Henry Kyobe Bosa

The 2026 Bundibugyo virus disease (BVD) outbreak in the DRC and Uganda raises urgent questions about the efficacy of existing Ebola virus (EBOV) monoclonal antibodies (mAbs) against Bundibugyo virus (BDBV). Here, we perform genomic and structural analyses of 44 BDBV sequences, including 12 from the 2026 outbreak, to assess mAb binding to the viral glycoprotein (GP). While the MBP134 cocktail epitopes remain conserved, mAb114 (Ebanga) binding is compromised by E112D and P116A mutations, causing off-target binding and reduced affinity. Structural modeling of Inmazeb shows that while Odesivimab maintains epitope binding, Atoltivimab and Maftivimab fail to bind their designated sites individually, though the complete trimeric cocktail demonstrates BDBV synergistic binding. These findings suggest that mAb114 could have reduced efficacy against BDBV due to epitope mutations affecting binding affinity, whereas MBP134 retains conserved targeting and holds promise as a broadly protective therapeutic. The complex binding behavior of Inmazeb components points to the importance of antibody combinatorial effects for treatment efficacy and warrants urgent experimental validation through neutralization assays.

Introduction: Recent increase in reported cases of Bundibugyo virus (species Orthoebolavirus bundibugyoense) in the Democratic Republic of the Congo and Uganda highlight the importance of understanding their evolutionary dynamics. Methodology: We analyzed publicly available genomes obtained from the Pathoplexus database representing 3 medically relevant species of the Orthoebolavirus genus: Ebola virus (n = 3,388), Zaire virus (n = 166), and Bundibugyo virus (n = 49). We investigated whether genetic divergence is associated with sampling time utilizing root-to-tip regression analyses derived from temporally calibrated phylogenies as an indicator of molecular clock behavior. Results: Sudan virus (R2 = 0.855) and Ebola virus (R2 = 0.709) exhibited significant temporal structures between sampling time and genetic divergence. Bundibugyo virus displayed strong clock-like behavior after exclusion of 2026 genomes (R2 = 0.983), which showed a marked substitution deficit relative to the historical molecular clock and deviated substantially from the inferred regression. Date randomization tests supported the presence of temporal signal across all datasets (p < 0.001), indicating that the temporal signals exceeded expectations under a null model without temporal structure. Conclusions: These results provide a comparative assessment of the temporal structures across 3 medically relevant Orthoebolavirus species. While historical genomes largely conformed to molecular clock expectations, the inclusion of genomes from the ongoing 2026 Bundibugyo virus outbreak deviated from these projections, suggesting an alternative evolutionary process for 2026 Bundibugyo virus, such as viral persistence in immune-privileged anatomical sites of previously infected individuals or an independent zoonotic spillover event in an alternative species, in which the virus evolved within its natural reservoir prior to human infection.

Bundibugyo virus disease (BVD) remains a high-consequence threat in Eastern and Central Africa, where cross-border mobility, nonspecific early symptoms, and delayed recognition can obscure transmission. In this case report, we describe Uganda's 2026 BVD index case: a male patient who traveled from the Democratic Republic of the Congo to Uganda and was admitted to a private hospital in Kampala on 11 May 2026 after more than two weeks of vomiting and diarrhea, with epigastric pain, weakness, and hiccups. He deteriorated rapidly, developing acute kidney injury, pulmonary edema, hepatic dysfunction, hypoxemia, delirium, atrial flutter, possible disseminated intravascular coagulation, and multiorgan failure, and died on 14 May. A posthumous EDTA whole-blood specimen tested at the Central Emergency Response and Surveillance Laboratory was positive for orthoebolavirus RNA and confirmed as Bundibugyo virus (BDBV) by RT-qPCR. Sequencing achieved 99% genome coverage at ≥100× depth. The 2026 BDBV genome formed a distinct lineage approximately equidistant from the 2007-2008 Butalya and 2012 Isiro variants, differing by 216-227 nucleotides (~1.2% sequence divergence). Here, we demonstrate the value of fatality surveillance, private-sector surveillance, diagnostic optimization through national specimen referral, and rapid molecular-genomic diagnostics for early detection, transmission chain interruption, and public health response coordination.

Objectives: This study mapped the landscape of public health emergency management (PHEM) training programmes and curricula in Africa from 2000 to 2025 to identify trends, strengths and persistent gaps. Design: The study was conducted following the Arksey and O’Malley framework, refined by Levac et al , and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. Data sources: A comprehensive search of peer-reviewed databases, including Ovid MEDLINE, PubMed, Scopus and CINAHL, was conducted in September 2025. Additional non-indexed resources were obtained from organisational repositories and websites of regional public health organisations, African Journals Online and Google Scholar. Eligibility criteria: Peer-reviewed articles, technical reports, theses and organisational publications published between 2000 and 2025 that described the design, delivery, implementation or evaluation of PHEM training programmes in Africa were included in the study. Data extraction and synthesis: Data were extracted using a standardised form capturing programme characteristics, competencies, delivery modalities, evaluation methods, outcomes and challenges. Qualitative data were analysed thematically and mapped against the review objectives. Results: Of 334 records identified, 32 met the inclusion criteria. Training initiatives ranged from short courses to fellowships and degree programmes, with a predominant focus on epidemic management. Critical domains such as leadership, humanitarian response, One Health, diagnostics and gender equity were under-represented. Few programmes reported formal competency assessments or long-term evaluation outcomes. Key challenges identified included reliance on donor funding, weak institutional ownership, poor integration with academic systems and limited sustainability. Emerging needs included training in the Prevention of Sexual Exploitation, Abuse and Harassment, the use of digital health technologies and integration of the humanitarian-development-peace nexus. Conclusion: PHEM training in Africa remains heavily oriented towards epidemic response, with insufficient emphasis on complex emergencies. Strengthening workforce resilience requires comprehensive and sustainably financed curricula.