Increasing Outbreak Preparedness by Strengthening Centralized and Decentralized Genomic Sequencing Activities to Decipher Monkeypox virus Transmission Dynamics in the Democratic Republic of the Congo

Mpox is an infectious disease caused by monkeypox virus (MPXV), which is a large DNA virus belonging to the genus Orthopoxvirus within the family Poxviridae. MPXV requires robust genomic surveillance to guide public health responses. Whole genome sequencing (WGS) plays a critical role in tracking viral evolution and transmission dynamics.
Mpox has long been framed as a predominantly zoonotic infection with limited human-to-human transmission. This paradigm shifted following the global Clade IIb outbreak originating in West Africa. In the Democratic Republic of the Congo (DRC), where Clade I is endemic, Clade Ib has shown efficient human transmission since 2023, whereas Clade Ia was presumed to arise mostly from repeated zoonotic spillovers. Together with my supervisory team, we recently identified sustained human-to-human transmission of a Clade Ia lineage in Kinshasa in 2024—designated sh2024/Ia—demonstrating that, under favorable conditions, multiple mpox subclades (Ib, IIb, and now Ia) can establish prolonged human transmission. The closest neighbours of the Kinshasa sh2024/Ia outbreak lineage are genomes identified in mpox virus samples from the Equateur province and neighbouring Mai-Ndombe province. In line with the low sequencing coverage, no sustained-human mpox outbreaks have been described in these provinces yet. This development underscores a critical knowledge gap regarding mpox transmission dynamics in the DRC. The objective of this project is to elucidate mpox transmission patterns -with emphasis on (i) tracing back and (ii) following up on the Kinshasa sh2024/Ia outbreak- by deploying centralized and decentralized whole-genome sequencing (WGS) of MPXV.