IGG Test Result Confusion

[dp1997]

I just read this question and answer from the Webmd Message Board:

What if you were diagnosed positive for herpes but have never had an outbreak before?

If you have a positive antibody test for HSV 2 at an index value of 3.5 or higher, then you are infected with HSV 2 and are infectious to others, even if you have no symptoms.

This confused me.  I thought that 1.10 was a positive result.  Digging deeper, I found posts on this site which indicate that there is some disagreement in the medical community as to what the appropriate cut off is for a positive test result.  Medical literature I found on the web also reveals the same debate (e.g., "Performance of Focus ELISA tests for herpes simplex virus type 1 (HSV-1) and HSV-2 antibodies among women in ten diverse geographical locations").  See also "The positive predictive value of the Focus HSV-2 ELISA increased from 80.5% to 95.6% when Biokit testing was performed on sera that were initially positive by Focus HSV-2 ELISA. Confirmatory testing increased the specificity markedly among sera with Focus EIA values between 1.1 and 3.5: only 35% of low positive (index values 1.1–3.5) Focus HSV-2 ELISA results confirmed as positive by Biokit and WB compared with 92% of those with index values >3.5. Mathematical modeling of the data resulted in expected positive predictive values over 98% for populations with antibody prevalences typical of clinical practices in the US and Europe."  http://www.pubmedcentral.nih.gov/articl ... id=1276011

Furthermore, in a previous post on this site, Dr. Handsfield wrote: ". . . only results of 3.5 and greater are definitely positive; the lower the number, the greater the possibility the result is false."  Definitely postive?  Huh?

I went to an on-line testing site for piece of mind and was told my score for HSV2 was 2.60, and .91 for HSV1, but I have no symptoms.  Should I accept the result or retest?  Also, what is the true positive cut-off?

Thanks

[H. Hunter Handsfield, M.D.]

You have carefully researched the topic and have already found the truth about HSV-2 antibody testing, which you accurately summarize in your question.  There is no "debate" about the issue; the data are clear.  The manufacturer of the most commonly used HSV antibody test in the US (HerpeSelect brand, produced by Focus Technologies) submitted data to the us Food and Drug Administration that showed that results with ELISA ratio values over 1.1 were positive for HSV-2.  Later research showed that values between 1.1 and 3.5 often are false positive; the lower the value, the more likely the result is false, even though technically positive.

However, FDA regulations do not permit the manufacturer to change their "normal" values unless they do more research and submit those results to FDA and request a change in the approved labeling of the product.  They must do their own research; published studies by other researchers are not acceptable.  Such studies are very expensive.  Therefore, the official information provided by the manufacturer, and used by many laboratories, is that any ELISA ratio over 1.1 is positive.  But experts in STD and infectious disease in general, and herpes in particular, know that only values 3.5 and greater are definitely positive.

As far as your own results are concerned, you are smack in the middle of the gray zone.  One research study suggests that the HSV-1 result also should be taken into consideration.  That study, done in men but not women, showed that if someone was also positive for HSV-1, the HSV-2 result was more likely to be false.  If that research is correct, then most likely your value of 2.6 for HSV-2 means you are infected.  I was one of the researchers, and I believe the conclusion is valid.  Therefore, my personal suspeciion is that you are infected with HSV-2.  But still, it is only one study.

You can sort this out one of two ways.  First, have another HSV-2 antibody test produced by a different manufacturer.  For example, get the BiokitUSA test, which is done in 20 minutes while waiting in the doctor's office.  If positive, it will almost certainly mean you are infected.  If negative, it will reinforce the possibility of a false positive test.  Second, have an HSV Western blot test (done at the University of Washington laboratory in Seattle, but can be sent to them by any lab).  WB is more expensive, but it is the gold standard test to sort out situations like yours.

I hope this helps.  Best wishes--  HHH, MD

[waringblender]

The most comprehensive explanation I've seen to date about this somewhat confusing issue. Worth bookmarking.