Elsevier

The Lancet

Volume 367, Issue 9528, 24–30 June 2006, Pages 2068-2074
The Lancet

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

https://doi.org/10.1016/S0140-6736(06)68930-7Get rights and content

Summary

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.

Section snippets

Research ethics

Our study was approved by the Papua New Guinea Medical Research Advisory Committee and by the local research ethics committees of St Mary's Hospital and National Hospital for Neurology and Neurosurgery, in London, UK. The full participation in the project from the communities, which was critical with respect to the ethics and operation of the study, was established and maintained through discussions with village leaders, communities, families, and individuals, and the field studies followed the

Results

The total number of cases of kuru from 1957 to 2004 exceeded 2700, with more than 200 dying every year in the late 1950s. This number fell to about six a year in the early 1990s and between one and two a year during the study; since July, 1996, we identified 11 kuru patients up to the end of June, 2004.

Table 1 shows the ages at onset of all 11 patients in the study. Age might not be accurately known or reported by individuals in these communities, but can be reliably and accurately estimated by

Discussion

The early clinical, epidemiological, and anthropological study of kuru; the recognition of its neuropathological, and then causal parallels to ovine scrapie;20 and then crucially, the experimental transmission of the disease to primates,21 originated the concept of the human transmissible spongiform encephalopathies, which was followed in turn by the eventual unifying concept of the mammalian prion diseases. However, in addition to the central historical importance of kuru, study of the

References (36)

  • J Collinge

    Prion diseases of humans and animals: their causes and molecular basis

    Annu Rev Neurosci

    (2001)
  • CA Donnelly et al.

    Implications of BSE infection screening data for the scale of the British BSE epidemic and current European infection levels

    Proc R Soc Lond B Biol Sci

    (2002)
  • AC Ghani et al.

    Updated projections of future vCJD deaths in the UK

    BMC Infect Dis

    (2003)
  • SE Lloyd et al.

    Identification of multiple quantitative trait loci linked to prion disease incubation period in mice

    Proc Natl Acad Sci USA

    (2001)
  • J Collinge

    Molecular neurology of prion disease

    J Neurol Neurosurg Psychiatry

    (2005)
  • MP Alpers

    Epidemiology and clinical aspects of kuru

  • MS Palmer et al.

    Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease

    Nature

    (1991)
  • HS Lee et al.

    Increased susceptibility to Kuru of carriers of the PRNP 129 methionine/methionine genotype

    J Infect Dis

    (2001)

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