Kuru (disease)

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Kuru
Classification and external resources
ICD-10A81.8
ICD-9046.0
OMIM245300
DiseasesDB31861
MedlinePlus001379
MeSHD007729
 
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Kuru
Classification and external resources
ICD-10A81.8
ICD-9046.0
OMIM245300
DiseasesDB31861
MedlinePlus001379
MeSHD007729

Kuru is an incurable degenerative neurological disorder endemic to tribal regions of Papua New Guinea. It is a type of transmissible spongiform encephalopathy, caused by a prion found in humans.[1]

The term "kuru" derives from the Fore word "kuria/guria" ("to shake"),[2] a reference to the body tremors that are a classic symptom of the disease; it is also known among the Fore as the laughing sickness due to the pathologic bursts of laughter people would display when afflicted with the disease. It is now widely accepted that Kuru was transmitted among members of the Fore tribe of Papua New Guinea via cannibalism.[3]

History[edit]

Kuru was first noted in the Fore tribes of Eastern Highlands and lowlands Provinces of Papua New Guinea as Australian administrators explored the area in 1953–1959. Kuru (Keru) was reported by W. T. Brown in Kainantu Patrol Report No 8 of 1953/54 (13 January 1954 - 20 February 1954.) .. "The first sign of impending death is a general debility which is followed by general weakness and inability to stand. The victim retires to her house. She is able to take a little nourishment but suffers from violent shivering. The next stage is that the victim lies down in the house and cannot take nourishment, and death eventually ensues." The same reports described the cannibalism practiced by the Fore people. It was in the late 1950s that the full extent of the disease was realized, after it had reached large infection rates in the South Fore of the Okapa Subdistrict, though the agent was unknown.

Awande Hospital was built in 1961 in the Eastern Highlands to accommodate kuru patients and research. Kuru was first noted in 1952-1953 by anthropologists Ronald Berndt and Catherine Berndt among the Fore, Yate, and Usanufa people. Charles O. Pfarr, Lutheran Medical Services, was brought to the area by tribal persons and reported the disease to Australian authorities. Dr. Vincent Zigas, District Medical Officer, began observation. Blood specimens and brain tissue were sent to Melbourne.

In 1957, Dr. Daniel Carleton Gajdusek of the National Institute of Health joined Dr. Zigas at the research center. Sister Eva Hasselbusch of Germany joined the hospital in 1959 to take care of the patients. Sister Maria Horn of Germany was the first trained sister to work with the doctors to study the disease. By 1968, the hospital ceased to function as a kuru hospital and was closed (1886-1986, The Lutheran Church in Papua New Guinea by Herwig Wagner and Hermann Reiner).

The disease was researched by Daniel Carleton Gajdusek as part of an international collaboration with Australian doctor (now Professor) Michael Alpers.[4] In the mid-1960s, Alpers collected post-mortem brain tissue samples from an 11-year-old Fore girl, Kigea, who had died of kuru. He took these samples to Gajdusek in the USA, who then injected two chimpanzees with the infected material. Within two years, one of the chimps, Daisy, had developed kuru, demonstrating that the unknown disease factor was transmitted through infected biomaterial and that it was capable of crossing the species barrier to other primates.

Subsequenty, E. J. Field spent large parts of the late 1960s and early 1970s in New Guinea investigating the disease,[5] connecting it to scrapie and multiple sclerosis.[6] He noted similarities in the diseases interactions with glial cells, including the critical observation that the infectious process may depend on structural re-arrangement of the host's molecules.[7] This was an early observation of what was to later become the prion hypothesis.[8]

In 1976, Gajdusek, along with Baruch S. Blumberg, was awarded the Nobel Prize in Physiology or Medicine,[9] in part for showing that kuru was transmissible to chimpanzees. This was the first time that this group of encephalopathies had been demonstrated to be infectious and therefore a major step forward in their investigation. As kuru is the only epidemic of human prion disease in known human history, it has provided important insights into Creutzfeldt–Jakob Disease (CJD) in humans and Bovine Spongiform Encephalopathy (BSE) in cattle.

Causes[edit]

Kuru is believed to be caused by prions and is related to Creutzfeldt–Jakob disease (CJD).[10] It is best known for the epidemic that occurred in Papua New Guinea in the middle of the twentieth century, and earlier.[11] Although it is considered a transmissible prion disease, there is some evidence that the origin of the outbreak was due to eating a human (or a corpse) with sporadic CJD, thus implying a common pathophysiology.[1]

Presentation[edit]

Kuru causes physiological as well as neurological effects that ultimately lead to death. It was endemic among the Fore tribe of Papua New Guinea and was confined to the Fore population and those nearby populations with whom they intermarried. It is characterized by truncal ataxia, preceded by headaches, joint pains and shaking of the limbs. Trembling is present in almost all patients with transmissible spongiform encephalopathy; Kuru is also known as "shiver".[12]

The preclinical or asymptomatic phase, also called the incubation period, lasts between possibly 5 to 20 years following initial exposure. The clinical stage lasts an average of 12 months.[13]

The symptoms of kuru are broken down into three specific stages. The first, ambulant stage, exhibits unsteady stance and gait, decreased muscle control, tremors, deterioration of speech and dysarthria (slurred speech). In the second stage, sedentary stage, the patient is incapable of walking without support, suffers ataxia (loss of muscle coordination) and severe tremors. Furthermore, the victim is emotionally unstable, depressed, yet having uncontrolled sporadic laughter. Interestingly, the tendon reflexes are still normal at this point.[12]

In the final, terminal stage, the patient is incapable of sitting without support, suffers severe ataxia (no muscle coordination), is unable to speak, is incontinent (unable to restrain natural discharges/evacuations of urine or feces), has dysphagia (difficulty swallowing), is unresponsive to their surroundings, and acquires ulcerations (sores with pus and necrosis). An infected person usually dies within 3 months to 2 years after the first symptoms, often because of pneumonia or pressure sores infection.[12]

Transmission[edit]

In 1961, Australian Michael Alpers conducted extensive field studies among the Fore accompanied by anthropologist Shirley Lindenbaum.[14] Their historical research suggested that the epidemic may have originated around 1900 from a single individual who lived on the edge of Fore territory and who is thought to have spontaneously developed some form of Creutzfeldt-Jakob Disease (CJD).[15] Alpers and Lindenbaum's research conclusively demonstrated that kuru spread easily and rapidly in the Fore people due to their endocannibalistic funeral practices, in which relatives consumed the bodies of the deceased to return the "life force" of the deceased to the hamlet, a Fore societal subunit.[16]

The dysmorphism evident in the infection rates — kuru was 8 to 9 times more prevalent in women and children than in men at its peak — is because, while the men of the village took the choice cuts, the women and children would eat the rest of the body, including the brain, where the prion particles were particularly concentrated. There is also the strong possibility that it was passed on to women and children more easily because they took on the task of cleaning relatives after death and may have had open sores and cuts on their hands.[2]

Although ingestion itself of the prion particles can lead to the disease,[17] there was a high degree of transmission if the prion particles could reach the subcutaneous tissue. With elimination of cannibalism because of Australian colonial law enforcement and the local Christian missionaries' efforts, Alpers' research showed that Kuru was already declining among the Fore by the mid‑1960s, although cases continued to appear for several more decades and the last sufferer died in 2005.[14] However, the mean incubation period of the disease is 14 years, and cases were reported with latencies of 40 years or more for those who were most genetically resilient.

Immunity[edit]

Simon Mead of University College London, and others, showed in their genetic and clinical assessment that people who survived the epidemic in Papua New Guinea were carriers of a prion-resistant factor. Mead's group has shown the source of immunity to be the inheritance of a genetic variant of prion protein G127V.[18][19] This work remains breaking news as of November 22, 2009, and further implications of the discovery, including evidence for rapid natural selection of populations, are being discussed.[20]

Kuru in popular culture[edit]

The history and epidemiology of kuru has been the subject of both fictional and non-fictional portrayals. The 2010 documentary Kuru: The Science and the Sorcery recounts the work of Alpers, Gajdusek and their colleagues in uncovering the link between kuru and endocannibalism in the Fore and the discovery of prions as the cause of the disease.[21]

The connection between kuru and cannibalism has been drawn in popular entertainment, where characteristic "shaking" or other kuru-like symptoms are an indicator of cannibalism.[citation needed] For example, in the 2010 post-apocalyptic film The Book of Eli, people are asked to show their hands before doing business as trembling hands are considered a sign of cannibalism. Similarly, in the video games Fallout 3 and Fallout: New Vegas, the player encounters townsfolk who display kuru-like symptoms after unwittingly consuming human flesh. In the 2013 movie We Are What We Are the matriarch of a cannibalistic family shows symptoms of Kuru disease and dies. The Patriarch of the family also shows signs of Kuru. The family has been eating humans for centuries.

A 1995 episode of the American science fiction television series The X-Files titled "Our Town" revolved around the residents of a fictional Arkansas town who displayed kuru-like symptoms, which apparently resulted from cannibalistic practices brought back from the South Pacific. The episode "Theef" also dealt with a victim seemingly suffering from the disease.

References[edit]

Notes
  1. ^ a b Wadsworth JD, Joiner S, Linehan JM et al. (March 2008). "Kuru prions and sporadic Creutzfeldt-Jakob disease prions have equivalent transmission properties in transgenic and wild-type mice". Proc. Natl. Acad. Sci. U.S.A. 105 (10): 3885–90. doi:10.1073/pnas.0800190105. PMC 2268835. PMID 18316717. 
  2. ^ a b "Kuru : Article by Paul A Janson". eMedicine. 2009-04-13. Retrieved 2010-02-01. 
  3. ^ Lindenbaum S (November 2008). "Review. Understanding kuru: the contribution of anthropology and medicine". Philos. Trans. R. Soc. Lond., B, Biol. Sci. 363 (1510): 3715–20. doi:10.1098/rstb.2008.0072. PMC 2735506. PMID 18849287. 
  4. ^ "Endocannibalism (ritual)". Monash University. Retrieved 2010-12-19. 
  5. ^ "Horizon - Season 8, Episode 6: Kuru - To Tremble with Fear". 
  6. ^ Field, EJ (7 Dec 1967). "The significance of astroglial hypertrophy in Scrapie, Kuru, Multiple Sclerosis and old age together with a note on the possible nature of the scrapie agent". J Neurology 192 (3): 265–274. 
  7. ^ Field, EJ (Feb 1978). "Immunological assessment of ageing: emergence of scrapie-like antigens". Age Ageing 7 (1): 28–39. PMID 416662. 
  8. ^ "BSE - mad cow - scrapie, etc.: Stimulated amyloid degeneration and the toxic fats". 
  9. ^ "Physiology or Medicine 1976 - Press Release". NobelPrize.org. Nobel Media AB. Retrieved 20 June 2013. 
  10. ^ Collinge J, Whitfield J, McKintosh E et al. (June 2006). "Kuru in the 21st century—an acquired human prion disease with very long incubation periods". Lancet 367 (9528): 2068–74. doi:10.1016/S0140-6736(06)68930-7. PMID 16798390. 
  11. ^ "Kuru Information Page: National Institute of Neurological Disorders and Stroke (NINDS)". Ninds.nih.gov. 2010-01-11. Retrieved 2010-02-01. 
  12. ^ a b c "Kuru: The Dynamics of a Prion Disease". As.ua.edu. Retrieved 2010-02-01. 
  13. ^ Collinge J, Whitfield J, McKintosh E et al. (November 2008). "A clinical study of kuru patients with long incubation periods at the end of the epidemic in Papua New Guinea". Philosophical Transactions of the Royal Society B: Biological Sciences (London, U.K.: Royal Society Publishing) 363 (1510): 3725–39. doi:10.1098/rstb.2008.0068. ISSN 1471-2970. PMC 2581654. PMID 18849289. Retrieved 2009-07-23. 
  14. ^ a b "A life of determination" (Michael Alpers biography), Monash University, School of Medicine, Nursing and Health Sciences
  15. ^ Kuru: The Science and the Sorcery (Siamese Films, 2010)
  16. ^ Diamond JM (1997). Guns, germs, and steel: the fates of human societies. New York: W.W. Norton. p. 208. ISBN 0-393-03891-2. 
  17. ^ Gibbs CJ, Amyx HL, Bacote A, Masters CL, Gajdusek DC (August 1980). "Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates". J. Infect. Dis. 142 (2): 205–8. PMID 6997404. 
  18. ^ Mead S, Whitfield J, Poulter M, Shah P, Uphill J, Campbell T, Al-Dujaily H, Hummerich H, Beck J, Mein CA, Verzilli C, Whittaker J, Alpers MP, Collinge J (November 2009). "A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure". N. Engl. J. Med. 361 (21): 2056–2065. doi:10.1056/NEJMoa0809716. PMID 19923577. 
  19. ^ Maggie Fox (November 18, 2009). "Gene protects brain-eaters from mad cow-type disease". Reuters. Retrieved 2009-11-30. 
  20. ^ Medical Research Council (United Kingdom) (November 21, 2009). "Brain Disease 'Resistance Gene' Evolves in Papua New Guinea Community; Could Offer Insights Into CJD". Science Daily (online) (Science News). Retrieved 2009-11-22. 
  21. ^ "Kuru: The Science and the Sorcery". IMDb. Retrieved 14 March 2014.