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Buenos Aires, Argentina

Libster R.,Fundacion INFANT | Libster R.,Vanderbilt University | Edwards K.M.,Vanderbilt University
Birkhauser Advances in Infectious Diseases | Year: 2011

Ecological and active population-based surveillance studies have clearly shown the large burden of seasonal influenza disease in children, both in hospital and in outpatient settings. Mortality and encephalitis due to seasonal influenza have also been reported. The recent emergence of a novel H1N1 strain and its global spread have also had a major impact on children. Two influenza vaccines are licensed for use in children: trivalent inactivated and live-attenuated vaccines. Both have been shown to be efficacious for the prevention of clinical and laboratoryconfirmed seasonal influenza. In recent comparative trials in young children, liveattenuated vaccines were shown to be more effective than trivalent inactivated vaccines for the prevention of laboratory-confirmed influenza. However, episodes of wheezing were increased in the youngest children receiving live-attenuated vaccine. Trivalent inactivated influenza vaccine has an excellent safety profile and has been mainly associated with minor local pain and tenderness at the injection site. Vaccine efficacy for the inactivated vaccine has been shown to be greater in older children. Vaccines for the prevention of the novel H1N1 strain have also been tested for safety and immunogenicity in children. The increased use of either inactivated or live influenza vaccines directed at seasonal and pandemic strains has the potential to reduce the influenza disease burden in children and to potentially extend herd protection to those who are unvaccinated. © Springer Basel AG 2011.

Scotta M.C.,Grande Rio University | Veras T.N.,Jeser Amarante Faria Childrens Hospital | Klein P.C.,Grande Rio University | Tronco V.,Grande Rio University | And 7 more authors.
Vaccine | Year: 2014

Introduction: 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. Methods: 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. Results: 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 (p<. 0.001). On the other hand, non-respiratory admission rates remained stable comparing both periods (p= 0.39). Conclusion: 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. © 2014 Elsevier Ltd.

Ciencewicki J.M.,U.S. National Institutes of Health | Wang X.,U.S. National Institutes of Health | Marzec J.,U.S. National Institutes of Health | Serra M.E.,Fundacion INFANT | And 4 more authors.
FASEB Journal | Year: 2014

Respiratory syncytial virus (RSV) is the primary cause of lower respiratory tract infection during childhood and causes severe symptoms in some patients, which may cause hospitalization and death. Mechanisms for differential responses to RSV are unknown. Our objective was to develop an in vitro model of RSV infection to evaluate interindividual variation in response to RSV and identify susceptibility genes. Populations of human-derived HapMap lymphoblastoid cell lines (LCLs) were infected with RSV. Compared with controls, RSV-G mRNA expression varied from ̃1- to 400-fold between LCLs. Basal expression of a number of gene transcripts, including myxovirus (influenza virus) resistance 1 (MX1), significantly correlated with RSV-G expression in HapMap LCLs. Individuals in a case-control population of RSVinfected children who were homozygous (n=94) or heterozygous (n=172) for the predicted deleterious A allele in a missense G/A SNP in MX1 had significantly greater risk for developing severe RSV disease relative to those with the major allele (n=108) (X2=5.305, P=0.021; OR: 1.750, 95% CI: 1.110, 2.758, P=0.021). We conclude that genetically diverse human LCLs enable identification of susceptibility genes (e.g., MX1) for RSV disease severity in children, providing insight for disease risk. © FASEB.

Acosta P.L.,Fundacion INFANT | Acosta P.L.,CONICET | Caballero M.T.,Fundacion INFANT | Polack F.P.,Fundacion INFANT | Polack F.P.,Vanderbilt University
Clinical and Vaccine Immunology | Year: 2016

In 1967, infants and toddlers immunized with a formalin-inactivated vaccine against respiratory syncytial virus (RSV) experienced an enhanced form of RSV disease characterized by high fever, bronchopneumonia, and wheezing when they became infected with wild-type virus in the community. Hospitalizations were frequent, and two immunized toddlers died upon infection with wild-type RSV. The enhanced disease was initially characterized as a "peribronchiolar monocytic infiltration with some excess in eosinophils." Decades of research defined enhanced RSV disease (ERD) as the result of immunization with antigens not processed in the cytoplasm, resulting in a nonprotective antibody response and CD4+ T helper priming in the absence of cytotoxic T lymphocytes. This response to vaccination led to a pathogenic Th2 memory response with eosinophil and immune complex deposition in the lungs after RSV infection. In recent years, the field of RSV experienced significant changes. Numerous vaccine candidates with novel designs and formulations are approaching clinical trials, defying our previous understanding of favorable parameters for ERD. This review provides a succinct analysis of these parameters and explores criteria for assessing the risk of ERD in new vaccine candidates. © 2016, American Society for Microbiology. All Rights Reserved.

Coviello S.,Fundacion INFANT | Wimmenauer V.,Fundacion INFANT | Polack F.P.,Fundacion INFANT | Polack F.P.,Vanderbilt University | And 2 more authors.
Human Vaccines and Immunotherapeutics | Year: 2014

Respiratory viruses cause significant morbidity and mortality in infants and young children worldwide. Current strategies to modulate the immune system and prevent or treat respiratory viral infections in this age group have shown limited success. Here, we demonstrate that a lysate derived from Gram-positive and Gram-negative organisms positively modulates protective antibody responses against both respiratory syncytial virus (RSV) and influenza virus in murine models of infection. Interestingly, despite the complex mixture of Toll-like receptor (TLR) agonists present in the bacterial lysate, the modulatory effects were mostly dependent on TLR4 signaling. Our results indicate that the use of simple formulations of TLR-agonists can significantly improve the immune response against critical pediatric respiratory pathogens. © 2014 Taylor & Francis Group, LLC.

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