Efficacy of single-dose oral secnidazole for the treatment of trichomoniasis in women co-infected with trichomoniasis and bacterial vaginosis: a post hoc subgroup analysis of phase 3 clinical trial data

Objectives Bacterial vaginosis (BV) and trichomoniasis are the most common causes of vaginitis. Both infections are associated with increased risk of acquisition and transmission of HIV and other sexually transmitted infections as well as adverse reproductive health outcomes. Co-infection is common, with rates ranging from 60% to 80%. We evaluated the efficacy of single-dose oral secnidazole 2 g for the treatment of trichomoniasis in a subgroup of women co-infected with BV and trichomoniasis.Design Post hoc analysis of data from a phase 3 randomised, double-blind, placebo-controlled, delayed-treatment study.Setting 10 centres in the USA.Participants Subgroup of women (aged ≥12 years) with a confirmed diagnosis of Trichomonas vaginalis and co-infection with BV clinically diagnosed using Amsel’s criteria.Intervention Single dose of secnidazole 2 g or placebo.Outcome measures The primary efficacy outcome was the microbiological cure (negative culture for T. vaginalis) at the test of cure (TOC) visit 6–12 days after dosing in the modified intent-to-treat population (mITT). At TOC, participants received the opposite treatment.Results Of the 131 T. vaginalis-infected participants in the mITT, 79 (60.3%) met ≥3 Amsel’s criteria for BV at enrolment. Microbiological cure rates for trichomoniasis at TOC among this subgroup of women were 97.7% (42/43) for secnidazole and 0% (0/36) for placebo.Conclusion Single-dose oral secnidazole 2 g was highly efficacious in curing trichomoniasis in women co-infected with BV. Appropriate and effective treatment options for co-infection are essential for reducing transmission and reinfection. Secnidazole is the only single-dose medication approved by the Food and Drug Administration for the treatment of BV in women and trichomoniasis in women and men.Trial registration number ClinicalTrials.gov, NCT03935217; post-results

The Role of <i>Prevotella</i> Species in Female Genital Tract Infections

Female genital tract infections (FGTIs) include vaginal infections (e.g., bacterial vaginosis [BV]), endometritis, pelvic inflammatory disease [PID], and chorioamnionitis [amniotic fluid infection]. They commonly occur in women of reproductive age and are strongly associated with multiple adverse health outcomes including increased risk of HIV/sexually transmitted infection acquisition and transmission, infertility, and adverse birth outcomes such as preterm birth. These FGTIs are characterized by a disruption of the cervicovaginal microbiota which largely affects host immunity through the loss of protective, lactic acid-producing Lactobacillus spp. and the overgrowth of facultative and strict anaerobic bacteria. Prevotella species (spp.), anaerobic Gram-negative rods, are implicated in the pathogenesis of multiple bacterial FGTIs. Specifically, P. bivia, P. amnii, and P. timonensis have unique virulence factors in this setting, including resistance to antibiotics commonly used in treatment. Additionally, evidence suggests that the presence of Prevotella spp. in untreated BV cases can lead to infections of the upper female genital tract by ascension into the uterus. This narrative review aims to explore the most common Prevotella spp. in FGTIs, highlight their important role in the pathogenesis of FGTIs, and propose future research in this area

Prevalence of and Factors Associated with Genital and Extragenital Chlamydia and Gonorrhea among Transgender Women in HIV Care in the United States; 2005-2016

BACKGROUND: Data on testing rates and prevalence of and factors associated with genital and extragenital chlamydia and gonorrhea among transgender women with HIV in the United States are limited. METHODS: This retrospective cohort analysis included transgender women living with HIV enrolled in the US Centers for AIDS Research Network of Integrated Clinical Systems cohort between January 2005 and December 2016 with chlamydia or gonorrhea testing performed in HIV clinic. The primary outcome was a positive test result for chlamydia or gonorrhea at urogenital or extragenital (rectal/pharyngeal) sites. Factors associated with infection were examined using logistic regression and generalized estimating equations to account for multiple tests per woman. RESULTS: Among 312 transgender women in HIV care, 252 (81%) were tested for chlamydia or gonorrhea at least once. Annual testing rates were low: 23% to 53% at genital sites and 24% to 47% at extragenital sites. A total of 88 infections were detected, and 22% of women (55/252) had at least one positive test result. Most infections occurred at extragenital sites (80% of chlamydia and 82% of gonorrhea positive test results). Factors associated with infection in an adjusted model were as follows: age 18 to 29 years compared with ≥50 years (adjusted odds ratio [aOR], 7.6; 95% confidence interval [CI], 1.8–31.2), CD4 count >350 compared with CD4 <200 (aOR, 5.5; 95% CI, 1.2–25.1), and higher engagement in HIV care (aOR, 2.2; 95% CI, 1.0–4.5). CONCLUSIONS: Among transgender women living with HIV testing rates for chlamydia and gonorrhea are inadequate, particularly at extragenital sites where most infections occur

Prevalence of and Factors Associated With Genital and Extragenital Chlamydia and Gonorrhea Among Transgender Women in HIV Care in the United States, 2005 to 2016.

BackgroundData on testing rates and prevalence of and factors associated with genital and extragenital chlamydia and gonorrhea among transgender women with HIV in the United States are limited.MethodsThis retrospective cohort analysis included transgender women living with HIV enrolled in the US Centers for AIDS Research Network of Integrated Clinical Systems cohort between January 2005 and December 2016 with chlamydia or gonorrhea testing performed in HIV clinic. The primary outcome was a positive test result for chlamydia or gonorrhea at urogenital or extragenital (rectal/pharyngeal) sites. Factors associated with infection were examined using logistic regression and generalized estimating equations to account for multiple tests per woman.ResultsAmong 312 transgender women in HIV care, 252 (81%) were tested for chlamydia or gonorrhea at least once. Annual testing rates were low: 23% to 53% at genital sites and 24% to 47% at extragenital sites. A total of 88 infections were detected, and 22% of women (55/252) had at least one positive test result. Most infections occurred at extragenital sites (80% of chlamydia and 82% of gonorrhea positive test results). Factors associated with infection in an adjusted model were as follows: age 18 to 29 years compared with ≥50 years (adjusted odds ratio [aOR], 7.6; 95% confidence interval [CI], 1.8-31.2), CD4 count &gt;350 compared with CD4 &lt;200 (aOR, 5.5; 95% CI, 1.2-25.1), and higher engagement in HIV care (aOR, 2.2; 95% CI, 1.0-4.5).ConclusionsAmong transgender women living with HIV, testing rates for chlamydia and gonorrhea are inadequate, particularly at extragenital sites where most infections occur

Impact of testosterone use on the vaginal microbiota of transgender men, including susceptibility to bacterial vaginosis: study protocol for a prospective, observational study

Introduction The effect of testosterone (T) therapy on the vaginal microbiota of transgender men (TGM) is not well characterised, although one cross-sectional study comparing the vaginal microbiota of cisgender women to TGM on T≥1 year found that, in 71% of the TGM, the vaginal microbiota was less likely to be Lactobacillus-dominated and more likely to be enriched with &gt;30 other bacterial species, many associated with bacterial vaginosis (BV). This prospective study aims to investigate changes in the composition of the vaginal microbiota over time in TGM who retain their natal genitalia (ie, vagina) and initiate T. In addition, we will identify changes in the vaginal microbiota preceding incident BV (iBV) in this cohort while investigating behavioural factors, along with hormonal shifts, which may be associated with iBV.Methods and analysis T-naïve TGM who have not undergone gender-affirming genital surgery with normal baseline vaginal microbiota (ie, no Amsel criteria, normal Nugent Score with no Gardnerella vaginalis morphotypes) will self-collect daily vaginal specimens for 7 days prior to initiating T and for 90 days thereafter. These specimens will be used for vaginal Gram stain, 16S rRNA gene sequencing and shotgun metagenomic sequencing to characterise shifts in the vaginal microbiota over time, including development of iBV. Participants will complete daily diaries on douching, menses and behavioural factors including sexual activity during the study.Ethics and dissemination This protocol is approved through the single Institutional Review Board mechanism by the University of Alabama at Birmingham. External relying sites are the Louisiana State University Health Sciences Center, New Orleans Human Research Protection Program and the Indiana University Human Research Protection Program. Study findings will be presented at scientific conferences and peer-reviewed journals as well as shared with community advisory boards at participating gender health clinics and community-based organisations servicing transgender people.Registration details Protocol # IRB-300008073

Microbial interactions among Gardnerella, Prevotella and Fannyhessea prior to incident bacterial vaginosis: protocol for a prospective, observational study

Introduction The aetiology of bacterial vaginosis (BV), a biofilm-associated vaginal infection, remains unknown. Epidemiologic data suggest that it is sexually transmitted. BV is characterised by loss of lactic acid-producing lactobacilli and an increase in facultative and strict anaerobic bacteria. Gardnerella spp are present in 95%–100% of cases; Gardnerella vaginalis has been found to be more virulent than other BV-associated bacteria (BVAB) in vitro. However, G. vaginalis is found in women with normal vaginal microbiota and colonisation is not sufficient for BV development. We hypothesise that Gardnerella spp initiate BV biofilm formation, but incident BV (iBV) requires incorporation of other key BVAB (ie, Prevotella bivia, Fannyhessea vaginae) into the biofilm that alter the transcriptome of the polymicrobial consortium. This study will investigate the sequence of microbiologic events preceding iBV.Methods and analysis This study will enrol 150 women aged 18–45 years with normal vaginal microbiota and no sexually transmitted infections at a sexual health research clinic in Birmingham, Alabama. Women will self-collect twice daily vaginal specimens up to 60 days. A combination of 16S rRNA gene sequencing, qPCR for Gardnerella spp, P. bivia and F. vaginae, and broad range 16S rRNA gene qPCR will be performed on twice daily vaginal specimens from women with iBV (Nugent score 7–10 on at least 2 consecutive days) and controls (with comparable age, race, contraceptive method and menstrual cycle days) maintaining normal vaginal microbiota to investigate changes in the vaginal microbiota over time for women with iBV. Participants will complete daily diaries on multiple factors including sexual activity.Ethics and dissemination This protocol is approved by the University of Alabama at Birmingham Institutional Review Board (IRB-300004547) and written informed consent will be obtained from all participants. Findings will be presented at scientific conferences and published in peer-reviewed journals as well as disseminated to providers and patients in communities of interest

Recruiting transgender men in the Southeastern United States for genital microbiome research: Lessons learned

Background: Transgender men (TGM) are underrepresented in genital microbiome research. Our prospective study in Birmingham, AL investigated genital microbiota changes over time in TGM initiating testosterone, including the development of incident bacterial vaginosis (iBV). Here, we present lessons learned from recruitment challenges encountered during the conduct of this study. Methods: Inclusion criteria were assigned female sex at birth, TGM or non-binary identity, age ≥18 years, interested in injectable testosterone but willing to wait 7 days after enrollment before starting, and engaged with a testosterone-prescribing provider. Exclusion criteria were recent antibiotic use, HIV/STI infection, current vaginal infection, pregnancy, or past 6 months testosterone use. Recruitment initiatives included community advertisements via flyers, social media posts, and referrals from local gender health clinics. Results: Between February 2022 and October 2023, 61 individuals contacted the study, 17 (27.9%) completed an in-person screening visit, and 10 (58.8%) of those screened were enrolled. The primary reasons for individuals failing study screening were having limited access to testosterone-prescribing providers, already being on testosterone, being unwilling to wait 7 days to initiate testosterone therapy, or desiring the use of topical testosterone. Engagement of non-White TGM was also minimal. Conclusion: Despite robust study inquiry by TGM, screening and enrollment challenges were faced including engagement by TGM not yet in care and specific study eligibility criteria. Excitement among TGM for research representation should be leveraged in future work by engaging transgender community stakeholders at the inception of study development, particularly regarding feasibility of study inclusion and exclusion criteria, as well as recruitment of TGM of color. These results also highlight the need for more clinical resources for prescribing gender-affirming hormone therapy, especially in the Southeastern US