Clinical Syndromes - Slow Diseases Caused by Prions

Clinical Syndromes

◗ Slow diseases caused by prions in humans

Prions cause following diseases in humans: (a) kuru, (b) CJD, (c) variant CJD, (d) GSS syndrome, and (e) fatal familial insomnia.

Kuru: Kuru is a fatal neurological disease described onlyamong Fore tribe inhabiting the highlands of New Guinea. The disease was spread by cannibalistic funeral practice of the tribal population. This involved the ritualistic practice by the closest female relatives and children usually consuming the brain of the person following his or her death. The brain which contained most of the infectious pathogen was the source of infection. Kuru has largely disappeared today because cannibalism has been abolished now among the Fore tribal people. Kuru is a fatal disease characterized by progressive cerebellar ataxia and tremors. The condition manifests initially as difficulty in walking, followed by cerebellar tremor, hence the name kuru, which means “trembling in fear”. Eventually the tremor worsens, followed by progressive cerebellar ataxia and eventual death within a year of onset of symptoms. The clinical course lasts for 3 months to 2 years.

Creutzfeldt–Jakob disease: CJD is the most common priondisease responsible for nearly 85% of all human prion diseases.

The condition was described by Creutzfeldt (1920) and Jakob (1921), after whom the disease is named. Creutzfeldt–Jakob disease is a subacute progressive encephalopathy characterized by a rapidly progressive dementia, associated with myoclonic jerks. Memory loss, behavioral changes, and confusion are the common clinical manifestations. The condition is also associated with ataxia, aphasia, visual loss, and hemiparesis. The condition progresses and in the terminal stage of the disease, the patient becomes mute and comatose. The condi-tion is associated with extensive cortical spongiosis, gliosis, and neural loss. The condition is invariably fatal and death occurs in about 8 months.

Variant CJD: The vCJD is a new disease affecting mostly adultsaged 45 years. The condition was first documented in Britain in 1985. It is BSE zoonoses, probably originating from a double species switch from sheep scrapie to BSE and then from BSE to human variant. The vCJD is believed to be caused by ingestion of BSE-infected beef products contaminated by neural tissues. This is because neural tissues have a much higher concentra-tion of PrPSC compared with any other non-neural tissue.

Gerstmann–Sträussler–Scheinker syndrome: The conditionwas originally described in 1936 as affecting humans. The main clinical findings of the condition are slowly progressive limb and truncal ataxia, as well as dementia. Death of the patient usually occurs within 3–8 years of presentation of symptoms.

Fatal familial insomnia: Patients with this illness presentwith intractable insomnia, dysautonomia, dementia, and motor paralysis. Death occurs within 6 months to 3 years following presentation. The clinical presentation of the disease, however, varies widely; hence definitive diagnosis of the condition is made by genotyping.

◗ Slow diseases caused by prions in animals

Prions cause following diseases in animals: (a) scrapie, (b) bovine spongiform encephalopathy, (c) feline spongiform encephalopathy, (d) transmissible mink encephalopathy, and (e) chronic wasting disease of deer, mule, and elk.

Scrapie: Scrapie is a prototype prion disease of animals. It is aslow virus disease of the sheep, known for centuries. The infection is transmitted vertically from ewe to lamb and less frequently by direct contact. Incubation period is nearly 2 years. The condition manifests as intense irritation, and to relieve that the infected animals scratch themselves, against trees and rocks, hence the name scrapie. The condition progresses to emaciation and paralysis and finally leads to death of the animal. Autopsy of the infected brain shows spongiform degeneration without inflammation in the brain tissue. The condition has been documented extensively.

Bovine spongiform encephalopathy (BSE):Also known as madcow disease. It is a disease of cattle. The condition has an incuba-tion period of 2–8 years. The disease is relentlessly progressive until the animal dies. The cattle feed containing prion-contami-nated meat and bone meal, which was used as a protein source, was the source of infection for transmission of BSE to cattle. The causative agent is believed to be originated from either scrapie affected sheep or cattle with unidentified prion-associated slow virus disease. The mad cow disease, documented in 1986, has been described in cattle in the European countries and in the United States. Till 2004, nearly 190,000 confirmed clinical cases of BSE in cattle have been reported worldwide; the majority of which were from the United Kingdom alone.

Transmissible mink encephalopathy: Transmissible minkencephalopathy is a scrapie-like disease of mink. The causative agent is believed to be a strain of scrapie virus, which is trans-mitted to mink by feeding the animals on scrapie-infected sheep meat.

Chronic wasting disease of deer, mule, and elk: Chronicwasting disease is a prion disease of deer, mule, and elk. It is a progressive wasting disease of these animals in the United States.