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      Zika virus displacement by a chikungunya outbreak in Recife, Brazil

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          Abstract

          Background

          Several arboviruses, including dengue virus (DENV), Zika virus (ZIKV) and chikungunya virus (CHIKV), transmitted by Aedes mosquitoes, circulate in northeast Brazil. Diseases caused by these viruses are of great public health relevance, however, their epidemiological features in areas where the three viruses co-circulate are scarce. Here, we present analyses of molecular and serological diagnostics in a prospective study of acute febrile patients recruited from May 2015 to May 2016 in Recife, Brazil.

          Methods

          Two hundred sixty-three acute febrile patients with symptoms suggestive of an arboviral disease who attended an urgent heath care clinic in the Recife Metropolitan Region in northeast Brazil were enrolled. Acute and convalescent blood samples were collected and tested using molecular and serological assays for infection with DENV, ZIKV and CHIKV.

          Results

          Quantitative real-time reverse-transcriptase polymerase chain reactions (qRTPCR) performed on acute phase sera detected no patients positive for DENV, but 26 (9.9%) positive for ZIKV and 132 (50.2%) positive for CHIKV. There were a few suspected and only one confirmed dengue case. Specific serological assays for ZIKV and CHIKV confirmed the qRTPCR data. Analyses of DENV IgM and IgG ELISAs in the context of qRTPCR results suggested high levels of cross reactive antibodies in ZIKV-positive samples. Results from neutralization assays highly corroborated those from qRTPCR and ZIKV ELISA, indicating very few positive DENV cases. ZIKV infections were temporally clustered in the first months of the study and started to decrease concomitantly with an increase in CHIKV infections in August 2015. The proportion of CHIKV infections increased significantly in September 2015 and remained high until the end of the study period, with an average of 84.7% of recruited patients being diagnosed from August 2015 to May 2016. ZIKV infections exhibited a female bias and the cases were spread over the study site, while CHIKV cases had a male bias and were spatially clustered in each month.

          Conclusions

          In 2015–2016 in the Recife Metropolitan Region, we detected the tail end of a Zika epidemic, which was displaced by a chikungunya epidemic. Few dengue cases were identified despite a high number of official dengue notifications in the area during this period. We show here important epidemiological features of these cases.

          Author summary

          Infection with Zika (ZIKV) and chikungunya (CHIKV) viruses can lead to severe symptoms or outcomes. These viruses are transmitted by the same mosquito vectors that transmit dengue virus (DENV) and the symptoms of all three diseases are similar, thus, it may be difficult for health professionals to diagnose them properly. This study was part of larger study aimed at improving the diagnosis of these diseases. We present data on a patient cohort from Recife, Brazil in which the majority of patients were infected with ZIKV or CHIKV. We show that when Zika cases started to decrease, chikungunya cases appeared and increased rapidly, remaining high until the end of the study. We also highlight the high levels of cross-reactivity on dengue serological assays with ZIKV-positive samples, emphasizing the importance of choosing appropriate tests in areas with simultaneous circulation of arboviruses. Other important epidemiological data are shown and discussed, such as the differential proportion of women and men infected with ZIKV or CHIKV, and the identification of strong hotspots of chikungunya cases. These data may help on the development of control and prevention interventions against arboviral diseases.

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          Most cited references23

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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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            Clade replacements in dengue virus serotypes 1 and 3 are associated with changing serotype prevalence.

            The evolution of dengue virus (DENV) is characterized by phylogenetic trees that have a strong temporal structure punctuated by dramatic changes in clade frequency. To determine the cause of these large-scale phylogenetic patterns, we examined the evolutionary history of DENV serotype 1 (DENV-1) and DENV-3 in Thailand, where gene sequence and epidemiological data are relatively abundant over a 30-year period. We found evidence for the turnover of viral clades in both serotypes, most notably in DENV-1, where a major clade replacement event took place in genotype I during the mid-1990s. Further, when this clade replacement event was placed in the context of changes in serotype prevalence in Thailand, a striking pattern emerged; an increase in DENV-1 clade diversity was associated with an increase in the abundance of this serotype and a concomitant decrease in DENV-4 prevalence, while clade replacement was associated with a decline in DENV-1 prevalence and a rise of DENV-4. We postulate that intraserotypic genetic diversification proceeds at times of relative serotype abundance and that replacement events can result from differential susceptibility to cross-reactive immune responses.
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              Zika Virus Seroprevalence, French Polynesia, 2014–2015

              During 2013–2014, French Polynesia experienced an outbreak of Zika virus infection. Serosurveys conducted at the end of the outbreak and 18 months later showed lower than expected disease prevalence rates (49%) and asymptomatic:symptomatic case ratios (1:1) in the general population but significantly different prevalence rates (66%) and asymptomatic:symptomatic ratios (1:2) in schoolchildren.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – original draft
                Role: Formal analysisRole: MethodologyRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Formal analysisRole: Methodology
                Role: MethodologyRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: MethodologyRole: Supervision
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Supervision
                Role: Data curationRole: MethodologyRole: Resources
                Role: Data curationRole: MethodologyRole: Resources
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                6 November 2017
                November 2017
                : 11
                : 11
                : e0006055
                Affiliations
                [1 ] Laboratory of Virology and Experimental Therapeutics, Aggeu Magalhaes Institute (Instituto Aggeu Magalhães-IAM), Oswaldo Cruz Foundation (Fundação Oswaldo Cruz-FIOCRUZ), Recife, Brazil
                [2 ] Arthropod-borne and infectious Diseases Laboratory (AIDL), Department of Microbiology, Immunology and Pathology, Colorado State University (CSU), Fort Collins, United States of America
                [3 ] Department of Parasitology, IAM, FIOCRUZ, Recife, Brazil
                [4 ] Institute of Integral Medicine Professor Fernando Figueira (Instituto de Medicina Integral Professor Fernando Figueira-IMIP), Recife, Brazil
                [5 ] Statistics and Geoprocessing Laboratory, IAM, FIOCRUZ, Recife, Brazil
                [6 ] Faculty of Medical Science, University of Pernambuco (Universidade de Pernambuco-UPE), Recife, Brazil
                [7 ] Urgent Health Care Unit (Unidade de Pronto Atendimento-UPA) of Paulista, IMIP, Paulista, Brazil
                [8 ] Section Clinical Tropical Medicine, Department of Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany
                [9 ] German Centre for Infection Research (DZIF), partner site Heidelberg, Heidelberg, Germany
                [10 ] Center for Vaccine Research, University of Pittsburgh, Pittsburgh, United States of America
                Center for Disease Control and Prevention, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-1474-0889
                Article
                PNTD-D-17-00822
                10.1371/journal.pntd.0006055
                5697888
                29108009
                48276c81-8417-4150-ac1b-45b1cd024bdc
                © 2017 Magalhaes 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
                : 20 May 2017
                : 19 October 2017
                Page count
                Figures: 7, Tables: 6, Pages: 25
                Funding
                Funded by: European Union
                Award ID: FP7-281803 IDAMS
                Award Recipient :
                Funded by: Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco
                Award ID: PPSUS APQ-0302-4.01/13
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100010686, H2020 European Institute of Innovation and Technology;
                Award ID: 734548
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
                Award ID: R21AI129464
                Funded by: funder-id http://dx.doi.org/10.13039/501100003593, Conselho Nacional de Desenvolvimento Científico e Tecnológico;
                Award ID: 472360/2013-2
                Award Recipient :
                This study was funded by the European Union's Seventh Framework Programme for research, technological development and demonstration (grant FP7-281803 IDAMS; http://www.idams.eu/), where it has been designated with publication reference number IDAMS 45; the State of Pernambuco funding agency (Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco-FACEPE; grant PPSUS APQ-0302-4.01/13); the European Union’s Horizon 2020 Research and Innovation Programme under ZIKAlliance (grant 734548); the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (grant R21AI129464); the ZikaCura (PITT-FIOCRUZ Alliance); and the Brazilian national funding agency (Conselho Nacional de Desenvolvimento Científico e Tecnológico of Brazil-CNPq; grant 472360/2013-2). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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