Multiple introductions and country-wide spread of DENV-2 genotype II (Cosmopolitan) in Brazil

Abstract

Dengue virus serotype 2, genotype Cosmopolitan (DENV-2-GII), is one of the most widespread DENV strains globally. In the USA, DENV-2 epidemics have been dominated by DENV-2 genotype Asian-American (DENV-2-GIII), and the first cases of DENV-2-GII were only described in 2019, in Peru, and in 2021 in Brazil. To gain new information about the circulation of DENV-2-GII in Brazil, we sequenced 237 DENV-2 confirmed cases sampled between March 2021 and March 2023 and revealed that DENV-2-GII is already present in all geographic regions of Brazil. The phylogeographic analysis inferred that DENV-2-GII was introduced at least four times in Brazil, between May 2020 and August 2022, generating multiple clades that spread throughout the country with different success. Despite multiple introductions of DENV-2-GII, analysis of the country-wide laboratory surveillance data showed that the Brazilian dengue epidemic in 2022 was dominated by DENV-1 in most states. We hypothesize that massive circulation of DENV-2-GIII in previous years in Brazil might have created a population immune barrier against symptomatic homotypic reinfections by DENV-2-GII, leading to sustained cryptic circulation in asymptomatic cases and localized outbreaks of this new genotype. In summary, our study stresses the importance of arboviral genomic surveillance to close monitoring and better understanding the potential impact of DENV-2-GII in the coming years.

Keywords: Brazil; dengue virus serotype 2; genomic surveillance; genotype Cosmopolitan; phylogeography.

Figure 1.

Spatiotemporal evolution of DENV-2 genotype II (Cosmopolitan) in South America and circulation dynamics of DENV serotypes in Brazil in recent years. (A) Time-scaled phylogenetic tree of eighty-eight DENV-2-GII genomes with ancestral locations inferred by the phylogeographic model. The branches are colored according to the most likely ancestral location, and pie charts show the posterior probability of each location for key nodes with high uncertainty. Error bars show the 95 per cent HPD of node heights related to introductions to Brazil. The dots on branches indicate a posterior probability higher than 0.9, and key branches are annotated with the posterior support. Inset map depicts the Brazilian states from which DENV-2 sequences were sampled. Colors on the map and phylogenetic tree correspond and the states directly sampled in this study are highlighted in bold. (B) The relative frequency of each DENV serotype (lines) and confirmed dengue cases per 100k habitants (histogram) for a selection of Brazilian states between 2018 and 2022. The acronyms for depicted states: AC—Acre, AM—Amazonas, RR—Roraima, RO—Rondônia, CE—Ceará, RN—Rio Grande do Norte, PB—Paraíba, PE—Pernambuco, SE—Sergipe, RJ—Rio de Janeiro, SP—São Paulo, GO—Goiás, PR—Paraná, SC—Santa Catarina, and RS—Rio Grande do Sul.