Publications (6)26.23 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: Hepatitis B virus transmission by blood transfusion during 4 years of individual-donation nucleic acid testing in South Africa: estimated and observed window period risk.
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ABSTRACT: Since October 2005, a total of 2,921,561 blood donations have been screened by the South African National Blood Service for hepatitis B virus (HBV) by individual-donation nucleic acid testing (ID-NAT). Over 4 years, 149 hepatitis B surface antigen-negative acute-phase HBV NAT-positive donations were identified (1:19,608). The lookback program identified one probable HBV transmission. The complete genomes of HBV isolated from the donor and recipient were sequenced, cloned, and analyzed phylogenetically. The HBV window period (WP) transmission risk was estimated assuming a minimum infectious dose of 3.7 HBV virions and an incidence rate correction factor of 1.34 for transient detectability of HBV DNA. Of 149 acute-phase HBV NAT yields, 114 (1:25,627) were classified as pre-antibody to hepatitis B core antigen (anti-HBc) WP and 35 (1:83,473) as post-anti-HBc WP. The acute-phase transmission risk in the HBV DNA-negative pre- and post-anti-HBc WPs (of 15.3 and 1.3 days, respectively) was estimated at 1:40,000 and 1:480,000, respectively. One HBV transmission (1:2,900,000) was identified in a patient who received a transfusion from an ID-NAT-nonreactive donor in the pre-anti-HBc WP. Sequence analysis confirmed transmission of HBV Subgenotype A1 with 99.7% nucleotide homology between donor and recipient strains. The viral burden in the infectious red blood cell unit was estimated at 32 (22-43) HBV DNA copies/20 mL of plasma. We report the first known case of transfusion-transmitted HBV infection by blood screened using ID-NAT giving an observed HBV transmission rate of 0.34 per million. The estimated pre-acute-phase transmission risk in the ID-NAT screened donor population was 73-fold higher than the observed WP transmission rate.Transfusion 10/2011; 52(4):880-92. · 3.22 Impact Factor -
Article: Impact of individual-donation nucleic acid testing on risk of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus transmission by blood transfusion in South Africa.
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ABSTRACT: In 2005, the South African National Blood Service introduced individual-donation (ID) nucleic acid test (NAT) screening for human immunodeficiency virus (HIV) RNA, hepatitis C virus (HCV) RNA, and hepatitis B virus (HBV) DNA. At the same time the use of ethnic origin to prioritize the transfusion of blood according to a hierarchy of residual risk was discontinued. ID-NAT (Ultrio on Procleix Tigris, Chiron) and serology (PRISM, Abbott) repeat test and confirmation testing algorithms were designed to enable differentiation between false-positive and true-NAT and -serology yields. After 1 year, the NAT and serology yield rates in first-time, lapsed, and repeat donors were analyzed and used to estimate the residual risk of HIV, HBV, and HCV infections by blood transfusion. The HIV, HBV, and HCV ID-NAT window phase yield rates in 732,250 blood donations were 1:45,765, 1:11,810, and 1:732,200, respectively. Seven of 16 HIV window phase donations with viral loads above 16,000 copies/mL were HIV p24 antigen enzyme-linked immunosorbent assay positive. PRISM detected anti-HIV and hepatitis B surface antigen (HBsAg) in 89.4 and 73.9% of early infections in repeat donors. The Procleix assay detected viremia in 99.7 and 95.5% of anti-HIV- and HBsAg-positive first-time donors. In these donors, the occult HBV DNA carrier rate was 1:5200. The residual transmission risk of ID-NAT HIV, HBV, and HCV window phase donations was estimated at 1:479,000, 1:61,500, and 1:21,000,000 respectively. One-year ID-NAT screening of 732,250 donations interdicted 16 HIV, 20 HBV, and 1 HCV window phase donations and 42 anti-hepatitis B core antigen-reactive infections during an early recovery or a later stage of occult HBV infection.Transfusion 03/2009; 49(6):1115-25. · 3.22 Impact Factor -
Article: Risk assessment and cost-effectiveness/utility analysis.
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ABSTRACT: Decision-makers at all levels of public health and transfusion medicine have always assessed the risks and benefits of their decisions. Decisions are usually guided by immediately available information and a significant amount of experience and judgment. For decisions concerning familiar situations and common problems, judgment and experience may work quite well, but this type of decision process can lack clarity and accountability. Public health challenges are changing as emerging diseases and expensive technologies complicate the decision-makers' task, confronting the decision-maker with new problems that include multiple potential solutions. Decisions regarding policies and adoption of technologies are particularly complex in transfusion medicine due to the scope of the field, implications for public health, and legal, regulatory and public expectations regarding blood safety. To assist decision-makers, quantitative risk assessment and cost-effectiveness analysis are now being more widely applied. This set of articles will introduce risk assessment and cost-effectiveness methodologies and discuss recent applications of these methods in transfusion medicine.Biologicals 03/2009; 37(2):78-87. · 1.70 Impact Factor -
Article: Characterization of occult hepatitis B virus strains in South African blood donors.
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ABSTRACT: Since October 2005, all blood units collected in South Africa were screened individually for human immunodeficiency virus (HIV)-1, hepatitis B and C virus (HBV, HCV) genomes uncovering preseroconversion window period (WP) infections for each virus and occult HBV infections (OBIs) defined as persistent HBV DNA without detectable hepatitis B surface antigen (HBsAg). Samples identified as HBsAg-negative/DNA-positive were confirmed by combining real-time quantitative polymerase chain reaction, nested amplification, anti-HBc and anti-HBs. Amplified basic core promoter/precore, pre-S/S, and whole genome were sequenced, analyzed, and compared to 73 HBsAg+ strains. Genotype was determined by phylogenetic analysis. From 109 samples examined, 54 were classified as OBI, 14 as WP, 20 as false-positive, five as other classification, and 16 as undetermined due to lack of serological or follow-up data. OBI donors were predominantly males (67%), median age 31 years, black (54%), with normal alanine aminotransferase levels. Viral load ranged between unquantifiable and 518 IU/mL (median 5 IU/mL). Genotype A1 was more frequent (23 strains) than genotype D (seven strains). Genotype A1 strains were little mutated. In the major hydrophilic region, 56.5% strains were wild type or with few amino acid substitutions. Most important, all 13 full genome sequences presented 1 to 7 mutations known to or assumed to negatively impact viral replication. In particular, 6/13 sequences had a stop codon in the HBx gene translated into deletion of 117 or 19-25 C-terminus amino acids not found in 15 HBeAg+ HBsAg+ strains. One WP sequence with an HBx stop codon suggested infectivity. CONCLUSION: Genotype A1 OBIs are different from genotype A2 and D OBIs in that there is little evidence of immune pressure as a major factor involved in OBI genesis. Limited replication appears mostly related to genetic viral defects.Hepatology 03/2009; 49(6):1868-76. · 11.66 Impact Factor
