Kuru (disease)

Not to be confused with Koro (medicine).
Kuru
Classification and external resources
Specialty Neurology
ICD-10 A81.8
ICD-9-CM 046.0
OMIM 245300
DiseasesDB 31861
MedlinePlus 001379
MeSH D007729

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 funerary cannibalism.[3]

Signs and symptoms

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 this transmissible spongiform encephalopathy; kuru is also known as "shiver".[4]

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.[5]

The symptoms of kuru are divided 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, sedentary stage, the patient is incapable of walking without support and suffers ataxia (loss of muscle coordination) and severe tremors. Furthermore, the victim is emotionally unstable and depressed, yet has uncontrolled sporadic laughter. Interestingly, the tendon reflexes are still normal at this point.[4]

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 faeces), has dysphagia (difficulty swallowing), is unresponsive to his or her surroundings, and acquires ulcerations (sores with pus and necrosis). An infected person usually dies within three months to two years after the first symptoms, often because of pneumonia or pressure sore infection.[4]

Causes

Those affected are usually people who follow the practice of family mortuary cannibalism.[6] In some parts of Papua New Guinea, bodies of those who died from kuru were dismembered to feast on the internal organs. "Often, they would feed morsels of brain to young children and elderly relatives."[6]

Kuru is believed to be caused by prions and is related to Creutzfeldt–Jakob disease (CJD).[7] Although it is considered a transmissible prion disease, some evidence shows the origin of the outbreak was due to eating a human (or a corpse) with sporadic CJD, thus implying a common pathophysiology.[1]

Transmission

In 1961, Australian Michael Alpers conducted extensive field studies among the Fore accompanied by anthropologist Shirley Lindenbaum.[8] Their historical research suggested 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 CJD.[9] 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.[10] Corpses of family members were often buried for days then exhumed once the corpses were infested with maggots at which point the corpse would be dismembered and served with the maggots as a side dish.[11]

The sexual dimorphism evident in the infection rates — kuru was eight to nine times more prevalent in women and children than in men at its peak — is because Fore men considered consuming human flesh to weaken them in times of conflict or battle, while the women and children were more apt to eat the bodies of the deceased, including the brain, where the prion particles were particularly concentrated. Also, the strong possibility exists 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 of the prion particles can lead to the disease,[12] a high degree of transmission occurred 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. 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, continuing to appear for several more decades. The last sufferer died in 2005.[8]

Immunity

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 genetic variant of prion protein G127V.[13][14] Further implications of the discovery, including evidence for rapid natural selection of populations, are being discussed.[15]

History

Kuru was first noted in the Fore tribes of the eastern highland and lowland 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. In the late 1950s, 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. Vincent Zigas, District Medical Officer, began observation. Blood specimens and brain tissue were sent to Melbourne.

In 1957, Daniel Carleton Gajdusek of the National Institute of Health joined 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 Gajdusek as part of an international collaboration with Australian Michael Alpers.[16] 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.

Subsequently, E. J. Field spent large parts of the late 1960s and early 1970s in New Guinea investigating the disease,[17] connecting it to scrapie and multiple sclerosis.[18] He noted similarities in the diseases interactions with glial cells, including the critical observation that the infectious process may depend on structural rearrangement of the host's molecules.[19] This was an early observation of what was to later become the prion hypothesis.[20]

In 1976, Gajdusek, along with Baruch S. Blumberg, was awarded the Nobel Prize in Physiology or Medicine,[21] in part for showing that kuru was transmissible to chimpanzees. This was the first time this group of encephalopathies had been demonstrated to be infectious, so was 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 in cattle.

References

  1. 1 2 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. 1 2 "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. 1 2 3 "Kuru: The Dynamics of a Prion Disease". As.ua.edu. Retrieved 2010-02-01.
  5. ↑ 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.
  6. 1 2 Mo Costandi (26 September 2013). "Mad cows, cannibalism and the shaking death". The Guardian. Retrieved 20 January 2016.
  7. ↑ 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.
  8. 1 2 "A life of determination". Monash University. Retrieved 20 January 2016.
  9. ↑ Kuru: The Science and the Sorcery (Siamese Films, 2010)
  10. ↑ Diamond JM (1997). Guns, germs, and steel: the fates of human societies. New York: W.W. Norton. p. 208. ISBN 0-393-03891-2.
  11. ↑ Liberski, P. P. (2009). "Kuru: Its ramifications after fifty years". Experimental Gerontology.
  12. ↑ 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. doi:10.1093/infdis/142.2.205. PMID 6997404.
  13. ↑ 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.
  14. ↑ Maggie Fox (November 18, 2009). "Gene protects brain-eaters from mad cow-type disease". Reuters. Retrieved 2009-11-30.
  15. ↑ 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.
  16. ↑ "Endocannibalism (ritual)". Monash University. Retrieved 2010-12-19.
  17. ↑ "Horizon - Season 8, Episode 6: Kuru - To Tremble with Fear".
  18. ↑ 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. doi:10.1007/bf00244170.
  19. ↑ Field, EJ (Feb 1978). "Immunological assessment of ageing: emergence of scrapie-like antigens". Age Ageing 7 (1): 28–39. doi:10.1093/ageing/7.1.28. PMID 416662.
  20. ↑ "BSE - mad cow - scrapie, etc.: Stimulated amyloid degeneration and the toxic fats".
  21. ↑ "Physiology or Medicine 1976 - Press Release". NobelPrize.org. Nobel Media AB. Retrieved 20 June 2013.
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