Detection of mutant examples of HBsAg

A Transfusion Medicine Services Medical Director in Denmark reports that his local "FDA" has criticized the use of an EU/CE approved HBsAg donor screening kit, using the argument that the particular kit does not detect one or more known HBsAg mutants. While the Denmark physician acknowledges the test kit does not detect all mutant examples of HBsAg, he points out that "One or more companies claim that they have a panel of relevant mutants, while other companies claim that such panels are subjective and the result of haphazard inclusion of mutants." He wonders if colleagues in the U.S. or elsewhere have resolved this matter?

The following comments have been received.

ADDENDA May 26, 2005

1. A transfusion medicine scientist in the USA who is very knowledgeable about blood donor screening technologies reports that in her opinion, there is no current "resolution" to the issue raised by the Denmark colleague. In her experience, HBsAg kit manufacturers attempt to use broad spectrum monoclonal antibodies (1-3 different antibodies per kit, manufacturer dependent) to ensure that at least the major, known mutants can be detected. There is no U.S. FDA guidance for this that she is aware of. She knows (and there have been published reports) that one manufacturer's HBsAg assay is able to detect variants that another manufacturer's assay does not detect. In addition, there is at least one assay that has weaker detection of the common "a" determinant mutations relative to other assays.
   
   
2. A second transfusion medicine scientist in the USA who is also very knowledgeable about blood donor screening technologies reports that in his opinion, it may be unrealistic to expect that there will be tests that detect ALL mutants of HBsAg.
   
   
3. A third transfusion medicine scientist in the USA who is also very knowledgeable about blood donor screening technologies reports that in his opinion the serological failure to detect HBsAg mutants is an unresolved problem, especially for blood banks that do not use anti-HBc testing in routine screening of donated blood. In his opinion, screening donors with anti-HBc improves the safety of the blood supply relative to HBV, compared to what the risk would be if anti-HBc screening was not routinely done. He adds that it should be recognized that at present the limit of NAT testing for blood-borne HIV/HCV/HBV performed on aliquots less of than 0.5 ml in volume, and the transfusion of about 300 ml plasma in a unit of plasma, amounts to a 600-fold differential in volume used for detection of viremia by NAT testing versus the volume of transfused product that might cause transmission of infection. He concludes that "Zero risk in transfusion may never be achievable by current screening tests. Fortunately, the defective interfering (DI) particles in RNA viruses make this risk lesser of a problem for HIV and HCV relative to HBV, a DNA virus replicating through a retroid mechanism. This fact is reflected in epidemiological studies on NAT tested blood showing higher incidence of HBV transmission than HIV or HCV."

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