- Evidence base limited: 29 primarily observational studies covering 1,593 cases; research constrained by sporadic outbreaks and geographic concentration in Uganda and DRC.
- Clinical profile includes fever, vomiting, diarrhoea, haemorrhage; estimated case fatality rate 32.8% (95% CI 25.8-40.2) from meta-analysis.
- Urgent coordinated investment needed in inclusive countermeasure trials including pregnant women and children, supported by observational studies and community engagement.
EClinicalMedicine. 2026 Sep 3;99:104179. doi: 10.1016/j.eclinm.2026.104179. eCollection 2026 Sep.
ABSTRACT
BACKGROUND: The 2026 Bundibugyo virus disease (BVD) outbreak in DRC and Uganda underscores that filoviruses remain an unpredictable global health threat, particularly in resource-limited settings. The sporadic occurrence of outbreaks has constrained evidence-generation. We implemented a Rapid Research Needs Appraisal (RRNA) to rapidly and systematically synthesise published research evidence and identify gaps in the evidence base to support management and research strategies.
METHODS: We searched Ovid Medline, Embase and Scopus for primary research studies published between Jan 1, 1999, and Feb 6, 2026 by combining keywords and thesaurus headings for Bundibugyo and humans. This search was supplemented by an updated search in PubMed and MedRxiv up to June 25, 2026. Searches were conducted in English, but without language restrictions. Eligible studies including humans or human samples focused on at least one of the RRNA domains (clinical characteristics, immune response, transmission, risk factors, medical countermeasures and associated social and behavioural factors). Two reviewers screened records for inclusion, one reviewer extracted data with a second reviewer checking a proportion of the data. Data were analysed descriptively.
FINDINGS: 29 primary studies were eligible for inclusion, accounting for 1593 probable or confirmed BVD cases. Of these 29 studies, most were observational (n = 28, 96.6%) and were most commonly conducted in Uganda (n = 15, 51.7%) and the DRC (n = 10, 34.5%). Only one interventional study was included, a non-randomized interventional study exploring EBOV, SUDV and BDBV cross-reactivity following EBOV vaccination. Among studies that reported age, most (58.6%, 17/29) included adults (18+ years), eight (27.6%) included children (0-18 years), and only two (6.9%) included pregnant women. Fever, vomiting, diarrhoea, headache, fatigue, dysphagia, anorexia, dyspnoea and abdominal pain were the most commonly reported symptoms. Haemorrhagic manifestations ranged from 10.4 to 54.0%, with a meta-analysis estimating a CFR of 32.8% (CI 25.8-40.2) based on past outbreaks. Evidence on cross-reactivity to previous Ebola exposure following natural infection of vaccination was sparse and conflicting. One study identified low levels of cross-reactivity in EBOV vaccinated participants, another among EBOV survivors, whereas a third did not detect cross-reactivity following EBOV vaccination. Long-term sequelae, persistent BVD survivor stigma and limited community awareness were also reported.
INTERPRETATION: Whilst acknowledging the limitations of such a rapid appraisal, our findings show that urgent, coordinated investment is needed in countermeasure trials inclusive of pregnant women and children, supported by observational studies community engagement and co-production.
FUNDING: The National Institute for Health Research (NIHR) and the Wellcome Trust.
PMID:42733561 | PMC:PMC13571551 | DOI:10.1016/j.eclinm.2026.104179
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