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HSV diagnostics pitfall
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HSV diagnostics pitfall

Hello Dr. Hook,
Am writing to get your opinion with regards to a troubling HSV diagnostics situation.  Summary of my results to date are below.  Note that all these tests took place well over 5 years from last possible exposure which should avoid conversion 'window' issues.  I tested due to concerns with past activity and have not had any noticeable symptoms to date.
Focus EIA:  type1: negative,  type2 - high positive (5.5 index)
Western blot: type1: negative, type2 - persistently indeterminate (3 times over 12 months)
Biokit POC assay:  type1: n/a, type2: negative (no degree of color change on indicator)
Resorted to once-daily PCR swabs for 60 days of which 59 were negative.  Incredibly, the last day turned up what was termed a "rare low copy" reading of partial HSV1 DNA.  Reportedly 22 copies were detected, which is only 2 copies over the negative cutoff index value of 20 copies.  This is inconsistent with both average PCR read levels (copies in the thousands) and blood testing which is negative for type1.  Some have mentioned contamination or cross-reaction may be behind this disparity; just don't know.
I also tested with experimental assays from research environments one of which was negative for type2.  The other showed partial reaction for type2 but again, not consistent with the vast majority of type2 infected individuals.
I would assess risk profile as at least moderate for type2.  Activities involved only genital to non-genital contact to visibly clear skin, close body contact, with no intercourse (of any kind) but involved multiple partners of unknown status.  There was only one episode of oral to near-genital contact (no entry).
Seems now I cannot tell whether my results are due to HSV1, HSV2, both, or neither of these viruses.  I have tested negative for all other STIs and have no immune system issues that I'm aware of.  
Would appreciate your perspective Dr. Hook and whether you have seen anything similar to this case in your experience.
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Welcome to the forum. Thanks for your question. Dr. Hook and I take new questions Interchangeably; users don't get to choose.  We have worked closely together for over 30 years, and although our styles differ, our opinions and advice almost never do.

You've really put yourself through the mill on this. To summarize the apparently positive results of all your HSV tests, you have had an IgG HSV-2 serology that is strongly positive (ELISA ratio 5.5); 3 HSV Western blot test, all interpreted as negative for HSV one and indeterminate for HSV-2; and a single weakly positive HSV-1 PCR among 60 genital specimens tested.
Not knowing the nature of the other experimental antibody test, I can't really interpret it's apparent equivocal result for HSV-2.

Perhaps the most confident response I can make is that I would dismiss the weakly positive PCR for HSV-1.  Because of their extreme sensitivity, PCR tests are relatively easily contaminated, and with the consistently negative HSV a blood test results (by several test methods), I am confident the PCR result was a false positive. It sounds like you already agree.

I'm afraid I have to throw up my hands, as you have done, about whether or not you are infected with HSV-2. My only other thought is to wonder whether you might have an HSV-2 infection at a site not tested by PCR.  You don't say where those specimens are from, but if they are entirely genital, it is conceivable you have an anal or oral infection.

There are two bright silver linings to the dark clouds of uncertainty. First, if you have a genital HSV-2 infection, apparently you are asymptomatic, or you would have mentioned it. Most likely you will stay that way. Second, the 60 negative PCR tests suggest you have infrequent asymptomatic shedding, suggesting a low potential for transmission to future sex partners. Of course, this isn't definite; you could still be shedding HSV-2 two percent of the time.  But that's a lot less than most people and I still think it is fair to assume you are not highly infectious for partners.

In summary, if I were a gambling man, I would bet you are not infected with either HSV-1 or 2; and that even if you have HSV-2, you're not likely to infect future sex partners.

Given all these tests, including experimental ones, as well as the sophisticated nature of your questions, I imagine you are under the care of a genuine herpes expert, or at least an infectious diseases specialist.  I will be interested to hear whether my opinion and advice is similar to what you have been told by her or him..

My last comment is intended primarily for other readers:  Be cautious in having blood tests for HSV without good reason.  Based on your sexual history and (apparent) lack of symptoms that suggest herpes, had you been my patient at the outset I would have recommended against having the blood test to start with.

Sorry I cannot give you the clear, definitive answer you were hoping for. Best wishes.

HHH, MD

8 Comments
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Avatar_m_tn
Dr. Handsfield,
Thanks for your feedback and thoughts.  To answer your questions:
- yes, I'm asymptomatic and have never had any noticeable symptoms
- the PCR sampling was performed on all genital areas (front, perianal, and anal)
- no PCR sampling was performed for the oral area
I should mention that on the experimental assay that provided a negative HSV2 reading, there was a very weak slight positive detected for type1.  This has led me to consider the possibility of HSV1 more seriously since this datapoint aligns with the weak type1 PCR reading.  Overall it remains doubtful as you point out.  Still, I am concerned that if type1 is truly behind all this it would ofcourse not be wise to expose myself to type2.
Yes, I have thankfully been in touch with several leading experts in HSV and their comments are well aligned with your assessment; tending towards an assumption that I'm not infected but nevertheless with a degree of uncertainty.  Some have described exposure without infection as a possibility here but I know that there are many who don't believe in such a possibility (although it's been documented for HSV, HCV, etc..).  I'm thinking that the only thing I can do is go on suppressive therapy which would probably do a good job of suppressing type1 and hopefully reduce type2 if it's there.
I notice you did not account for the Biokit HSV2 negative, is this test prone to false negatives?  Nonetheless, the failure to confirm with both the WB and Biokit not to mention the experimental methods also makes it difficult to self-inflict HSV2 exposure moving ahead.
Several doctors tried to dissuade me from initially testing but none explained the unimaginable possibility of this particular resulting circumstance;  which appears to be a worst case scenario from a diagnostics standpoint.  Would not wish this situation on anyone.

My general question is why has the medical establishment not formalized a more rigorous test protocol similar to that of other infectious disease antibody tests where a screening assay is confirmed with WB before reporting to the patient?  Seems with HSV the average person is forced to look "under the hood" to piece together available information and resources on their own.  
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Avatar_f_tn
It's not indicated to test for HSV in the absence of symptoms as a "screening assay". HSV is so common and a relatively benign infection that has been hyped up, in part by appearing on  TIME magazine in August 1982: 'Herpes: The New Scarlet Letter', which forever stigmatized HSV. Not to mention how much drug companies make on this disease, which also advertise really scary commercials on the topic.

I myself am the type of person who freaks out about STDs. I'm 30 and male and have never been tested for HSV because it's not warranted since i'm asymptomatic. I actually refused testing for HSV when I went for an STD screen because it's a ridiculous assay to subject oneself to when not indicated. Your situation is a case in point.
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I'm reassessing my judgment that there's a 50% chance you have HSV-2.  I'm now pretty convinced (at least 90%) you don't have it.  I asked Terri Warren, moderator of the herpes professional forum, to take a look at this discussion.  She agrees you probably are not infected with HSV-2.

Your negative Biokit test is one reason; it is not prone to false negatives.  Also, Terri reminds me that prior to 2008, the Focus HerpeSelect test, more often gave false positive results for HSV-2 (some people happen to have a protein in their blood that interferes with the test); if your initial HSV serology was tested with reagents produced up to that time, it might explain the initial positive result, with just about everything else pointing to negative.  Also, I misunderstood the result of the experimental HSV-2 blood test; I thought your result had been positive.  My mistake -- apologies.  (Was that test done at the University of Illinois?  A new HSV antibody test being developed there is believed to be very good.)  In addition, your sexual history is extremely low risk for HSV-2 or any other STD.  Finally, it is reassuring to know your self PCR testing included the entire genital and anal area.  That also contributes to my reassessment that it's unlikely you have HSV-2.

Exposure without infection?  As you have found, this is controversial.  But it's irrelevant to your situation.  The concept usually refers to people who might have a degree of cell-mediated immunity not detected by antibody tests.  If this happens at all, it probably results from repeated exposure, e.g. in the long-term partner of a known-infected person; not to a trivial exposure like yours.  And it doesn't explain a false positive IgG antibody test.

This sequence of events is very rare.  You're just unlucky, and I don't think you can blame your initial doctor for not trying harder to talk you out of the initial blood test.  Whether to screen asymptomatic people for HSV-2 isn't as clear as implied by the comment from Worriedsick14.  There is debate among the experts on this, but few people see it as black and white.  Some asymptomatic people should be screened, others not, depending on exposure history, risk level, and so on.  However, I do agree screening should not be done in anyone with the essentially zero risk implied by your sexual history.  Still, if someone in your situation insists, I don't try all that hard to talk them out of it.  The sort of outcome you have experienced is rare.

And by the way, I disagree with the notion that genital herpes stigma can be blamed on Time magazine. That admittedly dramatic cover story, and others in the 1980s, were more the result of growing stigma than the cause.

There is no regulatory requirement for the "medical establishment" to formalize test protocols in the way you imagine, for any medical condition.  Testing paradigms are driven by the biology and technology of the available tests (by chance, antibody testing for HIV is much more straighforward and the initial ELISA more accurate than for HSV), the danger of the infection (life-threatening for HIV, inconvenient but rarely serious for HSV), and so on.  Testing policies evolve from those factors, not the other way around.

My very strong advice is that you not take suppressive therapy, but that you go forward with the assumption you are not infected with HSV-2.  I'm not even certain you need to mention this whole business to futuere sex partners; for all the reasons above, I doubt you'll be putting them at risk of HSV-2, especially if you use condoms.  As a relationship matures and might become committed, you might discuss it then -- but with an optimistic spin on the transmission risk.
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Avatar_f_tn
Which asymptomatic people should be tested for HSV and who do you recommend against testing?
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This is going way beyond your personal situation.  There is no simple answer and as I said, this is a subject of debate among the experts.  Some asymptomatic people to be tested might include regular (not one-time) partners of persons with known HSV-2, commercial sex workers, gay men, persons with HIV, heterosexuals with multiple sex partners (a minimum of 10 lifetime unprotected vaginal/anal sex partners), and persons with other STDs (gonorrhea, chlamydia, etc) -- but not all experts would agree on even these.

Another way to put it is that testing shouldn't be done unless there is a fairly good probability (10-20%, maybe higher) that that the patient is infected.  Below that, most would agree testing is usually not a good idea.

That will wind up this thread.  I won't have any further comments or advice.
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Avatar_m_tn
Thanks for your additional analysis and clarification Dr. Handsfield.  Not sure if your last comment was intended for me or 'worriedsick514'.  Forgive my unintentional widening the discussion to a policy debate.

Just to respond to your questions:  regarding the Focus test, it was taken twice in 2010 which is well beyond the 2008 timeframe with results of 5.4, 5.5 index.  I repeated the Focus in mid-2012 and the index had lowered to 3.68.  I had 2 repeat Biokit assays (from 2 differing kit lot numbers) run over 3 months also in mid-2012 both returning clearly negative.  This is in addition to the type2 negative on the experimental assay showing weak reactivity to type1.  

Thanks for having Terri Warren take a look at my case.  It helps to have additional analysis from authorities such as yourselves.  Along those lines was wondering if I can similarly obtain Dr. Hook's inputs in case he may have additional comments; only because of the rarity of this situation.  Would be happy to resubmit online if that may be required.

Lastly, given your advice above, what are your concerns with long-term suppressive medication?

I'm still not sure if I can get past the psychological impact of the testing and lingering specter of transmission risk, however minimal.  The notion of precautionary suppressive therapy has occurred to me as perhaps the best I can do to deal with this messy situation.  

Thanks again.
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Dr. Hook and I do not comment on each other's threads except in unusual circumstances.  I can guarantee his perspectives would not be different than mine; and duplicate questions are not permitted on this forum and would be deleted without reply.

There are no concerns about long-term suppressive medication, i.e. side effects etc.  I just think you don't need it.  There are two reasons for suppressive thereapy for herpes.  One is to prevent recurrent symptoms, obviously irrelevant when there are no symptoms to start with.  The second is to help prevent transmission, but we have already discussed why your transmission potential is low; and in any case over the long term suppressive treatment  is only ~50% effective in preventing transmission, so it doesn't eliminate that problem or the need to inform partners.  I suspect this would simply prolong your anxieties, perhaps even serving as a daily reminder of your dilemma.

You shouldn't be looking to resolution of the "psychological impact" of all this through simple solutions like treatment.  Professional counseling may be part of the answer.  I think your problem goes a lot deeper than the test discrepancies; probably you woulnd't have been tested in the first place if you didn't have inflated fears of genital herpes.

That's definitely all for this thread.  Do your best to move on.
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