Related Experiment Videos
Risk of variant Creuzfeldt-Jakob disease from factor concentrates: current perspectives
1Therapeutic Goods Administration, Australian Commonwealth Department of Health and Aged Care; and World Federation of Haemophilia, Montréal, Canada. albert.farrugia@health.gov.au
Insights
Concerns over Creutzfeldt-Jakob disease (CJD) transmission via blood products have led to new safety measures. While plasma fractionation shows promise, developing screening tests and elimination methods for variant CJD (vCJD) is crucial for informed choices.
Area of Science:
- Transfusion Medicine
- Prion Diseases
- Biologics Safety
Background:
- Iatrogenic Creutzfeldt-Jakob disease (CJD) transmission concerns arose in the 1980s-1990s, impacting blood product availability.
- Regulatory actions, including product recalls, created plasma shortages, later rescinded due to evidence of non-transmission and effective fractionation.
Purpose of the Study:
- To address the emerging risk of variant Creutzfeldt-Jakob disease (vCJD) transmission through blood products.
- To evaluate the safety of plasma-derived factor concentrates in light of vCJD.
- To inform the blood product industry and users about vCJD risks and mitigation strategies.
Main Methods:
- Review of epidemiological evidence regarding CJD and vCJD transmission through blood.
- Assessment of plasma fractionation system efficacy in eliminating CJD-type agents.
- Analysis of current and potential vCJD risk mitigation strategies, including donor selection and pathogen elimination techniques.
Main Results:
- Plasma fractionation appears to reduce vCJD-like agents, but specific elimination methods like nanofiltration are under consideration.
- The primary vCJD risk factor is consumption of cattle products linked to bovine spongiform encephalopathy (BSE), primarily in the UK.
- Current screening and elimination methods are insufficient for vCJD; no specific blood test exists.
Conclusions:
- Cautious optimism exists for the safety of factor concentrates regarding vCJD, with evidence suggesting low risk from moderate BSE-affected regions.
- Development of vCJD blood screening tests and dedicated elimination methods are high priorities.
- Informed choices for blood product users, considering alternatives like recombinant concentrates, are essential.
Abstract:
The demonstration of iatrogenic transmission of Creuzfeldt-Jakob disease (CJD) through therapeutic interventions led to substantial concerns in communities requiring blood products in the 1980s and 1990s. These concerns led some regulatory authorities to adopt a very precautionary approach and require recall of plasma products, including factor concentrates, which included donors at risk of CJD. The FDA's approach on recall contributed to a substantial lack of plasma products on the world market in the mid- to late 1990s. Growing epidemiological evidence of non-transmission of CJD to humans through blood, as well as demonstration of the plasma fractionation system's ability to eliminate CJD-type agents, led the FDA to rescind its measures for product recall in 1998. Although no evidence exists that the variant strain of CJD (vCJD) will behave any differently to the classic strain (cCJD) of the disease during fractionation, indications that higher levels of the strain may be present in the blood in vCJD, as well as the uncertainty regarding the epidemiology of the disease, has led to a new round of precautionary measures aimed at minimizing vCJD risk. Currently, the traditional approach to product safety through appropriate donor selection, screening using laboratory tests and systematic pathogen elimination is not completely possible for addressing the risk of vCJD. The only definite risk factor for vCJD is residence in a country where meat products from cattle with bovine spongiform encephalopathy (BSE) have been consumed; currently this is predominantly the United Kingdom but the appearance of BSE in other European countries has stimulated non-European regulatory authorities to defer blood donors from most of Europe. There is currently no screening test available for vCJD. Plasma fractionation techniques fortuitously appear to eliminate substantial amounts of vCJD like agents but only one pathogen eliminating technique, nanofiltration, has been proposed for specifically eliminating vCJD-like agents. Despite the current uncertainty, it is possible to be cautiously optimistic regarding the safety of factor concentrates from the risk of vCJD. An accumulating body of evidence suggests that it is unlikely that the plasma pool from countries with moderate BSE epidemics will contain sufficient levels of vCJD agent to lead to an infective final product. Nevertheless, the development of a blood screening test and more dedicated elimination methods are high priorities for the blood industry as it faces this new threat. The community of blood product users, including people with haemophilia, need to be in a position to make an informed choice regarding the risk of this new agent. Such a choice needs to take into account the alternatives to plasma product therapy such as recombinant concentrates and the risks to product supply ensuing from an excessive reliance on one form of product.