Kuru in the 21st century—an acquired human prion disease with very long incubation periods
Abstract
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.
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8 of 10 of the last known kuru patients studied at the very end of the epidemic (1996-2004) were heterozygous at the PRNP codon 129.
“The last 11 known kuru patients studied at the very end of the epidemic (1996–2004) had an estimated minimum incubation period of 34 to 41 years; 8 of 10 were heterozygous at the PRNP codon 129 (39).”
From Kuru (2012) · cites this paper as [39]
The last 11 known kuru patients studied at the very end of the epidemic (1996-2004) had an estimated minimum incubation period of 34 to 41 years.
“The last 11 known kuru patients studied at the very end of the epidemic (1996–2004) had an estimated minimum incubation period of 34 to 41 years; 8 of 10 were heterozygous at the PRNP codon 129 (39).”
From Kuru (2012) · cites this paper as [39]
Kuru is a uniformly fatal and remarkably stereotyped cerebellar ataxic syndrome accompanied by tremor and choreiform and athetoid movements.
“Kuru is a uniformly fatal and remarkably stereotyped cerebellar ataxic syndrome accompanied by tremor and choreiform and athetoid movements (27, 39, 57–61)”
From Kuru (2012) · cites this paper as [39]
Kuru is associated with prolonged incubation periods that may exceed five decades.
“Kuru is associated with prolonged incubation periods that may exceed five decades.3”
From A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure (2009) · cites this paper as [3]
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- Authors
- Collinge, J., Whitfield, J., McKintosh, E., Beck, J., Mead, S., Thomas, D. J., & Alpers, M. P.
- Affiliations
- MRC Prion Unit (GB)
- Curtin University (AU)
- Corresponding author
- Collinge, John
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2006-06
- Volume
- 367
- Issue
- 9528
- Pages
- 2068-2074
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2112140556
- Semantic Scholar
- 4c435abf3bd542b6fed7258d56e2872a2cde0a71
- Cited by
- 427
- References
- 36
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 13 · 2023: 33 · 2022: 14 · 2021: 16 · 2020: 18 · 2019: 14 · 2018: 18 · 2017: 24 · 2016: 20 · 2015: 14 · 2014: 16 · 2013: 15 · 2012: 29
- FWCI
- 12.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Amyloidosis: Diagnosis, Treatment, Outcomes
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- kuru, human prion disease, incubation period, variant Creutzfeldt-Jakob disease, bovine spongiform encephalopathy, PRNP codon 129 polymorphism, genetic susceptibility, interspecies transmission
- MeSH terms
- Prion Proteins, Aged, Amyloid, Child, Female, Funeral Rites, Humans, Kuru, Male, Middle Aged, New Guinea, Polymorphism, Genetic, Population Surveillance, Prions, Protein Precursors, Time Factors
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