This confirms the epidemiological evidence that variant CJD is caused by BSE infection, and as such represents the only example of a human prion disease acquired from another species (Table 1). The most likely source of human exposure to BSE is the consumption

of contaminated meat products [13]. In keeping with an oral route of infection, both PrPSc and infectivity are detectable within lymphoid tissues, including the spleen, tonsil, lymph nodes, thymus and gut associated lymphoid tissue in variant CJD [9]; levels of infectivity in lymphoid tissues this website are approximately 2–3 logs lower than in brain tissue [14]. Abnormal PrP has been detected by immunohistochemistry in gut-associated lymphoid tissue within the appendix in two patients who had undergone appendicectomy up to 2 years before the onset of variant CJD [15]. These findings have lead to the suggestion that lymphocytes may carry infectivity in blood during the incubation period of variant CJD [16]. This suggestion has been reinforced by the detection of infectivity buy LY2606368 in the blood of sheep experimentally infected with BSE before the animals develop clinical signs and symptoms [17]. By February 2010,

172 cases of variant CJD have been confirmed in the UK, with 47 additional cases in 10 other countries (Table 3). The incidence of variant CJD has declined in the UK since 1999–2000; however, the number of asymptomatic infections in the UK remains uncertain; the results of earlier studies to detect abnormal PrP in tonsil and appendix tissues suggests MCE a prevalence of around 1 per 10 000 of the UK population [15,18,19]. This figure is higher than the current numbers of variant CJD cases in the UK would suggest, indicating that some variant CJD cases may have a prolonged asymptomatic carrier state, which perhaps does not result in clinical disease in all cases. Prion infectivity

in blood has been demonstrated in rodent models during the incubation period and after the clinical onset of disease [20,21]; the levels of infectivity in whole blood as measured by bioassay are around 10 ID mL−1. Most infectivity was found to be associated with white blood cells, but infectivity was also present in plasma and red blood cells [20]. Experimental BSE and scrapie infection in sheep has also demonstrated infectivity in blood during the incubation period and after the clinical onset of disease. Transmission rates of at least 40% were reported following blood transfusion, with most transmissions occurring from blood samples taken during the second half of the incubation period; transmission of scrapie was also reported with a relatively small volume of a buffy coat preparation [17]. The Transfusion Medicine Epidemiology Review was established in the UK to investigate the possibility of transmission of variant CJD by blood transfusion [22].