MMI 133: Microbe Assignment References 
A prion disease

Kuru

01

In Papua New Guinea, the Fore tribes of the north and south practiced cannibalistic rituals, leading to the spread of the prion disease Kuru.

02

The misfolding of naturally occurring proteins in the brain led to symptoms related to motor movements, such as slurred speech and poor coordination.

03 

There have been no discoveries regarding a cure or treatment that terminates the disease, only the discouragement of cannibalistic practices.


History

The Fore, both north and south, were tribes in Papua New Guinea where members practiced cannibalism for ritualistic purposes. Members of the Fore tribes would take the deceased corpse of their relatives and ingest their tissues, spreading infectious agents called prions. During the 1950s to the 1960s, the disease Kuru became became an epidemic that caused symptoms related to motor movements such as coordination and speech.


Image I: Men in South Fore
Transmissible Spongiform Encephalopathies (TSE's)

Classification: Prions

  1. Prions are infectious and misfolded proteins that cause the misfolding of other proteins.

  2. They are associated with the transmissible spongiform encephalopathies class, related to mad cow disease, chronic wasting disease, scrapie, and Creutzfeldt-Jakob disease.

  3. These abnormal and misfolded proteins accumulate in the brain, making it a deadly neurodegenerative prion disease.

Image II: Kuru in the spinal cord, brain, and brain stem
A prion disease

Kuru

Image III: Kuru patient's cerebellum

Biology & Mode of Transmission

Prions lack the ability to reproduce and are transmitted by those ingesting infected tissue. They incubate in the lymph nodes after progressing through the intestinal wall. Prions, as stated above, are transmissible spongiform encephalopathies (TSE). Attributes of TSEs affect proteins in the brain tissue and have long incubation periods, and as a result, those infected may not see symptoms immediately. Prion proteins are naturally found in the brain and are not foreign particles. When they become misfolded proteins and turn into a disease, there is no immunological response from the body and no antibodies are produced.

Image IV: Brain tissue of Kuru patient

Site of Infection & Pathology

A normal prion contains prion protein genes (PRNP), alpha helices, and goes through proteolysis, or the breakdown of proteins. The disease Kuru arises when a misfolded protein, PrPSc isoform, resists the enzyme that degrades it. Other prion proteins (PrP) are furthermore transformed into additional PrPSc isoforms, producing prion diseases. Symptoms that appear are related to motor movements since Kuru affects the cerebellum.

Image V: Youngest Kuru patient

Disease Symptoms

Compared to other prion diseases, Kuru's history is more predictable, as it encounters three observable and distinct phases. The ambulatory phase, or first phase, is distinguished by features such as body shivers, poor coordination, abnormal body movements, tremors, the curling of feet or toes, and uncontrollable laughter. The term "laughing disease", is derived from that particular feature of the ambulatory phase. Coordination and tremors worsen during the sedentary phase, as well as the appearance of new symptoms such as jerky eye movements. Without proper support, an infected individual is unable to sit or stand up. Becoming bedridden is a distinct characteristic of the of the terminal (third) stage, along with a fixed dystonic posture. Within 9 to 24 months of acquiring the disease, patients often die of an ulcerated wound infections or pneumonia.
Additional Information: Image
Kuru: A prion Disease

Diagnosis & Treatment

  • Further tests such as blood workup, vascular imaging, genetic studies, and pathological evaluations are used to differentiate between Kuru and different forms of dementia, which have similar signs and symptoms, but may be treatable.
  • Overall Kuru, like other prion diseases, does not have a treatable cure that controls or stops the disease. Cannibalistic practices in the Fore tribes of Papa New Guinea were discouraged, ultimately leading to the elimination of the disease. 
Additional Information: Image VI

(a) Kuru stained silver

(b) Linear Kuru plaques

(c) Kuru stained blue

(d) Human cerebellum contains glial cells with PrPSc deposits & Kuru plaque

(e) Kuru plaque: Electron Microscopic Image

(f) Kuru plaque-fibrils bundles

Images

  1. https://simplemaps.com/resources/svg-pg  (Map on Cover Page)

  2. https://www.researchgate.net/figure/Pathological-changes-in-the-kuru-cerebellum-brain-stem-and-spinal-cord-The-cerebellum_fig4_23312027 (Image II)

  3. https://www.mdpi.com/1999-4915/11/3/232  (Image VI)

  4. https://en.wikipedia.org/wiki/Kuru_%28disease%29 (Image III)

  5. https://www.researchgate.net/figure/Yani-the-youngest-kuru-patient-at-four-and-a-half-years-of-age-in-1957_fig8_23313701 (Image V)

  1. https://cosmosmagazine.com/science/biology/the-man-who-linked-kuru-to-cannibalism/ (Image I & IV)

References

Information                                                                                                                             

  1.  National Library of Medicine -https://www.ncbi.nlm.nih.gov/books/NBK559103/  

  2.  National Institute of Neurological Disorders and Stroke -https://www.ninds.nih.gov/health-information/disorders/kuru#:~:text=Brain%20tissue%20from%20individuals%20with,the%20Fore%20word%20for%20shiver 

  3. Liberski, P. P., Gajos, A., Sikorska, B., & Lindenbaum, S. (2019). Kuru, the First Human Prion Disease. Viruses, 11(3). https://doi.org/10.3390/v11030232

  4. Paradowski, R. J. . P. D. (2023). Kuru. Salem Press Encyclopedia of Health.

  5. Fahnert & Lostroh. 2023. Strelkauskas' Microbiology: A Clinical Approach, 3rd Ed. Garland Science.