Kuru (Prions): Proteins That Kill, Cannibals, Nobel Prizes, and More

Kuru is an infectious disease, a part of a group of illnesses called TSEs or Transmissible Spongiform Encephalopathies; they are also known as ‘Prions’. Prion stands for proteinaceous infectious particle. A strange fact about prion diseases is that these infections are not caused by viruses, bacteria, or parasites but proteins. The scariest part is that these proteins cannot be destroyed, at least, not yet, but prion scientists are working on it [1-3]. 

Proteins are not living organisms; many are core building blocks in our bodies. So, how do proteins like prions end up causing deadly diseases? 

Yes, proteins do not replicate because they have no genetic material, which makes the study of prions more fascinating. In our cells, DNA is converted to RNA, which is made into proteins. Different proteins fold in different ways — these folds are highly specialized and function as detailed instructions for many biological processes and structures. Think of them as architectural blueprints for a building.

Now, if a protein does not fold the right way, this type of misfolding can be the root cause of disorders like cystic fibrosis. Prions are misfolded proteins but the bigger problem is that become contagious. A prion acts like a bad influence or a rotten apple. It’s very proximity begins to affect neighbouring proteins and they begin to fold incorrectly. Eventually, the brains of infected individuals looked like sponges, with many pockets of missing nerve cells and no way to reverse it. 

It took a few decades for scientists to understand this phenomenon because the bodies of infected people did not show any signs of infection. This disease really had the experts stumped. It wasn’t until 1970s and 1980s that the idea of infectious proteins gathered steam, leading to a Nobel Prize for this landmark discovery [3,4,11]. 

Thankfully, kuru is now a thing of the past but prions cause other diseases in humans like Creutzfeldt-Jakob Disease (CJD), Gerstmann-Straussler-Scheinker Syndrome, and Fatal Familial Insomnia. Mad Cow Disease in cows and other bovine animals and scrapie in sheep are some prion diseases affecting animals [8]. So, the history, epidemiology, and further study of these mutating proteins are essential for advancing the fight against infectious diseases.

Kuru was first observed in 1936 by a gold prospector named Ted Ubank. It was later observed by anthropologists Berndt and Berndt during the early 1950s [14]. In 1951, Arthur Carey, a Colonial patrol officer, was the first to use the word “kuru” to refer to the newly discovered disease that mainly claimed the lives of the Fore women. He was also the first to describe the symptoms of the illness [1]. In 1953, Australian patrol officers in the Eastern Highlands of Papua New Guinea first mentioned the disease in their official records [14].

The disease was also described by other patrol officers stationed in the region in the subsequent years – John McArthur in 1953 and William Brown in 1954. In 1955, John Colman sent one of the cases to Kainantu, a town in the Eastern Highlands of Papua New Guinea, for medical observation. In the same year, a critical care medical practitioner named Frank Earl described the disease and suggested it might be a form of encephalitis. 

In 1957, an American physician and medical researcher, Daniel C. Gajdusek from the National Institutes of Health (NIH) moved to Papua New Guinea to work with a Lithuanian medical officer named Vin Zigas after having discovered that the disease became endemic in the region [8]. In the same year, they published their first report on kuru, which suggested it is a generative disease of the central nervous system [1,9].

Gajdusek’s observation suggested that the infectious pathogen causing the illness among the Fore linguistic community is transmitted through people eating the brain of their deceased relatives. It was part of an endocannibalism ritual usually carried out by women and children [6]. His observation gained attention when cases dropped significantly in the early 1960s after the Australian authorities banned cannibalism in the region [7]. It was one of the remarkable observations that helped demystify all false beliefs that Fore people had concerning the illness, as they believed it to be a psychosomatic outcome of the sorcery practices performed by their people [1,15].

More experiments were conducted in the subsequent years to understand the nature of the illness. In 1959, Gajdusek and Michael Alpers, an Australian doctor, conducted research by injecting the brain specimens of a girl who died from kuru into two chimpanzees. The objective was to understand the pathology of the disease. In two years, one of the two chimpanzees developed kuru. 

The experiment proved that the infectious agent could be transmitted from one species to another. It was the first experimental transmission of kuru and was seen as an important milestone in medicine, which led to Gajdusek receiving a Nobel Prize in Physiology or Medicine in 1976 [6].  

The discovery of kuru helped in understanding the diseases caused by a new class of pathogens called prions by Stanley B. Prusiner. He received a Nobel Prize in 1997 for discovering and studying prions [1]. This discovery led to further research on determining the structure of the prion protein by Kurt Wüthrich, which won him a Nobel Prize in 2002 [1,10].

Kuru is confined to a specific geographic location, mainly the Okapa district in the highlands of Papua New Guinea [2]. The region includes the natives of the Fore linguistic group and the neighboring linguistic groups, including Auiana, Awa, Gimi, Kamano, Kanite, Keiagana, and Usurufai. Prion diseases were common among a community called ‘Fore’ in the Eastern Highlands of Papua New Guinea during the 1950s [1,8]. 

Kuru mortality rate

Like all other prion diseases, a kuru infection was always fatal. It could take anywhere from three months to three years from the onset of symptoms until death. On average, however, it took 12 months. 

During the late 1950s, kuru claimed the lives of around 200 people living in the Eastern Highlands Province each year [4]. Kuru mortality rate in the 1940s and 1950s was around 35 per 1,000 population. 

During this time, this death rate made a significant impact on the sex ratio in the region. During the early years, women and children were most affected. So much so that the male-female sex ratio in the South Fore was distorted to 3:1 during the peak years of the epidemic [1].

Between 1957 and 1959: 

• 60% of cases were women
• 30% were children (both male and female)
• 2% were men

In time, both men and women were equally affected. Plus, with more knowledge about the origins of the disease, the incidence began to drop significantly. Affected individuals were between four and 60 years of age [4]. 

Kuru case count

Since 1957, over 2700 kuru cases have been documented among 36,000 people – all living in the region where kuru was endemic [2]. 

Between 1957 and 1959, 82% of of the kuru cases reported were from the Okapa district (where the Fore people live): 

• 61% of these cases were from the South Fore
• 21% were reported from the North Fore [4]. 

The early 1960s saw a considerable decline in cases compared to the late 1950s. For instance, kuru cases dropped 23% between 1961 and 1963. The mortality rate also decreased from 7.64 to 5.58 per 1,000. 

This change was more apparent among children, with a reduction of 57% in cases. This steep decline in the number of cases among children, particularly in South Fore, is because the Fore began to stop practicing cannibalism [1].

There is no definitive proof of how kuru spreads. However, the illness prevailed in areas where the practice of cannibalism was popular, making a heavy correlation between cannibalism and kuru. 

According to Gajdusek (the Nobel Prize winner for his work on kuru), these are the possible ways in which kuru could be transmitted: 

• Rubbing the brain tissue of the deceased on mourners during mortuary ceremonies
• Handling infectious parts of the flesh with bare hands during mortuary feasts 
• Butchering dead relatives with bamboo knives and bare hands and then eating the tissues with contaminated hands. This ritual was mainly performed by women and children
• People smearing themselves with their dead relatives’ brains and visceral tissues – again, usually done by women and children [5].

There is no evidence that kuru can be transmitted from infected mothers to their nursing children [2].

The mean incubation period of kuru is assumed to be between three to six years. The maximum period of incubation is believed to be between 10 and 14 years. The complete duration of the illness, starting from its onset until death, is between three and 23 months (12 months on average).

The illness progresses in three phases – ambulant, sedentary, and terminal. There is also a prodromal period which needs to be better defined. It lasts several months and is often characterized by

• Headaches
• Limb pains
• Joint pains – Starting with knees and ankles, followed by elbows and wrists
• Pain in the interphalangeal joints, abdominal pain, and weight loss (less common).

Ambulant phase

The ambulant phase begins after the prodromal phase. It is characterized by:

• An unsteadiness in the person’s manner of walking – is usually first noticed by the patient.
• Astasia- Inability to walk or stand in a usual way.
• Ataxia – Lack of coordination of the muscles, especially in the trunk and lower limbs.
• Patients may also exhibit withdrawal symptoms and are often quiet.
• Involuntary spontaneous, and action jerks.
• Clawing of the toes.
• Curling of the feet.
• Plantar reflex (observed temporarily).

As they approach the end of the ambulant phase, the patient cannot move freely without another person’s support [1].

Sedentary phase

The sedentary phase is characterized by:

• Patient’s inability to walk without constant support, wherein the patient leans heavily on another person. It is due to weakness in the hips and knees. 
• Postural instability – inability to maintain equilibrium under dynamic and static conditions.
• Severe ataxia.
• Tremors.
• Dysarthria – slurred or slow speech that can be difficult to understand.
• Deep reflexes.
• Jerky ocular movements.

The sedentary phase ends when the patient cannot sit without another person’s help or other support [1].

Terminal phase

The terminal phase is the final phase of the illness. During this phase…

• The patient is bedridden and has no or insufficient voluntary control over urination and the discharge of feces from the body.
• The person will experience difficulty in swallowing, leading to acute malnutrition.
• People will become unresponsive as they will lose their ability to speak.
• They will also develop chronic ulcerated wounds and become prone to other infections [1].

In general, prion diseases are diagnosed when symptoms become evident, as it is challenging to diagnose patients during the incubation period. 

Ultra-sensitive prion amplification methods are now used to accurately define biomarkers in Cerebrospinal Fluid (CSF) and serum. The latest Real-Time Quaking-Induced Conversion (RT-QuIC), an ultrasensitive in vitro prion amplification method, is used to detect prion seeds [11].

According to the National Institute of Neurological Disorders and Stroke (NINDS), there were (and are) no treatments to control or cure kuru. No treatments are also available to cure any TSE or prion diseases, which makes awareness and prevention even more critical [12].

According to the NINDS, kuru has largely disappeared. The most effective preventive method was to educate the Fore community to discourage and ban the practice of cannibalism and other high-risk behavior during funeral rites [12].

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