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      Dengue-specific serotype related to clinical severity during the 2012/2013 epidemic in centre of Brazil

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          Abstract

          Multilingual abstracts

          Please see Additional file 1 for translations of the abstract into the five official working languages of the United Nations.

          Background

          Currently, in Brazil, there is a co-circulation of the four dengue (DENV-1 to DENV-4) serotypes. This study aimed to assess whether different serotypes and antibody response patterns were associated with the severity of the disease during a dengue outbreak, which occurred in 2012/2013 in centre of Brazil.

          Methods

          We conducted a prospective study with 452 patients with laboratory confirmed dengue in central Brazil, from January 2012 to July 2013. The clinical outcome was the severity of cases: dengue, dengue with warning signs, and severe dengue. The patients were evaluated at three different moments. Blood sampling for laboratory testing and confirmatory tests for dengue infection were performed. We performed a multinomial analysis considering the three categories of the dependent variable, as outlined above. The odds ratios ( ORs) were calculated. A multinomial logistic regression model was applied for variables with a P-value <0.20. Statistical analysis was performed with STATA 12.0 software.

          Results

          Four hundred fifty-two patients (452/632, 71.5%) were diagnosed with dengue. The dengue virus (DENV) serotypes were identified in 243 cases. DENV-4 was detected in 135 patients (55.6%), DENV-1 in 91 (37.4%), DENV-3 in 13 (5.3%), and DENV-2 in 4 (1.6%). Patients with the DENV-1 serotype were more prone to present with several clinical and laboratory features as compared with DENV-4 patients, including spontaneous bleeding ( P = 0.03), intense abdominal pain ( P = 0.004), neurological symptoms ( P = 0.09), and thrombocytopenia ( P = 0.01). Secondary infection was more predominant among DENV-4 cases (80.0%) compared with DENV-1 cases (62.3%) ( P = 0.03). The univariate analysis showed that females ( OR = 2.12; 95% CI: 1.44–3.13; P < 0.01) had a higher risk of having dengue with warning signs. The multinomial analysis showed that severe dengue cases with secondary infection had an adjusted OR of 2.80 (95% CI: 0.78–10.00; P = 0.113) as compared with dengue fever with primary infection when adjusted for age and sex.

          Conclusion

          The current data show that 5.8% of patients recruited for treatment in healthcare centres and hospitals during the study period had severe dengue. DENV-4 was the predominant serotype, followed by DENV-1, in a large outbreak of dengue in central Brazil. Our findings contribute to the understanding of clinical differences and immune status related to the serotypes DENV-1 and DENV-4 in central of Brazil.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s40249-017-0328-9) contains supplementary material, which is available to authorized users.

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          Most cited references23

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          Pathogenesis of dengue: challenges to molecular biology.

          Dengue viruses occur as four antigenically related but distinct serotypes transmitted to humans by Aedes aegypti mosquitoes. These viruses generally cause a benign syndrome, dengue fever, in the American and African tropics, and a severe syndrome, dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), in Southeast Asian children. This severe syndrome, which recently has also been identified in children infected with the virus in Puerto Rico, is characterized by increased vascular permeability and abnormal hemostasis. It occurs in infants less than 1 year of age born to dengue-immune mothers and in children 1 year and older who are immune to one serotype of dengue virus and are experiencing infection with a second serotype. Dengue viruses replicate in cells of mononuclear phagocyte lineage, and subneutralizing concentrations of dengue antibody enhance dengue virus infection in these cells. This antibody-dependent enhancement of infection regulates dengue disease in human beings, although disease severity may also be controlled genetically, possibly by permitting and restricting the growth of virus in monocytes. Monoclonal antibodies show heterogeneous distribution of antigenic epitopes on dengue viruses. These epitopes serve to regulate disease: when antibodies to shared antigens partially neutralize heterotypic virus, infection and disease are dampened; enhancing antibodies alone result in heightened disease response. Further knowledge of the structure of dengue genomes should permit rapid advances in understanding the pathogenetic mechanisms of dengue.
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            The history of dengue outbreaks in the Americas.

            Dengue is a viral disease usually transmitted by Aedes aegypti mosquitoes. Dengue outbreaks in the Americas reported in medical literature and to the Pan American Health Organization are described. The outbreak history from 1600 to 2010 was categorized into four phases: Introduction of dengue in the Americas (1600-1946); Continental plan for the eradication of the Ae. aegypti (1947-1970) marked by a successful eradication of the mosquito in 18 continental countries by 1962; Ae. aegypti reinfestation (1971-1999) caused by the failure of the mosquito eradication program; Increased dispersion of Ae. aegypti and dengue virus circulation (2000-2010) characterized by a marked increase in the number of outbreaks. During 2010 > 1.7 million dengue cases were reported, with 50,235 severe cases and 1,185 deaths. A dramatic increase in the number of outbreaks has been reported in recent years. Urgent global action is needed to avoid further disease spread.
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              Neurological manifestations of dengue infection.

              Severe forms of dengue, the most important arboviral infection of man, are associated with haemorrhagic disease and a generalised vascular leak syndrome. The importance of dengue as a cause of neurological disease is uncertain. During 1995, all patients with suspected CNS infections admitted to a referral hospital in southern Vietnam were investigated by culture, PCR, and antibody measurement in serum and CSF for dengue and other viruses. Of 378 patients, 16 (4.2%) were infected with dengue viruses, compared with four (1.4%) of 286 hospital controls (odds ratio [95% CI] 3.1 [1.7-5.8]). Five additional dengue positive patients with CNS abnormalities were studied subsequently. No other cause of CNS infection was identified. Seven infections were primary dengue, 13 secondary, and one was not classified. Ten patients had dengue viruses isolated or detected by PCR, and three had dengue antibody in the CSF. 12 of the 21 had no characteristic features of dengue on admission. The most frequent neurological manifestations were reduced consciousness and convulsions. Nine patients had encephalitis. No patient died, but six had neurological sequelae at discharge. Phylogenetic analysis of the four DEN-2 strains isolated mapped them with a DEN-2 strain isolated from a patient with dengue haemorrhagic fever, and with other strains previously isolated in southern Vietnam. In dengue endemic areas patients with encephalitis and encephalopathy should be investigated for this infection, whether or not they have other features of the disease.
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                Author and article information

                Contributors
                benigno.rocha@gmail.com
                adrianaguilarde@gmail.com
                angelafarmaceutica@hotmail.com
                mariannatassara@yahoo.com.br
                lucimeireantonelli@yahoo.com.br
                isabelaciquini@yahoo.com.br
                marilia.turchi@gmail.com
                vcrisrezende@gmail.com
                turchicm@gmail.com
                Journal
                Infect Dis Poverty
                Infect Dis Poverty
                Infectious Diseases of Poverty
                BioMed Central (London )
                2049-9957
                2 August 2017
                2 August 2017
                2017
                : 6
                : 116
                Affiliations
                [1 ]ISNI 0000 0001 2192 5801, GRID grid.411195.9, Institute of Tropical Pathology and Public Health, , Federal University of Goiás, ; Goiânia, Brazil
                [2 ]ISNI 0000 0001 2192 5801, GRID grid.411195.9, Faculty of Pharmacy, , Federal University of Goiás, ; Goiânia, Brazil
                [3 ]School of Nursing, State University of Goiás, Ceres, Brazil
                Article
                328
                10.1186/s40249-017-0328-9
                5540539
                28764747
                a53836fd-686d-42a4-8a33-193e25613323
                © The Author(s). 2017

                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
                : 14 July 2016
                : 18 June 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100003593, Conselho Nacional de Desenvolvimento Científico e Tecnológico;
                Funded by: FundRef http://dx.doi.org/10.13039/501100005285, Fundação de Amparo à Pesquisa do Estado de Goiás;
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                dengue,secondary infection,severe dengue,dengue type 4,brazil

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