Monday, February 21, 2011

Feeling Positive?

Is a donor "reactive" for a particular infectious disease marker or is he "positive"? What does "repeat reactive" mean? Can you have a reactive test on a particular sample and still be categorized as "non-reactive"? When studying transfusion-transmitted diseases (podcast on this topic coming soon), you will read terminology that can sometimes be confusing to non-virologists of the world (I proudly include myself in that category!). This blog entry will discuss several confusing terms related to viral marker testing results.

I think the first "rule" that you should understand for discussing terminology is the following: There really aren't any rules! While what I am about to outline below is fairly standard, reading through the package inserts of the FDA-approved infectious disease screening tests shows some definite variation. However, I think what follows will serve you well in most situations.

As you are probably aware, for most blood donor testing, a screening test is used first, followed by a confirmatory test if the screening sample shows evidence of a potential transfusion-transmitted disease. For screening tests (most of which are either EIA or ChLIA), testing labs follow a fairly well-defined routine.

  • If a donor's test results fall below the threshold defined by the manufacturer, the donor is by definition "non-reactive" (NR) for the marker in question, and no further testing is done. The donated unit is released for transfusion (provided all the other disease marker tests are negative, of course!).
  • If a donor's test results fall above the manufacturer-defined threshold, the donor is by definition "initially reactive" (IR) for the marker in question. The sample will be re-tested in duplicate to further characterize the donor's results. The donated unit will not be released until the issue is resolved.
  • If either or both of the donor's duplicate repeat results fall above the manufacturer-defined threshold, the donor is by definition "repeat reactive" (RR) for the marker in question (this generally leads to deferral of the donor for a variable period of time or forever and destruction of his donated unit).
  • If, however, both of the donor's duplicate results fall below the manufacturer-defined threshold, the donor is by definition "non-reactive" for the marker in question (yes, exactly as if his result in the first bullet above was below the threshold). Just as in the first bullet above, the donated unit would be released for transfusion if there is no other disqualifying issue.

So, for screening tests, in general, the terminology used is "reactive" or "non-reactive" rather than "negative" or "positive." The opposite is generally true of confirmatory testing. So if, for example, a donor tested repeat reactive on the anti-Hepatitis C Virus (anti-HCV) test, his sample would usually be processed for the confirmatory test for anti-HCV, known as RIBA (recombinant immunoblot assay). If the RIBA results fall into a specific pattern, the results are "positive" and the donor is considered "positive" for anti-HCV.
NOTE: A strange little exception to this is with Nucleic Acid Testing (NAT), which is used for HIV-1 and HCV (and in some cases, though not yet required, for Hepatitis B Virus). NAT seems to fall into an intermediate category with terminology, and when you read the package inserts from the manufacturers, you will see that the result syntax is not consistent. Some use positive/negative, some use reactive/nonreactive.
General Summary: Donor screening tests are reactive/nonreactive. Donor confirmatory tests are positive/negative. Donors themselves, after testing, are positive/negative for disease.