Kuru was a rare, incurable, and fatal neurodegenerative disorder that was formerly common among the Fore people of Papua New Guinea. It was a prion disease that caused tremors and loss of coordination from neurodegeneration. The term kúru means 'trembling' and comes from the Fore word kuria or guria ("to shake"). It is also known as "laughing sickness" due to abnormal bursts of laughter from the patients. It was spread among the Fore people via funerary cannibalism: deceased family members were traditionally cooked and eaten, which was thought to help free the spirit of the dead. Women and children usually ate the brain, where infectious prions were most concentrated, and therefore were more commonly affected. The outbreak likely originated from a villager developing sporadic Creutzfeldt–Jakob disease, which then spread to others via the consumption of the deceased's brain. Due to a ban by the Australian administration of Papua New Guinea, the Fore had largely stopped eating human flesh around 1960, years before any connection between cannibalism and kuru was seriously considered. However, this did not quickly stop the emergence of new cases, due to the long incubation period of the disease, which can extend to over 50 years. Around 1957, during the peak of the outbreak, about 200 people died of the disease every year. More than half a century later, the outbreak ended, with the two last known deaths occurring in 2005 and 2009.
Signs and symptoms Kuru, a transmissible spongiform encephalopathy, is a disease of the nervous system that causes physiological and neurological effects which ultimately lead to death. It is characterized by progressive cerebellar ataxia, or loss of coordination and control over muscle movements. The preclinical or asymptomatic phase, also called the incubation period, averages 10–13 years, but can be as short as five and has been estimated to last as long as 50 years or more after initial exposure. The clinical stage, which begins at the first onset of symptoms, lasts an average of 12 months. The clinical progression of kuru is divided into three specific stages: ambulant, sedentary, and terminal. While there is some variation in these stages from individual to individual, they are highly conserved among the affected population. Before the onset of clinical symptoms, an individual can also present with prodromal symptoms including headache and joint pain in the legs.
Ambulant stage In the ambulant stage, so called because the individual is still able to walk despite symptoms, the infected individual may exhibit unsteady stance and gait, decreased muscle control, difficulty pronouncing words (dysarthria), and tremors (titubation).
Sedentary stage In the sedentary stage, the infected individual is incapable of walking without support and experiences ataxia and severe tremors. Furthermore, the individual shows signs of emotional instability and depression, yet exhibits uncontrolled and sporadic laughter. Despite the other neurological symptoms, tendon reflexes remain intact at this stage of the disease.
Terminal stage In the terminal stage, the infected individual's existing symptoms, like ataxia, progress to the point where it is no longer possible to sit up without support. New symptoms also emerge: the individual develops dysphagia (difficulty swallowing), which can lead to severe malnutrition, and may also become incontinent, lose the ability or will to speak, and become unresponsive to their surroundings despite maintaining consciousness. Towards the end of the terminal stage, those infected often develop chronic decubitus ulcerated wounds that can be easily infected. An infected person usually dies within three months to two years after the first terminal stage symptoms, often because of aspiration pneumonia or other secondary infections.
Neuropathology Studies from those infected with kuru have revealed explanations for the effects that the disease can have on the brain. In the early stages of the disease, infected people may experience withdrawal, poor coordination, tremors, and curling of the toes and feet. To understand the difficulties in balance and coordination, studies were conducted to analyse the brains of infected individuals. These studies found that neurons in a kuru-infected brain were abnormally small and lighter in color compared to their healthy counterparts. Affected neurons appear "moth-eaten" due to their characteristic deformations. These abnormalities in the neurons of the brain infected by kuru were similar to those with Creutzfeldt–Jakob disease (CJD).
Causes
Kuru is largely localized to the Fore people and people with whom they intermarried. The Fore people ritualistically cooked and consumed body parts of their family members following their death to incorporate "the body of the dead person into the bodies of living relatives, thus helping to free the spirit of the dead". Because infectious prions are particularly concentrated in the brain, women and children – the primary consumers of the brain matter – had a much higher likelihood of being infected than men, who typically consumed muscle.
Prion The infectious agent is a misfolded form of a host-encoded protein called prion (PrP). Prion proteins are encoded by the Prion Protein Gene (PRNP). The two forms of prion are designated as PrPC, which is a normally folded protein, and PrPSc, a misfolded form which gives rise to the disease. The two forms do not differ in their amino acid sequence; however, the pathogenic PrPSc isoform differs from the normal PrPC form in its secondary and tertiary structure. The PrPSc isoform is more enriched in beta sheets, while the normal PrPC form is enriched in alpha helices. The differences in conformation allow PrPSc to aggregate and be extremely resistant to protein degradation by enzymes or other chemical and physical means. The normal form, on the other hand, is susceptible to complete proteolysis and soluble in non-denaturing detergents. It has been suggested that pre-existing or acquired PrPSc can promote the conversion of PrPC into PrPSc, which goes on to convert other PrPC. This initiates a chain reaction that enables its rapid propagation, resulting in the pathogenesis of prion diseases.
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