PatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.
The viral haemorrhagic fevers (VHFs) are caused by four types of RNA virus:
- Filoviruses cause Ebola haemorrhagic fever (HF) and Marburg HF.
- Arenaviruses cause Lassa fever, Argentine HF and Bolivian HF.
- Bunyaviruses cause Korean HF (Hantavirus), Rift Valley fever and Crimean-Congo HF.
- Flaviviruses cause yellow fever and dengue fever.
Infected dendritic cells are largely impaired in their activation potency, likely contributing to the immune suppression that occurs during filovirus infection. Monocytes/macrophages, however, immediately activate after viral contact and release reasonable amounts of cytokines that target the vascular system, particularly the endothelial cells. Fibroblastic reticular cells, another prevalent infected cell type, are known to be a key regulator of circulatory and immune functions. Similar processes are thought to occur in arenavirus infection.
These three diseases are almost invariably found in Central Africa where outbreaks are usually sporadic but very infectious and have a very high mortality rate. Cases imported from endemic areas have been reported sporadically in the UK.
- Lassa fever is prevalent in the West African sub-region where about 3-5 million individuals are infected yearly.
- Lassa fever is known to be endemic in Guinea, Liberia, Sierra Leone, and Nigeria, and evidence of infection has been found in other neighbouring countries including Mali, Senegal and the Central African Republic.
- Recorded cases of Marburg virus disease are rare. Outbreaks and sporadic cases have been reported in Angola, Democratic Republic of Congo, Kenya, and South Africa (in a person who had recently travelled to Zimbabwe).
- Ebola HF outbreaks are more sporadic but mortality is 50-90%.
- Marburg HF outbreaks are also sporadic. There have been outbreaks in the Congo and Angola. Deaths in Europe have occurred in laboratory workers who handled green monkeys.
- Lassa fever is transmitted directly to humans by rodents, insect bites (especially mosquito), primates and patients.
- Marburg HF originated from a group of African green monkeys imported from Uganda but the usual vector for Ebola and Marburg HF is not known.
- There is transmission between humans in all three diseases. This tends to be from body fluids rather than droplet spread.
- Hospital-acquired infection - eg, reused needles, overcrowded hospitals, soiled sheets.
- Doctors and nurses who operate on infected patients are at risk.
In recent years some new VHFs have emerged in various parts of the world, usually where human habitation has encroached on rain forests.
- The incubation period is 4-21 days.
- Symptoms start with fever, headaches, myalgia and conjunctival suffusion.
- Symptoms of Ebola typically include fever (greater than 38.6°C), severe headache, muscle pain, weakness, diarrhoea, vomiting, abdominal pain, lack of appetite and unexplained bleeding or bruising.
- On about the fifth day of illness, a maculopapular rash may appear, mostly on the trunk.
Many systems are affected:
- Nausea and vomiting (perhaps bloody).
- Diarrhoea (bloody).
- Abdominal pain.
- Hepatitis with jaundice or pancreatitis.
- Hypertension or hypotension.
- Chest pain.
- Unilateral or bilateral deafness (usually Lassa fever).
Bleeding occurs in the nose, intestines or genitalia. Symptoms may increase in severity with rapid weight loss, prostration, delirium, shock, hepatic failure, massive haemorrhage and multi-organ failure. Bleeding is a less notable feature of Lassa fever than the others.
The disease is often fatal within a few days.
This is mostly between the various other VHFs. Serological tests can establish the exact cause and strain.
- FBC shows reduced leukocytes (except in Lassa fever) and platelets.
- Transaminases are elevated and INR prolonged.
- There may be signs of disseminated intravascular coagulation.
Note: keep investigations to a minimum to protect laboratory staff and handle all specimens with extreme care.
Treatment is symptomatic. Attention to hydration and blood loss may be required with IV fluids, blood, plasma and platelets. Oxygen may be needed.
Secondary prevention requires total isolation of affected patients.
- No effective treatments, prophylactic measures, therapies or vaccines are approved to treat or prevent Ebola HF and Marburg HF.
- However, possible treatments are currently being developed. Various antibody treatments provide the potential for effective treatments for Ebola infection - eg, ZMapp:
- ZMapp is an experimental treatment that may be effective.
- ZMapp was provided in the USA for two people infected during the 2014 Ebola outbreak in West Africa.
- Both of the infected US patients receiving treatment survived but the efficacy and safety of ZMapp are not proven.
- Supportive care and ribavirin remain the predominant strategies for treating most of the arenavirus-induced diseases, including Lassa fever.
Analgesics and antipyretics may be required. Avoid aspirin and IM injections because of bleeding.
- Hepatic failure is more common in Marburg HF and Ebola HF, as is disseminated intravascular coagulation.
- In pregnancy, fetal loss exceeds 80%.
- Deafness occurs in 25% of cases of Lassa fever, with half recovering some hearing after three months.
- Acute kidney injury is an uncommon complication of VHF but acute renal dysfunction has been reported.
- Marburg HF has a mortality rate around 25%.
- Mortality rates for Ebola vary from 50-90%. There are five different strains of Ebola HF: Bundibugyo, Côte d'Ivoire, Reston, Sudan and Zaire. Ebola Zaire is the deadliest known strain of the virus with a mortality rate as high as 90%.
- It is estimated that at least 10,000 people die of Lassa fever in West Africa annually. Mortality tends to be higher in children and the elderly.
- Those who recover from these infections have long-lasting immunity but lifelong immunity has not been demonstrated.
- There are currently no approved vaccines against Lassa fever for use in humans.
- A vaccine for Marburg HF is being developed.
- Patients are infectious as long as they are pyrexial but corpses are also infectious.
- Keep away from vectors such as rodents or infected primates. Control rodent populations, prevent them from entering homes and workplaces and clean up droppings. Avoid mosquito bites - along the same principles as with malaria. When treating patients use gloves, gowns, masks and goggles, as infection acquired from patients seems to be particularly virulent.
- Close surveillance of contacts for three weeks with isolation if they become pyrexial.
Further reading & references
- Common sense Ebola resources for General Practice, RCGP (Oct 2014)
- Aleksandrowicz P, Wolf K, Falzarano D, et al; Viral haemorrhagic fever and vascular alterations. Hamostaseologie. 2008 Feb;28(1-2):77-84.
- Steele KE, Anderson AO, Mohamadzadeh M; Fibroblastic reticular cells and their role in viral hemorrhagic fevers. Expert Rev Anti Infect Ther. 2009 May;7(4):423-35.
- Atkin S, Anaraki S, Gothard P, et al; The first case of Lassa fever imported from Mali to the United Kingdom, February 2009. Euro Surveill. 2009 Mar 12;14(10). pii: 19145.
- Kitching A, Addiman S, Cathcart S, et al; A fatal case of Lassa fever in London, January 2009. Euro Surveill. 2009 Feb 12;14(6). pii: 19117.
- Ibekwe T; Lassa fever: the challenges of curtailing a deadly disease. Pan Afr Med J. 2012;11:55. Epub 2012 Mar 23.
- Lassa Fever; Public Health England
- Marburg virus disease; Public Health England
- Ebola; World Health Organization
- Marburg haemorrhagic fever; World Health Organization
- Ebola; Public Health England
- Ebola Hemorrhagic Fever; Centers for Disease Control and Prevention
- Choi JH, Croyle MA; Emerging targets and novel approaches to Ebola virus prophylaxis and treatment. BioDrugs. 2013 Dec;27(6):565-83. doi: 10.1007/s40259-013-0046-1.
- Gene OG, Julia BE, Vanessa MR, et al; Drug targets in infections with Ebola and Marburg viruses. Infect Disord Drug Targets. 2009 Apr;9(2):191-200.
- Vela E; Animal models, prophylaxis, and therapeutics for arenavirus infections. Viruses. 2012 Sep;4(9):1802-29. doi: 10.3390/v4091802. Epub 2012 Sep 24.
- Lima EQ, Nogueira ML; Viral hemorrhagic fever-induced acute kidney injury. Semin Nephrol. 2008 Jul;28(4):409-15.
- Yun NE, Walker DH; Pathogenesis of Lassa fever. Viruses. 2012 Oct 9;4(10):2031-48. doi: 10.3390/v4102031.
- Geisbert TW, Bausch DG, Feldmann H; Prospects for immunisation against Marburg and Ebola viruses. Rev Med Virol. 2010 Nov;20(6):344-57. doi: 10.1002/rmv.661.
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Dr Laurence Knott
Dr Colin Tidy
Dr Adrian Bonsall