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Subject: "frequency of non-genital, non-oral hsv2 recurrences"     Previous Topic | Next Topic
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mbison
Member since Feb-28-12
9 posts
Feb-28-12, 08:23 PM (CST)
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"frequency of non-genital, non-oral hsv2 recurrences"
 
   Hello,

I am trying to understand how and why the frequency of non-genital ("boxer shorts" area) hsv2 recurrences differs from the frequency of hsv2 genital recurrences. In particular, I need help interpreting this study: Frequency and reactivation of nongenital lesions among patients with genital herpes simplex virus.

To summarize the relevant findings, the study followed 384 patients with initial hsv2 genital infection for an average of 63 weeks. The study separated oral outbreaks from non-genital outbreaks. So, when I say non-genital, I mean non-genital, non-oral outbreaks. The authors explain 3 possible ways to get non-genital hsv2 outbreaks: direct inoculation of a non-genital site, auto-inoculation of a non-genital site, or viremic spread within an infected nerve group.

Of the 384 people, 15 had a non-genital site included in the initial outbreak. The location was typically somewhere nearby on the trunk or legs that was inoculated in addition to the genitals. Of those 15, 9 (60%) had non-genital recurrences, with the location being the same as the point of inoculation (ie., somebody with initial infection on the genitals and left thigh was likely to have recurrences at both the genitals and left thigh). I will call this the "direct inoculation" group.

Of the other 369 whose initial infection was limited to the genitals, 20 (5.4%) went on to have non-genital recurrences. The location was typically the buttocks, which I assume is because it is in the same dermatome as the genitals. I will call this the "viremic spread" group.

To compare the frequency of genital hsv2 recurrences to the frequency of non-genital recurrences, the authors considered the "direct inoculation" group and the "viremic spread" group separately.

For the "direct inoculation" group, the authors found that the median time to first genital recurrence was 67 days while the median time to first non-genital recurrence was 725 days. The frequency of genital recurrence was also much higher than the frequency of non-genital recurrences in these people.

For the "viremic spread" group, the authors looked only at people who experienced recurrences on both the genitals and the buttocks. They found that genital recurrences occurred more than twice as often as buttocks recurrences in these people.

So to summarize the results, about 10% of people with genital HSV2 went on to have non-genital recurrences, due either to direct or auto inoculation of non-genital sites during the initial infection, or to viremic spread from the genitals (usually to the buttocks). Regardless of the cause, people with non-genital recurrences get them with much less frequency than genital recurrences.

I am trying to understand why the difference in frequency. The authors give the following explanation:

"Perhaps the greater distribution of peripheral nerve endings per millimeter of skin and the longer distance required to travel may be factors in these differences."

I want to get your thoughts on this study -- does my summary jive with your understanding of non-genital hsv2 recurrences? Regarding the authors' explanation for the difference in frequency, is there some way to quantify the different density of nerve endings at genital vs. non-genital sites? It makes sense to me that less nerve endings could lead to less paths to the surface and thus less recurrences. I don't understand what "longer distance" they are talking about. Does the virus have to travel further to get to say the buttocks than the genitals? Does the thickness of skin somehow affect this? Any other possible explanations for the difference in frequency?


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windyadmin
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8251 posts
Mar-01-12, 03:12 PM (CST)
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1. "RE: frequency of non-genital, non-oral hsv2 recurrences"
In response to message #0
 
LAST EDITED ON Mar-01-12 AT 03:13 PM (CDST)
 
> I am trying to understand why the difference in frequency. The authors give the following explanation:
>
>"Perhaps the greater distribution of peripheral nerve endings per millimeter of skin and the longer distance required to travel may be factors in these differences."


Nobody knows why the location of the infection affects the recurrence rate. Any explanation of this should (probably) include an explanation of why genital hsv1 recurs less than oral hsv1 and why oral hsv2 recurs less than genital hsv2. The lips and the genitals both have a high density of nerve endings, plus, the distance traveled from trigeminal ganglia to mouth is about the same as sacral ganglia to genitals, so I think the authors' guess is wrong on that point.

Thickness of skin might be relevant. It's possible to have recurrences of viral activity without having the virus erupt through the skin (or at least I read some discussion about this as a possible explanation). I'm thinking that there's relevant information in another study, either the one that looked at shedding throughout the day by swabbing four times a day or the one that found cellular immunity in some seronegative partners of people with ghsv2.


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mbison
Member since Feb-28-12
9 posts
Mar-04-12, 07:39 PM (CST)
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2. "RE: frequency of non-genital, non-oral hsv2 recurrences"
In response to message #1
 
   Thanks for responding to my question.

The authors also looked at some cases of oral hsv2 and genital hsv1. They noted the large difference in recurrence rates between hsv1 and hsv2 at the two locations, but didn't provide any theories as to why as far as I could tell.

So, there must be something fundamentally different between hsv1 and hsv2 that causes hsv1 to prefer oral and hsv2 to prefer genital. But I don't see that this shows that other factors couldn't affect the rates of hsv2 recurrences at genital vs. nearby, non-genital locations. Maybe I am missing something in the logic here? Also, I noticed upon re-reading the paper that they included some distant locations in the non-genital, non-oral group such as the fingers. Couldn't distance to travel still affect the recurrence rate at that location?

It makes sense to me that you could have recurrence of viral activity without outbreaks do to thickness of skin. I am curious to know how a study might demonstrate this.


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windyadmin
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Mar-05-12, 12:20 PM (CST)
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3. "RE: frequency of non-genital, non-oral hsv2 recurrences"
In response to message #2
 
Your logic is sound. There's nothing that says there can't be more than one factor that affects recurrence rate according to location. Distance traveled might be one of them.

To find out if virus is present under the skin, I think you'd have to look for viral dna in the intracellular fluid at every location that you would swab for a shedding study, and then compare that to swabs of the same area taken at the same time. Right now, I can't think of a practical way to get the samples.


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mbison
Member since Feb-28-12
9 posts
Mar-05-12, 04:03 PM (CST)
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4. "RE: frequency of non-genital, non-oral hsv2 recurrences"
In response to message #3
 
   Thanks, again. I have one more related question -- do you happen to know roughly how much thicker fully keratinized skin is compared to genital skin? It makes sense to me that the skin of say, the leg, is much thicker than the skin of the penis, but I can't find that quantified anywhere.

On a related note, my understanding is that the skin of the penis is not a mucous membrane -- is that right? It seems like if it were, that could be another factor that might affect frequency of recurrence.


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