Herpes what is shedding




















We defined shedding episodes as consecutive HSV-positive swab results; those that were preceded and followed by 2 consecutive negative swab results were deemed to have known duration.

Genital shedding rates were calculated by using the number of days with positive swab results divided by the total number of days with swabs collected for each subject. Confidence intervals CIs for average shedding and lesion rates were computed with an intercept-only Poisson regression model, which correctly accounts for multiple samples per person.

The amount of virus shed per sample was quantified as log 10 copies per milliliter. The annualized episode rate was calculated by scaling the number of shedding episodes to the follow-up period. Categories for variables such as age and recurrences per year were determined by using quantiles because graphic investigation demonstrated a lack of linear relationship.

Years since acquisition were categorized according to previous work showing that shedding decreases the first year after HSV-2 acquisition and then stabilizes. To characterize the predictors of genital shedding, Poisson regression analyses were performed, including a scale parameter for overdispersion. A 2-sided P value of. Four hundred ninety-eight HSV-2—seropositive, healthy participants collected at least 30 days' worth of genital swabs and were included in the analysis.

The mean age of study participants was Two hundred fifteen Two hundred sixty-eight Most participants were white ; Most participants ; The mean age at sexual debut was Four hundred ten participants Among persons with symptomatic genital herpes, the median time since HSV-2 infection was 8.

Overall, there were 33 days of observation; of these, 28 had genital swabs available for analysis. Participants were observed for a median of 57 days IQR, Table 1. The overall genital shedding rate was significantly higher in persons with symptomatic infection than with asymptomatic infection, of 23 days Genital HSV was detected at least once in of persons No genital lesions were reported on 25 days of follow-up Subclinical genital shedding rates were higher in persons with symptomatic infection compared with asymptomatic infection of 20 [ Genital lesions were reported on days with polymerase chain reaction swabs During prospective follow-up, In addition, 19 The frequency of lesions during the study was higher among persons with symptomatic vs asymptomatic genital HSV-2 of 26 days [ Overall, on days with detectable HSV, the median log 10 copy number was 4.

The median HSV log 10 copy number was significantly higher among persons with symptomatic than asymptomatic infection, 4. The median amount of HSV detected in the presence of lesions was also higher compared with the amount of HSV detected in the absence of lesions, 5. However, the median amount of HSV detected during subclinical genital shedding episodes was similar in persons with symptomatic and asymptomatic infection 4.

Among persons with symptomatic genital herpes, Viral shedding episodes associated with genital lesions were significantly longer than those without lesions median 5. Persons with symptomatic infection had more frequent genital shedding episodes compared with persons with asymptomatic infection median In univariate analyses, persons with asymptomatic HSV-2 infection had a shedding rate of A higher number of recurrences per year was found to be a predictor of genital shedding.

Persons with 8 or more recurrences per year had a shedding rate of Persons of white race had a higher viral shedding rate than persons reporting nonwhite race Herpes simplex virus type 1 infection did not influence the risk of HSV-2 genital shedding, with a shedding rate of Higher number of recurrences per year and white race also remained predictive of higher genital shedding rate in the adjusted analysis Table 2.

Asymptomatic infection was associated with lower rates of shedding in univariate analyses, with a shedding rate of 8. Women had a slightly increased subclinical genital shedding rate compared with men, Subclinical viral shedding was also more frequent among persons of white race compared with persons of other races, Persons with 8 or greater recurrences per year had a viral shedding rate of White race and frequent recurrences also remained significant predictors of higher subclinical shedding Table 2.

In univariate analyses, persons with asymptomatic HSV-2 infection had lower rates of genital lesions compared with those with symptomatic HSV-2 infection, 3. No differences in lesion rates were observed by HSV-1 status, with lesion rates of Persons of white race had a higher genital lesion rate compared with persons of other races, Persons reporting white race also had a persistently higher genital lesion rate.

Among the 88 persons who had asymptomatic HSV-2 infection, 19 persons reported genital signs and symptoms during follow-up. The participants who recognized lesions were slightly older than those who remained asymptomatic mean age 45 years, SD 9. The genital HSV shedding rate was The median log 10 copy number among the participants who reported lesions was 4. Among persons in the asymptomatic group who reported genital lesion during follow-up, the subclinical viral shedding rate was The uncertainty regarding the optimal management of asymptomatic persons who receive an HSV-2—seropositive test result derives in part from lack of information about the natural history of such infection.

To address this gap, we prospectively evaluated a large cohort of HSV-2—seropositive persons to determine the patterns of genital viral shedding among persons with symptomatic and asymptomatic genital HSV-2 infection. We found that the risk for genital shedding was twice as high and the risk for lesions almost 3 times as high among persons with symptomatic genital HSV-2 infection. The quantity of virus the median genital log 10 copy number shed subclinically was similar in persons with symptomatic and asymptomatic infection.

Lesions were associated with a higher quantity of virus shed compared with that in subclinical shedding. In addition, higher quantity of virus shed was associated with longer shedding duration. These findings extend earlier observations that genital HSV shedding in persons who are seropositive for this virus is likely universal but that the clinical manifestations of disease differ widely. However, even among persons with a history of genital HSV-2 infection, the spectrum of clinical disease is large, and our findings show that the virologic spectrum is also broad, with substantial overlap across the 2 groups.

Our study collected more than 28 genital swabs from persons infected with HSV Because the collection of genital swabs is time consuming, it is possible that participants who were concerned about genital HSV-2 infection were more likely to participate in this study.

When entered into the model simulations, viral infectivity predicted both the probability of transmission and the viral load in the genital tract when transmission events happened. The outcome from the model simulations was that an intervention that maintains viral load below 10, copies would prevent most if not all transmission events.

Antiviral medications can reduce viral shedding episodes both in duration and intensity. However, HSV-2 transmission from patients on therapy still occurs. Schiffer and colleagues had previously shown that this likely stems from the short half-lives of currently available antiviral drugs, resulting in periods of sub-therapeutic drug levels, during which the virus is able to actively replicate and achieve high viral loads in the genital tract Schiffer et al. It is during these periods that transmission likely occurs.

The results from the current study point to the possibility of preventing transmission via the use of pharmaceutical interventions able to maintain the viral load below this estimated threshold for transmission.

If you can get shedding below that level at all times you are likely to severely limit or eliminate transmission," said Schiffer. Current drug regimens are unable to achieve this level, but there are other antiviral medications currently coming through the pipeline. A recent study by Dr. A decrease in viral shedding was observed even when pritelivir was administered only once weekly, indicating a longer half-life of the drug than current antiviral therapies. Ideally, these clinical trials, together with the mathematical model studies, will ultimately lead to successful treatment and prevention for HSV-2 infection and transmission.

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Volume Article Contents References. Mertz Gregory J. Reprints or correspondence: Dr. Oxford Academic. Cite Cite Gregory J.

Select Format Select format. Permissions Icon Permissions. Extended duration of herpes simplex virus DNA in genital lesions by the polymerase chain reaction. Google Scholar Crossref. Search ADS. Virologic characteristics of subclinical and symptomatic genital herpes infections. Frequency of acquisition of first-episode genital infection with herpes simplex virus from symptomatic and asymptomatic source contacts.

Reasons for the absence of a history of recurrent genital infections in mothers of neonates infected with herpes simplex virus. Google Scholar PubMed. Frequency of asymptomatic shedding of herpes simplex virus in women with genital herpes.

Herpesvirus type 2: study of semen in male subjects with recurrent infections. Frequent genital herpes virus 2 shedding in immunocompetent women: effect of acyclovir treatment. Asymptomatic reactivation of herpes simplex virus in women after the first episode of genital herpes.

Herpes simplex virus type 2 shedding in HIV-negative men who have sex with men: frequency, patterns, and risk factors. Valacyclovir and acyclovir for suppression of shedding of herpes simplex virus in the genital tract. Once daily valacyclovir to reduce the risk of transmission of genital herpes.

Comparative efficacy of famciclovir and valacyclovir for suppression of recurrent genital herpes and viral shedding. A queueing model for chronic recurrent conditions under panel observation.



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