Lassa fever is a severe and often fatal hemorrhagic illness caused by Lassa virus. Since its original discovery in 1969 in the village of Lassa in Borno State, Nigeria, there have been countless outbreaks of various magnitude and severity across West Africa. Estimates of annual incidences of Lassa fever across this region reach as high as 300,000 infections and 5,000 deaths. However due to scarce resources to diagnose the illness as well as inadequate surveillance, many cases remain unaccounted.
Lassa virus is a member of the Arenaviridae virus family. Humans contract the virus primarily through contact with the contaminated excreta of Mastomys natalensis rodents (commonly known as the Multimammate rat), which is the natural reservoir for the virus. Little is known regarding the transmission of the virus from the rodent reservoir to the human host, although there is compelling evidence that Arenaviruses are stable and infectious by the aerosol route in nonhuman primates. The rodents live in houses with humans and deposit excreta on floors, tables, beds and food. Consequently the virus is transmitted to humans through cuts and scratches, or inhaled via dust particles in the air. In some regions Mastomys rodents are also consumed as food.
Secondary transmission of the virus between humans occurs through direct contact with infected blood or bodily secretions. This occurs mainly between individuals caring for sick patients although anyone who comes into close contact with a person carrying the virus is at risk of infection. Nosocomial transmission (transmission that occurs as a result of treatment in a hospital) and outbreaks in healthcare facilities in endemic areas represent a significant burden on the healthcare system.
In the early stages, Lassa fever is often misdiagnosed as influenza, typhoid or malaria, and as a result many patients fail to receive appropriate medical treatment. Making a correct diagnosis of Lassa fever is made difficult by the wide spectrum of clinical effects that manifest, ranging from asymptomatic to multi-organ system failure and death. The onset of the illness is typically indolent, with no specific symptoms that would distinguish it from other febrile illnesses. Early signs include fever, headache and general malaise, followed by a sore throat, nausea, vomiting, abdominal pain and diarrhea in some cases. After 4 to 7 days, many patients will start to feel better, but a small minority will proceed to display symptoms such as edema, hypertension, bleeding and shock. Death from Lassa fever most commonly occurs 10 to 14 days after symptom onset.
Because of its high case fatality rate, ability to spread easily by human-to-human contact, and potential for aerosol release, Lassa virus is classified as a Biosafety Level 4 (BSL4) and NIAID Biodefense category A agent. The potential use of Lassa virus as a biological weapon directed against civilian or military targets necessitates the development of counter-threat measures, such as diagnostic assays, vaccines and therapeutics. Moreover, the impact of the disease in endemic regions of West Africa is immense, and therefore means to diagnose, treat and prevent this viral hemorrhagic fever will provide a significant public health benefit.
No vaccine for Lassa fever is currently available for use in humans, and the only available drug, ribavirin, is only effective if administered early in infection (within the first 6 days after disease onset). One of the hallmarks of Lassa virus infection is the apparent absence of functional antibodies during acute infection. A fundamental understanding of the mechanisms of antibody-mediated neutralization of Lassa virus may have significant implications for the generation of antibody-based therapeutics or epitope-targeted vaccines.
Lassa fever is endemic to West Africa. Confirmed incidences have been recorded in Sierra Leone, Liberia, Guinea, Nigeria and Mali. However, concerns exist that there may be Lassa(-like) viruses in other countries such as Central African Republic, Ghana, Mali, Ivory Coast, Togo, Benin and Cameroon. Furthermore, Mastomys rodents are distributed across the African continent, indicating a strong possibility for the spread of the disease they carry.