Lassa fever
Lassa fever, also known as Lassa hemorrhagic fever, is a type of viral hemorrhagic fever caused by the Lassa virus. Many of those infected by the virus do not develop symptoms. When symptoms occur, they typically include fever, weakness, headaches, vomiting, and muscle pains. Less commonly there may be bleeding from the mouth or gastrointestinal tract. The risk of death once infected is about one percent and frequently occurs within two weeks of the onset of symptoms. Of those who survive, about a quarter have hearing loss, which improves within three months in about half of these cases.
Lassa fever is usually initially spread to humans via contact with the urine or feces of an infected multimammate mouse. Spread can then occur via direct contact between people. Diagnosis based on symptoms is difficult. Confirmation is by laboratory testing to detect the virus's RNA, antibodies for the virus, or the virus itself in cell culture. Other conditions that may present similarly include Ebola, malaria, typhoid fever, and yellow fever. The Lassa virus is a member of the Arenaviridae family of viruses.
There is no vaccine. Prevention requires isolating those who are infected and decreasing contact with the mice. Other efforts to control the spread of disease include having a cat to hunt vermin, and storing food in sealed containers. Treatment is directed at addressing dehydration and improving symptoms. The antiviral medication ribavirin has been recommended, but evidence to support its use is weak.
Descriptions of the disease date from the 1950s. The virus was first described in 1969 from a case in the town of Lassa, in Borno State, Nigeria. Lassa fever is relatively common in West Africa including the countries of Nigeria, Liberia, Sierra Leone, Guinea, and Ghana. There are about 300,000 to 500,000 cases which result in 5,000 deaths a year.
Signs and symptoms
Onset of symptoms is typically 7 to 21 days after exposure. These mild symptoms may include fever, tiredness, weakness, and headache. In 20% of people more severe symptoms such as bleeding gums, breathing problems, vomiting, chest pain, or dangerously low blood pressure may occur. Long term complications may include hearing loss. In women who are pregnant, miscarriage may occur with a likelihood of 95%. Lassa fever can be difficult to distinguish clinically from other viral hemorrhagic fevers, such as Ebola virus disease. A combination of pharyngitis, pain behind the sternum, presence of excess protein in the urine and fever can indicate Lassa fever with higher specificity.In cases in which death occurs, this typically occurs within 14 days of onset. About 1% of all Lassa virus infections result in death. Approximately 15%-20% of those who have required hospitalization for Lassa fever die. The risk of death is greater in those who are pregnant. A "Swollen baby syndrome" may occur in newborns, infants and toddlers with pitting edema, abdominal distension and bleeding.
Cause
Virology
is a member of the Arenaviridae, a family of negative-sense, single-stranded RNA viruses. Specifically it is an old world arenavirus, which is enveloped, single-stranded, and bi-segmented RNA. Lassa virus contains both a large and a small genome section, with seven lineages identified to date: Lineages I, II, and III from Nigeria; Lineage IV from Sierra Leone, Guinea, and Liberia; Lineage V from Cote D’Ivoire and Mali Lineage VI from Togo; and Lineage VII from Benin.Spread
Lassa virus commonly spreads to humans from other animals, specifically the Natal multimammate mouse or African rat, also called the Natal multimammate rat. This is probably the most common mouse in equatorial Africa, common in human households and eaten as a delicacy in some areas.The multimammate mouse can quickly produce a large number of offspring, tends to colonize human settlements, and is found throughout the west, central and eastern parts of the African continent.
Once the mouse has become a carrier, it will excrete the virus throughout the rest of its lifetime through feces and urine creating ample opportunity for exposure. The virus is probably transmitted by contact with the feces or urine of animals accessing grain stores in residences. No study has proven presence in breast milk, but the high level of viremia suggests it may be possible.
Individuals who are at a higher risk of contracting the infection are those who live in rural areas where Mastomys are discovered, and where sanitation is not prevalent. Infection typically occurs by direct or indirect exposure to animal excrement through the respiratory or gastrointestinal tracts. Inhalation of tiny particles of infectious material is believed to be the most significant means of exposure. It is possible to acquire the infection through broken skin or mucous membranes that are directly exposed to infectious material. Transmission from person to person has been established, presenting a disease risk for healthcare workers. The virus is present in urine for between three and nine weeks after infection, and it can be transmitted in semen for up to three months after infection.
Diagnosis
A range of laboratory investigations are performed, where possible, to diagnose the disease and assess its course and complications. The confidence of a diagnosis can be compromised if laboratory tests are not available. One comprising factor is the number of febrile illnesses present in Africa, such as malaria or typhoid fever that could potentially exhibit similar symptoms, particularly for non-specific manifestations of Lassa fever. In cases with abdominal pain, in countries where Lassa is common, Lassa fever is often misdiagnosed as appendicitis and intussusception which delays treatment with the antiviral ribavirin. In West Africa, where Lassa is most common, it is difficult to diagnose due to the absence of proper equipment to perform testing.The United States FDA has yet to approve a widely validated laboratory test for Lassa, but there are tests that have been able to provide definitive proof of the presence of the LASV virus. These tests include cell cultures, PCR, ELISA antigen assays, plaque neutralization assays, and immunofluorescence essays. However, immunofluorescence essays provide less definitive proof of Lassa infection. An ELISA test for antigen and Immunoglobulin M antibodies give 88% sensitivity and 90% specificity for the presence of the infection. Other laboratory findings in Lassa fever include lymphocytopenia, thrombocytopenia, and elevated aspartate transaminase levels in the blood. Lassa fever virus can also be found in cerebrospinal fluid.
Prevention
Control of the Mastomys rodent population is impractical, so measures focus on keeping rodents out of homes and food supplies, encouraging effective personal hygiene, storing grain and other foodstuffs in rodent-proof containers, and disposing of garbage far from the home to help sustain clean households. Gloves, masks, laboratory coats, and goggles are advised while in contact with an infected person, to avoid contact with blood and body fluids. These issues in many countries are monitored by a department of public health. In less developed countries, these types of organizations may not have the necessary means to effectively control outbreaks.Vaccine
There is no vaccine for humans as of 2023. Researchers at the United States Army Medical Research Institute of Infectious Diseases facility had a promising vaccine candidate in 2002. They have developed a replication-competent vaccine against Lassa virus based on recombinant vesicular stomatitis virus vectors expressing the Lassa virus glycoprotein. After a single intramuscular injection, test primates have survived lethal challenge, while showing no clinical symptoms.Treatment
Treatment is directed at addressing dehydration and improving symptoms.Medications
The antiviral medication ribavirin has been recommended, but evidence to support its use is weak. Some evidence has found that it may worsen outcomes in certain cases. Fluid replacement, blood transfusions, and medication for low blood pressure may be required. Intravenous interferon therapy has also been used.Indirect antivirals
A potential novel treatment, the NMT inhibitor, has been shown to completely inhibit lassa infection in cells based assays by targeting Z protein and SSP for degradation. Favipiravir, a nucleoside analogue, has been shown to be effective at treating Lassa fever in immunocompetent mouse, guinea pigs and macaques. A case report showed combination favipiravir with ribavirin is effective for lassa fever, with two patients survived. In vivo, the EC50 of favipiravir is 2.89 μg.mL−1and doses larger than 1200 mg twice a day should have the capability to strongly reduce the production infectious virus.Pregnancy
When Lassa fever infects pregnant women late in their third trimester, inducing delivery is necessary for the mother to have a good chance of survival. This is because the virus has an affinity for the placenta and other highly vascular tissues. The fetus has only a one in ten chance of survival no matter what course of action is taken; hence, the focus is always on saving the life of the mother.Prognosis
About 15–20% of hospitalized people with Lassa fever will die from the illness. The overall case fatality rate is estimated to be 1%, but during epidemics, mortality can climb as high as 50%. The mortality rate is greater than 80% when it occurs in pregnant women during their third trimester; fetal death also occurs in nearly all those cases. Abortion decreases the risk of death to the mother. Some survivors experience lasting effects of the disease, and can include partial or complete deafness.Because of treatment with ribavirin, fatality rates have declined.