Infectious Diseases, Viruses

Marburg Virus: All About Ebola’s Deadly Cousin

Author Chandana Balasubramanian , 10-Feb-2023

Marburg virus disease (MVD), or Marburg hemorrhagic fever (MHF), is a deadly infection caused by the Marburg virus (MARV). MVD belongs to the genus Marburgvirus of the filoviridae family. This family of pathogens also includes Ebola, a virus that causes an even more lethal type of hemorrhagic fever[1].

 

MARV can be transmitted to humans through fruit bats [2,3]. Since the virus is highly contagious, it easily spreads from person to person in a variety of different ways. This is one of the reasons that healthcare professionals who work with MVD patients are especially susceptible to contracting the disease. [4]. 

 

Tracking Marburg outbreaks is essential because the morbidity rate is as high as 50%, and this particular viral infection has one of the highest case-fatality rates among all hemorrhagic fevers. In some instances, the fatality rate has reached 90% [1]. The World Health Organization (WHO) categorizes MARV as a Risk Group 4 pathogen. The Centers for Disease Control and Prevention (CDC) identifies MARV as a Category A agent of bioterrorism [2,5]

 

Because MARV is highly transmissible, and has a high fatality rate, it can cause widespread panic. These factors, among others, necessitate an immediate and effective response by public health officials who need to utilize resources to tackle outbreaks and save lives. Due to continuing globalization and urbanization, even small outbreaks of infectious diseases like MVD need close surveillance to prevent a worldwide pandemic.  

History

 

Marburg virus disease was first described in Marburg, Germany during an outbreak in 1967 that affected both Germany and Serbia (which was part of Yugoslavia at the time) [6]. The first known victims of this disease included lab workers and healthcare professionals who treated the lab workers. 

MARV was discovered by Rudolf Siegert, a German physician, and his colleagues at the Institute of Virology at the University of Marburg. The virus was first isolated through the use of cell cultures gathered from infected guinea pigs. Interestingly, the Marburg virus was the first filovirus ever detected [7]. 

In 2005, the virus was given a new name: Lake Victoria Marburgvirus. However, the original name of the virus was reinstated in 2010 to honor the discoverers of this deadly virus and maintain consistency in the nomenclature used in scientific literature and press releases [7].

Epidemiology

 

Most outbreaks of Marburg virus have occurred in Sub-Saharan Africa. Sporadic cases have also been reported in various parts of Europe and the United States. In 2008, for example, cases that occurred in the US and Netherlands were traced to people who had visited Sub-Saharan Africa. [8]. 

Healthcare workers treating victims of MARV and the family members of these victims are especially susceptible to contracting the virus. People working at diagnostic centers, veterinarians, and those working at quarantine facilities are also at increased risk. People who venture into caves or mines inhabited by fruit bats have an increased risk of contracting MARV, as do those who travel to countries where the disease is endemic [9].

The first MARV outbreak (discussed above) occurred when laboratory workers who were experimenting on African green monkeys that were imported from Uganda were infected from the animals they were working with [8]. During this initial outbreak,  31 people were diagnosed, and seven died. This led to a case-fatality rate of approximately 23%.

In 1975, three cases were reported in Johannesburg, South Africa. The first person admitted to a hospital with MVD was a man with a recent travel history to Zimbabwe. The man’s traveling companion and a nurse who cared for him at the hospital also contracted the infection. The man passed away, while the two women survived.

In 1980, Kenya reported two cases of MVD. The first patient had visited a cave in Kenya’s Mount Elgon National Park and was admitted to a hospital in Nairobi under specialized care. The patient died after developing severe complications. The doctor who attended to the patient developed symptoms nine days later. Fortunately, the physician recovered.  

In 1987, Kenya reported a single MVD case that turned out to be fatal. It was a 15-year-old Danish teenager who presented with a recent history of headache, malaise, fever, and vomiting. Just like the cases from 1980, the teenager had visited a cave in Mount Elgon National Park. Despite all the care provided by the teenager’s healthcare team, he died on the 11th day of his illness. Three years later, in 1990, one case was reported in Russia. This case also resulted in a fatal outcome. It was the first MVD case ever reported in Russia [8].

The first massive MVD outbreak occurred between 1998 and 2000 in Durba, a village in the Haut-Uele Province of the Democratic Republic of Congo (DRC). Young men who worked at a gold mine near the town were the main victims. This outbreak resulted in 154 cases and 128 deaths (83% case-fatality rate) [2,8]. 

The second major MVD outbreak occurred between 2004 and 2005 in Angola. It began in Uige Province and became one of the deadliest MVD outbreaks the world has ever seen. Around 252 cases and 227 deaths were reported during this period. The case-fatality rate was almost 90%, one of the highest among all  viral hemorrhagic fevers outbreaks in history.

Between 2007 and 2017, there were sporadic cases reported in Uganda. During the 2007 outbreak, four young men who worked at a lead and gold mine in Kamwenge District became ill. One patient died, but the remaining three survived.

In 2008, one person was diagnosed with MVD in the United States after visiting a cave in the Maramagambo Forest in Uganda. He developed an illness four days after returning to the US. He was treated at a hospital and recovered. A similar case occurred in the Netherlands in the same year from a 40-year-old Dutch woman who visited the same Ugandan cave mentioned above. The woman died on the tenth day of her illness.

In 2012, another significant outbreak occurred in Kabale, Ibanda, Mbarara, and Kampala in Uganda, with 15 cases and four fatalities. In 2014, one more case was reported in the Kampala district of Uganda, which turned out to be fatal. The last outbreak in this country occurred in 2017 in the Kween district in the eastern part of the country. Four cases were reported, and three turned out to be fatal.

In 2021, the Ministry of Health of the Republic of Guinea reported a case of MVD. The outcome was fatal. In this instance, MVD was not confirmed until after the patient died. Subsequently, contact tracing was performed by healthcare officials, and around 170 high-risk contacts were identified and monitored for three weeks. They all tested negative, and no more cases were reported in the country [8].

The most recent Marburg outbreak occurred on July 7, 2022 in the southern Ashanti region of Ghana. Two suspected cases were definitively identified on July 15, 2022. Two more suspected cases were reported on July 25, 2022. One turned out to be positive for MVD. As of January 2023, there were three reported MVD cases, out of which two died. Comprehensive contact tracing was carried out in different parts of the country [8, 10].

How is it spread?

 

MVD is a contagious, life-threatening illness that can spread from one person to another. The Marburg virus can spread through the following ways: 

  • Prolonged exposure to fruit bats in mines or caves.
  • Direct contact with the bodily fluids of an infected person, including blood, urine, saliva, sweat, semen, feces, vomit, breast milk, and amniotic fluid. 
  • Direct contact with the body of a deceased person infected with the Marburg virus.
  • Indirect contact with materials or surfaces contaminated with the bodily fluids of an infected person. 
  • Handling infected patients without following proper infection control protocols [3].
  • Sexual intercourse with men who recently recovered from MVD. The virus can remain in the semen of the person even after the person has recovered [11]. 
  • Needles contaminated with the virus. This results in severe illness, rapid deterioration, and higher case mortality [3]. 
  • Close contact with non-human primates, including monkeys and apes, may increase the risk of contracting the virus [9].

Biology of the disease

 

The Marburg virus is a retrovirus (a virus made up of RNA instead of DNA). It is composed of a single strand of RNA enclosed in a lipid envelope. 

Once the virus enters the bloodstream or lymphatic system, it replicates within the monocytes, macrophages, and dendritic cells (the first line of defense in the body). The growing viral load eventually spreads and infects hepatocytes (liver cells), endothelial cells, epithelial cells (in the blood vessels, skin, and other organs), and fibroblasts (skin). 

The liver, spleen, and secondary lymphoid organs are the sites where most viral replication occurs. Uncontrolled viral replication at these sites can severely weaken the immune system and result in multiple organ failure [4].

Symptoms

 

According to the CDC, it takes two to 21 days following initial exposure for symptoms of Marburg hemorrhagic fever to appear. They begin suddenly with the following symptoms:

  • High fever
  • Headache
  • Severe malaise
  • Muscle pains

 

On the third day, the following symptoms appear:

  • Diarrhea – which can persist for about a week
  • Cramping
  • Abdominal pain
  • Nausea
  • Vomiting
  • Dull countenance
  • Tiredness [3]

 

In severe cases, infected individuals may exhibit some of these complications:

  • Jaundice
  • Pancreatic inflammation
  • Severe weight loss
  • Confusion, anxiety, incoherent speech, and hallucinations
  • Shock
  • Liver failure
  • Massive hemorrhage
  • Multi-organ failure [12]

 

Deaths often occur within 8 to 9 days following the onset of illness, primarily due to severe blood loss and shock [3].

Diagnosis

 

It is challenging to distinguish MVD from other infectious diseases, especially malaria, lassa, meningitis, typhoid, shigellosis (an intestinal bacterial infection), and other viral hemorrhagic fevers (including Ebola). The reason for the difficulty is that all of these illnesses show similar clinical signs to MVD. 

Laboratory testing of samples collected from infected individuals should be conducted under extreme safety conditions as the virus poses a major biohazard risk to lab workers. The following diagnostic methods are commonly used to detect the presence of the Marburg virus:

  • Antigen-capture detection tests such as enzyme-linked immunosorbent assay (ELISA).
  • Serological test – serum virus neutralization (SVN).
  • Reverse transcriptase – polymerase chain reaction (RT-PCR).
  • Viral culture.
  • Electron microscopy [3,13].

Treatment

 

Currently, there are no vaccines or approved antiviral medications for MVD. Infected individuals receive supportive care to improve survival and ease the pain and discomfort caused by symptoms. Supportive case includes the following:

  • Keeping the patient hydrated through oral or intravenous fluids.
  • Providing a completely balanced diet.
  • Maintaining optimal electrolytes, oxygen, and blood pressure levels. 
  • Using antiviral drugs such as remdesivir and favipiravir [3].  

 

Many potential MARV vaccines, including VSV-MARV and MVA-BN-Filo, are under clinical investigation. VSV-MARV protected hosts from MVD in animal models, and MVA-BN-Filo, a combination of Marburg and Ebola virus antigens, is reported to have the potential to protect against both infections. 

Attempts to develop several post-exposure therapies to cure MVD are also underway. These include MARV-specific monoclonal antibodies (mAbs) and small-molecule antivirals [1].

Prevention

 

The following preventive measures can help control the spread of MVD, at least to a certain degree:

  • Avoid close contact with people who are infected or suspected to be infected. It is especially important to stay clear of their body fluids.
  • Wash hands regularly after visiting infected people at the hospital or while handling sick people at home.
  • Wear gloves, masks, and other protective equipment while working in mines or caves. This can help reduce bat-to-human transmission of the virus, as fruit bats often inhabit these areas.
  • Healthcare workers must wear personal protective equipment and isolate their infected patients. All needles, medical equipment, and patient excretions should be sterilized and disposed of properly.
  • Wash and cook meat entirely before eating, especially during outbreaks.
  • People should be educated on the signs and symptoms of the disease, and containment is necessary during an outbreak. This includes the safe burial of the deceased, contact tracing, staying away from infected people, and maintaining a clean and hygienic environment.
  • Men, especially those who survived MVD, should follow safe sex practices for about one year following the onset of symptoms or until their semen tests negative for the Marburg virus twice.  
  • Samples collected for investigation should be handled by trained laboratory personnel since the pathogen is considered to be a major biohazard [3].

 

Marburg and Ebola are the most well-known filoviruses. This group of viruses is known to cause severe illnesses that have high fatality rates. They are dangerous pathogens with no vaccine, cure, or treatment available. Outbreak monitoring and rigorous epidemiological research can help combat these deadly diseases.

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References

[1] F. Zhao, Y. He, and H. Lu, “Marburg virus disease: A deadly rare virus is coming,” Biosci. Trends, vol. 16, no. 4, pp. 312–316, 2022.

[2] K. Shifflett and A. Marzi, “Marburg virus pathogenesis – differences and similarities in humans and animal models,” Virol. J., vol. 16, no. 1, p. 165, 2019.

[3] WHO, “Marburg Virus Disease,” World Health Organization, 2013. [Online]. Available: https://www.who.int/news-room/fact-sheets/detail/marburg-virus-disease 

[4] M. G. Kortepeter, K. Dierberg, E. S. Shenoy, T. J. Cieslak, and 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., vol. 99, pp. 233–242, 2020.

[5] CDC, “Bioterrorism Agents/Diseases,” Centers for Disease Control and Prevention, 15-May-2019. [Online]. Available: https://emergency.cdc.gov/agent/agentlist-category.asp 

[6] B. Beer, R. Kurth, and A. Bukreyev, “Characteristics of filoviridae: Marburg and Ebola viruses,” Sci. Nat., vol. 86, no. 1, pp. 8–17, 1999.

[7] A. A. Bukreyev et al., “Discussions and decisions of the 2012–2014 International Committee on taxonomy of Viruses (ICTV) Filoviridae Study Group, January 2012–June 2013,” Arch. Virol., vol. 159, no. 4, pp. 821–830, 2014.

[8] CDC, “History of Marburg virus disease (MVD) outbreaks,” Centers for Disease Control and Prevention, 05-Aug-2022. [Online]. Available: https://www.cdc.gov/vhf/marburg/outbreaks/chronology.html 

[9] CDC, “Marburg Virus Disease (MVD) – Risk of exposure,” Centers for Disease Control and Prevention, 13-Aug-2021. [Online]. Available: https://www.cdc.gov/vhf/marburg/exposure/index.html 

[10] R. W. Cross et al., “An introduction to the Marburg virus vaccine consortium, MARVAC,” PLoS Pathog., vol. 18, no. 10, p. e1010805, 2022.

[11] CDC, “Marburg Virus Disease (MVD) – Transmission,” Centers for Disease Control and Prevention, 13-Aug-2021. [Online]. Available: https://www.cdc.gov/vhf/marburg/transmission/index.html 

[12] CDC, “Marburg Virus Disease (MVD) – Signs and symptoms,” Centers for Disease Control and Prevention, 13-Aug-2021. [Online]. Available: https://www.cdc.gov/vhf/marburg/symptoms/index.html 

[13] CDC, “Marburg Virus Disease (MVD)- Diagnosis,” Centers for Disease Control and Prevention, 13-Aug-2021. [Online]. Available: https://www.cdc.gov/vhf/marburg/diagnosis/index.html 

Author
Chandana Balasubramanian

Chandana Balasubramanian is an experienced healthcare executive who writes on the intersection of healthcare and technology. She is the President of Global Insight Advisory Network, and has a Masters degree in Biomedical Engineering from the University of Wisconsin-Madison, USA.

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