Mention Ebola, and horrifying visions of an apocalyptic infectious disease that causes bleeding and death will cross the minds of many people. The Marburg virus, a member of the same Filoviridae family of viruses that includes Ebola, doesn’t have nearly the same scary name recognition, but outbreaks of Marburg virus disease in remote areas of the Democratic Republic of Congo, Angola, Uganda, Equatorial Guinea and Tanzania have had frighteningly large case fatality rates. And Marburg, like Ebola, can set loose a deadly cascade of fever, bleeding and organ failure.Experts have warned that the Marburg virus, which can be spread from human to human through bodily fluids, could fuel a dangerous pandemic.
Sabin Nsanzimana, M.D., Ph.D.
A 2024 outbreak of Marburg virus disease in Kigali, Rwanda, the country’s capital city, offers some hope that it won’t come to that. In contrast to the other outbreaks in sub-Saharan Africa, the Kigali outbreak had a relatively low case fatality of 23%. In an article about the outbreak published recently in the New England Journal of Medicine (NEJM), Sabin Nsanzimana, M.D., Ph.D., the Rwandan minister of health, and his colleagues credit early case identification, aggressive supportive care and access to investigational agents, including vaccination with a still-experimental vaccine, with curbing the number of deaths. They also point to a wide-angled, “One Health” approach to zoonotic diseases that encompasses human, animal and environmental health.
“The prevention of high mortality in future filovirus disease outbreaks will require faster recognition of viral hemorrhagic fevers through a One Health approach involving collaboration among community health workers, human health and genomics specialists, bat biologists, ecologists, conservationists, and other relevant experts,” Nsanzimana and his co-authors wrote in the discussion section of the article.
In their NEJM account, Nsanzimana and his colleagues trace the start of the outbreak in Kigali to a woman who was transferred to a hospital in the city on Aug. 26, 2024, after a cesarean delivery at a hospital outside of the city. She became feverish, had unusual bleeding and her liver enzyme level spiked. She died within 24 hours of being admitted to the hospital’s intensive care unit (ICU). The woman was not tested for Marburg virus, but epidemiologic investigators discovered that her husband was a miner who had been working in a tunnel inhabited by the type of bat that harbors Marburg virus. He had experienced fever, headache and fatigue in early August but did not seek medical attention. Testing later showed that he had high levels of antibodies against the Marburg virus, and investigators concluded that he was, in fact, the index case of the Rwandan outbreak.
Another telltale piece of the epidemiologic puzzle of the outbreak is that the first confirmed case was in a 37-year-old man who was treated for diabetic ketoacidosis in a bed in the ICU next to the woman who died untested. He was probably exposed to the Marburg virus through contaminated surfaces while he was receiving care in the ICU, Nsanzimana and his colleagues wrote in NEJM.
A street scene in Kigali. Photo by Peter Wehrwein
The Kigali outbreak had three clusters. The first involved staff and patients at the hospital where the woman was admitted and the first case identified. The second was at another hospital. A physician who worked there had been involved in the resuscitation attempts of the first confirmed case at the other hospital. The third cluster involved family members and other close contacts of the index case. Many of them had visited the index case — the 37-year-old man with diabetic acidosis — before he was diagnosed as having Marburg. Altogether 66 people had laboratory-confirmed cases of Marburg, and 15 of them died.
The supportive care included crystalloid fluids and, for patients with complications from bleeding, transfusions of packed red cells and fresh-frozen plasma. When secondary bacterial or fungal infections were suspected, patients were treated with antibiotics and antifungals.
Some patients were treated with remdesivir, the antiviral that was used to treat COVID-19, and MBP091, a monoclonal antibody that targets the Marburg virus. Neither are approved for Marburg, so the Rwandan drug regulators and ethicists approved them on an expedited basis. Remdesivir was first used on Sept. 30, 2024, and MBP091 on Oct. 5, 2024, according to Nsanzimana and his colleagues. Among the 52 patients treated with remdesivir, 3 (6%) died, and among those the 10 treated with MBP091, two (10%) died. Nsanzimana and his colleagues note that neither treatment was given in randomized fashion, so there could be other factors that explain the relatively low mortality rate.
There’s no approved vaccine against Marburg, but the chimpanzee adenovirus 3–vectored Marburg virus vaccine (ChAd3-MARV) had been shown to be safe in a phase 1 trial. As with the treatments, Rwandan drug regulators and ethicists gave the go-ahead to use the vaccine. A total of 1,710 people were vaccinated, including frontline healthcare workers and high-risk contacts. Following a World Health Organization protocol, Rwandan health officials organized use of the vaccine as a phase 2 trial.
By the third week of the response, the number of cases in the Kigali outbreak started to fall. The last patient at an outpatient clinic set up to monitor patients was discharged on Nov. 11, 2024, and on Dec. 20, 2024, the outbreak was declared over.
Nsanzimana and his colleagues’ prescription for prevention of high mortality in future filovirus outbreaks includes faster recognition of viral hemorrhagic fever through a One Health approach and investments in clinical trial infrastructure and vaccine stockpiling.
“These efforts will be critical to reducing morbidity and mortality from future filovirus disease outbreaks and strengthening global health security against emerging pathogens,” they wrote.