ABSTRACT:
Dengue virus (DENV) has become an increasing public health concern in Africa, particularly in West Africa, where all four serotypes (DENV-1 to DENV-4) have been documented in recent outbreaks. In Senegal, the viral landscape was historically dominated by sylvatic DENV-2 in the southern regions. However, in 2009, the country experienced its first urban epidemic linked to DENV-3. Since 2017, dengue outbreaks have occurred annually, yet data on the genetic diversity of circulating DENV strains remain limited. To address this gap, we leveraged genomic surveillance using nanopore sequencing through the 4S network, a sentinel syndromic surveillance program. Between 2019 and 2023, we analyzed remnant sera from 8,746 individuals, performing RNA extraction, RT-qPCR, and molecular serotyping with the CDC dengue typing kit. Whole genome sequencing was conducted using a serotype-specific multiplex PCR tiling approach on the Oxford Nanopore MinION. Out of 434 DENV-positive samples, DENV-3 was most prevalent (72.82%), followed by DENV-1 (17.41%) and DENV-2 (1.05%). A group of untypeable samples from southern Senegal were identified as sylvatic DENV-2 (genotype VI), which failed molecular serotyping due to mutations in primer/probe binding sites. We recovered 39 nearly complete genomes, revealing genetic diversity including clades within DENV-1 genotype V and DENV-3 genotype III, as well as both cosmopolitan and sylvatic DENV-2. Phylogeographic analysis suggests that sylvatic DENV-2/GVI has circulated cryptically since 2009. These findings highlight the need for integrated One Health surveillance and raise concerns about diagnostic accuracy and vaccine efficacy, emphasizing updated strategies for dengue control in Senegal and Africa.