Dynamics of emergence and genetic diversity of dengue virus in Reunion Island from 2012 to 2022

Abstract

Background: Dengue is a major public health concern in Reunion Island, marked by recurrent epidemics, including successive outbreaks of dengue virus serotypes 1 and 2 (DENV1 and DENV2) with over 70,000 cases confirmed since 2017.

Methodology/principal findings: In this study, we used Oxford Nanopore NGS technology for sequencing virologically-confirmed samples and clinical isolates collected between 2012 and 2022 to investigate the molecular epidemiology and evolution of DENV in Reunion Island. Here, we generated and analyzed a total of 499 DENV1, 360 DENV2, and 18 DENV3 sequences. By phylogenetic analysis, we show that different genotypes and variants of DENV have circulated in the past decade that likely originated from Seychelles, Mayotte and Southeast Asia and highly affected areas in Asia and Africa.

Conclusions/significance: DENV sequences from Reunion Island exhibit a high genetic diversity which suggests regular introductions of new viral lineages from various Indian Ocean islands. The insights from our phylogenetic analysis may inform local health authorities about the endemicity of DENV variants circulating in Reunion Island and may improve dengue management and surveillance. This work emphasizes the importance of strong local coordination and collaboration to inform public health stakeholders in Reunion Island, neighboring areas, and mainland France.

Fig 1. Summary of the serotyping and genotyping of dengue virus variants detected in Reunion Island from 2012 to 2022.

Panel A shows the distribution of serotypes as determined by RT-PCR (n = 4,792), along with the number of sequenced samples in this study. Panel B shows the genotypes of DENV sequences analyzed in this study (n = 877).

Fig 2. Genotyping of DENV1 (A), DENV2 (B), and DENV3 (C) sequences from Reunion Island from 2012 to 2022 based on E gene sequences.

Maximum likelihood (ML) trees were constructed to investigate the phylogenetic relationships among these sequences using all E sequences available in the NCBI GenBank database. The sequences from Reunion Island obtained in this study are represented by red dots.

Fig 3. Phylogenetic relationships of DENV1 (A) and DENV2 (B and C) from 2013–2016 in Reunion Island.

These subtrees, taken from S1 Fig, were generated by constructing ML trees using all DENV1 or DENV2 sequences from the GenBank database with lengths exceeding 5,000 nucleotides. They highlight the Reunion Island sequences from this study with circles: the 2016 DENV1 sequences in blue (A), the 2016 DENV2 sequences in red (B), and the 2013–2014 DENV2 sequences in red (C). The closest sequences from the GenBank database are represented by squares.

Fig 4. Phylogenetic relationships of DENV2 sequences from 2017 to 2020.

The subtree, taken from S1B Fig, was created by constructing a ML tree using all DENV2 sequences from the GenBank database that were longer than 5,000 nucleotides. It highlights the 2017–2020 DENV2 sequences from this study, which are depicted with circles and a red gradient according to their collection dates. The closest sequences from the GenBank database are presented with squares and color-coded according to their countries of origin.

Fig 5. Phylogenetic relationships of DENV1 genotype I sequences from 2019 to 2022.

The subtree, taken from S1A Fig, was generated by constructing a ML tree using all DENV1 sequences from the GenBank database that were longer than 5,000 nucleotides. It highlights the 2019–2022 genotype I DENV1 sequences from this study, which are depicted with circles and a blue gradient corresponding to their collection dates. The closest sequences from the GenBank database are presented with squares and color-coded according to their countries of origin.

Fig 6. Genetic relationships of DENV1 genotype V sequences from 2019 to 2022.

The subtree, taken from S1A Fig, was generated by constructing a ML tree using all DENV1 sequences from the GenBank database that were longer than 5,000 nucleotides. It highlights the 2019–2022 genotype V DENV1 sequences from Reunion Island in blue rounds and from Mayotte Island in purple rounds. The closest sequences from the GenBank database are represented by squares.

Fig 7. Genetic relationships of DENV3 genotype III sequences from 2019 to 2020.

The subtree, taken from S1C Fig, was generated by constructing a ML tree using all DENV3 sequences from the GenBank database that were longer than 5,000 nucleotides. It highlights the 2019–2020 DENV3 sequences from this study, represented in green rounds. The closest sequences from the GenBank database are represented by squares.