Variant Creutzfeldt-Jakob disease could have an incubation time of 30 years or longer and could affect a wider population than currently forecast, according to new research on patients with a similar human prion disease.
Researchers examined 11 recent cases of kuru, a prion protein disease that became an epidemic in the mid-1900s among several groups of Papua New Guinea natives, resulting from their ritual cannibalism, reported John Collinge, Ph.D., a professor of neurology at University College London, and his colleagues (Lancet 2006;367:2068–74).
Cannibalism practices were banned by the Australian authorities in the mid-1950s, and researchers are confident they have been nonexistent since 1960. However, because kuru disease still affects Papua New Guinea natives, researchers have been able to determine long incubation times.
Dr. Collinge and his colleagues monitored 11 cases of kuru disease in Papua New Guinea beginning in 1996, with disease onset between November 1994 and October 2001. The average age of patient onset was 46 years or older.
The oldest patient at disease onset was a 63-year-old man in 1996. The minimum incubation time for the patient was 36 years. However, because young boys traditionally stopped participating in the cannibalism ritual around the age of 7 years, the likely incubation period was 56 years, the researchers reported.
The mean incubation period for kuru is currently estimated to be about 12 years.
Of the 11 patients, 8 were heterozygous for valine and methionine at codon 129 of the human prion protein gene. That distribution of heterozygous genotypes within the kuru patients did not, however, differ markedly from the surrounding population.
Although kuru disease's lethality arose from intraspecies recycling of infectious prions, the results of the latest research suggest that prion diseases, such as variant Creutzfeldt-Jakob disease (vCJD), may have longer incubation times than current models now pose.
Genetic transmission barriers may limit the number of people who acquire vCJD by consuming meat infected with bovine spongiform encephalopathy (BSE). Those who have already suffered from the disease may have been genetically predisposed to have shorter incubation times. Meanwhile, the research on kuru patients demonstrates that prion diseases can also have very long incubation times, “approaching (and perhaps exceeding) the typical human life span,” according to the researchers.
“Therefore, a human BSE epidemic may be multiphasic, and recent estimates of the size of the vCJD epidemic based on uniform genetic susceptibility could be substantial underestimations,” they wrote.
“Genes implicated in species-barrier effects, which would further increase both the mean and range of human BSE incubation periods, are also probably relevant. In this context, a human epidemic will be difficult to accurately model until such modifier loci are identified and their gene frequencies in the population can be measured.”