title: A mathematical model for estimating residual transmission risk of occult hepatitis B virus infection with different blood safety scenarios.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Philips Handheld Diagnostics, Eindhoven, the Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Weusten
authors.affiliation: Biologicals Quality Control, Rijswijk, the Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: van Drimmelen
authors.affiliation: South African National Blood Service, Johannesburg, South Africa.
authors.forename: Marion
authors.initials: M
authors.lastname: Vermeulen
authors.affiliation: Biologicals Quality Control, Rijswijk, the Netherlands.|Lelie Research, Paris, France.
authors.forename: Nico
authors.initials: N
authors.lastname: Lelie
mesh_terms: D001782:Blood Donors; D058731:Blood Safety; D006509:Hepatitis B / Q000635:transmission*; D006515:Hepatitis B virus; D006801:Humans; D008954:Models, Biological; D011897:Random Allocation