Marburg Hemorrhagic Fever

What is Marburg hemorrhagic fever?
Marburg hemorrhagic fever is a rare, severe type of hemorrhagic fever which affects both humans and non-human primates. Caused by a genetically unique zoonotic (that is, animal-borne) RNA virus of the filovirus family, its recognition led to the creation of this virus family. The four species of Ebola virus are the only other known members of the filovirus family.

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). A total of 37 people became ill; they included laboratory workers as well as several medical personnel and family members who had cared for them. The first people infected had been exposed to African green monkeys or their tissues. In Marburg, the monkeys had been imported for research and to prepare polio vaccine.

Image: Negative stain image of an isolate of Marburg virus, showing filamentous particles as well as the characteristic "Shepherd's Crook".  Magnification approximately 100,000 times.  Image courtesy of Russell Regnery, Ph.D., DVRD, NCID, CDC..  Go to high-resolution version.

Where do cases of Marburg hemorrhagic fever occur?
Recorded cases of the disease are rare, and have appeared in only a few locations. While the 1967 outbreak occurred in Europe, the disease agent had arrived with imported monkeys from Uganda. No other case was recorded until 1975, when a traveler most likely exposed in Zimbabwe became ill in Johannesburg, South Africa – and passed the virus to his travelling companion and a nurse. 1980 saw two other cases, one in Western Kenya not far from the Ugandan source of the monkeys implicated in the 1967 outbreak. This patient’s attending physician in Nairobi became the second case. Another human Marburg infection was recognized in 1987 when a young man who had traveled extensively in Kenya, including western Kenya, became ill and later died.

Where is Marburg virus found?
Marburg virus is indigenous to Africa. While the geographic area to which it is native is unknown, this area appears to include at least parts of Uganda and Western Kenya, and perhaps Zimbabwe. As with Ebola virus, the actual animal host for Marburg virus also remains a mystery. Both of the men infected in 1980 in western Kenya had traveled extensively, including making a visit to a cave, in that region. The cave was investigated by placing sentinels animals inside to see if they would become infected, and by taking samples from numerous animals and arthropods trapped during the investigation. The investigation yielded no virus: The sentinel animals remained healthy and no virus isolations from the samples obtained have been reported.

How do humans get Marburg hemorrhagic fever?
Just how the animal host first transmits Marburg virus to humans is unknown. However, as with some other viruses which cause viral hemorrhagic fever, humans who become ill with Marburg hemorrhagic fever may spread the virus to other people. This may happen in several ways. Persons handling infected monkeys who come into direct contact with them or their fluids or cell cultures, have become infected. Spread of the virus between humans has occurred in a setting of close contact, often in a hospital. Droplets of body fluids, or direct contact with persons, equipment, or other objects contaminated with infectious blood or tissues are all highly suspect as sources of disease.

What are the symptoms of the disease?
After an incubation period of 5-10 days, the onset of the disease is sudden and is marked by fever, chills, headache, and myalgia. Around the fifth day after the onset of symptoms, a maculopapular rash, most prominent on the trunk (chest, back, stomach), may occur. Nausea, vomiting, chest pain, a sore throat, abdominal pain, and diarrhea then may appear.   Symptoms become increasingly severe and may include jaundice, inflammation of the pancreas, severe weight loss, delirium, shock, liver failure, massive hemorrhaging, and multi-organ dysfunction.

Because many of the signs and symptoms of Marburg hemorrhagic fever are similar to those of other infectious diseases, such as malaria or typhoid fever, diagnosis of the disease can be difficult, especially if only a single case is involved.

Which laboratory tests are used to diagnose Marburg hemorrhagic fever?
Antigen-capture enzyme-linked immunosorbent assay (ELISA) testing, IgM-capture ELISA, polymerase chain reaction (PCR), and virus isolation can be used to confirm a case of Marburg hemorrhagic fever within a few days of the onset of symptoms. The IgG-capture ELISA is appropriate for testing persons later in the course of disease or after recovery.  The disease is readily diagnosed by immunohistochemistry, virus isolation, or PCR of blood or tissue specimens from deceased patients.

Are there complications after recovery?
Recovery from Marburg hemorrhagic fever may be prolonged and accompanied by orchititis, recurrent hepatitis, transverse myelitis or uvetis. Other possible complications include inflammation of the testis, spinal cord, eye, parotid gland, or by prolonged hepatitis.

Is the disease ever fatal?
Yes.  The case-fatality rate for Marburg hemorrhagic fever is between 23-25%.

How is Marburg hemorrhagic fever treated?
A specific treatment for this disease is unknown. However, supportive hospital therapy should be utilized. This includes balancing the patient’s fluids and electrolytes, maintaining their oxygen status and blood pressure, replacing lost blood and clotting factors and treating them for any complicating infections.

Sometimes treatment also has used transfusion of fresh-frozen plasma and other preparations to replace the blood proteins important in clotting. One controversial treatment is the use of heparin (which blocks clotting) to prevent the consumption of clotting factors.  Some researchers believe the consumption of clotting factors is part of the disease process. 

Who is at risk for the illness?
People who have close contact with a human or non-human primate infected with the virus are at risk. Such persons include laboratory or quarantine facility workers who handle non-human primates that have been associated with the disease. In addition, hospital staff and family members who care for patients with the disease are at risk if they do not use proper A fuller understanding of Marburg hemorrhagic fever will not be possible until the ecology and identity of the virus reservoir are established. In addition, the impact of the disease will remain unknown until the actual incidence of the disease and its endemic areas are determined.

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1999 Special Pathogens Branch
Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases
Centers for Disease Control and Prevention
Public Health Service, U.S. Department of Health and Human Services