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      Factors in enhancing blood safety by nucleic acid technology testing for human immunodeficiency virus, hepatitis C virus and hepatitis B virus

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          Abstract

          In the last few decades through an awareness of transfusion transmitted infections (TTI), a majority of countries have mandated serology based blood screening assays for Human immunodeficiency virus (HIV), Hepatitis C virus (HCV), and Hepatitis B virus (HBV). However, despite improved serology assays, the transfusion transmission of HIV, HCV, and HBV continues, primarily due to release of serology negative units that are infectious because of the window period (WP) and occult HBV infections (OBI). Effective mode of nucleic acid technology (NAT) testing of the viruses can be used to minimize the risk of TTIs. This review compiles the examples of NAT testing failures for all three viruses; analyzes the causes for failure, and the suggestions from retrospective studies to minimize such failures. The results suggest the safest path to be individual donation testing (ID) format for highest sensitivity, and detection of multiple regions for rapidly mutating and recombining viruses. The role of blood screening in the context of the donation and transfusion practices in India, the donor population, and the epidemiology is also discussed. World wide, as the public awareness of TTIs increases, as the recipient rights for safe blood are legally upheld, as the possibility to manage diseases such as hepatitis through expensive and prolonged treatment becomes accessible, and the societal responsibility to shoulder the health costs as in the case for HIV becomes routine, there is much to gain by preventing infections than treating diseases.

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          Most cited references53

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          Nucleic acid testing to detect HBV infection in blood donors.

          The detection of hepatitis B virus (HBV) in blood donors is achieved by screening for hepatitis B surface antigen (HBsAg) and for antibodies against hepatitis B core antigen (anti-HBc). However, donors who are positive for HBV DNA are currently not identified during the window period before seroconversion. The current use of nucleic acid testing for detection of the human immunodeficiency virus (HIV) and hepatitis C virus (HCV) RNA and HBV DNA in a single triplex assay may provide additional safety. We performed nucleic acid testing on 3.7 million blood donations and further evaluated those that were HBV DNA-positive but negative for HBsAg and anti-HBc. We determined the serologic, biochemical, and molecular features of samples that were found to contain only HBV DNA and performed similar analyses of follow-up samples and samples from sexual partners of infected donors. Seronegative HIV and HCV-positive donors were also studied. We identified 9 donors who were positive for HBV DNA (1 in 410,540 donations), including 6 samples from donors who had received the HBV vaccine, in whom subclinical infection had developed and resolved. Of the HBV DNA-positive donors, 4 probably acquired HBV infection from a chronically infected sexual partner. Clinically significant liver injury developed in 2 unvaccinated donors. In 5 of the 6 vaccinated donors, a non-A genotype was identified as the dominant strain, whereas subgenotype A2 (represented in the HBV vaccine) was the dominant strain in unvaccinated donors. Of 75 reactive nucleic acid test results identified in seronegative blood donations, 26 (9 HBV, 15 HCV, and 2 HIV) were confirmed as positive. Triplex nucleic acid testing detected potentially infectious HBV, along with HIV and HCV, during the window period before seroconversion. HBV vaccination appeared to be protective, with a breakthrough subclinical infection occurring with non-A2 HBV subgenotypes and causing clinically inconsequential outcomes. (Funded by the American Red Cross and others.).
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            Experience of German Red Cross blood donor services with nucleic acid testing: results of screening more than 30 million blood donations for human immunodeficiency virus-1, hepatitis C virus, and hepatitis B virus.

            The risk of transfusion-transmitted human immunodeficiency virus-1 (HIV-1), hepatitis C virus (HCV), and hepatitis B virus (HBV) infections is predominantly attributable to donations given during the early stage of infection when diagnostic tests may fail. In 1997, nucleic acid amplification technique (NAT)-testing was introduced at the German Red Cross (GRC) blood donor services to reduce this diagnostic window period (WP). A total of 31,524,571 blood donations collected from 1997 through 2005 were screened by minipool NAT, predominantly with pool sizes of 96 donations. These donations cover approximately 80 percent of all the blood collected in Germany during that period. Based on these data, the WP risk in the GRC blood donor population was estimated by using a state-of-the-art mathematic model. During the observation period, 23 HCV, 7 HIV-1, and 43 HBV NAT-only-positive donations were detected. On the basis of these data and estimated pre-NAT infectious WPs, the residual risk per unit transfused was estimated at 1 in 10.88 million for HCV (95% confidence interval [CI], 7.51-19.72 million), 1 in 4.30 million for HIV-1 (95% CI, 2.39-21.37 million), and 1 in 360,000 for HBV (95% CI, 0.19-3.36 million). Based on observed cases of breakthrough infections, the risk of transfusion-related infections may be even lower. The risk of a blood recipient becoming infected with HCV, HIV-1, or HBV has reached an extremely low level. Introduction of individual donation testing for HCV and HIV-1 would have a marginal effect on interception of WP donations.
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              International survey on NAT testing of blood donations: expanding implementation and yield from 1999 to 2009.

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                Author and article information

                Journal
                Asian J Transfus Sci
                Asian J Transfus Sci
                AJTS
                Asian Journal of Transfusion Science
                Medknow Publications & Media Pvt Ltd (India )
                0973-6247
                1998-3565
                Jan-Jun 2014
                : 8
                : 1
                : 13-18
                Affiliations
                [1] Research Diagnostics Inc., Bengaluru, India
                Author notes
                Correspondence to: Dr. Venkatakrishna Shyamala, 46/1, Palace Loop Road, Vasanth Nagar, Bengaluru - 560 052, Karnataka, India. E-mail: vshyamala@ 123456netscape.net
                Article
                AJTS-8-13
                10.4103/0973-6247.126682
                3943137
                24678167
                f143dfc6-26de-4297-9d03-0f47d32d0ca1
                Copyright: © Asian Journal of Transfusion Science

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Review Article

                Hematology
                donor look back,individual donation nucleic acid technology testing,multi pool nucleic acid technology testing,recipient trace back,transfusion transmitted viral infections,window period and occult infections

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