Kuru
Kuru
Kuru, a disease once endemic to Papua New Guinea and now virtually eliminated, is one of several types of spongiform encephalopathies, all thought to be caused by abnormal proteins called prions that riddle the brain with holes.
According to proponents of the prion hypothesis, these diseases can arise by direct infection with prions, by inheriting genes that produce faulty proteins, or by accidental genetic mutation. While prion diseases are more frequently seen in animals in the form of scrapie (sheep and goats), transmissible mink encephalopathy, and bovine spongiform encephalitis (“mad cow disease”), human prion diseases are relatively rare.
Kuru occurred among the Fore highlanders of Papua New Guinea, who called it the “laughing death.” It was first noted by Vincent Zigas of the Australian Public Health Service and D. Carleton Gajdusek of the U.S. National Institute of Health in 1957. The disease caused its victims to lose coordination and often to develop dementia. This disease affects the brain, and it was probably spread by the Fore practice of honoring the dead by eating their brains. When the Fore highlanders were persuaded to cease consuming human brains, kuru disappeared from Papua New Guinea. About 2,600 cases were identified before the Fore highlanders ended this custom.
The course of the illness runs from three months to one year. Among the major signs of kuru are cerebellar abnormalities such as rigidity of the limbs and clonus (rapid contractions and relaxations of muscles). Often, the victim bursts out in wild laughter for no obvious reason. Toward the end of the disease, the person with kuru is very calm and quiet and unresponsive to stimulation. Finally, the victim succumbs to severe skin ulcers caused by lying in one position for extended periods of time; or to pneumonia caused by stagnation of the blood in the lungs.
Among the other human spongiform encephalopathies caused by prions are Creutzfeldt–Jakob disease (millions of cases worldwide characterized by dementia and loss of coordination); Gerstmann–Straussler–Scheinker disease (found in 50 extended families by 1995); and fatal familial insomnia (trouble sleeping, followed by dementia; found in nine extended families by 1995).
The concept of prions, a term coined by Stanley B. Prusiner as an acronym for “proteinaceous infectious particles,” was originally met with great skepticism by most scientists when Prusiner and his coworkers proposed the existence of these proteins 15 years ago. The controversy continues today, although additional evidence has accumulated to support the hypothesis that spongiform encephalopathies are caused by prions rather than viruses.
According to current theory, prion proteins multiply by inducing benign protein molecules to convert themselves into the dangerous form of the molecule simply by changing their shape. In addition, prions underlie both inherited (i.e., familial) and communicable forms of diseases. This dual nature of prions—inducing other proteins to become prions, while also being the basis of inherited disease—is otherwise unknown to medical science. Prions can also cause sporadic (i.e., noncommunicable, noninherited) neu–rodegenerative diseases.
Scientists had know for years that Creutzfeldt-Jakob disease and kuru could be induced by injecting extracts of diseased brains into the brains of healthy animals. Although these infections were at first thought to be caused by a slow-acting virus, such an agent was never found. Moreover, ultraviolet and ionizing radiation, which destroys genetic material, did not eliminate the ability of brain extracts to cause disease. Prusiner’s group eventually determined that scrapie prions contained a single protein that they called PrP (prion protein). Further studies showed that PrP is harmless in its so-called benign state—i.e., when the backbone of the protein is twisted into many helices (spirals). PrP converts into its prion form when the backbone stretches out, flattening the overall shape of the protein.
The prion protein multiplies in the brain by a process Prusiner describes as a domino effect. In one particularly favored hypothesis of prion propagation, a PrP molecule contacts a normal PrP molecule and induces it to refold into the abnormal, flattened form. The newly transformed proteins then force other proteins to refold into the abnormal form until the prion protein form accumulates to destructive levels.
The discovery that kuru was caused by consumption of infected human brains has serious implications in developed countries. For example, cats in England have been infected by eating pet food made from contaminated beef. This has prompted concern that humans might get a prion disease by eating meat from infected cows.
Resources
PERIODICALS
Kolata, Gina. “Viruses or Prions: An Old Medical Debate Still Rages.” The New York Times (4 October 1994). Prusiner, S. B. “The Prion Diseases.” Scientific American 272 (January 1995): 48-57.
OTHER
National Institutes of Health, National Institute of Neurological Disorders and Stroke “NINDS Kuru Information Page” <http://www.ninds.nih.gov/disorders/kuru/kuru.htm> (accessed December 2, 2006).
University of Alabama, College of Arts and Sciences. “Kuru: The Dynamics of a Prion Disease– <http://www.as.ua.edu/ant/bindon/ant570/Papers/McGrath/McGrath.htm> (accessed December 2, 2006).
Marc Kusinitz
Kuru
Kuru
Disease History, Characteristics, and Transmission
Introduction
Kuru is a progressive, fatal, brain disease which was discovered in the 1950s by the American physician Carleton Gajdusek among the Fore (fore-ay) people of the eastern highlands of New Guinea. The name kuru means trembling with fear in the Fore dialect and refers to the tremor that is characteristic of the disease. Gajdusek went on to win the Nobel Prize in medicine in 1976 for his research, which suggested that the disease was linked to the ritualistic handling or consumption of human brain tissue during funeral ceremonies. Kuru is one of a group of rare brain diseases called the transmissible spongiform encephalopathies (TSEs), which also includes Creutzfeldt-Jakob disease (CJD). Postmortem studies show that TSEs lead to the development of tiny holes in brain tissue, giving it a “spongy” appearance. Kuru has now disappeared, as the Fore stopped the funeral practices that led to its spread.
Disease History, Characteristics, and Transmission
Kuru affected the cerebellum, which is the area at the base of the brain that controls coordinated movement. Accordingly, the symptoms of kuru included ataxia, or unsteadiness, tremor, stiffness, rigidity, and slurred speech. Persons with kuru did not usually suffer from memory loss or dementia until a later stage of the disease, or at all, although mood changes were common. Eventually, victims of kuru would become unable to stand or eat and they would slip into a comatose state. Death, from starvation or pneumonia would usually occur between three and nine months after the onset of symptoms.
Transmission of kuru occurred by exposure to infected brain tissue. The Fore custom was to remove the brains of the deceased during a funeral, possibly for ritualistic cooking and eating. The task of handling the brain fell to women relatives who were probably infected through any cuts or sores on their skin, or by actually consuming tissue. The women could also transmit the infection to their children through unwashed hands over the next several weeks. Once the disease entered the Fore food chain, it reached epidemic proportions. TSEs, like kuru and CJD are unusual because the infective agent is a kind of infectious protein called a prion, rather than a bacterium or virus. The long incubation time of kuru, which can be up to 40 years, meant that new cases continued to appear even as the disease itself began to die out once the funerary practices were abolished.
Scope and Distribution
Kuru was always confined to the Fore people who lived in the eastern highlands of New Guinea. They were isolated from Western civilization and from other natives by very mountainous terrain and disease has never been found elsewhere. Women and children of either sex seemed to be most at risk in the early years. Later, when adults exposed as children began to develop the disease, it affected men and women equally. During the 1950s and 1960s, it reached epidemic proportions and wiped out the population of many Fore villages.
Treatment and Prevention
There was no treatment for kuru and, at the present time, there is also no treatment for any TSE. Prevention of kuru meant stopping the funerary practices that allowed exposure to the infective prion. After this happened, in 1959, occasional cases still arose because of the long incubation time of the disease. The disease was first described in 1957 and the Fore people said that it appeared only a few years before this. No one knows how kuru first arose. It is possible that a few cases of a TSE crossed the species barrier from an animal with a similar disease and was spread by the consumption of infected tissue.
Impacts and Issues
Kuru has both cultural and scientific significance. Decimated Fore populations in the twentieth century endured upheaval to their communities and customs. Because more women than men died from the disease, Fore men were sometimes executed by village rulers in order to even out the population. When scientists first considered the disease to be triggered by a genetic susceptibility in the 1950s, the Australian government restricted the movements of the Fore to their own villages in an attempt to prevent intermarriage with islanders considered not susceptible. After Gajdusek discovered that kuru was caused by an infectious agent, the custom of honoring the dead by cannibalizing their tissue and brains ceased out of necessity. There has not been a case of kuru among the Fore in those born since cannibalism was eliminated.
Kuru might have remained as no more than a medical curiosity, had it not turned out to be a TSE. The infective agent in all TSEs, including CJD, is neither a bacterium nor a virus, but an entity known as a prion, which is best described as an infectious protein. A prion is an abnormally shaped version of a protein that occurs naturally in the brain. When the normal prion protein comes into contact with the abnormal version, it is converted into the abnormal version and can go on to corrupt other normal prion protein molecules. This cascade of damage then spreads throughout the brain. Interest in kuru was heightened with the emergence of variant CJD in the United Kingdom in the mid–1990s. The clinical course of kuru resembles that of variant CJD, rather than classical CJD. Both are spread through consumption of exposure to infected tissue and both may have arisen in the population in a similar way. Kuru could have started from a TSE that jumped the species barrier from an unknown animal host. Variant CJD is the human form of bovine spongiform encephalopathy, a TSE of cattle thought to have started when scrapie, a sheep TSE, entered cattle feed. Therefore, rare as TSEs are, it is worthwhile studying their pathology, as circumstances could conspire to allow the emergence of a new type of this fatal brain disease.
WORDS TO KNOW
EMERGING DISEASE: New infectious diseases such as SARS and West Nile virus, as well as previously known diseases such as malaria, tuberculosis, and bacterial pneumonias that are appearing in forms that are resistant to drug treatments, are termed emerging infectious diseases.
ENCEPHALOPATHY: Any abnormality in the structure or function of the brain.
INCUBATION PERIOD: Incubation period refers to the time between exposure to disease causing virus or bacteria and the appearance of symptoms of the infection. Depending on the microorganism, the incubation time can range from a few hours (an example is food poisoning due to Salmonella) to a decade or more (an example is acquired immunodeficiency syndrome, or AIDS).
PRIONS: Prions are proteins that are infectious. Indeed, the name prion is derived from “proteinaceous infectious particles.” The discovery of prions and confirmation of their infectious nature overturned a central dogma that infections were caused by intact organisms, particularly microorganisms such as bacteria, fungi, parasites, or viruses. Since prions lack genetic material, the prevailing attitude was that a protein could not cause disease.
See AlsoBovine Spongiform Encephalopathy (“Mad Cow” Disease); Creutzfeldt-Jakob Disease-nv; Prion Disease.
BIBLIOGRAPHY
Books
Wilson, Walter R., and Merle A. Sande. Current Diagnosis & Treatment in Infectious Diseases. New York: McGraw Hill, 2001.
Web Sites
Jansen, Paul A. eMedicine. “Kuru” Oct 15, 2005. <http://www.emedicine.com/med/topic1248.htm> (accessed March 19, 2007).
National Institute of Neurological Disorders and Stroke. “Kuru Information Page.” Feb 14, 2007. <http://www.ninds.nih.gov/disorders/kuru/kuru.htm> (accessed March 19, 2007).
Kuru
Kuru
Kuru, a disease once endemic to Papua New Guinea and now virtually extinct, is one of several types of diseases called spongiform encephalopathies, all thought to be caused by abnormal proteins called prions , which riddle the brain with holes. According to proponents of the prion hypothesis, these diseases can arise by direct infection with prions, by inheriting genes that produce faulty proteins, or by accidental genetic mutation . While prion diseases are more frequently seen in animals in the form of scrapie (sheep and goats ), transmissible mink encephalopathy, and bovine spongiform encephalitis ("mad cow disease"), human prion diseases are relatively rare.
Kuru occurred among the Fore highlanders of Papua New Guinea, who called it the "laughing death". It was first noted by Vincent Zigas of the Australian Public Health Service and D. Carleton Gajdusek of the U.S. National Institute of Health in 1957. The disease caused its victims to lose coordination and often to develop dementia . This disease affects the brain, and it was probably spread by the Fore practice of honoring the dead by eating their brains. When the Fore highlanders were persuaded to cease consuming human brains, kuru disappeared from Papua New Guinea. About 2,600 cases were identified before the Fore highlanders ended this custom.
The course of the illness runs from three months to one year. Among the major signs of kuru are cerebellar abnormalities such as rigidity of the limbs and clonus (rapid contractions and relaxations of muscles). Often, the victim bursts out in wild laughter for no obvious reason. Toward the end of the disease, the person with kuru is very calm and quiet and unresponsive to stimulation. Finally, the victim succumbs to severe skin ulcers caused by lying in one position for extended periods of time; or to pneumonia caused by stagnation of the blood in the lungs.
Among the other human spongiform encephalopathies caused by prions are Creutzfeldt-Jakob disease (millions of cases worldwide characterized by dementia and loss of coordination); Gerstmann-Straussler-Scheinker disease (found in 50 extended families by 1995); and fatal familial insomnia (trouble sleeping, followed by dementia; found in nine extended families by 1995).
The concept of prions, a term coined by Stanley B. Prusiner as an acronym for "proteinaceous infectious particles," was originally met with great skepticism by most scientists when Prusiner and his co-workers proposed the existence of these proteins 15 years ago. The controversy continues today, although additional evidence has accumulated to support the hypothesis that spongiform encephalopathies are caused by prions rather than viruses.
According to current theory, prion proteins multiply by inducing benign protein molecules to convert themselves into the dangerous form of the molecule simply by changing their shape. In addition, prions underlie both inherited (i.e., familial forms) and communicable forms of diseases. This dual nature of prions-inducing other proteins to become prions, while also being the basis of inherited disease-is otherwise unknown to medical science. Prions can also cause sporadic (i.e., non-communicable, non-inherited) neurodegenerative diseases.
Creutzfeldt-Jakob disease and kuru had been known for many years to be experimentally caused by injecting extracts of diseased brains into the brains of healthy animals. Although these infections were at first thought to be caused by a slow-acting virus , such an agent was never found. Moreover, ultraviolet and ionizing radiation , which destroys genetic material, did not eliminate the ability of brain extracts to cause disease. Prusiner's group eventually determined that scrapie prions contained a single protein that they called PrP ("prion protein"). Further studies showed that PrP is harmless in its so-called benign state, i.e., when the backbone of the protein is twisted into many helices (spirals). PrP converts into its prion form when the backbone stretches out, flattening the overall shape of the protein.
The prion protein multiplies in the brain by a process Prusiner describes as a "domino effect." In one particularly favored hypothesis of prion propagation, a molecule of PrP contacts a normal PrP molecule and induces it to refold into the abnormal, flattened form. The newly transformed proteins then force other proteins to refold into the abnormal form until the prion protein form accumulates to destructive levels.
The discovery that kuru was caused by consumption of infected brains has serious implications in developed countries. For example, cats in England have been infected by eating pet food made from contaminated beef. This has prompted concern that humans might get a prion disease by eating meat from infected cows.
Resources
periodicals
Kolata, Gina. "Viruses or Prions: An Old Medical Debate Still Rages." The New York Times October 4, 1994.
Prusiner, S. B. "The Prion Diseases." Scientific American 272 (January 1995): 48-57.
Marc Kusinitz
Kuru
Kuru
Definition
Kuru is the name of a progressively disabling and ultimately fatal brain infection caused by a unique protein particle called a prion.
Description
Kuru was first described in a specific tribal group in Papua, New Guinea. The word "kuru" means "to shake or tremble" in this tribal group's language. Individuals in New Guinea are believed to have acquired the infection through a cannibalistic ritual involving the blood and brains of deceased tribal members.
Because infection with kuru may occur years or decades before the advent of actual symptoms of the disease, it belongs to a group of diseases originally known as slow virus infections. Currently, slow virus infections are classed together as transmissible spongiform encephalopathies (TSE). TSEs include kuru, Creutzfeldt-Jakob disease , Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia. The TSE new variant called Creutzfeldt-Jakob disease (also known colloquially as "Mad Cow Disease") has received a great deal of public attention. The TSEs, including kuru, involve abnormal clumps of protein that accumulate throughout the brain, destroying brain tissue and leaving spongy holes.
Demographics
Kuru reached epidemic proportions among tribal members in the 1950s. Since the practice of cannibalism was halted, the disease has essentially disappeared. Some sources suggest that as few as zero to 10 cases of kuru are diagnosed each year.
Causes and symptoms
Kuru is caused by an infectious protein particle called a prion, which stands for proteinaceous infectious particle. A prion is similar to a virus, except that it lacks any nucleic acid, which prevents it from reproducing. Prions are abnormal versions of proteins that are found in the membranes of normal cells. These abnormal proteins can be passed directly to individuals through the ingestion of prion-infected tissue or when open sores on the recipient's skin are exposed to prion-infected tissue. In addition to being transmissible (as are other infectious agents like viruses or bacteria), prions are unique because they can also be acquired through genetic inheritance.
Symptoms of kuru tend to begin in later middle age, years or decades after the prion was actually acquired. Early symptoms include lack of energy, intense fatigue , headache , weight loss, joint pain , difficulty walking, twitchy muscles, personality changes, mood swings, memory problems, and bizarre behavior. As the disease progresses, the individual experiences stiff muscles, involuntary movements, problems talking, hallucinations, increased confusion, blindness, and sometimes dementia . Death often occurs within three months to two years of the initial symptoms.
Diagnosis
Diagnosis is arrived at through characteristic abnormalities found on the electroencephalogram (EEG), a test of brain waves and electricity. Seventy-five percent of individuals with kuru will display these specific abnormalities on EEG. MRI studies and biopsies (tissue samples) from the brain may also show changes that are characteristic of slow virus infection.
Treatment team
Diagnosis of slow virus infection is usually made by a neurologist .
Treatment
There are no available treatments for kuru. It is relentlessly progressive, incurable, and fatal. Supportive care for the patient and his or her family is the only treatment.
Prognosis
Kuru is always fatal.
Resources
BOOKS
Berger, Joseph R., and Avindra Nath. "Slow virus infections." Cecil Textbook of Medicine, edited by Thomas E. Andreoli, et al. Philadelphia: W.B. Saunders Company, 2000.
Murray, T. Jock, and William Pryse-Phillips. "Infectious diseases of the nervous system." Noble: Textbook of Primary Care Medicine, edited by John Noble, et al. St. Louis: W.B. Saunders Company, 2001.
PERIODICALS
Sy, Man-Sun, Pierluigi Gambetti, and Wong Boon-Seng. "Human Prion Diseases" Medical Clinics of North America 86 (May 2002) 551–571.
WEBSITES
National Institute of Neurological Disorders and Stroke (NINDS). Kuru Fact Sheet. Bethesda, MD: NINDS, 2003.
Rosalyn Carson-DeWitt, MD
Kuru
Kuru
Kuru is a disease of the nervous system that is extremely rare today, but that once was common among people in certain tribes in Papua, New Guinea, who practiced cannibalism.
KEYWORDS
for searching the Internet and other reference sources
Cannibalism
Neuromuscular system
Prions
Spongiform encephalopathies
Mystery in New Guinea
In the 1950s, a strange disease of the nervous system was killing people in certain tribes in the highlands of New Guinea, an island north of Australia in the Pacific Ocean. An American scientist named Daniel Carleton Gajdusek traveled to New Guinea to study the disease, which the people there called kuru. Eventually, he traced the problem to cannibalism, the eating of human flesh by another human. In this case, cannibalism took the form of a ritual in which people ate the uncooked brains of relatives who had died. Today, those New Guinea tribes no longer practice this ritual, and kuru has almost vanished.
Gajdusek thought that kuru was passed from a dead person’s brain to a living person by a slow virus, a virus that takes years to cause symptoms. Most scientists no longer believe this theory, however. Instead, most now think that kuru is caused by a prion, a type of protein that can cause infection. Kuru belongs to a group of human and animal diseases of the brain, known as transmissible spongiform (SPUN-ji-form) encephalopathies (en-sef-a-LOP-a-theez), that may be caused by prions. The word “spongiform” refers to the way infected brains become filled with holes until they look like sponges under a microscope. The most common such disease in humans is Creutzfeldt-Jakob disease.
What Are the Symptoms?
People with kuru have trouble controlling their movements, and this problem gets worse over time. Their arms and legs may appear stiff, or they may have rapid muscle spasms. Occasionally, their muscles may twitch or jerk uncontrollably, or their fingers, hands, toes, and feet may move in a slow, writhing motion. As the disease gets worse, people with kuru may start to lose their mental abilities, such as thought, memory, and concentration. Death usually occurs within 3 to 12 months. Kuru is extremely rare today, but it still fascinates scientists who are studying related diseases.
See also