Longitudinal assessment of nonavalent vaccine HPV types in a sample of sexually active African American women from ten U.S. Cities.

BACKGROUND: Chronic infection with high-risk human papillomavirus is a necessary cause for cervical carcinogenesis. This study examined prevalence of nonavalent vaccine preventable HPV types over four months among sexually active women in the United States. METHODS: This sub-study obtained meta-data for 80 of the 1,365 women (18-25 years), enrolled in the BRAVO study, a randomized, open-label trial of home screening and treatment of asymptomatic bacterial vaginosis at high-risk for sexually transmitted infections conducted between 2008 and 2013. Participants were randomized to treatment or standard-of-care, and followed every 2-months for 12 months. Stored vaginal swabs from the first three visits were tested for the nine vaccine preventable HPV types using quantitative PCR. Prevalence and associated 95% confidence intervals for the HPV types were assessed using R (version 3.6.1). RESULTS: The average age of the participants was 21.5 (SD ± 2.11) years, with 60% having ever been pregnant and all were African-American. Majority (71%) reported ≥ two sex partners in the prior year with 89% having unprotected vaginal sex and 45% having a new sex partner in the prior year. About 30% had ≥ one of the nine nonavalent vaccine HPV types at all three time points over a period of four months, 15% at two of any three visits, 19% at one of the three visits and 36% were negative for all nine vaccine HPV types at all time points. The most frequently detected HPV vaccine types were 52, 58, 16, and 18. The prevalence of any vaccine HPV types, and high-risk HPV types was 63.8% and 58.8%, respectively. CONCLUSIONS: Our findings suggest that HPV vaccination which is currently recommended for all unvaccinated persons through age 26 years, is likely to be more beneficial than previously thought as nonavalent HPV vaccine was not available during the time these data were collected.

Clinical performance of the Solana® Point-of-Care Trichomonas Assay from clinician-collected vaginal swabs and urine specimens from symptomatic and asymptomatic women.

BACKGROUND: Solana® (Quidel) is a new rapid (<40 min.) point-of-care (POC) test for qualitative detection of Trichomonas vaginalis (TV) DNA. The assay has two steps: 1) specimen preparation, and 2) amplification and detection using isothermal Helicase-Dependent Amplification (HDA). The objective was to demonstrate the performance of Solana for vaginal swabs and female urines based on comparison to wet mount and TV culture. Performance was also compared to the Aptima-TV assay. METHODS: Urine and four clinician-collected vaginal swabs were collected. The first two were used for FDA composite reference (wet mount; InPouch TV Culture). The third swab was used for Solana. Sensitivity/specificity were based on the reference method. A specimen was considered positive if either test was positive. The fourth swab was for Aptima-TV. RESULTS: Vaginal swabs and urines were obtained from 501 asymptomatic and 543 symptomatic women. Prevalence of TV by was 11.5%. For swabs, Solana® demonstrated high sensitivity and specificity from asymptomatic (100%/98.9%) and symptomatic (98.6%/98.5%) women, as well as for urines from asymptomatic (98.0%/98.4%) and symptomatic (92.9%/97.9%) women, compared to the reference method. Compared to Aptima-TV, the sensitivity/specificity was 89.7%/99.0% for swabs and 100%/98.9% for urines. CONCLUSION: The Solana® assay performed well compared to the reference assays.

ESwab as an optional collection device for use with the Affirm VPIII microbial test system.

The ESwab collection device was compared to the collection swab provided as part of the Affirm VPIII microbial identification test kit for testing vaginal specimens with the Affirm test system. There was excellent agreement between the two sampling devices for Candida spp., Gardnerella vaginalis, and Trichomonas vaginalis.

Gardnerella vaginalis: Still a Prime Suspect in the Pathogenesis of Bacterial Vaginosis.

Bacterial vaginosis (BV) is the most common cause of vaginal infection, yet its pathogenesis remains controversial. Although it has never been proven to be a sexually transmitted diseases the epidemiological evidence favoring this is quite robust. Although BV is characterized by its polymicrobial nature, it is highly likely that the inciting organism is Gardnerella vaginalis.

Re-evaluating the treatment of nongonococcal urethritis: emphasizing emerging pathogens--a randomized clinical trial.

BACKGROUND: Nongonococcal urethritis (NGU) is a common chlamydia-associated syndrome in men; however, Trichomonas vaginalis and Mycoplasma genitalium are associated with its etiology and should be considered in approaches to therapy. We sought to determine whether the addition of tinidazole, an anti-trichomonal agent, to the treatment regimen would result in higher cure rates than those achieved with treatment with doxycycline or azithromycin alone. A secondary aim was to compare the efficacy of doxycycline therapy and with that of azithromycin therapy. METHODS: Randomized, controlled, double-blinded phase IIB trial of men with NGU. Participants were randomized to receive doxycycline plus or minus tinidazole or azithromycin plus or minus tinidazole and were observed for up to 45 days. RESULTS: The prevalences of Chlamydia trachomatis, M. genitalium, and T. vaginalis were 43%, 31%, and 13%, respectively. No pathogens were identified in 29% of participants. Clinical cure rates at the first follow-up visit were 74.5% (111 of 149 patients) for doxycycline-containing regimens and 68.6% (107 of 156 patients) for azithromycin-containing regimens. By the final visit, cure rates were 49% (73 of 149 patients) for doxycycline-containing regimens and 43.6% (68 of 156 patients) for azithromycin-containing regimens. There were no significant differences in clinical response rates among the treatment arms. However, the chlamydia clearance rate was 94.8% (55 of 58 patients) for the doxycycline arm and 77.4% (41 of 53 patients) for the azithromycin arm (P = .011), and the M. genitalium clearance rate was 30.8% (12 of 39 patients) for the doxycycline arm and 66.7% (30 of 45 patients) for the azithromycin arm (P = .002). CONCLUSIONS: Addition of tinidazole to the treatment regimen did not result in higher cure rates but effectively eradicated trichomonas. Clinical cure rates were not significantly different between patients treated with doxycycline and those treated with azithromycin; however, doxycycline had significantly better efficacy against Chlamydia, whereas azithromycin was superior to doxycycline for the treatment of M. genitalium.

Viability of Trichomonas vaginalis in Copan universal transport medium and eSwab transport medium.

We compared the use of universal transport medium and eSwab transport medium held at room temperature or 37 degrees C to bedside inoculation and immediate incubation of culture media for the detection of Trichomonas vaginalis. There were no significant culturable differences in the sensitivity of either of the transport media to that of bedside inoculation.

The polymicrobial hypothesis of bacterial vaginosis causation: a reassessment.

The cause of bacterial vaginosis remains controversial. The two leading hypotheses are that Gardnerella vaginalis is the specific aetiologic agent versus the polymicrobial hypothesis that G. vaginalis acts in concert with other bacteria, principally anaerobes, to produce the disease. Here we reassess the prevailing polymicrobial hypothesis, finding it conceptually problematical. No host initiating factors as postulated have been identified, nor is there conclusive evidence that G. vaginalis lacks diagnostic specificity for the disease. The polymicrobial hypothesis, presupposing a unique disruption of vaginal microecology, is inconsistent with the epidemiological profile of the syndrome, which is that of a sexually transmitted disease. The epidemiological and clinical similarities between bacterial vaginosis and trichomoniasis suggest a similar pathogenetic process; i.e., primary causation by a specific agent, with secondary anaerobic activation and resultant amine production.

A randomized trial of the duration of therapy with metronidazole plus or minus azithromycin for treatment of symptomatic bacterial vaginosis.

BACKGROUND: Bacterial vaginosis (BV) is the most common cause of vaginitis worldwide. Currently recommended treatments have poor efficacy and are associated with high rates of BV recurrence. We examined whether a longer duration of treatment with metronidazole or combination therapy with metronidazole and azithromycin would enhance the cure rates for BV. In addition, we examined factors other than drug therapy associated with cure. METHODS: Women with symptomatic BV (defined by a modified Amsel criteria) were enrolled in a 4-arm study that compared metronidazole for 7 days versus 14 days, plus or minus azithromycin on days 1 and 3. Data regarding interim behaviors were also obtained, as were vaginal specimens for Gram staining. RESULTS: At the first follow-up visit (7 days after the completion of therapy), there was a significant difference in cure rates among patients who received 7 days of metronidazole therapy, compared with those who received 14 days of therapy, combined across azithromycin therapy (P=.0003). There was no effect associated with azithromycin therapy. There were no differences in cure rates between any of the treatment groups at 21 days after completion of therapy. Abstinence or protected sex, refraining from douching, and a lower baseline Nugent score for the vaginal Gram stain were all significantly associated with cure. CONCLUSIONS: Cure rates for BV were significantly improved by 14 days of metronidazole treatment (compared with 7 days of treatment), but the effects were not sustained, suggesting that relapse or reinfection occurred. Combination therapy with the addition of azithromycin had no benefit. Lower baseline Nugent scores--presumably reflecting less complex vaginal flora--were significantly associated with cure, as was refraining from unprotected sex and from douching.

Vaginal leucocyte counts in women with bacterial vaginosis: relation to vaginal and cervical infections.

OBJECTIVES: To evaluate whether an elevated vaginal leucocyte count in women with bacterial vaginosis (BV) predicts the presence of vaginal or cervical infections, and to assess the relation of vaginal WBC counts to clinical manifestations. METHODS: We retrospectively analysed the relation of vaginal leucocyte counts to vaginal and cervical infections and to clinical manifestations in non-pregnant women diagnosed with BV at an STD clinic visit. RESULTS: Of 296 women with BV studied, the median age was 24 years and 81% were African-American. Elevated vaginal leucocyte counts were associated with objective signs of vaginitis and cervicitis and also predicted candidiasis (OR 7.9, 95% CI 2.2 to 28.9), chlamydia (OR 3.1, 95% CI 1.4 to 6.7), gonorrhoea (OR 2.7, 95% CI 1.3 to 5.4), or trichomoniasis (OR 3.4, 95% CI 1.6 to 7.3). In general, as a screening test for vaginal or cervical infections, vaginal leucocyte count had moderate sensitivities and specificities, low positive predictive values, and high negative predictive values. CONCLUSIONS: An elevated vaginal leucocyte count in women with BV was a strong predictor of vaginal or cervical infections. Vaginal leucocyte quantification may provide an alternative approach to assessing need for empirical therapy for chlamydia and gonorrhoea, particularly in resource-limited high STD risk settings that provide syndromic management.

Update of trichomoniasis.

Trichomoniasis remains an extremely common infection despite the fact that rates of other treatable sexually transmitted diseases are declining. Newer diagnostic techniques such as polymerase chain reaction (PCR) are documenting higher rates of infection in heterosexual men than have been previously found with culture. Although data on the association of vaginal trichomoniasis with preterm birth are controversial, the association of trichomoniasis with HIV acquisition seems clear. Despite being a readily diagnosed and treated STD, trichomoniasis is not a reportable infection and control of the infection has received relatively little emphasis from public health STD control programmes. More recently, however, appreciation of high rates of disease and of associations of trichomoniasis in women with adverse outcomes of pregnancy and increased risk for HIV infection suggest a need for increased control efforts.

An international study of the interobserver variation between interpretations of vaginal smear criteria of bacterial vaginosis.

An international workshop on vaginal smear-based diagnosis of bacterial vaginosis was organized where 13 investigators scoring 258 slides with smears from vaginal fluid. Interobserver reproducibility of interpretations of Nugent scores, Hay/Ison scores and wet smear scores for the diagnosis of bacterial vaginosis was shown to be high. Detailed analysis of individual scoring results however indicated that basic standards of quality control to ensure robust individual readings of slides must be adhered to.

Prevalence of infectious diseases in Bangladeshi women living adjacent to a truck stand: HIV/STD/hepatitis/genital tract infections.

BACKGROUND: Little is known about infection rates for human immunodeficiency virus (HIV) and other diseases that can be transmitted sexually in Bangladeshi women who may be at intermediate levels of risk--that is, women who are not commercial sex workers (CSWs) but whose sexual contacts may include men at high risk for STD. This study examines HIV/hepatitis/STD and other genital tract infections in women living near Tejgaon truck stand in Dhaka, Bangladesh. METHODS: This population based study was conducted from January to December 1998. A random sample of 384 women provided urine and blood samples and participated in an interview; 261 of them also had a physical examination in which vaginal and cervical specimens were taken. Laboratory tests included PCR on urine and cervical swabs for gonorrhoea and chlamydia, culture for trichomoniasis, serology tests for syphilis, herpes simplex 2, hepatitis B, C, D, HIV1, HIV2, and clinical diagnoses of other genital tract infections. RESULTS: None of the participants tested positive for HIV. In the 261 women who had a physical examination, trichomoniasis was detected in 19.5%, chlamydia in 3.4%, gonorrhoea in 5.4%, bacterial vaginosis in 37.2%, and candidiasis in 10%. In the full sample of 384 women, with tests of urine and blood, prevalence of infection with chlamydia, gonorrhoea, syphilis, and herpes simplex 2 was detected in 0%, 6.3%, 5.7%, and 32% respectively. Almost 50% of the subjects had ever been exposed to hepatitis B, 3.6% were currently infective, 1.6% had hepatitis C, and none had hepatitis D. CONCLUSION: The high prevalence of certain of these infectious diseases indicates the need to implement prevention interventions with these women and, perhaps more importantly, with their male partners. Qualitative research is needed to provide insights into their sexual behaviour and the contexts in which high risk behaviours occur.

Evaluation of the Affirm Ambient Temperature Transport System for the detection and identification of Trichomonas vaginalis, Gardnerella vaginalis, and Candida species from vaginal fluid specimens.

The objective of this study was to measure the performance of the Affirm Ambient Temperature Transport System (ATTS) over time and to estimate the length of time the system can preserve a vaginal specimen containing the three common organisms causing vaginitis: Trichomonas vaginalis, Candida species, and Gardnerella vaginalis (one of the causative agents of bacterial vaginosis). Women with symptoms of vaginitis presenting to one of three clinical centers were evaluated over a 4- to 8-week period. Four simultaneously obtained swabs were collected and tested by the Affirm VPIII assay at time zero with and without a preservative reagent, at 24 h with reagent, and at either 48 or 72 h with reagent. For each of the three organisms, Trichomonas, Gardnerella, and Candida, positivity at each time point was evaluated and compared to that at reference time zero with and without the ATTS. A total of 940 specimens were obtained from the three clinical sites. Eight hundred three were positive for one or more of the three organisms. Gardnerella had the highest overall positive rate (62%), followed by Candida with 18% and Trichomonas at 9%. The percent sensitivity versus control for Trichomonas ranged from 100% at time zero with and without reagent to 91% by 72 h. Gardnerella and Candida sensitivity remained at 100% for each time period. The Affirm VPIII ATTS system performed within 10% of the control swab (no transport reagent) at all four time points (0, 24, 48, and 72 h) for Trichomonas, Gardnerella, and Candida.

Midtrimester vaginal Mycoplasma genitalium in women with subsequent spontaneous preterm birth.

OBJECTIVE: We sought to determine the midtrimester prevalence of Mycoplasma genitalium in women who had subsequent spontaneous preterm birth. STUDY DESIGN: In a prospective study of lower genital tract infections, we identified 127 women who subsequently had spontaneous preterm birth. Vaginal samples were obtained between 21 and 25 weeks' gestation for pH, for bacterial vaginosis Gram stain, and cultures that yielded Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. M genitalium was identified by using validated polymerase chain reaction (PCR) primers, and the results were compared to pregnancy outcomes. RESULTS: Of 124 women with spontaneous preterm births, only five (3.9%) had PCR assays positive forM genitalium. The mean +/- SD delivery gestational age was similar for women with a positive PCR (34.6 +/- 2.2 weeks) and a negative PCR (34.0 +/- 2.7 weeks) (P =.62). None of the women with positive PCR results tested positive for any other sexually transmitted disease, whereas 36 (30%) women with negative PCR results tested positive. CONCLUSIONS: The occurrence of M genitalium in the vagina at midtrimester is infrequent in women with subsequent spontaneous preterm birth.

Prevalence of Mobiluncus spp among women with and without bacterial vaginosis as detected by polymerase chain reaction.

BACKGROUND: Mobiluncus spp are highly associated with bacterial vaginosis, but their role in its pathogenesis is unknown. The authors used polymerase chain reaction (PCR) to compare the prevalence of Mobiluncus in women with and without bacterial vaginosis. GOAL: To compare the prevalence of Mobiluncus spp among women with and without bacterial vaginosis and to compare the sensitivities of PCR and Gram stain for detection. STUDY DESIGN: Vaginal specimens from 74 women were analyzed by PCR and Gram stain for the presence of Mobiluncus spp. Comparisons were made between the prevalence of this organism between the two cohorts and between the Gram stain and PCR detection methods. RESULTS: Mobiluncus was detected by PCR in 84.5% of women with bacterial vaginosis and in 38% of women without infection. M curtisii was rarely detected in the latter group, though it was found in 65.3% of women with bacterial vaginosis. The sensitivity and specificity of Gram stain compared with PCR were 46.9% and 100%, respectively. CONCLUSIONS: Mobiluncus is more common in healthy women than previously suspected, with M mulieris as the predominant species. The significant difference in the prevalence of M curtisii between women with bacterial vaginosis and uninfected women suggests that this species could be involved in the pathogenesis of bacterial vaginosis.

Asymptomatic bacterial vaginosis: response to therapy.

OBJECTIVE: Bacterial vaginosis causes symptomatic vaginal discharge and has been associated with preterm birth and with the acquisition of human immunodeficiency virus. Half of all women with bacterial vaginosis are free of symptoms, and treatment of these women is controversial. The objective of this study was to determine the extent of poor symptom recognition in this group of women. STUDY DESIGN: Seventy-five women attending a sexually transmitted disease clinic who had asymptomatic bacterial vaginosis were entered into a randomized, double-blind, placebo-controlled trial comparing metronidazole gel with placebo. Subjects' perceptions about changes in vaginal discharge and odor were determined, and treatment and placebo groups were compared by means of standard statistical analysis. RESULTS: When subjects were stratified by treatment group, there were no differences in their retrospective assessments of vaginal discharge and odor. A subset of women who had normalization of clinical parameters or of Gram stain scores did admit retrospectively to improvement; however, the difference between this group and the group without normalization was not statistically significant. Twenty-one percent of treated women subsequently had vaginal candidiasis. CONCLUSIONS: A greater percentage of women with resolution of bacterial vaginosis did retrospectively notice improvement in vaginal discharge and odor in comparison with those women without resolution; however, this was not statistically significant. These findings do not support routine treatment of women with asymptomatic bacterial vaginosis.

Detection of trichomonosis in vaginal and urine specimens from women by culture and PCR.

Vaginal trichomonosis is a highly prevalent infection which has been associated with human immunodeficiency virus acquisition and preterm birth. Culture is the current "gold standard" for diagnosis. As urine-based testing using DNA amplification techniques becomes more widely used for other sexually transmitted diseases (STDs) such as gonorrhea and chlamydia, a similar technique for trichomonosis would be highly desirable. Women attending an STD clinic for a new complaint were screened for Trichomonas vaginalis by wet-preparation (wet-prep) microscopy and culture and for the presence of T. vaginalis DNA by specific PCR of vaginal and urine specimens. The presence of trichomonosis was defined as the detection of T. vaginalis by direct microscopy and/or culture from either vaginal samples or urine. The overall prevalence of trichomonosis in the population was 28% (53 of 190). The sensitivity and specificity of PCR using vaginal samples were 89 and 97%, respectively. Seventy-four percent (38 of 51) of women who had a vaginal wet prep or vaginal culture positive for trichomonads had microscopic and/or culture evidence of the organisms in the urine. Two women were positive for trichomonads by wet prep or culture only in the urine. The sensitivity and specificity of PCR using urine specimens were 64 and 100%, respectively. These results indicate that the exclusive use of urine-based detection of T. vaginalis is not appropriate in women. PCR-based detection of T. vaginalis using vaginal specimens may provide an alternative to culture.