Sexually transmitted diseases.

Sexually transmitted diseases (STDs) continue to be a global epidemic with significant risk of morbidity/mortality for the fetus. STDs with prominent cutaneous findings including condylomata acuminata, genital herpes infections, and syphilis are reviewed. Important clinical cutaneous findings help aid early diagnosis and facilitate treatment. Condylomata acuminata have the potential of causing cervical cancer, anogenital cancer, and oropharyngeal cancer. Significant advances have been made in human papilloma virus vaccinations and treatment. Genital herpes infection can produce significant physical and emotional distress to the patient and significant potential harm to the fetus. Early clinical recognition of STDs and their appropriate management is critical.

Norethisterone Enanthate Increases Mouse Susceptibility to Genital Infection with Herpes Simplex Virus Type 2 and HIV Type 1.

Norethisterone enanthate (NET-EN) and depot-medroxyprogesterone acetate (DMPA) are two forms of injectable progestin used for contraception. Whereas clinical research indicates that women using DMPA are more susceptible to HIV and other genital pathogens, causal relationships have not been determined. Providing an underlying mechanism for this connection, however, is recent work that showed DMPA weakens genital mucosal barrier function in mice and humans and respectively promotes susceptibility of wild-type and humanized mice to genital infection with HSV type 2 and HIV type 1. However, analogous effects of NET-EN treatment on antivirus immunity and host susceptibility to genital infection are much less explored. In this study, we show that compared with mice in estrus, treatment of mice with DMPA or NET-EN significantly decreased genital levels of the cell-cell adhesion molecule desmoglein-1 and increased genital mucosal permeability. These effects, however, were more pronounced in DMPA- versus NET-EN-treated mice. Likewise, we detected comparable mortality rates in DMPA- and NET-EN-treated wild-type and humanized mice after intravaginal infection with HSV type 2 or cell-associated HIV type 1, respectively, but NET-EN treatment was associated with slower onset of HSV-induced genital pathology and lower burden of systemic HIV disease. These findings reveal DMPA and NET-EN treatment of mice significantly reduces genital desmoglein-1 levels and increases genital mucosal permeability and susceptibility to genital pathogens while also implying that NET-EN generates less compromise of genital mucosal barrier function than DMPA.

Do short-term markers of treatment efficacy predict long-term sequelae of pelvic inflammatory disease?

OBJECTIVE: This study was undertaken to assess whether short-term markers, often used to measure clinical cure after treatment for pelvic inflammatory disease, predict sequelae of lack of pregnancy, recurrent pelvic inflammatory disease, and chronic pelvic pain. STUDY DESIGN: Women with mild-to-moderate pelvic inflammatory disease were assessed after treatment initiation at 5 days for tenderness (n = 713) and at 30 days for tenderness, cervical infections and endometritis (n = 298). Pregnancy, recurrent pelvic inflammatory disease, and chronic pelvic pain were evaluated after 84 months, on average. RESULTS: Pelvic tenderness at 5 and at 30 days significantly elevated the risk for developing chronic pelvic pain; tenderness at 30 days was also significantly associated with recurrent pelvic inflammatory disease. However, pelvic tenderness at 5 and at 30 days was only modestly clinically predictive of chronic pelvic pain or recurrent pelvic inflammatory disease (positive predictive values 22.1-66.9%). No short-term marker significantly influenced the likelihood of achieving a pregnancy. CONCLUSION: Tenderness at 5 or 30 days did not accurately predict the occurrence of pelvic inflammatory disease-related reproductive morbidities.

Effectiveness of treatment strategies of some women with pelvic inflammatory disease: a randomized trial.

OBJECTIVE: Among all women with pelvic inflammatory disease (PID), prevention of adverse reproductive consequences appears to be similarly achieved by outpatient treatment and inpatient treatment. We assessed whether outpatient is as effective as inpatient treatment in relevant age, race, and clinical subgroups of women with PID. METHODS: Women with clinical signs and symptoms of mild-to-moderate pelvic inflammatory disease (n = 831) were randomized into a multicenter trial of inpatient treatment, initially employing intravenous cefoxitin and doxycycline compared with outpatient treatment consisting of a single intramuscular injection of cefoxitin and oral doxycycline. Comparisons between treatment groups during a mean of 84 months of follow-up were made for pregnancies, live births, time to pregnancy, infertility, PID recurrence, chronic pelvic pain, and ectopic pregnancy. RESULTS: Outpatient treatment assignment did not adversely impact the proportion of women having one or more pregnancies, live births, or ectopic pregnancies during follow-up; time to pregnancy; infertility; PID recurrence; or chronic pelvic pain among women of various races; with or without previous PID; with or without baseline Neisseria gonorrhoeae and/or Chlamydia trachomatis infection; and with or without high temperature/white blood cell count/pelvic tenderness score. This was true even in teenagers and women without a previous live birth. Ectopic pregnancies were more common in the outpatient than the inpatient treatment group, but because these were so rare, the difference did not reach statistical significance (5 versus 1, odds ratio 4.91, 95% confidence interval 0.57-42.25). CONCLUSION: Among all women and subgroups of women with mild-to-moderate PID, there were no differences in reproductive outcomes after randomization to inpatient or outpatient treatment. LEVEL OF EVIDENCE: I.

Spontaneous resolution of asymptomatic Chlamydia trachomatis in pregnancy.

OBJECTIVE: We sought to estimate the rate of spontaneous resolution of asymptomatic Chlamydia trachomatis in pregnancy and to evaluate factors associated with its resolution. METHODS: A cohort of women enrolled in a large multicenter randomized bacterial vaginosis antibiotic trial (metronidazole versus placebo) that, when randomly allocated, had asymptomatic C trachomatis diagnosed by urine ligase chain reaction (from frozen archival specimens) between 16(0/7) and 23(6/7) weeks were included. The urine ligase chain reaction is a highly accurate predictor of genital tract chlamydial infection. A follow-up ligase chain reaction was performed between 24(0/7) and 29(6/7) weeks. RESULTS: A total of 1,953 women were enrolled in the original antibiotic trial; 1,547 (79%) had ligase chain reaction performed both at randomization and follow-up. Women receiving antibiotics effective against Chlamydia between randomization and follow-up or having symptomatic Chlamydia infection were excluded (26 women). Of the 140 women (9%) who were diagnosed as positive via the initial ligase chain reaction assay, 61 (44%) had spontaneous resolution of Chlamydia by the follow-up ligase chain reaction assay. Factors associated with spontaneous resolution included older age (P = .02), more than 5 weeks from randomization to follow-up (P = .02), and a greater number of lifetime sexual partners (P = .02). Using a logistic regression model, maternal age and a greater-than-5-week follow-up interval remained significant; for every 5-year increase in maternal age, the odds of a positive result on the ligase chain reaction test at follow-up decreased by 40% (odds ratio 0.6; 95% confidence interval 0.4-0.9). Race, substance abuse, parity, and treatment with metronidazole were not associated with spontaneous resolution. Gram stain score and vaginal pH at randomization and follow-up also were not associated. CONCLUSION: The prevalence of asymptomatic C trachomatis in pregnancy was 9%; infection resolved spontaneously in almost half of these women. The association of older age and increasing time interval to spontaneous resolution of Chlamydia is consistent with a host immune-response mechanism.

Chlamydia antibodies, chlamydia heat shock protein, and adverse sequelae after pelvic inflammatory disease: the PID Evaluation and Clinical Health (PEACH) Study.

BACKGROUND: Among women with pelvic inflammatory disease (PID), we assessed the associations among antibodies to Chlamydia trachomatis elementary bodies (EB), antibodies to chlamydia heat shock protein (Chsp60), rates of pregnancy, and PID recurrence. METHODS: Four hundred forty-three women with clinical signs and symptoms of mild to moderate PID enrolled in the PID Evaluation and Clinical Health Study were followed for a mean of 84 months for outcomes of time-to-pregnancy and time-to-PID recurrence. Antibodies to EB and Chsp60 were assessed in relation to these long-term sequelae of PID. RESULTS: Rates of pregnancy were significantly lower (adj. hazard ratio 0.47, 95% confidence interval 0.28-0.79) and PID recurrence higher (adj. hazard ratio 2.48, 95% confidence interval 1.00-6.27) after adjusting for confounding factors among women whose antibody titers to chlamydia EB measured in the final year of follow-up were in the highest tertile. CONCLUSION: Among women with mild to moderate PID, antibodies to C. trachomatis were independently associated with reduced rates of pregnancy and elevated rates of recurrent PID.

Is bacterial vaginosis a stronger risk factor for preterm birth when it is diagnosed earlier in gestation?

OBJECTIVE: It is stated commonly that the earlier in pregnancy bacterial vaginosis is diagnosed, the greater is the increase in risk of preterm birth compared with women without bacterial vaginosis. However, this contention is based on small numbers of women. STUDY DESIGN: In this analysis of 12,937 women who were screened for bacterial vaginosis as part of a previously conducted clinical trial, the odds ratio of preterm birth (<7 weeks of gestation) for asymptomatic bacterial vaginosis-positive versus bacterial vaginosis-negative women was evaluated among women who were screened from 8 to 22 weeks of gestation. RESULTS: The odds ratio of preterm birth among bacterial vaginosis-positive versus bacterial vaginosis-negative women ranged from 1.1 to 1.6 and did not vary significantly according to the gestational age at which bacterial vaginosis was screened. The odds ratio for preterm birth did not vary significantly by gestational age at diagnosis when bacterial vaginosis was subdivided into Gram stain score 7 to 8 or 9 to 10. CONCLUSION: Although bacterial vaginosis was associated with an increased risk of preterm birth, the gestational age at which bacterial vaginosis was screened for and diagnosed did not influence the increase.

Early pregnancy threshold vaginal pH and Gram stain scores predictive of subsequent preterm birth in asymptomatic women.

OBJECTIVE: The study was undertaken to identify early pregnancy vaginal markers predictive of subsequent preterm birth. STUDY DESIGN: In a multicenter Bacterial Vaginosis (BV) Trial, 21,554 women were screened with a vaginal pH and of these, two populations were studied. These included 12,041 who had a pregnancy outcome in the database and 6838 women who had a vaginal pH of 4.5 or greater and a Gram stain score and a pregnancy outcome in the database. ColorpHast Indicator Strips were used to determine the vaginal pH and the Nugent criteria were used to determine a vaginal Gram stain score of 0 to 10. RESULTS: Delivery at <37, <35, or <32 weeks' gestation was similar for women with a vaginal pH of less than 4.4 or 4.7 (P not significant) but was increased in women with a pH of 5.0 (P =.04,.02,.03, respectively) or with a pH of 5.0 or greater (at each gestational age P <.0001). The effect of pH of 5.0 or greater was similar for women who had a spontaneous preterm birth at each gestational age (P <.0001) or birth weight of less than 2500 g or less than 1500 g (P <.0005). Women with a vaginal pH of 4.5 or greater and a Gram stain score of 9 to 10 (compared with 0-8) had increased preterm births at <37, <35, and <32 weeks' gestation (P <.01), and birth weights less than 2500 g (P <.0001) or less than 1500 g (P <.01). Women whose vaginal pH was 5.0 or greater had a higher prevalence of vaginal fetal fibronectin > or =50 ng/mL (P <.0001), but the proportion of women with a vaginal fetal fibronectin > or =50 mg/mL did not differ by Gram stain score. CONCLUSION: Women with a vaginal pH of 5.0 or greater or a vaginal pH of 4.5 or greater and a Gram stain score of 9 to 10 had significantly increased preterm births at <37, <35, and 32 weeks' gestation and/or a birth weight less than 2500 g or less than 1500 g.

Sexual intercourse association with asymptomatic bacterial vaginosis and Trichomonas vaginalis treatment in relationship to preterm birth.

OBJECTIVE: The purpose of this study was to determine whether sexual intercourse was associated with the treatment efficacy or the incidence of preterm birth in two large randomized trials in which metronidazole treatment of bacterial vaginosis or Trichomonas vaginalis did not reduce preterm birth. STUDY DESIGN: Secondary analysis of two multicenter, double-blind, placebo-controlled trials in which women with asymptomatic bacterial vaginosis on Gram stain or asymptomatic T vaginalis on culture were randomized at 16 to 23 weeks of gestation to metronidazole or placebo. In both studies, women took 2 g of metronidazole or placebo in the presence of a nurse (first dose) and were given a second dose to take 48 hours later. This regimen was repeated (third and fourth doses) at 24 to 29 weeks. At the time of the third dose, bacterial vaginosis and T vaginalis specimens were collected again. Patients who were randomly selected to receive metronidazole were analyzed for bacterial vaginosis and T vaginalis at 24 to 29 weeks and for preterm birth of <37 weeks of gestation, according to intercourse between first and second doses and between the second and third doses. Continuous variables were compared with the use of the Wilcoxon rank-sum test; categoric variables were compared with the use of the chi(2 ) test, Fisher exact test, or the Mantel-Haenzel test of trend. RESULTS: Sexual intercourse between the first and second doses or between the second and third doses did not influence the incidence of bacterial vaginosis (18% vs 24%; relative risk, 0.7; 95% CI, 0.5-1.1; and 23% vs 20%; relative risk, 1.2; 95% CI, 0.9-1.6, respectively) or T vaginalis (4% vs 8%; relative risk, 0.5; 95% CI, 0.1-3.6; and 5% vs 10%; relative risk, 0.5; 95% CI, 0.2-1.1; respectively) at 24 to 29 weeks of gestation compared with no intercourse. In the T vaginalis trial, sexual intercourse between the first and second doses or between the second and third doses did not influence the incidence of preterm birth (13% vs 17%; relative risk, 0.8; 95% CI, 0.3-2.1; and 16% vs 17%; relative risk, 1.0; 95% CI, 0.6-1.6; respectively) compared with no intercourse. In the bacterial vaginosis trial, although sexual intercourse between the first and second doses did not influence the incidence of preterm birth (11% vs 12%; relative risk, 0.9; 95 % CI, 0.6-1.5), sexual intercourse between the second and third doses was associated with a reduction in the incidence of preterm birth (10% vs 16%; relative risk, 0.6; 95% CI, 0.4-0.9) compared with no intercourse. CONCLUSION: Sexual intercourse was associated with neither the efficacy of metronidazole treatment of bacterial vaginosis or T vaginalis nor with the incidence of preterm birth. In the bacterial vaginosis study, intercourse between the second and third doses had a negative association with preterm birth.