Geographic origin and evolution of dengue virus serotypes 1 and 3 circulating in Africa

Despite the increasing burden of dengue in Kenya and Africa, the introduction and expansion of the virus in the region remain poorly understood. The objective of this study is to examine the genetic diversity and evolutionary histories of dengue virus (DENV) serotypes 1 and 3 in Kenya and contextualize their circulation within circulation dynamics in the broader African region. Viral RNA was extracted from samples collected from a cohort of febrile patients recruited at clinical sites in Kenya from 2013 to 2022. Samples were tested by polymerase chain reaction (PCR) for DENV presence. Five DENV-positive samples were serotyped, and complete viral genomes for phylogenetic inference were obtained via sequencing on Illumina platforms. Sequences generated in our study were combined with global datasets of sequences, and Bayesian and maximum likelihood methods were used to infer phylogenetic trees and geographic patterns of spread with a focus on Kenya and Africa as a whole. Four new DENV-1 and one new DENV-3 genomes were successfully sequenced and combined with 328 DENV-1 and 395 DENV-3 genomes from elsewhere for phylogenetic analyses. The DENV-1 sequences from our study formed a monophyletic cluster with an inferred common ancestor in 2019 (most recent common ancestor 2019 and 95% high posterior density 2018-19), which was closely related to sequences from Tanzania. The single DENV-3 sequence clustered with sequences from Tanzania and Kenya, was collected between 2017 and 2019 and was related to recent outbreaks in the region. Phylogenetic trees resolved multiple clades of DENV-1 and DENV-3 concurrently circulating in Africa, introduced in the early-to mid-2000s. Three DENV-1 and four DENV-3 clades are highlighted, introduced between 2000 and 2015. Phylogeographic models suggest frequent, independent importations of DENV lineages into Kenya and Africa from East and South-East Asia via distinct geographic pathways. DENV-1 and DENV-3 evolutionary dynamics in Africa are characterized by the cocirculation of multiple recently introduced lineages. Circulating lineages are introduced via distinct geographic pathways that may be centered around regional nexus locations. Increased surveillance is required to identify key regional locations that drive spread, and dengue interventions should focus on interrupting spread at these locations.