Epidemiologia molecular dos vírus dengue em Goiânia-GO, 1994 - 2006: vigilância laboratorial e caracterização dos sorotipos circulares
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2008-08-06
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Universidade Federal de Goiás
Resumo
Nowadays, dengue constitute the major public health problem, because is relevant cause of
illness and death between thousands people that resident in the tropical and subtropical
regions in world. The dengue virus is classified as four serotypes (DENV-1, 2, 3 and 4)
according to antigenic differences and characterized intra-typical groups called genotypes.
The laboratorial surveillance enables the diagnostic confirmation of dengue infection and
monitoring serotypes circulating through the routine diagnostic techniques. Recently, the
use molecular techniques has contributed to characterize and monitoring of the genotypes
potentially virulent during epidemic and knowledge of biology of dengue virus. This thesis
was organized in an introduction section, that include a literature review on dengue, and
two manuscripts that describing the research conducted with focus on laboratory diagnostic
and molecular epidemiology. The first manuscript entitled Laboratorial Surveillance of
Dengue Virus in Central-Brazil, 1994-2003, was published at Journal of Clinical Virology,
2006 37 (3): 179-83. In this study we present the results of the virological surveillance for
dengue cases conducted in the city of Goiânia (~1,200,000 population) from 1994 to 2003.
Suspected cases were from the main public infectious disease reference hospital and
outpatient clinics covering the metropolitan area. Serological and virus isolation tests were
conduced at the regional reference laboratory. Our objective was to report dengue
circulating serotypes from 1994 to 2003 and the role of distinct serotypes on dengue
clinical outcomes in Central Brazil and to characterize serotypes and genotypes by reverse
transcriptase PCR (RT-PCR) and by restricted site-specific PCR (RSS-PCR) patterns in
selected samples. Laboratory surveillance identified mainly DEN-1 serotype from 1994 to
2002 shifting to a high circulation of DEN-3 in 2003. The adults (87,4%) were the most
affected group and dengue fever accounted for the majority of the cases. Diagnosis of dengue was confirmed in ~50% of the suspected and enhanced by RT-PCR. RSS-PCR
patterns for DEN-1 and DEN-3 corresponded to the circulating subtypes in the country.
The infection DENV-3 did not suggest a major role of infecting DEN-3 in increasing
disease severity during its first-year spread in Central Brazil. The second manuscript, to be
submitted for publication is entitled: Epidemiologia Molecular do Vírus Dengue tipo 3 em
Goiânia GO, 2005-2006. The objective of this manuscript was to characterize the
DENV-3 genotype circulating isolated from well-characterized clinical and laboratory
samples in Goiânia-GO/Brasil. Seven samples had sequences of the prM/M/E region
obtained and comparative analysis was performed with the reference strains. The results
showed the homology of the genomics sequences with genotype III strains. The nucleotide
identity of the all the samples varied from 97.0% to 99.6% and the amino acid sequences
from 97.5% to 99.5%. The analysis of the nucleotide sequence revealed silent mutation and
14 amino acid changes in the protein deduced from gene prM/M/E. In conclusion, the
study confirms that the strains of DENV-3 in Central Brazil relate to genotype III. The
genomic changes along Domain III of the protein E were observed, which could affect the
pathogenicity, but were not consistent between samples of DCC and DHF. Samples of
patients with dengue fever had mutations related to viral attenuation. More investigation is
necessary to evidence of genomic changes found in relationship with clinical forms.
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FÉRES, Valéria Christina de Rezende. Molecular epidemiology of dengue virus in Goiânia, 1994-2006: laboratorial surveillance and characterization of circulate serotypes. 2008. 149 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Goiás, Goiânia, 2008.