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      Zika Virus Outbreak in Rio de Janeiro, Brazil: Clinical Characterization, Epidemiological and Virological Aspects

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          Abstract

          Background

          In 2015, Brazil was faced with the cocirculation of three arboviruses of major public health importance. The emergence of Zika virus (ZIKV) presents new challenges to both clinicians and public health authorities. Overlapping clinical features between diseases caused by ZIKV, Dengue (DENV) and Chikungunya (CHIKV) and the lack of validated serological assays for ZIKV make accurate diagnosis difficult.

          Methodology / Principal Findings

          The outpatient service for acute febrile illnesses in Fiocruz initiated a syndromic clinical observational study in 2007 to capture unusual presentations of DENV infections. In January 2015, an increase of cases with exanthematic disease was observed. Trained physicians evaluated the patients using a detailed case report form that included clinical assessment and laboratory investigations. The laboratory diagnostic algorithm included assays for detection of ZIKV, CHIKV and DENV. 364 suspected cases of Zika virus disease were identified based on clinical criteria between January and July 2015. Of these, 262 (71.9%) were tested and 119 (45.4%) were confirmed by the detection of ZIKV RNA. All of the samples with sequence information available clustered within the Asian genotype.

          Conclusions / Significance

          This is the first report of a ZIKV outbreak in the state of Rio de Janeiro, based on a large number of suspected (n = 364) and laboratory confirmed cases (n = 119). We were able to demonstrate that ZIKV was circulating in Rio de Janeiro as early as January 2015. The peak of the outbreak was documented in May/June 2015. More than half of the patients reported headache, arthralgia, myalgia, non-purulent conjunctivitis, and lower back pain, consistent with the case definition of suspected ZIKV disease issued by the Pan American Health Organization (PAHO). However, fever, when present, was low-intensity and short-termed. In our opinion, pruritus, the second most common clinical sign presented by the confirmed cases, should be added to the PAHO case definition, while fever could be given less emphasis. The emergence of ZIKV as a new pathogen for Brazil in 2015 underscores the need for clinical vigilance and strong epidemiological and laboratory surveillance.

          Author Summary

          Zika virus (ZIKV) has been identified in 2015 in Brazil for the first time, causing outbreaks of an illness characterized by skin rash and absent or low grade and short-termed fever. It is difficult to distinguish ZIKV from Dengue (DENV) or (CHIKV) based on the acute clinical presentation. The virus is closely related to DENV, and therefore antibody tests also have problems distinguishing between the two viruses due to cross-reactivity. Recent findings suggest that in a minority of ZIKV cases neurological disease can develop, and that babies born from mothers reporting a ZIKV-like illness during pregnancy may suffer from congenital abnormalities, in many cases a small head or brain. Here we report about an outbreak of ZIKV disease in Rio de Janeiro in the first half of the year 2015, which reached its peak in May/June 2015. This is the first published description of a ZIKV outbreak in Latin America. It is interesting to note that confirmed cases appeared as early as January 2015. Cases were confirmed based on the detection of the viral genome in the blood of the patients. The clinical characterization of the confirmed cases and unconfirmed cases proved to be very similar. Itching or itching rash has been suggested to be added to the case definition issued by the Pan American Health Organization (PAHO).

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          Most cited references15

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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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            Rapid spread of emerging Zika virus in the Pacific area.

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              Emergence and potential for spread of Chikungunya virus in Brazil

              Background In December 2013, an outbreak of Chikungunya virus (CHIKV) caused by the Asian genotype was notified in the Caribbean. The outbreak has since spread to 38 regions in the Americas. By September 2014, the first autochthonous CHIKV infections were confirmed in Oiapoque, North Brazil, and in Feira de Santana, Northeast Brazil. Methods We compiled epidemiological and clinical data on suspected CHIKV cases in Brazil and polymerase-chain-reaction-based diagnostic was conducted on 68 serum samples from patients with symptom onset between April and September 2014. Two imported and four autochthonous cases were selected for virus propagation, RNA isolation, full-length genome sequencing, and phylogenetic analysis. We then followed CDC/PAHO guidelines to estimate the risk of establishment of CHIKV in Brazilian municipalities. Results We detected 41 CHIKV importations and 27 autochthonous cases in Brazil. Epidemiological and phylogenetic analyses indicated local transmission of the Asian CHIKV genotype in Oiapoque. Unexpectedly, we also discovered that the ECSA genotype is circulating in Feira de Santana. The presumed index case of the ECSA genotype was an individual who had recently returned from Angola and developed symptoms in Feira de Santana. We estimate that, if CHIKV becomes established in Brazil, transmission could occur in 94% of municipalities in the country and provide maps of the risk of importation of each strain of CHIKV in Brazil. Conclusions The etiological strains associated with the early-phase CHIKV outbreaks in Brazil belong to the Asian and ECSA genotypes. Continued surveillance and vector mitigation strategies are needed to reduce the future public health impact of CHIKV in the Americas. Electronic supplementary material The online version of this article (doi:10.1186/s12916-015-0348-x) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                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
                12 April 2016
                April 2016
                : 10
                : 4
                : e0004636
                Affiliations
                [1 ]Acute Febrile Illnesses Laboratory, Evandro Chagas National Institute of Infectious Diseases; Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil
                [2 ]Flavivirus Laboratory, Oswaldo Cruz Institute/ Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil
                [3 ]Scientific Computation Program, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil
                [4 ]Clinical Research Platform, Evandro Chagas National Institute of Infectious Diseases; Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil
                [5 ]Mosquito Transmitters of Hematozoans Laboratory, Oswaldo Cruz Institute/ Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil
                [6 ]Section Clinical Tropical Medicine, Department of Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany & German Center for Infectious Disease Research, Heidelberg, Germany
                Centers for Disease Control and Prevention, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: PB. Performed the experiments: PB GAC AMS AN MdSBQ OL RVdS CR HZ CdSB PCdS MCLdM. Analyzed the data: GAC MW. Contributed reagents/materials/analysis tools: PCdS MCLdM SSA RMRN AMBdF. Wrote the paper: PB GAC AMS MW RLdO MSC AMBdF TJ.

                Author information
                http://orcid.org/0000-0001-9555-7976
                Article
                PNTD-D-16-00204
                10.1371/journal.pntd.0004636
                4829157
                27070912
                3caa50c2-9efd-4298-9657-cbcf6fc39435
                © 2016 Brasil 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
                : 6 February 2016
                : 28 March 2016
                Page count
                Figures: 3, Tables: 2, Pages: 13
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100003593, Conselho Nacional de Desenvolvimento Científico e Tecnológico;
                Award ID: 402135/2011-3
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100004586, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro;
                Award ID: E- 26/010.001558/2014
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100000780, European Commission;
                Award ID: FP7-21803 IDAMS 33
                Award Recipient :
                We thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq (grant no. 484735/2013-6 and 402135/2011-3), the Fundação de Amparo a Pesquisa no Estado do Rio de Janeiro-FAPERJ (grant no. E- 26/010.001558/2014) and the European Commission, grant FP7-21803 IDAMS ( http://www.idams.eu), for having funded the study. 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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                Zika Virus
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