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Lassa Fever

by Craig R. Pringle, BSc, PhD

Lassa fever is an often fatal arenavirus infection that occurs mostly in West Africa. It may involve multiple organ systems. Diagnosis is with serologic tests and PCR. Treatment includes IV ribavirin.

Lassa fever outbreaks have occurred in Nigeria, Liberia, and Sierra Leone. Cases have been imported to the US and the United Kingdom. The reservoir is Mastomys natalensis , a rat that commonly inhabits houses in Africa. Most human cases probably result from contamination of food with rodent urine, but human-to-human transmission can occur via urine, feces, saliva, vomitus, or blood.

Based on serologic data, indigenous people in endemic areas have a very high rate of infection—much higher than their rate of hospitalization for Lassa fever—suggesting that many infections are mild and self-limited. However, some observational studies of missionaries sent to endemic areas show they have a much higher rate of severe illness and mortality. The Centers for Disease Control and Prevention (CDC) estimates that about 80% of infected people have mild disease and about 20% have severe, multisystem disease.

Symptoms and Signs

The incubation period is 5 to 16 days. Symptoms begin with gradually progressive fever, weakness, malaise, and GI symptoms (eg, nausea, vomiting, diarrhea, dysphagia, stomach ache); symptoms and signs of hepatitis may occur. Over the subsequent 4 to 5 days, symptoms progress to prostration with sore throat, cough, chest pain, and vomiting. The sore throat becomes more severe during the first week; patches of white or yellow exudate may appear on the tonsils, often coalescing into a pseudomembrane.

In 60 to 80% of patients, systolic BP is < 90 mm Hg with pulse pressures of< 20 mm Hg, and relative bradycardia is possible. Facial and neck swelling and conjunctival edema occur in 10 to 30%. Occasionally, patients have tinnitus, epistaxis, bleeding from the gums and venipuncture sites, maculopapular rash, cough, and dizziness. Sensorineural hearing loss develops in 20%; it is often permanent.

Patients who recover defervesce in 4 to 7 days. Progression to severe illness results in shock, delirium, rales, pleural effusion, and, occasionally, generalized seizures. Pericarditis occasionally occurs. Degree of fever and aminotransferase levels correlate with disease severity. Late sequelae include alopecia, iridocyclitis, and transient blindness.

Diagnosis

  • PCR or serologic testing

Lassa fever is suspected in patients with possible exposure if they have a viral prodrome followed by unexplained disease of any organ system. Liver function tests, urinalysis, serologic tests, and possibly CBC should then be done. Proteinuria is common and may be massive. AST and ALT levels rise (to 10 times normal), as do LDH levels. The most rapid diagnostic test is PCR, but demonstrating either Lassa IgM antibodies or a 4-fold rise in IgG antibody titer using an indirect fluorescent antibody technique is also diagnostic.

Although the virus can be grown in cell culture, cultures are not routine. Because infection is a risk, particularly in patients with hemorrhagic fever, cultures must be handled only in a biosafety level 4 laboratory.

Chest x-rays, obtained if lung involvement is suspected, may show basilar pneumonitis and pleural effusions.

Prognosis

Recovery or death usually occurs 7 to 31 days (average 12 to 15 days) after symptoms begin. In patients with severe, multisystem disease, mortality is 16 to 45%. Disease is severe during pregnancy. Mortality is 50 to 92% in women who are pregnant or who have delivered within 1 mo. Most pregnant women lose the fetus.

Treatment

  • Ribavirin

Ribavirin, if begun within the first 6 days, may reduce mortality up to 10-fold. Treatment with ribavirin is 30 mg/kg IV (maximum, 2 g) loading dose followed by 16 mg/kg IV (maximum, 1 g/dose) q 6 h for 4 days, then 8 mg/kg IV (maximum, 500 mg/dose) q 8 h for 6 days. Anti-Lassa fever plasma may be used as adjunctive therapy in very ill patients.

Supportive treatment, including correction of fluid and electrolyte imbalances, is imperative.

For infected pregnant women, particularly during the 3rd trimester, uterine evacuation appears to reduce maternal mortality.

Prevention

Universal precautions, airborne isolation (including use of goggles, high-efficiency masks, a negative-pressure room, and positive-pressure filtered air respirators), and surveillance of contacts are recommended. No vaccine is available.

Drugs Mentioned In This Article

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  • VIRAZOLE

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