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At least 19 recordsLinked to original sources
PubMed1975

Genetic studies in relation to Kuru. VI. Evaluation of increased liability to Kuru in Gc Ab-Ab individuals.

The validity of the reported association between GcAb and kuru is analyzed. Phenotypes with one or more GcAb genes have an increased incidence of the disease at the expense of Gc 1-1 and Gc 2-2. Incidence ratios of kuru associated with various phenotypes examined over the linguistic groups studied indicate that only Gc Ab-Ab persons have a significantly greater chance of dying of kuru. The association X2 for the incidence ratio for those phenotypes possessing only one GcAb gene is significant, but there is significant heterogeneity between groups studied. Those of the Gc Ab-Ab phenotype are six times as likely to contract kuru as the baseline group. Criticisms of this analysis include difficulties defining an adequate control group in such heterogeneous populations, errors in determination of Gc phenotypes, inclusion of persons incubating kuru in the control groups, and questions of validity of statistical tests in isolated inbred populations.

Blood Group Antigens↗
PubMed1978

Antibody studies in the Kuru region. Immunological epidemiology of population groups in and adjacent to the Kuru region in Papua New Guinea. I. Enteroviruses.

A serological survey is reported for antibodies to Coxsackie, ECHO and polioviruses on sera collected in the kuru region of Papua New Guinea during earliest European contacts with kuru-affected and control populations through the period of highest kuru incidence. The results are discussed in the light of increasing European contact over the period of investigation. Suggestions are made concerning possible immunization programs with polioviruses.

Adolescent↗
PubMed2004

Kuru: a half-opened window onto the landscape of neurodegenerative diseases.

Kuru, the first human neurodegenerative disease classified as a transmissible spongiform encephalopathy (TSE), prion disease or, in the past, as a slow unconventional virus disease, was first reported to Western medicine in 1957 by Gajdusek and Zigas. A complete bibliography of kuru through 1975 has been published by Alpers et al. The solution of the kuru riddle opened a novel field of biomedical sciences and initiated more than a quarter of century of research that has already resulted in two Nobel prizes (to D. Carleton Gajdusek in 1976 and to Stanley B. Prusiner in 1997) and was linked to a third (to Kurt Wüthrich who determined the structure of the prion protein). Kuru research has impacted the concepts of nucleation-polymerization "protein cancers", and "conformational disorders". This paper is dedicated to Dr. Carleton Gajdusek on the occasion of his 80th birthday. "Kuru" in the Fore (Fig. 1) language means to shiver from fever or cold. The Fore used the noun of the kuru-verb to describe the always fatal disease which decimated their children and adult women but rarely men. It has been and still is restricted to natives of the Fore linguistic group at Papua New Guinea's Eastern Highlands and those neighboring linguistic groups which exchange women with Fore people (Auiana, Awa, Usurufa, Kanite, Keiagana, late, Kamano, Kimi; Fig. 2). Neighboring groups into which kuru-affected people did not settle through marriage or adoption, such as the Anga (Kukukuku), and remote lagaria, Kamano and Auiana people, were not affected. It seems that Kuru first appeared at or shortly after the turn of XX century in Uwami village of Keiagana people and spread to the Awande in the North Fore where the Uwami had social contacts. Within 20 years it had spread further into the Kasokana (in 1922 according to Lindebaum) and Miarasa villages of North Fore, and a decade later had reached the South Fore at the Wanikanto and Kamira villages. Kuru became endemic in all villages that it entered and became hyperendemic in the South Fore region. All native informants stressed the relatively recent origin of kuru. Interestingly enough, when kuru first appeared, it was considered poetically by Fore as similar to "the swaying of casuarinas tree" and kuru was labeled cassowary disease to stress the similarity between cassowary quills and "waving casuarinas fronds". Gajdusek first learned about kuru from Dr. Roy Scragg, director of Public Health in Port Mosby, who had already read a report sent by Dr. Vin Zigas to Dr. John Gunter in 1956. In March 1957, Gajdusek joined Zigas, who at that time was a medical patrol officer in Kainantu, Eastern Highland District of the Territory of Papua New Guinea.

Adult↗
PubMed1989

Positive transmission of Creutzfeldt-Jakob disease verified by murine kuru plaques.

Kuru plaque is a pathognomonic feature in the brain of patients with Creutzfeldt-Jakob disease (CJD) and in the brain of CJD-infected mice. Kuru plaques from CJD-infected mice were immunolabeled with rabbit anti-murine prion protein (PrP) absorbed with human PrP, but not so with mouse anti-human PrP. Therefore, the murine kuru plaque is composed of the host (mouse) PrP and can be distinguished antigenically from human PrP. Immunostaining using the anti-murine PrP and formic acid enhancement on tissue sections revealed not only birefringent kuru plaques but also nonbirefringent diffuse and small PrP accumulations. This immunohistochemical detection of kuru plaques provides more positive evidence than heretofore employed histochemical approaches. There were kuru plaques in brains of the first passage mice inoculated with tissues from 30 (91%) of 33 patients with CJD, the 3 negative patients belonging to a type of Gerstmann-Sträussler syndrome. Tissues from 6 other demented patients did not produce kuru plaques. In the evaluation of spongiform changes, mice inoculated with tissues from 23 (70%) of 33 patients were considered cases of successful transmission. In some mice, kuru plaques were present in the absence of spongiform changes. Further inoculations from 9 mice with kuru plaques but no spongiform changes were successful in almost all mice. Therefore, mice with murine kuru plaques in the absence of spongiform changes are also infectious. Thus, the presence of murine-specific kuru plaques can serve as another hallmark of a successful transmission.

Adult↗
PubMed1990

Creutzfeldt-Jakob disease patients with congophilic kuru plaques have the missense variant prion protein common to Gerstmann-Sträussler syndrome.

Congophilic kuru plaques, one of the pathological hallmarks in kuru and Gerstmann-Sträussler syndrome, are sometimes present in patients with Creutzfeldt-Jakob disease (CJD). The congophilic kuru plaques are composed partly of a host-encoded prion protein, and a missense variant prion protein with the codon 102 proline-to-leucine change (Leu102) is commonly present in patients with Gerstmann-Sträussler syndrome. To investigate the relationship between this syndrome and CJD with congophilic kuru plaques, we made a sequence analysis of the prion protein gene from patients with CJD, with or without congophilic kuru plaques. We found no alterations other than the Leu102 change, common to Gerstmann-Sträussler syndrome, in one of the prion protein alleles of the patient with congophilic kuru plaques. In the prion protein genotype analysis of other patients with CJD, the Leu102 allele was revealed to be carried heterozygously by 6 of 7 patients who had CJD with congophilic kuru plaques, yet no patient with CJD without congophilic kuru plaques had this allele. Interestingly, the Leu102 allele was also carried by some unaffected relatives of 3 patients with CJD with congophilic kuru plaques but with no apparent familial occurrence of a similar neurological disorder. Our findings show that CJD with congophilic kuru plaques should be categorized as belonging to Gerstmann-Sträussler syndrome, not CJD, and also suggest that the variant prion protein with Leu102 is closely related to the amyloidogenesis seen in subjects with congophilic kuru plaques.

Adult↗
PubMed2004

Genetic studies in relation to kuru: an overview.

Kuru is a subacute neurodegenerative disease presenting with limb ataxia, dysarthria, and a shivering tremor. The disease progress to complete motor and mental incapacity and death within 6 to 24 months. Neuropathologically, a typical pattern of neuronal loss, astrocytic and microglial proliferation, characteristic "kuru-type" amyloid plaques, and PrP deposits in the cerebral cortex and cerebellum are observed. Kuru is the prototype of a group of human transmissible spongiform encephalopathies (TSEs), or "prion" diseases, that include hereditary, sporadic and infectious forms. The latest member of this group, the variant Creutzfeldt-Jakob disease (vCJD), linked to transmission of bovine spongiform encephalopathy (BSE) to humans, shows features similar to kuru. Kuru has emerged at the beginning of the 1900s in a small indigenous population of New-Guinean Eastern Highlands, reached epidemic proportions in the mid-1950s and disappeared progressively in the latter half of the century to complete absence at the end of the 1990s. Early studies made infection, the first etiologic assumption, seem unlikely and led to a hypothesis that kuru might be a genetically determined or genetically mediated illness. After transmissibility of kuru had been discovered and all major epidemiologic phenomena adequately explained by the spread of an infectious agent with long incubation period through the practice of cannibalism, the pattern of occurrence still continued to suggest a role for genetic predisposition. Recent studies indicate that individuals homozygous for Methionine at a polymorphic position 129 of the prion protein were preferentially affected during the kuru epidemic. The carriers of the alternative 129Met/Val and 129Val/Val genotypes had a longer incubation period and thus developed disease at a later age and at a later stage of the epidemic. Observations made during the kuru epidemic are helpful in the understanding of the current vCJD outbreak, and vice versa clinical and experimental data accumulated in studies of other TSE disorders contribute to better understanding of the documented kuru phenomena.

Animals↗
PubMed2005

The epidemiology of kuru in the period 1987 to 1995.

Kuru is an encephalopathy or neuro-degenerative disease found only in the Okapa District of the Eastern Highlands Province of Papua New Guinea. It is always fatal, with a subacute course, on average, of about 12 months from onset to death. In the 9-year period 1987 to 1995 there were 66 deaths from kuru, 17 males and 49 females. The number of deaths per year ranged from 3 to 12. All deaths occurred south of a line drawn through the centre of the kuru region perpendicular to the axis of social change. The mean age at death was 49 years, with a gradual increase in this age with time. The last patient aged in their 20s died in 1987 and the last in their 30s died in 1991. The period shows a waning epidemic, with dramatically fewer deaths than in the early years of epidemiological surveillance 30 years before. Nevertheless, the clinical features and duration of the disease were unchanged. Transmission of kuru stopped by 1960 and patients seen in the period 1987-1995 showed long incubation periods, which in 1995 would have been at least 35 years. The proportion of males was much higher than in the early years; because males were effectively exposed only in childhood their incubation periods were in many cases likely to be over 50 years. The work of the Kuru Surveillance Team in maintaining a rigorous surveillance of kuru epidemiology over this period is described.

Adult↗
PubMed1982

Kuru with incubation periods exceeding two decades.

The clinical characteristics of kuru in 15 patients are described. All the patients had a history of joint pains preceding difficulty walking. The severity of the neurological dysfunction varied from mild truncal and limb ataxia necessitating the use of a stick for walking to terminal illness accompanied by marked ataxia, rigidity, spasticity, and dementia. All the patients with kuru in this study had a apprehensive, frightened facial expression. Most of the patients examined showed diminished or absent optokinetic nystagmus bilaterally. Apprehensive facies and diminished optokinetic nystagmus have not previously been described in kuru. The other clinical features of the current patients with kuru are similar to those recorded twenty years ago. Epidemiological surveillance, anamnesis, and missionary reports strongly suggest that all the patients described in this study were exposed to the kuru agent more than two decades ago through ritualistic cannibalism. Thus the incubation period or time interval from exposure to the onset of clinical illness exceeds two decades, while the duration of illness is two years or less. The cause of these extraordinarily long incubation periods is unknown but may result in part from exposure to small doses of the kuru agent through an inefficient oral route.

Adult↗
PubMed2006

Kuru in the 21st century--an acquired human prion disease with very long incubation periods.

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.

Aged↗
PubMed1975

Experimental kuru in the spider monkey. Histopathological and ultrastructural studies of the brain during early stages of incubation.

The brains of 10 spider monkeys inoculated intracerebrally with brain suspension from kuru patients have been studied histologically and ultrastructurally. The animals were killed by perfusion of fixative from four to forty-one weeks after inoculation, when healthy and free of neurological signs. Definite histopathological changes had occurred as early as four weeks after inoculation, when moderate numbers of bi-nucleated neurons were found within the limbic cortex, striatum, the hypothalamus and amongst the Purkinje cells of the cerebellum. At later stages of incubation a moderate loss of neurons in the cerebral and cerebellar cortex and a mild to moderate proliferation of fibrous astrocytes here and also in the hypothalamus were the most striking features. None of our cases showed either status spongiosus or the generalized astrocytic proliferation and hypertrophy, characteristic of fully developed experimental kuru, in any region of the brain. The principal ultrastructural abnormalities consisted of the formation of membrane-bound intracytoplasmic vacuoles, predominantly within dendrites, and of concentric laminar arrays derived from the endoplasmic reticulum. The former were seen in all regions of the brain examined and at all stages of incubation. Concentric laminar arrays were confined to the cerebellar nodulus, where they were most numerous in dendrites and neuronal perikarya four weeks after inoculation. Both changes are interpreted as an indication that the kuru agent acts upon the plasma membrane from an early stage onwards and, by stimulating its growth, leads to the formation of complex, membrane-bounded vacuoles and to hyperplasia of the endoplasmic reticulum. The formation of vacuoles is further regarded as the first sign of status spongiosus on an ultrastructural level. Attention is drawn to the great similarities between the changes observed in the present material and those described in the brains of patients dying from kuru and of primates with fully developed experimental kuru. The significance of the relatively rapid spread of the kuru agent throughout the brain is discussed in relation to the concept of "slow virus" diseases.

Animals↗