Clinical Features

Lassa fever

The onset of illness is insidious, with fever and shivering accompanied by malaise, headache and generalised aching. Sore throat is a common early symptom. In some cases the tonsils and pharynx may be inflamed with patches of white or yellowish exudate and occasionally small vesicles or shallow ulcers. (Importantly, a similar appearance may be seen in cases of malignant tertian malaria). As the illness progresses the body temperature may rise to 41ºC with daily fluctuations of 2-3ºC. The duration and severity of fever is very variable. The average duration is 16 days but extremes of 6-30 days have been reported. A feature of severe attacks is lethargy or prostration disproportionate to the fever. During the second week of illness there may be oedema of the head and neck, encephalopathy, pleural effusion and ascites. Vomiting and diarrhoea may aggravate the effects of renal and circulatory failure. Severe cases develop significant haemorrhage and multi-organ failure with widespread oedema and bleeding into the skin, mucosae and deeper tissues. In non-fatal cases the fever subsides and the patient's condition improves rapidly although tiredness may persist for several weeks. There is usually a leucopenia early in the course, though a high polymorphonuclear leucocytosis may occur with severe tissue damage. Another common late complication is sensorineural deafness.

Congo-Crimean Haemorrhagic Fever

The illness begins abruptly with fever, chills, malaise, irritability, headache and severe pains in the limbs and loins, followed by anorexia, nausea, vomiting and abdominal pain. Fever is usually continuous but may be remittent and sometimes biphasic, resolving by crisis after 8 days. The face and neck are flushed and oedematous, the conjunctivae and pharynx are injected, and there is oedema of the soft palate. Patients are often depressed and somnolent. In most cases a fine petechial rash begins on the trunk and then covers the entire body. A haemorrhagic exanthem appears on the soft palate and uvula early in the illness and other bleeding manifestations, including haematemesis and melaena, appear on about the fourth or fifth day in over three-quarters of patients. Leucopenia and severe thrombocytopenia are common. Large ecchymotic areas caused by subcutaneous extravasation of blood occur at times. Severe gastric and nasal haemorrhages often lead to death. The liver is enlarged in about half the cases but the respiratory system is unaffected. Involvement of the central nervous system is seen in 10-25% of patients and usually indicates a poor prognosis; features include neck rigidity, excitation and coma. The mortality rate in outbreaks is often as high as 30-50%. Death is usually due to shock, blood loss or intercurrent infection.

Ebola virus

The disease begins with acute fever, diarrhoea, which can be bloody, and vomiting. Headache, nausea, and abdominal pain are common. Conjunctival infection, dysphagia, hiccups, and haemorrhagic symptoms such as epistaxis, gum haemorrhage, haematemesis, melaena, and purpura may further develop. Some patients may also show a maculopapular rash on the trunk at 3-8 days, this is followed by desquamation. Appearance of haemorrhagic manifestations is an indicator of poor prognosis. Dehydration and significant wasting occur as the disease progresses. At a later stage, there is frequent involvement of the CNS, manifested by somnolence, delirium, or coma. By the second week of illness, the patient will either markedly improve and convalesce or will have multi-organ failure and septic shock. Autopsies show panencephalitis, cerebral oedema, and serious renal damage. The case fatality rate ranges from 90% in outbreaks caused by Zaire strain, 50% in those caused by Sudan strain and 0% in Reston strain.

Marburg virus

The course of Marburg infection is similar to that of Ebola although Marburg tends to be less severe.

 

Mortality

Lassa fever

Approximately 15%-20% of patients hospitalised for Lassa fever die from the illness. However, in endemic countries, probably only about 1% of patients who become infected through contact with Mastomys rodents, die from their disease. The death rates are particularly high for women in the third trimester of pregnancy and their foetuses. The factors affecting disease severity are unknown but there is some suggestion that Nigerian strains cause more severe disease and that route and dose of inoculum may influence pathogenicity.

Congo-Crimean Haemorrhagic Fever

The death rate is often as high as 30-50% in outbreaks.

Ebola virus

Ebola virus outbreaks have shown a wide range of outcomes, from almost 90% mortality in the outbreaks of 1976 and 1995 the in the Democratic Republic of Congo through to 50% in Sudanese outbreaks. The mortality rate is dependent on strain; the Reston strain, identified in imported monkeys from the Philippines, was associated with subclinical infection in the few human cases.

Marburg virus

The Marburg virus outbreak in Germany and Yugoslavia in 1967 had a mortality rate of 28% in primary cases. Other outbreaks, affecting Central Africa in the 1990s and early 2000s have had case fatality rates varying from 40-70%.

Antiviral sensitivity

Ribavirin can be effective if given in the first week of Lassa fever. There is also in vitro evidence that ribavirin is effective against CCHF. No antiviral agent has any effect in Ebola or Marburg haemorrhagic fevers. Convalescent plasma is effective for some arenavirus infections such as Junin (Argentinean Haemorrhagic Fever), but its effectiveness for Lassa fever and Ebola/ Marburg in humans has never been demonstrated.

Legal issues

Currently, if a person is suspected to have VHF, they should be managed by one of the two High Security Infectious Disease Units (HSIDUs) according to the guidelines issued by the Advisory Committee on Dangerous Pathogens (ACDP) on The management and control of Viral Haemorrhagic Fevers (HMSO 1996). The Health and Safety Executive can prosecute if there is deviation from these guidelines.

In the event of a deliberate release, the number of patients will exhaust the current capacity to allow adherence to these strict protocols. Other ways of managing these patients may need to be put in place, for instance, cohort nursing in a dedicated ward. In such a situation, advice and support can be sought from the HSIDUs.

This guideline on bioterrorism has relied extensively on ACDP protocols and if there is a deliberate release of VHF agents it should be used in conjunction with the ACDP, VHFguidelines. Useful advice on infection control, personal protection and specimen-taking can also be found in the Cardinal Signs and Tips document.

Last reviewed: 11 May 2011