SYNOPSIS: A rising number of cases of Marburg virus disease, which is caused by one of the most virulent human pathogens, have been reported in Rwanda. Marburg virus infections in humans are rare but can present with a rapidly progressive febrile illness that can lead to multi-organ failure and shock with case-fatality rates of up to 80% to 90%.
SOURCE: Volkmer A. Marburg virus: First cases in Rwanda spark international alarm. BMJ 2024;387:q2155.
Marburg virus is a negative-sense, single-stranded ribonucleic acid (RNA) virus that is a member of the Filoviridae family, which also includes Ebola virus.1 It can cause a severe and often rapidly fatal disease.2 The first recognized outbreak of filovirus disease was caused by Marburg virus in 1967 after several laboratory workers in Europe involved in poliomyelitis vaccine development became ill after handling infected tissues derived from vervets (Chlorocebus pygerythrus), nonhuman primates that had been imported from Uganda.3 The disease was called Marburg virus disease (MVD) after the West German town of Marburg, where most human infections occurred, but the outbreak also occurred in Frankfurt, West Germany, and Belgrade, Yugoslavia.4 In addition to infections among laboratory personnel who had direct contact with vervet tissue, secondary transmission to medical staff and family members also occurred.3 Thirty-one total cases were documented, and seven of these patients died, with an overall fatality rate of 23%.
Since then, several isolated, sporadic outbreaks have occurred, all of which have been in Sub-Saharan Africa, mostly in Uganda.5 The outbreaks have ranged in size from a few cases to 252 cases, which occurred in Angola in 2004-2005.5,6 The Angola epidemic was not only the largest to date but also was the deadliest, with a case fatality rate of 90%, potentially because of a more pathogenic variant.5 The epidemic was largely driven by nosocomial transmission.7 The Marburgvirus genus includes a single species with two known variants, Lake Victoria marburgvirus and Ravn marburgvirus. The vast majority of cases have been caused by the Lake Victoria marburgvirus variant, but the two variants appear to cause similar diseases.7
An outbreak of MVD in Rwanda was reported by the Republic of Rwanda’s Ministry of Health on Sept. 27, 2024.8 No cases of MVD had been reported previously in Rwanda. Cases were confirmed by reverse transcription polymerase chain reaction (RT-PCR) blood tests. The source of the outbreak has not been established. As of Oct. 12, 2024, 61 confirmed cases and 14 deaths have been reported.9 The majority of cases have occurred among healthcare workers from two centers in Kigali, the capital city. No community transmission has yet been detected.
There is evidence that Egyptian fruit bats (Rousettus aegyptiacus) likely serve as the primary natural reservoir for Marburg virus, based on repeated isolation of Marburg virus from R. aegyptiacus caught at multiple locations in Uganda where miners and tourists had contracted MVD, and based on experimental studies of R. aegyptiacus becoming infected after subcutaneous inoculation without evidence of morbidity or mortality.5,10,11 Studies also have found significant evidence of viral shedding through oral secretions of R. aegyptiacus.10 Marburg virus also has been isolated from R. aegyptiacus from Sierra Leone, prior to any know outbreak in Sierra Leone, indicating a wide geographic distribution of chronically infected bats throughout sub-Saharan Africa and an ongoing risk for sporadic spillover events.12 There has been no evidence of arthropod vectors.
The incubation period of MVD is approximately two to 21 days (mean, four to 10 days), and illness is characterized by sudden onset of fever, malaise, myalgias, headache, nausea, vomiting, diarrhea, and other nonspecific symptoms.13 Later in the disease course, an erythematous, maculopapular rash may be observed, and signs of hematologic disorders, such as petechial hemorrhages, continued oozing from venipuncture sites, and gastrointestinal bleeding, may occur.13 MVD can lead to a dramatic and rapidly progressive illness with multi-organ failure, shock, and death. Laboratory abnormalities associated with MVD include leukopenia, lymphocytopenia, thrombocytopenia, elevated liver enzymes, and abnormal coagulation indices.13 The diagnosis of MVD is confirmed primarily through detection of virus in blood or other tissues with the use of RT-PCR tests. Enzyme-linked immunosorbent assays (ELISA) also are used for the detection of Marburg virus antigen.14
Person-to-person transmission of Marburg virus occurs through direct contact with blood and other bodily fluids of infected individuals. Several outbreaks have involved a high degree of transmission to healthcare workers. Infections also have occurred among people involved in preparing cadavers for burials. Marburg virus also has been reported to have been transmitted through improperly sterilized medical equipment and sexually through semen.15,16
There are no available specific treatments for MVD. Clinical management consists of intensive supportive care to maintain effective blood volume and electrolyte balance. Prevention of MVD depends on infection prevention and control measures. There are no approved vaccines or postexposure treatment modalities available.
Commentary
Marburg virus is one of the world’s deadliest pathogens. The latest outbreak of MVD in Rwanda highlights the importance of broadening and strengthening Marburg virus surveillance mechanisms and the critical need to rapidly detect MVD and prevent onward transmission through robust and coordinated infection prevention and control measures. Further investigations into the development of targeted therapies, such as monoclonal antibodies and antiviral therapies, and effective vaccines are urgently needed.
REFERENCES
- Emanuel J, Marzi A, Feldmann H. Filoviruses: Ecology, molecular biology, and evolution. Adv Virus Res 2018;100:189-221.
- Kortepeter MG, Dierberg K, Shenoy ES, Cieslak TJ; Medical Countermeasures Working Group of the National Ebola Training and Education Center’s (NETEC) Special Pathogens Research Network (SPRN). Marburg virus disease: A summary for clinicians. Int J Infect Dis 2020;99:233-242.
- Slenczka WG. The Marburg virus outbreak of 1967 and subsequent episodes. Curr Top Microbiol Immunol 1999;235:49-75.
- Ristanović ES, Kokoškov NS, Crozier I, et al. A forgotten episode of Marburg virus disease: Belgrade, Yugoslavia, 1967. Microbiol Mol Biol Rev 2020;84(2):e00095-19.
- Towner JS, Amman BR, Sealy TK, et al. Isolation of genetically diverse Marburg viruses from Egyptian fruit bats. PLoS Pathog 2009;5(7):e1000536.
- Gear JS, Cassel GA, Gear AJ, et al. Outbreake of Marburg virus disease in Johannesburg. Br Med J 1975;4(5995):489-493.
- Bausch DG, Nichol ST, Muyembe-Tamfum JJ, et al. Marburg hemorrhagic fever associated with multiple genetic lineages of virus. N Engl J Med 2006;355(9):909-919.
- Volkmer A. Marburg virus: First cases in Rwanda spark international alarm. BMJ 2024;387:q2155.
- Rwanda Ministry of Health. Oct. 12, 2024. https://x.com/RwandaHealth/status/1845139678120263863/photo/2
- Amman BR, Jones MEB, Sealy TK, et al. Oral shedding of Marburg virus in experimentally infected Egyptian fruit bats (Rousettus aegyptiacus). J Wildl Dis 2015;51(1):113-124.
- Towner JS, Pourrut X, Albariño CG, et al. Marburg virus infection detected in a common African bat. PLoS One 2007;2(8):e764.
- Amman BR, Bird BH, Bakarr IA, et al. Isolation of Angola-like Marburg virus from Egyptian rousette bats from West Africa. Nat Commun 2020;11(1):510.
- Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis 2011;204 Suppl 3:S810-816.
- Grolla A, Lucht A, Dick D, et al. Laboratory diagnosis of Ebola and Marburg hemorrhagic fever. Bull Soc Pathol Exot 2005;98(3):205-209.
- Peters CJ. Marburg and Ebola — arming ourselves against the deadly filoviruses. N Engl J Med 2005;352(25):2571-2573.
- Coffin KM, Liu J, Warren TK, et al. Persistent Marburg virus infection in the testes of nonhuman primate survivors. Cell Host Microbe 2018;24(3):405-416.e3.
Jake Scott, MD, is Clinical Assistant Professor, Infectious Diseases and Geographic Medicine, Stanford University School of Medicine; Antimicrobial Stewardship Program Medical Director, Stanford Health Care Tri-Valley.
