Revised nucleic acid test window periods: Applications and limitations in organ donation practice.

BACKGROUND: Nucleic acid test window periods for HIV, HCV, and HBV facilitate estimation of the residual risk of unexpected disease transmission and assist clinicians in determining the timeframe in which a recently acquired infection is at risk of nondetection. OBJECTIVES: Firstly, to provide revised estimates of the NAT window periods based on a currently used triplex NAT assay. Secondly, to examine their validity in organ donation and transplantation practice. METHOD: Estimates were based on the Procleix Ultrio Elite Assay (Grifols Diagnostic Solutions Inc. California, USA). The manufacturer's X50 and X95 limits of detection (LOD) were utilised. Viral doubling times of 0.85, 0.45, and 2.56 days and conversion factors for IU per ml to copies per mL of 0.6, 3.4, and 5 were assumed for HIV, HCV, and HBV respectively. Window periods were derived from the X50 and X95 LODs, based on a range of potential inoculum volumes. RESULTS: Calculated X50 window periods were 5.1 (4.5-5.8), 2.7 (2.4-2.9), and 16.6 (14.2-19.1) days for HIV, HCV, and HBV respectively. Calculated X50 window periods, based on whole body plasma volume, were 11.8 (10.3-13.3), 6.2 (5.6-6.8) and 36.7 (31.3-42.1) days respectively. CONCLUSION: X50 NAT window periods were significantly shorter for HBV and HCV and sit at the lower range of previously published estimates for HIV .  Current modeling assumptions may not account for all unexpected transmission events and may no longer be suitable for application to organ donation and transplantation.

Safety Analysis of Extended Platelet Shelf-Life with Large-Volume Delayed Sampling on BACT/ALERT® VIRTUO® in Australia.

Transfusion-transmitted bacterial infection (TTBI) is the leading cause of transfusion-transmitted infections. Platelet components are more likely to be associated with bacterial contamination due to their storage requirements. Australian Red Cross Lifeblood introduced the bacterial contamination screening (BCS) of all platelet components in 2008. The process was recently updated with the use of BACT/ALERT® VIRTUO®, a large-volume delayed sampling (LVDS) protocol and extending platelet shelf-life to seven days. This article describes the results from the routine BCS of platelet components in Australia. Use of VIRTUO has resulted in lower false-positive rates, reducing wastage and improving platelet inventory. Our findings show that the combination of LVDS and VIRTUO improves the safety of platelet transfusions through earlier time to detection, especially for pathogenic bacterial species. Pathogenic bacteria grew within 24 h of incubation with a clear delineation between pathogenic and non-pathogenic species. The data show this protocol is very safe, with no TTBI cases during this time. There were no TTBI reports in recipients of platelet components that subsequently had a positive culture with Cutibacterium species, probably due to the low pathogenic potential of these organisms and slow replication in aerobic platelet bags. We conclude there is no advantage in incubating culture bottles beyond five days.

Recently Acquired Blood-borne Virus Infections in Australian Deceased Organ Donors: Estimation of the Residual Risk of Unexpected Transmission.

Unexpected donor-derived infections of hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV are rare but important potential complications of deceased organ transplantation. The prevalence of recently acquired (yield) infections has not been previously described in a national cohort of Australian deceased organ donors. Donor yield infections are of particularly significance, as they can be used to gain insights in the incidence of disease in the donor pool and in turn, estimate the risk of unexpected disease transmission to recipients. Methods: We conducted a retrospective review of all patients who commenced workup for donation in Australia between 2014 and 2020. Yield cases were defined by having both unreactive serological screening for current or previous infection and reactive nucleic acid testing screening on initial and repeat testing. Incidence was calculated using a yield window estimate and residual risk using the incidence/window period model. Results: The review identified only a single yield infection of HBV in 3724 persons who commenced donation workup. There were no yield cases of HIV or HCV. There were no yield infections in donors with increased viral risk behaviors. The prevalence of HBV, HCV, and HIV was 0.06% (0.01-0.22), 0.00% (0-0.11), and 0.00% (0-0.11), respectively. The residual risk of HBV was estimated to be 0.021% (0.001-0.119). Conclusions: The prevalence of recently acquired HBV, HCV, and HIV in Australians who commence workup for deceased donation is low. This novel application of yield-case-methodology has produced estimates of unexpected disease transmission which are modest, particularly when contrasted with local average waitlist mortality. Supplemental Visual Abstract; http://links.lww.com/TXD/A503.

Analysis of sample-to-cutoff ratios on chemiluminescent immunoassays used for blood donor screening highlights the need for serologic confirmatory testing.

BACKGROUND: High sample-to-cutoff (s/co) ratios on hepatitis C virus antibody (anti-HCV) screening immunoassays (IAs) are indicative of confirmed-positive results and, according to some reports, can be used to determine anti-HCV status without the need for confirmatory testing. The purpose of this study was to determine whether s/co ratios on hepatitis B surface antigen (HBsAg), antibody to human immunodeficiency virus Types 1 and 2 (anti-HIV-1/2), anti-HCV, and antibody to human T-lymphotropic virus Types I and II (anti-HTLV-I/II) chemiluminescent immunoassays (ChLIAs) can be used to discriminate between biologic false-reactive (BFR) and confirmed-positive results. STUDY DESIGN AND METHODS: In a blood donor population the s/co ratio distributions for BFR and confirmed-positive results were compared for the Abbott PRISM HBsAg, HIV O Plus, HCV, and HTLV-I/II ChLIAs to determine the extent of overlap between the two distributions for each assay. RESULTS: The s/co ratio distributions for BFR and confirmed results overlapped in the range of 10.00 to 60.00, 1.00 to 6.00, 3.00 to 15.00, and 1.00 to 100.00 for the PRISM HIV O Plus, HCV, HTLV-I/II, and HBsAg assays, respectively. CONCLUSION: Although high s/co ratios were predictive of confirmed-positive results in all four assays, a number of confirmed-positive samples gave low values while some biologic false-positive samples showed high values. As the s/co ratio distributions for BFR and confirmed-positive results overlapped for all four PRISM assays, this study highlights the importance of serologic confirmatory testing and the need for caution when using screening IA results to assign a final donor status.

Assessing the accuracy of three viral risk models in predicting the outcome of implementing HIV and HCV NAT donor screening in Australia and the implications for future HBV NAT.

BACKGROUND: Risk modeling is now the most practical method of estimating the residual risk of viral transmission in developed countries. One method of assessing the accuracy of a risk model is to measure the observed against the predicted outcome after implementing a new screening method. The primary objective of this paper is to assess the accuracy of three published models in predicting the impact of implementing HIV and HCV NAT in Australia. STUDY DESIGN AND METHODS: Viral screening data on Australian donors for 2000 and 2001 were retrospectively analyzed. The data were applied to the three models to estimate the risk of transmission and predicted NAT yield for HIV, HCV, and HBV. RESULTS: The median risk estimates for the three models were 1 in 3,415,000 for HIV NAT, 1 in 911,000 for HCV NAT, and 1 in 483,000 for HBsAg. The predicted NAT yield for the three models ranged from 0.17 to 0.30 per million donations for HIV, 1.20 to 5.55 for HCV, and 0.47 to 1.01 for HBV. The observed NAT yield was not significantly different from the expected yield with any of the three models for either HIV or HCV. CONCLUSIONS: First, the residual risk in Australian donors is small in comparison with other transfusion complications and comparable to or lower than the risk in US and European nonremunerated donors. Second, mathematical risk modeling has sufficient precision to be used as a predictive tool for risk-benefit assessments of novel screening procedures. Finally, in relation to the case for implementing HBV NAT and/or anti-HBc in Australia, we conclude that at present, there is inadequate information about our donor population to perform an evidence-based risk-benefit analysis.