Kuru Disease

11 Key excerpts on "Kuru Disease"

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  Brain Damage

  Bridging Between Basic Research and Clinics

  • Alina Gonz and #225;lez-Quevedo(Author)
  • 2012(Publication Date)
  • IntechOpen

    (Publisher)

  However, the clinical and epidemiological profiles suggested that this was indeed a peculiar disease, as brains autopsies showed spongiform encephalopathy, suggesting that, like scrapie, kuru was an infectious disease (Gajdusek and Zigas, 1959; Zetterstrom, 2010; Harper, 1977). A genetic explanation was initially proposed based in the apparent restriction of the disease to a particular tribal group and the remarkable familial clustering, with vertical transmission from generation to another (Harper, 1977). The elucidation of the causative factors of kuru came from the elegant experimental approaches and epidemiological studies carried out by Gajdusek and others (Harper, 1977;Zetterstrom, 2010). They demonstrated that ritual cannibalism of the brain and other parts of deceased relatives, practiced by the family, particularly by women and children, as an act of mourning and respect, provided the clue to the discovery that consumption of kuru-contaminated tissue was the means of transmitting the disease (Gajdusek, 1977). These findings led to the successful transmission of the disease to chimpanzees by the intracerebral inoculation of brain tissue from kuru patients (Harper, 1977;Gajdusek et al., 1966). Brain Damage – Bridging Between Basic Research and Clinics 192 As in scrapie, the infectious agent of kuru accumulated in great quantities in the brain and did not have the features of a typical viral pathogen. These observations led Gajdusek to speculate that an unconventional type of virus might be the etiological agent of kuru, and this view was supported by the experimental transmission of kuru, scrapie and also Creutzfeldt–Jakob disease to chimpanzees during the 1960s and 1970s (Gajdusek et al., 1966). These findings led to a new vision of the etiology of various neurodegenerative diseases, which garnered Gajdusek the Nobel Prize in 1976 (Zetterstrom, 2010). However, the “protein only” hypothesis came from the mind of J.

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  Plagues and Epidemics

  Infected Spaces Past and Present

  • D. Ann Herring, Alan C. Swedlund, D. Ann Herring, Alan C. Swedlund(Authors)
  • 2020(Publication Date)
  • Routledge

    (Publisher)

  plague, the Fore, too, spoke of kuru as both a demographic and a social disaster. The topic of cannibalism, the key to the transmission of the infectious agent, was addressed in different ways by the three sets of actors.

  The Medical Assessment of Kuru

  The first published reports of kuru (Gajdusek and Zigas 1957; Zigas and Gajdusek 1959) provided a clinical description of the disease and its patterns of occurrence. Kuru was described as an almost invariably fatal, acute, progressive, degenerative disease of the central nervous system, said to be restricted to members of the Fore cultural and linguistic group and their immediate tribal neighbors, with whom they intermarried. The victims were predominantly women and adolescents of both sexes. Adult men were rarely victims, and no cases had been found in children under four or five years of age. One percent of the Fore population was thought to be affected. Cases removed from the Fore environment did not recover. A framework for future clinical and epidemiological research was thus quickly established.

  By 2005, continued surveillance of the population by the Institute of Medical Research in Papua New Guinea allowed its director, Michael Alpers (2005), to report a waning epidemic during the period 1987-1995, although the clinical features and duration of the disease were unchanged, averaging about twelve months from onset to death. With the cessation of cannibalism by 1960, the transmission of kuru had stopped, and by 1995 the incubation period had reached at least thirty-five years. With no kuru death in 2005 and only one in 2007, the epidemic appears to be coming to an end.

  Summarizing etiological hypotheses a few years after his 1959 report, Gajdusek suggested that "infectious, toxic, deficiency, or hypersensitivity factors may operate with genetic dependence" (Gajdusek 1963: 164). Nonetheless, he observed, "we are investing our maximum effort ... in an attempt to discover a virus aetiology" (p. 159). As Warwick Anderson (this volume) notes, the mantle of ethnographer and geographer that Gajdusek adopted on first encountering the disease had already shifted to that of microbe hunter. For the remainder of the 1960s and during the early 1970s he continued to provide an abundance of medical hypotheses: infectious etiology, possible plant toxins, metallic poisoning (Reid and Gajdusek 1969; Sorenson and Gajdusek 1969), and a return to an earlier supposition that the genetic constitution of the kuru-affected populations could not be dismissed (Plato and Gajdusek 1972). Cannibalism was discounted or given low priority, perhaps because Gajdusek's 1957 data on Fore cannibalism were inaccurate (Lindenbaum 1982) or because he thought the idea was too exotic (Anderson 2008: 169; Glasse and Lindenbaum 1992; Rhodes 1997: 103).

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  Eat Me

  A Natural and Unnatural History of Cannibalism

  • Bill Schutt(Author)
  • 2017(Publication Date)
  • Wellcome Collection

    (Publisher)

  New England Journal of Medicine. Kuru, the authors claimed, was a degenerative disease of the central nervous system. They described the clinical course of the disease as well as its curious preference for striking three times as many women as men. The skewed sex ratios were difficult to pick up, however, since more men were being killed for having been kuru sorcerers. For the Fore, ritual murder had become the great equaliser. Significantly, Gajdusek also noted that kuru occurred equally in children of both sexes.

  The researchers sent off blood and tissue samples for analysis but the results showed no evidence of viral infection, nor did they appear to indicate the presence of a toxin (they had suspected that the Fore were being poisoned by heavy metals in their diet). But a number of the tissue specimens did show something remarkable. After examining the brains of eight kuru victims, scientists at the National Institute of Health (NIH) in Bethesda, Maryland, reportedly found no evidence of inflammation or any immune response whatsoever. That meant the victim’s body had not been fighting off a pathogenic organism like a virus, bacterium or fungus. In most cases, at the first signs of a viral, bacterial or fungal intruder, the body initiates a sustained, multi-pronged defence consisting of responses like swelling and inflammation, cell-mediated responses (like an attack by white blood cells), and the production of antibodies – proteinaceous particles that bind to surface proteins found on foreign cells and viruses.

  What the investigators did find, however, was that large regions of the cerebellum (which sits like a small head of cauliflower behind the cerebral hemispheres) were full of holes. Igor Klatzo, a NIH researcher, had seen a disease like this only once before. The closest condition he could think of was that described by Jakob and Creutzfeldt.

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  Kuru Sorcery

  Disease and Danger in the New Guinea Highlands

  • Shirley Lindenbaum(Author)
  • 2015(Publication Date)
  • Routledge

    (Publisher)

  Meanwhile, in 1959, William Hadlow had made the seminal connection between the neuropathological features of kuru and scrapie, a disease in sheep. Moreover, he said that scrapie was transmissible by inoculation. Hadlow's observation inspired Gajdusek and his co-workers to test the trans-missibility of kuru on chimpanzees, which was successfully carried out in 1966. Kuru, like scrapie, was now considered to be an infectious disease, caused by a "slow virus" of very long incubation.

  The transmissibility of kuru provided a major medical piece of the puzzle. John Mathews, who as a medical student had heard Burnet talk about kuru, arrived in Papua New Guinea in 1964 to begin his own research. Based on quantitative analysis of our Fore genealogies, Mathews published papers in 1965 and 1967 that confirmed that kuru was of limited time depth and that the average age of kuru cases was rising each year, evidence hard to accommodate with the original genetic theory, but consistent with the cannibalism hypothesis.7 In 1967 Robert Glasse presented the case for cannibalism as the mode of transmission to the Division of Anthropology at the New York Academy of Sciences,8 and in 1968, Robert and I joined Mathews in a publication that would reach a wider audience.9 Our paper showed that the cannibalism theory was supported by a wealth of epidemiological and ethnographic data, and was consistent with stories about named individuals who had taken part in mortuary feasts and who had themselves died from kuru. In 1968, Alpers' analysis of a comprehensive body of epidemiological data also concluded that cannibalism was the mode of transmission.10

  Some still doubted the cannibalism hypothesis. Perhaps the most surprising resistance came from Gajdusek, who proposed an alternative route of disease transmission. The mechanism, he said, lay in the contamination of highly infective tissues through cuts and scrapes on the hands of mourners, as well as from brain tissue purposely rubbed on the body during mortuary ceremonies, a practice the Fore have denied.11 While the handling of infectious body parts could possibly be a means of occasional self-inoculation, Gajdusek had begun to overstate the case. His resistance to the idea of oral ingestion as the route of disease transmission has elicited speculation from many who knew him. He and his colleagues were said to have found it difficult to imagine how social and cultural studies could be rendered commensurate with contemporary biological research and pathological findings. The ecological mantle Gajdusek had adopted on first encountering the disease had shifted to a narrower focus on microbe hunting.12 The sensitivity of the topic may also explain some unwillingness to accept the role of cannibalism. In recent years, many well-documented accounts of cannibalism have been published by anthropologists who once thought the topic was too delicate to discuss, given the image of the cannibal as an icon of primitivism.13 It is also the case that Gajdusek's data on cannibalism were inaccurate. His published letters and field notes14 indicate that, based on information provided by men, he thought the human brain was not consumed.15

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  Subviral Pathogens of Plants and Animals: Viroids and Prions

  • Karl Maramorosch(Author)
  • 2012(Publication Date)
  • Academic Press

    (Publisher)

  Bahmanyar has demonstrated that amyloid plaques are developed in most of the affected mule deer. Now a similar chronic wasting disease with a subacute spongiform encephalopathy is occurring in the adjacent herd of captive elk (66). XIII. ORIGIN AND SPREAD OF KURU Unanswered crucial questions posed by all of these agents are related to their biological origin and mode of survival in nature. The diseases they evoke are not artificial diseases, produced by researchers tampering with cellular macromolecular structures, as some would have it. They are naturally occurring diseases, for none of which do we know the mode of dissemination or maintenance which is adequate to explain their long-term persistence. For kuru we have a full explanation of the unique epidemiological findings and their change over the past two decades: the contamination of close kinsmen withina mourning family group by the opening of the skull of dead victims in a rite of cannibalism, during which all girls, women, babes-in-arms, and toddlers of kuru vie- C o u n t r y W h e r e S c r a p i e H a s B e e n E r a d i c a t e d SUBACUTE SPONGIFORM ENCEPHALOPATHIES 531 tim f s family were thoroughly contaminated with the virus. The disease is gradually disappearing with the cessation of cannibalism and has already disappeared in children, adoles-cents, and young adults with progressively increasing age of the youngest victims. However, this does not provide us with a satisfactory explanation for the origin of kuru. Was it the unlikely event of a sporadic case of worldwide CJD, which in the usual cultural setting of New Guinea produced a unique epidemic? A spontaneous case of CJD has been seen in a na-tive 26-year-old Chimbu New Guinean from the Central High-lands, whose clinical diagnosis was proved by light-and electronmicroscopy of a brain biopsy specimen.

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  Molecular Detection of Human Viral Pathogens

  • Dongyou Liu(Author)
  • 2016(Publication Date)
  • CRC Press

    (Publisher)

  Kuru was the first chronic or subacute degenerative disease in humans that was shown to be provoked by a slow virus infection, and as such has attracted worldwide attention and stimulated the search for similar virus infections as the possible cause of other subacute and chronic diseases in humans [12–17]. Such a slow progressive infection in humans, with an incubation period of many years and an absence of any inflammatory responses to the slow destruction of brain cells, was previ-ously unknown. In veterinary medicine, Sigurdsson [17] had shown such slow virus infection in sheep. The elucidation of the etiology of kuru has led to the discovery that worldwide presenile dementias, CJD and its variants, with basically similar cellular lesions, are also transmissible and caused by a very similar, unconventional “virus” or prion [18]. In all of TCA in humans, infectious amyloids are formed from the TCA amyloid precursor protein (PrP) specified on the short arm of chromosome 20 in human and chromosome 2 in mouse. There are other slow infections of the CNS in humans that are caused by conventional viruses, including measles virus, papovaviruses (JCV and SV40-PML), rubella virus, cyto-megalovirus, herpes simplex virus, adenovirus types 7 and 32, Russian spring-summer encephalitis (RSSE) viruses, and the human retroviruses (human T-cell lymphotropic virus-es-I: HTLV1, and human immunodeficiency viruses: HIV; Table 97.2). However, unlike the conventional viruses, the “unconven-tional viruses” of the subacute spongiform encephalopathies are truly slow in their replication, with long doubling times. These unconventional viruses have made it necessary to alter our conceptions of the possible range of virus structure.

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  Pathology and Pathogenesis of Human Viral Disease

  • John E. Craighead(Author)
  • 2000(Publication Date)
  • Academic Press

    (Publisher)

  Carlton Gajdusek, whose subsequent experimental work established the spongiform encephalopathies as a transmissible clinical and pathological entity (Figure 30.6). It was almost invariably seen in women and children, most probably because they (but not adult males) consumed human brain during the ritualistic ceremonies of cannibalism practiced by the tribe. Inasmuch as kuru was the major cause of premature death among the Foré (Gajdusek, 1979), those who consumed the brains of the dead were at high risk of acquiring the infection. With the elimination of cannibalism in the 1950s, the disease gradually disappeared among the Foré (Figure 30.7). The cerebral and cerebellar cortices in patients with kuru show diffuse spongiform changes, with prominent plaques predominantly comprised of amyloid and prion protein (Figure 30.8). FIGURE 30.6 Drs. D. Carlton Gajdusek (right) and V. Gikas (left) examining a child with kuru in the eastern highlands of Papua, New Guinea in 1957. Reprinted with permission and through the courtesy of W. Pendlebury, MD. FIGURE 30.7 The overall incidence of kuru deaths in male and female patients by year since its discovery in 1957 through 1977. More than 2500 patients died of kuru in this 20-year period of surveillance, and there has been a slow irregular decline in the number of patients. The decline in incidence of the disease followed the cessation of cannibalism, which occurred between 1957 and 1962 in various villages. Reprinted with permission from Masters et al. (1979). FIGURE 30.8 Diffuse spongiform changes in the brain at autopsy from a case of kuru. Note the prominent degenerative changes in neurons. Gliosis is not prominent. Fatal Familial Insomnia (FFI) First described in 1986 by Lugaresi et al., this extremely rare (approximate prevalence = 1 per 10 × 10 6) disease is first manifest as increasingly severe insomnia associated with diverse autonomic symptomatology

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  Neurogenetics

  Scientific and Clinical Advances

  • David R. Lynch(Author)
  • 2005(Publication Date)
  • CRC Press

    (Publisher)

  28 Prion Diseases William S. Baek and James A. Mastrianni Department of Neurology, University of Chicago Hospitals, Chicago, Illinois, U.S.A. INTRODUCTION Also known as transmissible spongiform encephalopathies (TSEs), and previously considered to result from a ‘‘slow virus,’’ this unique family of transmissible neurodegenerative disorders results from the accumulation within the brain of misfolded prion protein (PrP). Prion disease (PrD) is typified by its most common phenotype, Creutzfeldt–Jakob disease (CJD), which presents as a rapidly progressive dementia associated with ataxia and myoclonus; however, at least four other phenotypes are recognized, namely Gerstmann–Stra ¨ussler–Scheinker disease (GSS), fatal insomnia (FI), new variant (v) CJD, and kuru. While the majority of cases occur on a sporadic basis, approximately 15% are associated with an autosomal dominant mutation within the PrP gene ( PRNP ), and a susceptibility poly-morphism at codon 129 within PRNP appears to play a role in both. This chapter will review PrD, with special attention to the genetic aspects of disease. HISTORICAL BACKGROUND Human PrD was first described by Creutzfeldt and then Jakob in 1929 (1–3), as a progressive dementia with associated gait abnormalities and with histo-pathology consisting of extensive vacuolation and astrocytic gliosis of the brain. Later, in the mid-1950s, Gajdusek described kuru, a disease endemic to the natives living in the highlands of New Guinea. Kuru, translated as 729 ‘‘abnormal gait,’’ is characterized as a progressive gait ataxia in conjunction with behavioral abnormalities, myoclonus, and a progressive course to death. The pathologic features of kuru and CJD overlap with scrapie, a natural disease of sheep, also known to be transmissible. Each produced extensive vacuolation of the neuropil, also referred to as ‘‘spongiform change’’ (4).

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  Clinical Virology

  • Douglas D. Richman, Richard J. Whitley, Frederick G. Hayden, Douglas D. Richman, Richard J. Whitley, Frederick G. Hayden(Authors)
  • 2016(Publication Date)
  • ASM Press

    (Publisher)

  Experimental injection of the kuru-affected brain into macaques was subsequently shown to cause a spongiform encephalopathy and led to the realization that kuru was spreading among the Fore as an infectious disease from endocannibalistic practices (9). For these findings, Gadjusek was awarded the Nobel Prize in Medicine or Physiology in 1976 for “discoveries concerning new mechanisms for the origin and dissemination of infectious diseases.” The pioneering discovery of kuru as an infectious disease set the stage for the recognition of other rapidly progressive neurodegenerative diseases as part of a family of prion diseases, including Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) or “mad cow” disease in cattle, scrapie in sheep and goats, and chronic wasting disease (CWD) of deer and elk. The history of the nomenclature for CJD is complicated. Alfons Jakob published four papers in 1921 and 1923 describing five uncommon cases of rapidly progressive dementia, stating that his cases were quite similar to a previously published case reported by his professor, Hans Creutzfeldt, in 1920. This disease was referred to as Jakob’s or Jakob–Creutzfeldt disease for many decades until a prominent researcher in the field, Clarence J. Gibbs, began using the term Creutzfeldt–Jakob disease, as its acronym, CJD, was closer to his own initials (12). Interestingly, the cases Jakob described were in fact very different than Creutzfeldt’s case, in that only two of Jakob’s five cases had pathological evidence of the disease that we now consider to be prion disease, whereas Creutzfeldt’s case did not have prion disease (13). Thus, the name for human clinical prion disease should be Jakob’s disease or possibly Jakob–Creutzfeldt disease

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  Handbook of Dementing Illnesses

  • John Morris, James E. Galvin, David M. Holtzman, John Morris, James E. Galvin, David M. Holtzman(Authors)
  • 2006(Publication Date)
  • CRC Press

    (Publisher)

  15 Prion Diseases and Dementia James A. Mastrianni Center for Comprehensive Care and Research on Memory Disorder and Department of Neurology, University of Chicago, Chicago, Illinois, U.S.A. INTRODUCTION The prion diseases (PrD) are a group of unusual neurodegenerative disorders that affect both humans and animals, are associated with a variety of phenotypes, and are transmissible. The earliest description of PrD was that of Creutzfeldt and then Jakob in the early 1900s (1,2) as a progressive dementia associated with gait abnormalities and extensive vacuolation and astrocytic gliosis of the brain. In the mid-1950s, while studying primitive cultures in the Highlands of New Guinea, Carleton Gajdusek recognized and described a disease the Fore people, living in this region, called “kuru.” Sufferers of kuru developed a progressive gait ataxia, unusual behavior, and a relatively rapid progression to death. Gajdusek’s studies suggested that this disease was the result of a transmissible agent carried within the brain of the affected individual that was horizontally transmitted during rituals that involved cannibalism. Women and children were most affected by the disease, likely due to their greater contact with infectious tissue during both the preparation of the feast and the ritualistic ceremony. Pathologic examination of the kuru brain revealed the same pattern of vacuolation (also called spongiform change) that was observed in the disease described by Creutzfeldt and Jakob. Most importantly, however, this same pathology was astutely recognized by the veterinarian William Hadlow as the same pathology present in scrapie, a known transmissible disease of sheep associated with similar features of gait dysfunction, behavioral changes, and a rapid progression to death. It was natural to speculate that Creutzfeldt-Jakob disease (CJD) and kuru were similarly transmissible, which was confirmed in the mid-1960s (3,4).

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  Deadly Feasts

  Tracking The Secrets Of A Terrifying New Plague

  • Richard Rhodes(Author)
  • 1999(Publication Date)
  • Simon & Schuster

    (Publisher)

  Lancet; the letter went off on July 18. Three days later, concerned that a printers’ strike then under way in England might delay publication, Hadlow sent a copy of the letter to Gajdusek at the NIH. The letter was forwarded to Kainantu, where Joe Smadel’s near-genius privateer read it in early August.

  Hadlow’s Lancet letter compared the two pathologies. “Each disease,” the veterinarian wrote, “is endemic in certain confined populations, whether this be flock or tribe, in which the usual incidence is low, about one to two percent. Sheep, or persons, may become clinically affected months after they have been moved from flocks, or communities… . Moreover, scrapie may appear in a previously non-affected flock following introduction of a ram or ewe from a flock in which the disease is known to exist. Likewise, kuru may be introduced through marriage to populations previously free of the disease. Yet … the exact mechanism underlying the ‘spread’ of scrapie or kuru is obscure.” So was the cause: “No microbiological agent has been isolated, nor is there convincing evidence that either scrapie or kuru is an infectious disease in the generally recognized sense.” The natural history and the signs and symptoms of both diseases were “strikingly similar,” Hadlow thought. “Onset of each disorder is insidious and occurs in the absence of signs of antecedent illness.” Both diseases developed without fever and were relentlessly progressive. “Both diseases usually end fatally within three to six months after onset.” Both had similar signs: loss of coordination “which becomes progressively more severe, tremors, and changes in behavior are features of both diseases.” Remarkably similar were the changes in the brain: widespread nerve degeneration; astrogliosis; lack of inflammation; most of all those characteristic holes: “Large single or multilocular ‘soap bubble’ vacuoles in the [bodies] of nerve cells have long been regarded as a characteristic finding in scrapie; this extremely unusual change, apparently seldom seen in human neuropathologic material, also occurs in kuru.”

  Then Hadlow came to his electrifying point. Scrapie could be transmitted experimentally from sheep to sheep and sheep to goat. If a disease of sheep in Britain and a disease of humans in New Guinea were improbably alike in so many other ways, then it might follow that kuru could also be transmitted experimentally—thus proving that it was also an infectious disease. Hadlow didn’t say what was obvious, that scientists couldn’t experiment on humans. He proposed the next-best alternative (from the human point of view), that “it might be profitable … to examine the possibility of the experimental induction of kuru in a laboratory primate.” Successfully infect a chimpanzee or a monkey with kuru and it would then be possible to pursue laboratory studies to identify the infectious agent.

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