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Multiple HBV transfusion transmissions from undetected occult infections: revising the minimal infectious dose
  1. Daniel Candotti1,
  2. Sonny Michael Assennato2,
  3. Syria Laperche1,
  4. Jean-Pierre Allain2,
  5. Snezna Levicnik-Stezinar3
  1. 1 Department of Blood Transmitted Agents, National Institute of Blood Transfusion, Paris, France
  2. 2 Department of Haematology, University of Cambridge, Cambridge, UK
  3. 3 Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia
  1. Correspondence to Dr Daniel Candotti, Department of Blood Transmitted Agents, National Institute of Blood Transfusion, 75015 Paris, France; dcandotti{at}


Objective HBV infection by blood components is currently prevented in most developed countries by combining sensitive HBV surface antigen (HBsAg) assays, nucleic acid testing (NAT) and in a few of them antibodies against the HBV core antigen (anti-HBc) screening. HBV transmissions by blood components from three repeat donors tested negative for HBsAg and HBV DNA with a highly sensitive screening test (limit of detection (LOD): 3.4 IU/mL) were investigated.

Design 30 of the 47 recipients of components produced from these three donors were examined. Transfusion transmission was confirmed by phylogenetic analysis of viral sequences obtained from recipients and donors following viral particle concentration.

Results 9 of 31 (29%) recipients were infected: 7 infections were related to 200 mL of fresh frozen plasma and 2 infections to red blood cells containing 20 mL plasma. Transfusion transmission was confirmed by >99% identity of donor/recipient sequences in five cases, probable in three and possible in one. HBV active infection remained unsuspected for 24–57 months in three recipients. Five non-infected recipients carried anti-HBs when transfused. Six patients transfused with platelet concentrates treated with a pathogen reduction method were not infected. These data enabled to revise previous estimate of the minimal infectious dose from approximately 100 to 16 copies (or 3 IU) of HBV DNA.

Conclusions HBV transfusion transmission from occult HBV infection carrying extremely low viral loads is related to plasma volume transfused and possibly prevented by anti-HBs. HBV blood safety could be further improved by either anti-HBc screening, HBV DNA NAT with a LOD of 0.8 copies/mL (0.15 IU/mL) or pathogen reduction of blood components.

  • Hepatitis B
  • Transfusion-transmitted Infectious Disease
  • Diagnostic Virology
  • Chronic Viral Hepatitis
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  • Contributors DC designed the study, performed molecular investigations, analysed data and wrote manuscript. SMA performed molecular experiments, contributed to data analysis, reviewed manuscript. SL contributed to experiment design, data analysis and manuscript writing. J-PA contributed to study design, data analysis and manuscript writing. SL-S designed the study, identified and collected samples, analysed data and wrote manuscript.

  • Funding This work was supported by a Grifols Diagnostics research grant to DC.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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