Recent outbreaks of Marburg virus in Africa: an urgent call for public concern

Abstract

Introduction Marburg virus (MARV), a zoonotic and highly virulent virus, is the causative agent of Marburg virus disease (MVD). MVD is one of the deadliest infectious diseases known to man, with an associated 90% case fatality rate. This virus belongs to Filoviridae, a viral family that contains negative sense, single-stranded RNA viruses with the potential to cause severe hemorrhagic fever in both humans and nonhuman primates. Members of this viral family belong to 3 main genera, including Marburgvirus (containing MARVs), Ebolavirus (containing Ebola viruses), and Cuevavirus1. While Lloviu virus, the only known member of genus Cuevavirus, is noninfectious in humans, both Marburg and Ebola viruses (except for Ebola Reston virus that causes disease in nonhuman primates) can cause severe, pathogenic illnesses in humans2. There is strong evidence that the reservoir host of MARV is the African fruit bat (Rousettus aegyptiacus). Like Ebola virus, MARV is primarily transmitted to humans through direct contact with infected animals, such as fruit bats, monkeys, and other primates. Secondary transmissions can also occur through contact with the bodily fluids of infected individuals. In addition, the virus can be transmitted through contaminated needles, materials, and surfaces3. The incubation period of MVD is between 2 and 21 days, and its symptoms typically begin with a sudden onset of fever, severe headache, muscle pain, sore throat, and fatigue. These symptoms are often followed by nausea, vomiting, diarrhea, and stomach pain. Presentation of neurological complications, including coma, seizures, confusion, and agitation can sometimes be observed during the later stages of disease. As MVD progresses, many patients can present severe hemorrhagic manifestations, both internally and externally, leading to shock, organ failure, and death3,4. Historical accounts MARV was first discovered in 1967 during simultaneous outbreaks of hemorrhagic fever in Marburg (the origin of the virus name) and Frankfurt, Germany, as well as in Belgrade, Yugoslavia (present day Serbia). Of the 31 individuals infected through exposure to African green monkeys (Cercopithecus aethiops) imported from Uganda, 7 died, resulting in fatality rate of 22%5. Although MARV is endemic to Africa, its precise endemic location is unknown, however suspected areas include Uganda, Kenya, and Angola. Since the initial outbreaks in 1967, there have been several outbreaks and sporadic cases of MVD in different parts of the world, including in several African countries, such as the Democratic Republic of Congo, Angola, South Africa, Kenya, and Uganda, as well as in Europe and America. Between 1998 and 2000, an outbreak occurred in the Democratic Republic of Congo, resulting in >120 deaths with an associated case fatality rate of 83%. What was regarded as the largest MARV outbreak in history occurred in Angola between 2004 and 2005 with 374 cases, resulting in a fatality rate of almost 90%6. In 2008, however, 2 cases of MVD were imported outside Africa and were reported among tourists who had visited caves inhabited by bat colonies in Uganda. One of the tourists, a Dutch woman, died, while the other, an American, recovered7. Several suspected and confirmed outbreaks have also been observed in Uganda, with the most recent cases recorded in 2017, which resulted in 3 deaths and a case fatality rate of 100%4. Upon containment of this outbreak through concerted efforts from both Uganda’s Ministry of Health and the World Health Organization (WHO), no cases of MVD were reported globally between 2018 and 2020. The status quo: recent outbreaks In what was known as the first West African outbreak in history, Guinea detected its first case of MVD in Guéckédou Prefecture village, near Liberia and Sierra Leone border, in August 20218. Unfortunately, the victim died and postmortem analysis of the sample from the patient confirmed MARV. Although the outbreak was well contained, the quick containment could be partly attributed to the country’s past experience with other viral hemorrhagic fever outbreaks, including Ebola and Lassa fever. Moreover, the resources, the community health workers, and WHO technical team who remained on the ground after the country’s Ebola outbreak in June 2021 were repurposed against the MVD outbreak8,9. Concerningly, yet another outbreak in West Africa occurred in Ghana between June 28 and September 16, 2022. This represented the first MVD outbreak in Ghana. More concerning is the fact that this outbreak occurred in less than a year after the last known MVD outbreak in Guinea in 2021. However, there is not yet evidence of epidemiological links between these 2 outbreaks. This outbreak resulted in 2 deaths with an associated case fatality rate of 67%10. The latest outbreak of MVD is currently ongoing in Equatorial Guinea. Although this is yet another de novo MVD outbreak in a new country in Africa, it represents the third outbreak of MVD since the beginning of the coronavirus-19 (COVID-19) pandemic, thus highlighting the need for increased efforts toward epidemic preparedness and response. The current outbreak was declared in February 2023 following reports of deaths linked to a hemorrhagic fever in Kie Ntem Province near Cameroon and Gabon11. So far, a total of 9 cases (1 confirmed case and 8 suspected cases) have now been reported, and all the cases are dead. Because of the limited testing capacity in Equatorial Guinea, samples had to be sent outside of the country to the Institut Pasteur reference laboratory in Senegal and the Centre Interdisciplinaire de Recherches Médicales de Franceville in Gabon, for testing. Two suspected cases of MVD have also been reported in Cameroon in patients with no previous travel history to the outbreak epicenter in Equatorial Guinea. Moreover, as many people have crossed land borders to neighboring countries since the beginning of the outbreak, there is a need for these countries to exercise anticipatory actions, prepare urgent prevention and control strategies, and remain on high alert. Further investigations are ongoing by the Equatorial Guinean Health Authorities to understand the origin of the current outbreak, to break the chain of transmission, and to control and deter further spread of the virus. Moreover, teams of health emergency experts specializing in case management, epidemiology, infection prevention and control, community engagement, laboratory, and risk communication have been deployed by the WHO to complement the national response and control efforts11. Recommendations and future outlook Although many research institutes and pharmaceutical companies, including Sabin Vaccine Institute in Washington DC, Janssen in Belgium, Auro Vaccines, Public Health Vaccines, and the International Aids Vaccine Initiative are already racing to test their experimental vaccine candidates during this outbreak, no vaccines are yet approved for human use12. With no antiviral treatment options and vaccines in sight, supportive care (rehydration) should be administered to keep patients hydrated and to improve their chances of survival. Moreso, robust infection prevention and control programmes should be implemented to break the chain of disease transmission. Effective contact tracing using various technologies should be established, and suspected cases should be actively searched and monitored. Moreover, considering the resemblance of the initial clinical symptoms of MVD with other illnesses, including Ebola, COVID-19, malaria, typhoid fever, flu, leptospirosis, rickettsial infections, etc., the establishment of specialized laboratories with highly sensitive diagnostic tools is necessary to avoid misdiagnosis of cases. Furthermore, the risks associated with the outbreak should be clearly communicated with people in their local languages without inducing fear, people should be sensitized on preventative measures, individuals should avoid coming in contact with and consuming wild animals, and animal products should be properly cooked before consumption. Health care professionals should take standard precautions, such as strictly wearing correct personal protective equipment when caring for any patients, regardless of their MVD status; sterilization and proper disposal of needles and contaminated materials. In addition, with lessons from COVID-19 pandemic, public health emergency and isolation centers should be established and robust point-of-entry surveillance should be initiated to prevent border transmission and global spread. More importantly, due to its high mortality rate, ease of dissemination, its potential to pose severe threats to public health and to induce social disruption, MARV is regarded as a Category a Priority Pathogen and a Select Agent that requires urgent attention13. Concerningly, since imported cases have been reported previously outside Africa, including in the United States and the Netherlands, there is an urgent concern for a global spread. Although the risk for a global spread is lower relative to a regional spread, it is important that the aforementioned measures are fully implemented to quickly contain the current outbreak and to further prevent transborder transmissions. In addition, since many of the recent cases of MVD are only detected postmortem, the establishment of robust epidemic preparedness and response facilities globally is pertinent to allow early detection, deterrence of future outbreaks, and prevention of a likely pandemic. As seen with COVID-19 pandemic, genomic sequencing remains a viable tool for pathogen identification and tracking, establishing transmission routes and aiding outbreak control, hence it is highly recommended that well-planned genomic surveillance be instituted within and around the affected regions with a view to timely detect and respond to future viral outbreaks including MVD. Ethical approval None. Source of funding None. Authors’ contribution A.J.: conceptualization, data curation, writing—original draft preparation, writing—reviewing, and editing. S.S.: conceptualization, data curation, writing—original draft preparation, and writing—reviewing and editing. A.U. data curation, writing—original draft preparation and writing—reviewing and editing. T.B.E.: writing—original draft preparation, writing—reviewing and editing, and visualization. Conflicts of interest disclosure The authors declare that they have no financial conflict of interest with regard to the content of this report. Research registration unique identifying number (UIN) None. Guarantor None.