The prion protein that causes variant Creutzfeldt–Jakob disease destroys neurons in the brain. As a new study in the British Medical Journal reveals that 1 in 2000 people in the UK may harbour the infectious prion protein which causes variant Creutzfeldt–Jakob disease (vCJD), Nature explains what this means. The usually fatal condition is the human form of bovine spongiform encephalopathy (BSE) — dubbed ‘mad cow disease’ in the UK after an outbreak of the disease in the 1980s. Both diseases are caused by misfolded proteins called prions, which induce other proteins in the brain to clump, eventually destroying neurons. Humans are thought to contract the disease by consuming beef containing infected bovine brain or other central nervous system tissue. But it also spreads through blood transfusions, and some worry that the prion disease is transmitted via contaminated surgical instruments. The BSE outbreak in the 1980s and 1990s led to a surge in British vCJD cases, and a total of 177 have been detected in the UK to date, with just one in the last two years. Cases of vCJD peaked in 2000, leading some scientists to speculate that the disease takes about a decade to develop. Yet other studies of different forms of CJD suggest its incubation time could be much longer, indicating that many people in Britain could be carrying the infection without symptoms.
Studies have come to varying conclusions as to just how many people harbour the abnormal prion protein (PrP) that causes vCJD. Surveys of tens of thousands of appendices and tonsils, discarded after surgery, have shown PrP prevalence rates ranging from 1 in 40,002 to 1 in 10,0003 or even zero4. Because of the uncertainty over just how many people have the abnormal prion, a body that advises the government on the disease called for a comprehensive prevalence survey in 2008. The study was led by Sebastian Bradner, a neuropathologist at University College London, and it tested for Prp in 32,441 appendices from anonymized donors, collected from 41 UK hospitals. The researchers found 16 positive cases, translating to a prevalence rate of about 1 in 2,0001. Not especially, according to Roland Salmon, a retired consultant epidemiologist who wrote an editorial in the British Medical Journal to accompany Bradner’s paper. The number reported by Bradner’s team is of the same magnitude of the prevalence rate found in a previous survey that found 3 positives in 12,674 patients.
Does this mean that 1 in 2000 people in United Kingdom will develop vCJD? This is unlikely. Animal studies have suggested that the lymphoid system, which includes the spleen and tonsils, is more easily infected with PrP than the brain. But the relationship between infection in the lymphoid system and in the brain is not clear. These cases of detected prions could represent silent carriers, who will not go on to develop clinical vCJD.
“We have no idea if none or a proportion of these people will develop clinical disease, that remains to be seen,” says Graham Jackson, at the MRC Prion Unit at University College London. “Whatever the reasons for infected individuals entering a long term asymptomatic state, much depends on whether this could be expected to last indefinitely, or eventually lead to clinical symptoms,” said the UK government’s advisory committee on dangerous pathogens when the raw numbers were released in 2012. The committee’s predecessor, which commissioned the report said, “The precautionary assumption is that further clinical cases may appear after much longer incubation periods than those seen so far, though their number could be significantly reduced by intervening deaths from other causes.” That’s still an open question. The United Kingdom has taken extraordinary measures to protect its blood supply from vCJD, such as banning blood donation from people who received transfusions after 1980. It is not yet clear whether people with lymphoid-system infections can transmit PrP through their blood. Jackson says the latest study underscores the need for better diagnostics to detect prion infection in blood. “Despite the merciful lack of clinical cases it tells us this problem has not gone away, far from it.”
October 29, 2013
Original web page at Nature