ABSTRACT
Creutzfeldt-Jakob disease (CJD), GerstmannSträussler-Scheinker disease (GSS) and fatal familial insomnia (FFI) belong to a group associated with fatal, neurodegenerative, subacute, transmissible spongiform encephalopathy (TSE) in humans.1,2 Overall, TSE diseases are rare in humans, with an incidence of approximately one case/million people per year, and have remained stable over the past few decades.1,3 Epidemiological studies have so far failed to provide any link between gender, occupational exposures, geographical locations, environmental factors and the frequency of disease. The exception is in cases where there is a familial link between the affected individuals.1-3
Cases of CJD and GSS have been known since the 1930s.4,5 However, owing to their rarity, these diseases had not received much attention for decades, until the 1950s when a new disease, kuru, was discovered.6 ‘Kuru’ means ‘to tremble’ in the Fore language of the east highland of Papua New Guinea, thus, kuru vividly describes the clinical symptoms of the disease.6 The disease occurs mostly in women and children. It was postulated that kuru was caused by some genetic factors in association with unknown
social and environmental factors. A major advance in the understanding of kuru was the serendipitous discovery that the spongiform histopathology seen in the brain of kuru patients was similar to that found in scrapie, a TSE in sheep and goats.6,7
Scrapie has existed in Britain since the 1750s.8 While earlier attempts by Gajdusek and colleagues to transmit kuru from human to primates were unsuccessful, based on this new lead, Gajdusek and Gibbs were able to transmit first kuru, then CJD and then GSS from human to non-human primates.2,9 It was speculated that natural transmission of kuru might have occurred through cannibalism, which was practiced during the funeral ceremony by the Fore people. Cessation of cannibalism since the 1950s has gradually eliminated the disease in that region of the world. The incubation period of kuru could be as long as 4-5 decades.1,2
Recently, human TSE diseases have been classified according to the pathogenic mechanisms of the disease.1 Therefore, human TSE
diseases are classified as inherited, infectious and of a sporadic nature.1 Infectious human TSE disease was most vividly demonstrated in kuru. Physicians in a variety of medical procedures have also inadvertently transmitted diseases, which are commonly referred to as the iatrogenic CJD.1 The recently emerged variant CJD (vCJD) mostly in Great Britain is believed to be acquired from cattle affected by bovine spongiform encephalopathy (BSE).10,11 Approximately 10-15% of human TSE is inherited. Most of the cases of human TSE diseases occur sporadically, and the pathogenic mechanisms remain unknown3 (Table 46.1).
