monitored infants at high risk.

We conducted a prospective, observational study to characterize the clinical manifestations of respiratory infections caused by human metapneumovirus (hMPV) and other viruses in 194 premature infants and young children with chronic lung disease or congenital heart disease in Buenos Aires. Children had 567 episodes of respiratory illness and were monitored until they were 2 years old or until the completion of the study. hMPV elicited 12 infections (2%) year-round; 30% were of moderate or greater severity. Human parainfluenza virus type 3 caused 24 infections (4%), and 5 (25%) of 20 lung infections led to hospitalization. Respiratory syncytial virus (RSV) caused 33 episodes--17% of infections and 32% of hospitalizations during the respiratory season. None of the 10 children infected with influenza virus had severe disease. The present study of at-risk children suggests that hMPV and influenza virus are infrequent agents of severe disease and highlights the need for preventive interventions against RSV in developing countries.

The purpose of the study was to establish the frequency of, reasons for, and outcome of formula changes in infants. In this survey, we interviewed a convenience sample of 100 parents in our pediatric outpatient clinic and 75 parents in private pediatric office practices regarding their baby's initial formula, changes in formula, age at change, reason for change, initiator of the change, and outcome. The infants were 30-210 days old. Sixteen of the 175 infants (9%) were started on nonstandard formulas at birth. Fifty-eight of the remaining 159 infants (36%) were changed from regular to nonstandard formulas. After using nonstandard formulas, only seven infants (4%) were ever challenged subsequently with regular formula and all did well. Colic and regurgitation were the main reasons for switching formulas. In 47% the decision to change the formula was made by the mother and in 44% by the pediatrician. Following the formula change, mothers reported improvement or complete resolution of symptoms in 80% of infants. Although published estimates of formula intolerance range from 2% to 7.5%, one in three infants experiences a formula change, suggesting that nonstandard formulas are used excessively by both mothers and physicians. Nevertheless, in the vast majority of cases, parents report that the changes result in improvement or resolution of symptoms. Thus, while this practice appears to be a simple and effective intervention, it produces a significant population of soy and other nonstandard formula-fed babies who should be drinking regular formulas. Such changes encourage a belief by parents that their infants are allergic or otherwise abnormal and could have a negative impact on subsequent child development.

Elevated sweat chloride concentration in a patient with Mauriac syndrome has been reported only once. The authors of that report regarded their patient's underlying malnutrition, and not Mauriac syndrome per se, as the cause of the elevated sweat chloride concentration. We describe a second example of transient elevation of sweat chloride concentration, which confirms that the malnutrition intrinsic to Mauriac syndrome, rather than the syndrome itself, was the probable cause of elevated sweat chloride values. (J P EDIATR 1995;126:261-3)