Safe-Testing Algorithm for Individual-Donation Nucleic Acid Testing: 10 Years of Experience in a Low-Prevalence Country

Abstract

Introduction: A highly sensitive and specific nucleic acid test (NAT) for the blood-borne viruses human immunodeficiency virus (HIV), hepatitis C (HCV), and hepatitis B (HBV) is essential for the safety of blood components. Since more than 2 decades, NAT screening of blood donations has become standard in developed countries that have implemented the individual-donation (ID-NAT) and mini-pool NAT (MP-NAT) approaches. With this powerful technique, confirmation of initial reactive (IR) NAT samples becomes a challenge. Different algorithms are currently in use to eliminate false reactive results. To show that the algorithm implemented in 2007, that uses repeat testing of IR samples in duplicate runs, is a safe strategy, especially in low endemic countries, data from a 10-year experience of ID-NAT were extensively analyzed when follow-up data were available. Methods: From July 2007 to December 2014, the Procleix Ultrio assay on a Procleix Tigris system, and from January 2015 to December 2017, the cobas MPX on a cobas 8800 platform, were used for ID-NAT screening. All IR samples were subjected to repeat testing in duplicate independent runs. Only when both tests remained negative were the products released. Donor data from the last 10 years were investigated retrospectively, looking for the reoccurrence of a reactive result in a follow-up sample. Only those donors with at least an x + 1 donation result were included for the confirmation of a false reactive result. Results: From the 1,830,657 donations tested, 2,450 samples were IR (0.13%); only 228 were repeat reactive ([RR], 18 HIV, 61 HCV, and 149 HBV samples), and 2,222 were non-RR (0.12%). Follow-up data were available from 1,267 donors (57%) for further analysis. All except one of these donors were ID-NAT-negative in all follow-up samples. The one exception was from a donor who acquired a fresh HBV infection 10 years after the IR donation (in the x + 28 donation) and subsequently seroconverted. Subsequent serological tests from all succeeding donations (x + 1, x + 2, etc.) were negative in all the other cases, proving that no seroconversion took place after the IR ID-NAT result. Conclusions: The algorithm to deal with IR ID-NAT donations using duplicate repeat testing is very safe and cost-effective in low-prevalence countries. There is no unnecessary destruction of blood products, no counseling of false reactive donors, and also no need to add further complexity to the screening algorithm.

Algorithms for the Testing of Tissue Donors for Human Immunodeficiency Virus, Hepatitis B Virus, and Hepatitis C Virus

“…Other authors have described that in particular HBV NAT does not always show clear results [46, 47]. In addition to OBI, false-positive results and early window periods have been mentioned as possible causes [48-50].…”

Excluding Occult Hepatitis B Infection before Assigning False-Positive Status to Non-Repeatable NAT Reactivity: Concerning Stolz et al. “Safe-Testing Algorithm for Individual-Donation Nucleic Acid Testing: 10 Years of Experience in a Low-Prevalence Country” [Transfus Med Hemother. 2019 Apr;46(2):104–10]

“…Additional contributions are as follows: C.E.S. initially identified the risk of OBI potentially missed by the Stolz et al algorithm [1], acquired and analyzed the new data here presented, drafted the work, and consolidated critical feedback. A.C. contributed to the acquisition and analysis of the new data presented and critically reviewed the manuscript.…”

“…Stolz et al in their recent article [1] outlined the algorithm used by the Interregional Blood Transfusion Swiss Red Cross (Bern) for investigating samples that are initially reactive on individual-donation nucleic acid testing (ID-NAT), using the Procleix Ultrio or cobas MPX assays. If samples were negative on two further ID-NAT replicates (non-repeat-reactive, NRR) and also non-reactive on routine serological donor screening (which does not include anti-HBc), they were deemed to be NAT false positive and the donation was released for use with no further testing.…”

“…This analysis by Stolz et al [1] demonstrates that NAT NRR results in their donor population are unlikely to represent early window period infections, at least among those donors available for follow-up. However, we believe some caution is required as the authors’ algorithm and follow-up analysis is not sufficient to exclude occult HBV infection (OBI) among NRR donors.…”

“…Additionally, as these donations were not tested for anti-HBc and therefore the prevalence is unknown among this group, it is unclear how an accurate assessment of OBI risk from NRR donations could be made. The algorithm presented by Stolz et al [1] would not be appropriate in Australia because of the risk of TT-HBV, despite a similarly low anti-HBc prevalence of approximately 2% among Australian and Swiss blood donors [2, 10]. We believe that anti-HBc testing for NAT NRR donations is an efficient and cost-effective way to help reduce the associated risk of OBI, and anti-HBc non-reactivity should be a minimum requirement prior to release of fresh blood components associated with NAT NRR results.…”