Publications (4)12.87 Total impact
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Article: Sensitivity of individual-donation and minipool nucleic acid amplification test options in detecting window period and occult hepatitis B virus infections.
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ABSTRACT: BACKGROUND: Several comparison studies showed that the Ultrio assay (Novartis Diagnostics) used in individual-donation nucleic acid amplification testing (ID-NAT) format was as sensitive as the TaqScreen assay (Roche) on minipools of six donations (MP6), but the sensitivity of HBV DNA detection has been improved in the new Ultrio Plus version of the assay. A head-to-head comparison study was designed to compare the clinical sensitivity of the Ultrio and Ultrio Plus assay in ID, MP4, and MP8 formats using TaqScreen MP6 as a reference assay. STUDY DESIGN AND METHODS: Plasma samples of 107 hepatitis B surface antigen (HBsAg)-negative, HBV ID-NAT (Ultrio) positive-yield samples and 29 HBV DNA-negative, HBsAg-positive samples were used for comparison of NAT options in replicate testing of dilutions. Viral loads and relative sensitivities were determined by probit analysis against the Eurohep standard. RESULTS: Ultrio Plus detected a significantly (p < 0.00001) higher proportion of replicate assays on HBV NAT yields (77%) than Ultrio ID (62%) and TaqScreen MP6 (47%), whereas Ultrio Plus MP4 and MP8 detected 53 and 41%, respectively. On HBsAg-yield samples missed by Ultrio screening, the reactivity rate increased significantly (p < 0.0001) from 23% in Ultrio to 65% in Ultrio Plus and further to 72% (p = 0.10) in the TaqScreen assay. The overall improvement factor of the analytical sensitivity offered by the target enhancer reagent in the Ultrio Plus assay was 2.5 (2.0-3.1)-fold on the Ultrio yield samples, but 43 (11-350)-fold on the HBsAg yields. In ID-NAT format the analytical sensitivity of TaqScreen relative to Ultrio Plus was 2.0 (1.0-4.2), 0.9 (0.7-1.3), and 1.6 (0.9-3.0) on the Eurohep standard, HBV NAT-, and HBsAg-yield samples respectively. CONCLUSION: The clinical sensitivity of the currently available commercial NAT methods is mainly driven by the pool size.Transfusion 04/2013; · 3.22 Impact Factor -
Article: Comparison of human immunodeficiency virus assays in window phase and elite controller samples: viral load distribution and implications for transmission risk.
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ABSTRACT: BACKGROUND: After 3 years of individual-donation nucleic acid test (ID-NAT) screening by the South African National Blood Service (SANBS), a repository of 73 human immunodeficiency virus antibody (anti-HIV)-negative window period (WP)-yield samples and 28 anti-HIV-positive, HIV-RNA-negative elite controllers (ECs) became available for comparison of a p24 antigen (p24 Ag) assay (Innogenetics), two viral load assays (Siemens branch DNA [bDNA] 3.0 and Abbott real-time polymerase chain reaction [RT-PCR]), and three triplex NAT assays (Novartis Diagnostics Ultrio and Ultrio-Plus and Roche TaqScreen) by replicate testing of dilutions. STUDY DESIGN AND METHODS: Viral loads were assessed by bDNA and RT-PCR assays and if below 100 copies (cps)/mL, by Ultrio limiting dilution probit analysis. The probability of virus transmission by WP and EC donations was estimated for different levels of the 50% minimum infectious dose (ID50 ) using Poisson distribution statistics. RESULTS: The equal distribution of WP donations plotted by log HIV-RNA levels indicated a random appearance of donors in the ramp-up phase. The HIV p24 Ag assay detected 45% of WP samples and the cutoff crossing point was estimated at 8140 (bDNA)/22,710 (RT-PCR) cps/mL. On replicate retesting of 40 HIV p24 Ag-negative ID-NAT WP-yield samples Ultrio minipool (MP)8, Ultrio-Plus MP8, and TaqScreen MP6 detected 79, 81, and 78%, respectively. Modeling with an estimated ID50 of 31.6 virions/RBC indicated that 15% of p24 Ag-negative ID-NAT WP-yield donations would have transmitted HIV if MP6-8 NAT had been used. Only 2% of RBC transfusions from ECs are estimated to be infectious with a worst-case ID50 estimate of 316 virions. CONCLUSION: Our analysis of viremia and infectivity of WP and EC donations enables comparison of the efficacy of NAT options in preventing HIV transmission risk.Transfusion 02/2013; · 3.22 Impact Factor -
Article: Refinement of a viral transmission risk model for blood donations in seroconversion window phase screened by nucleic acid testing in different pool sizes and repeat test algorithms.
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ABSTRACT: In minipool nucleic acid test (MP-NAT) screening protocols, the donations implicated in reactive test pools are released for transfusion when they are nonreactive in a repeat test on the individual samples, but in individual-donation (ID)-NAT screening algorithms the release of nonrepeatable reactive (NRR) donations is under discussion. A previously developed window phase (WP) transmission risk model for NAT-screened blood transfusions has been refined to take the effect of repeat tests of initially reactive (IR) MP- or ID-NAT results into account. The model has then been applied to simulate the effect of different screening algorithms with ULTRIO and the new-generation ULTRIO Plus assay (Novartis Diagnostics) on transmission risk for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). We calculated WP risk-day equivalents for MP16-, MP8-, and ID-NAT with and without duplicate retesting of IR results of 3.1, 2.7, 1.5, and 1.3 days for HCV; 6.3, 5.5, 3.3, and 2.9 days for HIV; and 24.4, 22.2, 15.6, and 14.1 days for HBV, respectively. These latter infectious HBV WPs reduced to 20.4, 18.2, 11.6, and 10.3 days, respectively, with the more sensitive ULTRIO Plus assay. ULTRIO Plus ID-NAT screening reduces the virus transmission risk in the WP by 54% to 58% compared to ULTRIO MP16-NAT, while the incremental risk caused by releasing donations with duplicate ID-NAT NRR results is 5% to 6%. To achieve maximum safety and specificity a similar repeat test algorithm can be applied to ID-NAT as used for serologic assays.Transfusion 01/2011; 51(1):203-15. · 3.22 Impact Factor -
Article: Sensitivity of two hepatitis B virus, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) nucleic acid test systems relative to hepatitis B surface antigen, anti-HCV, anti-HIV, and p24/anti-HIV combination assays in seroconversion panels.
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ABSTRACT: Accurate determination of the infectious window period (IWP) that remains with individual-donation (ID) or minipool (MP) NAT compared to those with serology assays is essential for residual risk estimations. The relative sensitivity of the Procleix Tigris system (Gen-Probe/Chiron) used in ID-NAT format and cobas s 201 (Roche Molecular Systems) applied in 1:6 diluted samples to mimic six-minipool (MP6) nucleic acid test (NAT) was assessed by quadruplicate testing of five seroconversion panels per marker. A mathematical analysis based on the log-linear increase of viremia in the ramp-up phase, as established with bDNA 3.0 assays enabled estimation of the IWP for human immunodeficiency virus (HIV) and hepatitis B virus (HBV) assays. The mean IWPs were Tigris HIV RNA 5.5 days, s 201 (1:6) HIV RNA 7.4 days, GenScreen Plus p24/anti-HIV 17.8 days, PRISM anti-HIV 19.0 days, Tigris HBV DNA 20.6 days, s 201 (1:6) HBV DNA 22.6 days, Bio-Rad hepatitis B surface antigen (HBsAg) 37.8 days, and PRISM HBsAg 35.5 days. At estimated 50 percent NAT seroconversion rates, s 201 (1:6) and Tigris showed mean window-period reduction times (WPRTs) of 30.5 to 35.5 days to hepatitis C virus antibody (anti-HCV) assays, 10.4 to 13.5 days to anti-HIV, or combination p24/anti-HIV assays and 12.8 to 17.2 days to HBsAg assays. Tigris ID-NAT detected HIV RNA 2 days earlier than s 201 MP6-NAT, but the difference in sensitivity between the two NAT systems was not significant in HBV seroconversion panels. Insufficient seroconversion samples were available for reliable modeling of WPRT in early HCV infection, but 1.4 to 2.0 days could be predicted by translating analytical sensitivity data. Both multiplex NAT systems demonstrate significant WPRTs compared to (combined) antigen and antibody assays.Transfusion 03/2009; 49(2):301-10. · 3.22 Impact Factor
