Reexamination of Human Rabies Case with Long Incubation, Australia

To the Editor: Long incubation periods are an occasional feature of infection with rabies virus and should be considered in human cases of acute encephalitis in rabies-free countries where there has been a history of travel to rabies-endemic areas (1). Until 1987 Australia had recorded only 1 case of travel-acquired rabies. However, in 1990 an extreme case of long-incubation rabies was diagnosed. The patient was a 10-year-old girl of Vietnamese origin in whom rabies developed after she had lived continuously in Australia for almost 5 years (2). A thorough investigation of the case history by public health offi cers concluded that the likely source of infection was Vietnam, which the girl left in July 1984, suggesting an incubation period >6.5 years. Preliminary sequence analysis of a fragment of the rabies virus genome extracted from postmortem samples taken from the patient confi rmed that the likely origin was Southeast Asia (3). Since that time, 2 major developments occurred that suggested that the case should be reexamined. The fi rst was the discovery of a bat lyssavirus in Australia (4). In addition to being closely related to rabies virus, Australian bat lyssavirus (ABLV) had been isolated from 2 patients with fatal cases in Australia, one of whom was deduced to have had a potential incubation period of 27 months (5). The second development was the increase in phylogenetic investigations of rabies viruses in many countries across Asia including Sri Lanka, the Philippines, India, People's Republic of China (6), Indonesia, and, importantly , Vietnam (7). After the patient's death, a decomposed sample of the patient's brain was sent to the Australian Animal Health Laboratory at Geelong. Although live virus was not isolated from this sample, several short sequences of the viral genome were am-plifi ed by PCR. From one of these, a 200-bp sequence of the nucleoprotein gene was derived that confi rmed the clinical diagnosis of rabies. This sequence was compared to a small panel of virus sequences known at the time. Although limited, with no representative sequences from Vietnam, this early comparison indicated that the virus was of Asian origin (3). To reinvestigate this case, we reassessed one of the other virus sequences originally generated from this case with a panel of rabies virus sequences from Southeast Asia, including viruses from Vietnam, China, and examples of ABLV. The original DNA fragment that yielded this sequence was also amplifi ed from post-mortem …