Marburg Hemorrhagic Fever, April 2005
Abstract & Commentary
With Comment by Lin H. Chen, MD, Assistant Clinical Professor, Harvard Medical School Director, Travel Resource Center, Mt. Auburn Hospital, Cambridge, Mass., and Associate Editor, Travel Medicine Advisor.
Synopsis: The largest Marburg virus hemorrhagic fever outbreak has just occurred in Angola, and the appearance in urban centers has caused fear of its epidemic spread. Although virus transmission usually requires contact with blood and body fluids of infected individuals, travelers to affected regions should take precautions to avoid exposures.
Sources: CDC. Brief Report: Outbreak of Marburg Virus Hemorrhagic Fever—Angola, October 1, 2004-March 29, 2005; MMWR. 2005;54(12):308-309; WHO. Marburg Haemorrhagic Fever in Angola—Update 11. Communicable Disease Surveillance and Response, Disease Outbreak News, 13 Apr 2005. Available at www.who.int/csr/don/2005_04_13/en/. Accessed April 13, 2005.
The World Health Organization announced that Marburg virus is the cause of an outbreak of viral hemorrhagic fever in Angola. The Centers for Disease Control and Prevention reported that between October 1, 2004, and March 29, 2005, 124 cases were identified, 117 of which were fatal. Testing by the CDC identified the virus in 9 of 12 fatal cases. About 75% of all cases occurred in children under 5 years of age. Patients have presented primarily with fever, hemorrhage, vomiting, cough, diarrhea, and jaundice.
As of April 11, 2005, some 231 cases of Marburg hemorrhagic fever have been reported in Angola, with 210 fatalities. Initial cases were identified in Uige Province, but Luanda, Cabinda, Malange, Kuanza Norte, Kuanza Sul, and Zaire provinces have also reported cases. Uige remains the center of the outbreak, accounting for almost 90% of the cases and deaths. Although this disease has occurred generally in rural settings, the outbreak in Angola has taken place in urban centers. Currently there are no US travel restrictions to Angola.
Comment
Marburg is one of 2 filoviruses (the other being Ebola) that are pathogenic for primates and lead to hemorrhagic fever. Marburg virus infections in humans occurred in Germany and Yugoslavia (1967), Zimbabwe and South Africa (1975), Kenya (1980 and 1987), Zimbabwe (1982), Russia (1990), and the Democratic Republic of the Congo (1998-2000).1,2,3 The RNA virus can be pleomorphic, appearing as branching filaments or shorter folded forms.1 The first reported outbreak occurred in 1967 among laboratory workers who were exposed to infected monkeys imported from Uganda.2 Marburg virus has been found in forested areas of Kenya, Uganda, and Zimbabwe; the natural host of Marburg is not known, but exposure to bats has been associated with some infections.4 Until the outbreak in Angola occurred, the neighboring Democratic Republic of Congo had seen the largest recorded Marburg hemorrhagic fever outbreak from late 1998 to late 2000. At that time, about 150 cases were identified, with a case fatality rate of 82%.5 The DRC outbreak affected many workers at a gold mine in Durba, and appeared to be associated with bat exposure.5 The current predominance of infection among young children in Angola is unique.
Marburg hemorrhagic fever develops after an incubation period of 5-10 days, and is associated with fever, malaise, and followed by asthenia, diarrhea, nausea, vomiting, abdominal pain, chest, back, head pain, maculopapular rash, and sore throat.1 Patients develop petecchial hemorrhages and ecchymoses of skin, mucous membranes, and internal organs. Bleeding from puncture sites or mucous membranes, and anuria are ominous signs, usually followed by death.6,7 Marburg virus infections in the past caused mortality rates of 25-82%. The deadly outbreak in Angola has a higher mortality rate of 90%.
Pathologic findings in Marburg victims include visceral effusions, focal necrosis in vital organs, interstitial edema, alveolar damage in lungs, and myocardial edema and necrosis.1 Pathogenesis is not well understood, but appears to involve microvascular damage and mediators of inflammation.1 Diagnosis of Marburg virus infection is made by antigen capture ELISA, RT-PCR, or virus isolation.
The origin of exposure to the Marburg virus in Angola remains elusive, but the virus has spread readily via close contact with infected individuals.
Both Marburg and Ebola viruses are spread by exposure to blood and body fluids; persons who care for their ill family members are at high risk because gloves, gowns, and masks are not normally used. Persons who handle and prepare the body for burial are also at risk, unless contact precautions are carried out. Additionally, nosocomial transmission in the health care setting is a major concern; the lack of barrier precautions and the reuse of needles or syringes without sterilization are major routes of transmission. The WHO reported 12 cases in health care workers as of March 31.8 According to the New York Times (April 12, 2005), at least 2 doctors and 14 nurses have become victims of Marburg hemorrhagic fever in Angola. Aerosol transmission also appears possible in the laboratory.9
There is no antiviral therapy for Marburg hemorrhagic fever. Prevention depends on recognizing and isolating suspected cases, adhering to barrier precautions, appropriate sterilization techniques, and strict infection control in hospitals. In Angola, these preventive measures are in conflict with traditional ways of caring for ill family members and burying the deceased, so these practices may be difficult to accept. Furthermore, decades of civil unrest have resulted in a poorly equipped hospital system with little infection control.
Several patients with symptoms of Marburg hemorrhagic fever have sought medical care in the capitol, Luanda, setting off fear that the infection can escalate into an epidemic in the densely populated city. A recent case of Lassa fever in a US resident returning from Sierra Leone illustrates the possibility of potential dissemination through travel; fortunately, no secondary case resulted.10 Hemorrhagic fevers should be considered a diagnostic possibility in any seriously ill traveler returning from endemic regions. Differential diagnoses of Marburg virus infections include malaria, typhoid, shigellosis, leptospirosis, plague, borreliosis, rickettsial diseases, meningococcemia, dengue hemorrhagic fever/dengue shock syndrome, as well as other viral hemorrhagic fevers including Ebola, Lassa, yellow fever, Rift Valley fever, and Crimean Congo hemorrhagic fever.11
The CDC has posted recommendations for travelers on the web site (www.cdc.gov/travel/other/marburg_vhf_angola_2005.htm). Travelers should undergo pre-travel health assessment and identify health care resources at destination. First aid kits should include a thermometer, household disinfectant, and alcohol-based hand sanitizer. Travelers should wash hands frequently and carefully, avoid contact with potentially infected persons, and avoid contact with dead or ill animals. Travelers who develop fever or other symptoms such as chills, muscle aches, nausea, vomiting, or rash within 10 days of return home should seek medical attention immediately. Clinicians should carefully review the travel history in febrile returned travelers, and consider the diagnosis of Marburg virus hemorrhagic fever, particularly in those who have traveled in Angola, had direct contact with blood or body fluid from a suspected case (person or animal) of hemorrhagic fever, or worked in a laboratory that handles the viral hemorrhagic fever viruses.
Resources
- For more information about Marburg infections, see www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/marburg.htm, and www.who.int/csr/disease/marburg/en/.
- For guidance for travelers, see www.cdc.gov/travel/other/marburg_vhf_angola_2005.htm.
- For health-care workers in the African health care setting see www.cdc.gov/ncidod/dvrd/spb/mnpages/vhfmanual.htm.
- For management of patients in the United States with suspected viral hemorrhagic fever, see MMWR. 1995; 44:475-479.
- www.who.int/csr/don/2005_03_31a/en/.
References
1. Sanchez A, et al. Filovirus Infections in Tropical Infectious Diseases. Churchill Livingstone. 1999;ISBN 0-443-07908-0:1240-1251
2. Monath TP. Ecology of Marburg and Ebola Viruses: Speculations and Directions for Future Research. J Infect Dis. 1999;179:S127-138.
3. Bausch DG, et al. Risk Factors for Marburg Hemorrhagic Fever, Democratic Republic of the Congo. Emerg Infect Dis 2003;9:1531-1537.
4. Conrad JL, et al. Epidemiologic Investigation of Marburg Virus Disease, Southern Africa, 1975. Am J Trop Med Hyg. 1978;27:1210-1215.
5. World Health Organization. Marburg Virus Disease in Angola—Update. Available at: www.who.int/csr/don/2005_03_23/en. Accessed April 13, 2005.
6. Spence IM, et al. Marburg Virus Disease—An Indicator Case in South Africa. S Afr Med J. 1982;62:796.
7. Johnson ED, et al. Characterization of a New Marburg Virus Isolated from a 1987 Fatal Case in Kenya. Arch Virol Suppl. 1996;11:101-114.
8. WHO. Marburg Virus Disease in Angola—Update 4. Available at www.who.int/csr/don/2005_03_31a/en/. Accessed April 13, 2005.
9. Jaxx N, et al. Transmission of Ebola Virus (Zaire Strain) to Uninfected Control Monkeys in a Biocontainment Laboratory. Lancet 1995;346:1669-1671.
10. CDC. Imported Lassa Fever New Jersey, 2004. MMWR. 2004;53(38):894-897.
11. Isaacson M. Viral Hemorrhagic Fever Hazards for Travelers in Africa. Clin Infect Dis. 2001;33:1707-1712.
The largest Marburg virus hemorrhagic fever outbreak has just occurred in Angola, and the appearance in urban centers has caused fear of its epidemic spread.
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