Lassa fever is a potentially fatal viral infection that primarily occurs in West Africa. The virus is spread through contact with rodent secretions and person-to-person transmission is possible through direct contact. The majority of infections are asymptomatic and mild, but in rare cases, severe multiorgan failure may result in fatal outcome. The diagnosis is made by serologic and molecular techniques, while early ribavirin treatment has shown significant benefit.
The mean time from viral contraction to the appearance of symptoms (the incubation period) is 7-21 days. The majority of patients exhibit either asymptomatic or milder forms of infection, which may include symptoms such as fever, myalgia, arthralgia, nausea and weakness that last only a few days. Studies report various, but very small percentages of patients who develop severe infection, which includes the appearance of symptoms such as abdominal and chest pain, vomiting, diarrhea, headaches, pharyngitis, conjunctivitis and dysuria. These symptoms usually appear in the first two weeks of illness, while more severe findings that indicate major organ damage appear in the third week. Central nervous system findings, such as encephalitis and hearing loss, which can be permanent , are not uncommon. Visceral hemorrhage, respiratory distress, facial edema and hypotension is frequently encountered. Severe deterioration of the patient may follow, and pleural effusions, shock, delirium, very high fever and seizures are observed . Because of the rapid progression of symptoms and potentially fatal outcomes, early diagnosis and treatment within the first several days of illness are of critical value for the patient.
A clinical suspicion of Lassa fever can be made only by obtaining proper patient history, including recent travel to endemic areas and contact with animals and other individuals that exhibited similar symptoms. Once the history suggests Lassa fever as the probable cause of symptoms, a full workup should be performed, including complete blood count (CBC), liver function tests (AST, ALT, coagulation time), values of lactate dehydrogenase (LDH), urinalysis to evaluate for proteinuria, serum electrolytes and hemodynamic evaluation for hypotension. AST, ALT, and LDH usually show extremely high values, due to significant hepatic involvement. Imaging techniques, including chest X-rays, abdominal ultrasound, computed tomography (CT) and other modalities should be used to assess the general condition of the patient.
A definite diagnosis is made through microbiological investigation. Serologic testing for IgM or large titers of IgM antibodies against Lassa virus is recommended, but RT-PCR shows detects viral DNA, and shows greater specificity . Because Lassa virus may be highly contagious, significant safety measures must be adopted during diagnostic blood sampling, as well as during patient interaction.
Treatment of patients with Lassa fever comprises strict isolation measures, symptomatic therapy, and ribavirin.
Ribavirin is an antiviral drug used against several viral pathogens, including Lassa virus, and it inhibits RNA-depended mechanisms of viral protein synthesis, thus disrupting normal viral replication . Early administration of ribavirin (within the first 6-7 days of illness) reduces mortality rates significantly. The recommended regimen includes a 30 mg/kg IV loading dose, followed by 15 mg/kg IV q6h for 4 days, and 7.5 mg/kg q8h for 6 days. This drug is shown to be safe and causes few adverse effects, the most common being mild reversible anemia . Symptomatic therapy is vital in maintaining normal blood pressure and tissue perfusion through correction of electrolytes and adequate hydration. Severe respiratory distress may require assisted or artificial ventilation.
Because very high mortality rates are observed in pregnant women, labor induction is performed whenever possible, because the virus readily crosses the placental barrier and can cause both maternal and fetal death .
This viral infection can be fatal despite available treatment. Patients in whom treatment is initiated within the first week of illness, have significantly better outcomes while mortality rates for patients with severe infection range from 16-45% . Mortality is very high among pregnant women and medical personnel involved in managing patients with this infection. High viral load, together with very high values of liver transaminases, are significant predictors of mortality in patients .
The causative agent of Lassa fever is Lassa virus and it belongs to the group of viral pathogens that are responsible for causing viral hemorrhagic fevers. Due to its morphology and sandy appearance on electron microscopy, it is classified into arenaviruses (arenosus in latin denotes the term sandy), together with lymphocytic choriomeningitis virus (LCM), Junin virus and Machupo virus. Lassa virus contains two single-stranded RNA segments, and the size of the virion ranges from 40-200 nm in diameter. Because the virus is transmitted from rodents to humans, it is classified as a zoonotic infection. The principal vector and reservoir is Mastomys natalensis, a multimammate mice, in which high viral loads are maintained without harming the host . As a result, viral shedding through its secretions, including saliva, urine and feces occurs.
It is estimated that Lassa fever affects between 100,000 to 300,000 individuals in West Africa and causes about 5,000 deaths , but it is assumed that the actual rates of this viral infection are unknown due to incomplete surveillance. Apart from the fact that West Africa is considered to be an endemic region, infection in travelers to these areas may occur, making travel history an important part of the diagnostic workup.
The mode of transmission for this virus is inhalation of contaminated aerosols, consumption of mice that contain the virus (which is not uncommon in the local population), or contact with infected fomites . Human-to-human transmission is possible through direct contact with infectious material, while healthcare workers can be at significant risk when being in contact with patients, which is why biosafety level 3 or even level 4 measures are recommended when handling patients and diagnostic material.
The pathogenesis of Lassa fever is not completely understood, but several key facts have been discovered in terms of its initial route and spread through the human host. Once the virus is contracted by the human individual, dendritic cells and macrophages are the initial targets where viral replication occurs. Dendritic cells belong to the group of antigen-presenting cells (APCs) together with macrophages, which are also performing various other functions . Because of their rapid circulation through different tissues, APCs shed the virus and thus contribute to viral replication in various organs. It is established that Lassa virus synthesizes nuclear proteins (NPs) that can inhibit the innate immune response and production of various proinflammatory cytokines, including natural killer (NK cells), interferon gamma (IFN-γ) and various interleukins (ILs). The NPs of the Lassa virus significantly delay the host immune response so that the virus is able to replicate freely and makes it impossible for adaptive immune mechanisms to eradicate it from the human host . Consequently, the virions are able to survive intracellularly and eventually reach the reticuloendothelial system and secondary lymphoid organs, including the liver, spleen, kidneys and endothelial cells. These are the sites where the virus rapidly replicates and causes extensive tissue damage. As a result, various pathological changes are observed, including hepatic necrosis, myocarditis, aplasia of the bone marrow, significant proteinuria and disruption of splenic structure . Interestingly, alterations in the circulatory system are not as severe as in other viral hemorrhagic fevers. It is hypothesized that vascular damage occurs secondary to activation of the immune response by proinflammatory cytokines and not due to cytopathic effects of the virus.
Ideally, prevention of contact with Mastomys rodents, their infected secretions, or aerosols containing this virus would significantly reduce the burden of Lassa fever. Additionally, avoiding rodents as a source of food, as well as proper isolation of patients with suspected Lassa fever are measures that should be readily conducted. Healthcare workers should be especially warned and properly equipped when handling patients with this infection, as healthcare-associated infections carry high mortality rates. At this moment, a vaccine has yet been developed, but steps toward this goal have commenced .
Lassa fever is a potentially fatal infection caused by Lassa virus, which belongs to the group of viral hemorrhagic fevers together with Ebola virus, Crimean-Congo hemorrhagic fever, and several others . This group of viruses is characterized by symptoms of fever, severe vascular damage, and multiorgan failure. Lassa fever was initially described in Lassa, Nigeria during the 1960s amongst healthcare workers who were presumably in direct contact with an infected patient . Since its discovery, various countries in West Africa, including Sierra Leone, Guinea, Ivory Coast and many others have been reported to be endemic areas of Lassa fever. The reservoir for this virus is a rodent, specifically mastomys species, in which chronic asymptomatic carriage is observed. As a result, this vector is able to shed the virus in its secretions, including urine, saliva, and feces. Humans contract the virus either through inhalation of aerosols containing the virus or consumption of contaminated food, but contact with fomites may be a mode of transmission as well. Once the virus reaches the human host, person-to-person spread via direct contact is possible, which is why isolation of patients is vital in preventing both community and nosocomial outbreaks. The pathogenesis is incompletely understood, but presumably, the virus interferes with several mechanisms of the immune system that should eradicate the virus from the organism. The incubation period ranges from one to three weeks, but the majority of individuals have an asymptomatic or mild form of infection. Symptoms, when present, include fever, headache, pharyngitis, myalgia, abdominal pain and other constitutional complaints. In rare cases, severe multiorgan damage may occur, including hepatitis with extensive liver necrosis, kidney failure resulting in facial edema and proteinuria, central nervous system involvement including meningoencephalitis and diffuse capillary leakage, resulting in hypotension and possibly shock. The diagnosis of Lassa fever is made by isolating the virus from blood using serologic and molecular techniques, including enzyme-linked immunosorbent assay (ELISA) that detects IgM and IgG antibodies to this virus and real-time polymerase chain reaction (RT-PCR) to isolate viral DNA. It is established that early administration of ribavirin, an antiviral agent belonging to the group of nucleoside analogs, significantly reduces the risk of fatal outcomes, which is why it is recommended for treatment. However, this infection can still be fatal despite treatment, which is why establishing the diagnosis in its early stages can be life-saving. Moreover, significant steps in prevention of further viral transmission can be made through proper handling of material used for microbiological diagnosis, limitation of contact with patients with known viral shedding and vector control.
Lassa fever is an infection caused by Lassa virus. It is endemic in West African countries, including Nigeria, Sierra Leone, Guinea and other neighboring countries. The primary reservoir of the virus are rodents, specifically multimammate rats and mice. The virus is shed through rodent secretions, including saliva, feces and urine. Humans acquire the virus through inhalation of infected air particles or ingestion of food contaminated by rodent secretions. Because human-to-human transmission is possible by direct contact and because this Lassa fever may be fatal, several precautions are necessary when Lassa is suspected to be a cause of the symptoms. Pregnant women and healthcare workers are at particular risk when infected by this virus, as mortality rates are much higher in this population. The majority of individuals who contract the virus have an asymptomatic or mild form of infection and do not require any form of treatment. In rare cases, a severe and life-threatening form of disease may develop, and symptoms appear 7-21 days after contracting the virus. Fever, headache, sore throat, nausea, vomiting, as well as chest and abdominal pain may be reported in the initial stages, while severe deterioration may occur in later stages of infection, with the onset of hypotension, swelling of the face, extensive liver damage, delirium, and eventually shock. Hearing loss can occur and may become permanent after resolution of the infection. The diagnosis is made through obtaining blood samples for isolation of the virus and viral antibodies, but extensive safety measures must be adopted (Lassa fever requires biosafety level 4, which is required for Ebola virus as well). Treatment comprises of symptomatic measures, such as fluid administration, maintenance of blood pressure, respiration, oxygen levels, heart function and administration of ribavirin, an antiviral drug used for various viral infections. It is established that ribavirin administration within the first few days of illness significantly improves survival rates of patients with life-threatening forms of infection and it is should be given intravenously. Some preventive measures include avoiding travel to endemic areas, avoiding contact with rodents that are known to be carriers of this virus and ensuring proper handling of infectious material by healthcare workers.