Marburg virus disease: lesson learned from the first outbreak encounter in Tanzania

Abstract

Introduction Viral hemorrhagic fevers (VHFs) have been of public health threat globally for years due to their nature of occurrence as outbreaks. Most of them are of zoonotic concern characterized by outbreaks, some interepidemic, which are hard to predict1,2. The Arenavirus, Bunyaviridae, filovirus, and Flaviviridae viruses are known to cause different diseases that have common presentations and hence, termed VHFs2. VHFs are multisystem syndrome but primarily target the vascular and coagulation system. Human infection is a result of direct contact between humans and infected animal body excretions, like rats2,3. The ongoing trends in global population, aging, international travel, change in land use, culture, and climate change have a synergistic influence on their outbreaks, spread, and distribution4. Africa is endemic to Marburg virus diseases (MVDs), Ebola, Crimean Congo hemorrhagic fever, rift valley fever, Lassa fever, yellow fever, and the recent emerging Arenavirus3,5. In the recent decade, several outbreaks of hemorrhagic fever diseases have occurred in neighborhood countries, predominantly being Ebola virus and Marburg virus in Uganda and Congo, respectively. In Tanzania, such outbreaks are not common. However, bordering countries with frequent outbreaks, geographical factors, cultural practices, and low public health awareness makes Tanzania vulnerable with increased susceptibility to VHFs6,7. In the absence of these outbreaks, still, several studies showed a seroprevalence of different VHFs, including Crimean-Congo hemorrhagic fever, Ebola virus disease, MVD, Rift Valley fever, and yellow fever in different geographical areas in Tanzania7–9. This article highlights the epidemiology, clinical pathology of MVD, the situation of the outbreak in Tanzania, and stresses on the interventions, which should be considered in the prevention and control of such outbreaks. History, epidemiology, and clinical pathology of Marburg virus disease MVD is a severe and often fatal illness caused by the Marburg virus, a member of the Filoviridae family10. The virus was first identified in 1967, following outbreaks that occurred simultaneously in Marburg and Frankfurt, Germany, and Belgrade, Yugoslavia (now Serbia)11. The first cases were of laboratory workers who had been handling imported African green monkeys from Uganda. The monkeys had been captured in the wild and transported to Europe for medical research. The workers became ill with a severe and deadly hemorrhagic fever, characterized by a high fever, bleeding, and organ failure. The virus is named after the city of Marburg, Germany, where the first cases were identified11. The virus is closely related to the Ebola virus, and both viruses belong to the Filoviridae family7,8. Since the initial outbreaks, there have been sporadic cases of MVD in several countries, including Uganda, Angola, and the Democratic Republic of Congo reported in the Congo (1998–2000), Angola (2004–2005), Uganda (2007, 2012, 2014, 2017), Kenya (1990, 1987, 1980), Ghana (2022) Guinea (2021), along with a laboratory accident in Russia12–14. These outbreaks have typically been linked to contact with infected animals, such as fruit bats, or with the handling of infected human remains. MVD is a rare disease, with sporadic outbreaks occurring primarily in central and eastern Africa. But since its discovery in 1967, there have been <20 known outbreaks of MVD, mostly in Uganda and the Democratic Republic of Congo12. The Marburg virus is primarily transmitted to humans from infected animals, such as fruit bats and non-human primates10,15,16. The virus can also spread from person to person through direct contact with bodily fluids, including blood, urine, and saliva, of infected individuals. Outbreaks of MVD tend to occur in isolated and rural areas, where individuals may come into contact with infected animals during hunting, butchering, or handling of animal carcasses17. Health care workers who care for MVD patients are also at high risk of infection if they are not properly trained and equipped with personal protective equipment (PPE). The average case fatality rate of MVD is around 50% and the high mortality, ranges from 24% to 88%, depending on the outbreak, early diagnosis, and the quality of medical care available10,14. There is currently no specific treatment or vaccine for MVD, and management is largely supportive, focusing on managing symptoms and preventing complications18,19. Treatment is largely supportive, focusing on managing symptoms and providing fluid and electrolyte replacement. Hence, early identification and isolation of cases, along with infection control measures, are critical to preventing the spread of the virus. The Marburg virus is an enveloped RNA virus that belongs to the family Filoviridae. The virus targets cells of the immune system, including macrophages and dendritic cells, and causes damage to the vascular system and multiple organs18,20. After entering the body through contact with infected bodily fluids, the virus replicates in the lymphatic system and spreads to other organs through the bloodstream17,21. The virus then infects and damages the endothelial cells that line blood vessels, causing leakage of blood and other fluids into surrounding tissues. This results in severe hemorrhagic fever and multiorgan dysfunction, with symptoms, such as high fever, headache, muscle aches, vomiting, diarrhea, and bleeding from various sites including the skin, gums, and gastrointestinal tract18,20. The virus also interferes with the immune response, leading to a decreased number of immune cells, impaired production of antibodies, and an overproduction of inflammatory cytokines21,22. This can result in a state of immune suppression that makes individuals more susceptible to secondary infections and complications. The exact mechanisms, by which the Marburg virus causes disease and death, are not fully understood23–27. However, it is believed that the virus interferes with multiple cellular processes, leading to a disruption of normal physiology and a severe inflammatory response. Research is ongoing to better understand the pathogenesis of the Marburg virus and to develop effective treatments and vaccines to prevent its spread and manage its symptoms28–30. Situation in Tanzania On March 21, 2023, Tanzania reported the first Marburg outbreak that occurred in the Bukoba district, Kagera region, North-western Tanzania (Fig. 1)12,31,32. As of March 22, 2023, there were 8 cases and 5 deaths with a case fatality ratio: 65.2%, without any case reported out of the Bukoba district33. Different intervention measures have been implemented in Tanzania for the prevention and control of the outbreak. World Health Organization, National, Regional, and district-level Rapid Response Teams have been deployed to investigate and implement response measures34. Moreover, contact tracing activities have been implemented to monitor people with similar symptoms in the community and at health facilities, including contacts of the known cases. A total of 161 contacts have been identified and 140 have been followed up and monitored by health professionals on March 21, 2023. Risk communication activities have also been initiated in the Kagera Region to provide health awareness education and prevention messages. As of March 22, 2023, Tanzania has issued a travel advisory after the outbreak to prevent the further spread of the diseases to unaffected areas. Tanzania developed an emergency budget and secured funds amounting to 695,640,000 Tanzania Shillings (297, 282.05 USD) from Government internal sources for 7 days of urgent priority response interventions, while a total of 100,000,000 TZS (42, 735. 04 USD) have been from the World Health Organization (WHO).Figure 1: Map of Tanzania showing affected regions with Marburg virus disease.Generally, the Tanzania health system has proved to be strong in response to the situation. The emergency response team had achieved a contact tracing of up to 86.9%, providing PPEs, and close monitoring of the points of entry. Not only that, there were multi-professional involvement, involvement of international agencies, and close monitoring of activities done by the response team. These measures had a significant contribution to preventing the spread of the disease. Despite the efforts which have been done, still Tanzania is faced with several challenges as reported in the first situational report of the outbreak by the Ministry of Health Tanzania35. Inadequate resources, funds, vehicles, and human resources to support interventions, especially contact tracing, geographical limitations of the areas as some of them are unreachable with formal transport, inadequate special designated ambulances for cases, and inadequate health care providers were among the key challenges outlined in the report. Moreover, community case detection was delayed. It took 15 days from the death of the index case for the health system to detect the presence of the disease, and 5 more days to confirm the disease. Among the infected two health workers in primary health centers, one death case is a concern on either inability to recognize the VHF case or breach in Infection Prevention and Control protocols hence more effort to train health care workers on case definition for VHFs and to observe Infection Prevention and Control. Laboratories in primary health care centers were unable to perform supportive rapid laboratory tests. These might have contributed to the fact that there was hesitance and the late response of health care providers to give supportive therapy as part of medical care to patients. Furthermore, this might be associated with a lack of expertise, misconceptions, and a shortage of PPEs. The shortage of tools like Case Investigation Form forms, contact listing forms, and contact follow-up forms may have obscured the effectiveness of the response team. Home isolation of the contact person and misconceptions of the disease among community members may be the other key challenges35. Conclusion and recommendation Emerging infectious diseases, particularly VHF have been a public health concern as they pose a great challenge to the health systems due to their outbreak nature of the occurrence. Their occurrence mostly happens like an ambush on the health system and leaves several both economic and public health catastrophic consequences. As most of them are fatal, with no cure and diagnostic limitations, especially in low-resource settings, there should be close surveillance and monitoring programs, especially in areas with increased susceptibility to such outbreaks. These programs will be effective and sustainable when a specific budget is in place to cater to the planned activities together with political will and community engagement. Due to increased land use change, globalization dynamics, particularly global physical interconnectivity through traveling, this outbreak in Tanzania is of global health concern too. In addition to the efforts, which have been done in Tanzania as a response to the outbreak, intensive public health awareness campaigns should be deployed. Moreover, capacity building on different likely outbreaks among community health care workers and health care providers to the lowest health facilities should be implemented to keep the team prepared always. This will not only lead to more rapid response in case of new outbreaks but also enhance the effectiveness of such responses. Deployed interventions should encourage both multisectoral and intersectoral collaboration among different relevant stakeholders given the complex nature of prevention and control of outbreaks. International support from organizations like World Health Organization and the Center for Disease Control should be embraced too. Finally, routine reevaluation of the situation by the Ministry of Health is crucial to keep the implemented interventions up to date in terms of strength and relevance to the situation. Ethical approval Not applicable Sources of funding Not Applicable. Author contributions HLM and LMK conceptualized the manuscript. All authors did data curation. LMK, BLM and EAK wrote the first manuscript. HLM and ERS reviewed and edited the first draft manuscript. HLM supervised and administered the process. All authors proofread and approved the manuscript for publication. Conflict of interest disclosures 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) Not applicable. Guarantor Harold L. Mashauri.