Epidemiological and genomic evolution of the ongoing outbreak of clade Ib mpox virus in the eastern Democratic Republic of the Congo

Abstract

In September 2023, an ongoing mpox outbreak emerged in South Kivu (Democratic Republic of the Congo) that spread to other regions and countries. Here we describe the epidemiological and genomic evolution of the outbreak between September 2023 and June 2024. Samples were collected from hospitalized patients, along with data on residence and possible exposures. Employee numbers and locations were recorded for bars with sex workers. Where possible, exposures were linked to genomic sequencing data for cluster analysis. In total, 670 cases were admitted to Kamituga General Referral Hospital from 17 health areas. Among the cases, 52.4% were in females and 47.6% in males. The majority (83.4%) were linked to professional sexual interactions. Seven deaths occurred, and three healthcare workers acquired mpox. Eight out of 14 pregnant women had fetal loss. Phylogenetic analysis revealed three clade Ib clusters. Longer branches of a sequence clustering with sequences from Kenya, Uganda, Sweden and Thailand indicate more undocumented spread. Mutations were mostly APOBEC3-type mutations indicative of sustained human-to-human transmission. No clear link between sequence cluster, bar or health area was observed. These data suggest rapid spread mostly through sexual contact within densely populated areas. The spread to neighboring countries highlights the need for extended cross-border collaboration, health education strategies focusing on sex workers, contact tracing, clinical care and surveillance.

Fig. 1. Phylogenetic analysis.

Zoom-in of phylogenetic tree specific for the currently shared and newly sequenced clade Ib sequences. A phylogenetic tree with detailed tip labels is shown in Extended Data Fig. 3. Left: the phylogenetic tree with colored tips indicating the health area of the originating patient. The colored asterisks indicate sequences from different samples of the same patient. Proposed clusters are shown by shading and annotated by markings on the right side of the tree. Middle: linking mutations, present in two or more cases. Right: unique mutations. Differences from the majority rule consensus are highlighted in color. Mutations with characteristic APOBEC3 signature are marked with a black box. Positions that were masked by manual curation or due to too little coverage are indicated with ‘N’. Ambiguous nucleotides are marked in dark gray.

Extended Data Fig. 1. Epicurve and geographic spread of admissions.

(A) Epicurve of outbreak based on Kamituga health zone surveillance dataset for the mpox patients’ admissions at Kamituga hospital and the deaths per epidemiological week between September 29th, 2023 to June 29th, 2024. (B) Map showing evolution of the outbreak in time and space within health areas of Kamituga health zone. Black dots indicate in what epidemiological week and health area a first complete genome sequence was generated. Grayed-out areas are outside of Kamituga health zone, the others represent all health areas in Kamituga health zone. Contains information from the Humanitarian Data Exchange, which is made available under the Open Database License (ODbL).

Extended Data Fig. 2. Population, sex worker, and case counts.

(A) reports population density (2023) per health area in Kamituga health zone, between September 29th, 2023 and April 21st, 2024, South-Kivu, DRC, (B) reports number of sex workers per 1000 inhabitants, (C) reports number of mpox cases per 1000 inhabitants. Gray areas do not have any recorded population (A), sex workers (B), or have not reported any cases (C). Contains information from the Humanitarian Data Exchange, which is made available under the Open Database License (ODbL).

Extended Data Fig. 3. Zoomed in phylogeny and mutations.

Zoom-in of phylogenetic tree with detailed tip labels specific for the currently shared and newly sequenced Clade Ib sequences. Left panel shows the phylogenetic tree with colored tips indicating the health area of the originating patient. Colored asterisks indicate sequences from different samples of the same patient. Proposed clusters are shown by shading and annotated by markings on the right side of the tree. Middle panel shows linking mutations, present in two or more cases. Right panel shows unique mutations. Differences from the majority rule consensus are highlighted in color. Mutations with characteristic APOBEC3 signature are marked with a black box. Positions that were masked by manual curation or due to too little coverage are indicated with ‘N’. Ambiguous nucleotides are marked in dark gray.