Kuru (disease)

Kuru is an incurable degenerative neurological disorder that is a type of transmissible spongiform encephalopathy, caused by a prion found in humans. 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 cannibalism.

History
Kuru was first noted in the Fore tribe of the Eastern Highlands Province 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 practised 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 R. M. and C. H. Berndt amoung 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. D. C. 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. 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.

In 1976 Gajdusek, along with Baruch S. Blumberg, was awarded the Nobel Prize in Physiology or Medicine 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 forwards in their investigation. As kuru is the only epidemic of human prion disease in known human history, it has provided important insights into the variant CJD.

Causes
Kuru is believed to be caused by prions and is related to Creutzfeldt-Jakob disease (CJD). It is best known for the epidemic that occurred in Papua New Guinea in the middle of the twentieth century, and earlier. Although it is considered a transmissible prion disease, there is some evidence that the origin of the outbreak was due to consumption of an individual (cannibalism) with sporadic CJD, thus implying a common pathophysiology.

Presentation
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."

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.

The symptoms of Kuru are then broken down into three specific stages. The first, ambulant stages, 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. Finally, the patient enters terminal stage, at which point he 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 his 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.

Transmission
Beginning in 1961, Australian doctor (now Professor) Michael Alpers conducted extensive field studies among the Fore, which were supported by the work of anthropologist Shirley Lindenbaum. Their historical research with the Fore suggests that the epidemic may have originated around 1900 from a single individual who lived on the edge of Fore territory, who is thought to have spontaneously developed some form of Creutzfeldt-Jakob Disease (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 8–9 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. Although ingestion itself of the prion particles can lead to the disease, 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 decades more, and the last sufferer died in 2005. 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
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. 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.

Kuru in popular culture

 * 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.
 * The Fore and kuru are a central element of the novel Dream Park by Larry Niven and Steven Barnes, which includes the explanation that kuru is transmitted via endocannibalism.
 * In the episode "My Balancing Act" of Scrubs, J.D. misdiagnoses a patient with Kuru, causing Dr. Cox to teach him about the zebra principle.
 * In the 2010 post-apocalyptic action film The Book of Eli people are asked to show their hands before conducting business, this is because kuru causes limb-shaking (called "the shakes" in the movie) and has become a method to recognize cannibals, as the main cause of kuru was cannibalism.
 * In the 2010 post-apocalyptic role-playing video game Fallout: New Vegas, the player meets a character named "Old Ben" who recalls a story of a butcher who sold "strange meat." In the story, after the local townsfolk began consuming this meat, people began developing "the shakes" and "going mad," which Old Ben describes as only occurring from the consumption of human flesh. This is likely a reference to cannibalism being a primary cause for kuru, although the disease itself is not explicitly mentioned in the game dialog.
 * In the episode "Theef" of The X-Files, Scully diagnoses a patient with Kuru, caused by some kind of Voodoo priest in a doctor who killed himself after a psychotic crisis.
 * In the novel "Meat" by Joseph D'Lacey, a town subsists on farmed humans, subsequently causing 'the shakes' to key characters in the story.
 * In the 2011 video game "Dead Island", the cause of the zombie epidemic is hinted to be a mutated strain of Kuru.
 * In Deadtime Stories: Volume 2 by George A. Romero the first story titled "The Gorge" Hints at signs of Kuru (mostly the shakes).