JUA KIVU

The challenge

A new strain of clade I mpox, named clade Ib, was identified in eastern parts of the Democratic Republic of the Congo (DRC) in 2024. Many aspects of this variant, including its origins, spread and interactions with other infections, remain poorly understood.

The discovery of the clade Ib mpox virus emerged from activities undertaken as part of the Global Health EDCTP3-funded GREAT-LIFE project, which is working to build capacity for genomic surveillance in eastern African countries, including Burundi, the DRC, Rwanda, and Tanzania. As part of a capacity-building project, mpox samples from the South Kivu outbreak were sequenced and found to constitute a distinct cluster within the clade I branch of the mpox virus family tree, likely the result of a recent zoonotic spillover that has become established in the human population.

The epicentre of this clade Ib outbreak in the DRC is a densely populated mining area, with multiple bars, a thriving sex industry, and many migratory workers, including regular border crossings. This environment provides opportunities for the extensive spread of the new mpox virus variant.

The project

Through the JUA-KIVU project, the team responsible for identifying the clade Ib mpox virus is carrying out more genome sequencing and other studies to provide additional insights into the outbreak.

Around 200 additional mpox clinical isolates have been collected during the outbreak and will be sequenced to shed light on the virus's evolution and the pathways through which it is transmitted.

Other work will focus on the possible origins of the virus. Local researchers collected samples from multiple wild animals, bushmeat and hunters before and during the outbreak, which will be analysed for signs of the virus and to pinpoint its emergence in the human population.

The project team is also investigating the impact of co-infections on the severity of mpox disease.  Co-infections, for example, affecting mpox skin lesions, appear to be a common cause of death in mpox patients. This effect will be systematically investigated through metagenomic studies to identify all microbes present in patients’ skin lesions and to assess their association with poor outcomes. The antimicrobial susceptibility of co-infections is also being investigated.

It is likely that not all clade Ib infections are being detected, as the numbers are based on analyses of cases seen in health facilities. The project is also carrying out serosurveys to identify how many people show signs of past infection, with a particular focus on high-risk populations such as sex workers, hunters, household members of patients, and travellers. Samples taken from latrines at multiple border crossings are being analysed to provide insights into virus circulation within the wider population. Further data are coming from wastewater surveillance activities that were already part of the GREAT-LIFE project.

The JUA-KIVU project team is also assessing immunological responses to clade Ib infections, comparing both antibody and cell-based responses to those seen following infection with other mpox virus clades and after vaccination.

JUA-KIVU is one of nine projects funded through an emergency call for proposals launched in response to the mpox outbreak in the DRC and other sub-Saharan African countries, which was declared a Public Health Emergency of International Concern (PHEIC) by WHO and a Public Health Emergency of Continental Security (PHECS) by Africa CDC in 2024.

Impact

The JUA-KIVU project will provide new insights into the mpox clade Ib outbreak in the eastern DRC. It will:

• Provide a clearer picture of the likely origins of the outbreak.
• Shed light on the extent to which clade Ib virus has been circulating and is currently being transmitted through high-risk populations.
• Reveal the extent to which co-infections are driving poor outcomes associated with clade I mpox infection.

These activities will inform the treatment of mpox patients, particularly the management of co-infections, and will also provide policymakers with insights to enable them to plan strategies to control the virus's circulation and prevent new spillovers.