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The term "kuru" derives from the Fore word "kuria/guria" ("to shake"), 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.
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".
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.
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 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 sore infection.
Those affected are usually people who follow the practice of family mortuary cannibalism. 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."
Kuru is believed to be caused by prions and is related to CJD. 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.
In 1961, Australian Michael Alpers conducted extensive field studies among the Fore accompanied by anthropologist Shirley Lindenbaum. 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. 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.
The dysmorphism 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.
Although ingestion of the prion particles can lead to the disease, 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[quantify] 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.
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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. Further implications of the discovery, including evidence for rapid natural selection of populations, are being discussed.
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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. 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, connecting it to scrapie and multiple sclerosis. 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. This was an early observation of what was to later become the prion hypothesis.
In 1976, Gajdusek, along with Baruch S. Blumberg, was awarded the Nobel Prize in Physiology or Medicine, 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.
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