Joint Understanding and Analysis of clade I monkeypox epidemiology, evolution and immunology in South Kivu

We recently described the novel clade Ib mpox virus from Kamituga, South Kivu, which fast spread in the region and severe symptoms are the reason for the emergency call for mpox research. Further information on its transmission, origin, adaptation, the protective serological response from different population groups, possibilities to improve frontline treatment and possibilities for early detection of the extent of the outbreak is urgently needed to combat the outbreak. The research proposed here is in close collaboration with local researchers and authorities and linked with already established capacity building projects covering DRC, Burundi, Rwanda and Tanzania. We aim to 1) determine the adaptation of the novel clade by performing on-site whole genome sequencing on a unique already available isolate collection covering the duration of the outbreak, 2) identify the origin of this clade by investigating bush meat and hunters, 3) investigate the importance of co-infections and the potential usefulness of real-time metagenomic sequencing treatment guidance, 4) determine the extent of the outbreak by serological and pit latrine surveillance in the cross-border regions of DRC, Burundi, Rwanda and Tanzania and 5) determine the specific immunological response to the novel clade from selected populations. We are uniquely positioned to conduct the proposed research, as we have the necessary technical skills and competences through on-going activities, all ethical permission are in place to investigate mpox as a disease X scenario and we have established collaboration with cross-border health authorities. We expect to create knowledge on the evolution and epidemiology of the novel clade, information on the expected immune response, and novel methods to perform early warning surveillance and improved treatment including of secondary infections. Almost all data generation and analyses will be performed locally, thus also ensuring capacity building for future epidemics.