Overview of Infectious Disease Testing

Background

A number of infectious diseases can be transfusion transmitted, and the agents responsible for these infectious diseases have four elements in common ( Table 11.2 ).

Recognition of transfusion-associated infectious risk began in the 1940s after cases of transfusion-transmitted syphilis; this led to routine donor testing for syphilis. Later, viral hepatitis (hepatitis B and C) and HIV would become the major infectious risks to the blood supply. Advances in testing methodologies and strategies, immunology, and molecular biology have led to improved understanding of the biology of these infectious agents; they have also spurred development and subsequent implementation of highly sensitive and specific tests to mitigate transfusion-transmission risk.

Approach to Testing

In the United States, blood products and prerelease tests that are used in component manufacturing are classified as “biologics” by the FDA. As such, infectious disease tests used in the blood industry undergo extensive clinical trials before FDA licensure. A list of current FDA-licensed tests can be found at www.FDA.gov/cber/products/testkits.htm .

Generally, the following scheme is used ( Table 11.3 ) :

• 1.

  Each blood donation is tested: testing is performed on a sample drawn at time of donation, and the donated units are placed in quarantine until test results are completed, deemed negative, and reviewed. Exception is serologic testing for Trypanosoma cruzi , agent of Chagas disease, which requires testing only once at the time of first donation.

• 2.

  With exception of most viral nucleic acid testing (NAT), each donor sample is tested individually. NAT is an expensive yet sensitive technology that reduces the window period (period when the patient is first infected and viremic, but current testing methodologies are unable to detect the virus). To optimize the cost-effectiveness of screening, NAT is performed, mostly, using a pooled aliquot (i.e., minipool) from 6 to 16 donor samples. Minipool size is informed both by the incidence of the target infection in the donor population and assay sensitivity.

• 3.

  Nonreactive tests are considered to be negative for infectious marker, and related blood products may be released from quarantine and issued.

• 4.

  Samples with initially reactive screening tests are typically retested in duplicate. If both repeat test results are nonreactive, sample is classified as negative and corresponding products may be released from quarantine. If one or both repeat tests are reactive (termed repeatedly reactive), products cannot be released for transfusion and are destroyed.

• 5.

  Samples that are repeatedly reactive undergo confirmatory with, or without, supplementary testing. Confirmatory testing is typically performed using assays with different sensitivity and specificity characteristics than the initial screening tests. Some screening tests, such as hepatitis B core antigen, do not have a confirmatory test. Results of confirmatory testing improve accuracy and predictive value of results while supplementary tests aid significantly in donor notification and counseling.