Title: Surveillance for Asymptomatic Prion Infection in Primary Immunodeficiency Patients Exposed to UK Sourced Immunoglobulin
Funder: Department of Health (England)

Abstract: Background The possibility that the abnormal prions responsible for variant Creutzfeldt-Jakob disease (vCJD) may be transmitted through plasma products has considerable ramifications for patients with Primary Immunodeficiency (PID) receiving immunoglobulin. Although abnormal prions are transmissible by whole blood between animals, there are no data showing this can happen between humans. Abnormal prions can now be detected in lymphoid tissue from asymptomatically infected individuals with reasonable specificity and sensitivity. The technology to detect abnormal prions in blood samples is also improving. The proposed project will be carried out on approximately 130 PID patients exposed to UK sourced immunoglobulin between 1996 and 1998, attending PID centres across the UK. The proposal is to produce: - a confidential data base containing exposure details and prospective clinical evaluations - a retrospective and prospective collections of lymphoid and spleen material for histological prion analysis. - a retrospective and prospective collection of serum, plasma and urine. Testing will be carried out when it becomes available (the costs of blood testing are not included in this application). - a collection of DNA to determine prion genotype and to investigate other, currently un identified, polymorphisms Aims HISTORIC PROJECT - all available project details have been transferred to respective fields in this database. Plan of Investigation The study is monitoring primary immunodeficiency patients who received immunoglobulin replacement therapy with either Vigam (BPL) or Normal Human Immunoglobulin (SNBTS) between 1997 and 2000. This group has been targeted because they received immunoglobulin made from UK sourced plasma and therefore have a slight, theoretical risk of infection with variant Creutzfeldt Jakob Disease(vCJD). There have, to date, been no cases of transmission of vCJD via immunoglobulin. Since the design of the study in 2005, there have been 2 further cases of vCJD attributable to blood transfusion, bringing the current total to 4. ( TMER, 2007). This gives very good evidence that vCJD can be transmitted via blood products (Hewitt et al, 2006) and reinforces the need for surveillance of those who may be at risk of transmission via immunoglobulin. Potential Impact HISTORIC PROJECT - all available project details have been transferred to respective fields in this database. Policy Relevance If the proposed project shows that abnormal prion infection in PID patients exposed to UK sourced immunoglobulin is significantly higher than the UK background, the inference will be that immunoglobulin is capable of prion transmission. The data will give approximate numbers of patients infected and inform planning for the clinical and social needs of these individuals. More broadly, the finding of infected immunoglobulin recipients would improve our understanding of prion biology in humans. This finding would suggest that fractionation of British plasma should not be reintroduced and that the risk assessment for other British blood products should be reviewed. Infection control strategies for patients exposed to British plasma products undergoing surgery would need to be considered. Failure to detect infected individuals would not rule out a low risk of prion transmission in these patients, but would inform the risk assessments for blood products, which are currently based on in vitro or animal data. Depending on the number of samples that become available and the sensitivity of the tests involved, negative results would also reassure patients, add weight to the arguments that British plasma may safely be fractionated and that these patients do not require special infection control measures.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: NEUROLOGICAL