[Question #2040] Non-primary HSV2 serology

46 months ago

I’m concerned about having contracted HSV2 from sexual encounter approx. 6 months ago, despite repeated negative serological tests. I’m suspicious that my pre-existing HSV1+ status has prevented my body from making HSV2 antibodies. My research indicates this is a plausible scenario (maybe 20% chance). I’d appreciate your reactions.


Nearly 6mos ago I engaged in unprotected genital (penis-vagina) and oral (both ways) sex with new partner. Following that I experienced redness, swelling, painful red bumps on my penis glans, a later balanitis-looking rash, and unexplained urethritis, over next 6 weeks. Approx. one month later a pustule developed on my scrotum unlike anything I've seen before. (It laid lay more on the top of my skin than in it; for a few days wept clear fluid almost continuously; I messed with it and it came to look much like a particularly-gruesome popped pimple; it has since "healed" to look like a mole.) I had a number of other suspicious genital, oral and general symptoms that I didnt always recognize at the time (like what I believed to be extremely chapped lips; bumps in mouth; a cold sore or two; peripheral neuropathy; night sweats). Crucially, a later partner (when I was still oblivious) fell ill about a month after our encounter, and seems to have since developed cold sores. She reported only mild vaginal itching after our encounter. Has had no testing


My testing history: HSV2 IGG Negative (via HerpesSelect, Diasorin) at 1, 4, 5, 8, 10, 12, 14, 16, 18, 20 and 22 weeks. (HSV1+ each time; when a number was presented it was typically around 32.50.) Also negative for HSV2 via Western Blot at 23 weeks (again HSV1+). I did have a culture swab (not PCR) of the pustule come back negative, but was probably taken too late to be accurate. Also HSV2 IGM neg at 1, 4, 5, 16 wks. Tests aplenty…


BUT: could my HSV1 be masking my newly acquired HSV2?

I want to try to have a baby soon, so I cant afford to be wrong. Thanks.

Terri Warren, RN, Nurse Practitioner
Terri Warren, RN, Nurse Practitioner
46 months ago
If you had only had the IgG testing done, I would suggest that you have a western blot because of the scrotum lesion, but you had the western blot at 23 weeks, and that test is incredibly sensitive for HSV 2 - there is less than a 1% chance it will miss a true HSV 2 infection.  The fact that you had a negative culture is also great, even if it wasn't a PCR.  The fact that you've had a cold sore or two fits with your HSV 1 status, as I'm sure you know.  And the fact that a partner developed cold sores after being with you is not a surprise as we know you are HSV 1 positive and get cold sores.

I have rarely, if ever, seen new herpes only the head of the penis - I have seen recurrences there, but almost all new herpes that I've seen also involves lesions on the shaft of the penis so the rash sounds far more fungal than herpetic. 

The thing is, you've done what you can here - there is no better antibody test than the western blot with terrific sensitivity for HSV 2.  With the number of tests that you've had done, you are clearly focused on this issue big time. What do you think it would take to convince you that you don't have HSV 2?

46 months ago

Thanks, Terri. Yours is a good question; in past weeks I had thought that 16 weeks, or 20, and then WB blood test results would have been enough to put this to rest. And believe me I dont think I've ever wanted anything more than to do so. However, the totality of symptoms just stack up too enormously for me to brush them off as a coincidence. If I could be convinced of the trustworthiness of my blood test results, I like to think that would do it.


To highlight the most concerning things that have led me to suspicion of HSV2: the initial symptoms could well have been (and at the time were) diagnosed as simple balanitis/fungal infection; but then the urethritis (approx. 6 wks from encounter) came with what appeared to be white blisters inside my urethra, and a clear mucoid discharge; later, the unprecedented pustule on my scrotum, which appeared right after my immune system was down from being really sick, was painful and seemed to act like what I understand of a herpes blister. Further, the later partner I mentioned first showed general symptoms (swollen glands, sore throat, awful sick feeling, but no actual flu) approx. 3/4 wks after our encounter, and in addition to cold sores had some weird rash appear on her forehead and her neck. And even now I continue to have what even my dermatologist has allowed could be oral H symptoms- he thinks its just my HSV1, but I dont remember it ever being around, much less this constantly. Then there are the general symptoms, including weird pain in my lower back/upper butt. Like I said - lots of coincidences.


So, that leads us to the testing. First off, the swab was done with what would have then been a recurrent (not primary) lesion, using an older, less accurate testing method, and was done several days if not a full week or so after it appeared - so we might rule it out, entirely. And that leaves us with the serology. Having taken 12 tests, including the gold standard WB, I believe that I would feel OK if I knew this was a primary infection. But I’ve encountered a fair amount of research, and more than a few anecdotal stories that appear to show non-primary HSV2 being more difficult to pick up via blood tests.


For instance: there’s study showing that only 83 percent of non-primary HSV2 patients seroconverted (by HerpeSelect & WB combined) by 6 months, compared to 100 for primary HSV1 and HSV2; and this other 2003 study in which serology was not useful for an example patient with non-primary HSV2; a this Johns Hopkins page, which states that “serotype specific serology is useful to confirm seroconversion in primary infection; role in non-primary infection diagnosis is poorly defined.”  And this is not to say anything of the stories I've encountered, on sites like Honeycomb, of similar individuals who failed to seroconvert but tested positive via swab.

1 in 5 are good odds, but I’m not satisfied with them, given the stakes. Can you please explain why you believe I should trust the serology? Thank you

Terri Warren, RN, Nurse Practitioner
Terri Warren, RN, Nurse Practitioner
46 months ago
You are looking at studies that are using an older version of the ELISA, for one thing (it has been changed several times since 2003) and I doubt that the Johns Hopkins study applies to western blots.  In fact, I doubt that any of these refer to western blots, though I don't know about people's anecdotal posting on internet websites.  It is true that people who have HSV 1 seroconvert more slowly than those who have neither infection initially.  Also in the 2003 study that you cite, the authors note that those who were non-seroconverters by WB were followed for a significantly shorter time period than those who seroconverted.
Are there people who take longer to seroconvert than others?  Yes.  Was use of antiviral therapy as a factor included in this study?  No, I don't believe that it was and now we know that is a huge factor in the ability of the tests to pick up infection. 

You don't have to trust the serology - you can continue to worry about this and retest later.  I believe that you and I have talked a lot and my job here is really not to try to convince you of anything but rather to try to give you information based on my 33 years of practice, using these particular tests, using the odds.  I know you want greater certainty than these tests appear to provide for you.  There is nothing I can do about that for you.  Are there exceptions to the statistics we have?  yes.  Could you be one?  yes.  So what do you propose to do about that?

Terri  ---