Variant Creutzfeldt–Jakob disease
|Variant Creutzfeldt–Jakob disease|
|Synonyms||New variant Creutzfeldt–Jakob disease (nvCJD)|
|Biopsy of the tonsil in variant CJD. Prion protein immunostaining.|
|Symptoms||Psychiatric problems, behavioral changes, painful sensations|
|Usual onset||Less than 30 years old|
|Causes||Eating beef from animals with bovine spongiform encephalopathy|
|Diagnostic method||Brain biopsy|
|Prognosis||~13 month life expectancy|
|Frequency||Less than 250 reported cases as of 2012|
Variant Creutzfeldt–Jakob disease (vCJD) is a type of brain disease within the transmissible spongiform encephalopathy family. Symptoms include psychiatric problems, behavioral changes, and painful sensations. The length of time between exposure and the development of symptoms is unclear, but is believed to be years. Average life expectancy following the onset of symptoms is 13 months.
It is caused by prions, which are mis-folded proteins. Spread is believed to be primarily due to eating bovine spongiform encephalopathy (BSE)-infected beef. Infection is also believed to require a specific genetic susceptibility. Spread may potentially also occur via blood products or contaminated surgical equipment. Diagnosis is by brain biopsy but can be suspected based on certain other criteria. It is different from classic Creutzfeldt–Jakob disease, though both are due to prions.
Treatment for vCJD involves supportive care. As of 2012 about 170 cases of vCJD have been recorded in the United Kingdom, and 50 cases in the rest of the world. The disease has become less common since 2000. The typical age of onset is less than 30 years old. It was first identified in 1996 by the National CJD Surveillance Unit in Edinburgh, Scotland.
Signs and symptoms
Symptoms include psychiatric problems, behavioral changes, and painful sensations. The length of time between exposure and the development of symptoms is unclear, but is believed to be years. Average life expectancy following the onset of symptoms is 13 months.
In the UK, the primary cause of vCJD has been eating beef tainted with bovine spongiform encephalopathy. A 2012 study by the Health Protection Agency showed that around 1 in 2000 people in the UK shows signs of abnormal prion accumulation.
As of 2018 evidence suggest that while there may be prions in the blood of individuals with vCJD, this is not the case in individuals with sporadic CJD.
In 2004, a report showed that vCJD can be transmitted by blood transfusions. The finding alarmed healthcare officials because a large epidemic of the disease could result in the near future. A blood test for vCJD infection is possible but is not yet available for screening blood donations. Significant restrictions exist to protect the blood supply. The UK government banned anyone who had received a blood transfusion since January 1980 from donating blood. Since 1999 there has been a ban in the UK for using UK blood to manufacture fractional products such as albumin. Whilst these restrictions may go some way to preventing a self-sustaining epidemic of secondary infections the number of infected blood donations is unknown and could be considerable. In June 2013 the government was warned that deaths—then at 176—could rise five-fold through blood transfusions.
On May 28, 2002, the United States Food and Drug Administration instituted a policy that excludes from donation anyone having spent at least six months in certain European countries (or three months in the United Kingdom) from 1980 to 1996. Given the large number of U.S. military personnel and their dependents residing in Europe, it was expected that over 7% of donors would be deferred due to the policy. Later changes to this policy have relaxed the restriction to a cumulative total of five years or more of civilian travel in European countries (six months or more if military). The three-month restriction on travel to the UK, however, has not been changed.
In New Zealand, the New Zealand Blood Service (NZBS) in 2000 introduced measures to preclude permanently donors having resided in the United Kingdom (including the Isle of Man and the Channel Islands) for a total of six months or more between January 1980 and December 1996. The measure resulted in ten percent of New Zealand's active blood donors at the time becoming ineligible to donate blood. In 2003, the NZBS further extended restrictions to permanently preclude donors having received a blood transfusion in the United Kingdom since January 1980, and in April 2006, restrictions were further extended to include the Republic of Ireland and France.
Similar regulations are in place in France and in Germany, where anyone having spent six months or more living in the UK between January 1980 and December 1996 is permanently banned from donating blood.
In Canada, individuals are not eligible to donate blood or plasma if they have spent a cumulative total of three months or more in the UK or France from January 1, 1980 to December 31, 1996. They are also ineligible if they have spent a cumulative total of five years or more in Western Europe outside the UK or France since January 1, 1980 through December 31, 2007 or spent a cumulative total of six months or more in Saudi Arabia from January 1, 1980 through December 31, 1996 or if they have had a blood transfusion in the UK, France or Western Europe since 1980.
In the Czech Republic, anyone having spent more than six months in the UK or France between the years 1980 and 1996 or received transfusion in the UK after the year 1980 is not allowed to donate blood.
In the U.S., the FDA has banned import of any donor sperm, motivated by a risk of variant Creutzfeldt-Jakob disease, inhibiting the once popular import of Scandinavian sperm. Despite this the scientific consensus is that the risk is negligible, as there is no evidence Creutzfeldt–Jakob is sexually transmitted.
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 patients with the disease. The human PRNP protein which is subverted in prion disease can occur with either methionine or valine at amino acid 129, without any apparent difference in normal function. 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.
- 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.
- 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.
- Routine investigations do not suggest an alternative, non-CJD diagnosis.
- No history of receipt of cadaveric human pituitary growth hormone or a dura mater graft.
- No history of CJD in a first degree relative or prion protein gene mutation in the person.
vCJD is a separate condition from classic Creutzfeldt–Jakob disease (though both are caused by PrP prions). Both classic and variant CJD are subtypes of Creutzfeld–Jakob disease. There are three main categories of CJD disease: sporadic CJD, hereditary CJD, and acquired CJD, with variant CJD being in the acquired group along with iatrogenic CJD.The classic form includes sporadic and hereditary forms. Sporadic CJD is the most common type.
The Lancet in 2006 suggested that it may take more than 50 years for vCJD to develop, from their studies of kuru, a similar disease in Papua New Guinea. The reasoning behind the claim is that kuru was possibly transmitted through cannibalism in Papua New Guinea when family members would eat the body of a dead relative as a sign of mourning. In the 1950s, cannibalism was banned in Papua New Guinea. In the late 20th century, however, kuru reached epidemic proportions in certain Papua New Guinean communities, therefore suggesting that vCJD may also have a similar incubation period of 20 to 50 years. A critique to this theory is that while mortuary cannibalism was banned in Papua New Guinea in the 1950s, that does not necessarily mean that the practice ended. Fifteen years later Jared Diamond was informed by Papuans that the practice continued. Kuru may have passed to the Fore people through the preparation of the dead body for burial.
These researchers noticed a genetic variation in some people with kuru that has been known to promote long incubation periods. They have also proposed that individuals having contracted CJD in the early 1990s represent a distinct genetic subpopulation, with unusually short incubation periods for bovine spongiform encephalopathy (BSE). This means that there may be many more vCJD patients with longer incubation periods, which may surface many years later.
Prion protein is detectable in lymphoid and appendix tissue up to two years before the onset of neurological symptoms in vCJD. Large scale studies in the UK have yielded an estimated prevalence of 493 per million, higher than the actual number of reported cases. This finding indicates a large number of asymptomatic cases and the need to monitor.
Society and culture
In 1997, a number of people from Kentucky developed vCJD. It was discovered that all had consumed squirrel brains, although a coincidental relationship between the disease and this dietary practice may have been involved. In 2008, UK scientists expressed concern over the possibility of a second wave of human cases due to the wide exposure and long incubation of some cases of vCJD. In 2015, a man from New York developed vCJD after eating squirrel brains. From November 2017 to April 2018, four suspected cases of the disease arose in Rochester.
Researchers believe one in 2,000 people in the UK is a carrier of the disease linked to eating contaminated beef (vCJD). The survey provides the most robust prevalence measure to date—and identifies abnormal prion protein across a wider age group than found previously and in all genotypes, indicating "infection" may be relatively common. This new study examined over 32,000 anonymous appendix samples. Of these, 16 samples were positive for abnormal prion protein, indicating an overall prevalence of 493 per million population, or one in 2,000 people are likely to be carriers. No difference was seen in different birth cohorts (1941–1960 and 1961–1985), in both sexes, and there was no apparent difference in abnormal prion prevalence in three broad geographical areas. Genetic testing of the 16 positive samples revealed a higher proportion of valine homozygous (VV) genotype on the codon 129 of the gene encoding the prion protein (PRNP) compared with the general UK population. This also differs from the 177 patients with vCJD, all of whom to date have been methionine homozygous (MM) genotype. The concern is that individuals with this VV genotype may be susceptible to developing the condition over longer incubation periods.
- Jonathan Simms person who died from vCJD
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