Isolation and characterization of the subacute spongiform virus encephalopathies of man: kuru and Creutzfeldt-Jakob disease.

Kuru, a chronic subacute heredofamilial disease of man in the eastern highlands of New Guinea, and Creutzfeldt-Jakob disease, one of the presenile dementias which occurs sporadically and in familial patterns in man throughout the world, are caused by infectious agents which are experimentally transmissible from man to chimpanzees and several Both kuru and Creutzfeldt-Jakob disease are associated with long, asymptomatic incubation periods of from several months to several years. Although they have infection as their aetiology neither disease manifests the cardinal signs associated with acute viral infections. There is no cerebrospinal fluid pleocytosis or significant elevated proteins, haemato-logical values and clinical chemistry findings are within normal limits, and there is no febrileresponse at any stage of disease. Both diseases always terminate in death of the patient or experimentally affected animal following a clinical course of ataxia, incoordination, disturbed gait, titubation, myo-clonus, fasciculations, and wasting lassitude. Histo-pathological lesions are restricted to the central nervous system, primarily the grey matter of the brain, and consist of neuronal vacuolation and dropout, astrocytic hypertrophy and proliferation, and varying degrees of intracellular status spongiosis. In addition, in the primary disease in man PAS-positive, doubly refractive birefringent amyloid plaques and a loss of Purkinje cells are observed in the brain. Evidence of inflammatory reaction is either totally lacking or only minimally present. However, these clinical and histopathological findings are not entirely specific for kuru and Creutzfeldt-Jakob disease but are also characteristic for two animal diseases, scrapie of sheep and mink encephalopathy. Both animal diseases, like their human counterparts, are transmissible to a wide variety of experimental hosts. Because of the striking similarities clinically and histologically between these four diseases-kuru, Creutzfeldt-Jakob disease, scrapie, and mink encephalopathy-we have designated them the prototype viruses of a new group of infectious agents which we have called the subacute spongiform encephalopathies. Such virus-induced spongiform encephalopathies can no longer be looked upon as medical exotica (Asher, Gajdusek, and Gibbs, 1971). They are transmissible diseases which present actual problems of concern to neurologists, neuropathologists, gerontologists, and infectionists as well as to virol-ogists. Indeed, as Dr Gajdusek has already pointed out in the preceding paper, during the past seven years since kuru has been transmitted, it has become increasingly evident that there are many human patients dying with presenile degenerative diseases of the brain which are difficult to classify but which may well be 'slow infections' of virus aetiology. Such subacute and chronic inflammatory …