North-south pathways, emerging variants, and high climate suitability characterize the recent spread of dengue virus serotypes 2 and 3 in the Dominican Republic

Abstract

We employ a multidisciplinary approach, integrating genomics and epidemiology, to uncover recent dengue virus transmission dynamics in the Dominican Republic. Our results highlight a previously unknown north-south transmission pathway within the country, with the co-circulation of multiple virus lineages. Additionally, we examine the historical climate data, revealing long-term trends towards higher theoretical potential for dengue transmission due to rising temperatures. These findings provide information for targeted interventions and resource allocation, informing as well towards preparedness strategies for public health agencies in mitigating climate and geo-related dengue risks.

Keywords: Caribbean; Dengue virus; Dominican Republic; genomic epidemiology.

Figure 1.. Dynamics of DENV-2 and DENV-3 in the Dominican Republic.

A) Map of the Dominican Republic (DR) depicting the sampling of new DENV-2 and DENV-3 genome sequences by region and district. The color and size of the circles represent the number of new genomes generated in this study: black for DENV-2 and white for DENV-3. B) Time series of dengue cases reported monthly in Dominican Republic, presented as incidence per 100,000 inhabitants (gray bars) versus the climate-based suitability (index P, blue line) for the period data where available. The shaded areas in pink mark visually identifiable waves of cases (between April of consecutive years, see main text) and green marks the year 2023 from which all genomic samples were obtained. C) Long-term time series of monthly climate-based suitability (index P, 1981–2023, blue line). The moving average of suitability (plus-minus 18 months) is presented in black before the year 2001 and in red thereafter (the shaded gray area highlights this time period separation).

Figure 2.. Dispersion dynamics of DENV-2-III in the Dominican Republic.

A) Maximum likelihood (ML) phylogenetic analysis of 29 new complete genome sequences of DENV-2-III generated in this study combined with 661 sequences from GenBank. The scale bar represents units of nucleotide substitutions per site (s/s) and the tree is mid-pointed rooted. Colors represent geographic sampling locations. B) The highlight on the right (panel B) shows the phylogeographic reconstruction of the Dominican Republic Clade (n=43). Solid curved lines denote the links between nodes and the directionality of movement. Circles represent nodes of the MCC phylogeny and are colored according to their inferred time of occurrence. Shaded areas represent the 80% highest posterior density interval and depict the uncertainty of the phylogeographic estimates for each node.

Figure 3.. Dispersion dynamics of DENV-3-III in the Dominican Republic.

A) Maximum Likelihood (ML) phylogenetic analysis of 56 new complete genome sequences of the DENV-3-III genotype from this study, in addition with 1,760 sequences from GenBank representing various DENV-3 genotypes. The scale bar represents units of nucleotide substitutions per site (s/s) and the tree is mid-pointed rooted; B) Maximum clade credibility tree (MCC) of the DENV-3-III emerging American lineage II from 2022–2023, including n=56 complete genome sequences from the Dominican Republic from this study combined with 168 additional genomes for context. Sequences are colored according to sampling location. C) Phylogeographic reconstruction of the Dominican Republic Clade (n=56). Circles represent nodes of the MCC phylogeny and are colored according to their inferred time of occurrence. Shaded areas represent the 80% highest posterior density interval and depict the uncertainty of the phylogeographic estimates for each node. Solid curved lines denote the links between nodes and the directionality of movement.