Marburg virus is a hemorrhagic fever virus of the Filoviridae family of viruses and a member of the species Marburg marburgvirus, genus Marburgvirus.
It causes Marburg Virus Disease (MVD) in primates, a form of viral hemorrhagic fever. The virus is considered to be extremely dangerous.
Marburg virus was first recognized in 1967, when outbreaks of hemorrhagic fever occurred simultaneously in laboratories in Marburg and Frankfurt, Germany and in Belgrade, Yugoslavia (now Serbia).
This disease was named Marburg virus disease (MVD) after the West German town of Marburg ander Lahn, where most human infections and deaths had been recorded.
How do humans get Marburg virus?
Specifically, details of the initial transmission of MVD to humans remain incompletely understood. Transmission most likely occurs from Egyptian fruit bats or another natural host, such as non-human primates or through the consumption of bushmeat, but the specific routes and body fluids involved are unknown.
However, Human-to-human transmission of MVD occurs through direct contact with infected bodily fluids such as blood. The virus spreads through contact with blood or other body fluids such as urine, saliva, sweat, feces, vomit, breast milk, amniotic fluid, and semen; resulting from broken skin or mucous membranes in the eyes, nose, or mouth of a person who is suffering from or has died from Marburg Virus disease.
Marburg, similar to Ebola virus, causes severe hemorrhagic disease in humans with high fatality rates The infection spreads to the liver, spleen and later other organs via blood and lymph flow.
Marburgviruses are highly infectious, but not very contagious. They do not get transmitted by aerosol during natural MVD outbreaks.
Historically, the people at highest risk include family members and hospital staff who care for patients infected with Marburg virus and have not used proper infection prevention and control measures.
Transmission events are relatively rare – there have been only 11 recorded outbreaks of MARV between 1975 and 2011, with one event involving both MARV and RAVV
Causes: MVD is caused by two viruses; Marburg virus (MARV) and Ravn virus (RAVV), family Filoviridae. Marburgviruses are endemic in arid woodlands of equatorial Africa.
Most marburgvirus infections were repeatedly associated with people visiting natural caves or working in mines. Another risk factor is contact with nonhuman primates, although only one outbreak of MVD (in 1967) was due to contact with infected monkeys
In 2009, the successful isolation of infectious MARV and RAVV was reported from healthy Egyptian fruit bat caught in caves. This isolation strongly suggests that Old World fruit bats are involved in the natural maintenance of Marburg viruses and that visiting bat-infested caves is a risk factor for acquiring Marburg virus infections.
Further studies are necessary to establish whether Egyptian rousettes are the actual hosts of MARV and RAVV or whether they get infected via contact with another animal and therefore serve only as intermediate hosts.
DIAGNOSIS: MVD is clinically similar to Ebola virus disease (EVD), and can also easily be confused with many other diseases prevalent in Equatorial Africa, such as other viral hemorrhagic fevers, falciparum malaria, typhoid fever, shigellosis, rickettsial diseases such as typhus, cholera, gram-negative sepsis, borreliosis such as relapsing fever or EHEC enteritis.
Other infectious diseases that ought to be included in the differential diagnosis include leptospirosis, scrub typhus, plague, Q fever, candidiasis, histoplasmosis, trypanosomiasis, visceral leishmaniasis, hemorrhagic smallpox, measles, and fulminant viral hepatitis.
Non-infectious diseases that can be confused with MVD are acute promyelocytic leukemia, hemolytic uremic syndrome, snake envenomation, clotting factor deficiencies/platelet disorders, thrombotic thrombocytopenic purpura, hereditary hemorrhagic telangiectasia, Kawasaki disease, and even warfarin intoxication.
The most important indicator that may lead to the suspicion of MVD at clinical examination is the medical history of the patient, in particular the travel and occupational history (which countries and caves were visited?) and the patient’s exposure to wildlife (exposure to bats or bat excrements?).
MVD can be confirmed by isolation of marburgviruses from or by detection of marburgvirus antigen or genomic or subgenomic RNAs in patient blood or serum samples during the acute phase of MVD.
Marburgvirus isolation is usually performed by inoculation of grivet kidney epithelial Vero E6 or MA-104 cell cultures or by inoculation of human adrenal carcinoma SW-13 cells, all of which react to infection with characteristic cytopathic effects. Filovirions can easily be visualized and identified in cell culture by electron microscopy due to their unique filamentous shapes, but electron microscopy cannot differentiate the various filoviruses alone despite some overall length differences.
Immunofluorescence assays are used to confirm marburgvirus presence in cell cultures.
During an outbreak, virus isolation and electron microscopy are most often not feasible options. The most common diagnostic methods are therefore RT-PCRin conjunction with antigen-capture ELISA, which can be performed in field or mobile hospitals and laboratories. Indirect immunofluorescence assays (IFAs) are not used for diagnosis of MVD in the field anymore.
Treatment: There are no specific treatments or a vaccine for the virus. Currently, there is no Food and Drug Administration-approved vaccines for the prevention of MVD. Though many candidate vaccines have been developed and tested in various animal model, the most promising ones are DNA vaccines or based on Venezuelan equine encephalitis virus replicons,vesicular stomatitis Indiana virus (VSIV) or filovirus-like particles (VLPs) as all of these candidates could protect nonhuman primates from marburgvirus-induced disease. DNA vaccines have entered clinical trials.
However, a range of blood products, drug and immune therapies are being developed, the World Health Organization says Doctors may be able to alleviate the symptoms by utilizing supportive hospital therapy, which includes balancing the patient’s fluids and electrolytes, maintaining oxygen status and blood pressure, replacing lost blood and clotting factors and treating any complicating infections.
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Prevention: Due to the absence of an approved vaccine, prevention of MVD therefore relies predominantly on quarantine of confirmed or high probability cases, proper personal protective equipment, and sterilization and disinfection.
- Avoid contact with blood and body fluids (such as urine, feces, saliva, sweat, vomit, breast milk, amniotic fluid, semen, and vaginal fluids) of people who are sick.
- Avoid contact with semen from a person who has recovered from Marburg, until testing shows that the virus is gone from their semen.
Endemic zones: The natural maintenance hosts of marburgviruses remain to be identified unequivocally. However, the isolation of both MARV and RAVV from bats and the association of several MVD outbreaks with bat-infested mines or caves strongly suggests that bats are involved in Marburg virus transmission to humans. Avoidance of contact with bats and abstaining from visits to caves is highly recommended, but may not be possible for those working in mines or people dependent on bats as a food source.
Travelers such as tourist who visit areas where bats are common should wear protective clothing that prevents direct contact with objects in and outside the caves. The frequent use of sanitizers may also be helpful.
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During outbreaks: Since marburgviruses are not spread via aerosol, the most straightforward prevention method during MVD outbreaks is to avoid direct (skin-to-skin) contact with patients, their excretions and body fluids, and any possibly contaminated materials and utensils. Patients should be isolated, but still are safe to be visited by family members. Medical staff should be trained in and apply strict barrier nursing techniques (disposable face mask, gloves, goggles, and a gown at all times). Traditional burial rituals, especially those requiring embalming of bodies, should be discouraged or modified, ideally with the help of local traditional healers.
In the laboratory: Marburgviruses are World Health Organization Risk Group 4 Pathogens, requiring Biosafety Level 4-equivalent containment, laboratory researchers have to be properly trained in BSL-4 practices and wear proper personal protective equipment.
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