Ebola virus disease at the human–animal–environment interface: a scoping review of recent outbreaks, transmission dynamics, and future preventive strategies

Abstract

BackgroundEbola Virus Disease (EVD) remains among the most lethal zoonotic hemorrhagic fevers, with case fatality rates (CFRs) of 25% to over 90%. Since 2018, successive major outbreaks; the 10th Democratic Republic of the Congo (DRC) epidemic (2018–2020), the 2021 Guinea resurgence, the Uganda Sudan ebolavirus outbreaks (2022, 2025), the 16th DRC (Kasai) outbreak (2025), and the 2026 Bundibugyo virus emergency declared a Public Health Emergency of International Concern have claimed thousands of lives, underscoring EVD’s persistent threat at the human–animal–environment interface and critical preparedness gaps.ObjectivesThis scoping review synthesizes recent evidence on EVD outbreak dynamics, zoonotic transmission, genomic epidemiology, therapeutic and vaccine developments, and the sociocultural and ecological drivers of outbreaks.MethodsFollowing PRISMA-ScR, we searched PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar (inception to May 2026), supplemented by WHO outbreak reports. Fifty eligible sources were included, over 90% published 2018–2026.ResultsThe DRC 10th outbreak (3,470 cases; CFR 66.2%) was exacerbated by armed conflict, nosocomial transmission, and community resistance. The 2021 Guinea resurgence was genetically linked to a 2014–2016 survivor, revealing viral persistence in immune-privileged tissues. The 2022 Uganda outbreak (164 cases; CFR 46.3%) highlighted super-spreading and inadequate infection control at private facilities. Frugivorous Pteropodidae bats remain the likely reservoir. Approved monoclonal antibodies Inmazeb and Ebanga showed 28-day mortality of 33.5% and 35.1% versus 49.7% for ZMapp; rVSV-ZEBOV protects against Zaire but not Sudan ebolavirus. Recent events reinforced these themes: 2025 Uganda (14 cases; CFR 29%) saw the first SUDV ring-vaccination trial; 2025 DRC-Kasai (64 cases; CFR 70.3%) was contained within ~ 3 months; and 2026 Bundibugyo again exposed absent countermeasures for non-Zaire species.ConclusionIntegrated One Health surveillance, equitable therapeutic and vaccine access, community engagement, and genomic epidemiology must anchor future EVD prevention. Urgent investment in Sudan ebolavirus vaccines and outbreak-resilient health systems is essential.This is the first comprehensive scoping review to integrate evidence from all three major post-2018 EVD outbreaks namely the DRC 10th epidemic, the 2021 Guinea resurgence, and the 2022 Uganda Sudan ebolavirus outbreak within a unified One Health framework.We provide a novel synthesis of genomic epidemiology alongside clinical, ecological, and sociocultural transmission determinants, bridging the gap between laboratory science and public health practice.The review critically appraises FDA-approved therapeutics (Inmazeb, Ebanga) and vaccine strategies (rVSV-ZEBOV) within the context of ongoing outbreaks caused by non-Zaire ebolaviruses for which no approved medical countermeasures currently exist.Our analysis highlights the paradigm-shifting finding that EVD can re-emerge years after an epidemic through persistence of Zaire ebolavirus in survivor immune-privileged tissues, with direct implications for long-term surveillance policies.

Health & Medical Collection (Module)