Genomic epidemiology of dengue virus serotype 3 lineage 3III_B.3.2 in Brazil: insights into its spread and dengue severity amid co-circulation of multiple dengue serotypes.

BACKGROUND

After over a decade of minimal circulation, DENV-3 reemerged in Brazil in 2023, driven by the newly detected lineage 3III_B.3.2. Elucidating the patterns of DENV-3 spread and impact on public health, is critically important in the context of Brazil's hyperendemic dengue scenario. Here, we aimed to investigate the spatiotemporal dispersion of this new lineage and its epidemiological impact in Brazil.

METHODS

We generated 87 near-complete DENV-3 genomes, sampled in nine different Brazilian states, that were analysed with publicly available sequences. Phylogeographic reconstructions inferred introduction events and spatial dispersion of lineage 3III_B.3.2. In parallel, dengue cases notifications (2023-2025) were used to fit multiple logistic regression models assessing associations between DENV serotypes and severity, adjusting for demographic and spatiotemporal covariates.

FINDINGS: We detected at least 14 introductions of lineage 3III_B.3.2 into Brazil during 2023-2024, followed by diversification into six region-specific clades. Epidemiological analyses applied to the RT-qPCR dengue confirmed cases showed an adjusted odds ratios for severe dengue ranging from 1.24 to 1.71 for DENV-2 and from 1.47 to 1.94 for DENV-3, across different settings and using DENV-1 infection as the reference category. Sensitivity analysis to evaluate potential recent heterotypic infection among infants ≤2 years adjusted by confunders showed an association between DENV-2 and severe dengue, while DENV-3 estimates were not statistically significant.

INTERPRETATION: Our results reveal a dynamic pattern of multiple introductions and regionally structured spread of 3III_B.3.2, which may represent a general feature as a similar reconstructed history has also been observed for other DENV serotypes/lineages in Brazil. Although the association observed between DENV-2 and DENV-3 and dengue severity may be influenced by secondary infections, our findings underscore that the co-circulation of multiple serotypes contributes to more severe epidemic outcomes and emphasize the need for ongoing DENV genomic surveillance.

FUNDING: DECIT, CGLAB, Fiocruz, CNPq, and FAPES.