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      High Zika Virus Seroprevalence in Salvador, Northeastern Brazil Limits the Potential for Further Outbreaks

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          ABSTRACT

          During 2015 to 2016, Brazil reported more Zika virus (ZIKV) cases than any other country, yet population exposure remains unknown. Serological studies of ZIKV are hampered by cross-reactive immune responses against heterologous viruses. We conducted serosurveys for ZIKV, dengue virus (DENV), and Chikungunya virus (CHIKV) in 633 individuals prospectively sampled during 2015 to 2016, including microcephaly and non-microcephaly pregnancies, HIV-infected patients, tuberculosis patients, and university staff in Salvador in northeastern Brazil using enzyme-linked immunosorbent assays (ELISAs) and plaque reduction neutralization tests. Sera sampled retrospectively during 2013 to 2015 from 277 HIV-infected patients were used to assess the spread of ZIKV over time. Individuals were georeferenced, and sociodemographic indicators were compared between ZIKV-positive and -negative areas and areas with and without microcephaly cases. Epidemiological key parameters were modeled in a Bayesian framework. ZIKV seroprevalence increased rapidly during 2015 to 2016, reaching 63.3% by 2016 (95% confidence interval [CI], 59.4 to 66.8%), comparable to the seroprevalence of DENV (75.7%; CI, 69.4 to 81.1%) and higher than that of CHIKV (7.4%; CI, 5.6 to 9.8%). Of 19 microcephaly pregnancies, 94.7% showed ZIKV IgG antibodies, compared to 69.3% of 257 non-microcephaly pregnancies ( P = 0.017). Analyses of sociodemographic data revealed a higher ZIKV burden in low socioeconomic status (SES) areas. High seroprevalence, combined with case data dynamics allowed estimates of the basic reproduction number R 0 of 2.1 (CI, 1.8 to 2.5) at the onset of the outbreak and an effective reproductive number R eff of <1 in subsequent years. Our data corroborate ZIKV-associated congenital disease and an association of low SES and ZIKV infection and suggest that population immunity caused cessation of the outbreak. Similar studies from other areas will be required to determine the fate of the American ZIKV outbreak.

          IMPORTANCE

          The ongoing American Zika virus (ZIKV) outbreak involves millions of cases and has a major impact on maternal and child health. Knowledge of infection rates is crucial to project future epidemic patterns and determine the absolute risk of microcephaly upon maternal ZIKV infection during pregnancy. For unknown reasons, the vast majority of ZIKV-associated microcephaly cases are concentrated in northeastern Brazil. We analyzed different subpopulations from Salvador, a Brazilian metropolis representing one of the most affected areas during the American ZIKV outbreak. We demonstrate rapid spread of ZIKV in Salvador, Brazil, and infection rates exceeding 60%. We provide evidence for the link between ZIKV and microcephaly, report that ZIKV predominantly affects geographic areas with low socioeconomic status, and show that population immunity likely caused cessation of the outbreak. Our results enable stakeholders to identify target populations for vaccination and for trials on vaccine efficacy and allow refocusing of research efforts and intervention strategies.

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          First report of autochthonous transmission of Zika virus in Brazil

          In the early 2015, several cases of patients presenting symptoms of mild fever, rash, conjunctivitis and arthralgia were reported in the northeastern Brazil. Although all patients lived in a dengue endemic area, molecular and serological diagnosis for dengue resulted negative. Chikungunya virus infection was also discarded. Subsequently, Zika virus (ZIKV) was detected by reverse transcription-polymerase chain reaction from the sera of eight patients and the result was confirmed by DNA sequencing. Phylogenetic analysis suggests that the ZIKV identified belongs to the Asian clade. This is the first report of ZIKV infection in Brazil.
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            Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus.

            Zika virus (ZIKV) is an emerging mosquito-borne flavivirus of significant public health concern. ZIKV shares a high degree of sequence and structural homology compared with other flaviviruses, including dengue virus (DENV), resulting in immunological cross-reactivity. Improving our current understanding of the extent and characteristics of this immunological cross-reactivity is important, as ZIKV is presently circulating in areas that are highly endemic for dengue. To assess the magnitude and functional quality of cross-reactive immune responses between these closely related viruses, we tested acute and convalescent sera from nine Thai patients with PCR-confirmed DENV infection against ZIKV. All of the sera tested were cross-reactive with ZIKV, both in binding and in neutralization. To deconstruct the observed serum cross-reactivity in depth, we also characterized a panel of DENV-specific plasmablast-derived monoclonal antibodies (mAbs) for activity against ZIKV. Nearly half of the 47 DENV-reactive mAbs studied bound to both whole ZIKV virion and ZIKV lysate, of which a subset also neutralized ZIKV. In addition, both sera and mAbs from the dengue-infected patients enhanced ZIKV infection of Fc gamma receptor (FcγR)-bearing cells in vitro. Taken together, these findings suggest that preexisting immunity to DENV may impact protective immune responses against ZIKV. In addition, the extensive cross-reactivity may have implications for ZIKV virulence and disease severity in DENV-experienced populations.
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              Differential Susceptibilities of Aedes aegypti and Aedes albopictus from the Americas to Zika Virus

              Background Since the major outbreak in 2007 in the Yap Island, Zika virus (ZIKV) causing dengue-like syndromes has affected multiple islands of the South Pacific region. In May 2015, the virus was detected in Brazil and then spread through South and Central America. In December 2015, ZIKV was detected in French Guiana and Martinique. The aim of the study was to evaluate the vector competence of the mosquito spp. Aedes aegypti and Aedes albopictus from the Caribbean (Martinique, Guadeloupe), North America (southern United States), South America (Brazil, French Guiana) for the currently circulating Asian genotype of ZIKV isolated from a patient in April 2014 in New Caledonia. Methodology/Principal Findings Mosquitoes were orally exposed to an Asian genotype of ZIKV (NC-2014-5132). Upon exposure, engorged mosquitoes were maintained at 28°±1°C, a 16h:8h light:dark cycle and 80% humidity. 25–30 mosquitoes were processed at 4, 7 and 14 days post-infection (dpi). Mosquito bodies (thorax and abdomen), heads and saliva were analyzed to measure infection, dissemination and transmission, respectively. High infection but lower disseminated infection and transmission rates were observed for both Ae. aegypti and Ae. albopictus. Ae. aegypti populations from Guadeloupe and French Guiana exhibited a higher dissemination of ZIKV than the other Ae. aegypti populations examined. Transmission of ZIKV was observed in both mosquito species at 14 dpi but at a low level. Conclusions/Significance This study suggests that although susceptible to infection, Ae. aegypti and Ae. albopictus were unexpectedly low competent vectors for ZIKV. This may suggest that other factors such as the large naïve population for ZIKV and the high densities of human-biting mosquitoes contribute to the rapid spread of ZIKV during the current outbreak.
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                Author and article information

                Contributors
                Role: Invited Editor
                Role: Editor
                Journal
                mBio
                MBio
                mbio
                mbio
                mBio
                mBio
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                2150-7511
                14 November 2017
                Nov-Dec 2017
                : 8
                : 6
                : e01390-17
                Affiliations
                [a ]Hospital Universitário Professor Edgard Santos, Universidade Federal de Bahia, Salvador, Brazil
                [b ]Instituto Brasileiro para a Investigação da Tuberculose/Fundação José Silveira (IBIT/FJS), Salvador, Brazil
                [c ]Institute of Virology, University of Bonn Medical Centre, Bonn, Germany
                [d ]Institute for Hygiene and Public Health, GeoHealth Centre, WHO Collaborating Centre for Health Promoting Water Management & Risk Communication, University of Bonn, Bonn, Germany
                [e ]Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
                [f ]Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
                [g ]German Centre for Infection Research (DZIF), Germany
                [h ]Maternidade Climério de Oliveira, Universidade Federal da Bahia, Salvador, Brazil
                [i ]Aix Marseille Université, IRD French Institute of Research for Development, EHESP French 19 School of Public Health, EPV UMR_D 190 “Emergence des Pathologies Virales,” Marseille, France
                [j ]IHU Institute hospitalo-universitaire Méditerranée Infection, APHM Public Hospitals of Marseille 21, Marseille, France
                [k ]Section Clinical Tropical Medicine, Department for Infectious Diseases, INF 324, Heidelberg University Hospital, Heidelberg, Germany
                [l ]Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, Germany
                Centers for Disease Control and Prevention
                Emory University School of Medicine
                Author notes
                Address correspondence to Carlos Brites, crbrites@ 123456ufba.br , or Jan Felix Drexler, felix.drexler@ 123456charite.de .

                E.M.N., A.M.-S., and C.P. contributed equally to this work.

                Article
                mBio01390-17
                10.1128/mBio.01390-17
                5686533
                29138300
                54a2c182-39fa-46e1-a7a4-254001735c26
                Copyright © 2017 Netto et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                : 7 August 2017
                : 12 October 2017
                Page count
                supplementary-material: 8, Figures: 5, Tables: 2, Equations: 0, References: 56, Pages: 14, Words: 10283
                Funding
                Funded by: Deutsches Zentrum für Infektionsforschung (DZIF) https://doi.org/10.13039/100009139
                Award Recipient : Thomas Jaenisch Award Recipient : Jan Felix Drexler
                Funded by: EC | Horizon 2020 Framework Programme (H2020) https://doi.org/10.13039/100010661
                Award ID: 734548
                Award Recipient : Beate Mareike Kümmerer Award Recipient : Xavier de Lamballerie Award Recipient : Thomas Jaenisch Award Recipient : Oliver J. Brady Award Recipient : Jan Felix Drexler
                Categories
                Research Article
                Custom metadata
                November/December 2017

                Life sciences
                zika virus,microcephaly,risk factors,serology,socioeconomic status
                Life sciences
                zika virus, microcephaly, risk factors, serology, socioeconomic status

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