What is Marburg Virus Disease?
Marburg Virus Disease (MVD), previously referred to as Marburg Hemorrhagic Fever, stands as a formidable and often fatal affliction for human beings. This viral agent triggers severe and debilitating hemorrhagic fever in its human hosts, with an average case fatality rate hovering around 50%. Notably, the case fatality rates have exhibited a wide range, fluctuating between 24% and a staggering 88%, contingent on the specific viral strain and the quality of case management. But what exactly is Marburg Virus Disease?
Survival rates significantly improve with early supportive care and symptomatic treatment, predominantly centered around rehydration. It’s crucial to note that, to date, there exists no licensed treatment with confirmed efficacy in neutralizing this virus. Nevertheless, ongoing developments in the realm of blood products, immune therapies, and pharmaceutical treatments hold promise for future breakthroughs.
The Marburg virus finds its natural refuge in Rousettus aegyptiacus, the fruit bats belonging to the Pteropodidae family. This virus makes its journey to human hosts via these fruit bats and spreads further among humans through person-to-person transmission.
The key to effectively managing outbreaks lies in active community engagement.
Marburg virus is the culprit behind Marburg Virus Disease (MVD), a malady notorious for its potential fatality rate of up to 88%. However, meticulous patient care has demonstrated the capability to significantly reduce this mortality rate. The first appearance of Marburg Virus Disease traces back to 1967 in Marburg and Frankfurt, Germany, from where it subsequently extended its reach to Belgrade and Serbia.
Marburg and Ebola viruses, both members of the Filoviridae family, exhibit striking clinical similarities despite stemming from distinct viral origins. These two diseases, although rare, possess the ominous potential to spark epidemics with alarming mortality rates.
The initial recognition of this disease transpired in 1967 during two concurrent outbreaks in Marburg and Frankfurt, Germany, and Belgrade, Serbia. These outbreaks were intricately linked to laboratory experiments involving African green monkeys (Cercopithecus aethiops) imported from Uganda. Subsequently, sporadic cases and outbreaks have been reported in regions such as Angola, the Democratic Republic of the Congo, Kenya, South Africa (in an individual with recent travel history to Zimbabwe), and Uganda. In 2008, two separate cases emerged in Uganda, both involving travelers who had ventured into caves inhabited by Rousettus bat colonies.
The onset of human MVD infection typically results from extended exposure to caves inhabited by Rousettus bat colonies. Marburg spreads through contact with the blood, secretions, organs, or other bodily fluids of infected individuals, as well as through contaminated surfaces and materials.
Healthcare workers have frequently fallen victim to infection while treating patients with suspected or confirmed MVD, often due to lapses in enforcing stringent infection control measures. Transmission can also occur through the use of contaminated injection equipment or accidental needlestick injuries, leading to more severe illness, rapid deterioration, and potentially higher mortality rates.
Funeral ceremonies involving direct contact with the deceased’s body can also contribute to Marburg transmission. Individuals remain contagious as long as the virus persists in their bloodstream.
Symptoms of Marburg Virus Disease manifest within an incubation period ranging from 2 to 21 days. The disease unfolds abruptly, featuring high fever, intense headaches, and profound weakness. Muscle aches frequently accompany these initial symptoms, which are followed by severe watery diarrhea, abdominal pain, cramps, nausea, and vomiting on the third day. Diarrhea can persist for up to a week, and patients often adopt a ghostly appearance, characterized by sunken eyes, expressionless countenances, and extreme drowsiness. During the 1967 European epidemic, a nonpruritic rash emerged in most patients 2 to 7 days after symptom onset.
Within 5 to 7 days, many patients progress to severe hemorrhagic manifestations, often presenting bleeding from multiple sites, including fresh blood in vomit and stool, nosebleeds, gum bleeding, and vaginal bleeding. Spontaneous bleeding at vascular access sites, used for administering fluids or collecting blood samples, can pose significant challenges. In the advanced stages, patients experience high fevers, with central nervous system involvement leading to confusion, irritability, and aggression. Orchitis, inflammation of one or both testicles, has occasionally surfaced in the later stages of the disease, typically around the 15-day mark.
In fatal cases, death typically occurs 8 to 9 days after symptom onset, usually preceded by severe blood loss and shock.
Diagnosis of Marburg Virus Disease requires precise methods due to its clinical resemblance to various other infectious diseases, including malaria, typhoid fever, shigellosis, meningitis, and other viral hemorrhagic fevers. Confirmatory diagnostics entail:
- Antibody capture enzyme-linked immunosorbent assay (ELISA)
- Antigen capture detection tests
- Serum neutralization test
- Reverse transcriptase polymerase chain reaction (RT-PCR) test
- Electron microscopy
- Virus isolation through cell culture.
Collecting samples from infected patients presents an extreme biohazard risk, necessitating stringent precautions during laboratory tests. All biological specimens mandate triple-packaging for both national and international shipping.
As of now, no approved vaccines or antiviral treatments specifically target MVD. However, supportive care, including rehydration through oral or intravenous fluids, and symptom-focused treatment have proven effective in enhancing survival rates. Monoclonal antibodies (mAbs) are under development, as are antiviral agents like Remdesivir and Favipiravir, which have undergone clinical trials for Ebola Virus Disease (EVD) and hold potential for application in MVD, pending further research and cautious utilization.
In May 2020, the EMA granted marketing authorization to Zabdeno (Ad26.ZEBOV) and Mvabea (MVA-BN-Filo). Mvabea incorporates a modified virus, Vaccinia Ankara Bavarian Nordic (MVA), capable of producing proteins from the Zaire Ebola virus and three other viruses from the Filoviridae group. While this vaccine holds promise for safeguarding against MVD, its efficacy remains unproven in clinical trials.
Marburg Virus in animals centers on Rousettus aegyptiacus bats, recognized as natural carriers of the Marburg virus. Curiously, fruit bats appear unharmed by this virus, leading to potential overlap in the geographic distribution of the Marburg virus with the habitat of Rousettus bats.
During the initial Marburg outbreak, African green monkeys (Cercopithecus aethiops) imported from Uganda served as a source of infection for humans.
Experimental research involving different Ebola viruses has identified pigs as susceptible to filovirus infection, with the potential for viral shedding. Consequently, pigs should be regarded as potential amplifying hosts during MVD outbreaks. Although no other domestic animals have been definitively linked to filovirus outbreaks, precautionary measures should consider them as potential amplifier hosts until proven otherwise.
Effective prevention and control strategies for MVD hinge on a multi-faceted approach, encompassing case management, surveillance, contact tracing, robust laboratory services, dignified and secure burial practices, and community mobilization. Active community involvement remains pivotal in successfully curtailing outbreaks. Raising awareness of Marburg infection risk factors and educating individuals about protective measures represents a potent strategy for reducing human transmission.
Risk reduction measures should emphasize:
- The necessity of wearing gloves and appropriate protective attire, including masks, when engaging in activities involving prolonged exposure to caves inhabited by fruit bat colonies, whether for work, research, or tourism. During outbreaks, all animal products (blood and meat) should undergo thorough cooking before consumption.
- Avoiding direct or close contact with infected patients, particularly their bodily fluids, to mitigate human-to-human transmission within the community. Proper personal protective equipment, including gloves, should be worn when caring for sick individuals at home. Frequent handwashing should follow visits to sick relatives in the hospital or caring for them at home.
- Ensuring comprehensive public awareness regarding the disease’s nature and essential epidemic control measures in affected communities.
- Implementing rigorous epidemic containment measures, such as timely, safe, and dignified burials, contact tracing for individuals exposed to infected persons, isolation of the sick from the healthy to prevent further transmission, and provision of care for confirmed cases. Patients themselves should uphold good hygiene practices and maintain a clean environment.
- Reducing the risk of potential sexual transmission: Following further research analysis, WHO recommends that male survivors of Marburg virus disease practice safer sex and hygiene until they test negative for Marburg virus twice, with a 12-month period starting from symptom onset. This entails avoiding contact with bodily fluids and practicing thorough handwashing with soap and water. WHO does not advocate for the isolation of convalescent patients, both male and female, who test negative for Marburg virus.
- Infection Control in Healthcare: Healthcare professionals should consistently adhere to standard precautions when treating patients, regardless of the presumed diagnosis. This includes fundamental practices like hand hygiene, respiratory hygiene, utilization of personal protective equipment (to prevent contact with infected materials), safe injection techniques, and dignified burial practices. Healthcare workers handling suspected or confirmed MVD cases should employ extra infection control measures to minimize contact with the patient’s blood, bodily fluids, contaminated surfaces, clothing, and bedding. Close contact (within 1 meter) with MVD patients warrants the use of a face shield or medical mask and goggles, along with a non-sterile long-sleeved gown and sterile gloves.
- Laboratory workers engaged in Marburg infection investigations must undergo specialized training and operate within suitably equipped facilities.
The Marburg virus is known to persist in specific immune-privileged areas within individuals who have recuperated from the disease. These areas include the testicles and the interior of the eye.
In pregnant women infected during pregnancy, the virus lingers in the placenta, amniotic fluid, and the developing fetus.
In cases where infection occurs during breastfeeding, the virus may persist in breast milk.
While rare, symptomatic relapse, occurring without re-infection, has been documented in individuals recovering from MVD. The underlying mechanisms driving this phenomenon remain incompletely understood.
Notably, transmission of the Marburg virus through infected semen has been observed for up to seven weeks following clinical recovery. To address this, ongoing surveillance and research efforts are imperative. In light of current evidence, WHO recommends:
- Male survivors of Marburg virus disease should enroll in semen testing programs upon discharge, accompanied by counseling. Semen testing can commence when individuals are mentally and physically prepared within three months from the onset of illness. Testing should continue until two consecutive negative test results are achieved.
- All Marburg survivors and their sexual partners should receive counseling to ensure the practice of safer sexual behaviors until their semen returns two consecutive negative tests for Marburg virus.
- Survivors should be provided with condoms.
- Survivors and their sexual partners should:
- Abstain from all sexual activities or adhere to safer sexual practices, employing correct and consistent condom use, until their semen tests negative for Marburg virus twice.
- Exercise good hand and personal hygiene by promptly and thoroughly washing with soap and water after any physical contact with semen, including post-masturbation hygiene. Proper disposal of used condoms during this period is crucial to avoid contact with seminal fluids.
This comprehensive overview illuminates the intricate web of challenges surrounding Marburg Virus Disease, from its clinical manifestations to its transmission dynamics and prevention strategies.