Lassa Fever Marburg and Ebola Virus

The viral haemorrhagic fevers (VHF) are caused by 4 types of RNA virus:

• Filoviruses cause Ebola and Marburg
• Arenaviruses cause Lassa Fever, Argentine HF and Bolivian HF
• Bunyaviruses cause Korean HF, Rift Valley Fever and Crimean-Congo HF
• Flaviviruses cause Yellow Fever and Dengue

Of these Lassa Fever, Marburg and Ebola are the most significant.

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. A study in Gabon showed that 6% of the population had had contact with Ebola¹ but not Marburg or Lassa.

• Lassa fever affects between 300,000 and 500,000 people annually in West Africa of whom about 5,000 die.²
• Probably 80% of Lassa Fever is subclinical but in the other 20% it can take a complicated course. Subclinical infection in Marburg and Ebola is much rarer.
• Ebola outbreaks are more sporadic but mortality is 50-90%.³
• Marburg is also sporadic. Recent outbreaks have been in Congo and Angola. Deaths in Europe have occurred in laboratory workers who handled green monkeys.⁴

There is no apparent difference in predilection between sex and races.

• Lassa fever is transmitted directly to humans by rodents, insect bites, especially mosquitoes, from primates and from patients.
• Marburg originated from a group of African green monkeys imported from Uganda but the usual vector for Ebola and Marburg is not known.
• There is transmission between humans in all 3 diseases. This tends to be from body fluids rather than droplet spread.
• In some African hospitals needles are used for more than one patient, patients may share beds and soiled sheets can transmit disease. This is called nosocomial infection and is a major cause of spread.⁵
• 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.

It is said that both the USA and USSR developed the VHF viruses, especially Lassa, Marburg and Ebola, for use in biological warfare. Conceivably other states and terrorist organisations could do the same⁶ and the lack of familiarity with such diseases would increase the risk.⁷

• The incubation period is 4 to 21 days.
• Symptoms start with fever, headaches, myalgia and conjunctival suffusion.
• On about the fifth day of illness, a maculopapular rash may appear, mostly on the trunk.

Many systems are affected:

Gastrointestinal Tract

• Nausea and vomiting (perhaps bloody)
• Diarrhoea (bloody)
• Abdominal pain
• Constipation
• Dysphagia
• Hepatitis with jaundice or pancreatitis

Cardiovascular System

• Pericarditis
• Hypertension or hypotension
• Tachycardia

Respiratory Tract

• Cough
• Chest pain
• Dyspnoea
• Pharyngitis

Nervous System

• Encephalitis
• Meningitis
• Unilateral or bilateral deafness (usually Lassa fever)
• Seizures

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 usually fatal within a few days.

This is mostly between the various other VHFs. Serological tests can establish the exact cause and strain.

• Meningococcal septicaemia
• Henoch-Schonlein Purpura
• Measles
• Hepatitis
• Malaria
• Haemolytic uraemic syndrome

• FBC shows reduced leukocytes (except in Lassa Fever) and platelets.
• Transaminases are elevated and INR prolonged.
• There may be signs of disseminated intravascular coagulation (DIC).

Non-Drug

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.

Drugs

• Lassa Fever, South American HFs and possibly Crimean-Congo Fever and Rift Valley HF may be treated by a slow intravenous infusion of ribavirin.
• Adults require a loading dose of 2 grams (30mg/kg) followed by 1gram (15mg/kg) every 6 hours for 4 days, followed by 500 mg (7.5mg/kg) every 8 hours for 6 days.
• The dose in children is uncertain.
• It should be started as soon as possible but the cost of this drug in Central African countries is often prohibitive.

Analgesics and antipyretics may be required. Avoid aspirin and IM injections because of bleeding.

• Hepatic failure is more common in Marburg and Ebola as is disseminated intravascular coagulation (DIC).
• In pregnancy, fetal loss exceeds 80%.
• Deafness occurs in 25% of cases of Lassa fever, with half recovering some hearing after 3 months.

• Marburg has a mortality rate around 25%. Ebola³ kills between 50 and 90%.
• There are four different strains of Ebola virus: Zaire, Sudan, Reston, and Tai. Ebola Zaire is the deadliest known strain of the virus with a mortality rate as high as 90%.
• In Lassa fever of those who are admitted to hospital about 15 to 20% die giving an overall mortality of between 1 and 3% but in epidemics it can be up to 50%. Mortality tends to be higher in children and the elderly. It is more severe if contracted from a patient.
• Those who recover from these infections have long-lasting immunity but life-long immunity has not been demonstrated.

• Of the various haemorrhagic fevers only Yellow Fever has a vaccine. A vaccine against Lassa fever⁸ and Ebola⁹ may not be far off.
• A vaccine for Marburg is being developed.¹⁰
• Patients are infectious a 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 3 weeks with isolation if they become pyrexial.