Diagnosis and Management of Bacterial Vaginosis: Summary of Evidence Reviewed for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infections Treatment Guidelines.

In preparation for the 2021 Centers for Disease Control and Prevention (CDC) sexually transmitted infections (STIs) treatment guidelines, the CDC convened an advisory group in 2019 to examine recent literature addressing updates in the epidemiology, diagnosis, and management of STIs. This article summarizes recent data in each of these key topic areas as they pertain to bacterial vaginosis (BV), the most common cause of vaginal discharge. The evidence reviewed primarily focused on updates in the global epidemiology of BV, risk factors for BV, data supportive of sexual transmission of BV-associated bacteria, BV molecular diagnostic tests, and novel treatment regimens. Additionally, recent literature on alcohol abstinence in the setting of 5-nitroimidazole use was reviewed.

Phase 2 Randomized Study of Oral Ibrexafungerp Versus Fluconazole in Vulvovaginal Candidiasis.

BACKGROUND: Vulvovaginal candidiasis affects approximately 75% of women in their lifetime. Approved treatment options are limited to oral or topical azoles. Ibrexafungerp, a novel, first-in-class oral triterpenoid glucan synthase inhibitor, has demonstrated broad fungicidal Candida activity and a favorable tolerability profile. The primary objective of this dose-finding study was to identify the optimal dose of oral ibrexafungerp in patients with acute vulvovaginal candidiasis. METHODS: Patients with vulvovaginal signs and symptoms score ≥7 were randomized equally to 6 treatments groups: 5 treatment doses of oral ibrexafungerp or oral fluconazole 150 mg. The primary endpoint was the percentage of patients with a clinical cure (complete resolution of vulvovaginal signs and symptoms) at the test-of-cure visit (day 10). RESULTS: Overall, 186 patients were randomized into the 6 treatment groups. Results, using the modified intent-to-treat population (baseline positive culture), are reported for ibrexafungerp 300 mg twice daily (BID) for 1 day (n = 27), which was the dose selected for phase 3 studies, and fluconazole 150 mg for 1 day (n = 24). At day 10, the clinical cure rates for ibrexafungerp and fluconazole were 51.9% and 58.3%, respectively; at day 25, patients with no signs or symptoms were 70.4% and 50.0%, respectively. During the study ibrexafungerp patients required less antifungal rescue medications compared with fluconazole (3.7% vs 29.2%, respectively). Ibrexafungerp was well tolerated, with the most common treatment-related adverse events being mild gastrointestinal events. CONCLUSIONS: Ibrexafungerp is a well-tolerated novel antifungal with comparable efficacy to fluconazole in the treatment of acute vulvovaginal candidiasis. CLINICAL TRIALS REGISTRATION: NCT03253094.

Ibrexafungerp Versus Placebo for Vulvovaginal Candidiasis Treatment: A Phase 3, Randomized, Controlled Superiority Trial (VANISH 303).

BACKGROUND: Current treatment of vulvovaginal candidiasis (VVC) is largely limited to azole therapy. Ibrexafungerp is a first-in-class triterpenoid antifungal with broad-spectrum anti-Candida fungicidal activity. The objective of this study was to evaluate the efficacy and safety of ibrexafungerp compared with placebo in patients with acute VVC. METHODS: Patients were randomly assigned 2:1 to receive ibrexafungerp (300 mg twice for 1 day) or placebo. The primary endpoint was the percentage of patients with a clinical cure (complete resolution of vulvovaginal signs and symptoms [VSS] = 0) at test-of-cure (day 11 ± 3). Secondary endpoints included the percentage of patients with mycological eradication, overall success (clinical cure and mycological eradication), clinical improvement (VSS ≤ 1) at test-of-cure, and symptom resolution at follow-up (day 25 ± 4). RESULTS: Patients receiving ibrexafungerp had significantly higher rates of clinical cure (50.5% [95/188] vs 28.6% [28/98]; P = .001), mycological eradication (49.5% [93/188] vs 19.4% [19/98]; P < .001), and overall success (36.0% [64/178] vs 12.6% [12/95]; P < .001) compared with placebo. Symptom resolution was sustained and further increased with ibrexafungerp compared with placebo (59.6% [112/188] vs 44.9% [44/98]; P = .009) at follow-up. Post hoc analysis showed similar rates of clinical cure and clinical improvement at test-of-cure for Black patients (54.8% [40/73] and 63.4% [47/73], respectively) and patients with a body mass index >35 (54.5% [24/44] and 68.2% [30/44], respectively) compared with overall rates. Ibrexafungerp was well tolerated. Adverse events were primarily gastrointestinal and mild in severity. CONCLUSIONS: Ibrexafungerp provides a promising safe and efficacious oral treatment that mechanistically differs from current azole treatment options for acute VVC.

Association of Bacterial Vaginosis With Higher Vaginal Indole Levels.

ABSTRACT: We adapted a simple hydroxylamine-based indole assay to detect indole from stored vaginal swab specimens from women with and without bacterial vaginosis (BV). Women with BV had significantly higher vaginal indole levels compared with women without BV (6451.5 vs 5632.4 µM; P = 0.01), suggesting that indole-producing bacteria are a component of BV.

Evaluating the Efficacy of Eradicating Gardnerella vaginalis Vaginal Colonization With Amoxicillin: A Randomized, Double-Blind, Phase 2 Study.

BACKGROUND: Research suggests that Gardnerella vaginalis (GV) is the keystone pathogen in bacterial vaginosis (BV). Knowledge gaps exist regarding the role of GV eradication in the development of BV. This study was designed to test the hypothesis that vaginal colonization with GV could be eradicated by treatment of women without BV with amoxicillin, a drug highly active against GV. If GV is necessary for the development of BV, then eradication of GV may prevent the development of BV. METHODS: We conducted a randomized control trial of amoxicillin 500 mg twice daily versus placebo for 7 days in women aged 18 to 45 years without vaginitis who screened positive for vaginal colonization with GV by quantitative polymerase chain reaction. Test-of-cure visit for GV was conducted at day 21. RESULTS: One hundred seventy-two women met preliminary criteria and were screened for enrollment. Ninety-seven GV-positive women were randomized to receive amoxicillin versus placebo. Eradication of GV occurred in 21% of women randomized to amoxicillin versus 16% on placebo (P = 0.757). In the 4 weeks between screening and test-of-cure visit, 16 of 92 (17%) of participants developed Nugent scores greater than 3 with 8 of 92 (9%) having BV. All of these were in participants in whom GV was not eradicated (P = 0.035). CONCLUSIONS: The study failed to show a benefit of treatment with amoxicillin to eradicate GV. No participants in whom GV was eradicated had progression to abnormal vaginal flora during the study period.

Treatment of Male Sexual Partners of Women With Bacterial Vaginosis: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: We aimed to determine if treatment of male sexual partners of women with recurrent bacterial vaginosis (BV) with oral metronidazole 2×/day for 7 days (ie, multidose metronidazole) significantly decreased BV recurrence rates in the female. METHODS: This was a multicenter, 2-arm, double-blind, placebo-controlled study. Women with recurrent BV and current diagnosis of BV by Amsel and Nugent were enrolled. Multidose metronidazole for 7 days was dispensed to women. Male partners were randomized to placebo versus multidose metronidazole for 7 days and asked to refrain from unprotected sex for 14 days. Female follow-up visits were conducted at day 21 and 8 and 16 weeks. Male follow-up visits occurred at days 14-21. BV cure was defined as 0-2 Amsel criteria and Nugent score 0-6 in the female partner with the primary endpoint at 16 weeks. RESULTS: 214 couples were enrolled. In the intent-to-treat population, there was no significant difference between treatment arms for the primary outcome. BV treatment failure occurred in 81% and 80% of women in the metronidazole and placebo arms through the third follow-up visit, respectively (P > .999). However, women whose male partners adhered to study medication were less likely to fail treatment (adjusted relative risk, .85; 95% CI, .73-.99; P = .035). This finding persisted in post hoc comparisons in the metronidazole arm. CONCLUSIONS: Overall, this study did not find that male partner treatment with multidose metronidazole significantly reduces BV recurrence in female partners, although women whose partners adhered to multidose metronidazole were less likely to fail treatment. CLINICAL TRIALS REGISTRATION: (NCT02209519).

Efficacy and Safety of Single Oral Dosing of Secnidazole for Trichomoniasis in Women: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled, Delayed-Treatment Study.

BACKGROUND: Trichomonas vaginalis is the most prevalent nonviral sexually transmitted infection. We evaluated the efficacy and safety of secnidazole vs placebo in women with trichomoniasis. METHODS: Women with trichomoniasis, confirmed by a positive T. vaginalis culture, were randomized to single-dose oral secnidazole 2 g or placebo. The primary endpoint was microbiological test of cure (TOC) by culture 6-12 days after dosing. At the TOC visit, participants were given the opposite treatment. They were followed for resolution of infection afterward and offered treatment at subsequent visits, if needed. Fifty patients per group (N = 100) provided approximately 95% power to detect a statistically significant difference between treatment groups. RESULTS: Between April 2019 and March 2020, 147 women enrolled at 10 sites in the United States. The modified intention-to-treat (mITT) population included 131 randomized patients (secnidazole, n = 64; placebo, n = 67). Cure rates were significantly higher in the secnidazole vs placebo group for the mITT population (92.2% [95% confidence interval {CI}: 82.7%-97.4%] vs 1.5% [95% CI: .0%-8.0%]) and for the per-protocol population (94.9% [95% CI: 85.9%-98.9%] vs 1.7% [95% CI: .0%-8.9%]). Cure rates were 100% (4/4) in women with human immunodeficiency virus (HIV) and 95.2% (20/21) in women with bacterial vaginosis (BV). Secnidazole was generally well tolerated. The most frequently reported treatment-emergent adverse events (TEAEs) were vulvovaginal candidiasis and nausea (each 2.7%). No serious TEAEs were observed. CONCLUSIONS: A single oral 2 g dose of secnidazole was associated with significantly higher microbiological cure rates vs placebo, supporting a role for secnidazole in treating women with trichomoniasis, including those with HIV and/or BV. CLINICAL TRIALS REGISTRATION: NCT03935217.

Clinical Validation of the Aptima Bacterial Vaginosis and Aptima Candida/Trichomonas Vaginitis Assays: Results from a Prospective Multicenter Clinical Study.

Infectious vaginitis due to bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and Trichomonas vaginalis accounts for a significant proportion of all gynecologic visits in the United States. A prospective multicenter clinical study was conducted to validate the performance of two new in vitro diagnostic transcription-mediated amplification nucleic acid amplification tests (NAATs) for diagnosis of BV, VVC, and trichomoniasis. Patient- and clinician-collected vaginal-swab samples obtained from women with symptoms of vaginitis were tested with the Aptima BV and Aptima Candida/Trichomonas vaginitis (CV/TV) assays. The results were compared to Nugent (plus Amsel for intermediate Nugent) scores for BV, Candida cultures and DNA sequencing for VVC, and a composite of NAAT and culture for T. vaginalis The prevalences of infection were similar for clinician- and patient-collected samples: 49% for BV, 29% for VVC due to the Candida species group, 4% for VVC due to Candida glabrata, and 10% for T. vaginalis Sensitivity and specificity estimates for the investigational tests in clinician-collected samples were 95.0% and 89.6%, respectively, for BV; 91.7% and 94.9% for the Candida species group; 84.7% and 99.1% for C. glabrata; and 96.5% and 95.1% for T. vaginalis Sensitivities and specificities were similar in patient-collected samples. In a secondary analysis, clinicians' diagnoses, in-clinic assessments, and investigational-assay results were compared to gold standard reference methods. Overall, the investigational assays had higher sensitivity and specificity than clinicians' diagnoses and in-clinic assessments, indicating that the investigational assays were more predictive of infection than traditional diagnostic methods. These results provide clinical-efficacy evidence for two in vitro diagnostic NAATs that can detect the main causes of vaginitis.

Host-vaginal microbiota interactions in the pathogenesis of bacterial vaginosis.

PURPOSE OF REVIEW: The cause of bacterial vaginosis, the most common cause of vaginal discharge in women, remains controversial. We recently published an updated conceptual model on bacterial vaginosis pathogenesis, focusing on the roles of Gardnerella vaginalis and Prevotella bivia as early colonizers and Atopobium vaginae and other bacterial vaginosis-associated bacteria (BVAB) as secondary colonizers in this infection. In this article, we extend the description of our model to include a discussion on the role of host-vaginal microbiota interactions in bacterial vaginosis pathogenesis. RECENT FINDINGS: Although G. vaginalis and P. bivia are highly abundant in women with bacterial vaginosis, neither induce a robust inflammatory response from vaginal epithelial cells. These early colonizers may be evading the immune system while establishing the bacterial vaginosis biofilm. Secondary colonizers, including A. vaginae, Sneathia spp., and potentially other BVAB are more potent stimulators of the host-immune response to bacterial vaginosis and likely contribute to its signs and symptoms as well as its adverse outcomes. SUMMARY: Elucidating the cause of bacterial vaginosis has important implications for diagnosis and treatment. Our current bacterial vaginosis pathogenesis model provides a framework for key elements that should be considered when designing and testing novel bacterial vaginosis diagnostics and therapeutics.

Use of a Novel Couples' Verification Tool in a Male Partner Treatment Study of Women With Recurrent Bacterial Vaginosis.

Verification of relationship status beyond self-report is an important aspect in sexually transmitted infection research, including partner treatment studies where primary sexual partners are targeted for enrollment. This exploratory study describes the use of a novel couples' verification tool in a male partner treatment study of women with recurrent bacterial vaginosis.

A systematic review of the literature on mechanisms of 5-nitroimidazole resistance in Trichomonas vaginalis.

BACKGROUND: Trichomonas vaginalis is the most common non-viral sexually transmitted infection. 5-Nitroimidazoles [metronidazole (MTZ) and tinidazole (TDZ)] are FDA-approved treatments. To better understand treatment failure, we conducted a systematic review on mechanisms of 5-nitroimidazole resistance. METHODS: PubMed, ScienceDirect and EMBASE databases were searched using keywords Trichomonas vaginalis, trichomoniasis, 5-nitroimidazole, metronidazole, tinidazole and drug resistance. Non-English language articles and articles on other treatments were excluded. RESULTS: The search yielded 606 articles, of which 550 were excluded, leaving 58 articles. Trichomonas vaginalis resistance varies and is higher with MTZ (2.2-9.6%) than TDZ (0-2%). Resistance can be aerobic or anaerobic and is relative rather than absolute. Differential expression of enzymes involved in trichomonad energy production and antioxidant defenses affects 5-nitroimidazole drug activation; reduced expression of pyruvate:ferredoxin oxidoreductase, ferredoxin, nitroreductase, hydrogenase, thioredoxin reductase and flavin reductase are implicated in drug resistance. Trichomonas vaginalis infection with Mycoplasma hominis or T. vaginalis virus has also been associated with resistance. Trichomonas vaginalis has two genotypes, with greater resistance seen in type 2 (vs type 1) populations. DISCUSSION: 5-Nitroimidazole resistance results from differential expression of enzymes involved in energy production or antioxidant defenses, along with genetic mutations in the T. vaginalis genome. Alternative treatments outside of the 5-nitroimidazole class are needed.

An Updated Conceptual Model on the Pathogenesis of Bacterial Vaginosis.

Bacterial vaginosis (BV) is the most common cause of vaginal discharge. It is associated with an increased risk of preterm delivery, pelvic inflammatory disease, and an increased risk of acquisition of sexually transmitted infections including human immunodeficiency virus (HIV). The epidemiology of BV supports sexual transmission. However, its etiology remains unknown. At the center of the debate is whether BV is caused by a primary pathogen or a polymicrobial consortium of microorganisms that are sexually transmitted. We previously published a conceptual model hypothesizing that BV is initiated by sexual transmission of Gardnerella vaginalis. Critics of this model have iterated that G. vaginalis is found in virginal women and in sexually active women with a normal vaginal microbiota. In addition, colonization does not always lead to BV. However, recent advances in BV pathogenesis research have determined the existence of 13 different species within the genus Gardnerella. It may be that healthy women are colonized by nonpathogenic Gardnerella species, whereas virulent strains are involved in BV development. Based on our results from a recent prospective study, in addition to an extensive literature review, we present an updated conceptual model for the pathogenesis of BV that centers on the roles of virulent strains of G. vaginalis, as well as Prevotella bivia and Atopobium vaginae.

Trichomonas vaginalis Virus Among Women With Trichomoniasis and Associations With Demographics, Clinical Outcomes, and Metronidazole Resistance.

BACKGROUND: Trichomonas vaginalis virus (TVV) is a non-segmented, 4.5-5.5 kilo-base pair (kbp), double-stranded RNA virus infecting T. vaginalis. The objectives of this study were to examine the TVV prevalence in US Trichomonas vaginalis isolates and TVV's associations with patient demographics, clinical outcomes, and metronidazole resistance. METHODS: Archived T. vaginalis isolates from the enrollment visits of 355 women participating in a T. vaginalis treatment trial in Birmingham, Alabama, were thawed and grown in culture. Their total RNA was extracted using a Trizol reagent. Contaminating, single-stranded RNA was precipitated using 4.0 M Lithium Chloride and centrifugation. The samples were analyzed by gel electrophoresis to visualize a 4.5 kbp band representative of TVV. In vitro testing for metronidazole resistance was also performed on 25/47 isolates obtained from the women's test of cure visits. RESULTS: TVV was detected in 142/355 (40%) isolates at the enrollment visit. Women with TVV-positive (TVV+) isolates were significantly older (P = .01), more likely to smoke (P = .04), and less likely to report a history of gonorrhea (P = .04). There was no association between the presence of clinical symptoms or repeat T. vaginalis infections with TVV+ isolates (P = .14 and P = .44, respectively). Of 25 test of cure isolates tested for metronidazole resistance, 0/10 TVV+ isolates demonstrated resistance, while 2/15 TVV-negative isolates demonstrated mild to moderate resistance (P = .23). CONCLUSIONS: Of 355 T. vaginalis isolates tested for TVV, T. vaginalis isolates tested for TVV, the prevalence was 40%. However, there was no association of TVV+ isolates with clinical symptoms, repeat infections, or metronidazole resistance. These results suggest that TVV may be commensal to T. vaginalis.

Incubation period and risk factors support sexual transmission of bacterial vaginosis in women who have sex with women.

OBJECTIVE: The epidemiology of bacterial vaginosis (BV) favours sexual transmission of BV-associated bacteria. We examined incubation period and risk factors for incident BV (iBV) in a prospective study of women who have sex with women (WSW). METHODS: Using daily self-collected vaginal swabs, WSW with normal vaginal microbiota (no Amsel criteria and a Nugent score of 0-3) were followed for 90 days or until iBV (Nugent score 7-10 on at least 2-3 consecutive days). Daily diaries of sexual activity and menses were completed. Time to iBV was estimated. Accounting for differing lengths of follow-up and age, rates of sexual activities (per 100 person-days (pd)) were compared according to iBV status. The relationship between menses and iBV was also investigated. RESULTS: Of the 36 WSW, the mean age was 30 years (SD 8) and 92% were African American. The probability of iBV at 30 and 60 days was 20% (SD 7%) and 36% (SD 8%), respectively; 14 (39%) developed iBV by 90 days. In WSW with iBV versus those without iBV, the relative rate of any sexual activity prior to iBV was 40% higher (20.4 vs 14.6 per 100 pd; p=0.010), sex with a woman was 38% higher (14.3 vs 10.3 per 100 pd; p=0.038), digital-vaginal sex was 57% higher (14.3 vs 9.1 per 100 pd; p=0.005) and digital-anal sex was 5.6 times higher (2.9 vs 0.5 per 100 pd; p<0.001). iBV was more likely for those WSW with menses in the prior 2 days as compared with those without recent menses (HR 3.4; p=0.029). Sexual activity occurred in 93% WSW at a median of 4 days (95% CI 2 to 6) prior to iBV. CONCLUSION: iBV was common and associated with sexual activity in this cohort of predominantly African American WSW. An incubation period of 4 days is consistent with other bacterial STIs.

Delay in Seeking Health Care Services After Onset of Urethritis Symptoms in Men.

BACKGROUND: Symptom awareness, behavioral factors, and other barriers associated with timely sexually transmitted infection (STI) health care provision in men is not well studied. METHODS: Men attending an STI clinic answered a questionnaire regarding their symptoms, sexual behavior, and sociodemographic and behavioral characteristics. Characteristics of symptomatic men were compared between those who did and did not delay seeking health care services. Delayed care seeking was defined as clinic attendance longer than 7 days after symptoms, whereas early care seeking was defined as clinic attendance of 7 days or less. RESULTS: Over a quarter (n = 43 [27.7%]) of men with urethritis symptoms (urethral discharge or dysuria) delayed seeking care for more than 7 days. Compared with men who sought treatment within 7 days, those that delayed care worried for longer periods that their symptoms were STI-related, were more likely to attempt self-treatment of STI symptoms, were more likely to continue engaging in sexual activity, and were less likely to use a condom during their last sexual encounter. Conversely, men that delayed care seeking were less likely to have urethral discharge on physical examination, to have 5 or more polymorphonuclear leukocytes, and to test positive for Neisseria gonorrhoeae. When compared with men that sought care earlier, men that delayed care seeking had fewer overall and new partners in the past 30 days. CONCLUSIONS: Our data suggest that over a quarter of men aware of STI symptoms delay seeking health services. Interventions that promote better patient understanding of the importance of symptom recognition and that facilitate timely access to care may provide new opportunities to reduce STI transmission.

Identification of Key Bacteria Involved in the Induction of Incident Bacterial Vaginosis: A Prospective Study.

Background: The sequence of events preceding incident bacterial vaginosis (iBV) is unclear. Methods: African American women who have sex with women, who had no Amsel criteria and Nugent scores of 0-3, were followed for 90 days to detect iBV (defined as a Nugent score of 7-10 on at least 2-3 consecutive days), using self-collected vaginal swab specimens. For women with iBV (cases) and women maintaining normal vaginal flora (healthy women), 16S ribosomal RNA gene sequencing targeting V4 was performed. Longitudinal vaginal microbiome data were analyzed. Results: Of 204 women screened, 42 enrolled; of these, 45% developed iBV. Sequencing was performed on 448 specimens from 14 cases and 8 healthy women. Among healthy women, Lactobacillus crispatus dominated the vaginal microbiota in 75%. In contrast, prior to iBV, the vaginal microbiota in 79% of cases was dominated by Lactobacillus iners and/or Lactobacillus jensenii/Lactobacillus gasseri. The mean relative abundance of Prevotella bivia, Gardnerella vaginalis, Atopobium vaginae, and Megasphaera type I became significantly higher in cases 4 days before (P. bivia), 3 days before (G. vaginalis), and on the day of (A. vaginae and Megasphaera type I) iBV onset. The mean relative abundance of Sneathia sanguinegens, Finegoldia magna, BV-associated bacteria 1-3, and L. iners was not significantly different between groups before onset of iBV. Conclusion: G. vaginalis, P. bivia, A. vaginae, and Megasphaera type I may play significant roles in iBV.

In Vitro Study of the Susceptibility of Clinical Isolates of Trichomonas vaginalis to Metronidazole and Secnidazole.

Nitroimidazoles (metronidazole [MTZ] and tinidazole [TNZ]) are the only drugs recommended for treatment of Trichomonas vaginalis infections. MTZ resistance occurs in 4% to 10% of cases of vaginal trichomoniasis (R. D. Kirkcaldy et al., Emerg Infect Dis 18:939-943, 2012; J. R. Schwebke and F. J. Barrientes, Antimicrob Agents Chemother 50:4209-4210, 2006) and TNZ resistance in 1% of cases (J. R. Schwebke and F. J. Barrientes, Antimicrob Agents Chemother 50:4209-4210, 2006). Emerging nitroimidazole-resistant trichomoniasis is concerning, because few alternatives to standard therapy exist. We assessed the prevalence of in vitro aerobic MTZ and secnidazole resistance among T. vaginalis isolates collected in 2015 to 2016 from 100 women in Birmingham, Alabama, with positive cultures. Archived specimens were treated with secnidazole or MTZ (0.2 to 400 µg/ml) for 48 h, according to U.S. Centers for Disease Control and Prevention protocols. Ninety-six (96%) of the 100 clinical Trichomonas isolates tested demonstrated lower minimum lethal concentrations for secnidazole than for MTZ, suggesting that secnidazole has better in vitro activity than MTZ.

Diagnostic Performance of a Molecular Test versus Clinician Assessment of Vaginitis.

Vaginitis is a common complaint, diagnosed either empirically or using Amsel's criteria and wet mount microscopy. This study sought to determine characteristics of an investigational test (a molecular test for vaginitis), compared to reference, for detection of bacterial vaginosis, Candida spp., and Trichomonas vaginalis Vaginal specimens from a cross-sectional study were obtained from 1,740 women (≥18 years old), with vaginitis symptoms, during routine clinic visits (across 10 sites in the United States). Specimens were analyzed using a commercial PCR/fluorogenic probe-based investigational test that detects bacterial vaginosis, Candida spp., and Trichomonas vaginalis Clinician diagnosis and in-clinic testing (Amsel's test, potassium hydroxide preparation, and wet mount) were also employed to detect the three vaginitis causes. All testing methods were compared to the respective reference methods (Nugent Gram stain for bacterial vaginosis, detection of the Candida gene its2, and Trichomonas vaginalis culture). The investigational test, clinician diagnosis, and in-clinic testing were compared to reference methods for bacterial vaginosis, Candida spp., and Trichomonas vaginalis The investigational test resulted in significantly higher sensitivity and negative predictive value than clinician diagnosis or in-clinic testing. In addition, the investigational test showed a statistically higher overall percent agreement with each of the three reference methods than did clinician diagnosis or in-clinic testing. The investigational test showed significantly higher sensitivity for detecting vaginitis, involving more than one cause, than did clinician diagnosis. Taken together, these results suggest that a molecular investigational test can facilitate accurate detection of vaginitis.

Clinical Evaluation of the Cepheid Xpert TV Assay for Detection of Trichomonas vaginalis with Prospectively Collected Specimens from Men and Women.

Trichomoniasis is the most prevalent curable sexually transmitted disease (STD). It has been associated with preterm birth and the acquisition and transmission of HIV. Recently, nucleic acid amplification tests (NAAT) have been FDA cleared in the United States for detection of Trichomonas vaginalis in specimens from both women and men. This study reports the results of a multicenter study recently conducted using the Xpert TV (T. vaginalis) assay to test specimens from both men and women. On-demand results were available in as little as 40 min for positive specimens. A total of 1,867 women and 4,791 men were eligible for inclusion in the analysis. In women, the performance of the Xpert TV assay was compared to the patient infected status (PIS) derived from the results of InPouch TV broth culture and Aptima NAAT for T. vaginalis The diagnostic sensitivities and specificities of the Xpert TV assay for the combined female specimens (urine samples, self-collected vaginal swabs, and endocervical swabs) ranged from 99.5 to 100% and 99.4 to 99.9%, respectively. For male urine samples, the diagnostic sensitivity and specificity were 97.2% and 99.9%, respectively, compared to PIS results derived from the results of broth culture for T. vaginalis and bidirectional gene sequencing of amplicons. Excellent performance characteristics were seen using both female and male specimens. The ease of using the Xpert TV assay should result in opportunities for enhanced screening for T. vaginalis in both men and women and, hopefully, improved control of this infection.

Defining the Urethritis Syndrome in Men Using Patient Reported Symptoms.

To evaluate self-reported symptoms to guide urethritis diagnosis, symptomatic men being evaluated for urethritis were asked about 7 symptoms captured during history taking. Discharge and dysuria were significantly associated with urethritis and, when combined with genital irritation and itching, identified 95% of urethritis cases; odor and urinary frequency performed poorly.