Kuru is a very rare prion disease today. It causes a rapid increase in mental and intellectual disturbances, problems with the central nervous system, and loss of coordination. In kuru, an abnormal glycoprotein known as prion protein (PrP) accumulates in the brain. Prion proteins are naturally produced in the nervous system. Their role is not fully understood, but there is a version that PrPs are involved in the development of neurodegenerative, and Alzheimer’s disease.

The disease is widespread in communities living on the islands of New Guinea. The name “kuru” is translated as “shaking from fear” or “trembling”, which fully corresponds to the symptomatic manifestations of the disease. Kuru is sometimes also called a “laughing disease” because of the pathological attacks of laughter in patients. More often, there was a high mortality rate from the disease in the Fore tribe due to the funeral rite with endocannibalism.

The ritual included the preparation of the dead (the oldest woman of the tribe was responsible for the removal of the brain, as it underwent special processing and wrapping in fern leaves), after which the entire tribe ate it. These kinds of rituals were forbidden, which reduced mortality. With the abolition of ritual cannibalism, cases of the disease did not stop. Now prions can be infected at the time of internal organ transplantation, blood transfusion, or eating animal meat.

What is a prion?

A prion is an “infectious protein” that itself assumes incorrect information and is able to force other protein molecules to fold in the same way, catalyzing a chain reaction of the formation of new prions. The protein is found in the body of all mammals, including humans, and in its normal form is not dangerous, although its role in the body is still not entirely clear. Perhaps it is involved in the transmission of nerve impulses, ion exchange, maintenance of daily cycles of activity, and rest in cells, organs, and the body as a whole – there is no consensus among researchers today. But it is all concerns protein in normal, alpha form. When the usual forms of proteins are converted into prions, α-helices are replaced by β-sheets.

Prion characteristics:

  • Prions cause the formation of amyloids – protein aggregates (clusters), in which all proteins are stacked in the same way, in the form of densely packed ß-sheets that make up fibrils (protein ropes). These fibrils grow from two ends, and when broken, they begin to grow from four.
  • Known human prion diseases: kuru, Creutzfeldt-Jakob disease, fatal familial insomnia, Gerstmann-Straussler-Scheinker syndrome, and others. All of them affect the nervous system and are currently incurable.
  • All known diseases in mammals are caused by the protein PrP, which is normally called PrPC, and in its infectious form, it is called PrPSc.

The prion disease hypothesis was first proposed in the 1960s when radiobiologist Tikvah Alper and mathematician John Stanley Griffith discovered that the object they were studying was too small for the virus and required much higher doses of ionizing radiation (the effect of which is greater the larger the particle size).

For the description of prion diseases, several Nobel Prizes were awarded at once:

  • In 1976 – for proof of the infectious nature of kuru disease among the natives of New Guinea, who had a tradition of eating the brains of the dead (from which they, as it turned out, became infected).
  • In 1997 – for research in this area, which made it possible to isolate and purify prion proteins to establish their structure.

The origin of the prions is unclear. Probably, we are talking about a spontaneous change under the influence of an external factor or cell mutation. Some researchers go further, believing that normally a certain amount of prion protein formations constantly arise in the body, which is immediately eliminated. Violation for some reason of the ability to “self-purify” cells leads to an increase in the concentration of “wrong” proteins above the permissible level, after which the process goes out of control. A similar mechanism explains the emergence of kuru disease in a genetically isolated population (divorced from the civilization of the tribe), and ritual cannibalism is the mechanism of its spread.

Symptoms and diagnosis of kuru disease

Symptoms and diagnosis of kuru disease.

The symptoms of kuru disease concern disorders of the nervous system with rapid progression and death. Mild headaches appear first, which get worse over time. The patient feels pain in the joints. The clinical manifestations of the disease depend on the stage of development of the pathology. The main signs are:

  • cerebellar ataxia;
  • tremor of the limbs;
  • convulsive seizures;
  • euphoria;
  • emotional instability;
  • the disappearance of reflexes;
  • dementia.

With the progression of the pathology, patients lose mobility, sensory, motor, and cranial nerves atrophy. Death occurs within two years. Physical manifestations of the disease:

  1. First stage. Muscle weakness is observed. A person quickly gets tired of physical exertion, and limbs begin to shake, problems with movement are felt. The patient moves with support on a stick, crutches, or in a wheelchair.
  2. Second phase. The person shows signs of a mental disorder with emotional instability and confusion.
  3. Stage three. The patient loses mobility, and the brain ceases to function; death occurs.

Neurological signs:

  • the grasping reflex worsens;
  • squint develops;
  • involuntary twitching of the eyeballs;
  • convulsions;
  • loss of the ability to swallow, chew, move;
  • involuntary urination and defecation appear.

A person dies from complications of the nervous system that provoke the disease: bedsores, inability to eat, or pneumonia.

Until now, spongiform encephalopathy, including kuru, could be diagnosed only posthumously – pathomorphological analysis of the substance of the brain. Even the most advanced instrumental methods, in this case, are not effective and not informative, which extremely complicates the research process and, in particular, epidemiological monitoring. Only in the last few years, reports of successful experiments on contrast staining of the affected tissue, the detection of specific antibodies to prions began to appear in serious specialized sources, which gives reasonable hope for a speedy solution to the problem of intravital diagnostics.

Pathomorphologically, kuru disease manifests itself in demyelination, neuronal death, accumulation of leukocytes and mononuclear cells in the brain. Since cannibalism has now been eliminated and no other mechanisms of transmission of pathogens have been identified, the disease may be of purely historical significance.

Kuru medical history

The discovery was made by the American Carlton Gaidushek, a pediatric infectious disease specialist sent to New Guinea to study endemic viral diseases. Gaidushek and his assistant Igor Klatzo settled among the Fores, opened a hospital with funds from the Australian Department of Health and their own savings, and began to study the lethal tremors and other abnormalities in the nervous system. Since he treated the natives for syphilis and dysentery, he was allowed to do anything – even to open the bodies of kuru victims and send their organs to America for analysis.

While dissecting the woman’s cerebellum Fore, which looked like a sponge due to the death of neurons, Clatzo recalled that he had already seen something similar in his practice: the brain of a person who died from a rare Creutzfeldt-Jakob disease. Now it is famous all over the world as “mad cow disease”, and then only 20 cases were described. Clatzo sent Phore’s cerebellar preparation to a medical exhibition in London. There he was noticed by the English veterinarian Bill Hadlow and immediately wrote that this spongiform encephalopathy – one in one known since 1732 scrapie – a disease of sheep, transmitted to goats. Hadlow suggested that Gaidushek infect the monkeys by feeding them with the brain of people who had died from kuru. Gaidushek did just that with five chimpanzees. And also with dozens of chickens, mice, rats, and guinea pigs. All to no avail. It remained to think that kuru was a hereditary disease. The locals believed that this was a curse that the shamans of other tribes sent on them, which is why they continued their rituals of cannibalism in order to protect themselves from the disease.

The Glass family anthropologists came to the aid of the researchers – Robert and Shirley. The couple drew the patients’ family trees and made sure that not all of them are related. In addition, before 1910, people did not know any kuru. However, it turned out that adult men constantly took the meat, and the rest got the brain and entrails. And the most important thing: after the prohibition of the dead, sometimes they still ate in secret. 

Then it dawned on Gaidushek – the infection does not necessarily occur in the stomach. The women, with their hands, laid raw brains on bamboo tubes, then they caressed the children, itched, rubbed their eyes, scratches, and bites. In order not to guess, the cerebellar gruel of the dead from the kuru was injected directly into the brain of two chimpanzees. Hadlow’s veterinarian warned that the infection could have a long incubation period. After 21 months, a female named Georgette showed nervous system disorders and symptoms of kuru. Georgette’s cerebellum caused illness in the next generation in just a year, by January 67th.

Causes of kuru

Causes of kuru

In kuru, an abnormal glycoprotein known as prion protein (PrP) accumulates in the brain. Prion proteins are naturally produced in the nervous system. Their role is not fully understood, but there is a version that PrPs are involved in the development of neurodegenerative disease, Alzheimer’s disease.

Kuru most often suffered from women and children. This was due to the fact that they were given the brain, the most infected part of the body. These rituals have been forbidden since the 1950s, so the kuru has practically disappeared. Very few, people are currently suffering from kuru. However, 11 cases of kuru were reported between 1996 and 2004. These cases suggest that symptoms may not develop after a person is infected for more than 50 years.

Treatment of kuru

To date, there is no effective etiopathogenetic therapy for prion spongiform encephalopathies: usually within 4-12 months (at best, up to 24 months) from the moment the first symptoms appear, the patient will inevitably die. All treatment known today is of a palliative, symptomatic nature and focuses on maintaining the somatic-neurological status.

However, it should be noted that functional cells are not completely defenseless against prion invasion and, in particular, they are trying to use intensive oxygenation to destroy the foreign protein. The problem is that prions block oxygen, which is dangerous for them, inside the cell itself, which only accelerates its destruction and degeneration. In recent years, as in the case of diagnostics, there have appeared quite optimistic information about experiments on activating protective cellular mechanisms, stimulating the immune response, and overcoming the defensive barriers of the prion protein, which suggests the emergence, in the foreseeable future, of effective etiopathogenetic treatment of spongiform encephalopathies. …It is also known that in 2009 American scientists made an unexpected discovery: some members of the Fore tribe, thanks to a new polymorphism of the PRNP gene that appeared in them in a relatively recent time, have an innate immunity to kuru. They published the results of their research in the New England Medical Journal.

FAQ
  • How is kuru disease transmitted?

    Kuru is transmitted through the already infected brain tissue of people that are consumed in food. Also, contact with open wounds and eyes may be the cause.
  • How long can you live with kuru?

    Today, kuru disease is considered incurable, so the lifespan of an infected person is up to 24 months after the onset of symptoms. Usually, a person dies as a result of pneumonia or infection due to pressure sores.
  • Who is at risk of kuru?

    Kuru is a disease of the nervous system, which is clearly endemic, region-specific prion disease (the Fore people in the highlands of New Guinea suffered from it).
  • What are the stages of kuru disease?

    Kuru has three clinical stages: ambulant, sedentary, and terminal.
  • What is the meaning of the word kuru?

    The word “kuru” in the language of the Fore tribe has two meanings – “trembling” and “spoilage”.