Kuru

Kuru is a rare, fatal neurologic disease that is restricted to the highlands of New Guinea, where it has infected the Fore (pronounced for-ay), a tribe of remote highland natives. The word kuru means "trembling with fear" in the native language. Kuru occurred at epidemic levels during the 1950s-60s and was mainly the result of the practice of ritualistic cannibalism among the Fore, in which relatives prepared and consumed the tissues (including brain) of deceased family members. Brain tissue from individuals with kuru was highly infectious, and the disease was transmitted either through eating or by contact with open sores or wounds. Government discouragement of the practice of cannibalism led to a continuous decline in the disease. Today, kuru is virtually nonexistent.^[1]

Kuru belongs to a class of infectious diseases called transmissible spongiform encephalopathies (TSEs), also known as prion diseases. The hallmark of a TSE disease is misshapen protein molecules that clump together and accumulate in brain tissue. Scientists believe that misshapen prion proteins have the ability to change their shape and cause other proteins of the same type to also change shape. Other TSEs include Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia in humans, bovine spongiform encephalopathy in cattle (also known as mad cow disease), scrapie in sheep and goats, and chronic wasting disease in deer and elk.

Signs and Symptoms

The symptoms of kuru are so classic that the Fore people have been able to diagnose it with great accuracy themselves, even in the early forms. A report exists of a four-year-old child who was able to diagnose himself; his mother had already died of kuru.

The early stages of the disease are characterized by unspecific symptoms such as headache and joint pains. Six to 12 weeks later, walking becomes difficult and a tremor develops. Kuru means "trembling in fear" in the language of the Fore. This tremor disappears during sleep and is worsened in situations of stress and anxiety. Patients soon require assistance with walking, and either need to use a stick or accept support from family members.

The tremor eventually becomes course, making an upright position difficult to maintain, and the person becomes bedridden.

As the disease progresses, swallowing and eating become impossible and the body begins to waste away. Death usually occurs in three months to two years, with most patients dying within a year of symptom onset. Death usually results from starvation, complicated by pneumonia, or decubitus ulcers (pressure sores).

The disease may also be associated with progressive dementia, but this is not always a prominent part of the illness, as is the case with classic CJD. Some authorities believe the dementia of kuru may have a metabolic origin.

Patients with kuru have a tendency to laugh or cry without apparent reason.

Usually memory is spared until the disease becomes advanced, and people may not recognize their families.

The time interval between infection and symptom onset (incubation period) can be up to 30 years or longer.

Causes

Kuru is a prion disease transmitted by cannibalism (eating infected brain tissue). The name prion has only recently gained wide acceptance, replacing previously used terms such as slow virus, infectious proteins, infectious amyloids, and crystal protein.

Prions are thought to be both the infectious agent and the cause of spongiform encephalopathy in animals and humans. The prion is a naturally occurring protein (termed prion protein [PrP]) found in the Central Nervous System (CNS) and elsewhere. They replicate in host organisms by changing the shape of other proteins. Disease probably results because prions resist degradation. This resistance allows prions to accumulate within the CNS. This causes deposition of another protein, amyloid, in the brain and results in neurologic symptoms. At this stage, the brain appears spongiform, hence the classification as a spongiform encephalopathy. Spongiform brain tissue contains many holes, like a sponge.

Diagnosis

For a diagnosis in a member of the Fore tribe, symptoms must be present along with a history of attending cannibalistic feasts, and especially of consuming brain or nervous tissue. The amount of infected tissue eaten probably plays a role in development of the disease. Walking ability is most commonly used for diagnostic purposes.

Exams and tests

Kuru cannot be diagnosed based on laboratory tests. A conclusive diagnosis can be only be confirmed by examining brain tissue during an autopsy.

Brain Biopsy

In kuru, the brain shows characteristic amyloid collections, particularly in the cerebellum but also elsewhere in the brain. This gives the classic spongiform appearance of the prion diseases.

Treatment

No treatment or cure for kuru exists, and therapy is supportive.

Prevention

Discouraging cannibalism is the only way to prevent kuru.

Chances of Developing Kuru

The disease has essentially vanished because cannibalism is no longer practiced by the Fore.

Risk factors

Very few people in the world are at risk for kuru because it has not been found outside the context of cannibalism among the Fore tribe of Papau New Guinea who had practiced cannibalism and had eaten brain and CNS material, or had handled infected material. But several risk factors do exist for members of the tribe.

Sex

Cases of kuru predominantly occurred in women and children because they were more likely to consume the brain during cannibalistic feasts. As the disease disappeared, the ratio of infected men to infected women equalized, reflecting the result of exposure in childhood. Children no longer developed the disease.

Age

The age of onset has steadily risen because only Fore who participated in the feasts are developing the disease, and the feasts have not been practiced since the 1970s.

How Kuru is Spread

The prion of kuru is spread by consuming infected material or by introducing the prion directly into tissue. Nonhuman primates can also become infected

Kuru is spread through cannibalistic ingestion of infected human brain and CNS matter. It is also spread when a person's hands become contaminated while handling the body of a person who had died from kuru.

Kuru has not been passed on to a fetus or a nursing infant.

Related Problems

Most patients die of pressure sores, infections (including pneumonia), or other complication.

Clinical Trials

More information about clinical trials and kuru can be found at NIH Clinical Trials Website

Research

The National Institute for Neurological Disease and Stroke (NINDS) funds research to better understand the genetic, molecular, and cellular mechanisms that underlie the TSE diseases. Findings from this research will lead to ways to diagnose, treat, prevent, and ultimately cure these diseases.

Controversy

One of the enduring mysteries of kuru is its origin. If it did not exist until the middle of the 20th century, where did it originate? A recent origin is likely, given the statements of the Fore and the fact that the disease's effects were so devastating that they could not have existed if the epidemic had been prolonged. Kuru differs clinically and pathologically from classic CJD, and it more closely resembles vCJD (variant CJD), which is associated with BSE and, therefore, scrapie.

BSE is spread by the consumption of infected beef. A similar spread of kuru from infected meat is possible. Kuru may have been introduced into the Fore culture as a single (or a few) case(s) of a transmissible spongiform encephalopathy that crossed the species barrier and became widespread as a result of the cannibalistic rituals practiced by the Fore.

The Fore believe the disease began with the arrival of white men, and the idea that kuru may have began when individuals with CJD were introduced into the cannibalistic ritual has been proposed.

No new cases of kuru have been reported for several decades; the disease may be extinct.

Expected Outcome

The disease has no effective treatment and is uniformly fatal within six months to two years once the disease develops.

Because kuru mainly affects the cerebellum, which is responsible for coordination, the usual first symptoms are an unsteady gait, tremors, and slurred speech. Unlike most of the other TSEs, dementia is either minimal or absent. Mood changes are often present. Eventually, an infected individual becomes comatose and dies.

Survival rates

Kuru is universally fatal. Death usually occurs within 1 year after the first sign of symptoms.

History

Kuru is believed to have existed for only a short time before it was first described in 1957. At that time, the older members of the fore tribe said that it had not existed during their youth, which would mean that it had existed for only 10–20 years. The Fore were isolated both from Western civilization and from other natives by very mountainous terrain, and kuru has not been described in any other location.

Kuru was spread by the endocannibalistic funeral practices of the Fore. Family members were ritualistically cooked and eaten following their death, with the closest female relatives and children usually consuming the brain, which was the most infectious organ. The women scooped the brain tissue out with their bare hands and did not subsequently wash them for weeks. During this time, they were handling, caring for, and possibly infecting their young children.

The effects on the Fore were devastating, wiping out whole villages at the height of the disease.

Scope and impact

Only one report of a transmissible subacute spongiform encephalopathy outside the Fore tribe exists. This occurred in a visitor to the eastern highlands of New Guinea (Grabow, 1976).

During the late 1950s, when the disease was first described, it had an incidence of approximately 1 case per 100 residents.

Interesting Facts

Kuru has entered our culture at many levels—some medical as a prototype of prion disease and some cultural.

A San Francisco–based rock group has chosen the name kuru and received airplay of their music in April 2005. One of their pieces is titled "Brain Bleeding Cannibal Core," perhaps fitting for the disease for which they are named.

Other Resources

• Almond JW. Bovine spongiform encephalopathy and new variant Creutzfeldt-Jakob disease. Br Med Bull. 1998;54(3):749-59.

• Brown P, Bradley R. 1755 and all that: a historical primer of transmissible spongiform encephalopathy. BMJ. Dec 19-26 1998;317(7174):1688-92.

• Brown P, Will RG, Bradley R, et al. Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease: background, evolution, and current concerns. Emerg Infect Dis. Jan-Feb 2001;7(1):6-16.

• Carp RI, Kascsak RJ, Wisniewski HM, et al. The nature of the unconventional slow infection agents remains a puzzle. Alzheimer Dis Assoc Disord. Spring-Summer 1989;3(1-2):79-99.

• Chakraborty C, Nandi S, Jana S. Prion disease: a deadly disease for protein misfolding. Curr Pharm Biotechnol. Apr 2005;6(2):167-77.

• Collinge J. Variant Creutzfeldt-Jakob disease. Lancet. Jul 24 1999;354(9175):317-23.

• Collinge J. Molecular neurology of prion disease. J Neurol Neurosurg Psychiatry. Jul 2005;76(7):906-19.

• Fiorino AS. Sleep, genes and death: fatal familial insomnia. Brain Res Brain Res Rev. Oct 1996;22(3):258-64.

• Gajdusek DC. Kuru and Creutzfeldt-Jakob disease. Experimental models of noninflammatory degenerative slow virus disease of the central nervous system. Ann Clin Res. Oct 1973;5(5):254-61.

• Gajdusek DC. Kuru: an appraisal of five years of investigation. Eugen Q. Mar 1962;9:69-74.

• Gajdusek DC, Zigas V. Studies on kuru. I. The ethnologic setting of kuru. Am J Trop Med Hyg. Jan 1961;10:80-91.

• Gajdusek DC, Zigas V. Degenerative disease of the central nervous system in New Guinea; the endemic occurrence of kuru in the native population. N Engl J Med. Nov 14 1957;257(20):974-8.

• Gajdusek DC, Zigas V, Baker J. Studies on kuru. III. Patterns of kuru incidence: demographic and geographic epidemiological analysis. Am J Trop Med Hyg. Jul 1961;10:599-627.

• Gajdusek DC, Reid LH. Studies on kuru. IV. The kuru pattern in Moke, a representative Fore village. Am J Trop Med Hyg. Jul 1961;10:628-38.

• Gajdusek DC, Gibbs CJ Jr, Alpers M. Transmission and passage of experimental "kuru" to chimpanzees. Science. Jan 13 1967;155(759):212-4.

• Gajdusek DC. Unconventional viruses and the origin and disappearance of kuru. Science. Sep 2 1977;197(4307):943-60.

• Gardashian AM. [Kuru]. Zh Nevropatol Psikhiatr Im S S Korsakova. 1969;69(5):767-72.

• Grabow JD, Campbell RJ, Okazaki H, et al. A transmissible subacute spongiform encephalopathy in a visitor to the eastern highlands of New Guinea. Brain. Dec 1976;99(4):637-58.

• Hadlow WJ. Scrapie and Kuru. Lancet. 1959;2:289-290.

• Hornabrook RW. Kuru. Contemp Neurol Ser. 1975;12:71-90;294.

• Keohane C. The human prion diseases. A review with special emphasis on new variant CJD and comments on surveillance. Clin Exp Pathol. 1999;47(3-4):125-32.

• Lampert PW, Gajdusek DC, Gibbs CJ. Subacute spongiform virus encephalopathies. Scrapie, Kuru and Creutzfeldt-Jakob disease: a review. Am J Pathol. Sep 1972;68(3):626-52.

• Lee HS, Brown P, Cervenakova L, et al. Increased susceptibility to Kuru of carriers of the PRNP 129 methionine/methionine genotype. J Infect Dis. Jan 15 2001;183(2):192-196.

• Liberski PP, Brown P. Kuru: a half-opened window onto the landscape of neurodegenerative diseases. Folia Neuropathol. 2004;42 Suppl A:3-14.

• Miller MW, Williams ES. Chronic wasting disease of cervids. Curr Top Microbiol Immunol. 2004;284:193-214.

• Mocsny N. The spongiform encephalopathies: prion diseases. J Neurosci Nurs. Oct 1998;30(5):302-6.

• Nagai M, Kubota R, Greten TF, et al. Increased activated human T cell lymphotropic virus type I (HTLV-I) Tax11-19-specific memory and effector CD8+ cells in patients with HTLV-I-associated myelopathy/tropical spastic

paraparesis: correlation with HTLV-I provirus load. J Infect Dis. Jan 15 2001;183(2):197-205.

• Owen F. The molecular biology of the transmissible dementias. Mol Cell Biol Hum Dis Ser. 1994;4:110-32.

• Polo JM. [The history and classification of human prion diseases]. Rev Neurol. Jul 16-31 2000;31(2):137-41.

• Prusiner SB. Novel proteinaceous infectious particles cause scrapie. Science. Apr 9 1982;216(4542):136-44.

• Ridley RM, Baker HF. The myth of maternal transmission of spongiform encephalopathy. BMJ. Oct 21 1995;311(7012):1071-5; discussion 1075-6.

• Serpell LC, Sunde M, Blake CC. The molecular basis of amyloidosis. Cell Mol Life Sci. Dec 1997;53(11-12):871-87.

• Simpson NE. The map of chromosome 20. J Med Genet. Dec 1988;25(12):794-804.

• Sy MS, Gambetti P, Wong BS. Human prion diseases. Med Clin North Am. May 2002;86(3):551-71, vi-vii.

• Toledano-Gasca A. Hypotheses concerning the aetiology of Alzheimers disease. Pharmacopsychiatry. Aug 1988;21 Suppl 1:17-25.

• Tyler KL. Prions and prion diseases of the central nervous system. Curr Clin Top Infect Dis. 1999;19:226-51.

• Verdrager J. Kuru and "new variant" CJD. Southeast Asian J Trop Med Public Health. Sep 1997;28(3):535-40.

• Will RG, Ironside JW, Zeidler M, et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet. Apr 6 1996;347(9006):921-5.

• Wojtowicz S. Multiple sclerosis and prions. Med Hypotheses. Jan 1993;40(1):48-54.

• Zigas V, Gajdusek DC. Kuru: clinical study of a new syndrome resembling paralysis agitans in natives of the Eastern Highlands of Australian New Guinea. Med J Aust. Nov 23 1957;44(21):745-54.

References

1. ↑ Wadsworth, JDF, Joiner,S, et al. Kuru prions and sporadic Creutzfeldt–Jakob disease prions have equivalent transmission properties in transgenic and wild-type mice. Proc Natl Acad Sci 2008 March 11; 105(10): 3885–3890. Full Text

Article by Paul A. Janson,MD Tufts University School of Medicine. Emedicine Kuru Webpage.