Unexplained Rabies in Three Immigrants in the United States

BACKGROUND: Extensive investigation of three patients who died of rabies in the United States failed to reveal any source of exposure to the disease. The three patients had immigrated to the United States from areas in Laos, the Philippines, and Mexico where rabies is endemic. METHODS: We studied rabies viruses isolated from the three patients, other patients with a known source of exposure, and animals in the United States, Thailand (as a proxy for Laos), the Philippines, and Mexico. The viruses were characterized by indirect immunofluorescence and neutralization tests according to their reactions to panels of monoclonal antibodies. Transcribed complementary DNA from these isolates was amplified by the polymerase chain reaction; the DNA product was then analyzed by differential digestion with restriction enzymes. RESULTS: The viral isolate from each of the three patients was a rabies variant with distinctive antigenic or genetic characteristics. For each of the three isolates, identical variants were found in specimens from rabid animals obtained from or near the country in which the patient lived before immigrating to the United States. None of these variants were found among the isolates collected from rabid animals in the United States. CONCLUSIONS: Rabies infection in these three patients did not originate in the United States but resulted from exposures in Laos, the Philippines, and Mexico. Since the three patients had lived in the United States for 4 years, 6 years, and 11 months, our findings suggest that the onset of the clinical manifestations of rabies occurred after long incubation periods.