Abstract
Natural changes that occur in blood and tissue after death may result in false positive results in antigen and antibody detection tests performed to identify markers of viral infection in potential tissue donors. Such tissue, which might otherwise be acceptable for therapeutic purposes, would not meet current standards for safe tissue banking. This is especially important in the context of insufficiency in the tissue supply. In this study, a series of blood samples collected during routine post-mortem examination was assayed using a range of commercially available kits for the detection of HBsAg, anti-HCV and anti-HIV 1 + 2 antibody/antigen. Results of tests on 104 samples collected from 97 individuals indicate that some kits result in a higher number of initial reactive samples than others. Approximately 40% of samples were reactive in one or more HBsAg assay, less than 10% in at least one anti-HIV kit and only 1 sample at low level on an anti-HCV kit. Liver or lymph node samples from individuals whose serum sample gave reactive results in antigen/antibody assays were tested for viral nucleic acid in the corresponding nucleic acid amplification test. Only one individual’s sample was confirmed to test positive for HBsAg in a confirmatory neutralisation test and by nucleic acid amplification technology, and a second individual whose serum was scored reactive for anti-HCV, but negative for HBsAg, had a liver sample which was HBV DNA positive and HCV RNA negative. The results of the study indicate that antibody/antigen assays are not as specific as NAT using state of the art DNA extraction techniques. Both types of assay complement each other and used together will help assure the safety of tissues for transplantation.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Abbreviations
- AIDS:
-
Acquired immuno-deficiency syndrome
- GZ:
-
Grey zone
- HBsAg:
-
Hepatitis B surface antigen
- HBV:
-
Hepatitis B virus
- HCV:
-
Hepatitis C virus
- HIV:
-
Human immunodeficiency virus
- NAT:
-
Nucleic acid amplification techniques
- RNA:
-
Ribonucleic acid
- RT-PCR:
-
Reverse transcriptase polymerase chain reaction
- DNA:
-
Deoxy-ribonucleic acid
References
J. Ball U. Desselberger H. Whitwell (1991) ArticleTitleLong lasting viability of HIV after patient’s death The Lancet 338 63 Occurrence Handle10.1016/0140-6736(91)90063-U
N. Berry C. Davis A. Jenkins D. Wood P. Minor G. Schild M. Bottiger H. Holmes N. Almond (2001) ArticleTitleVaccine safety: analysis of oral polio vaccine CHAT stocks Nature 410 IssueID6832 1046–1047 Occurrence Handle10.1038/35074176 Occurrence Handle11323658
G. Burtonboye C. Delloye (1996) ArticleTitlePolymerase chain reaction in cadaveric blood and tissues Transplant. Proc 28 2927–2928 Occurrence Handle8908127
M. Busch L. Lee G. Satten D. Henrard H. Farzadegan K. Nelson S. Read R. Dodd L. Petersen (1995) ArticleTitleTime course of detection of viral and antigen and antibody detection markers preceding human immunodeficiency virus type 1 seroconversion: implication for screening of blood and tissue donors Transfusion 35 91–97 Occurrence Handle10.1046/j.1537-2995.1995.35295125745.x Occurrence Handle7825218
P.R. Cieslak K. Hedberg A.R. Thomas (2003) ArticleTitleHepatitis C virus transmission from an antibody negative organ and tissue donor – United States 2000–2002 MMWR 52 273–276
Committee for Proprietary Medicinal Products 1997. Introduction of Genomic Amplification Technology (GAT) for the detection of hepatitis C virus RNA in plasma pools. Addendum for Guidance on Plasma Derived Products CPMP/BWP/390/97.
E. Conrad D. Gretch K. Obermeyer M. Moogk M. Sayer J. Wilson D. Strong (1995) ArticleTitleThe transmission of hepatitis C virus by tissue transplantation J. Bone Joint Surg 77-A 214–224
Council of Europe 2004. Guide to Safety and Quality Assurance for Organs, Tissues and Cells. Council of EuropeISBN ISBN 92–871–5518–6.
B.C. Dow (2000) ArticleTitle‘Noise’ in microbiological screening assays Transfusion Med 10 97–106 Occurrence Handle10.1046/j.1365-3148.2000.00248.x
B.C. Dow I. Buchannan H. Munro E.A.C. Follett F. Davidson L.E. Prescott P.L. Yap P. Simmonds (1996) ArticleTitleRelevance of RIBA-3 supplementary test to HCV PCR positivity and genotypes for HCV confirmation of blood donors J. Med. Virol 49 132–136 Occurrence Handle10.1002/(SICI)1096-9071(199606)49:2<132::AID-JMV10>3.0.CO;2-G Occurrence Handle8991936
D.T. Eastlund (1995) ArticleTitleInfectious disease transmission through cell, tissue and organ transplantation: reducing the risk through donor selection Cell Transplant 4 455–477 Occurrence Handle10.1016/0963-6897(95)00035-V Occurrence Handle8520830
D.T. Eastlund (2000) ArticleTitleHemodilution due to blood loss and transfusion and reliability of cadaver tissue donor infectious disease testing Cell and Tissue Banking 1 121–127 Occurrence Handle10.1023/A:1010120115451 Occurrence Handle15256957
Guidelines for Blood Transfusion Services in the UK. Sixth Edition 2002. The Stationary OfficeLondon. (Available at http://www.transfusionguidelines.org.uk).
A. Heim D. Wagner T. Rothamel U. Hartmann J. Flik W. Verhagen (1999) ArticleTitleEvaluation of antigen and antibody detection screening of cadaveric sera for donor selection for cornea transplantation J. Med. Virol 58 291–295 Occurrence Handle10.1002/(SICI)1096-9071(199907)58:3<291::AID-JMV16>3.0.CO;2-D Occurrence Handle10447426
S. Kleinman M. Busch J. Korelitz G. Schreiber (1997) ArticleTitleThe incidence/window period model and its use to assess the risk of transfusion-transmitted human immunodeficiency virus and hepatitis C virus infection Transfusion Med. Rev 11 155–172 Occurrence Handle10.1053/tmrv.1997.0110155
W.M. LeFor A.F. McGonigle D.L. Wright D.L. Shires SuffixIII (1996) ArticleTitleThe frequency of false positive HBsAg screening test results with cadaver tissue donors is dependent upon the assay procedure used Tissue and Cell Report 3 297–300
Martinez O.V. and Malinin T.I. 1996. The effect of postmortem interval and manner of death on blood and bone marrow cultures from non-septic cadaver donors of tissues for transplantation. Abstracts of the 96th Meeting of the American Society for Microbiology. New Orleans,Louisiana
H. Meisel (2003) ArticleTitleTransmission of hepatitis B virus 2 months prior to hepatitis B surface antigen positivity of donor blood Transfusion Med. Hemotherapy 30 228–231 Occurrence Handle10.1159/000074288
M. Miédougé M. Chatelut J-M. Mansuy (2002) ArticleTitleScreening of blood from potential organ and cornea donors for viruses J. Med. Virol 66 571–575 Occurrence Handle10.1002/jmv.2183 Occurrence Handle11857539
S.L. Novick J.A. Schrager J.A. Nelson B.L. Baskin (1993) ArticleTitleA comparison of two hepatitis B surface antigen and two human immunodeficiency virus type 1 (p24) antigen enzyme immunoassay kits using hemolyzed cadaveric blood specimens Transfusion 33 619
D.J. Padley S.B. Lucas J. Saldanha (2003) ArticleTitleElimination of false negative HCV RNA results by removal of inhibitors in cadaver donor blood specimens Transplantation 76 IssueID2 432–434 Occurrence Handle10.1097/01.TP.0000072780.66347.B1 Occurrence Handle12883207
J. Saldanha P. Minor (1996) ArticleTitleCollaborative study to assess the suitability of an HCV RNA reference sample for detection of an HCV RNA in plasma pools by PCR Vox Sang 70 148–151 Occurrence Handle8740006
R.J. Simonds S.D. Holmberg R.L. Hurwitz (1992) ArticleTitleTransmission of human immunodeficiency virus type 1 from a seronegative organ and tissue donor NEJM 326 726–732 Occurrence Handle1738377
S.J. Stanworth R.M. Warwick M. Ferguson J.A. Barbara (2000) ArticleTitleA UK Survey of virological testing of cadaver tissue donors Vox Sanguinis 79 227–230 Occurrence Handle10.1159/000056735 Occurrence Handle11155074
US Department of Health and Human Services, Food and Drug Administation. 2000. Guidance for industry. Availability of Licensed Donor Screening Tests Labelled for use with Cadaveric Blood Specimens http://www.fda.gov/cber/ gdlns/cadbld.pdf.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Padley, D., Ferguson, M., Warwick, R. et al. Challenges in the Testing of Non-Heart-Beating Cadavers for Viral Markers: Implications for the Safety of Tissue Donors. Cell Tissue Banking 6, 171–179 (2005). https://doi.org/10.1007/s10561-005-5421-9
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10561-005-5421-9