Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Kuru”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1997

Kuru and "new variant" CJD.

Acquired transmissible spongiform encephalopathies in humans include Kuru (a disease which was associated with ritualistic cannibalism in Papua New Guinea), iatrogenic Creutzfeldt-Jakob disease and a newly recognized variant form of Creutzfeldt-Jakob disease (nvCJD). Clinical and neuropathological features of nvCJD are reminiscent of Kuru: early and progressive cerebellar ataxia and numerous characteristic Kuru-type amyloid plaques surrounded by spongiform change. In contrast to typical cases of sporadic CJD, Kuru and nvCJD affect young patients. The newly recognized form of CJD has been identified in ten young people in the UK in 1996, approximately 10 years after the beginning of the bovine spongiform encephalopathy (BSE) epidemic in the UK. Molecular analysis has shown that nvCJD has strain characteristics that are distinct from other types of CJD but similar to those of BSE. In the UK an estimated half a million BSE-infected cows entered the human food chain before the bovine offal ban of 1989. To be effective the oral route probably requires high-infectivity titers which are encountered only in the brain, spinal cord and eyes of naturally infected cows. In patients with Kuru, titers of more than 10(8) infectious doses per gram were reported in the brain tissues. As a result of the estimated very long incubation period of nvCJD (10 to 30 years or more) the predicted nvCJD epidemic will have the shape of a normal distribution curve with a peak expected in 2009. The epidemic may extend until 2030. There is already an example to illustrate such a curve in its descending line: the decline of Kuru deaths following the interruption of ritual cannibalism.

Animals↗
PubMed1999

Movement disorders in Kuru.

OBJECTIVE: To describe the gamut of movement disorders (MD) seen during the clinical course of kuru. BACKGROUND: Kuru is a subacute spongiform encephalopathy that was confined to several adjacent cultures in the Eastern Highlands of New Guinea and resulted from contamination with brain tissue during the ritual endocannibalism practiced in those societies. This unique neurologic disease was recorded extensively with film between 1957 and 1976, and these comprehensive research documents have been donated to the American Academy of Neurology archives by one of the authors (DCG). METHODS: The comprehensive assembly of film record of kuru, which was collected by one of the authors (DCG) was reviewed. This comprised two parts: The first were films from 1957-1964 and included 17.397 ft of 16-mm film featuring 204 patients (children and adults); the second is assembled from films made from 1967-1976 and includes 9138 ft. of film featuring 47 adult patients. Two MD specialists categorized all MDs observed and a representative videotape was produced. RESULTS: Tremor is the most frequently encountered MD in kuru and is typically of the action/intention type, which appears early in the disease and is soon associated with other clinical signs of cerebellar dysfunction. Widespread clonus is characteristic of advanced disease and can be difficult to differentiate from tremor. Dystonia/athetosis and choreiform jerks also appear as the disease progresses. Dystonia can involve the torso, distal limbs, neck, or jaw. Myoclonic jerks can be superimposed on the cerebellar or dystonic features usually with an enhanced startle response. Parkinsonian symptomatology, other than resting tremor is frequent among the filmed subjects especially in the second stage of the disease. CONCLUSION: The clinical manifestations of kuru involved a wide array of MDs during all three stages of the degenerative illness.

Adult↗
PubMed1994

Relationship of microglia and scrapie amyloid-immunoreactive plaques in kuru, Creutzfeldt-Jakob disease and Gerstmann-Sträussler syndrome.

Kuru, Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler syndrome (GSS) are transmissible dementias affecting humans characterized neuropathologically by intraneuronal vacuolation, spongiform change, astrocytic hypertrophy and hyperplasia and the variable presence of amyloid plaques. It has been suggested that microglia are amyloid-forming cells, which play an essential role in amyloid plaque formation. To study the relationship between microglia and amyloid plaques in kuru, CJD and GSS, cerebellar tissues were examined by the double-immunostaining technique using anti-ferritin antibodies as the microglial marker and anti-scrapie amyloid antibody as plaque marker. Ferritin-immunoreactive microglia were observed interdigitating with and among unicentric, multicentric and diffuse types of scrapie amyloid-immunoreactive plaques and were found to a lesser extent in the neuropil. In kuru and CJD, scrapie amyloid-immunoreactive plaques were predominantly unicentric and were observed in the granular layer. In kuru, 53% of the amyloid plaques were associated with microglia, whereas only 30% of plaques in CJD were. In contrast, scrapie-amyloid-immunoreactive plaques in GSS were of the multicentric type, predominantly observed in the molecular layer, and 90% of these plaques were associated with microglia. Our data indicate that microglia are frequently associated with scrapie amyloid-immunoreactive plaques in GSS, less commonly in kuru and to a much lesser extent in CJD, suggesting that microglia may play a variable but important role in the formation of plaques in the transmissible spongiform encephalopathies.

Adolescent↗
PubMed1992

Immunohistochemical study of kuru plaques using antibodies against synthetic prion protein peptides.

Prion protein (PrP) is a protein closely associated with the transmission of scrapie and Creutzfeldt-Jakob disease (CJD). Kuru plaques are composed of this protein. PrP33-35 is converted to protease-resistant PrP27-30 by proteinase K digestion. It has not yet been determined which of these PrPs is present in kuru plaques in vivo. Accordingly we synthesized two peptides (peptide-N and peptide-M) that, respectively, corresponded to the protease-sensitive and protease-resistant portions of PrP33-35, based on the amino acid sequence deduced from human PrP cDNA. These two synthetic peptides were used to immunize rabbits and produce antisera (anti-N and anti-M). Both antisera stained kuru plaques in a patient with Gerstmann-Sträussler syndrome and one with CJD. Peptide-N has an amino acid sequence which does not exist in PrP27-30. Staining of kuru plaques by the antiserum against peptide-N indicated that the entire molecule, including the N-terminal portion of PrP33-35, was deposited in the kuru plaques.

Aged↗
PubMed2002

The incubation period of kuru.

BACKGROUND: Kuru is a transmissible spongiform encephalopathy that was identified in Papua New Guinea in the late 1950s. Several thousand cases of the disease occurred during a period of several decades. Epidemiologic investigations implicated ritual endocannibalistic funeral feasts as the likely route through which the infectious agent was spread. METHODS: We estimated the incubation period distribution of kuru using a back-calculation model and explored the relation among sex, age at infection, and incubation period. Key assumptions in the model were that the number of new kuru infections in a year was proportional to the number of kuru cases dying that year, and that the epidemic arose from a single case of sporadic Creutzfeldt-Jakob Disease occurring around 1900. RESULTS: The mean incubation period of kuru was estimated at between 10.3 and 13.2 years. Point estimates of the 90th percentile ranged from 21.1 to 27.0 years. The incubation period in females was estimated to be shorter than that in males. The shortest incubation periods were estimated in adult women, who may have been exposed to the largest doses of infectious material. CONCLUSIONS: Our findings suggest that the relatively young age of cases of variant Creutzfeldt-Jakob disease probably reflects increased levels of exposure in young people, rather than age-dependency in the incubation period.

Adolescent↗
PubMed1983

A clinico-pathological study of a case of kuru.

Kuru was diagnosed in a 42-year-old Melanesian male from the Eastern Highlands Province of Papua New Guinea. The clinical features indicated predominant cerebellar degeneration together with widespread cortical neuronal dysfunction and involvement of the diencephalon, hippocampus and basal ganglia. Dementia was an early and prominent feature. The duration of clinical illness was about 12 months and atypically he spent the last 7 months in hospital allowing continuous assessment. At autopsy, spongiform encephalopathy was demonstrated, and inoculation of brain tissue into 4 squirrel monkeys and 1 capuchin monkey resulted in the development of kuru. This is the longest continuous study of kuru in a hospital setting to be recorded in the adult human subject. The virus isolated from the brain of this patient has been adopted as a standard reference strain of kuru for future use and repository.

Adult↗
PubMed2002

Kuru: the old epidemic in a new mirror.

The kuru epidemic lasted almost a century; it started in 1901-1902, reached epidemic proportions in the mid-1950s, and disappeared in the 1990s. Kuru is the prototype member of a group of disorders known as transmissible spongiform encephalopathies (TSEs) or prion diseases. Recent data on the genetics and pathogenesis of TSEs contribute to a better understanding of the documented kuru phenomena, and vice versa, observations made during the kuru epidemic are immensely helpful in understanding the epidemic of variant Creutzfeldt-Jakob disease that is currently developing in Europe. The major goal of this review is to identify and illustrate these points.

Cannibalism↗
PubMed2000

Increased susceptibility to Kuru of carriers of the PRNP 129 methionine/methionine genotype.

Kuru reached epidemic proportions by the mid-twentieth century among the Fore people of New Guinea and disappeared after the abolition of cannibalistic rituals. To determine susceptibility to kuru and its role in the spread and elimination of the epidemic, we analyzed the PRNP gene coding sequences in 5 kuru patients; no germline mutations were found. Analysis of the PRNP 129 methionine (M)/valine (V) polymorphism in 80 patients and 95 unaffected controls demonstrated that the kuru epidemic preferentially affected individuals with the M/M genotype. A higher representation of M/M carriers was observed among the affected young Fore males entering the age of risk, whereas a lower frequency of M/M homozygotes was found among the survivors. M/V and V/V genotypes predisposed to a lower risk of disease development and longer incubation times. These findings are relevant to the current outbreak of variant Creutzfeldt-Jakob disease (vCJD) in the United Kingdom, because all vCJD patients tested thus far have been M/M carriers.

Amyloid↗
PubMed1975

Cellular sensitization in kuru, Jakob-Creutzfeldt disease and multiple sclerosis: with a note on the biohazards of slow infection work.

Following intramuscular injection of Kuru and Jakob-Creutzfeldt brain material into chimpanzees, circulating lymphocytes became sensitized to scrapie mouse brain (and spleen) to a greater degree than to normal tissue. This sensitization subsided after about a month, to be followed some 90 days later by a secondary peak attributed to establishment of changes in the nervous system. Special sensitization to scrapie material occurs in Kuru and Jakob-Creutzfeldt disease, but is not specific to them. The immunological evidence suggests that parenchymatous destruction may precede astroglial hypertrophy in these diseases. An early peak occurred in animals inoculated with multiple sclerosis brain and normal brain, but neither showed a delayed second peak. Thus there was no evidence of establishment of infection, even though all four animals were in intimate contact for over 200 days, and no evidence of the injection of MS material itself having established an infection. Biohazards in Kuru, Jakob-Creutzfeldt and MS work appear to be very low. The significance of the increased sensitilization to scrapie material in Kuru and Jakob-Creutzfeldt disease, especially in relation to normal ageing (where it also increases), is discussed.

Animals↗
PubMed1995

Neuropathology and the scrapie-kuru connection.

When their kinship was surmised 35 years ago, scrapie and kuru were linked mainly by their neuropathologic similarity. Most notable were neuronal degeneration and intense astrocytosis with little, if any, inflammation. Especially eye-catching in kuru were the vacuolated neurons--the histologic hall-mark of scrapie that drew me to the human disease from the start. Because spongiform change in gray matter neuropil is variable and usually lacks prominence in both scrapie and kuru, it was not part of the resemblance I saw in them. Amyloid plaques, so characteristic of kuru, also did not figure in the similarity, for they had not yet been reported in scrapie. Despite the uncertainty at the time about the pathologic essence of scrapie, the two diseases still looked alike. Their eventual connection--however tenuously held together initially by the few likenesses--has survived as a tribute to morphologic observation. It provided the essential link that helped ensure the kinship a lasting place in comparative neuropathology.

Animals↗
PubMed1982

Heterogeneic autoantibody against neurofilament protein in the sera of animals with experimental kuru and Creutzfeldt-Jakob disease and natural scrapie infection.

Heterogeneic autoantibodies against axonal neurofilament proteins of mature mouse neurons grown in vitro were detected by the indirect immunofluorescence technique in 12.7% (9 of 71) of the sera from nonhuman primates infected with kuru, in 14.5% (17 of 117) and 4% (1 of 25), respectively, of the sera from nonhuman primates and laboratory rodents infected with Creutzfeldt-Jakob disease, and in 35% (7 of 20) of the sera from sheep naturally infected with scrapie. Autoantibody titers ranged from 1:16 to 1:512 in Creutzfeldt-Jakob disease-infected animals, 1:32 to 1:512 in kuru-infected animals, and 1:64 to 1:1,024 in sheep with natural scrapie. The sera from 11 monkeys and 17 hamsters infected with scrapie and from 19 chimpanzees inoculated with brain tissues from humans with other neurological diseases did not contain autoantibodies. Of the 41 chimpanzees with Creutzfeldt-Jakob disease, 6 had autoantibodies against neurofilament proteins before experimental inoculation, whereas 6 others developed autoantibodies after inoculation, 4 developed autoantibodies during the asymptomatic phase, and 2 developed autoantibodies during the terminal clinical phase. Of the 48 chimpanzees with kuru, 2 had autoantibodies before inoculation, 6 developed autoantibodies after inoculation, 3 developed autoantibodies during the asymptomatic phase, and 3 developed autoantibodies during the terminal clinical phase. Among the normal nonhuman primate controls, 4.6% (9 of 195) had autoantibodies. In contrast, no autoantibodies were detected in 49 control rodents and 13 control sheep. The increased incidence of autoantibodies against neurofilament proteins in animals with kuru, Creutzfeldt-Jakob disease, and scrapie constitutes the first evidence of an immunological reaction in this group of atypical infections caused by unconventional viruses and suggests that neurofilaments may be involved in pathogenesis.

Animals↗
PubMed1975

Kuru.

Theis report discusses problems involved in the diagnosis of kuru. The gentic and epidemiological pattern is also reviewed. This reveals a continuing overall reduction in kuru incidence with the disappearance of juvenile cases and increasing age of male kuru patients a reduction in the age of female cases. The significance of these trends in relation to the transmission of kuru is discussed.

Adolescent↗
PubMed1975

Kuru.

Kuru is a progressive, invariably fatal cerebellar degeneration which occurs in a limited area of the New Guinea Highlands. The word kuru is derived from a term in the Fore language meaning to shake from fear, and it stems from the trembling which is a conspicuous symptom. Few neurologic diseases have attracted the attention of specialists in so many disciplines. No rare disease can have aroused more interest among the laity. Apart from an extensive scientific and anthropological literature, kuru has been the source of inspiration to journalists and travel writers, and it even occupies a prominent position in the plot of a popular novel. The facts concerning kuru are no less remarkable than the mythology that has grown up around it.

Adult↗
PubMed2001

Gerstmann-Sträussler-Scheinker syndrome,fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathies.

Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), fatal familial insomnia (FFI) and kuru constitute major human prion disease phenotypes. Each has been successfully transmitted in animal models and all are invariably fatal neurodegenerative disorders, with the brains of affected individuals harbouring variable amounts of an abnormal, protease-resistant form of the prion protein (PrPres), which is inextricably linked to pathogenesis and transmissibility. Classical sporadic CJD is the most common human transmissible spongiform encephalopathy (TSE), but recently the variant form (vCJD), first described in the UK in 1996, has drawn considerable attention. In contrast to sporadic CJD, FFI and GSS are almost invariably genetically determined TSEs, caused by a range of mutations within the open reading frame of the prion protein gene (PRNP) on chromosome 20. By definition, the nosologic term FFI is reserved for patients manifesting prominent insomnia, generally in combination with dysautonomia, myoclonus, and eventual dementia, with the predominant pathologic changes lying within the thalami and a specific underlying mutation in PRNP. GSS, however, encompasses a more diverse clinical spectrum ranging from progressive cerebellar ataxia or spastic paraparesis (both usually in combination with dementia), to isolated cognitive impairment resembling Alzheimer's disease. Additional extra-pyramidal features, which may respond to dopaminergic therapy can also be seen. Neuropathological findings are also relatively diverse, partly overlapping with those found in Alzheimer's disease, especially the presence of neurofibrillary tangles (NFTs). Although GSS and FFI in their classical forms are differentiable clinical profiles, such divisions may have no intrinsic biological validity given the considerable intra-familial clinico-pathological diversity so commonly seen. Kuru constitutes a horizontally transmitted prion disease, which after a lengthy incubation period, presents clinically as a progressive cerebellar ataxia associated with tremors. It has now almost disappeared since the cessation of ritualistic endocannibalism in the late 1950s but was previously exclusively endemic amongst the Fore linguistic group and neighbouring tribes in the Eastern Highlands of New Guinea. Uniform topographical central nervous system histopathology includes spongiform change and neuronal loss, with amyloid (kuru) plaques in approximately 75% of cases.

Gerstmann-Straussler-Scheinker Disease↗
PubMed1998

Phenotype-genotype studies in kuru: implications for new variant Creutzfeldt-Jakob disease.

The PRNP polymorphic (methionine/valine) codon 129 genotype influences the phenotypic features of transmissible spongiform encephalopathy. All tested cases of new variant Creutzfeldt-Jakob disease (nvCJD) have been homozygous for methionine, and it is conjectural whether different genotypes, if they appear, might have distinctive phenotypes and implications for the future "epidemic curve" of nvCJD. Genotype-phenotype studies of kuru, the only other orally transmitted transmissible spongiform encephalopathy, might be instructive in predicting the answers to these questions. We therefore extracted DNA from blood clots or sera from 92 kuru patients, and analyzed their codon 129 PRNP genotypes with respect to the age at onset and duration of illness and, in nine cases, to detailed clinical and neuropathology data. Homozygosity at codon 129 (particularly for methionine) was associated with an earlier age at onset and a shorter duration of illness than was heterozygosity, but other clinical characteristics were similar for all genotypes. In the nine neuropathologically examined cases, the presence of histologically recognizable plaques was limited to cases carrying at least one methionine allele (three homozygotes and one heterozygote). If nvCJD behaves like kuru, future cases (with longer incubation periods) may begin to occur in older individuals with heterozygous codon 129 genotypes and signal a maturing evolution of the nvCJD "epidemic." The clinical phenotype of such cases should be similar to that of homozygous cases, but may have less (or at least less readily identified) amyloid plaque formation.

Adolescent↗
PubMed1980

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

Animals↗
PubMed1977

An autopsy case of Creutzfeldt-Jakob disease with kuru-like neuropathological changes.

An autopsy case of Creutzfeldt-Jakob disease with Kuru-like neuropathological changes which revealed clinically extrapyramidal, pyramidal and psychic symptoms is presented in this report. On microscopic examination, status spongiosus, neuronal degeneration, proliferation of hypertrophic astrocytes and numerous plaques were observed in the cerebrum and cerebellum accompanied with widespread demyelinization. These plaques which suggested Kuru plaques measuring 10 to 60 micron were strongly PAS positive and had a dense central core surrounded by a halo of fine radially arranged fibrils. As for the relationship between Creutzfeldt-Jakob disease and Kuru, the significance of these morphological changes is discussed.

Adult↗
PubMed1997

Pathology and immunocytochemistry of a kuru brain.

We report here results of modern staining techniques including anti-prion protein (PrP) immunocytochemistry to a set of archival brain specimens of a 16 year-old male who died from kuru in 1967. Brain suspensions transmitted disease to chimpanzees and New World monkeys. The PrP gene is homozygous for valine at the polymorphic codon 129. Histology shows neuronal loss, spongiform change, and astrogliosis. Lesions are maximal in parasagittal and interhemispheric areas of frontal, central and parietal cortex, cingulate cortex, striatum, and thalamus, and are accentuated in middle and deep cerebral cortical layers. PrP accumulates as diffuse synaptic type deposits and mostly unicentric plaques. PrP deposition is maximal in parasagittal and interhemispheric areas of frontal, central and parietal cortex, cingulate cortex, basal ganglia, and cerebellar cortex. Plaques are prominent in the striatum, thalamus, and granular layer of cerebellar cortex. Meticulous examination reveals only rare "florid" plaques with surrounding vacuolation. We conclude that 1) pathology including immunomorphology of PrP deposition in this kuru brain is within the lesion spectrum of Creutzfeldt-Jakob disease although plaques are unusually prominent and widespread; 2) kuru does not share the neuropathological hallmarks of the new Creutzfeldt-Jakob disease variant recently reported in the UK and France; 3) topographic prominence of PrP deposition parallels that of spongiform change and/or astrogliosis.

Adolescent↗