Current concepts in serological testing – TTID

Abstract

Introduction Blood components play a major part in a huge number of therapeutic interventions in oncology, haematology, surgery and other medicine disciplines. Therefore, the supply of safe blood products is a major ongoing challenge for blood transfusion services. Serology screening tests were developed to improve blood safety. As screening for antibodies reflects an immune reaction in response to infection, the diagnostic window period is longer for antibody tests than for direct screening assays, such as nucleic amplification tests (NAT). The introduction of mini‐pool NAT (MP‐NAT) and individual donation NAT (ID‐NAT) as well as the development of antigen screening assays, such as the hepatitis C virus antigen test (which detects the NS3 antigen) and the p24 antigen assay for HIV‐1, have been able to reduce the diagnostic window period.Methods Currently, blood donor screening for HBsAg, anti‐HBc, anti‐HCV, anti‐HIV‐1/2 and syphilis antibodies is mandated by the German authority (the Paul Ehrlich Institute). All blood donations must also be screened for HCV and HIV‐1 using MP‐NAT. The German Red Cross Blood Donor Services Baden‐Württemberg‐Hessen has implemented additional blood donor screening for anti‐CMV (for platelet products from repeat donors) and MP‐NAT screening for HBV, HAV and Parvovirus B19 on a voluntary basis.Results The epidemiology data within the last 4 years have found that 98% and 89% of hepatitis B and hepatitis C positive donors belonged to the first time donor population. Between 1997 and 2005, the German Red Cross Blood Donor Services detected hepatitis B, hepatitis C and HIV‐1 in 43, 23 and 7 donors, respectively, using NAT. About 50% (22 out of 43) of these HBV‐infected donors were in the acute phase of infection, while 21 were in the occult phase. Improvements in NAT technology, especially the introduction of full‐automated extraction robot systems (e.g. the Zelos × 100), have been able to reduce the diagnostic window period, especially for hepatitis B, by improving the 95% level of detection. Nevertheless, five cases of NAT failures in detecting HIV‐1 have been reported to the Paul‐Ehrlich‐Institute within the last decade. In 2010 in particular, three cases occurred in Germany due to mutations in the primer and probe binding regions. These cases restarted a discussion about risk analysis for NAT screening tests and serology methods in general.Conclusion In Germany, blood donor screening is performed using parallel serological assays (antigen and antibody detection) and by MP‐NAT for hepatitis B, hepatitis C and HIV‐1. The risk of false‐negative test results due to mutations in primer and probe binding regions is higher for NAT systems than for antibody/antigen detection tests. Therefore, the manufactures of the NAT systems are advised to improve their systems by utilising amplification in at least two conserved regions (dual‐ or triple‐targeting). The diagnostic window period for new screening strategies (e.g., antigen screening for HCV)