Molecular epidemiology of recurrent zoonotic transmission of mpox virus in West Africa

Abstract

Nigeria and Cameroon reported their first mpox cases in over three decades in 2017 and 2018 respectively. The outbreak in Nigeria is recognised as an ongoing human epidemic. However, owing to sparse surveillance and genomic data, it is not known whether the increase in cases in Cameroon is driven by zoonotic or sustained human transmission. Notably, the frequency of zoonotic transmission remains unknown in both Cameroon and Nigeria. To address these uncertainties, we investigated the zoonotic transmission dynamics of the mpox virus (MPXV) in Cameroon and Nigeria, with a particular focus on the border regions. We show that in these regions mpox cases are still driven by zoonotic transmission of a newly identified Clade IIb.1. We identify two distinct zoonotic lineages that circulate across the Nigeria-Cameroon border, with evidence of recent and historic cross border dissemination. Our findings support that the complex cross-border forest ecosystems likely hosts shared animal populations that drive cross-border viral spread, which is likely where extant Clade IIb originated. We identify that the closest zoonotic outgroup to the human epidemic circulated in southern Nigeria in October 2013. We also show that the zoonotic precursor lineage circulated in an animal population in southern Nigeria for more than 45 years. This supports findings that southern Nigeria was the origin of the human epidemic. Our study highlights the ongoing MPXV zoonotic transmission in Cameroon and Nigeria, underscoring the continuous risk of MPXV (re)emergence.

Extended Data Figure 1:

Estimates of the evolutionary rate for zoonotic Clade IIb and Clade IIa combined under the different clock models

Figure 1:

A) Map of Nigeria and Cameroon showcasing the ecological setting of zoonotic MPXV in Nigeria and Cameroon. The forest cover, including the discontiguous cross-border forest belt referenced in the text, are highlighted in green. The border between Nigeria and Cameroon is annotated in deep red, with the Rivers Niger in Nigeria and Sanaga in Cameroon highlighted in light blue. Our sampling sites across the border are annotated in orange and blue respectively for Cameroon and Nigeria, and states of interest annotated with highlighted borders. B) Reconstructed SNPs mapped onto the branches of the Clade IIb phylogeny. APOBEC3 mutations are annotated in yellow and red, with non-APOBEC3 mutations in gray and black. The novel lineage sampled from Cameroon and Akwa Ibom in Nigeria named Clade IIb.1, is highlighted in the gray box and annotated. Our new zoonotic outgroup from Abia is annotated as “Zx”, and forms part of Clade IIb.2 which is annotated in the darker blue box. Lineage A, representing the sustained human epidemic in Nigeria, is highlighted in the light blue box as hMPXV-1. C) The number of APOBEC3 SNPs out of all mutations for the novel zoonotic lineage Clade IIb.1, the hMPXV-1 subtree (highlighted and annotated in Figure B) and the Zoonotic subtree of Clade IIb.2 (KJ642617 and Zx annotated in Figure B).

Figure 2:

The time-resolved phylogeny of Clade IIb. hMPXV-1, representing the human epidemic in Nigeria, is collapsed. Our new zoonotic outgroup from Abia is annotated as “Zx”, with Clade IIb.2 annotated in the dark blue box. Clade IIb.1 is annotated in text. Distributions on the x-axis represent the tMRCA of the color matching node.

Figure 3:

A) Global MPXV phylogeny of Clade I, Clade IIa and Clade IIb. Our Clade IIb sequences are annotated as tip points B) Comparison of the evolutionary rate of the hMPXV-1 APOBEC3, hMPXV-1 Non-APOBEC3, Zoonotic Clade IIa and Zoonotic Clade IIb.1 under the two-epoch partitioned model the local clock model (Clade IIa, Clade IIb.1) respectively.