Weusten J.,Philips |
van Drimmelen H.,Biologicals Quality Control |
Vermeulen M.,South African National Blood Service |
Lelie N.,Biologicals Quality Control |
Lelie N.,Lelie Research
Transfusion | Year: 2017
BACKGROUND: If anti-hepatitis B core antibody testing is not mandated blood donors with occult hepatitis B infection (OBI) may transmit hepatitis B virus (HBV) to a recipient in spite of the use of nucleic acid amplification technology (NAT) or pathogen inactivation (PI). STUDY DESIGN AND METHODS: We developed a model to estimate OBI transmission risk based on three components: the probability distribution of the viral load (VL) in a randomly selected OBI donor, the probability that a given VL remains undetected, and the probability that this VL causes infection in the recipient. A subset of 217 South African OBI samples identified by individual donation (ID)-NAT screening were quantified by replicate testing using an ID-NAT assay (Ultrio Plus) against HBV DNA standard dilution series. The observed log VLs could be described by a Gumbel distribution. A correction was included to compensate for OBI samples missed by initial ID-NAT screening. RESULTS: The model estimates that 3.3% of all OBI donations are undetected by ID-NAT (Ultrio Plus) and cause infection by a blood component containing 20 mL plasma, going up to 8.7% when using minipools of 6 (MP6)-NAT. For 200-mL plasma transfusion these risks were estimated at 14 and 28%, respectively, while PI with modest (2 log) reduction capacity would reach 4.8% without NAT and 1.3 or 0.4% when combined with MP6- or ID-NAT. CONCLUSION: The model can be used to compare different screening and/or PI strategies in reducing viral transmission risk and could serve as a tool in evaluating efficacy of alternative blood safety scenarios. © 2017 AABB
Manak M.,Seracare Life Sciences, Inc. |
Manak M.,Foundation Medicine |
Sina S.,Foundation Medicine |
Anekella B.,Seracare Life Sciences, Inc. |
And 14 more authors.
AIDS Research and Human Retroviruses | Year: 2012
The continued global spread and evolution of HIV diversity pose significant challenges to diagnostics and vaccine strategies. NIAID partnered with the FDA, WRAIR, academia, and industry to form a Viral Panel Working Group to design and prepare a panel of well-characterized current and diverse HIV isolates. Plasma samples that had screened positive for HIV infection and had evidence of recently acquired infection were donated by blood centers in North and South America, Europe, and Africa. A total of 80 plasma samples were tested by quantitative nucleic acid tests, p24 antigen, EIA, and Western blot to assign a Fiebig stage indicative of approximate time from initial infection. Evaluation of viral load using FDA-cleared assays showed excellent concordance when subtype B virus was tested, but lower correlations for subtype C. Plasma samples were cocultivated with phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from normal donors to generate 30 viral isolates (50-80% success rate for samples with viral load >10,000 copies/ml), which were then expanded to 10 7-10 9 virus copies per ml. Analysis of env sequences showed that sequences derived from cultured PBMCs were not distinguishable from those obtained from the original plasma. The pilot collection includes 30 isolates representing subtypes B, C, B/F, CRF04-cpx, and CRF02-AG. These studies will serve as a basis for the development of a comprehensive panel of highly characterized viral isolates that reflects the current dynamic and complex HIV epidemic, and will be made available through the External Quality Assurance Program Oversight Laboratory (EQAPOL). © Copyright 2012, Mary Ann Liebert, Inc.
Kassanjee R.,Stellenbosch University |
Kassanjee R.,University of Witwatersrand |
Welte A.,Stellenbosch University |
McWalter T.A.,Stellenbosch University |
And 5 more authors.
PLoS ONE | Year: 2011
Introduction: Biomarker-based cross-sectional incidence estimation requires a Recent Infection Testing Algorithm (RITA) with an adequately large mean recency duration, to achieve reasonable survey counts, and a low false-recent rate, to minimise exposure to further bias and imprecision. Estimating these characteristics requires specimens from individuals with well-known seroconversion dates or confirmed long-standing infection. Specimens with well-known seroconversion dates are typically rare and precious, presenting a bottleneck in the development of RITAs. Methods: The mean recency duration and a 'false-recent rate' are estimated from data on seroconverting blood donors. Within an idealised model for the dynamics of false-recent results, blood donor specimens were used to characterise RITAs by a new method that maximises the likelihood of cohort-level recency classifications, rather than modelling individual sojourn times in recency. Results: For a range of assumptions about the false-recent results (0% to 20% of biomarker response curves failing to reach the threshold distinguishing test-recent and test-non-recent infection), the mean recency duration of the Vironostika-LS ranged from 154 (95% CI: 96-231) to 274 (95% CI: 234-313) days in the South African donor population (n = 282), and from 145 (95% CI: 67-226) to 252 (95% CI: 194-308) days in the American donor population (n = 106). The significance of gender and clade on performance was rejected (p-value = 10%), and utility in incidence estimation appeared comparable to that of a BED-like RITA. Assessment of the Vitros-LS (n = 108) suggested potentially high false-recent rates. Discussion: The new method facilitates RITA characterisation using widely available specimens that were previously overlooked, at the cost of possible artefacts. While accuracy and precision are insufficient to provide estimates suitable for incidence surveillance, a low-cost approach for preliminary assessments of new RITAs has been demonstrated. The Vironostika-LS and Vitros-LS warrant further analysis to provide greater precision of estimates. © 2011 Kassanjee et al.
Bruhn R.,Blood Systems Research Institute |
Lelie N.,Lelie Research |
Busch M.,Blood Systems Research Institute |
Kleinman S.,University of British Columbia |
And 39 more authors.
Transfusion | Year: 2015
BACKGROUND: The relative contribution of serologic screening and nucleic acid testing (NAT) to prevent hepatitis C virus (HCV) transmission has not been rigorously addressed. STUDY DESIGN AND METHODS: Twenty-one blood organizations in seven geographical regions performing individual-donation (ID)-NAT in parallel with anti-HCV screening provided data from 10,897,105 donations to establish HCV infection rates in first-time, lapsed, and repeat donations. Screening efficacy was modeled for: anti-HCV alone, HCV antigen/antibody (combo), minipool (MP)-NAT in pools of 8 and 16 with anti-HCV, ID-NAT and anti-HCV, and ID-NAT alone. Probabilities of infectivity for red blood cell transfusions were estimated as 100% from window period (WP) and concordant HCV RNA/antibody-positive (concordantly positive [CP]) donations and 0.028% from anti-HCV-positive and RNA-negative probable resolved (PR) donations. RESULTS: There were 5146 confirmed infections (30 WP, 3827 CP, and 1289 PR). Infection rates and transmission risks varied substantially across regions and by donation status. Residual risk with ID-NAT and serology screening was estimated at one in 250,000 in Egypt and at one in 10,000,000 in other regions combined; risk would increase to one in 7300 and one in 312,000, respectively, if NAT had not been performed. ID-NAT with or without anti-HCV testing showed higher efficacy than either MP-NAT or combo assays, particularly in lapsed or repeat donors in whom 99.2, 98.5, and 93.2% of infectious donations were estimated to be interdicted by these respective testing strategies. CONCLUSIONS: The incremental efficacy of anti-HCV testing when ID- NAT screening is performed was minimal, particularly for screening lapsed and repeat donations. © 2015 AABB.
Pruett C.R.,University of California at San Francisco |
Vermeulen M.,South African National Blood Service |
Zacharias P.,Safe Blood for Africa Foundation |
Ingram C.,South African National Blood Service |
And 3 more authors.
Transfusion Medicine Reviews | Year: 2015
Infectious risk associated with blood transfusion remains a major public health challenge in Africa, where prevalence rates of the major transfusion-transmissible infections (ie, hepatitis B, hepatitis C, human immunodeficiency virus, and syphilis) are among the highest in the world. Resource-limited blood services often operate with minimal predonation screening safeguards, prompting exclusive reliance on laboratory testing to mitigate infectious risk. Transfusion screening with rapid diagnostic tests (RDTs) has been adopted in areas that lack the capacity to support the routine use of more sophisticated technologies. However, uncertainty surrounding the performance of some RDTs in the field has spurred debate regarding their application to blood donation screening. Our review of the literature identified 17 studies that evaluated RDTs for the infectious screening of blood donors in Africa. The review highlights the variable performance of available RDTs and the importance of their use in a quality-assured manner. Deficiencies in performance observed with some RDTs underscore the need to validate test kits prior to use under field conditions with locally acquired samples. Suboptimal sensitivities of some available tests, specifically hepatitis B virus rapid assays, question their suitability in single-test algorithms, particularly in high-prevalence regions. Although RDTs have limitations, many of which can be addressed through improved training and quality systems, they are frequently the only viable option for infectious screening in resource-poor African countries. Therefore, additional studies and specific guidelines regarding the use of RDTs in the context of blood safety are needed. © 2015 Elsevier Inc..
van den Berg K.,South African National Blood Service |
van den Berg K.,University of the Free State |
Murphy E.L.,University of California at San Francisco |
Murphy E.L.,Blood Systems Research Institute |
And 3 more authors.
Transfusion and Apheresis Science | Year: 2014
Cytopaenias, especially anaemia, are common in the HIV-infected population. The causes of HIV related cytopaenias are multi-factorial and often overlapping. In addition, many of the drugs used in the management of HIV-positive individuals are myelosuppresive and can both cause and exacerbate anaemia. Even though blood and blood products are still the cornerstone in the management of severe cytopaenias, how HIV may affect blood utilisation is not well understood. The impact of HIV/AIDS on blood collections has been well documented. As the threat posed by HIV on the safety of the blood supply became clearer, South Africa introduced progressively more stringent donor selection criteria, based on the HIV risk profile of the donor cohort from which the blood collected. The implementation of new testing technology in 2008 which significantly improved the safety of the blood supply enabled the removal of what was perceived by many as a racially based donor risk model. However, this new technology had a significant and sustained impact on the cost of blood and blood products in South Africa.In contrast, it would appear little is known of how HIV influences the utilisation of blood and blood products. Considering the high prevalence of HIV among hospitalised patients and the significant risk for anaemia among this group, there would be an expectation that the transfusion requirements of an HIV-infected patient would be higher than that of an HIV-negative patient. However, very little published data is available on this topic which emphasises the need for further large-scale studies to evaluate the impact of HIV/AIDS on the utilisation of blood and blood products and how the large-scale roll-out of ARV programs may in future play a role in determining the country's blood needs. © 2014 Elsevier Ltd.
Pretorius E.,University of Pretoria |
Crookes R.,South African National Blood Service |
Oberholzer H.M.,University of Pretoria |
van der Spuy W.J.,University of Pretoria
Transfusion and Apheresis Science | Year: 2010
In thrombotic events and diseases such as cancer, HIV/AIDS, dysfibrinogenaemia, as well as acute incidents (e.g. burn wounds), ultrastructure of platelets and fibrin networks change. In the current study, we compare the ultrastructure of platelets and fibrin networks of apheresis platelets stored in citrated human plasma (CP) and in a first-generation platelet additive solution (PAS) (T-Sol), to that of fresh donor plasma (FP). Eighteen apheresis platelet donors donated platelets on Trima®-Accel™ V5.2 and V5.1 cell separators. Six collections were stored for five days in autologous citrated plasma (CP); six collections were stored in 40% citrated human plasma and 60% PAS solution (CP/PAS) controlled, for the duration of storage, at a constant temperature (22 ± 2 °C) with continuous flat-bed agitation; and six collections were stored in conditions uncontrolled for temperature and without continuous agitation. On days 1, 3 and 5, equal volumes of human thrombin were mixed with platelets collected in either CP or CP/PAS to form a coagulum (fibrin network containing platelet aggregates), followed by preparation for scanning electron microscopy. Results were compared with platelets and fibrin networks in FP. Typically, in FP, platelet aggregates with smooth membranes and pseudopodia are seen and fibrin networks arrange to form major, thick fibers and scattered, minor, thin fibers. On day 1, in CP and in all CP/PAS units, platelet ultrastructure compared well to that of FP, although the fibrin fibers were denser, with the minor fibers forming a matted layer over the major fibers. On day 3, in platelet units uncontrolled for temperature and without continuous agitation during storage, some platelet aggregates in CP/PAS showed typical apoptotic morphology, with shrinkage and membrane damage, but comparable fibrin networks were present. On day 5 however, in those units where storage conditions were uncontrolled and where the pH had decreased to below 6.4, no platelet aggregates were seen and fibrin was arranged into short, lumpy masses with no separate major or minor fibrin fibers visible. In those units stored at 22 °C with continuous flat-bed agitation, where pH was maintained >7.0, ultrastructure of platelets and fibrin network in CP/PAS was typical and similar to FP and CP at the end of five days of storage. Examining platelet and fibrin network ultrastructure may be useful, in addition to conventional laboratory analysis, in assessing the viability and potential clinical efficacy of platelets for transfusion and could play a role in the evaluation of new generation platelet additive solutions. © 2010 Elsevier Ltd.
PubMed | Blood Systems Research Institute, Red Cross, University of British Columbia, South African National Blood Service and Lelie Research
Type: Journal Article | Journal: Transfusion | Year: 2016
Twenty-two users of individual donation nucleic acid amplification technology (ID-NAT) in six geographical regions provided detailed hepatitis B virus (HBV) infection data in first-time, lapsed, and repeat donations and classified confirmed HBV-positive donors into different infection categories. These data were used to compare the clinical sensitivity of hepatitis B surface antigen (HBsAg) and HBV-DNA testing.In total 10,981,776 donations from South Africa, Egypt, the Mediterranean, North and Central Europe, South East Asia, and Oceania were screened for HBV-DNA using the Ultrio assay (Grifols/Hologic) and for HBsAg using a chemiluminescence immunoassay, and 9455 HBV-infected donations were identified. HBsAg-negative window period (WP), HBsAg-positive and occult HBV infection (OBI) stages were determined using supplemental serology, quantitative polymerase chain reaction, and replicate multiplex and discriminatory HBV NAT test strategies. For two regions, additional data sets using the more sensitive Ultrio Plus assay were assessed.Regional HBV detection rates in first-time donors varied between 0.08% and 1.07%, with WP NAT yield rates varying between 1:7700 and 1:294,000 and OBI NAT yield rates varying from 1:3900 to 1:59,000. HBsAg CLIA detected 97.0% of infections in first-time donors, 62.7% in lapsed donors, and 41.0% in repeat donors; whereas Ultrio detected 93.1%, 95.0%, and 98.3% of infections in these respective groups. HBV-DNA detection rates in HBsAg-positive donors varied from 90.2% to 96.3% between regions but increased significantly (range, 95.2-98.2%) with the Ultrio Plus assay.ID-NAT and serology are complementary in detecting HBV infection in first-time donors, but HBV-DNA is superior to HBsAg detection in repeat donors.