We tested whether genital herpes simplex virus (HSV) shedding is an appropriate surrogate outcome for the clinical outcome of genital herpes lesions in studies of HSV-2 antiviral interventions.
The effect of female sex hormones on the natural history of herpes simplex virus (HSV) is poorly understood. Studies suggest that vaginal immunity varies throughout the menstrual cycle, with increased inflammatory cytokines and decreased innate immune factors observed during the luteal (post-ovulatory) phase. Whether HSV shedding or presence of genital lesions vary throughout the menstrual cycle is unknown.
Methods
We studied HSV-2 seropositive women enrolled in prospective studies of genital herpes at the University of Washington Virology Research Clinic. Participants were eligible if they had established HSV-2 infection, performed daily genital swabbing for HSV DNA, recorded a menstrual diary, and were not using hormonal contraception. We used Poisson mixed effects models to determine if genital HSV DNA detection or lesion frequency differed throughout the menstrual cycle, categorised into four seven-day phases based on most proximate first day of menstrual bleeding: early and late for each of follicular and luteal.
Results
In 189 women aged 19–46 (median age 33) who collected 9307 genital swabs, HSV was detected on 1822 days (20%). The rate of shedding was 21% during the early follicular phase versus 18% during late luteal (RR=1.2, 95% CI 1.0–1.4, p=0.04), 21% during late follicular (RR=1.2 relative to late luteal, 95% CI 1.0–1.5, p=0.06), and 19% during early luteal (RR 1.1 relative to late luteal, 95% CI 0.9–1.3, p=0.53). In sensitivity analyses reducing misclassification of phase by excluding samples>10 days from day 1 of menses, these observations were strengthened. The pattern was similar for genital lesions, present on 13% of days during the follicular phase and 11% during the luteal phase.
Conclusion
In women with established HSV infection, genital HSV-2 shedding and lesions were slightly more common during the early follicular phase of the menstrual cycle than in the luteal phase. These cyclic variations may be related to changes in oestrogen and progesterone affecting vaginal immunity.
This study compared the rate of isolation of herpes simplex virus (HSV) from >36000 samples of mucosal secretions obtained from 296 HSV-infected persons versus the rate of detection of HSV DNA, by means of a real-time quantitative polymerase chain reaction (PCR) assay. Overall, HSV was isolated in 3.0% of samples, and HSV DNA was detected in 12.1% of samples. The mean number of HSV DNA copies was 10(4.9) in samples obtained on days when HSV lesions were present and 10(4.4) in samples from days when HSV lesions were absent. There was a linear relationship between the ability to isolate virus in culture and the log number of copies of HSV DNA in the sample; this relationship persisted in samples from men or women, in samples from human immunodeficiency virus-negative or -positive participants, and in samples obtained on days when lesions were present or absent. In home-collected specimens, the ratio of PCR positivity to viral-culture positivity rose from 3.8:1 in the winter to 8.8:1 in the summer months, reflecting the lability of viral-culture specimens transported during warm weather.
Objective To determine bacterial vaginosis (BV) status at multiple time points among adolescent girls and young women (AGYW) and assess the impact of pregnancy on their BV status. Design Longitudinal cohort study. Setting Thika, Kenya. Participants AGYW aged 16–20 years enrolled prior to first sex or reporting only a single lifetime partner. Main outcome measures The primary outcome was relative risk (RR) of BV during pregnancy compared with before pregnancy by analysing longitudinal trends in BV over time. BV risk was estimated using Poisson regression models. Results A total of 121 AGYW became pregnant in the parent cohort and had BV results before, during or after pregnancy. Point prevalence of BV was 11.0% at visits >12 months pre-pregnancy, 13.0% at 3–12 months pre-pregnancy, 22.1% at <3 months pre-pregnancy and 13.4% during pregnancy. Compared with visits during pregnancy, RR of BV was 1.65 (95% CI: 1.00 to 2.71; p=0.05) at visits <3 months pre-pregnancy, 0.97 (95% CI: 0.62 to 1.52; p=0.90) at visits 3–12 months pre-pregnancy and 0.82 (95% CI: 0.44 to 1.53; p=0.53) at visits 12 months pre-pregnancy. An adjusted analysis including age, income, residence, date of first sex, recent sexual activity and positive sexually transmitted infection test resulted in small changes in risk estimates, with adjusted RR of BV of 1.66 (95% CI: 1.04 to 2.67; p=0.04) at visits <3 months pre-pregnancy compared with visits during pregnancy. Conclusions BV risk during pregnancy was lower than during the immediate pre-pregnancy period. Hormonal changes in pregnancy may reduce BV.
Background US Food and Drug Administration-approved enzyme-linked immunoassays (EIA) for determining type-specific herpes simplex virus (HSV) serostatus are widely used in clinical practice. We compared the performance of such assays with the University of Washington Western blot (UW WB) in patients who sought confirmation of their HSV serology result. Methods We reviewed charts of all persons evaluated at the Westover Heights Clinic in Portland, Oregon, from July 2010 through September 2015, who had a HSV EIA, followed by UW WB. Results Of 864 persons, 47% were women. The median age was 36 years (range, 18–73 years). Using UW WB to define infection status, 286 (33%) persons were HSV-1 seropositive only, 104 (12%) were HSV-2 seropositive only, 134 (16%) were both HSV-1 and HSV-2 seropositive, 235 (27%) were HSV seronegative, and 105 (12%) had indeterminate results. Compared with the UW WB as the criterion standard, EIA was 70.2% sensitive and 91.6% specific for HSV-1, and 91.9% sensitive and 57.4% specific for HSV-2. Among 278 persons who were HSV-1 seropositive by EIA, 255 were confirmed by the UW WB (positive predictive value [PPV], 91.7%). Of the 360 persons that were HSV-1 seronegative by the EIA, 252 were seronegative by UW WB (negative predictive value [NPV], 70.0%). Among 381 persons with HSV-2 EIA seropositivity, 193 tested HSV-2 seropositive by the UW WB (PPV, 50.7%). Of the 270 persons HSV-2 seronegative by EIA, 17 were seropositive with the UW WB (NPV, 93.7%). Among 261 persons with an EIA HSV-2 index value = 1.1–2.9, 39.8% of results were confirmed by UW WB, compared with 78.6% of the 70 persons with an EIA index value of 3 or greater ( P < 0.001). The risk of false-positive HSV-2 EIA results was higher in those with HSV-1 antibody (47.1% vs 37.1%, P = 0.036). Conclusions US Food and Drug Administration-approved EIAs have poor PPV for HSV-2 and poor NPV for HSV-1 in clinical practice. More accurate rapid type-specific HSV antibody tests are needed.
A stochastic mathematical model suggests that very low numbers of herpes simplex virus 2 particles are released frequently into the genital tract in infected individuals.
Abstract We evaluated the immunologic response to a novel vaccine regimen that included 2 doses of NVX-CoV2373 (Novavax) followed by 1 dose of BNT162b2 (Pfizer-BioNTech) monovalent booster vaccine. A durable neutralizing antibody response to Omicron BA.4/BA.5 and BA.1 variants was observed at month 6 after the booster, while immune escape was noted for the XBB.1.5 variant.
Neonatal herpes most commonly results from fetal exposure to infected maternal genital secretions at the time of delivery. The risk of transmission from mother to infant as it relates to maternal herpes simplex virus (HSV) serologic status and exposure to HSV in the maternal genital tract at the time of labor has not been quantified. Furthermore, no data exist on whether cesarean delivery, the standard of care for women with genital herpes lesions at the time of delivery, reduces HSV transmission.
Objective
To determine the effects of viral shedding, maternal HSV serologic status, and delivery route on the risk of transmission of HSV from mother to infant.
Design
Prospective cohort of pregnant women enrolled between January 1982 and December 1999.
Settings
A university medical center, a US Army medical center, and 5 community hospitals in Washington State.
Patients
A total of 58 362 pregnant women, of whom 40 023 had HSV cultures obtained from the cervix and external genitalia and 31 663 had serum samples tested for HSV.
Main Outcome Measure
Rates of neonatal HSV infection.
Results
Among the 202 women from whom HSV was isolated at the time of labor, 10 (5%) had neonates with HSV infection (odds ratio [OR], 346; 95% confidence interval [CI], 125-956 for neonatal herpes when HSV was isolated vs not isolated). Cesarean delivery significantly reduced the HSV transmission rate among women from whom HSV was isolated (1 [1.2%] of 85 cesarean vs 9 [7.7%] of 117 vaginal; OR, 0.14; 95% CI, 0.02-1.08;P= .047). Other risk factors for neonatal HSV included first-episode infection (OR, 33.1; 95% CI, 6.5-168), HSV isolation from the cervix (OR, 32.6; 95% CI, 4.1-260), HSV-1 vs HSV-2 isolation at the time of labor (OR, 16.5; 95% CI, 4.1-65), invasive monitoring (OR, 6.8; 95% CI, 1.4-32), delivery before 38 weeks (OR, 4.4; 95% CI, 1.2-16), and maternal age less than 21 years (OR, 4.1; 95% CI, 1.1-15). Neonatal HSV infection rates per 100 000 live births were 54 (95% CI, 19.8-118) among HSV-seronegative women, 26 (95% CI, 9.3-56) among women who were HSV-1–seropositive only, and 22 (95% CI, 4.4-64) among all HSV-2–seropositive women.
Conclusion
Neonatal HSV infection rates can be reduced by preventing maternal acquisition of genital HSV-1 and HSV-2 infection near term. It can also be reduced by cesarean delivery and limiting the use of invasive monitors among women shedding HSV at the time of labor.
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