Arenaviruses: Lassa Fever, Lujo Hemorrhagic Fever, Lymphocytic Choriomeningitis, and the South American Hemorrhagic Fevers

Abstract

Arenaviruses are single-stranded RNA viruses that are grouped taxonomically into Old World/lymphocytic choriomeningitis (i.e., Africa, Europe, Asia, and Oceania) and New World/Tacaribe (i.e., the Americas) complexes. Over 40 arenaviruses have been identified to date, although a minority are recognized human pathogens. Arenaviruses are maintained in nature by chronic infection in rodents of the Muridae and Cricetidae families. There is a tight reservoir rodent–virus species pairing that limits the endemic area of each arenavirus to the geographic distribution of its specific reservoir. The geographic distribution of infected rodents is usually considerably restricted relative to the entire range of the species. Since most rodent reservoirs inhabit rural sylvatic niches, primary arenavirus infection in humans occurs almost exclusively in rural and often remote settings. The incidence of human infection may vary considerably with variations in rodent population densities that may relate to climatic and seasonal weather changes and human-induced habitat perturbation, especially agricultural expansion converting forest to cultivated fields. Infected rodents shed virus in urine, feces, and saliva and primary human infection occurs through contact with these biological substances. Secondary human-to-human transmission may occur, especially with viruses of the Old World complex, through contact with bodily fluids, most often to those caring for sick persons at home or in healthcare centers. However, secondary attack rates are generally low as long as strict barrier nursing practices are observed. Large outbreaks are almost always fueled by nosocomial transmission, usually in resource-poor regions where barrier nursing practices may not be maintained. Arenaviruses classically cause two distinct syndromes in humans—central nervous system disease (lymphocytic choriomeningitis and Dandenong viruses) and hemorrhagic fever (Lassa and Lujo viruses in Africa and Junín, Machupo, Guanarito, Sabiá, and Chapare viruses in South America)—although many arenavirus infections may be asymptomatic or result in a nonspecific febrile illness. Treatment options include the antiviral drug ribavirin and convalescent immune plasma. Some arenaviruses are considered “Select Agents” that could possibly be used as bioweapons. The nonspecific clinical presentation and general lack of readily available laboratory testing for arenavirus infection pose significant challenges to diagnosis. The remote and geographically restricted endemic areas, often in resource-poor countries, apparent rarity of most arenaviral infections in humans, and challenges to diagnosis make surveillance and reliable estimates of infection and disease difficult. Control methods generally involve integrated pest management strategies to limit human contact with rodent excreta and the use of appropriate personal protective materials for those at occupational risk through patient care, laboratory exposure, or fieldwork. During outbreaks, intensive rodent trap** in villages, as well as aggressive case identification, patient isolation, and contact tracing may all be needed. Vaccines are generally in the development stages. Further research and public health advances are needed to understand the complex epizoologic, epidemiologic, and ecologic interplay of arenaviruses that result in human disease, with the ultimate goal being the capacity to predict the emergence of these viruses and thus take steps to prevent human infections.