Human Prion Diseases
المؤلف:
Baijayantimala Mishra
المصدر:
Textbook of Medical Virology
الجزء والصفحة:
2nd Edition , p286-288
2025-12-18
43
Prion diseases can occur both in humans and animals. The uniqueness of prion protein among all other infective agents are: (i) Sporadic or spontaneous, (ii) heritable or genetic, and (iii) acquired or infectious. Accordingly, human prion diseases have been classified into three different types. Examples of different types of human and animal prion diseases are given in Table 1.
Table1. Human and animal prion diseases
Sporadic prion disease: Conversion of PrPc to PrPSc occurs spontaneously or due to mutations in PRNP gene without prior presence of PrPSc, e.g. sporadic CJD.
Heritable prion disease: Mutation in PRNP gene occurs which makes the cellular PrPc more vulnerable for conversion to PrPSc.
Infectious or acquired prion disease: PrPSc is acquired by the host from some other tissues carrying the pathological prion protein PrPSc which transforms the normal PrPc to pathological PrPSc and causes the disease.
Sporadic Human Prion Disease
Creutzfeldt-Jakob disease (CJD): This is the most common form of human prion disease. It can present in either of the three types of prion disease; sporadic, hereditary, iatrogenic or infectious. Of these, sporadic CJD is the commonest form, worldwide in distribution and constitute 80–95% of all CJD cases. Heritable or genetic CJD is seen in 10–15% and infectious type is seen in <1%.
The mean age of onset of sporadic CJD is 50 70 years. Majority die within one year of disease onset. The typical clinical manifestations of sporadic CJD are rapid progressive dementia, behavioral abnormality, ataxia and myoclonus. Marked neuronal loss, vacuolation, astrogliosis along with PrPSc deposits are the characteristic histopathological changes.
Heritable Human Prion Disease
Familial Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker (GSS) syndrome and fatal familial insomnia (FFI) are inheritable prion diseases caused by autosomal dominant mutations in the PRNP gene. Familial CJD is the commonest amongst three, whereas the other two are rare.
Acquired Human Prion Disease
Kuru: Kuru was the first identified acquired human prion disease. Kuru is restricted to the Fore ethnic group in Papua New Guinea of Eastern Highlands. The term Kuru in the Fore language of Papua New Guinea means “to tremble from fever”. The disease was acquired due to the practice of ritualistic endocannibalism which involved eating of brain and other viscera of a dead relative to pay respect. Infection occurs when the tissues of dead person are contaminated with prion proteins.
Tremor and ataxia are the first symptoms from which the name of disease was derived. Later manifestations are chorea, athetosis and myoclonus. Death usually occurs within 1 2 years from disease onset. Disease is more common among women and children. Disease has virtually disappeared after the ritual practice of cannibalism was prohibited. Heterozygosity in codon 127 and 129 in PRNP gene, a marker of prion resistance, has been found among the elderly survivors of kuru epidemic.
Variant Creutzfeldt-Jakob disease: Variant CJD is the only zoonotic human prion disease. First case of vCJD was seen during 1994–95 in United Kingdom (UK). The disease was transmitted from cattle with bovine spongiform encephalopathy (also called “mad cow disease”).
Origin of vCJD: Cattle in UK were given meat bone meal prepared from sheep carcasses and offal. When this meal contained prion protein contaminated products from scrapie infected sheep the scrapie prion crossed the species barrier and got established in cattle. This led to development of bovine spongiform encephalopathy (BSE) in cattle which was also called mad cow disease. More and more diseased cattle were slaughtered and provided to produce meat-bone meal. When food products prepared from infected cattle were taken by humans it led to development of prion disease in them which was named variant CJD.
Peak epidemic of BSE occurred in 1992–93 when 37,000 BSE cases were diagnosed in cattle only in a single year. Maximum number of vCJD were detected during 1999–2000 in UK, 6–7 years after the peak BSE outbreak in cattle. Export of cattle feed from UK spread the disease to several other European countries. More than 200 vCJD cases were reported by 2015. Majority of cases were from UK and France. Strict measures were taken to prohibit the use of meat, offal and cattle products in cattle feed, restrictions on animal movement and isolation and euthanasia of cases led to decline in cases. Apart from European countries, vCJD has also been reported from US, Canada, Saudi Arabia, Japan and Taiwan. All these cases possibly had acquired the infection during their stay in UK or golf countries. A total of three cases of vCJD associated with transfusion of blood products also have been documented.
Variant CJD is so named because it differs from classical CJD in many respects. Mean age in vCJD is 28 years. Clinical presentation starts with prodrome of psychiatric and behavioral symptoms which continues for about 6 months before onset of typical neurologic symptoms. vCJD has a longer median period of disease duration of about 14.5 months. It also differs from other human prion diseases in having PrPSc in lymphoreticular tissue in addition to central nervous system. The differences between classical and variant CJD are shown in Table 2.
Table2. Differences between sporadic and variant Creutzfeldt-Jakob disease
Iatrogenic prion diseases: Iatrogenic CJD can be caused by transplantation or use of prion contaminated neurological tissues for various purpose, e.g. dura mater, human growth hormone, gonadotropin hormone. Three cases of blood transfusion
الاكثر قراءة في مواضيع عامة في علم الامراض
اخر الاخبار
اخبار العتبة العباسية المقدسة
