Jos Weusten1, Harry van Drimmelen2, Marion Vermeulen3, Nico Lelie2,4. 1. Philips Handheld Diagnostics, Eindhoven, the Netherlands. 2. Biologicals Quality Control, Rijswijk, the Netherlands. 3. South African National Blood Service, Johannesburg, South Africa. 4. Lelie Research, Paris, France.
Abstract
BACKGROUND: If anti-hepatitis B core antibody testing is not mandated blood donors with occult hepatitis B infection (OBI) may transmit hepatitis B virus (HBV) to a recipient in spite of the use of nucleic acid amplification technology (NAT) or pathogen inactivation (PI). STUDY DESIGN AND METHODS: We developed a model to estimate OBI transmission risk based on three components: the probability distribution of the viral load (VL) in a randomly selected OBI donor, the probability that a given VL remains undetected, and the probability that this VL causes infection in the recipient. A subset of 217 South African OBI samples identified by individual donation (ID)-NAT screening were quantified by replicate testing using an ID-NAT assay (Ultrio Plus) against HBV DNA standard dilution series. The observed log VLs could be described by a Gumbel distribution. A correction was included to compensate for OBI samples missed by initial ID-NAT screening. RESULTS: The model estimates that 3.3% of all OBI donations are undetected by ID-NAT (Ultrio Plus) and cause infection by a blood component containing 20 mL plasma, going up to 8.7% when using minipools of 6 (MP6)-NAT. For 200-mL plasma transfusion these risks were estimated at 14 and 28%, respectively, while PI with modest (2 log) reduction capacity would reach 4.8% without NAT and 1.3 or 0.4% when combined with MP6- or ID-NAT. CONCLUSION: The model can be used to compare different screening and/or PI strategies in reducing viral transmission risk and could serve as a tool in evaluating efficacy of alternative blood safety scenarios.
BACKGROUND: If anti-hepatitis B core antibody testing is not mandated blood donors with occult hepatitis B infection (OBI) may transmit hepatitis B virus (HBV) to a recipient in spite of the use of nucleic acid amplification technology (NAT) or pathogen inactivation (PI). STUDY DESIGN AND METHODS: We developed a model to estimate OBI transmission risk based on three components: the probability distribution of the viral load (VL) in a randomly selected OBI donor, the probability that a given VL remains undetected, and the probability that this VL causes infection in the recipient. A subset of 217 South African OBI samples identified by individual donation (ID)-NAT screening were quantified by replicate testing using an ID-NAT assay (Ultrio Plus) against HBV DNA standard dilution series. The observed log VLs could be described by a Gumbel distribution. A correction was included to compensate for OBI samples missed by initial ID-NAT screening. RESULTS: The model estimates that 3.3% of all OBI donations are undetected by ID-NAT (Ultrio Plus) and cause infection by a blood component containing 20 mL plasma, going up to 8.7% when using minipools of 6 (MP6)-NAT. For 200-mL plasma transfusion these risks were estimated at 14 and 28%, respectively, while PI with modest (2 log) reduction capacity would reach 4.8% without NAT and 1.3 or 0.4% when combined with MP6- or ID-NAT. CONCLUSION: The model can be used to compare different screening and/or PI strategies in reducing viral transmission risk and could serve as a tool in evaluating efficacy of alternative blood safety scenarios.