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Outbreak in Angola

Chibuzo Odigwe and Daniel G Bausch give an overview of Marburg haemorrhagic fever and its latest outbreak in Angola

Last October, a haemorrhagic fever hit the inhabitants of northeastern Angola, and it has been spreading throughout the region ever since.w1 Alarmed at the death toll and the devastating effects of the disease, the local authorities sent samples for analysis to the US Centers for Disease Control and Prevention (CDC).w2 The results of the sample analysis returned positive for Marburg virus infection. At the last count, 423 cases with 357 deaths, a rate of 84%, has been recorded.w3

Marburg hemorrhagic fever (MHF) results from infection with Marburg virus. MHF typically begins with fever, headache, sore throat, and muscle pain, followed by abdominal pain, vomiting, and diarrhoea. Early in the illness there may be a transient rash. Bleeding may occur as the disease progresses. High viral loads of Marburg virus may be found in the blood and a host of other organs, especially tissues of the reticuloendothelial system.

Outbreaks of Marburg haemorrhagic fever
Year Site Deaths/cases(%)
1967 Germany and Yugoslavia 7/32 (22%)
1975 Zimbabwe/South Africa 1/3 (33%)
1980 Kenya 1/2 (50%)
1987 Kenya 1/1 (100%)
1990 Russia (laboratory acquired) 1/0 (-)
1998-2000 Democratic Republic of the Congo 125/150 (83%)*
2004 (ongoing) Angola 357/423 (84%)

*A total of 154 cases were recorded, but outcomes were unknown for 4 cases.

Marburg virus belongs to the Filoviridae family, along with Ebola virus. Marburg virus, first recognised in Marburg, Germany, in 1967, was traced back to the importation of African green monkeys, Cercopithecus aethiops, from Uganda. This resulted in the transmission of Marburg viruses to humans in Marburg and Frankfurt, Germany, and Belgrade, Yugoslavia (now Serbia and Montenegro).w1 w2 Since then, five naturally occurring outbreaks have been recorded, including the present one in Angola (table). Before the ongoing outbreak in Angola, the largest one occurred in the Democratic Republic of the Congo in 1998-2000, with 154 cases and 128 deaths (case fatality 83%).w1 w2 w3

Marburg virus is a single stranded RNA virus with virions that typically form thread-like filaments, often in the shape of a U, a circle, or like the number 6. Viral filaments may measure up to 14 000 nm in length and have a uniform diameter of 80 nm. The virus is lipid enveloped from budding through the host cell membranes.w4 Marburg virus glycoprotein plays an important role in cell tropism, spread of infection, and pathogenicity.w5-w7 Endothelial cell entry and damage leading to capillary leak and coagulopathy mediated by both direct viral effects and induced inflammatory mediators appears to be the primary pathogenic hallmark.w5-w8 Cells infected with Marburg virus also secrete a soluble glycoprotein that may interfere with the host immune response.w6

Marburg is transmitted between humans by close contact with blood and body fluids,w1-w3 but the natural reservoir of Marburg virus is unknown. Data obtained after the outbreak in Congo showed entry into mines to be a significant risk factor, suggesting that the reservoir inhabits such settings, for example bats, rodents, or arthropods.w4

The early presentation of MHF is difficult to distinguish from a host of other febrile illnesses, making laboratory confirmation imperative. Testing of blood by enzyme linked immunosorbent assay for Marburg specific antigen, and IgM and IgG antibodies, is the mainstay of laboratory diagnosis. Virus isolation, reverse transcriptase polymerase chain reaction, and immunohistochemistry staining of postmortem tissues are useful adjuncts and research tools. Virus culture must be performed in a maximum containment laboratory.

The treatment of MHF is supportive, directed at the maintenance of haemodynamic and electrolyte equilibrium.w5 Controlling the primary transmission of this disease is difficult because the natural reservoir is still unknown. In epidemics, control relies on the prevention of secondary transmission between humans through strict isolation of suspected cases, barrier nursing precautions, and tracing of contacts.w1 w2 w9

In the current epidemic in Angola, hospital transmission in paediatric wards is thought to have resulted in large numbers of infected children.w2 w3 Erosion of the public health system and barrier nursing precautions in Angola due to years of civil war are probably atthe root of the epidemic.w3 The government of Angola and the WorldHealth Organization are coordinating the international response, with the aid of many organisations, including Médecins Sans Frontières,w9 CDC, and Health Canada. A network of experts and laboratories in the United States, Canada, Germany, and South Africa supports field activities. An appeal through the United Nations for $2.4m (£1.3m; €2m) to support response efforts has met with favourable replies from several European Union countries. In view of the fact that the epidemic incites great anxiety in the affected communities, education campaigns have been launched to improve public understanding of MHF to increase local participation and cooperation in control measures.w1-w3 Médecins Sans Frontières has been playing a key role in the area of case management and training of local personnel, and contact tracing. Isolation units have been established in the provincial hospital in Uige, as well as in Luanda, Negage, Songo, and Camebatela.w9


FLORENCE PANOUSSIAN/AFP/GETTY

Health workers cleaning outside an emergency
ward where Marburg virus patients are treated

Given the fact that so much about MHF is still unknown, the need for intensified research, both laboratory and clinical, cannot be overemphasised. International donors should pool their resources to improve research capacity in developing countries while maintaining links with established centres in the industrialised world.



Chibuzo Odigwe, fifth year medical student, University of Calabar, Nigeria
Email: chibuzo2k2@yahoo.com

Daniel G Bausch, associate professor, department of tropical medicine, Tulane School of Public Health and Tropical Medicine, New Orleans, LA 70112-2699, USA
Email: dbausch@Tulane.edu


studentBMJ 2005;13:265-308 July ISSN 0966-6494

  1. Odigwe C. Attempts to contain Marburg disease epidemic have limited effect. BMJ 2005;330:864.
  2. World Health Organization. Marburg haemorrhagic fever: fact sheet. Geneva: WHO, 2005. www.who.int/csr/disease/marburg/factsheet/en (accessed 21 Jun 2005).
  3. World Health Organization. Marburg haemorrhagic fever in Angola. Updates 1-22. Geneva: WHO. www.who.int.
  4. 8 Centers for Disease Control and Prevention. Filovirus fact sheet. Atlanta: CDC. (accessed 21 Jun 2005).
  5. Brooks GF, Butel JS, Morse SA. Jawetz, Melnick and Adelberg’s medical microbiology. 22nd ed. Boston: Appleton & Lange/Mc Graw Hill, 2002.
  6. Schnittler H-J, Feldman H. Viral hemorrhagic fever: a vascular disease? Thromb Haemost 2003;89:967-72.
  7. Aman MJ, Bosio CM, Panchal RG, Burnett JC, Schmaljohn A, Bavari S. Molecular mechanisms of filovirus cellular trafficking. Microbes Infect 2003;5:639-49. (Corrected in Microbes Infect 2003;5:1287.)
  8. Bausch DG, Borchert M, Grein T, Roth C, Swanepoel R, Libande ML, et al. Risk factors for Marburg hemorrhagic fever, Democratic Republic of the Congo. Emerg Infect Dis 2003;9:1531-7.
  9. Médecins Sans Frontières. Stronger measures needed in Marburg fever outbreak in Angola. Geneva: MSF, 2005.


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