Kassanjee R.,Stellenbosch University |
Kassanjee R.,University of Witwatersrand |
Welte A.,Stellenbosch University |
McWalter T.A.,Stellenbosch University |
And 5 more authors.
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. Source
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
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. Source
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
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. Source
Bruhn R.,Blood Systems Research Institute |
Lelie N.,Lelie Research |
Busch M.,Blood Systems Research Institute |
Kleinman S.,University of British Columbia |
And 38 more authors.
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. Source
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
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.. Source