Lassa Fever

Abstract& Commentary

Synopsis: Importation of Lassa fever remains a continuing danger.

Sources: Lassa Fever, Imported-USA (New Jersey) ex Liberia. CDC. M MWR. 2004:53:894-897; United Kingdom: Probable Lassa Fever in Traveler Returning From West Africa. www.promedmail.org.

A 38-year-old man returned to the United States from west Africa, where he had spent the last 4 months in Liberia and Sierra Leone where he owned farms. Two days before his August 2004 return, he developed fever, chills, and severe sore throat, and shortly after his arrival, he was hospitalized with, in addition to these complaints, diarrhea and back pain. He deteriorated, developing ARDS and requiring mechanical ventilation, despite receipt of antibacterials and antimalarials. Lassa fever was considered, and administration of ribavirin was planned, but the patient died before receiving this antiviral medication. The diagnosis of Lassa fever was confirmed by serum antigen detection, immunohistochemical staining of postmortem liver tissue, virus isolation in cell culture, and genome sequencing.

A man returned to the United Kingdom in September 2004 after traveling for a month in Chad and Cote d’Ivoire, becoming febrile the following day. He sought care 2 days later and was admitted to the hospital and transferred to a medium security facility. After preliminary tests suggested Lassa fever, ribavirin therapy was initiated and he was transferred to a high security infectious disease facility. He became afebrile and was discharged from the hospital. Confirmatory tests are pending.

In both cases, extensive contact investigations were performed, including healthcare and laboratory workers, household contacts, and in the first case in which the patient traveled while symptomatic, airline passengers seated within 6 feet.

Comment by Stan Deresinski, MD, FACP

Lassa fever, named after the Nigerian town where it was first identified, should be considered in any patient who has a negative malaria smear with fever, who’s recently returning from west Africa. It is caused by a single-stranded RNA virus of the arenavirus, and is known to be endemic in Sierra Leone, Guinea, and Nigeria. In addition, seropositivity has been detected in a number of other countries of the region, including Mali, Senegal, the Central African Republic, and the Democratic Republic of Congo.1

Lassa fever is a zoonosis, transmitted by rats of the genus Mastomys, that are distributed throughout west, central, and eastern Africa. Infection of the rodents is persistent, and the virus is shed in urine and feces. Humans are infected by contact with rats, which may be actively sought since they serve as a protein source in many areas. Human-to-human transmission may also occur, including in the healthcare setting. As a conse quence, patients with suspected Lassa fever require careful infection control. Excretion of the virus in urine persists for 3 to 9 weeks, and for 3 months in semen.1

Approximately 80% of those infected remain asymptomatic or develop only mild illness after an incubation period of 6 to 21 days. The onset is usually gradual, and the presenting signs and symptoms are largely nonspecific. The complex of fever, retrosternal pain, and proteinuria, with the development of severe pharyngitis with white tonsillar patches, is suggestive. Progression may lead to the development of a hemorrhagic fever syndrome. Sensorineural hearing loss is a frequent complication. Ribavirin administration within the first 6 days of illness is reported to be associated with reduced mortality.2 Ribavirin has also been used, in the absence of evidence of benefit, as prophylaxis in contacts. The virus is also inhibited in vitro by both interferon alpha and interferon gamma.3 The differential diagnosis includes malaria, bacterial sepsis, and other viral hemorrhagic fevers, such as Ebola.

Only approximately 20 cases of imported infection have been reported. The United Kingdom patient is only the 7th case imported there. Nonetheless, its timely recognition is important because of the potential for human-to-human transmission.

References

1. Richmond JK, et al. Lassa Fever: Epidemiology, Clinical Features, and Social Consequences. BMJ. 2003; 327:1271-1275.

2. McCormick JB, et al. Lassa Fever: Effective Therapy With Ribavirin. N Engl J Med. 1986;314:20-26.

3. Asper M, et al. Inhibition of Different Lassa Virus Strains By Alpha and Gamma Interferons and Comparison With a Less Pathogenic Arenavirus. J Virol. 2004;78:3162-3169.

Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.