From mad cows to sensible blood transfusion: the risk of prion transmission by labile blood components in the United Kingdom and in France

Abstract

Transfusion transmission of the prion, the agent of variant Creutzfeldt-Jakob disease (vCJD), is now established. Subjects infected through food may transmit the disease through blood donations. The two nations most affected to date by this threat are the United Kingdom (UK) and France. The first transfusion cases have been observed in the UK over the past 5 years. In France, a few individuals who developed vCJD had a history of blood donation, leading to a risk of transmission to recipients, some of whom could be incubating the disease. In the absence of a large-scale screening test, it is impossible to establish the prevalence of infection in the blood donor population and transfused patients. This lack of a test also prevents specific screening of blood donations. Thus, prevention of transfusion transmission essentially relies at present on deferral of "at-risk" individuals. Because prions are present in both white blood cells and plasma, leukoreduction is probably insufficient to totally eliminate the transfusion risk. In the absence of a screening test for blood donations, recently developed prion-specific filters could be a solution. Furthermore, while the dietary spread of vCJD seems efficiently controlled, uncertainty remains as to the extent of the spread of prions through blood transfusion and other secondary routes.

Bioassay of prion-infected blood plasma in PrP transgenic Drosophila

“…Our studies here support the view that the level of prion infectivity in blood from prion-diseased individuals may be underestimated when assessed by intracerebral inoculation of rodents in comparison with bioassay of similar material in other experimental systems. This is particularly pertinent to our assessment here of prion-infected plasma that could be diluted by several orders of magnitude and still trigger a phenotypic response in the PrP transgenic Drosophila, but appears to contain a low level of infectivity when assayed in other systems [10,[15][16][17][18][19][20][21]. One possibility for the efficient detection of scrapie-infected sheep plasma by PrP transgenic Drosophila is that this invertebrate host does not normally express PrP and may therefore not have evolved suitable defence mechanisms that efficiently remove or sequester misfolded neurotoxic forms of this protein.…”

“…Collectively, these studies revealed that prion infectivity titres of blood samples harvested during the asymptomatic phase of prion disease were up to 10-fold less than those collected during the clinical phase [10,19,20,22]. Infectious prions were found to be associated with white and red blood cells, platelets and plasma, although interspecies variations existed with regard to the distribution of prion infectivity in these different blood fractions [10,[15][16][17][18][19][20][21]. Studies in ruminants have analysed bioassays of autologous whole or fractionated blood by the intravenous route [19,20].…”

“…The occurrence of vCJD prions in human lymphoid tissue, together with the detection of prion infectivity in the blood of animals with asymptomatic experimental prion disease [10,11], raised the possibility for the potential of blood-borne vCJD transmission. These concerns were realised with the emergence of cases of vCJD in individuals within the U.K. who had received red blood cell concentrates [12][13][14][15]. In addition, abnormal prion protein was detected in a post-mortem spleen sample from a haemophilic patient who had received purified Factor VIII prepared from plasma batches that included donations from individuals who later developed vCJD [12].…”

“…The bioassay of blood-borne prion infectivity has been performed for a variety of different species, such as rodents, sheep, cervids and primates including humans, undergoing, collectively, either experimental or natural prion disease [10,[15][16][17][18][19][20][21]. These bioassays have typically involved intracerebral inoculation of blood, or blood fractions, into a recipient indicator species, usually rodents including mice with a PrP transgene autologous for the donor species.…”

Magnetic microparticle-based multimer detection system for the detection of prion oligomers in sheep

“…37,38 Depending on the titer of transmitted PrP Sc , the detection of preclinical scrapie in recipient lambs may take anywhere from between 594 days and 1,089 days posttransmission. CWD infectivity in white-tailed deer was not found in platelet-poor plasma but in the platelets, whereas infectivity was observed in the plasma of sheep, hamsters, and humans.…”