Kuru: more detail

What is the epidemiological outline?

Kuru affected the Fore people and neighbouring groups in the eastern highlands of Papua New Guinea. Oral histories place its first appearance around the start of the twentieth century in a Keiagana village, reaching the North Fore around 1920 and spreading through the region over following decades, with some southwestern and southeastern areas unaffected until the 1940s.

Australian patrol officers described it first: Arthur Carey asked for a medical diagnosis in 1951, John McArthur described it in 1953 and Frank Earl suggested in 1955 that it might be a form of encephalitis. The first medical publications were by Gajdusek and Zigas in 1957, and Klatzo and colleagues published the first neuropathological examination in 1959.

Transmission was through endocannibalism in mortuary ritual, with women and children most exposed. The practice was suppressed by 1956 and had effectively ceased by 1960, and the authors of the 2008 clinical study state that transmission through traditional mortuary practice had ceased by that year. No other route was identified.

What do the incubation data show?

They are the longest documented in human disease. The 2008 study identified 11 patients between July 1996 and June 2004, seven men and four women, with ages at onset of 46 to 63 years. Counting from 1960, minimum incubation periods were 34 to 41 years. For the seven men, counting from age 7, likely incubation was 39 to 56 years, and the authors state that periods in some cases exceeded 50 years.

The authors attributed the persistence of cases for four decades after transmission stopped to incubation length rather than to continued transmission. They also noted the selection problem in their own series: shorter-incubation cases are likely overrepresented, because many people with longer incubation would have died of other causes first.

From this they argued that mean incubation periods of 30 years or more should be considered possible, and perhaps probable, for human BSE infection, given the additional cattle-to-human transmission barrier. That inference is the main reason kuru data still appear in variant CJD risk assessment and in donor deferral discussions. Iatrogenic CJD: more detail sets out the comparable figures for medical routes, where growth hormone cases ran to 42 years.

How was the clinical course staged?

The Fore staging is still the clearest description of a prion syndrome dominated by cerebellar involvement.

A prodrome of headache, limb aches and joint pain lasted several months. Stage 1, the ambulatory stage, was progressive gait ataxia with a mean duration of about eight months. Stage 2, sedentary, began with the loss of unsupported walking and lasted about two to three months. Stage 3, recumbent, began with the inability to sit unsupported and was followed by a terminal phase of one to two months.

In the 11 patients, total illness duration ranged from 10 to 25 months with a mean of 17 months. Two patients had marked cognitive impairment in stage 2, which the authors noted was not typical of earlier descriptions, so the classical account of late cognitive involvement should be read as a tendency rather than a rule.

The pathology also differed from variant CJD in one respect worth noting. In a patient who underwent tonsil biopsy there was no evidence of prion colonisation of lymphoreticular tissue, unlike the uniform finding in variant CJD. Peripheral tissue involvement is therefore not a general property of acquired human prion disease.

What did kuru establish about PRNP?

Two findings, both still in use.

The first is codon 129. In the 2008 series DNA was available for 10 of the 11 patients: eight were methionine-valine heterozygotes, one methionine homozygous and one valine homozygous, and the two homozygotes had the shortest illnesses, at 12 and 10 months. Heterozygote excess among late cases is consistent with heterozygosity conferring longer incubation and partial resistance, which is the same polymorphism that now modifies risk and survival across the sporadic, acquired and inherited forms. PRNP variants sets out its role.

The second is codon 127. A 2009 study assessed more than 3,000 people from the Eastern Highlands, including 709 who had taken part in mortuary feasts, of whom 152 later died of kuru. A variant, G127V, was found only in the kuru region, was present in about half of otherwise susceptible women from the highest-exposure area who were 129 methionine homozygotes, and was absent from kuru patients and from unexposed populations worldwide. Families carrying the allele had significantly lower kuru incidence than geographically matched controls. The authors described it as an acquired prion disease resistance factor selected during the epidemic, and presented codons 127 and 129 together as an example of recent natural selection in humans.

G127V has since been taken up as a starting point for therapeutic work on dominant-negative inhibition of prion propagation. That literature is laboratory work rather than clinical evidence, and kuru for researchers is where it belongs.

What should be said to families who raise kuru?

Two things, usually. Kuru does not occur now: the practices that transmitted it ended more than six decades ago, and CDC lists it among the historical human prion diseases. And its transmission route says nothing about ordinary contact with a person who has CJD, for which there is no evidence of spread. Myths and facts is the page written for that conversation.

The one point that does transfer is incubation length, which is relevant to people who had a documented medical exposure decades ago rather than to the general public.

Where next?

Kuru is the plain version for families. The history of prion disease places the kuru work in sequence, how prion disease is diagnosed covers current diagnosis and what to expect the care of a progressive cerebellar syndrome.

This page summarises published literature and is not clinical advice.