[Question #653] HSV 2 negative index value range query | Confused with differing views?

53 months ago
Earnest Request: Could Dr. HHH/Dr. Hook/Ms.Terri read this please: 

My recent question (#630 - please read) was addressed by Dr. Hook and I am confused after reading Ms. Terri's response to question #639 around HSV IGG numerical value.

My 6 week HSV2 IGG value [I’m HSV1 positive] came out 0.85 (<0.9 for negative) and Dr. Hook confirmed that the value being closer to 0.9 doesn’t imply I might be seroconverting as a negative is negative.

Ms. Terri’s response to #639 
Excerpt:
I would disagree that there is little difference between .01 and 0.5.  If I saw both, and the 0.5 was after the .01, I would be concerned about seroconversion happening - going from negative to positive.

I always thought the numerical value is sort of meaningless unless it's between 1.1 and 3.5 where it could be a false positive or one could genuinely be seroconverting during window period.

Some reliable posts with excerpts:

1) http://www.medhelp.org/posts/STDs/What-is-the-range-for-a-positive-HSV-1-IgG-test/show/1507256

Dr. HHH’s:
No conclusion can be drawn from the numerical result (technically, it is an optical density ratio) of an HSV-1 (or HSV-2) IgG test, especially in the strongly positive range.  If you were to be tested 5 more times, the OD ratio might vary from 2.0 to 8.0; that could happen even if the same blood specimen were tested 5 times, using different batches of test reagents. The OD ratio value does not directly reflect the amount of antibody in the blood; it is more dependent on the chemistry of the test.  Similarly, the numerical value says nothing about duration of infection, its severity, the frequency of outbreaks, or the effectiveness of the immune system.  In a way, it is unfortunate that labs even report the numerical values of HSV test results.  A verbal report of negative, positive, or (sometimes) equivocal would be a more accurate representation of the meaning of the test

2) http://www.medhelp.org/posts/Herpes/high-reference-range-number-for-negative-results-on-igg-test/show/1424623

gracefromHHP: your igg results will not be the exact same every time. they will differ from test to test somewhat. no you don't have any reason to suspect that you are slowly creeping up into the hsv2+ range because of the change in your results. 

3) http://www.thehelpernewsletter.org/index.php?option=com_content&view=article&id=55:testing-winter-2009&catid=176:herpes-testing&Itemid=237
The function of the index value is simply to indicate whether the test is positive or negative. according to Dr. Morrow. “If you get an ELISA and an index value is reported to be over about 5 or under 0.9, you should believe the result.”

My questions:

1) Based on my exposure and HSV 2 result, do I have a reason to worry? What are the % chances that I’d have caught HSV 2 and is 0.85 index value a concern (I’m seroconverting?). Do I being HSV 1 positive could have any role to play in this high but negative index value?

2) When Dr. HHH says that numerical value (OD) is not a direct measure of the amount of antibodies, then why Ms. Terri would be more concerned with a 0.5 value as compared to 0.01? Dr. HHH even mentions that if the same sample gets tested 5 times, you could get different results. 
Aren’t these values supposed to differ between labs who could have different baseline/control/cut off values set? So in my case, is it possible that the lab might have set a higher negative baseline cut off? E.g. 0.7 instead of 0.01 or whatever?

It’s been 8 weeks and I’m really concerned of my chances of having gotten HSV2 with a single brief protected exposure. Waiting another 8 weeks to test seems a really long and killing wait.

Please help clarify. 
53 months ago
One more question: Kindly read my previous question #630 for complete details:

3) If I had to get HSV 2 outbreak within 2-12 days, where would that be ? At the end of the shaft of penis (where condom ends and if the skin gets exposed)? Could I have got it on anus ? (heard men mostly get on penis). I had some anus related discomfort (mild itching) on the 17th day after exposure (note: anus wasn't exposed to CSW's skin) where I scratched my anus and caused swelling/inflamation on the opening that healed on its own in about 10 days. I had no tingling/burning/lesions/sores/blisters and to the best of my understanding, it didn't seem like a herpes outbreak as I know how that actually feels with my HSV1 since childhood. It more seemed like a self inflicted inflammation due to scratching and touching driven by anxiety/stress.
Terri Warren, RN, Nurse Practitioner
Terri Warren, RN, Nurse Practitioner
53 months ago
I'm going to respond to this and so might Dr. Handsfield or Dr. Hook

When I try to help people assess their risk of having acquired an STI, I always look back at the nature of the encounter to help make that assessment.  In your situation, one episode of protected intercourse is very low risk indeed.  And in that context, I will try to answer the rest of your questions.


1) Based on my exposure and HSV 2 result, do I have a reason to worry? What are the % chances that I’d have caught HSV 2 and is 0.85 index value a concern (I’m seroconverting?). Do I being HSV 1 positive could have any role to play in this high but negative index value?

I do not think you have reason to worry here, no, because your encounter was so low risk to start with.  And again, I look at index values always through the lens of the kind of encounter someone has.  If I have a patient who has a higher risk exposure, and they initially test with a baseline  index value of .02 and then at 4 weeks they test again and it is .5 and then four weeks later they test again at .85, that person is a concern to me.  They have risk, and they have moved from soundly negative into a far grayer area.  Do you see the difference between that situation and yours?  These situations are vastly different so my response would be different. 

2) When Dr. HHH says that numerical value (OD) is not a direct measure of the amount of antibodies, then why Ms. Terri would be more concerned with a 0.5 value as compared to 0.01? Dr. HHH even mentions that if the same sample gets tested 5 times, you could get different results. 
Aren’t these values supposed to differ between labs who could have different baseline/control/cut off values set? So in my case, is it possible that the lab might have set a higher negative baseline cut off? E.g. 0.7 instead of 0.01 or whatever?

I agree that index value can vary, yes.  We do about 80 of these tests per month in my practice and have since 2007, so I see lots of values come through and I don't know if I've ever seen one be exactly the same as the previous one in the same patient where the result didn't change, just the index values.  And why I would be concerned about that kind of change is explained above.  I would not always be concerned, just if there is risk, which I don't believe you had.  The ranges of normal and abnormal should be stated on each test results - negative, equivocal and positive.  And remember that even when some people have a low positive result (about 5.5% of total patients who test) half of those are false positives.  The cutoffs for negative and positive can be very very different ,based on the test used.  So you should check on that.

If you were going to get herpes symptoms within 2-12 days, they would most likely be on the penis.  If you are certain that you scratched your anus enough to cause swelling and inflammation, then there is no need to worry about that further, right?

I hope this help to clarify my response

Terri



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Edward W. Hook M.D.
Edward W. Hook M.D.
53 months ago
I will add my agreement to Terri's comments.  Laboratory tests are helpful but as Ms. Warren has pointed out, they should always be interpreted in the context of an exposure and other findings.  As I have already said, your guilt and anxiety over your exposure is causing you to take things out of context and mis-interpret them.  My advice, like Ms. Warren's above, and Dr. Handsfield's earlier is that you should relax, understand that you were not infected by the event that you described and move forward without concern.  If you cannot do that you do not need more testing, you need to talk with a counselor or mental health professional to help you work through why you continue to worry despite negative tests and expert advice that you were not infected.  EWH.
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H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
53 months ago
Greetings, Ranjan. Terri invited me to add a comment, since you quoted me (among others).

I agree exactly with Terri's responses, and with Dr. Hook's in your earlier thread. That reply, Terri's, and the quotes you found in your online searching are not in conflict with one another.

It is definitely true that the same specimen, tested several times for HSV antibody by ELISA, will almost never give the precise same number; and that number can vary quite widely, especially if tested with different lot numbers of the test reagents. That's exactly why a ratio, also called index value, is used. Because of this natural variation, it is the ratio between the patient's serum and a negative control that gives valid resuls, not the absolute number on the patient's specimen. The amount of variation wouldn't often be as great as 0.1 to 0.85; that could happen, but variance between say 0.3 and 0.6 would be more common. And as Terri said, a CHANGE from say 0.1 to 0.5, or certainly up to 0.85, would raise eyebrows more than a single random test value. The older quote from Terri does not say that such a change would prove someone had a new HSV infection, only that it might warrant additional evaluation, including both clinical assessment (risk level, symptoms, physical exam) and repeat testing.

It is also true that initial herpes outbreaks almost always involve the anatomic sites most exposed. In animal research, e.g. guinea pigs or mice, you can't even get HSV to cause an infection unless the virus is vigorously rubbed into the animal's skin, to the point of irritation and even slight bleeding. While the mechanics of human transmission haven't been studied in that detail, the large majority of new infections occur at sites that receive the maximum friction during sex, e.g. head and shaft of the penis, and the vaginal opening and labia minor in women -- and not on nearby areas like the scrotum, upper thighs, etc, even though these areas often (usually?) come into contact with partners' genital fluids. This suggests that, as in animals, the virus must be "massaged" into the tissues for infection to take hold. This is also one of the main reasons casual, non-sexual contact or exposure to genital fluids on toilets, towels, etc do not transmit genital herpes.

In your case, I agree that the most likely site of symptoms, if you had acquired HSV2, would be the upper penis, above the condom protected area. Certainly the anus would be unlikely, and anal itching is among the most common day to day symptoms experienced by all human beings. Its occurrence at this time doesn't remotely suggest herpes as the cause.

Based on the nature of your exposure and lack of symptoms to suggest genital herpes, your mistake was to be tested for HSV in the first place, and I would recommend you not continue with additional testing. That said, I do understand why an index value of 0.85 makes you nervous, and I imagine you're going to have further tests regardless of our advice on this forum. If you do that, I would recommend waiting until 12 or even weeks after the event instead of 8 weeks. My prediction is that any additional testing will remain negative, and likely at an index value well below 0.85.

In the meantime, I would suggest not continuing to search the internet on this. Like many persons who search about topics they are anxious about, it seems you are being drawn to information that inflames those anxieties. As the famous statistician Nate Silver (fivethirtyeight.com) put it, "Give an anxious person an internet connection in a dark room and soon he'll be mistaking his common cold for the bubonic plague" (approximate quote).

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H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
53 months ago
I also agree exactly with Dr. Hook's comment above. He and I were writing our replies at the same time. Also, I meant to write "recommend waiting until 12 or even 16 weeks...."
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53 months ago
Thank you Mr. Terri, Dr. Handsfield and Dr. Hook for your responses. Much appreciated.

Terri - Whatever you’ve said makes sense to me. It’s just that a high negative index value concerned me even though it was just a standalone test in my case. While I think I’ve understood the 0.01 -> 0.5 -> 0.85 index value rise situation that you explained, I feel that’ll happen (only?) if a person sticks to one lab/testing method and results might go off if one changes the lab. Do let me know if you think that’s inaccurate.

Dr. Hook - Thank you for the time & feedback that you’ve given me and appreciate your comments that testing results should be interpreted in context of the exposure and other clinical findings. May be that’s the reason you and Dr. Handsfield are confident with my 6 week testing results (especially HIV).

I admit that I’ve extreme guilt and anxiety from this mistake. It’s just that I’m usually a very cautious and risk averse person when it comes to my family having a very loving wife and a child so I want to be around to be able to take care of them. I wouldn’t be so worried, if it was just about me.

I’ve taken reassurance from both of your responses and kindly accept my sincere appreciation.

Dr. Handsfield - Thank you so much for your time and valuable comments. Specifically where you elaborate on how the HSV virus must be ‘massaged’ into the tissues for infection to transfer. That comment seems extremely inline to how I think I ended up giving my HSV 1 to my wife 12 years after marriage (another guilt I can’t get over but fortunately she didn’t have any recurrence yet - touchwood). Since it took 12 years, your numerous other comments that I’ve read around low stats of HSV transfer to a long term partner make a lot of sense. Further reassures me that I’d be safe after a somewhat reluctant and brief protected exposure. 

I’ll try my best to move forward from here, not read internet (i’d still re-read all of your responses though whenever I feel the need) and see if I can avoid testing myself at 12 or 16 week - that’ll be a challenge for me !

It’s a BLESSING to have the 3 of you accessible for people around the world through this forum and no one can thank you enough for the service that you all are doing. Wish you all the very best of everything.

PS:  I really hope I don’t come up with a need for follow up questions but would request this thread to be kept open for a few weeks if that isn’t against the forum guidelines (i.e. close by default after X weeks).

Terri Warren, RN, Nurse Practitioner
Terri Warren, RN, Nurse Practitioner
53 months ago
You accurately interpreted what I said, yes.

Terri
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