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Marburg Virus Disease in Tanzania: The most recent outbreak

Authors:
Novonil Deb at North Bengal Medical College
Novonil Deb
Poulami Roy at North Bengal Medical College
Poulami Roy
Vikash Jaiswal at Larkin Community Hospital
Vikash Jaiswal
Aroop Mohanty at All India Institute of Medical Sciences Gorakhpur
Aroop Mohanty
  • All India Institute of Medical Sciences Gorakhpur
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Letter to the Editor
Marburg Virus Disease in Tanzania: The most recent outbreak
Dear Editor
Marburg virus (MARV) is a member of the filoviridae family causing
viral haemorrhagic fever. After conducting laboratory tests in response to
reports of cases and fatalities in the nation's north-western Kagera dis-
trict, Tanzania today verified it's first-ever cases of the Marburg Virus
Disease [1]. Following the onset of symptoms such as fever, vomiting,
bleeding, and kidney failure in eight persons, Tanzania's National Public
Health Laboratory examined samples to identify the illness's source. Of
the eight cases, five have resulted in death, one of whom was a healthcare
worker [1]. The other three are still being treated. A total of 161 contacts
have been found and are being kept under vigilance [1]. With Case Fa-
tality Rate ranging from 24.0% to 90.0%, high virulence and symptom-
atic management, community engagement has become quintessential in
containing the outbreak [2].
1. Epidemiology
The first ever case of MVD was recognised in 1967 after simultaneous
outbreaks in Marburg and Frankfurt in Germany; and in Belgrade, Serbia,
when laboratory workers in Behringwerke were working with tissue or
tissue cultures of infected Chlorocebus aethiops with inadequate PPE. The
exact location in Uganda from which the infected grivets were imported
to the laboratory still remains unexposed. Out of the 31 personnel (25
primary and six secondary infections) who manifested severe symptoms,
seven of them died [3]. Recent outbreaks in Equitorial Guinea in
February 2023 reported 11 fatalities out of 29 suspected cases [4].
(Table 1). However, new data reports spread of virus within 90 of the
center and there is an increased suspicion of chain of transmission among
undetected contacts [4].
The timeline of recent events related to the MVD outbreak has been
shown in Fig. 1.
2. Signs and symptoms
The incubation period is 2–21 days. The presenting symptoms of
MARV mimic Enteric Fever or malaria, making it a diagnostic hurdle. The
disease exacerbates as a rapid progression from non-specific symptoms to
severe symptoms like tachypnea, coma, convulsions, shock-like features
to MODS, DIC and ultimately, death. Although haemorrhagic presenta-
tion is a touchstone of MVD, it manifests in only one-third of the patients
at the peak.
3. Possible risks and precautionary measures
3 cases of laboratory accidents have been reported in Russia in the
years 1988, 1991, 1995, in which, the first two perished. Indicative of
being extremely bio-hazardous (Risk Group 4 pathogen), laboratory
testing of samples should be conducted only by trained staff, under
biosafety level 4-equivalent containment, maintaining strict standards
and protocols.
Sporadic cases have also been reported in people who gave a travel
history to a cave inhabited by Rousettus aegyptiacus bat colony in Uganda.
People visiting such caves fall under high risk of exposure, thus, they
should take proper protective practices like wearing masks, gloves, PPE
or quarantine in suspected cases. Experimental inoculation of pigs with
different Ebola viruses have shown that they are susceptible to infection
and can shed the virus (amplifier). Other animals should be considered as
potent amplifiers unless stated otherwise as a precautionary measure.
Further, pig farms should be under strict surveillance so that pigs aren't
infected by fruit bats. When there are reported cases of outbreak, animal
products (like meat, blood, etc.) should be properly cooked before
consumption.
While the exact mode of transmission from animals to humans still
remains under the microscope, human-to-human transmission is via
direct contact with blood or other bodily fluids of infected people, and
with surfaces or materials that are contaminated with the same. HCW
might contract the infection in cases of unintentional exposure. Direct
contact with an infected deceased person's body during cremation might
also cause transmission of the virus. Antibody fluorescence test showed
that the sperm of an infected male hosted infectious material. His wife
contracted the disease via sexual intercourse [5]. Safer sex for at least 12
months from the onset or symptoms, or till the semen tests negative twice
for Marburg virus has been recommended by WHO to male survivors.
Certain immune-privileged sites (like testicles, eye) have shown
Table 1
Table 1: Marburg virus cases with deaths from 1967 to 2023 AD.
Year Place Cases Deaths CFR
1967 Marburg, West Germany 31 7 23
1975 South Africa 3 1 33
1980 Kenya 2 1 50
1987 Kenya 1 1 100
1988 Koltsovo, Soviet Union 1 1 100
1990 Koltsovo, Soviet Union 1 1 100
1998–2000 Democratic Republic of Congo 154 128 83
2004–2005 Angola 374 329 88
2007 Uganda 4 1 25
2008 Uganda and Netherlands 1 1 100
2012 Uganda 18 9 50
2014 Uganda 1 1 100
2017 Uganda 3 3 100
2021 Guinea 1 1 100
2022 Ghana 4 3 75
2023 Equitorial Guinea 11 29 264
2023 Tanzania 8 5 63
Contents lists available at ScienceDirect
New Microbes and New Infections
journal homepage: www.journals.elsevier.com/new-microbes-and-new-infections
https://doi.org/10.1016/j.nmni.2023.101123
Received 25 March 2023; Accepted 27 March 2023
Article published online: 18 April 2023
2052-2975/©2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
New Microbes and New Infections 53 (2023) 101123
persistence of MARV even after recovery. Relapse cases in the absence of
re-infection, although rare, have been reported.
4. Available treatment modalities
No specific therapy is available for MARV infection. Management is
done by balancing fluids and electrolytes in case of dehydration,
administration of anticoagulants to prevent and control DIC (in early
stages), administration of procoagulants (in late stages) to control hae-
morrhaging, administration of antifungal or antiviral drugs to prevent or
treat secondary infections, pain management, etc. Several clinical trials
have been conducted on monoclonal antibodies that were developed for
Ebola virus disease under expanded access licence. In addition to this
Zabdeno and Mvabea were granted authorisations by EMA in 2020.
These vaccines are said to be effective against the filoviridae group (same
as MARV), however the clinical efficacy has still not been established.
5. Future scopes for research
1. Studies need to be conducted to confirm if the Egyptian rousettes are
actual or intermediate hosts of MARV
2. Factors like heavy rain after prolonged period of arid weather have
been shown to be associated with EVD, similar triggering factors of
MVD in the human population needs to be studied.
3. All the natural maintenance host of MARV must be identified.
6. Conclusion
Marburg virus infection has the potential to cause a global pandemic.
A global initiative must be taken to devise proper management and
vaccines for this virus. Due to absence of vaccines targeted against the
virus and specific antiviral drugs, the virus poses an imminent threat to
human life. Without proper management protocols and treatment, this
might lead to high CFR and mortality. Thorough research must be con-
ducted about pathogenesis and vaccine development in order to stop the
next global pandemic.
Funding
None.
Ethical approval
NA.
Consent
NA.
Declaration of competing interest
We hereby declare that there is no conflict of interest among all the
authors of this manuscript.
References
[1] World Health Organization. Tanzania confirms first-ever outbreak of Marburg virus
disease. World Health Organization. Retrieved March 23, 2023, from, https://www
.afro.who.int/countries/united-republic-of-tanzania/news/tanzania-confirms-fi
rst-ever-outbreak-marburg-virus-disease.
[2] World Health Organization. Marburg virus disease. World Health Organization.
Retrieved March 23, 2023, from, https://www.who.int/news-room/fact-sheets/deta
il/marburg-virus-disease.
[3] Centers for Disease Control and Prevention. Marburg haemorrhagic fever (Marburg
HF): Marburg Outbreaks 2004-2014 [online] [Accessed on: April 22, 2020] Available
at: https://www.cdc.gov/vhf/marburg/outbreaks/summaries.html.
[4] Branswell H. Marburg fever outbreak in Equatorial Guinea widens, who reports.
STAT; 2023, March 22. Retrieved March 24, 2023, from, https://www.statnews.co
m/2023/03/22/marburg-fever-outbreak-equatorial-guinea-widens/.
[5] Martini GA. Marburg agent disease: in man. Trans R Soc Trop Med Hyg 1969;63(3):
295–302.
Novonil Deb, Poulami Roy
North Bengal Medical College and Hospital, West Bengal, India
E-mail addresses: novonil1999@gmail.com (N. Deb),
poulami3613@gmail.com (P. Roy).
Vikash Jaiswal
Department of Cardiovascular Research, Larkin Community Hospital, South
Miami, Fl, USA
E-mail address: vikash29jaxy@gmail.com.
Aroop Mohanty
Department of Clinical Microbiology, AIIMS Gorakhpur, Gorakhpur,
273008, India
E-mail address: aroopmohanty7785@yahoo.com.
Fig. 1. Timeline showing the recent trends of Marburg Disease Virus outbreak in 2023.
Letter to the Editor New Microbes and New Infections 53 (2023) 101123
2
Sanjit Sah
Global Consortium for Public Health and Research, Datta Meghe Institute of
Higher Education and Research, Jawaharlal Nehru Medical College, Wardha,
442001, India
SR Sanjeevani Hospital, Kalyanpur-10, Siraha, Nepal
E-mail address: sanjitsah101@gmail.com.
Ranjit Sah
*
Tribhuvan University Teaching Hospital, Institute of Medicine, Kathmandu,
Nepal
Department of Microbiology, Dr. D.Y. Patil Medical College, Hospital and
Research Centre, Dr. D.Y. Patil Vidyapeeth, Pune, 411018, Maharashtra,
India
Department of Public Health Dentistry, Dr. D.Y. Patil Dental College and
Hospital, Dr. D.Y. Patil Vidyapeeth, Pune, 411018, Maharashtra, India
*
Corresponding author.
E-mail address: ranjitsah57@gmail.com (R. Sah).
Letter to the Editor New Microbes and New Infections 53 (2023) 101123
3
... Also, sporadic cases have been reported in people who gave a travel history, like a cave inhabited by the Rousettus aegyptiacus bat colony in Uganda. That is why the risk of exposure to MVD is very high for people who visit such caves, and more people are at risk because of a lack of awareness and inadequate safety precautions such as wearing masks, gloves, and PPE [28] . It should be noted that addressing all these issues is vital for effective combat and control of the disease. ...
... 1 Avoid contact with bodily fluids [29] Avoid contact with blood, urine, feces, saliva, sweat, vomit, breast milk, amniotic fluid, semen, and vaginal fluids of infected individuals 2 Transfer suspected cases to healthcare system [30] Any suspected case should instantly be transferred to a healthcare system for treatment and isolation instead of managing at home 3 Proceed with caution during aerosol-generating procedures [31] When doing procedures that generate aerosols, proceed with utmost caution 4 Use protective gear when handling wildlife [30] Use gloves and other suitable protective gear while handling wildlife 5 Use infection prevention and control measures [32] Health and care providers should use IPC measures, such as conventional and transmission-based precautions when caring for patients with confirmed or suspected MVD 6 Safer sexual activities for male survivors [28] Male MVD survivors must engage in safer sexual activities and maintain better personal hygiene until their semen tests Marburg virus-free twice 7 Safely dispose of infected dead bodies [31] MVD infected dead bodies should be safely disposed of ...
View
... According to grivets' reports, staff employees were primarily exposed to these sick wild animals' meat and organs, which caused them to contract MV (Mehedi et al., 2011;Languon and Quaye, 2019). Seven patients died as a result of the sickness, which affected a total of 31 patients and was caused by 25 primary and 6 secondary infections (Deb et al., 2023). ...
... On 29 November 2012, the Ugandan Ministry of Health declared MV infection in Uganda. The Ugandan districts of Kabale, Ibanda, Mbarara, and Kampala have recorded about 15 fatalities and 8 probable cases (Deb et al., 2023). This outbreak in the Ibanda district occurred concurrently with the 2007 MV disease outbreak in the Kitaka mining region. ...
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The Marburg virus (MV), identified in 1967, has caused deadly outbreaks worldwide, the mortality rate of Marburg virus disease (MVD) varies depending on the outbreak and virus strain, but the average case fatality rate is around 50%. However, case fatality rates have varied from 24% to 88% in past outbreaks depending on virus strain and case management. Designated a priority pathogen by the National Institute of Allergy and Infectious Diseases (NIAID), MV induces hemorrhagic fever, organ failure, and coagulation issues in both humans and non-human primates. This review presents an extensive exploration of MVD outbreak evolution, virus structure, and genome, as well as the sources and transmission routes of MV, including human-to-human spread and involvement of natural hosts such as the Egyptian fruit bat (Rousettus aegyptiacus) and other Chiroptera species. The disease progression involves early viral replication impacting immune cells like monocytes, macrophages, and dendritic cells, followed by damage to the spleen, liver, and secondary lymphoid organs. Subsequent spread occurs to hepatocytes, endothelial cells, fibroblasts, and epithelial cells.MV can evade host immune response by inhibiting interferon type I (IFN-1) synthesis. This comprehensive investigation aims to enhance understanding of pathophysiology, cellular tropism, and injury sites in the host, aiding insights into MVD causes. Clinical data and treatments are discussed, albeit current methods to halt MVD outbreaks remain elusive. By elucidating MV infection's history and mechanisms, this review seeks to advance MV disease treatment, drug development, and vaccine creation. The World Health Organization (WHO) considers MV a highconcern filovirus causing severe and fatal hemorrhagic fever, with a death rate ranging from 24% to 88%. The virus often spreads through contact with infected individuals, originating from animals. Visitors to bat habitats like caves or mines face higher risk. We tailored this search strategy for four databases: Scopus, Web of Science, Google Scholar, and PubMed. we primarily utilized search terms such as "Marburg virus," "Epidemiology," "Vaccine," "Outbreak," and "Transmission." To enhance comprehension of the virus and associated disease, this summary offers a comprehensive overview of MV outbreaks, pathophysiology, and management strategies. Continued research and learning hold promise for preventing and controlling future MVD outbreaks
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... Epidemiology and case fatality rate of all outbreaks related to MARV infection(Zhao et al. 2022;Deb et al. ...
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View
... 11 Similar to that, human-to-human transmission occurs when an individual comes into direct contact with another infected person's body fluid or blood, along with surfaces or objects (cloth or bedding) infected with the same. 22 The probability of Marburg virus transmission via sexual contact had been speculated when the virus was found in the sperm of a previously infected patient in 1968, who later transferred the virus to his wife. 23 In 1975, Marburg virus was found in the aqueous humor of an MVD survivor who had uveitis. ...
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The World Health Organization (WHO) defined Disease X as an upcoming disease with the potential to cause a pandemic. Pathogen X is responsible for Disease X. Marburg virus disease (MVD) is one of the diseases from the priority disease list published by WHO. Marburg virus is a filamentous, negative-sense RNA virus that belongs to the same filovirus family as the lethal Ebola virus. Since the first discovery of this virus in 1967, 17 outbreaks occurred sporadically till 2023. Rousettus aegyptiacus acts as the natural reservoir of the virus. With an average incubation period of 5 to 10 days, its first target is the mononuclear phagocytic system cells. It is highly contagious and can be easily transmitted from animal to human and human to human via direct contact with blood or body fluid, feces, and semen of the infected host. Although Marburg disease has a high case fatality rate of close to 90%, unfortunately, there is no approved vaccines or treatments are available. The most recent outbreak of Marburg virus in Equatorial Guinea and Tanzania in 2023 caused an alert for global health. However, based on the last global pandemic of COVID-19 and the sudden re-emerging of monkeypox around the world, we can assume that the Marburg virus has the potential to cause a global pandemic. Our modern world depends on globalization, which helps the virus transmission among countries. The Marburg virus can easily be transmitted to humans by fruit bats of the Pteropodidae family. This virus causes severe hemorrhagic disease, and there are no specific vaccines and treatments available to combat it. Therefore, community engagement and early supportive care for patients are keys to successfully controlling MVD.
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... Our results indicate that even at a low dose VSV-MARV elicits distinct immune responses that correlate with protection against MVD. Despite increased outbreaks of MARV reported as recently as February 2023 in Equatorial Guinea [30] and March 2023 in the United Republic of Tanzania [31], an approved vaccine to protect vulnerable populations remains unavailable. A low dose of VSV-MARV should be evaluated in clinical trials as it may be an option to deliver beneficial public health outcomes to more people in the event of future outbreaks. ...
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Infection with Marburg virus (MARV), the causative agent of Marburg virus disease (MVD), results in hemorrhagic disease and high case fatality rates (>40%) in humans. Currently, there are two outbreaks ongoing in Equatorial Guinea and Tanzania. Despite its public health relevance, there are no licensed vaccines or therapeutics to prevent or treat MVD. A vesicular stomatitis virus (VSV)-based vaccine expressing the MARV glycoprotein (VSV-MARV) is currently in clinical development. Previously, a single 10 million PFU dose of VSV-MARV administered 1-5 weeks before lethal MARV challenge conferred uniform protection in nonhuman primates (NHPs), demonstrating fast-acting potential. Additionally, our group recently demonstrated that even a low dose VSV-MARV (1000 PFU) protected NHPs when given 7 days before MARV challenge. Establishing the minimum protective vaccine dose and administration period, as well as mechanisms behind the associated protection, is essential for delivering the most beneficial public health outcomes. In this study, we longitudinally profiled the transcriptional responses of NHPs vaccinated with a low dose of VSV-MARV either 14 or 7 days before lethal MARV challenge. NHPs vaccinated 14 days before challenge presented with transcriptional changes consistent with an anti-viral response before challenge. Limited gene expression changes were observed in the group vaccinated 7 days before challenge. After challenge, genes related to lymphocyte-mediated immunity were only observed in the group vaccinated 14 days before challenge, indicating that the length of time between vaccination and challenge influenced gene expression. Our results indicate that a low dose VSV-MARV elicits distinct immune responses that correlate with protection against MVD. A low dose of VSV-MARV should be evaluated in clinical rails as it may be an option to deliver beneficial public health outcomes to more people in the event of future outbreaks.
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... It is necessary to determine all of the Marburg virus natural maintenance hosts. Designing effective tactics to combat the deadly Marburg virus requires proactive planning and intense collaboration among researchers, public health specialists, policymakers, and biologists 4,5 . ...
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Marburg fever outbreak in Equatorial Guinea widens, who reports. STAT; 2023
  • Mar 2023
  • H Branswell
Branswell H. Marburg fever outbreak in Equatorial Guinea widens, who reports. STAT; 2023, March 22. Retrieved March 24, 2023, from, https://www.statnews.co m/2023/03/22/marburg-fever-outbreak-equatorial-guinea-widens/.