Background: Monkeypox virus (MPV) is a member of the Poxviridae family that includes smallpox, cowpox and chickenpox viruses. Endemic to equatorial Africa following casual human to animal or human to human transmission , recent events have seen an increased incidence with indications of sexual transmission. The disease is characterized by fever, muscle aches, skin rash, lymphadenopathy, oral sores, sore throat, cough, etc. Within any cluster of high risk contacts of a case mpox; however, not everyone exposed develops clinical disease. Moreover, among those contacts who develop mpox, not everyone gets severe disease or dies. Hypothesis: Host genetic & viral factors explain the differential outcomes following exposure to MPV. Objectives: To determine the host genetic and viral determinants of mpox disease in Kamituga area, South Kivu province, DRC. Specifically, we will (I) establish well phenotyped cohorts of house-hold contacts, (II) determine rare variants via family trios; (III) undertake RNASeq for transcriptomics, and (IV) study differential cellular immunity profiles using digital cell sorting (DCS) , (V) identify viral variants that drive severe disease Methods: Whole exome sequencing (WES), transcriptomics and DCS studies of house-family contacts clinically prequalified by PCR and serological testing. Virus gDNA will be reverse transcribed from sequenced host RNA and characterized by comparative genomics and phylogeny. Potential impact: This project will elucidate host genetic & viral determinants of susceptibility to mpox disease in context of natural exposure and infection; that may serve as correlates of immune protection following vaccination.

The current Mpox outbreak affecting the Democratic Republic of the Congo, ongoing since 2023, has resulted in more than 19,000 causes and over 1,000 deaths, with women accounting for more than half of those affected. The previous global Mpox outbreak in 2022 was alleviated in part with use of preventive vaccination using modified vaccina Ankara (MVA) vaccine. However, whether this vaccine induces sufficient immune responses in women and those with immunosuppression, which is common in affected areas, and how long vaccine-induced immunity lasts is not well defined. Furthermore, outbreak responses within Africa are also limited by lack of robust diagnostics. The Mpox AFRIVAC Project will engage with key stakeholders and the community to address these knowledge gaps and capacity limitations by adapting a phase 4 clinical trial of pre-exposure vaccination against Mpox currently underway in Europe to African sites affected by the current outbreak. This will be accompanied by technology transfer to develop Mpox immune diagnostics and knowledge transfer to develop a regional vaccinee-focused Clinical Trials Unit. Together, these activities will address key strategic priorities within the region, address knowledge gaps and significantly contribute to regional capacity and public health response to bring an end to the Mpox outbreak.

Every year, about a million children under 15 years are diagnosed with Tuberculosis (TB) worldwide, and about a quarter die. However, over 60% of children with TB remain undiagnosed, particularly in sub-Saharan Africa, which accounts for about 20% of the global burden of paediatric TB cases. In 2022, WHO issued an interim general recommendation to use integrated Treatment-Decision Algorithms (TDAs) to diagnose TB in children under 10 years. However, this recommendation was based on very low certainty of evidence. Therefore, we are seeking funding to address four objectives: 1) To compare the effectiveness of TDAs and the Standard of Care in routine clinical settings 2) To identify processes and contextual factors that influence the effectiveness and fidelity in the implementation of TDAs 3) To compare the costs, cost-effectiveness, and the population level impact of the TDA strategies on the burden of TB and 4) To validate the diagnostic performance (sensitivity, specificity, negative and positive predictive values) of the TDAs in various health system settings and clinical context. A four-year pragmatic open-label cluster randomized controlled trial will be conducted in 120 primary health facilities in Tanzania, Uganda, and DR Congo. The primary outcome is the proportion of children detected and initiated on TB treatment. About 60,000 children with presumptive TB will be screened. We anticipate that this project will yield results that address the issue of low detection rates of paediatric TB in sub-Saharan Africa and beyond, build research capacity in conducting implementation research in low-income countries, and foster networking and collaboration between the partner institutions.

Scientific tools are widely applied across the EU and the AU to support strategic planning for climate-compatible development. They are used by national and local authorities, research institutes and civil society organisations, very often with the support of development partners, academia and consulting firms. They are an important part of the energy planning ecosystem. However, the scientific insights derived from these tools have not always supported the strategic energy planning process successfully. Sometimes uncoordinated and biased approaches to model design and application by the involved actors on the EU and AU side have led to poor reflection of country-specific social, economic, and environmental conditions (Gardumi et al., 2022). The result is often a lack ownership and credibility and thus limited uptake in planning and policymaking processes. In order to address this gap, the overall aim of RE-INTEGRATE is to establish within existing energy planning ecosystems across the AU and EU an enabling and non-exclusive environment for the sharing of knowledge, fit-to-context modelling toolkits and modelling expertise on climate-compatible development. RE-INTEGRATE addresses the need – expressed in the Work Programme - for fostering modelling approaches and expertise in the AU, which are not heavily reliant on the developed countries, by structurally enabling multi-lateral sharing of knowledge and research infrastructure. While doing so, it develops and tests fit-for-purpose 3E models in 8 AU contexts, building on local expertise and analysing climate-compatible development pathways.

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.