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

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

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

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

Personnalité métaphysique et rites traditionnels mortuaires Sud Fore

Ethnographic studies on Melanesian concepts of the human body and religion have expanded our understandings of the concept of personhood. Melanesian ethnographers have used a number of descriptive words to describe the metaphysical components of the person, including: soul, spirit, life force, ghost, and vital and spiritual essence. By investigating the traditional mortuary rites of the South Fore people in Papua New Guinea, which included the practice of endocannibalism, investigators were able to distinguish the 5 souls of the composite metaphysical person and their relationship to the humors of the body. An understanding of the South Fore cosmology and its relationship to its human inhabitants was required to understand these deeply embedded concepts. The South Fore person was found to be composed of 5 souls and bodily humors which together formed a composite individual, yet partible through division. We elucidated the concepts of the 5 souls of the Fore person, which revealed a strong correlation between the landscape with its overlying cosmology and the cultural bodily humors, and demonstrated their relationship to the power of the land.Les études ethnographiques sur les concepts mélanésiens du corps humain et la religion ont élargi notre compréhension de la notion de personnalité. Les ethnographes mélanésiens ont utilisé un certain nombre de mots descriptifs pour décrire les composants métaphysiques de la personne, y compris l'âme, l'esprit, la force de vie, le fantôme et l'essence vitale et spirituelle. En enquêtant sur les rites funéraires traditionnels du peuple du Sud Fore (PNG), avec une pratique de l’endocannibalisme, les enquêteurs ont été en mesure de distinguer les cinq âmes de la personne métaphysique composite et leur relation avec les humeurs du corps. Une bonne compréhension de la cosmologie du Sud Fore et sa relation avec ses habitants humains ont été nécessaires pour comprendre ces concepts profondément ancrés. La personne du Sud Fore est donc composée de cinq âmes et humeurs corporelles qui, ensemble, forment un individu composite, encore divisible. Ici est donc élucidé le concept des cinq âmes de la personne Fore, qui révèle une forte corrélation entre le paysage avec sa cosmologie sus-jacente et les humeurs corporelles culturelles, et la preuve de leur relation à la puissance de la terre

Genetic susceptibility, evolution and the kuru epidemic

The acquired prion disease kuru was restricted to the Fore and neighbouring linguistic groups of the Papua New Guinea highlands and largely affected children and adult women. Oral history documents the onset of the epidemic in the early twentieth century, followed by a peak in the mid-twentieth century and subsequently a well-documented decline in frequency. In the context of these strong associations (gender, region and time), we have considered the genetic factors associated with susceptibility and resistance to kuru. Heterozygosity at codon 129 of the human prion protein gene (PRNP) is known to confer relative resistance to both sporadic and acquired prion diseases. In kuru, heterozygosity is associated with older patients and longer incubation times. Elderly survivors of the kuru epidemic, who had multiple exposures at mortuary feasts, are predominantly PRNP codon 129 heterozygotes and this group show marked Hardy–Weinberg disequilibrium. The deviation from Hardy–Weinberg equilibrium is most marked in elderly women, but is also significant in a slightly younger cohort of men, consistent with their exposure to kuru as boys. Young Fore and the elderly from populations with no history of kuru show Hardy–Weinberg equilibrium. An increasing cline in 129V allele frequency centres on the kuru region, consistent with the effect of selection in elevating the frequency of resistant genotypes in the exposed population. The genetic data are thus strikingly correlated with exposure. Considering the strong coding sequence conservation of primate prion protein genes, the number of global coding polymorphisms in man is surprising. By intronic resequencing in a European population, we have shown that haplotype diversity at PRNP comprises two major and divergent clades associated with 129M and 129V. Kuru may have imposed the strongest episode of recent human balancing selection, which may not have been an isolated episode in human history

Application of a Polymerase Chain Reaction-ELISA to Detect Wuchereria bancrofti in Pools of Wild-Caught Anopheles punctualatus in a Filariasis Control Area in Papua New Guinea

Chemotherapy-based eradication programs are aimed at stopping transmission of Wuchereria bancroftiby its obligatory mosquito vector. This study compares one year post-treatment W. bancrofti infection rates of Anopheles punctulatus, the main vector of lymphatic filariasis in Papua New Guinea, using traditional dissection techniques and a polymerase chain reaction (PCR)-based ELISA of a parasite-specific Ssp I repeat. A total of 633 mosquitoes in 35 batches were dissected. Six batches contained W. bancrofti-infected mosquitoes, giving a minimum infection rate of 0.9%. This value was not different than the actual infection rate, which was 9 (1.4%) of 633 mosquitoes (P� 0.48). The DNA was extracted from 47 pools containing a mean of 13.2 mosquitoes per pool. A total of 621 mosquitoes were processed for the PCR-ELISA, including 486 caught by human bait and 135 by light trap, which included both dead and live mosquitoes. Of 23 pools of alcohol-preserved human-bait mosquitoes, seven were positive by the PCR-ELISA, giving an infection rate identical to that obtained by dissection of individual mosquitoes (1.4%). The minimum infection rates for pools of light-trap mosquitoes found dead and alive were 2.7% (2 of 74) and 4.9% (3 of 61), respectively. These values did not differ from each other (P � 0.84), but the overall infection rate of light- trap mosquitoes was greater than that of mosquitoes captured by human bait (3.7% versus 1.4%; P � 0.09). These data indicate that the PCR-ELISA of a W. bancrofti Ssp I repeat using pools of mosquitoes is comparable to traditional dissection techniques for monitoring transmission intensity following introduction of mass chemotherapy. This approach may also be useful for rapid and cost-effective assessment of transmission in endemic areas where the frequency of overt lymphatic pathology is low

Spatial variation of Anopheles-transmitted Wuchereria bancrofti and Plasmodium falciparum infection densities in Papua New Guinea.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.The spatial variation of Wuchereria bancrofti and Plasmodium falciparum infection densities was measured in a rural area of Papua New Guinea where they share anopheline vectors. The spatial correlation of W. bancrofti was found to reduce by half over an estimated distance of 1.7 km, much smaller than the 50 km grid used by the World Health Organization rapid mapping method. For P. falciparum, negligible spatial correlation was found. After mass treatment with anti-filarial drugs, there was negligible correlation between the changes in the densities of the two parasites

A Recombinant Blood-Stage Malaria Vaccine Reduces Plasmodium falciparum Density and Exerts Selective Pressure on Parasite Populations in a Phase 1-2b Trial in Papua New Guinea

The malaria vaccine Combination B comprises recombinant Plasmodium falciparum ring-infected erythrocyte surface antigen and 2 merozoite surface proteins (MSP1 and MSP2) formulated in oil-based adjuvant. A phase 1-2b double-blind, randomized, placebo-controlled trial in 120 children (5-9 years old) in Papua New Guinea demonstrated a 62% (95% confidence limits: 13%, 84%) reduction in parasite density in children not pretreated with sulfadoxine-pyrimethamine. Vaccinees had a lower prevalence of parasites carrying the MSP2-3D7 allelic form (corresponding to that in the vaccine) and a higher incidence of morbid episodes associated with FC27-type parasites. These results demonstrate functional activity of Combination B against P. falciparum in individuals with previous malaria exposure. The specific effects on parasites with particular msp2 genotypes suggest that the MSP2 component, at least in part, accounted for the activity. The vaccine-induced selection pressure exerted on the parasites and its consequences for morbidity strongly argue for developing vaccines comprising conserved antigens and/or multiple components covering all important allelic type