In a previous blog, I examined the scientific literature on fatal familial insomnia (FFI), an incredibly rare genetic sleep disorder cause caused by a genetic mutation that leads to prion disease. Today’s blog takes a brief look at another prion disease – ‘kuru’. Like FFI, kuru is also an incurable and degenerative neurological disorder (i.e., a transmissible spongiform encephalopathy) although the only people known to have experienced it are a few cannibalistic tribes in the Eastern Highlands Province of New Guinea (most notably the Fore tribe) where it is known as the ‘laughing sickness’ or the ‘laughing disease’ (that refer to one of the disease’s most noticeable symptoms – the hysterical and pathological outbursts of laughter that suffering individuals produce in the latter stages of the disease).
The disease has a relatively long incubation period (5 to 20 years, with an average of 10 to 13 years according to a study led by Dr. Jerome Huillard d’Aignaux in a 2002 issue of the journal Epidemiology. However, a study published by Dr. R.L. Klitzman and colleagues in an earlier issue of Neuroepidemiology reported that:
“Epidemiological data were collected on…65 kuru patients who died or were diagnosed between 1977 and 1981. From these…2 or more participants were exposed to the infectious agent for the first time and died within weeks or months of each other 25–30 years later. Thus, it is shown that the natural incubation period of kuru could be as long as 25–30 years”
A more recent paper by Dr. John Collinge and colleagues in The Lancet identified 11 kuru sufferers from July 1996 to June 2004 all living in the South Fore. They reported that the minimum estimated incubation periods ranged from 34 to 41 years. However, they also noted that the likely incubation periods in men ranged from 39 to 56 years and could have been up to 7 years longer. Therefore, incubation periods could be very long.
According to Dr. Robert Will (in a 2003 issue of the British Medical Bulletin), over 2700 cases of kuru have been recorded since 1957 (in a total population within the kuru region of 36,000 people). Those infected with kuru typically die between 3 and 24 months following the first symptoms. Because of the long incubation period, it is thought that the last person to die of kuru in New Guinea was only seven years ago (i.e., 2005).
The word ‘kuru’ (not to be confused with ‘koro’, the culture bound genital retraction syndrome typically found in south-east Asia) is derived from the Fore tribe’s word ‘to shake’ (‘kuria’). Research carried out in the 1960s and 1970s demonstrated beyond doubt that kuru was transmitted from one individual to another via the cannibalistic practices of the Fore tribe (particularly the South Fore of the Okapa Subdistrict that showed the most large and notable kuru infection rates). The first recorded cases of kuru were made by a number of Australians back in the early 1950s. W.T. Brown reported that
“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”.
It was in the early 1960s at the Eastern Highlands Awande Hospital that kuru sufferers underwent medical research in an effort to locate the cause of the disease. It was the pioneering work Daniel Gajdusek and Michael Alpers that led to the discovery of the causative agent of kuru. Brain tissue samples were taken from an 11-year old girl who had died of kuru and subsequently injected into a couple of chimpanzees. One of the chimps developed kuru within 24 months, and the research showed unequivocally that kuru was capable of infection cross-species. According to Dr. Robert Will, “this seminal discovery led to the successful laboratory transmission of [Creutzfeldt-Jakob disease] and initiated research into the epidemiology and pathogenesis of human prion disease”
It is now generally believed that the kuru outbreak began following the consumption of an infected human brain with sporadic Creutzfeldt-Jakob disease (CJD) by people in the Fore tribe in around 1900. Kuru then spread to other nearby tribes following inter-tribe marrying (gradually spreading to the 169 villages and hamlets according to a 2010 paper by Dr. Nils Pedersen and Dr. Else Smith in a 2010 issue of Acta Pathologica Micobiologica Et Immunologica Scandinavica). Once infected with kuru, the disease has three distinct phases (ambulant, sedentary, and terminal):
- Ambulant phase: Symptoms typically include decreased muscle and motor control leading to an unsteady gait and stance, tremors, and deterioration and slurring of speech (dysarthria).
- Sedentary phase: Symptoms typically include deterioration of muscle coordination (ataxia) and severe tremors. Sufferers are unable to walk unaided and they suffer bouts of hysterical and uncontrolled laughter.
- Terminal phase: Symptoms typically include complete loss of muscle co-ordination, incontinence, being unable to talk or sit unaided, great difficulty in swallowing food (dysphagia) (difficulty swallowing), and the outbreak of necrotic ulcerations (sores with pus).
The early research by Michael Alpers and colleagues showed that kuru spread very rapidly as a result of the Fore tribe’s endocannibalistic practice (i.e., of eating the flesh of human beings from within the same community after the person had died and taking on that individual’s ‘life force’). Interestingly, Alper’s research also showed that kuru infection was far more prevalent in women and children (in fact, up to 9 times more prevalent). Dr. Pedersen and Dr. Smith noted that the youngest ever kuru sufferer was five years old, and that 67% of those with kuru were adult women, 23% were children and adolescents, and only 10% were adult men.
There are two reasons why kuru might be more prevalent among women and children compared to men. Firstly, men in the tribe had first choice of which parts of the infected dead tribe member to eat. Once the men had eaten the ‘choice cuts’, women and children could only eat what was left and this included the dead person’s brain (where the infected prion particles were at their most concentrated). Secondly, women and children were far more likely than men to clean the bodies of the infected dead people. If those cleaning the body had open cuts or sores on their hands, the infection may have spread through the bloodstream. The 2002 research led by Dr. Jerome Huillard d’Aignaux and colleagues also demonstrated that the incubation period in females was shorter than that in males because adult women may have been exposed to the largest doses of infectious material. However, Dr. Robert Will has noted that as time has passed, the incidence of kuru has declined and the proportion of affected adult males and females has become more similar. Research (for example by Dr. Simon Mead) has also indicated that some members of the Fore tribe were immune from catching kuru as they carried a prion-resistant factor. Dr. Will also reported that:
“No children born after 1959 have been affected and there is no evidence of vertical transmission of infectivity in kuru, despite the breast-feeding of infants by many hundreds of clinically affected mothers”.
Most recent papers on kuru (such as one by Dr. Laura Manuelidis and colleagues in a 2009 issue of Proceedings of the National Academy of Sciences) have noted that the disease has now died out due to the cessation of the endocannibalistic rituals and therefore is not created spontaneously by the human host.
Dr Mark Griffiths, Professor of Gambling Studies, International Gaming Research Unit, Nottingham Trent University, Nottingham, UK
Collinge, J., Whitfield, J.W., McKintosh, E., Beck, J., Mead, S., Thomas, D.J., & Alpers, M.P. (2006). Kuru in the 21st century—an acquired human prion disease with very long incubation periods. The Lancet, 367, 2068-2074.
Gajdusek, D.C., Gibbs, C.J. & Alpers, M. (1966). Experimental transmission of a Kuru-like syndrome to chimpanzees. Nature, 209, 794-796.
Gajdusek, D.C & Zigas, V. (1957). Degenerative disease of the central nervous system in New Guinea. The epidemic occurrence of ‘‘Kuru’’ in the native population. New England Journal of Medicine, 257, 974-978.
Huillard d’Aignaux, J.N., Cousens, S.N., Maccario, J., Costagliola, D., Alpers, M.P., Smith, P.G., Alpérovitch, A. (2002). The incubation period of kuru. Epidemiology, 13, 402-408.
Klitzman, R.L., Alpers, M.P. & Gajdusek, D.C. (1984). The natural incubation period of kuru and the episodes of transmission in three clusters of patients. Neuroepidemiology, 3, 3-20.
Lindenbaum, S. (1979). Kuru sorcery: Disease and danger in the New Guinea highlands. Palo Alto, CA: Mayfield.
Manuelidis, L., Chakrabarty, T., Miyazawa, K., Nduom, N. & Emmerling, K. (2009). The kuru infectious agent is a unique geographic isolate distinct from Creutzfeldt–Jakob disease and scrapie agents Proceedings of the National Academy of Sciences, 106, 13529-13534.
Pedersen, N.S. & Smith, E. (2010). Prion diseases: Epidemiology in man. Acta Pathologica Micobiologica Et Immunologica Scandinavica, 110, 14-22.
Will, R.G. (2003). Acquired prion disease: iatrogenic CJD, variant CJD, kuru. British Medical Bulletin, 66, 255-265.