Highlights
- The 2024 Marburg virus outbreak in Rwanda was characterized by a relatively low case fatality rate of 23%, likely due to rapid implementation of containment and advanced supportive care.
- Health care workers constituted the majority (77%) of confirmed cases, underscoring the critical need for enhanced infection prevention and control (IPC) in healthcare settings.
- Investigational therapeutics including remdesivir and the monoclonal antibody MBP091 were used through expanded access and clinical trial protocols, reflecting advances in filovirus treatment.
- Rapid deployment of the chimpanzee adenovirus 3-vectored vaccine ChAd3-MARV under emergency use authorization for frontline workers and high-risk contacts exemplifies effective vaccine response strategies during outbreaks.
Background
Marburg virus disease (MVD), a severe hemorrhagic fever caused by a filovirus closely related to Ebola virus, carries historically high case fatality rates ranging from 25% to over 80% in African outbreaks. The virus is zoonotic, primarily transmitted to humans from Egyptian fruit bats and via human-to-human contact. Rwanda reported its first-ever MVD outbreak on September 27, 2024, following identification of viral hemorrhagic fever cases at urban hospitals, prompting a multifaceted public health and clinical response. This outbreak provided a pivotal opportunity to evaluate early detection, clinical management, novel therapeutic interventions, and vaccine deployment in a resource-limited setting.
Key Content
Epidemiology and Outbreak Dynamics
The Rwanda outbreak involved 66 laboratory-confirmed cases identified among 6340 suspected patients tested. Of these, 77% (51 cases) were health care workers, highlighting occupational risk during outbreaks of viral hemorrhagic fevers. The median incubation period was estimated at 10 days (IQR 8–13), consistent with prior MVD observations. Symptom onset preceded hospital admission by a median of 2 days (IQR 1–3), emphasizing a narrow window for early intervention.
Epidemiological investigations pinpointed a zoonotic origin linked to exposure to Egyptian fruit bats at a mining site, consonant with the recognized natural reservoir of Marburg virus. The overall case fatality rate (CFR) was 23%, significantly lower than previous outbreaks which have reported CFRs upwards of 50%, indicating potential beneficial effects of enhanced clinical care and early interventions.
Clinical Manifestations and Disease Progression
Clinical presentation included the classical features of filovirus disease: acute onset of fever, malaise, myalgia, gastrointestinal symptoms including diarrhea and vomiting, and hemorrhagic signs in some cases. Disease progression showed that early hospitalization facilitated initiation of supportive therapy, which is critical for improving survival. The case series analysis revealed that patients receiving advanced supportive care alongside investigational antiviral and monoclonal antibody therapies had improved outcomes, although precise attributable benefit requires further controlled studies.
Therapeutics and Vaccine Interventions
Remdesivir and the monoclonal antibody MBP091 were administered under expanded access and randomized clinical trial protocols. Both agents target viral replication or neutralize viral particles, potentially modifying disease severity. Notably, this outbreak marked one of the first real-world deployments of these investigational treatments for Marburg virus.
Concurrently, 1710 frontline healthcare workers and high-risk contacts received the chimpanzee adenovirus 3-vectored vaccine ChAd3-MARV, authorized for emergency use and administered within a phase 2 clinical trial framework. Phase 1b data demonstrate that this vaccine is safe, well-tolerated, and rapidly induces durable Marburg glycoprotein-specific IgG antibody responses, with seroconversion observed by day 14 and peak response by day 29 post-vaccination. The rapid initiation of vaccination 10 days post-outbreak declaration underscores the strategic integration of outbreak preparedness with clinical research.
Public Health and Infection Control Measures
Comprehensive containment measures included intensified case finding, contact tracing, isolation protocols, and rigorous infection prevention and control (IPC) practices within healthcare facilities. The concentration of cases among healthcare workers early in the outbreak reinforced the urgency for IPC training and provision of appropriate personal protective equipment (PPE).
Quarantine and health monitoring of contacts, along with the establishment of screening checkpoints at entry points, contributed to curtailing further spread. The collaborative effort across government health agencies, international partners, and research institutions exemplified a robust outbreak response model.
Expert Commentary
The Rwanda 2024 MVD outbreak response reflects major advances in filovirus disease control, integrating clinical research and public health practice. The relatively low CFR compared to historical outbreaks suggests that early hospital admission, improved critical care support, and investigational therapeutics may reduce mortality. Nonetheless, the predominance of cases among health workers highlights persistent vulnerabilities in IPC adherence, PPE availability, and training, especially in resource-constrained settings.
Vaccination efforts with ChAd3-MARV demonstrate feasibility and immunogenicity during active outbreaks but require further phase 3 efficacy data and assessment of durability in diverse populations. The early deployment of remdesivir and MBP091 marks a promising evolution towards evidence-based antiviral therapy for MVD, addressing a previously unmet therapeutic gap.
Mechanistically, understanding the interaction of these antivirals and antibodies with Marburg virus glycoprotein-mediated entry and replication offers pathways to improved drug design. The rapid progression from outbreak identification to investigational drug and vaccine deployment in Rwanda exemplifies the growing global capacity for filovirus outbreak research and response.
However, limitations remain. The relatively small case number and open-label drug usage during the outbreak limit inference on therapeutic efficacy, underscoring the need for randomized controlled trials and standardized endpoints. Additionally, ongoing surveillance is critical to detect spillover events promptly, particularly in regions of known bat reservoirs.
Conclusion
The 2024 Rwanda Marburg virus outbreak highlights the evolving landscape of filovirus preparedness and response. Early detection, integration of investigational therapeutics, rapid vaccine deployment, and stringent infection control collectively contributed to a lower case fatality rate. Strengthening routine surveillance, expanding healthcare worker protection measures, and further clinical evaluation of novel antivirals and vaccines remain priorities to mitigate future outbreaks. This integrated model serves as a benchmark for timely, evidence-based responses to emerging viral hemorrhagic fevers globally.
References
- Nsanzimana S, Remera E, Nkeshimana M, et al.; Rwanda MVD Outbreak Response Team. Marburg Virus Disease in Rwanda, 2024 – Public Health and Clinical Responses. N Engl J Med. 2025 Sep 11;393(10):983-993. doi: 10.1056/NEJMoa2415816. PMID: 40929633.
- Goldberg J, Fletcher TE, Giuliani R, et al. Safety, tolerability, immunogenicity, and plasmapheresis-based antibody collection in a phase 1b open label trial of two investigational monovalent chimpanzee adenoviral vectored filovirus vaccines, cAd3-Sudan and cAd3-Marburg, in healthy adults. EBioMedicine. 2025 Sep;119:105889. doi: 10.1016/j.ebiom.2025.105889. PMID: 40907247.
- Fletcher TE, Remera E, Nsanzimana S, et al. How Rwanda mounted a research response with an investigational vaccine just ten days into a Marburg outbreak. NPJ Vaccines. 2025 Aug 1;10(1):178. doi: 10.1038/s41541-025-01224-8. PMID: 40750585.
- Firew T, Semakula M, Seruyange E, et al. Marburg virus disease in Rwanda: an observational study of the first 10 days of outbreak response, clinical interventions, and outcomes. BMC Med. 2025 May 20;23(1):292. doi: 10.1186/s12916-025-04123-w. PMID: 40394565.
