Blood-bank testing for infectious diseases: how safe is blood transfusion?

D. Michael Strong and Louis Katz

Trends in Molecular Medicine 10.1016/S1471-4914(02)02361-4

Remarkable progress has been made in transfusion safety from infection over the past three decades. Donor deferrals for at-risk behaviors, the introduction of more-sensitive viral-screening assays and the recent introduction of nucleic-acid amplification technology have nearly eliminated transmission of HIV and hepatitis C virus (HCV) by blood transfusion in North America. Nevertheless, risks of other infectious agents for which such robust screening tools have not been developed, such as bacteria and parasites, still remain. As a result of these successes, the non-infectious risks such as misidentification of patients and inadequate and inappropriate transfusion have become the primary sources of transfusion risk.

Safety from transfusion-transmitted infectious disease has improved remarkably over the past three decades with the implementation of more-stringent donor-eligibility criteria and the development of increasingly sensitive serological and, most recently, nucleic-acid assays for viral detection [1]. Testing is routine for: HIV-1 and -2; hepatitis B virus (HBV) and HCV; human T-cell leukemia virus (HTLV)-I and -II; syphilis; and, for selected blood recipients, cytomegalovirus. The major remaining source of post-transfusion viral infection is if blood is collected from the donor during the earliest stages of infection (the so-called 'seronegative window period'), at a time when the donor is asymptomatic but viremic, and is still nonreactive in tests for viral antibodies or antigens. Therefore, nucleic-acid amplification testing (NAT) has been implemented to increase the sensitivity of detection in donations during the seronegative window period. Future material improvements in transfusion safety will probably require a more intense focus on other real and theoretical infection risks and on serious noninfectious hazards.

Immunoassays and NAT

Enzyme-linked immunoassay (ELISA) is the primary method used to screen blood donors. The use of monoclonal antibodies and synthetic peptides have made these tests more sensitive and specific, and have facilitated the automation needed for daily screening of hundreds or thousands of samples under the constant pressure for rapid release of blood for transfusion. New technologies to improve sensitivity and specificity, including chemiluminescent immunoassays (ChLIA), are awaiting approval by the Food and Drug Administration (FDA).

Until recently, exquisitely sensitive and specific NAT was not feasible for donor screening owing to the lack of automation, time pressures, space restrictions in blood centers and cost. However, in 1999, two systems were applied to US donors under an investigational new drug (IND) exemption from the FDA: the Roche Molecular Systems COBAS Ampliscreen

tests for HCV and HIV and the Gen-Probe/Chiron Procleix

Pooled Plasma HIV-1/HCV Amplified Assay. The latter received FDA licensure in February 2002. Testing is carried out on pooled samples from 24 and 16 donors, respectively, reducing the number of tests required, the time to perform testing and the cost. HIV and HCV nucleic-acid levels rise rapidly in recently infected individuals, so pooling has a minimal impact on NAT sensitivity. Compared with licensed serological assays, the window period from infection to detection of HIV has fallen from 16 to 10 days and for HCV from 70–80 days to fewer than 30 days.

Roche Molecular Systems COBAS AmpliScreen

Following sample pooling using a Hamilton pipetter, the Roche tests comprise five procedures: specimen preparation by ultra-centrifugation to concentrate virus particles; reverse transcription of target RNA to obtain cDNA; PCR amplification of target cDNA using virus-specific complementary primers; hybridization of the amplified products to oligonuceotide probes specific to the target; and detection of the amplified products by colorimetry. An internal control is included in each reaction. Reverse transcription and PCR amplification of the viral target and internal control target occur simultaneously. After amplification, a target-specific probe is hybridized to the amplicon and the detection of amplified DNA is performed using avidin–horseradish peroxidase conjugate. Except for the specimen preparation, all procedures are fully automated on the COBAS

instrument. In total, the process takes around six hours.

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19th June - 2nd July 2002

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