Kuru: Clinical Study of a New Syndrome Resembling Paralysis Agitans in Natives of the Eastern Highlands of Australian New Guinea

Zigas, Vincent; Gajdusek, D. Carleton

doi:10.5694/j.1326-5377.1957.tb60287.x

Cited by 109 publications

(36 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the groups from Papua New Guinea are the most relevant in the replication phase because our only precedent of a major acquired human prion disease epidemic is kuru, which was historically transmitted by cannibalism and had a devastating effect on the Fore and neighbouring linguistic groups of the Eastern Highland region of Papua New Guinea 5 . Kuru was extensively documented at its peak in the mid-20th century 22 . We amplified DNA from this archive and continued surveillance of kuru in the Fore in the late 20th century to identify recent cases of kuru with long incubation times and elderly Fore women with long-term survival after exposure to high doses of prions.…”

Section: Discussionmentioning

confidence: 99%

Genetic risk factors for variant Creutzfeldt–Jakob disease: a genome-wide association study

Mead

Poulter

Uphill

et al. 2009

The Lancet Neurology

134

128

View full text Add to dashboard Cite

SummaryBackgroundHuman and animal prion diseases are under genetic control, but apart from PRNP (the gene that encodes the prion protein), we understand little about human susceptibility to bovine spongiform encephalopathy (BSE) prions, the causal agent of variant Creutzfeldt–Jakob disease (vCJD).MethodsWe did a genome-wide association study of the risk of vCJD and tested for replication of our findings in samples from many categories of human prion disease (929 samples) and control samples from the UK and Papua New Guinea (4254 samples), including controls in the UK who were genotyped by the Wellcome Trust Case Control Consortium. We also did follow-up analyses of the genetic control of the clinical phenotype of prion disease and analysed candidate gene expression in a mouse cellular model of prion infection.FindingsThe PRNP locus was strongly associated with risk across several markers and all categories of prion disease (best single SNP [single nucleotide polymorphism] association in vCJD p=2·5×10−17; best haplotypic association in vCJD p=1×10−24). Although the main contribution to disease risk was conferred by PRNP polymorphic codon 129, another nearby SNP conferred increased risk of vCJD. In addition to PRNP, one technically validated SNP association upstream of RARB (the gene that encodes retinoic acid receptor beta) had nominal genome-wide significance (p=1·9×10−7). A similar association was found in a small sample of patients with iatrogenic CJD (p=0·030) but not in patients with sporadic CJD (sCJD) or kuru. In cultured cells, retinoic acid regulates the expression of the prion protein. We found an association with acquired prion disease, including vCJD (p=5·6×10−5), kuru incubation time (p=0·017), and resistance to kuru (p=2·5×10−4), in a region upstream of STMN2 (the gene that encodes SCG10). The risk genotype was not associated with sCJD but conferred an earlier age of onset. Furthermore, expression of Stmn2 was reduced 30-fold post-infection in a mouse cellular model of prion disease.InterpretationThe polymorphic codon 129 of PRNP was the main genetic risk factor for vCJD; however, additional candidate loci have been identified, which justifies functional analyses of these biological pathways in prion disease.FundingThe UK Medical Research Council.

show abstract

Section: Discussionmentioning

confidence: 99%

Genetic risk factors for variant Creutzfeldt–Jakob disease: a genome-wide association study

Mead

Poulter

Uphill

et al. 2009

The Lancet Neurology

134

128

View full text Add to dashboard Cite

show abstract

“…Although this should be interpreted with caution in view of the small numbers, it is possible that the high mean duration overall in these cases of long incubation period reflects an effect of PRNP heterozygosity on disease duration. In sharp contrast to sporadic CJD, dementia is not prominent in kuru and is indeed characteristically thought to be absent until the late or terminal stage of the disease (Zigas & Gajdusek 1957; Simpson et al . 1959; Alpers 1964 b , 1987; Hornabrook 1968).…”

Section: Discussionmentioning

confidence: 99%

A clinical study of kuru patients with long incubation periods at the end of the epidemic in Papua New Guinea

Collinge

Whitfield

McKintosh

et al. 2008

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

Kuru is so far the principal human epidemic prion disease. While its incidence has steadily declined since the cessation of its route of transmission, endocannibalism, in Papua New Guinea in the 1950s, the arrival of variant Creutzfeldt–Jakob disease (vCJD), also thought to be transmitted by dietary prion exposure, has given kuru a new global relevance. We investigated all suspected cases of kuru from July 1996 to June 2004 and identified 11 kuru patients. There were four females and seven males, with an age range of 46–63 years at the onset of disease, in marked contrast to the age and sex distribution when kuru was first investigated 50 years ago. We obtained detailed histories of residence and exposure to mortuary feasts and performed serial neurological examination and genetic studies where possible. All patients were born a significant period before the mortuary practice of transumption ceased and their estimated incubation periods in some cases exceeded 50 years. The principal clinical features of kuru in the studied patients showed the same progressive cerebellar syndrome that had been previously described. Two patients showed marked cognitive impairment well before preterminal stages, in contrast to earlier clinical descriptions. In these patients, the mean clinical duration of 17 months was longer than the overall average in kuru but similar to that previously reported for the same age group, and this may relate to the effects of both patient age and PRNP codon 129 genotype. Importantly, no evidence for lymphoreticular colonization with prions, seen uniformly in vCJD, was observed in a patient with kuru at tonsil biopsy.

show abstract

“…The colleagues who worked with Gajdusek and Zigas in 1957 are acknowledged in the second paper on kuru (Zigas & Gajdusek 1957) and the sequence of research workers who followed is given in the Introduction to these proceedings (Collinge & Alpers 2008). Indeed, the reminiscences and reflections of many of them are included in the proceedings.…”

Section: Geography and Historymentioning

confidence: 99%

The epidemiology of kuru: monitoring the epidemic from its peak to its end

Alpers

2008

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

Kuru is a fatal transmissible spongiform encephalopathy restricted to the Fore people and their neighbours in a remote region of the Eastern Highlands of Papua New Guinea. When first investigated in 1957 it was found to be present in epidemic proportions, with approximately 1000 deaths in the first 5 years, 1957–1961. The changing epidemiological patterns and other significant findings such as the transmissibility of kuru are described in their historical progression. Monitoring the progress of the epidemic has been carried out by epidemiological surveillance in the field for 50 years. From its peak, the number of deaths from kuru declined to 2 in the last 5 years, indicating that the epidemic is approaching its end. The mode of transmission of the prion agent of kuru was the local mortuary practice of transumption. The prohibition of this practice in the 1950s led to the decline in the epidemic, which has been prolonged into the present century by incubation periods that may exceed 50 years. Currently, the epidemiological surveillance is being maintained and further studies on human genetics and the past mortuary practices are being conducted in the kuru-affected region and in communities beyond it.

show abstract

Kuru: Clinical Study of a New Syndrome Resembling Paralysis Agitans in Natives of the Eastern Highlands of Australian New Guinea

Cited by 109 publications

References 7 publications

Genetic risk factors for variant Creutzfeldt–Jakob disease: a genome-wide association study

Genetic risk factors for variant Creutzfeldt–Jakob disease: a genome-wide association study

A clinical study of kuru patients with long incubation periods at the end of the epidemic in Papua New Guinea

The epidemiology of kuru: monitoring the epidemic from its peak to its end

Contact Info

Product

Resources

About