Phylogeography of Dengue Virus Serotype 4, Brazil, 2010–2011

Marcio Roberto Teixeira Nunes, Nuno Rodrigues Faria, Helena Baldez Vasconcelos, Daniele Barbosa de Almeida Medeiros, Clayton Pereira Silva de Lima, Valéria Lima Carvalho, Eliana Vieira Pinto da Silva, Jedson Ferreira Cardoso, Edivaldo Costa Sousa, Keley Nascimento Barbosa Nunes, Sueli Guerreiro Rodrigues, Ana Barroso Abecasis, Marc A. Suchard, Philippe Lemey, and Pedro Fernando da Costa Vasconcelos

Author affiliations: Instituto Evandro Chagas, Ananindeua, Brazil (M.R.T. Nunes, H. Baldez Vasconcelos, D. Barbosa de Almeida Medeiros, C. Pereira Silva de Lima, V. Lima Carvalho, E. Vieira Pinto da Silva, J. Ferreira Cardoso, E. Costa Sousa Jr, K.N. Barbosa Nunes, S.G. Rodrigues, P.F. da Costa Vasconcelos); KU Leuven, Leuven, Belgium (N. Rodrigues Faria, P. Lemey); Universidade Nova de Lisboa, Lisbon, Portugal (A. Barroso Abecasis); University of California, Los Angeles, California, USA (M.A. Suchard); and Universidade do Estado do Pará, Belém, Brazil (P.F. da Costa Vasconcelos)

Abstract

Dengue virus serotype 4 (DENV-4) reemerged in Roraima State, Brazil, 28 years after it was last detected in the country in 1982. To study the origin and evolution of this reemergence, full-length sequences were obtained for 16 DENV-4 isolates from northern (Roraima, Amazonas, Pará States) and northeastern (Bahia State) Brazil during the 2010 and 2011 dengue virus seasons and for an isolate from the 1982 epidemic in Roraima. Spatiotemporal dynamics of DENV-4 introductions in Brazil were applied to envelope genes and full genomes by using Bayesian phylogeographic analyses. An introduction of genotype I into Brazil from Southeast Asia was confirmed, and full genome phylogeographic analyses revealed multiple introductions of DENV-4 genotype II in Brazil, providing evidence for >3 introductions of this genotype within the last decade: 2 from Venezuela to Roraima and 1 from Colombia to Amazonas. The phylogeographic analysis of full genome data has demonstrated the origins of DENV-4 throughout Brazil.

Dengue virus (DENV), a widespread arthropod-borne virus that commonly affects humans, belongs to the family Flaviviridae, genus Flavivirus, and is classified into 4 distinct serotypes (DENV 1–4). DENV is most prevalent in tropical and subtropical areas, where eco-epidemiologic conditions appear to sustain the virus. In particular, these regions harbor 2 competent DENV vectors (Aedes aegypti and A. albopictus mosquitoes) and have environments favorable for DENV (1). In past decades, the number of countries reporting DENV cases and those with endemic DENV has increased dramatically. These increases reflect the expanding habitat of the Aedes spp. mosquito vectors, the poorly planned urbanization of many cities in developing countries, an increased number of susceptible human hosts, and the rapid spread of DENV serotypes through global human travel networks (2–4). According to the World Health Organization, ≈3 billion persons living in >100 countries are at risk of being infected at least once annually by 1 of the 4 DENV serotypes (4).
In Brazil, DENV-1–3 were responsible for ≈5 million cases of DENV infection during 1990–2009, resulting in >15,000 reported cases of dengue hemorrhagic fever and ≈1,000 DENV-related deaths (5–7). DENV-4 reemerged in Brazil in 2010, 28 years after it was last detected in the country; the site of the reemergence was Roraima State, northern Brazil (8), the same state in which DENV-4 had last been detected in 1982 (9). Brazilian Ministry of Health data for 2010 and 2011 show there were 1,666,208 cases of DENV infection, including 26,659 severe cases and 1,097 associated deaths (10).
We describe the genetic characterization and spatiotemporal patterns of spread for DENV-4 strains isolated from 4 Brazilian states: Pará, Amazonas, and Roraima in northern Brazil and Bahia in northeastern Brazil. To characterize the origins of DENV-4 reemergence, we performed discrete Bayesian phylogeographic analysis on 98 full-length DENV-4 genomes and compared the results with those of a similar analysis on 314 envelope gene sequences.