Spatio-Temporal Tracking and Phylodynamics of an Urban Dengue 3 Outbreak in Sao Paulo, Brazil

Author(s)

Mondini, Adriano ^[1] ; de Moraes Bronzoni, Roberta Vieira ^[1] ; Pereira Nunes, Silvia Helena ^[1] ; Chiaravalloti Neto, Francisco ^{[1, 2]} ; Massad, Eduardo ^[3] ; Alonso, Wladimir J. ^[4] ; Lazzaro, Eduardo S. M. ^[5] ; Ferraz, Amena Alcantara ^[5] ; de Andrade Zanotto, Paolo Marinho ^[6] ; Nogueira, Mauricio Lacerda ^[1]

Affiliation

^[1] Fac Med Sao Jose do Rio Preto, Sao Jose Do Rio Preto - Brazil

^[2] Superintendencia Controle Endemias, Sao Jose Do Rio Preto - Brazil

^[3] Univ Sao Paulo, Fac Med, LIM HCFMUSP 01, Sao Paulo - Brazil

^[4] NIH, Forgarty Int Ctr, Bethesda, MD 20892 - USA

^[5] Secretaria Municipal Saude & Higiene Sao Jose do, Sao Jose Do Rio Preto - Brazil

^[6] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, LEMB, BR-05508 Sao Paulo - Brazil

• Document type: Journal article
• Source: PLoS Neglected Tropical Diseases; v. 3, n. 5 MAY 2009.
• Web of Science Citations: 41

Abstract

The dengue virus has a single-stranded positive-sense RNA genome of similar to 10.700 nucleotides with a single open reading frame that encodes three structural (C, prM, and E) and seven nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins. It possesses four antigenically distinct serotypes (DENV 1-4). Many phylogenetic studies address particularities of the different serotypes using convenience samples that are not conducive to a spatio-temporal analysis in a single urban setting. We describe the pattern of spread of distinct lineages of DENV-3 circulating in Sao Jose do Rio Preto, Brazil, during 2006. Blood samples from patients presenting dengue-like symptoms were collected for DENV testing. We performed M-N-PCR using primers based on NS5 for virus detection and identification. The fragments were purified from PCR mixtures and sequenced. The positive dengue cases were geo-coded. To type the sequenced samples, 52 reference sequences were aligned. The dataset generated was used for iterative phylogenetic reconstruction with the maximum likelihood criterion. The best demographic model, the rate of growth, rate of evolutionary change, and Time to Most Recent Common Ancestor (TMRCA) were estimated. The basic reproductive rate during the epidemics was estimated. We obtained sequences from 82 patients among 174 blood samples. We were able to geo-code 46 sequences. The alignment generated a 399-nucleotide-long dataset with 134 taxa. The phylogenetic analysis indicated that all samples were of DENV-3 and related to strains circulating on the isle of Martinique in 2000-2001. Sixty DENV-3 from Sao Jose do Rio Preto formed a monophyletic group (lineage 1), closely related to the remaining 22 isolates (lineage 2). We assumed that these lineages appeared before 2006 in different occasions. By transforming the inferred exponential growth rates into the basic reproductive rate, we obtained values for lineage 1 of R(0) = 1.53 and values for lineage 2 of R(0) = 1.13. Under the exponential model, TMRCA of lineage 1 dated 1 year and lineage 2 dated 3.4 years before the last sampling. The possibility of inferring the spatio-temporal dynamics from genetic data has been generally little explored, and it may shed light on DENV circulation. The use of both geographic and temporally structured phylogenetic data provided a detailed view on the spread of at least two dengue viral strains in a populated urban area. (AU)

• FAPESP's process: 06/01070-9 - Spatial analisys ot dengue transmission and molecular characterization of the virus in São José do Rio Preto, São Paulo State
• Grantee: Francisco Chiaravalloti Neto
• Support Opportunities: Regular Research Grants