Fatal Illnesses Associated With a New World Arenavirus --- California, 1999--2000

The California Department of Health Services (CDHS) and the University of Texas Medical Branch (UTMB) recently identified evidence of infection with an arenavirus in three patients hospitalized with similar fatal illnesses. This report summarizes the investigation of these cases.

Patients had onset of illness during June 1999--May 2000. They were aged 14, 30, and 52 years; all were female. Two resided in southern California and the third in the San Francisco Bay area. The patients did not have any activities in common, and none had a history of travel outside California during the 4 weeks preceding their illness.

Illnesses were associated with nonspecific febrile symptoms including fever, headache, and myalgias. Within the first week of hospitalization, lymphopenia (25--700 per mm³) was observed in all three patients, and thrombocytopenia (30,000--40,000 per mm³) was seen in two. All three patients had acute respiratory distress syndrome and two developed liver failure and hemorrhagic manifestations. All patients died 1--8 weeks after illness onset.

Arenavirus-specific RNA was detected in one or more materials from each patient using a nested RT-PCR assay. In addition, infectious arenavirus was recovered from materials from the 14-year-old patient by cultivation of the virus in monolayer cultures of Vero E6 cells; virus isolation attempts on materials from the 30-year-old patient are under way. The nucleotide sequence of the PCR products amplified from the patients essentially were identical and shared 87% identity with the Whitewater Arroyo (WWA) virus prototype strain (an arenavirus recovered from a Neotoma albigula [white-throated woodrat]) from New Mexico in the early 1990s). Serologic assays (indirect fluorescent antibody assay and IgG enzyme immunoassay) for arenavirus antibody were negative for all three patients.

Family members of the three patients were interviewed about activities and potential exposure sites during the month before illness onset. One patient reportedly cleaned rodent droppings in her home during the 2 weeks before illness onset; no history of rodent contact was solicited for the other two patients.

Reported by: RG Byrd, MD, LA Cone, MD, BC Commess, MD, Riverside County; D Williams-Herman, MD, JM Rowland, MD, B Lee, MD, Alameda County; MW Fitzgibbons, MD, Orange County; CA Glaser, MD, MT Jay, DVM, Cl Fritz, DVM, MS Ascher, MD, M Cheung, MD, VL Kramer, PhD, K Reilly, DVM, DJ Vugia, MD, Acting State Epidemiologist, California Dept of Health Svcs. CF Fulhorst, DVM, ML Milazzo, RN Charrel, MD, Center for Tropical Diseases, Univ of Texas Medical Br, Galveston, Texas. Special Pathogens Br, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases.

Editorial Note:

Arenaviruses are rodentborne enveloped RNA viruses. Several arenaviruses cause viral hemorrhagic fever syndromes in Africa and South America. The Old World arenaviruses include the agents of Lassa fever and lymphocytic choriomeningitis (LCM). LCM virus, associated with the house mouse (Mus musculus), is the only Old World arenavirus that occurs in the Americas. The South American hemorrhagic fever viruses belong to the Tacaribe complex or New World arenaviruses (e.g., Guanarito, Junin, Machupo, and Sabia).

WWA is found in North America among woodrats (Neotoma spp.) (1,2) and has not previously been known to cause disease in humans. Of 20 Neotoma spp. with species status, nine occur in the United States (3). The geographic range of these species incorporates most of the United States. At least five of the nine U.S. species may harbor the virus; however, complete description of its distribution requires further study (1,2). The abundance and habits of woodrats suggest that potential contact between Neotoma spp. and humans is limited.

Preventive measures for arenavirus infections include control and exclusion of rodents in and around human dwellings. Direct contact with rodents, their excreta, and nesting materials should be avoided. Areas and surfaces potentially contaminated by rodent excreta should be wet with a disinfectant before removal. Rodent carcasses and materials should be double-bagged before disposal. Although rare, person-to-person transmission has been documented for some New World viruses; nosocomial transmission can occur through direct contact with an infected patient's blood, urine, or pharyngeal secretions (4,5). Standard precautions should be used during treatment of patients with suspected arenavirus infection and standard precautions plus contact/droplet/aerosol-specific precautions should be used for patients with severe clinical manifestations (6,7).

CDHS and UTMB, in cooperation with CDC and other agencies, are continuing to investigate these three cases. A determination of the spectrum of illness with WWA will require increased clinical surveillance and community studies to define a precise disease-to-infection ratio and case fatality.

Appropriate laboratory diagnostic tests are being developed to support these efforts. In clinical specimens, the virus is either present in low concentrations or is difficult to isolate with methods commonly used for other arenaviruses. Efforts are under way to evaluate whether specific detection of virus antigens in blood or tissues, presence of specific IgM in the serum of patients, or postmortem diagnostic tests (e.g., immunohistochemistry) can be added to virus isolation and RT-PCR for laboratory diagnosis of infection with this virus. Suspected cases should be reported to local and state health departments or to CDC's Special Pathogens Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, telephone (404)639-1510.

References

1. Kosoy MY, Elliot LH, Ksiazek TG, et al. Prevalence of antibodies to arenaviruses in rodents from the southern and western United States: evidence for an arenavirus associated with the genus Neotoma. Am J Trop Med Hyg 1996;54:570--6.
2. Fulhorst CF, Bowen MD, Ksiazek TG, et al. Isolation and characterization of Whitewater Arroyo virus, a novel North American arenavirus. Virol 1996;224:114--20.
3. Musser GG, Carleton MD, Family M, Wilson DE, Reeder DM, eds. Mammal species of the world: a taxonomic and geographic reference. 2nd ed. Washington, DC, and London: Smithsonian Institution Press, 1993.
4. Peters CJ, Kuehne RW, Mercado RR, Le Bow RH, Spertzel RO, Webb PA. Hemorrhagic fever in Cochabamba, Bolivia, 1971. Am J Epidemiol 1974;99:425--33.
5. CDC. Bolivian hemorrhagic fever---El Beni Department, Bolivia, 1994. MMWR 1994;43:942--5.
6. CDC. Management of patients with suspected viral hemorrhagic fever. MMWR 1988;37:1--16.
7. CDC. Update: management of patients with suspected viral hemorrhagic fever---United States. MMWR 1995;44:475--9.

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