Screening and confirmatory testing strategies for the major transfusion-transmissible viral infections

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Abstract

Background

Testing donated blood for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human T-cell lymphotropic virus (HTLV) is important as all are transfusion-transmissible viral infections (TTVIs). A particular challenge in donor screening for TTVIs is that donor selection seeks to minimize the prevalence of TTVIs which in the context of testing substantially increases the likelihood that reactive test results represent ‘false’ rather than ‘true’ reactivity. To address this donor testing algorithms seek to combine strategies to optimize both sensitivity (optimal detection of the ‘target’ pathogen) and specificity (minimising ‘false’ reactivity)

Aims

First, review the fundamental principles underpinning TTVI screening and confirmatory algorithms and discuss key challenges. Second, using working examples illustrate how sound design can lead to optimal, cost-effective solutions.

Materials and Methods

Screening algorithms vary dependent on a number of factors including the epidemiology of the TTVI in the donor population and the available resources (e.g. funding, automation level, technical skill). TTVI screening tests include rapid tests (RT), immunoassays (IA) and nucleic acid tests (NAT). RTs and IAs target ‘serological’ markers of infection (anti-HIV, HIV p24 antigen, anti-HCV, HBsAg, anti-HBc or anti-HTLV) whereas NAT targets viral RNA (HCV and HIV) or DNA (HBV). NAT has the advantage of earlier detection because viral RNA/DNA appears in the bloodstream before serological markers. However NAT is comparatively expensive requiring higher levels of automation and more skilled staff. Confirmatory testing seeks to ‘confirm’ the presence of the pathogen of interest optimizing donor counselling and referral. The appropriate confirmatory strategy will be dependent primarily on the screening strategy and available resourcing.

Results

While optimal screening strategies for HIV, HCV and HBV generally include NAT for its superior ability to identify donors with early infection, there are alternative strategies which can provide almost equivalent safety. For example, the use of HIV and HCV ‘combo’ IAs which combine antibody with antigen (HIV p24Ag or HCV Ag) detection significantly improve sensitivity for early infection. In resource poor settings RT for HIV, HCV and to a lesser extent HBV can still provide a high level of safety particularly where carefully selected. Repeating samples reactive on a primary screening test on a second screening test (termed a ‘sequential immunoassay’ or SI algorithm) and assigning a final status based on concordant reactivity has been shown to improve effectiveness although is dependent on judicious test selection. For HIV, HCV and HTLV antibody based screening strategies immunoblots are often used to confirm the presence of antibody. However, immunoblots are relatively costly and can have poor specificity making it important to optimise the specificity of the screening algorithm. Immunoblotting subsequent to a sequential immunoassay approach has been shown to improve the efficiency and effectiveness of the strategy. Since NAT for HIV, HCV and HBV have demonstrated very high specificity, they now form an independent method of confirming infection for serology reactive samples. In some countries, samples concordantly reactive on serology and NAT screening tests are considered ‘confirmed’ without the need for immunoblotting.

Conclusions

Even in resource constrained settings optimally designed screening and confirmatory strategies can significantly reduce the risk of transfusion-transmissible viral infection.

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