Lassa fever

The disease is caused by Lassafever virus (LSAV). It is a bipartite single-stranded RNA virus belonging to the Arenaviridae family.
An important feature is the high genetic variability of some strains of the virus, which are capable of evolving and mutating over time. This variability is relevant to the design of diagnostic tools and the development of a universal vaccine that can be used in different geographical settings regardless of the circulating strain. Different strains also influence the symptomatology and severity of infection.
The animal reservoir for LASV is typically the "multimamma rat" Mastomys natalensis, a rodent of the genus Mastomys ubiquitous in West Africa: the infection affects the uterus of rodents that remain affected for the rest of their lives. These rats do not get sick, but continue to shed the virus in urine and feces. Although M. natalensis is considered the natural reservoir of LASV, there are also other rodent reservoirs (Mastomys erythroleucus and Hylomyscus pamfi) that recent discoveries have identified as being among those responsible for the distribution of Lassa fever.

Transmission occurs mainly by direct or indirect contact with infected rodents. During the dry season, Mastomys rodents invade inhabited houses in search of food, and humans are exposed to LSAV infection through contact with urine, feces, blood, or meat of infected Mastomys rodents. Infection is thought to result from direct inoculation of mucous membranes or inhalation of aerosols produced when rodents urinate or defecate. The frequency of infection related to these modes of transmission remains unknown.
Person-to-person transmission usually occurs among individuals living in overcrowded dwellings, in a care setting for sick people, or in individuals involved in burial practices. LASV can also be transmitted through direct contact with blood, urine, feces or other bodily secretions or even through accidental inoculation with sharp needles and contact with contaminated equipment.
Cases of sexual transmission occurring months after recovery from acute illness have been reported.
Lassa fever can affect all age groups and both sexes, in pediatric subjects it occurs most commonly in male children for reasons still unknown.

Lassa fever as mentioned is endemic in West Africa with cases reported in Nigeria, Benin, Liberia, Sierra Leone, Guinea, Mali, Senegal, and Ghana.The epidemiology of the virus is complex as most cases are asymptomatic, surveillance systems are ineffective, and specific diagnostic tests for Lassa fever are often lacking. Cases of Lassa fever have been documented associated with travel outside West Africa to the United States, Canada, the United Kingdom, the Netherlands, Israel, and Germany by aid workers, missionaries, and foreign military personnel.

The incubation period of Lassa fever ranges from 2 to 21 days. Symptoms are usually mild (which complicates diagnosis), with a gradual onset characterized by nonspecific symptoms such as fever, general weakness, malaise, and headache.
After a few days, symptoms become more acute and are followed by sore throat, muscle pain, chest pain, nausea, vomiting, diarrhea, cough, arthralgia, and abdominal and back pain.
Up to one-fifth of infected individuals experienced progression resulting in more severe symptoms such as facial swelling, bruising, respiratory distress, hepatitis, renal failure, convulsions, tremors, gait disturbances, disorientation, loss of consciousness, and bleeding from the mucosa of the mouth, nose, vagina, or gastrointestinal tract. Bleeding is a feature reported by 30% of patients with Lassa fever.

Finally, the most severe cases of LASV manifest excessive clotting, pleural or pericardial effusion (accumulation of fluid around the lungs or heart), spontaneous abortion, renal failure, multiorgan failure, hypovolemic shock (sudden reduction in circulating blood volume) similar to sepsis, headache, and bilateral or unilateral deafness.
The mortality rate is around 30% in children with generalized edema, abdominal distension, and bleeding. Genetic and immunological studies are underway to better understand the evolution of the disease and the defensive mechanisms underlying Lassa fever.
Lassa fever occurring during pregnancy can cause severe illness, high maternal mortality rates in the third trimester, and miscarriage, with an estimated 95% mortality in fetuses.

Early identification of patients with Lassa fever is critical to maximize the benefit of available antiviral therapy and to institute infection control measures.Nonspecific symptoms make Lassa fever difficult to distinguish from other common endemic microbial causes such as malaria, shigellosis, typhoid fever, and other viral hemorrhagic fevers such as Ebolavirus disease and yellow fever, both endemic to West Africa.A range of diagnostic tests are available from cell culture, immunofluorescence assays, complement fixation assays, enzyme-linked immunosorbent assays for LASV antigens and IgM antibodies, polymerase chain reaction with different assays and targets, lateral flow assays, and other rapid tests.Currently, molecular biology assays are mainly used for diagnosis, amplifying nucleic acid extracted from biological materials by classical or Real-Time RT-PCR.

Supportive therapy is important; adequate water and electrolyte balance, good oxygenation and blood pressure control must be maintained. Sometimes dialysis is necessary to maintain renal function. Secondary bacterial infections should be treated with antibiotics.
Specific antiviral therapy with the antiviral agent ribavirin may improve treatment outcome if administered early in the course of the disease. However, although ribavirin has been widely used for treatment and as post-exposure prophylaxis, treatment of Lassa fever with ribavirin is still under investigation.
More recent therapies include favipiravir, a broad-spectrum RNA inhibitor against RNA viruses, which has been shown to reduce LASV viremia in animal models.

In risk areas, contact with Mastomys rodents should be avoided to reduce the risk of LASV transmission to humans. Measures to be taken in such cases are placing food in rodent-proof containers, cleaning the house and surroundings, generally attempting to reduce rodent populations and contact with their droppings or urine.
Strict adherence to standard infection prevention and control precautions is mandatory to prevent the spread of human LSAV infection in healthcare settings, particularly when treating patients with fever of undetermined origin and suspected viral hemorrhagic fevers in endemic areas. Such measures include basic hand hygiene, respiratory hygiene, use of personal protective equipment, and safe injection practices.
There are currently no effective vaccines for Lassa fever, but there are several under development, including LASSARAB and an inactivated recombinant LASV. The recombinant vesicular stomatitis virus (VSV) vaccine expressing the LASV glycoprotein (VSV-LASV-GPC) is among the leading candidates developed so far and is targeted for accelerated development by The Coalition for Epidemic Preparedness Innovations Foundation, which is supporting the development of Lassa vaccine candidates.