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      Co-circulation and simultaneous co-infection of dengue, chikungunya, and zika viruses in patients with febrile syndrome at the Colombian-Venezuelan border

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          Abstract

          Background

          In Colombia, the dengue virus (DENV) has been endemic for decades, and with the recent entry of the chikungunya virus (CHIKV) (2014) and the Zika virus (ZIKV) (2015), health systems are overloaded because the diagnosis of these three diseases is based on clinical symptoms, and the three diseases share a symptomatology of febrile syndrome. Thus, the objective of this study was to use molecular methods to identify their co-circulation as well as the prevalence of co-infections, in a cohort of patients at the Colombian-Venezuelan border.

          Methods

          A total of 157 serum samples from patients with febrile syndrome consistent with DENV were collected after informed consent and processed for the identification of DENV (conventional PCR and real-time PCR), CHIKV (conventional PCR), and ZIKV (real-time PCR). DENV-positive samples were serotyped, and some of those positive for DENV and CHIKV were sequenced.

          Results

          Eighty-two patients were positive for one or more viruses: 33 (21.02%) for DENV, 47 (29.94%) for CHIKV, and 29 (18.47%) for ZIKV. The mean age range of the infected population was statistically higher in the patients infected with ZIKV (29.72 years) than in those infected with DENV or CHIKV (21.09 years). Both co-circulation and co-infection of these three viruses was found. The prevalence of DENV/CHIKV, DENV/ZIKV, and CHIKV/ZIKV co-infection was 7.64%, 6.37%, and 5.10%, with attack rates of 14.90, 12.42, and 9.93 cases per 100,000 inhabitants, respectively. Furthermore, three patients were found to be co-infected with all three viruses (prevalence of 1.91%), with an attack rate of 4.96 cases per 100,000 inhabitants.

          Conclusion

          Our results demonstrate the simultaneous co-circulation of DENV, CHIKV, ZIKV and their co-infections at the Colombian-Venezuelan border. Moreover, it is necessary to improve the differential diagnosis in patients with acute febrile syndrome and to study the possible consequences of this epidemiological overview of the clinical outcomes of these diseases in endemic regions.

          Electronic supplementary material

          The online version of this article (10.1186/s12879-018-2976-1) contains supplementary material, which is available to authorized users.

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          Most cited references52

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          Dengue, Urbanization and Globalization: The Unholy Trinity of the 21st Century

          Dengue is the most important arboviral disease of humans with over half of the world’s population living in areas of risk. The frequency and magnitude of epidemic dengue have increased dramatically in the past 40 years as the viruses and the mosquito vectors have both expanded geographically in the tropical regions of the world. There are many factors that have contributed to this emergence of epidemic dengue, but only three have been the principal drivers: 1) urbanization, 2) globalization and 3) lack of effective mosquito control. The dengue viruses have fully adapted to a human-Aedes aegypti-human transmission cycle, in the large urban centers of the tropics, where crowded human populations live in intimate association with equally large mosquito populations. This setting provides the ideal home for maintenance of the viruses and the periodic generation of epidemic strains. These cities all have modern airports through which 10s of millions of passengers pass each year, providing the ideal mechanism for transportation of viruses to new cities, regions and continents where there is little or no effective mosquito control. The result is epidemic dengue. This paper discusses this unholy trinity of drivers, along with disease burden, prevention and control and prospects for the future.
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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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              Zika virus: following the path of dengue and chikungunya?

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                Author and article information

                Contributors
                mayecahe_90@hotmail.com
                julian.ruizs@campusucc.edu.co
                esehjcslab@gmail.com
                sergio.gomez@udes.edu.co
                +57-7-6356624 , marlen.martinezg@campusucc.edu.co
                Journal
                BMC Infect Dis
                BMC Infect. Dis
                BMC Infectious Diseases
                BioMed Central (London )
                1471-2334
                30 January 2018
                30 January 2018
                2018
                : 18
                : 61
                Affiliations
                [1 ]GRID grid.442158.e, Grupo de Investigación en Ciencias Animales-GRICA, , Universidad Cooperativa de Colombia, ; Calle 30A #, 33-51 Bucaramanga, Colombia
                [2 ]GRID grid.442204.4, Universidad de Santander UDES, Facultad de Ciencias de la Salud, Programa de Bacteriología y Laboratorio clínico, Grupo de investigación en manejo clínico – CLINIUDES, ; Bucaramanga, Colombia
                [3 ]GRID grid.442204.4, Maestría en Investigación en Enfermedades Infecciosas, , Universidad de Santander, ; Bucaramanga, Colombia
                [4 ]ISNI 0000 0000 8882 5269, GRID grid.412881.6, Doctorado en Ciencias Básicas Biomedicas, , Universidad de Antioquia, ; Medellin, Colombia
                [5 ]Laboratorio Clínico, E.S.E. Jorge Cristo Sahium Hospital, Norte de Santander Cúcuta, Colombia
                Author information
                http://orcid.org/0000-0002-9429-0058
                Article
                2976
                10.1186/s12879-018-2976-1
                5791178
                29382300
                97897b73-76fb-4f0c-8253-c942f52e0e3b
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 4 October 2016
                : 23 January 2018
                Funding
                Funded by: Universidad Cooperativa de Colombia
                Award ID: Convocatoria Sostenibilidad 2014 and Grant 1882-2017
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Infectious disease & Microbiology
                dengue virus,chikungunya virus,zika virus,co-infection,co-circulation

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