The human PRNP protein which is subverted in prion disease can occur with either methionine or valine at amino acid 129, without any apparent physiological difference. Of the overall Caucasian population, about 40% have two methionine-containing alleles, 10% have two valine-containing alleles, and the other 50% are heterozygous at this position. Only a single person with vCJD tested was found to be heterozygous; most of those affected had two copies of the methionine-containing form. It is not yet known whether those unaffected are actually immune or only have a longer incubation period until symptoms appear. Diagnosis
Definitive
Examination of brain tissue is required to confirm a diagnosis of variant CJD. The following confirmatory features should be present:
Numerous widespread kuru-type amyloid plaques surrounded by vacuoles in both the cerebellum and cerebrum – florid plaques. Spongiform change and extensive prion protein deposition shown by immunohistochemistry throughout the cerebellum and cerebrum. Suspected
Current age or age at death less than 55 years (a brain autopsy is recommended, however, for all physician-diagnosed CJD cases). Psychiatric symptoms at illness onset and/or persistent painful sensory symptoms (frank pain and/or dysesthesia). Dementia, and development ≥4 months after illness onset of at least two of the following five neurologic signs: poor coordination, myoclonus, chorea, hyperreflexia, or visual signs. (If persistent painful sensory symptoms exist, ≥4 months delay in the development of the neurologic signs is not required). A normal or an abnormal EEG, but not the diagnostic EEG changes often seen in classic CJD. Duration of illness of over 6 months.
Occupational contamination
In France, the last two victims of variant Creutzfeldt-Jakob disease, who died in 2019 and 2021, were research technicians at the National Research Institute for Agriculture, Food and the Environment (INRAE). Emilie Jaumain, who died in 2019, at the age of 33, had been the victim of a work accident in 2010, during which she had pricked herself with a tool contaminated with infected brain. The efficacy of this route of contamination has been unambiguously demonstrated in primates. Pierrette C., who died in 2021, had been victim of the same type of work accident. After her diagnosis, a moratorium was initiated in all French laboratories on research activities on infectious prions. In March 2022, INRAE recognized the occupational cause of these two deaths. This raises serious questions about the safety of personnel in these laboratories. Indeed, inspections have noted serious failures in the protection of agents in the face of this deadly risk, and the long incubation period of this disease leads to fears of new cases in the future, hence great concern. Other causes
Eating other types of brains such as those from squirrels is not recommended as one person contracted vCJD from eating the brain of a squirrel. Mechanism
Despite the consumption of contaminated beef in the UK being high, vCJD has infected a small number of people. One explanation for this can be found in the genetics of people with the disease.