Kuru in the 21st century--an acquired human prion disease with very long incubation periods.

BACKGROUND: Kuru provides the principal experience of epidemic human prion disease. Its incidence has steadily fallen after the abrupt cessation of its route of transmission (endocannibalism) in Papua New Guinea in the 1950s. The onset of variant Creutzfeldt-Jakob disease (vCJD), and the unknown prevalence of infection after the extensive dietary exposure to bovine spongiform encephalopathy (BSE) prions in the UK, has led to renewed interest in kuru. We investigated possible incubation periods, pathogenesis, and genetic susceptibility factors in kuru patients in Papua New Guinea.

METHODS: We strengthened active kuru surveillance in 1996 with an expanded field team to investigate all suspected patients. Detailed histories of residence and exposure to mortuary feasts were obtained together with serial neurological examination, if possible.

FINDINGS: We identified 11 patients with kuru from July, 1996, to June, 2004, all living in the South Fore. All patients were born before the cessation of cannibalism in the late 1950s. The minimum estimated incubation periods ranged from 34 to 41 years. However, likely incubation periods in men ranged from 39 to 56 years and could have been up to 7 years longer. PRNP analysis showed that most patients with kuru were heterozygous at polymorphic codon 129, a genotype associated with extended incubation periods and resistance to prion disease.

INTERPRETATION: Incubation periods of infection with human prions can exceed 50 years. In human infection with BSE prions, species-barrier effects, which are characteristic of cross-species transmission, would be expected to further increase the mean and range of incubation periods, compared with recycling of prions within species. These data should inform attempts to model variant CJD epidemiology.