title: Experience of mandatory nucleic acid test (NAT) screening across all blood organizations in Germany: NAT yield versus breakthrough transmissions.
abstract: BACKGROUND
  Mandatory nucleic acid test (NAT) blood screening was introduced in Germany in 1999 for hepatitis C virus (HCV) RNA and in 2004 for human immunodeficiency virus Type 1 (HIV-1) RNA. Minimal sensitivity limits of 5000 IU HCV RNA/mL and 10,000 IU HIV-1 RNA/mL were defined for the individual donation facilitating testing of minipools (MPs). The NAT yield obtained from all blood organizations is summarized. Transfusion-associated virus transmissions despite NAT screening ("breakthrough transmissions") are analyzed.
  
  
  METHODS
  In Germany, a variety of NAT assays is applied for NAT screening pool sizes of up to 96 donations. Subsets of NAT yield cases were characterized with regard to viral loads by quantitative NAT and with regard to viral genotypes. Confirmed breakthrough transmissions were analyzed using different molecular and serologic assays.
  
  
  RESULTS
  Ninety-two HCV NAT yield cases among 40.8 million and 11 HIV-1 NAT yield cases among 17.1 million donations were identified. During this period, one transmission case was confirmed for HCV and one for HIV-1. The two incidents escaped NAT detection because of low-level viremia and/or suboptimal amplification efficiency. Evidence was obtained for a case of HIV-1 nontransmission by a low-level HIV-1 contaminated red blood cell unit.
  
  
  CONCLUSIONS
  NAT screening of MPs identified the vast majority of window-phase donations. A significant number of transmission cases was interdicted; breakthrough transmissions may still occur as rare events, even with individual-donation NAT in place. Sensitivity limits might be adapted to the current "state of the art" taking account of viral dynamics during early infection, incidence rates, and costs.
authors.affiliation: Sections of Molecular Virology, Transfusion Medicine and Hemovigilance, Paul-Ehrlich-Institut, Langen, Germany. nuemi@pei.de
authors.forename: C Micha
authors.initials: CM
authors.lastname: Nübling
authors.forename: Margarethe
authors.initials: M
authors.lastname: Heiden
authors.forename: Michael
authors.initials: M
authors.lastname: Chudy
authors.forename: Julia
authors.initials: J
authors.lastname: Kress
authors.forename: Rainer
authors.initials: R
authors.lastname: Seitz
authors.forename: Brigitte
authors.initials: B
authors.lastname: Keller-Stanislawski
authors.forename: Markus B
authors.initials: MB
authors.lastname: Funk
mesh_terms: D001769:Blood / Q000821:virology*; D001771:Blood Banks / Q000706:statistics & numerical data*; D005858:Germany; D015658:HIV Infections / Q000175:diagnosis / Q000635:transmission; D006679:HIV Seropositivity; D015497:HIV-1 / Q000302:isolation & purification; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D006526:Hepatitis C / Q000175:diagnosis / Q000635:transmission; D006801:Humans; D018580:Mandatory Testing / Q000706:statistics & numerical data*