Circulação dos vírus dengue no estado de Goiás: vigilância laboratorial (1994-2013) e perfil de anticorpos neutralizantes sorotipo específico durante o surto de 2013 em Goiânia

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2014-12-19

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Universidade Federal de Goiás

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Dengue is an endemic disease in Goias state with current circulation of the four serotypes. In the last five years has been occurred a significant increase in cases, hospitalizations and deaths caused by dengue in the region. In this thesis the first manuscript analyzed data from the virological surveillance of DENV in Goias during 1994-2013. Virus isolation in C6/36 (A.albopictus) cell culture followed by indirect immunofluorescence using monoclonal antibodies were performed in LACEN-GO. During the study period the four serotypes have been identified with introduction of DENV-1 in 1994, DENV-2(1998), DENV-3(2002) and DENV-4(2011). Among 21,684 virus isolation tests performed 4,839(22.3%) were positive. DENV-1 was isolated in 3,023(62.5%), DENV-3 in 1,051 (21.7%), DENV-4 in 413(8.5%) and DENV-2 in 352(7.3%) samples respectively. There were changes in the predominance of serotypes throughout the study period with dominance of DENV-1 between 1994-2002 and 2009-2011, DENV-3 in 2003-2008 and DENV-4 in 2013. The DENV-2 was never prevalent among serotypes isolated in LACEN-GO. The time series of the virological surveillance of dengue in Goias showed the introduction and the temporal sequence of circulation of DENV in the state. This study contributes to characterize the epidemiological scenario of dengue in Goias with possible implications for epidemiological surveillance of the disease in the region. The second manuscript evaluated the presence of dengue serotype-specific neutralizing antibodies (NAb) in patients involved in a clinical dengue cohort established during epidemic of 2012-2013 in Goiania, state of Goias. Among 452 participants of the cohort we analyzed the paired samples from 60 patients classified as severe dengue (n=40) or dengue fever (n=20). The eligibility criteria were confirmation of the infection by IgM, NS1Ag and /or RT-PCR; IgG positive in at least one of the samples. Monotypic or multitypic response were defined: PRNT50≥1/20 for only one serotype or ≥1/20 for two or more serotypes simultaneously. The infecting serotype was defined by ≥4 fold increase in the title of NAb in paired samples. Overall 73.3% of patients had NAb against DENV-4, 68.3% against DENV-1, 68.3% against DENV-2 or 61.6% against DENV-3. The patients' ages ranged from 3 to 81 years. Regardless of age group 85% of patients had multitypic response while 15% had monotypic response. Patients infected with DENV-4 showed the greatest difference in NAb titers in comparison to other serotypes indicating predominance of seroconversion for serotype 4. There was no correlation among preexistent NAb and disease severity. The characterization of dengue serotype-specific immune response is important to study the relationship of preexistence of neutralizing antibodies with clinical outcomes of disease also facing the perspective of introducing of antidengue vaccines to identify protective immunity.

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ARGOLO, Angela Ferreira Lopes de Teive e. Circulação dos vírus dengue no estado de Goiás: vigilância laboratorial (1994-2013) e perfil de anticorpos neutralizantes sorotipo específico durante o surto de 2013 em Goiânia. 2014. 110 f. Tese (Doutorado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2014.