Assessing the risk of transmission of vCJD via blood transfusion and identifying potential for diagnosis and prevention

In the UK four patients appear to have developed variant Creutzfeldt-Jakob disease (vCJD) after transfusion of blood from a donors infected with vCJD. These cases raise concern as the blood donors did not show any clinical signs of vCJD at the time the blood donations were made. Whether many more individuals will also develop disease after transfusion of vCJD-contaminated blood is currently uncertain, as is the number of people in the UK infected with vCJD but not showing clinical disease. These factors currently make the diagnosis and prevention of further human to human transmissions of vCJD extremely difficult. This project aims to addresses the major issues surrounding the transmission of vCJD via transfusion of blood or blood products. We aim to assess the risk of transmission of vCJD by blood and to determine whether the disease is modified after human-to-human transmission. For example, transmission of vCJD from one human to another may result in a disease in the recipient that is more aggressive, that targets different sites or appears different from the original disease in current laboratory tests. We will also study how the vCJD agent contaminates the blood stream, and which blood cells or components are affected. This programme will provide an important basis for assessing the risk of vCJD transmission via blood transfusion, and for developing accurate diagnostic tests to prevent further human to human transmission of vCJD.

The recent announcement of a fourth possible transmission of variant Creutzfeldt-Jakob disease (vCJD) through blood transfusion raises concern that an epidemic of vCJD could be sustained through human to human transmission. While transmission from clinical cases of vCJD is not likely to result in a self-sustaining epidemic, current concern over the level of pre or sub-clinical vCJD in the population raises this as an important issue for risk assessment and disease prevention. This programme of work addresses the major issues surrounding the transmission of vCJD via transfusion of blood or blood products. Using our extensive expertise, our unique murine models of TSE disease and access to important samples from blood transfusion vCJD transmissions (made available to us by the National CJD Surveillance Unit) we aim to assess the risk of transmission of vCJD by blood and to define whether modifications in vCJD have occurred during these human-to-human transmission of vCJD, which may affect host range and pathogenicity. In order to assess the risk posed to individuals with different PrP genotypes, we aim to establish how polymorphisms in the PrP gene influence human to human transmissions of vCJD. We will also establish, using our well-defined animal models, where and when the vCJD agent infects the blood stream.
Using our extensive expertise, unique resources, access to critical vCJD samples and our well defined TSE disease models the research in this proposal aims to address the urgent issues regarding the transmission of vCJD via blood transfusion. Experiments will be performed to answer the following questions:
-Are the strain characteristics of the vCJD agent modified by human to human transmission via blood transfusion?
-How does host PrP influence the human to human transmission of vCJD?
-How does infection of the blood stream occur and what components are affected?
This programme will provide an important basis for assessing the risk of vCJD transmission via blood transfusion, and for developing accurate diagnostic tests to prevent further human to human transmission of vCJD.