Outbreak of Acute Illness -- Southwestern United States, 1993

Beginning in May 1993, cases of acute illness characterized by fever, myalgias, headache, and cough, followed by rapid development of respiratory failure, have been reported to the New Mexico Department of Health (NMDOH), Arizona Department of Health Services (ADHS), Colorado Department of Health (CDH), and Utah Department of Health (UDH). This report presents preliminary findings from an ongoing investigation of this problem, which suggest this illness is associated with a previously unrecognized hantavirus.

On May 14, the NMDOH was notified by the Office of the Medical Investigator that two persons living in the same household had died within 5 days of each other. Their illnesses were characterized by abrupt onset of fever, myalgias, headache, and cough, followed by the rapid development of respiratory failure. Tests for Yersinia pestis and other bacterial and viral pathogens were negative. After additional persons who had recently died following a similar clinical course were reported to the the NMDOH by the Indian Health Service (IHS), the ADHS, CDH, and UDH were contacted by the NMDOH seeking other possible cases.

To identify cases, public health officials established a provisional surveillance case definition of 1) radiographic evidence of unexplained bilateral pulmonary interstitial infiltrates with hypoxemia (arterial oxygen saturation of less than 90% while breathing room air) or 2) an autopsy finding of unexplained noncardiogenic pulmonary edema occurring during 1993. Through June 7, a total of 24 case-patients have been identified. Case-patients had onsets of illness beginning in December 1992; most (14) had onset in May (Figure 1). The most recent case-patient had onset of illness June 1. Case-patients resided in New Mexico (17), Arizona (five), Utah (one), and Colorado (one). Their median age was 34 years (range: 13-87 years; 17 were aged 18-50 years). Thirteen were male. Fourteen case-patients were American Indians, nine were white, and one was Hispanic. Twelve (50%) case-patients have died.

Clinical and autopsy specimens are being processed and analyzed by CDC. Preliminary results include detection of rising titers of antibodies to hantaviruses in paired serum specimens from two of the nine case-patients; elevated single antibody titers were present in four other of the nine case-patients. The pattern of cross-reactivity to four different hantaviruses suggests that the infection is due to a previously unknown hantavirus. The NMDOH, ADHS, CDH, UDH, IHS, and CDC, with the assistance of the Navajo Nation Division of Health, are conducting intensive epidemiologic, laboratory, and environmental investigations to further define this unexplained illness cluster, determine the etiology of the illness, identify the source and mode of transmission, and develop prevention and control measures.

Reported by: F Koster, MD, H Levy, MD, G Mertz, MD, S Young, PhD, K Foucar, MD, J McLaughlin, PhD, B Bryt, MD, Univ of New Mexico School of Medicine, T Merlin, MD, Lovelace Medical Center, Albuquerque; R Zumwalt, MD, P McFeely, MD, K Nolte, MD, New Mexico Office of the Medical Examiner; M Burkhart, MPH, Secretary of Health, N Kalishman, MD, M Gallaher, MD, R Voorhees, MD, M Samuel, DrPH, M Tanuz, G Simpson, MD, L Hughes, PhD, E Umland, MD, G Oty, MS, L Nims, MS, CM Sewell, DrPH, State Epidemiologist, New Mexico Dept of Health. L Sands, DO, K Komatsu, MPH, C Kioski, MPH, K Fleming, MA, J Doll, PhD, C Levy, MS, TM Fink, P Murphy, B England, MD, M Smolinski, MD, B Erickson, PhD, W Slanta, G Gellert, MD, State Epidemiologist, Arizona Dept of Health Svcs. P Schillam, MSPH, RE Hoffman, MD, State Epidemiologist, Colorado Dept of Health. S Lanser, MPH, CR Nichols, MPA, State Epidemiologist, Utah Dept of Health. L Hubbard-Pourier, MPH, Div of Health, Navajo Nation, Window Rock, Arizona. J Cheek, MD, A Craig, MD, R Haskins, MPH, B Muneta, MD, B Tempest, MD, Indian Health Svc. Div of Field Epidemiology, Epidemiology Program Office; National Center for Environmental Health; Div of Bacterial and Mycotic Diseases, Div of Vector-Borne Infectious Diseases, and Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: The preliminary laboratory findings of this investigation suggest a possible role for a hantavirus or related agent as a cause of this outbreak. Although this unexplained illness shares some clinical features with syndromes caused by hantaviruses, it lacks the prominent renal involvement and hemorrhagic manifestations previously reported with these agents (1). Additional data are necessary to confirm these preliminary results. If verified, the role of this agent in the pathogenesis of the illnesses will require further study.

Isolation of the first recognized hantavirus (Hantaan virus) was reported from Korea in 1978 (2). Although there are four recognized members (Hantaan, Puumala, Seoul, and Prospect Hill) of the genus Hantavirus of the family Bunyaviridae (3), additional unidentified members likely exist. Hantaan, Puumala, and Seoul viruses are known human pathogens; Prospect Hill has not been associated with disease. Since the 1930s, epidemic and sporadic hantavirus-associated disease has been described throughout Eurasia, especially in Scandinavia and northeastern Asia. In the 1950s, thousands of United Nations military personnel were infected with hantaviruses during the Korean conflict (1); more recently, transmission has been documented among U.S. military personnel training in Korea (4). Hantaviruses have been isolated from rodents in the United States (5), and serologic studies have documented human infections with hantaviruses (6). However, acute disease associated with infection by pathogenic hantaviruses has not previously been reported in the Western Hemisphere.

The clinical manifestations of infection with these viruses vary; illness resulting from Hantaan virus infection generally includes fever, renal abnormalities, and in severe cases, shock, bleeding, and pulmonary edema (1). The incubation period for the known pathogenic hantaviruses, although highly variable, generally ranges from 2 to 4 weeks (3).

Rodents are the natural hosts for all known hantaviruses (3). Humans are thought to be at risk for infection after exposure to rodent excreta, either through the aerosol route or direct inoculation. There is no evidence of person-to-person transmission for any of the known hantaviruses, nor has occupational transmission been documented to health-care workers. Laboratory workers practicing universal precautions while processing routine clinical materials (such as blood, urine, and respiratory specimens) are not considered to be at increased risk for hantavirus infection. However, laboratory-acquired infections have occurred among persons who handled infected wild or laboratory rodents (7). Therefore, laboratory work that may result in propagation of hantaviruses should be conducted in a biosafety level 3 facility (8).

No restriction of travel to areas affected by this outbreak is considered necessary; however, activities that may disrupt rodent burrows or result in contact with rodents or aerosolization of rodent excreta should be avoided. In the affected area, measures prudent for rodent control should be carried out in domestic settings, including wetting of rodent nests and dead rodents with disinfectant before their removal, securing foods from rodent access, and trapping rodents indoors. Broader measures to control rodents will be recommended once the specific rodent host(s) has been identified and the expected effects on the ecology of local rodentborne diseases, particularly plague, have been considered.

In one controlled study, intravenous administration of the antiviral drug ribavirin was effective in treating severe cases of hantavirus infection when administered early in the course of illness (9). However, intravenous ribavirin is not licensed for use in the United States. Therefore, in the affected areas of the Southwest, clinicians considering use of ribavirin for treatment of potential cases should consult with their state health department.

The surveillance case definition used in this investigation is provisional. As additional information is gathered and the etiologic agent is characterized, the definition may require revision. Suspected cases should be reported immediately to public health authorities for further investigation. CDC has established a hotline to provide updated information on the unexplained illness outbreak and to report suspected cases; the number is (800) 532-9929.

This cluster of unexplained acute illnesses in the Southwest illustrates the potential for new infectious disease problems to emerge at any time within the United States (10). These diseases may emerge because of microbial adaptation, environmental disturbances or changes, or population shifts. Vigilance and surveillance are required to rapidly recognize and determine the etiology of these emerging microbial threats to health so that prevention and control strategies can be implemented.

References

1. Sheedy JA, Froeb HF, Batson HA, et al. The clinical course of epidemic hemorrhagic fever. Am J Med 1954;16:619-28.

2. Lee HW, Lee PW, Johnson KM. Isolation of the etiologic agent of Korean hemorrhagic fever. J Infect Dis 1978;137:298-308.

3. McKee KT Jr, LeDuc JW, Peters CJ. Hantaviruses. In: Belshe RB, ed. Textbook of human virology, 2nd ed. St. Louis: Mosby Year Book, 1991:615-32.

4. CDC. Korean hemorrhagic fever. MMWR 1988;37:87-90,95-6.

5. LeDuc JW, Smith GA, Johnson KM. Hantaan-like viruses from domestic rats captured in the United States. Am J Trop Med Hyg 1984;33:992-8.

6. Childs JE, Glass GE, Korch GW, et al. Evidence of human infection with a rat-associated hantavirus in Baltimore, Maryland. Am J Epidemiol 1988;127:875-8.

7. Desmyter J, LeDuc JW, Johnson KM, Brasseur F, Deckers C, van Ypersele de Strihou C. Laboratory rat associated outbreak of haemorrhagic fever with renal syndrome due to Hantaan-like virus in Belgium. Lancet 1983;2:1445-8.

8. CDC/National Institutes of Health. Biosafety in microbiological and biomedical laboratories. 2nd ed. Atlanta: US Department of Health and Human Services, CDC, 1988; DHHS publication no. (CDC)88-8395.

9. Huggins JW, Hsiang CM, Cosgriff TM, et al. Prospective, double-blind, concurrent, placebo-controlled clinical trial of intravenous ribavirin therapy for hemorrhagic fever with renal syndrome. J Infect Dis 1991;164:119-27.

10. Lederberg J, Shope RE, Oaks SC Jr, eds. Emerging infections: microbial threats to health in the United States. Washington, DC: National Academy Press, 1992.

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