AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Kuru is a 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.

The disease is now almost nonexistent and 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 tribe said that it had not existed during their youth, which would mean that it had existed for only 10-20 y.) 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. Kuru is caused by a prion and serves as a prototype for a group of prion diseases (scrapie in sheep, transmissible mink spongiform encephalopathy, bovine spongiform encephalopathy [BSE; also called mad cow disease]). It reached epidemic proportions by entering the Fore food chain. In humans, other prion diseases, including familial Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia, are transmitted by genetic mutations.

Kuru has largely disappeared today because cannibalism has been abolished among the Fore. The place of kuru in medicine is as a model for prion diseases such as BSE and the so-called variant Creutzfeldt-Jakob disease (vCJD), which is thought to be the consequence of the spreading of the BSE prion to humans.

One of the enduring mysteries of kuru is the 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, which is associated with BSE and, therefore, scrapie.

BSE is spread from the consumption of infected beef. A similar spread of kuru from infected meat and, possibly, scrapie from imported sheep is possible.

Classic CJD is predominantly a dementing disease with relatively minor movement dysfunction, while kuru and vCJD are diseases that show profound disordered movement, tremors, and less dementia. In the case of kuru, there may be no dementia at all. 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 endocannibalistic rituals practiced by the Fore.

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

Pathophysiology

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 CNS and elsewhere.

In the alpha-helical configuration, PrP usually is sensitive to protease degradation and is termed PrP-sen. Disease results when the PrP is reconfigured into the beta-sheet configuration, which is resistant to protease degradation. This configuration is termed PrP-res. The PrP-res proteins are resistant not only to protease degradation but also to radiation, heat, and most other processes that destroy proteins. Neither the transmissible agent nor the disease-producing agent contains any DNA or RNA. Because they are naturally occurring proteins, immunologic response to the infection is absent.

The prion of kuru is infectious orally and is capable of transmission to nonhuman primates by this route and by direct introduction into various tissues. Scrapie may be transmitted to sheep from pastures that have previously been grazed by scrapie-infected sheep and have remained unused for as many as 30 years, demonstrating the extreme resistance of prions to degradation. CJD also has been transmitted iatrogenically by transplanted tissue such as dura mater grafts. Potential transmission via the blood supply has been suggested but never demonstrated.

Prions are capable of replicating themselves in organisms; or, more correctly, prions are capable of changing the existing PrP-sen to PrP-res. This change takes place particularly in the CNS. Resistance to degradation is the probable source of disease because prions accumulate within the CNS, causing amyloid collections and resulting in neurologic symptoms and the spongiform appearance on pathologic examination. Hence, the term spongiform encephalopathy is applied to this group of diseases.

The name prion has only recently gained wide acceptance, replacing previously used terms such as slow virus, infectious proteins, infectious amyloids, and crystal protein. Mice that lack the gene responsible for PrP cannot be infected with the agent causing spongiform encephalopathy. The lack of this protein has no apparent effect, except an alteration in the circadian rhythm of these mice. They have a normal life span. For this reason, the PrP has been proposed to be a redundant protein.

The PRNP gene has recently been identified as altering the susceptibility to prion infection. The gene has a polymorphism at site 129 for either methionine or valine and has been noted as showing a strong increase in susceptibility to kuru if methionine is present on both genes (M/M). All cases of vCJD in the United Kingdom have occurred in people of the M/M genotype as well.

The pathologic similarity between the spongiform encephalopathies and other degenerative brain diseases, such as Alzheimer disease, is the subject of speculation at this point.

Frequency

United States

This disease does not occur in the United States.

International

Kuru is restricted to the Fore, a people found in the New Guinea highlands; although one report exists of a case of a transmissible subacute spongiform encephalopathy in a visitor to the eastern highlands of New Guinea (Grabow, 1976). Kuru was acquired during endocannibalistic funeral rituals that are no longer practiced; therefore, the disease is disappearing as well. During the late 1950s, when the disease was first described, it had an incidence of approximately 1 case per 100 residents. The incubation period may be as long as 3 decades. 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.

Mortality/Morbidity

The disease has no effective treatment and is uniformly fatal within 6 months to 2 years once the disease develops. The incubation period may be as short as 4 years or as long as 3 decades.

Race

Kuru has affected only the Fore of New Guinea.

Sex

Cases of kuru predominantly occurred in women and children because they were more likely to consume the brain during endocannibalistic feasts. As the disease began to disappear, the ratio of men to women became equal, reflecting the result of exposure in childhood, and 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.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Kuru was present in only the Fore, a New Guinea highland tribe, but has now progressively disappeared following cessation of endocannibalism. Kuru has not been found outside this context; therefore, the possibility of any practitioner now encountering a case of kuru is extremely remote.

• To establish the diagnosis of kuru, a member of the Fore tribe must have a clinical disease that is characteristic and should have a history of attending cannibalistic feasts.
• • A history of the consumption of brain or nervous tissue was especially important.
  • The amount of infected tissue eaten probably plays a role in development of the disease. The incubation period may be as long as 3 decades.
• The clinical presentation of Kuru is (was) remarkably uniform. The prodromal symptoms of headache and joint pains are followed 6-12 weeks later by difficulty in walking and then a cerebellar tremor, hence the name, which 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, either using a stick or accepting support from family members.
• The tremor then becomes course, making an upright position difficult for patients to maintain, and they become bedridden.
• Eventually, patients can no longer swallow or eat, and progressive wasting results.
• Death follows a clinical course of 3 months to 2 years, with most patients dying within a year of symptom onset.
• The disease may also be associated with progressive dementia, but this certainly 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.
  • Memory usually is relatively spared until the disease becomes advanced, when patients may not recognize their families.
• This disease is so classic in its presentation that the Fore have been able to diagnose it with great accuracy themselves, even in the early forms. A report exists of a 4-year-old child who was able to diagnose himself: His mother had already died of kuru.

Physical

• Physical findings are initially limited to the CNS.
• • The disease is characterized by ataxia and muscular weakness early in the course. At this point, unaided ambulation is still possible.
  • The disease progresses to a stage in which patients must use a stick, crutch, or human assistance to walk.
  • In the later stages, dysarthria and convergent strabismus develop.
  • Eventually, patients can no longer stand without assistance and may even be unable to sit, raise their head, or roll over.
  • Patients eventually lose the ability to chew, swallow, or control excretory processes. They then become progressively wasted.
  • Death results from starvation, complicating pneumonia, or decubitus ulcers.
• Dementia is not a prominent part of the disease, and some authors, such as Zigas et al, feel that little or no dementia exists.
• • As noted above, the lack of dementia is in contradistinction to classic CJD, which is characterized by predominant dementia and less so by ataxia and muscular findings (see History).
  • Emotional lability is well described, with inappropriate laughing being one of the classic features.
• In a classic screening test, the affected patient was asked to stand on just one foot.

Causes

Kuru is a prion disease transmitted by endocannibalism. No evidence indicates spread in utero or via human milk.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Creutzfeldt-Jakob disease
Variant Creutzfeldt-Jakob disease
Gerstmann-Sträussler-Scheinker syndrome
Fatal familial insomnia

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• No laboratory studies are helpful in diagnosing kuru except postmortem pathologic evaluation of CNS tissue.

Imaging Studies

• No imaging studies are helpful in diagnosing kuru.

Histologic Findings

The brain shows characteristic amyloid collections of PrP-res, particularly in the cerebellum but also elsewhere in the brain. This gives the classic spongiform appearance of the prion diseases.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

No treatment for kuru exists, and therapy was directed at supportive measures.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

No medications are indicated in the treatment of kuru.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Deterrence/Prevention:

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

Complications:

• Most patients die of complications such as decubiti, infections, and pneumonia.

Prognosis:

• The disease is uniformly fatal.

Patient Education:

• For excellent patient education resources, visit eMedicine's Brain and Nervous System Center. Also, see eMedicine's patient education article Mad Cow Disease and Variant Creutzfeldt-Jakob Disease.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Special Concerns

• Kuru has been transmitted to monkeys and mice under laboratory conditions, but it has no real veterinary implications. Other prion diseases are of major veterinary importance, and an understanding of kuru is helpful in understanding these other prion diseases. All prion diseases have similar proteins as their causative agents, and, although species barriers exist, transmission between species is well documented.
• The oldest known prion disease is scrapie, a disease found in sheep that was described as early as the 17th century. In England, during the 18th century, recommended measures for control of the disease included the slaughtering of infected sheep away from the flock. Giving the meat to the servants to eat was considered safe. In 1936, the disease was shown to be transmissible when sheep were kept for an 18-month incubation for the first time. Also at that time, the disease was transmitted when sheep were accidentally inoculated with a preparation that had been derived from sheep infected with scrapie. Earlier efforts at transmission had probably been unsuccessful because the animals had been observed for only a few months.
• • Scrapie has also been proposed as possibly being transmitted to humans in areas where large quantities of sheep brain are eaten, such as northern Africa. Here, an unusually high incidence of a particular form of CJD exists.
  • Scrapie is thought to be the source of the prion that causes BSE and the resultant new vCJD in humans that is now seen in Great Britain.
• CJD occurs in 3 patterns.
• • A familial form and a sporadic form of CJD exist; both have been described for many years, and both are thought to be caused by prions. In the case of the familial disorder, an abnormal gene on chromosome 20 has been documented. The sporadic form is thought to be caused by a spontaneous mutation at the same site.
  • A new form of this disease, termed vCJD, presents in younger patients and has been associated with BSE. As noted above, the clinical features of vCJD and kuru are similar, and both differ from classic CJD.
• Prion spongiform encephalopathy also is present in mink on mink farms, where epidemics have occurred.
• Chronic wasting disease may be present in as many as 2.5-10% of wild deer and elk in northern Colorado and southern Wyoming in the United States. Although cases have been investigated by the Centers for Disease Control and Prevention (CDC), no transmission to humans has been documented.
• Other prion diseases may be present in animals and humans, but the difficulties encountered in demonstrating the prion have hampered investigation.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Oct 15, 2005