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      Investigation of an outbreak of acute respiratory disease in an indigenous village in Brazil: Contribution of Influenza A(H1N1)pdm09 and human respiratory syncytial viruses

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          Abstract

          Analyses of the 2009 H1N1 influenza pandemic and post-pandemic years showed high attack rates and severity among indigenous populations. This study presents the characteristics of the first documented influenza outbreak in indigenous peoples in Brazil, that occurred from 30th March to 14th April 2016 in a Guarani village in Southeast Region. Acute respiratory infections were prospectively investigated. The majority of the 73 cases were influenza-like illness (ILI) (63.0%) or severe acute respiratory infection (SARI) (20.5%). The ILI+SARI attack rate (35.9%) decreased with increasing age. There was a high influenza vaccination rate (86.3%), but no statistically significant difference in vaccination rates between severe and non-severe cases was seen (p = 0.334). Molecular analyses of 19.2% of the cases showed 100% positivity for influenza A(H1N1)pdm09 and/or hRSV. Influenza A(H1N1)pdm09 was included in the 6B.1 genetic group, a distinct cluster with 13 amino acid substitutions of A/California/07/2009-like. The hRSV were clustered in the BA-like genetic group. The early arrival of the influenza season overlapping usual hRSV season, the circulation of a drifted influenza virus not covered by vaccine and the high prevalence of risk factors for infection and severity in the village jointly can explain the high attack rate of ARI, even with a high rate of influenza vaccination. The results reinforce the importance of surveillance of respiratory viruses, timely vaccination and controlling risk factors for infection and severity of in the indigenous populations in order to preventing disease and related deaths, particularly in children.

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          Preexisting CD8+ T-cell immunity to the H7N9 influenza A virus varies across ethnicities.

          The absence of preexisting neutralizing antibodies specific for the novel A (H7N9) influenza virus indicates a lack of prior human exposure. As influenza A virus-specific CD8(+) T lymphocytes (CTLs) can be broadly cross-reactive, we tested whether immunogenic peptides derived from H7N9 might be recognized by memory CTLs established following infection with other influenza strains. Probing across multiple ethnicities, we identified 32 conserved epitopes derived from the nucleoprotein (NP) and matrix-1 (M1) proteins. These NP and M1 peptides are presented by HLAs prevalent in 16-57% of individuals. Remarkably, some HLA alleles (A*0201, A*0301, B*5701, B*1801, and B*0801) elicit robust CTL responses against any human influenza A virus, including H7N9, whereas ethnicities where HLA-A*0101, A*6801, B*1501, and A*2402 are prominent, show limited CTL response profiles. By this criterion, some groups, especially the Alaskan and Australian Indigenous peoples, would be particularly vulnerable to H7N9 infection. This dissection of CTL-mediated immunity to H7N9 thus suggests strategies for both vaccine delivery and development.
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            Evolutionary dynamics of local pandemic H1N1/2009 influenza virus lineages revealed by whole-genome analysis.

            Virus gene sequencing and phylogenetics can be used to study the epidemiological dynamics of rapidly evolving viruses. With complete genome data, it becomes possible to identify and trace individual transmission chains of viruses such as influenza virus during the course of an epidemic. Here we sequenced 153 pandemic influenza H1N1/09 virus genomes from United Kingdom isolates from the first (127 isolates) and second (26 isolates) waves of the 2009 pandemic and used their sequences, dates of isolation, and geographical locations to infer the genetic epidemiology of the epidemic in the United Kingdom. We demonstrate that the epidemic in the United Kingdom was composed of many cocirculating lineages, among which at least 13 were exclusively or predominantly United Kingdom clusters. The estimated divergence times of two of the clusters predate the detection of pandemic H1N1/09 virus in the United Kingdom, suggesting that the pandemic H1N1/09 virus was already circulating in the United Kingdom before the first clinical case. Crucially, three clusters contain isolates from the second wave of infections in the United Kingdom, two of which represent chains of transmission that appear to have persisted within the United Kingdom between the first and second waves. This demonstrates that whole-genome analysis can track in fine detail the behavior of individual influenza virus lineages during the course of a single epidemic or pandemic.
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              Nutritional status of indigenous children: findings from the First National Survey of Indigenous People’s Health and Nutrition in Brazil

              Introduction The prevalence of undernutrition, which is closely associated with socioeconomic and sanitation conditions, is often higher among indigenous than non-indigenous children in many countries. In Brazil, in spite of overall reductions in the prevalence of undernutrition in recent decades, the nutritional situation of indigenous children remains worrying. The First National Survey of Indigenous People’s Health and Nutrition in Brazil, conducted in 2008–2009, was the first study to evaluate a nationwide representative sample of indigenous peoples. This paper presents findings from this study on the nutritional status of indigenous children < 5 years of age in Brazil. Methods A multi-stage sampling was employed to obtain a representative sample of the indigenous population residing in villages in four Brazilian regions (North, Northeast, Central-West, and Southeast/South). Initially, a stratified probabilistic sampling was carried out for indigenous villages located in these regions. Households in sampled villages were selected by census or systematic sampling depending on the village population. The survey evaluated the health and nutritional status of children < 5 years, in addition to interviewing mothers or caretakers. Results Height and weight measurements were taken of 6,050 and 6,075 children, respectively. Prevalence rates of stunting, underweight, and wasting were 25.7%, 5.9%, and 1.3%, respectively. Even after controlling for confounding, the prevalence rates of underweight and stunting were higher among children in the North region, in low socioeconomic status households, in households with poorer sanitary conditions, with anemic mothers, with low birthweight, and who were hospitalized during the prior 6 months. A protective effect of breastfeeding for underweight was observed for children under 12 months. Conclusions The elevated rate of stunting observed in indigenous children approximates that of non-indigenous Brazilians four decades ago, before major health reforms greatly reduced its occurrence nationwide. Prevalence rates of undernutrition were associated with socioeconomic variables including income, household goods, schooling, and access to sanitation services, among other variables. Providing important baseline data for future comparison, these findings further suggest the relevance of social, economic, and environmental factors at different scales (local, regional, and national) for the nutritional status of indigenous peoples.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: VisualizationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: ResourcesRole: VisualizationRole: Writing – review & editing
                Role: Data curationRole: ResourcesRole: VisualizationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: ResourcesRole: VisualizationRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: VisualizationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: ResourcesRole: VisualizationRole: Writing – review & editing
                Role: MethodologyRole: VisualizationRole: Writing – review & editing
                Role: Funding acquisitionRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                8 July 2019
                2019
                : 14
                : 7
                : e0218925
                Affiliations
                [1 ] Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
                [2 ] London School of Hygiene and Tropical Medicine, London, United Kingdom
                [3 ] Instituto Oswaldo Cruz—Fiocruz, Rio de Janeiro, RJ, Brazil
                [4 ] Universidade Federal Fluminense, Niterói, RJ, Brazil
                [5 ] Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
                [6 ] Secretaria Especial de Saúde Indígena, Curitiba, PR, Brazil
                [7 ] Secretaria Municipal de Saúde de Paraty, Paraty, RJ, Brazil
                [8 ] Secretaria de Vigilância em Saúde, Brasília, DF, Brazil
                The University of Hong Kong, CHINA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ‡ These authors also contributed equally to this work.

                Author information
                http://orcid.org/0000-0002-7591-7791
                Article
                PONE-D-18-28246
                10.1371/journal.pone.0218925
                6613774
                31283762
                e74435e1-ae66-44bd-b891-bba6d42683fc
                © 2019 Cardoso et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 27 September 2018
                : 13 June 2019
                Page count
                Figures: 3, Tables: 4, Pages: 15
                Funding
                Funded by: National Research Council Brazil (CNPq - www.cnpq.br)
                Award ID: Universal 14/2011 - 47.4008/2011-8
                Award Recipient :
                Funded by: National Research Council Brazil (CNPq - www.cnpq.br)
                Award ID: Universal 01/2016 - 428284/2016-7
                Award Recipient :
                Funded by: National Research Council Brazil (CNPq - www.cnpq.br)
                Award ID: Universal 431975/2016-7
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100006507, Fundação Oswaldo Cruz;
                Award ID: INOVA ENSP II 2013 - 25388.000556/2013-52
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100006507, Fundação Oswaldo Cruz;
                Award ID: PAPES VII - Young scientist 2014 - 401789/2015
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100006507, Fundação Oswaldo Cruz;
                Award ID: ENSP 2016/2018 - 25388.000526/2017-70
                Award Recipient :
                Funded by: Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (BR)
                Award ID: PPSUS FAPERJ/SES-RJ/MS-DECIT/CNPq 35/2013-E-26/110.275/2014
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100002322, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior;
                Award ID: Finance Code 001
                Award Recipient :
                This project was funded by the following institutions: Received by AMC - National Research Council (CNPq - www.cnpq.br) Universal 14/2011 - 47.4008/2011-8 and CNPq Universal 01/2016 - 428284/2016-7; Oswaldo Cruz Foundation (Fiocruz - www.fiocruz.br) - INOVA ENSP II 2013 - 25388.000556/2013-52, PAPES VII - Young scientist 2014 - 401789/2015-2 and ENSP 2016/2018 - 25388.000526/2017-70; Research Foundation of the State of Rio de Janeiro (FAPERJ - www.faperj.br) PPSUS FAPERJ/SES-RJ/MS-DECIT/CNPq 35/2013-E-26/110.275/2014; and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES - www.capes.gov.br) - Finance Code 001; Received by MMS - CNPq Universal 431975/2016-7, used for the molecular analysis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
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                Custom metadata
                Influenza A(H1N1)pdm09 sequences obtained in this study were deposited in the Global Initiative on Sharing All Influenza Data (GISAID) database under the accession numbers EPI_ISL_271538, EPI_ISL_271539, EPI_ISL_274050, EPI_ISL_274051 and EPI_ISL_274061 and the hRSV strains in Genbank under the accession numbers (MH719234 and MH719235). Meritorious proposals for access to data will be considered subject to ethical and legal restrictions, the terms of the original informed consent agreement with participant community, and Guarani community protocols for authorizing studies. Due to the small size of the study community, the minimal dataset cannot be adequately anonymized to permit open access while protecting participants’ identities. Data requests may be sent to Reinaldo Souza dos Santos, Head of Department, Departamento de Endemias Samuel Pessoa, Escola Nacional de Saúde Pública, Fundação Oswaldo Cruz, located at Rua Leopoldo Bulhões 1480, Rio de Janeiro, RJ 21041-210, Brazil. Phone: +55 (21) 2598-2683. Email: rssantos@ 123456ensp.fiocruz.br .

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