Marburg virus disease (MVD), previously called Marburg haemorrhagic fever, is a serious and often lethal illness that affects humans. The virus results in a severe viral haemorrhagic fever. The average fatality rate for MVD cases is about 50%. In previous outbreaks, case fatality rates have ranged from 24% to 88%, depending on the virus strain and how cases are managed.
Although there is currently no licensed treatment that has been proven to neutralize the virus, early supportive care involving rehydration and symptomatic treatment can enhance survival. A variety of blood products, immune therapies, and drug therapies are currently being developed.
Fruit bats of the Pteropodidae family, particularly Rousettus aegyptiacus, are considered the natural hosts of the Marburg virus. The virus is transmitted to humans from fruit bats and spreads among humans via human-to-human transmission.
Successful control of outbreaks relies on community engagement.
Marburg virus is the infectious agent responsible for Marburg virus disease (MVD), which has a case fatality ratio that can be as high as 88%, but can be reduced with good patient care. MVD was first identified in 1967 following simultaneous outbreaks in Marburg and Frankfurt in Germany, as well as in Belgrade, Serbia.
Marburg and Ebola viruses are both members of the Filoviridae family (filovirus) and have similar clinical presentations, despite being caused by different viruses. These diseases are rare and have the potential to trigger outbreaks with high fatality rates.
The initial identification of MVD was the result of two large outbreaks that occurred simultaneously in Marburg and Frankfurt in Germany, and in Belgrade, Serbia, in 1967. These outbreaks were linked to laboratory work involving African green monkeys (Cercopithecus aethiops) imported from Uganda. Since then, MVD outbreaks and sporadic cases have been reported in Angola, the Democratic Republic of the Congo, Kenya, South Africa (in a person with recent travel history to Zimbabwe), and Uganda. In 2008, two independent cases were reported in individuals who had visited a cave inhabited by Rousettus bat colonies in Uganda.
The initial human infection with MVD typically occurs after prolonged exposure to mines or caves inhabited by Rousettus bat colonies.
Marburg virus can spread from person to person via direct contact with infected individuals' blood, bodily fluids, organs, or other tissues, as well as contaminated surfaces and materials like bedding or clothing.
Healthcare workers are at risk of contracting MVD while caring for patients with suspected or confirmed infections, particularly when infection control measures are not rigorously enforced. Transmission through contaminated injection equipment or needle-stick injuries can lead to more severe disease, rapid deterioration, and potentially a higher fatality rate.
Marburg can also be transmitted through traditional burial ceremonies that involve direct contact with the body of the deceased.
Individuals remain contagious as long as their blood contains the virus.
Symptoms of Marburg virus disease:
The incubation period for Marburg virus, or the time between infection and symptom onset, can range from 2 to 21 days.
Marburg virus typically causes an abrupt onset of symptoms, including high fever, severe headache, and extreme fatigue. Muscle aches and pains are also common. On the third day of illness, patients may experience severe watery diarrhea, abdominal pain, cramping, nausea, and vomiting that can last up to a week. Patients may appear "ghost-like" during this phase, with sunken eyes, expressionless faces, and extreme lethargy. In the 1967 outbreak in Europe, a non-itchy rash was observed in most patients between 2 and 7 days after the onset of symptoms.
Between days 5 and 7, many patients develop severe bleeding and hemorrhagic manifestations, which are often fatal. Fresh blood in vomit and stool may be accompanied by bleeding from the gums, nose, and vagina. Spontaneous bleeding from intravenous access sites can also occur. Patients experience sustained high fevers during this phase, and involvement of the central nervous system can lead to confusion, irritability, and aggression. In some cases, inflammation of one or both testicles (orchitis) may occur during the late phase of the disease (around day 15).
In fatal cases, death typically occurs between days 8 and 9 after the onset of symptoms, often preceded by severe blood loss and shock.
MVD can be challenging to differentiate clinically from other infectious diseases, such as malaria, typhoid fever, shigellosis, meningitis, and other viral haemorrhagic fevers. To confirm that symptoms are caused by Marburg virus infection, the following diagnostic methods are employed:
Antibody-capture enzyme-linked immunosorbent assay (ELISA)
Antigen-capture detection tests
Serum neutralization test
Reverse transcriptase polymerase chain reaction (RT-PCR) assay
Virus isolation by cell culture
Since samples collected from patients pose an extreme biohazard risk, laboratory testing on non-inactivated samples should be conducted under maximum biological containment conditions. When transporting biological specimens nationally and internationally, the triple packaging system should be used.
Treatment and vaccines:
At present, no vaccines or antiviral medications have been approved specifically for the treatment of MVD. Nevertheless, supportive care including hydration with oral or intravenous fluids and management of individual symptoms has been shown to improve survival rates.
Although there are no approved treatments for MVD, monoclonal antibodies (mAbs) and antivirals such as Remdesivir and Favipiravir have been evaluated in clinical studies for the treatment of Ebola Virus Disease (EVD), and may be applicable to MVD, either through compassionate use or expanded access programs.
In May 2020, the European Medicines Agency (EMA) granted marketing authorization for two drugs, Zabdeno (Ad26.ZEBOV) and Mvabea (MVA-BN-Filo), for the treatment of EVD. Mvabea contains a modified virus, Vaccinia Ankara Bavarian Nordic (MVA), which produces four proteins from Zaire ebolavirus and three other viruses from the same family (filoviridae). While this vaccine could potentially offer protection against MVD, clinical trials have not yet confirmed its efficacy.
Marburg virus in animals:
Animals, especially bats, are considered natural hosts for Marburg virus. Rousettus aegyptiacus bats do not develop any apparent disease from the virus, which means the virus may have a similar geographic distribution to the bats.
During the first Marburg outbreak, African green monkeys (Cercopithecus aethiops) imported from Uganda were the source of infection for humans.
Research shows that pigs are susceptible to filovirus infection and can shed the virus, potentially making them amplifier hosts during MVD outbreaks. Although no other domestic animals have yet been confirmed as having an association with filovirus outbreaks, it is important to consider them as potential amplifier hosts as a precautionary measure.
To prevent pigs from becoming infected with Marburg virus through contact with fruit bats, precautionary measures are needed in pig farms in Africa. This is crucial in avoiding potential amplification of the virus, which could lead to MVD outbreaks.
Prevention and control:
To prevent and control Marburg virus disease (MVD) outbreaks, a comprehensive approach involving various interventions is required. Effective outbreak control requires case management, surveillance, contact tracing, laboratory services, safe and dignified burials, and social mobilization. Community engagement is crucial for successfully controlling outbreaks by raising awareness of risk factors for Marburg infection and protective measures that individuals can take to reduce human transmission.
Risk reduction messaging should focus on the following factors:
Reducing the risk of bat-to-human transmission from mines or caves inhabited by fruit bat colonies. People should wear gloves and other appropriate protective clothing, including masks, when working or visiting these places. All animal products, such as blood and meat, should be thoroughly cooked before consumption during outbreaks.
Reducing the risk of human-to-human transmission in the community through direct or close contact with infected patients, particularly with their body fluids. Close physical contact with Marburg patients should be avoided, and appropriate personal protective equipment, including gloves, should be worn when taking care of ill patients at home. Regular hand washing should be performed after visiting sick relatives in hospital and after taking care of ill patients at home.
Communities affected by Marburg should ensure that the population is well informed about the nature of the disease itself and necessary outbreak containment measures.
Outbreak containment measures include prompt, safe, and dignified burial of the deceased, identifying people who may have been in contact with someone infected with Marburg and monitoring their health for 21 days, separating the healthy from the sick to prevent further spread, providing care to confirmed patients, and maintaining good hygiene and a clean environment.
To reduce the risk of possible sexual transmission, male survivors of MVD should practice safer sex and hygiene for 12 months from the onset of symptoms or until their semen tests negative for Marburg virus twice. Contact with body fluids should be avoided, and washing with soap and water is recommended. WHO does not recommend the isolation of male or female convalescent patients whose blood has been tested negative for Marburg virus.
Marburg viral persistence in in people recovering from Marburg virus disease:
Marburg virus can persist in immune-privileged sites such as the testicles and inside the eye in some individuals who have recovered from Marburg virus disease. In women infected during pregnancy, the virus can remain in the placenta, amniotic fluid, and fetus. In breastfeeding women, the virus can persist in breast milk. Although relapse-symptomatic illness in the absence of re-infection is rare, it has been reported and is not yet fully understood.
Transmission of Marburg virus through infected semen has been documented up to seven weeks after clinical recovery. More research is needed to understand the risks of sexual transmission and the prevalence of viable and transmissible virus in semen over time. In the meantime, WHO recommends the following:
Male survivors of Marburg virus disease should be enrolled in semen testing programs when discharged and offered semen testing when mentally and physically ready, within three months of disease onset. Semen testing should be offered upon the attainment of two consecutive negative test results.
All Marburg survivors and their sexual partners should receive counseling to ensure safer sexual practices until their semen has twice tested negative for Marburg virus. Survivors should be provided with condoms.
Marburg survivors and their sexual partners should either abstain from all sexual practices or practice safer sex through correct and consistent condom use until their semen has twice tested negative for Marburg virus.
Survivors of Marburg virus disease should practice safer sexual practices and hygiene for 12 months from the onset of symptoms or until their semen twice tests negative for Marburg virus.
Until their semen has twice tested negative for Marburg, survivors should practice good hand and personal hygiene by immediately and thoroughly washing with soap and water after any physical contact with semen, including after masturbation. Used condoms should be handled and disposed of safely to prevent contact with seminal fluids.
All survivors, their partners, and families should be treated with respect, dignity, and compassion.
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