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The American Sexually Transmitted Diseases Association has, for several years, been conducting a cross-sector workshop to bring together a variety of stakeholders to develop ideas for collaboratively improving the sexually transmitted infection control efforts in the United States. In this summary, we share the content of discussions and ideas of the fourth annual workshop for future research and potential changes to practice with a focus on diagnostic capacity.

Background In vitro fluconazole resistance in vaginal C. albicans has rarely been reported in the U.S. Little is known about the characteristics of patients who demonstrate fluconazole resistance vs. sensitivity, or how likely resistant strains are to persist over time. Hence we sought to describe patterns of fluconazole resistance in clinician ordered vaginal cultures positive for C. albicans at our center. We compared patient characteristics between those with fluconazole sensitive versus resistant isolates. Methods We conducted a chart review of patients with clinician ordered vaginal cultures positive for C. albicans undergoing fluconazole susceptibility testing in our medical center’s clinical mycology lab from January 2017 to April 2021. Patient characteristics were compared using chi-square and ANOVA tests and correlated to fluconazole resistance with logistic regression models. Results Of N=92 patients with vaginal C. albicans, 3.3% were sensitive dose-dependent (SDD: minimal inhibitory concentration (MIC) =4) to fluconazole, and 30.4% were resistant (R: MIC > =8). Amongst those with at least 2 previous episodes of vulvovaginal candidiasis (VVC) in the past 6 months (N=45), 50% had R and 6.5% had SDD isolates. Compared to those with sensitive (S: MIC < =2) isolates, patients with SDD or R were younger and more likely to have the following characteristics: Black race, bacterial vaginosis (BV) in the past year, high or multi-dose azole treatment, fluconazole suppressive therapy in the past 6 months, and more VVC and BV episodes in the previous 6 months (Table 1). Of N=10 patients who had a follow-up culture with initial R isolates, 28.6% had a sensitive C. albicans vaginal isolate. Conclusion The frequency of C. albicans vaginal isolates with in vitro resistance to fluconazole in this study was high. Our findings highlight the importance of obtaining cultures and sensitivity testing in patients with recurrent or refractory VVC. However, resistant vaginal strains may not necessarily persist over time. Future, larger studies on those with recurrent VVC are needed to verify factors associated with fluconazole resistance, how frequently azole-resistant strains persist over time, and how well in vitro resistance correlates to in vivo treatment response. Disclosures Susan Tuddenham, MD, MPH, Luca Biologics: Advisor/Consultant|Medscape/WebMD: Honoraria|UpToDate: Royalties.

Background Limited data suggest that personal lubricants may damage the vaginal mucosal epithelium, alter the vaginal microbiota, and increase inflammation. We compared vaginal cytokine profiles and microbiota before and after vaginal lubricant use and condomless vaginal sex. Methods Reproductive-age women were recruited to a 10-week observational cohort study and were asked to self-collect vaginal samples and behavioral diaries daily. This nested case–control analysis utilized samples collected before and after self-reported condomless sexual activity with lubricants (22 case participants) and without lubricants (22 control participants). Controls were matched to cases on race/ethnicity. Microbiota composition was characterized by sequencing amplicons of the 16S rRNA gene V3–V4 regions. Cytokine concentrations were quantified using a magnetic bead 41-plex panel assay and read using a Bio-Plex 200 array reader. Wilcoxon signed-rank tests were used to assess baseline differences in vaginal cytokines between cases and controls as well as differences pre- and post-exposure. Linear mixed effects models were used to examine differences in relative post-to-pre change in each individual cytokine between matched cases and controls. Similar analyses were conducted for the microbiota data. Results Mean age was 29.8 years (SD 6.8), and 63.6% were African American. There were few statistically significant changes in cytokines or microbiota before and after exposure in cases or controls. In mixed-effects modeling, the mean relative post-to-pre change of cytokines was higher in cases vs. controls for macrophage derived chemokine (MDC) (p = 0.03). The microbiota data revealed no significant changes when measured by similarity scores, diversity indexes and descriptive community state types (CST) transition analyses. However, post sexual activity, the mean relative abundance of L. crispatus decreased for those who used lubricants (particularly those who were L. iners-dominated prior to exposure). Conclusions Although there were overall few differences in the vaginal microbiota and cytokine profiles of lubricant users and controls before and after condomless vaginal sex, there was a trend toward decreases in relative abundance of L. crispatus following use of lubricant. Future larger studies that take into account osmolarity and composition of lubricants may provide additional insights.

The goal of this study was to assess awareness of, interest in, and sources of knowledge about pre-exposure prophylaxis (PrEP) among 1,464 HIV-uninfected patients from public STD clinics in Baltimore. Logistic regression analyses were conducted to examine factors associated with PrEP awareness and interest. Results suggest PrEP awareness and interest in knowing more about PrEP was highest among men who reported sex with men or with both men and women. White patients were more likely to be aware of PrEP than African American patients, and those reporting consistent condom use were more likely to have heard about PrEP than those who never used condoms. The major source of knowledge about PrEP was health care providers. Findings can inform future prioritization of locally targeted PrEP programs to enhance access to and uptake of PrEP among those most at risk for HIV transmission.

A panel of experts generated 5 “key questions” in the management of adult syphilis. A systematic literature review was conducted and tables of evidence were constructed to answer these questions. Available data suggest no clinical benefit to >1 dose of benzathine penicillin G for early syphilis in human immunodeficiency virus (HIV)–infected patients. While penicillin remains the drug of choice to treat syphilis, doxycycline to treat early and late latent syphilis is an acceptable alternate option if penicillin cannot be used. There are very limited data regarding the impact of additional antibiotic doses on serologic responses in serofast patients and no data on the impact of additional antibiotic courses on long-term clinical outcomes. In patients with isolated ocular or otic signs and symptoms, reactive syphilis serologic results, and confirmed ocular/otic abnormalities at examination, a diagnostic cerebrospinal fluid (CSF) examination is not necessary, because up to 40% and 90% of patients, respectively, would have no CSF abnormalities. Based on the results of 2 studies, repeated CSF examinations are not necessary for HIV-uninfected patients or HIV-infected patients on antiretroviral therapy who exhibit appropriate serologic and clinical responses after treatment for neurosyphilis. Finally, several important gaps were identified and should be a priority for future research.

Bacterial vaginosis (BV), a condition in which vaginal Lactobacillus spp. are in low abundance, is associated with vulvovaginal symptoms, obstetric outcomes and urogenital infections. Recurrent BV is difficult to manage, and emerging data indicate a reduced risk of BV with the use of hormonal contraception (HC). Despite widespread use, little longitudinal data is available on whether, and in what timeframe, combined oral contraceptive pills (COCs) may act to affect vaginal microbiota stability and Lactobacillus dominance.We compared the vaginal microbiota of reproductive-age cisgender women during intervals on combined estrogen and progestin COCs with non-use intervals in a 2-year observational study. Vaginal microbiota were characterized by 16S rRNA gene amplicon sequencing.COC users were more likely to have Lactobacillus-dominated microbiota and more stable microbiota over time. Stability increased and then plateaued four weeks after COC initiation. The associations between COCs and Lactobacillus spp. dominance, and microbiota stability, were statistically significant for White, but not African American women; however sample size was limited for African American participants. Findings were similar for other forms of HC and when excluding samples collected during menses.Our study provides a methodologic framework to evaluate observational longitudinal microbiota data with exposure crossovers. We found COCs are associated with vaginal microbiota stability and a Lactobacillus-dominated state. COCs appear to impact stability within a month of initiation. Our findings have clinical implications for how soon benefits can be expected in (at least White) patients initiating COCs, and support the need for larger prospective trials to verify our results in ethnically diverse populations.R01-AI089878.

The human microbiome is constituted by an extensive network of organisms that lie at the host/environment interface and transduce signals that play vital roles in human health and disease across the lifespan. Frailty is a critical aging-related syndrome marked by diminished physiological reserve and heightened vulnerability to stress, predictive of major adverse clinical outcomes including death. While recent studies suggest the microbiome may impact key pathways critical to frailty pathophysiology, direct evaluation of the microbiome-frailty relationship remains limited. In this article, we review the complex interplay of biological, behavioral, and environmental factors that may influence shifts in gut microbiome composition and function in aging populations and the putative implications of such shifts for progression to frailty. We discuss HIV infection as a key prototype for elucidating the complex pathways via which the microbiome may precipitate frailty. Finally, we review considerations for future research efforts.

We reviewed the relevant syphilis diagnostic literature to address the following question: what are the performance characteristics, stratified by the stage of syphilis, for nontreponemal serologic tests? The database search included key terms related to syphilis and nontreponemal tests from 1960–2017, and for data related to the venereal disease research laboratory test from 1940–1960. Based on this review, we report the sensitivity and specificity for each stage of syphilis (primary, secondary, early latent, late latent, or unknown duration; tertiary as well as neurosyphilis, ocular syphilis, and otic syphilis). We also report on reactive nontreponemal tests in conditions other than syphilis, false negatives, and automated nontreponemal tests. Overall, many studies were limited by their sample size, lack of clearly documented clinical staging, and lack of well-defined gold standards. There is a need to better define the performance characteristics of nontreponemal tests, particularly in the late stages of syphilis, with clinically well-characterized samples. Published data are needed on automated nontreponemal tests. Evidence-based guidelines are needed for optimal prozone titrations. Finally, improved criteria and diagnostics for neurosyphilis (as well as ocular and otic syphilis) are needed.

Recent studies have raised interest in the possibility that dysbiosis of the gut microbiome (i.e., the communities of bacteria residing in the intestine) in HIV-infected patients could contribute to chronic immune activation, and, thus, to elevated mortality and increased risk of inflammation-related clinical diseases (e.g., stroke, cardiovascular disease, cancer, long-bone fractures, and renal dysfunction) found even in those on effective antiretroviral therapy. Yet, to date, a consistent pattern of HIV-associated dysbiosis has not been identified. What is becoming clear, however, is that status as a man who has sex with men (MSM) may profoundly impact the structure of the gut microbiota, and that this factor likely confounded many HIV-related intestinal microbiome studies. However, what factor associated with MSM status drives these gut microbiota-related changes is unclear, and what impact, if any, these changes may have on the health of MSM is unknown. In this review, we outline available data on changes in the structure of the gut microbiome in HIV, based on studies that controlled for MSM status. We then examine what is known regarding the gut microbiota in MSM, and consider possible implications for research and the health of this population. Lastly, we discuss knowledge gaps and needed future studies.

Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) are two highly prevalent bacterial sexually transmitted infections (STIs) with a significant rate of co-infection in some populations. Vaginal metabolites are influenced by resident vaginal microbiota, affect susceptibility to sexually transmitted infections (STIs), and may impact local inflammation and patient symptoms. Examining the vaginal metabolome in the context of CT mono (CT+) and CT/MG co-infection (CT+/MG+) may identify biomarkers for infection or provide new insights into disease etiology and pathogenesis. Yet, the vaginal metabolome in the setting of CT infection is understudied and the composition of the vaginal metabolome in CT/MG co-infected women is unknown. Therefore, in this analysis, we used an untargeted metabolomic approach combined with 16S rRNA gene amplicon sequencing to characterize the vaginal microbiota and metabolomes of CT+, CT+/MG+, and uninfected women. We found that CT+ and CT+/MG+ women had distinct vaginal metabolomic profiles as compared to uninfected women both before and after adjustment for the vaginal microbiota. This study provides important foundational data documenting differences in the vaginal metabolome between CT+, CT+/MG+ and uninfected women. These data may guide future mechanistic studies that seek to provide insight into the pathogenesis of CT and CT/MG infections.

Young people aged less than 25 years bear the highest burden of sexually transmitted infections (STIs) in the United States. Here we sought to characterize patients aged 15–24 compared with patients ≥age 25 utilizing a database of first visits to two STI clinics in Baltimore, USA from 2011 to 2016. Acute STI (aSTI) was defined as gonorrhea (GC), trichomonas, or early syphilis (ES) in women and non-gonococcal urethritis, GC, Chlamydia (CT), and ES in men. Proportions were compared using the Chi square test and logistic regression was used to assess aSTI predictors in younger versus older groups, stratified by gender. Fifteen thousand four hundred and sixty-three first visits for patients

Approximately 1 in 5 adults in the US had a sexually transmitted infection (STI) in 2018. This review provides an update on the epidemiology, diagnosis, and treatment of gonorrhea, chlamydia, syphilis, Mycoplasma genitalium, trichomoniasis, and genital herpes.From 2015 to 2019, the rates of gonorrhea, chlamydia, and syphilis increased in the US; from 1999 to 2016, while the rates of herpes simplex virus type 1 (HSV-1) and HSV-2 declined. Populations with higher rates of STIs include people younger than 25 years, sexual and gender minorities such as men and transgender women who have sex with men, and racial and ethnic minorities such as Black and Latinx people. Approximately 70% of infections with HSV and trichomoniasis and 53% to 100% of extragenital gonorrhea and chlamydia infections are asymptomatic or associated with few symptoms. STIs are associated with HIV acquisition and transmission and are the leading cause of tubal factor infertility in women. Nucleic acid amplification tests have high sensitivities (86.1%-100%) and specificities (97.1%-100%) for the diagnosis of gonorrhea, chlamydia, M genitalium, trichomoniasis, and symptomatic HSV-1 and HSV-2. Serology remains the recommended method to diagnose syphilis, typically using sequential testing to detect treponemal and nontreponemal (antiphospholipid) antibodies. Ceftriaxone, doxycycline, penicillin, moxifloxacin, and the nitroimidazoles, such as metronidazole, are effective treatments for gonorrhea, chlamydia, syphilis, M genitalium, and trichomoniasis, respectively, but antimicrobial resistance limits oral treatment options for gonorrhea and M genitalium. No cure is available for genital herpes. Effective STI prevention interventions include screening, contact tracing of sexual partners, and promoting effective barrier contraception.Approximately 1 in 5 adults in the US had an STI in 2018. Rates of gonorrhea, chlamydia, and syphilis in the US have increased, while rates of HSV-1 and HSV-2 have declined. Ceftriaxone, doxycycline, penicillin, moxifloxacin, and the nitroimidazoles are effective treatments for gonorrhea, chlamydia, syphilis, Mycoplasma genitalium, and trichomoniasis, respectively, but antimicrobial resistance limits oral therapies for gonorrhea and Mycoplasma genitalium, and no cure is available for genital herpes.

BACKGROUND Bacterial vaginosis (BV) is the most cited cause of vaginal complaints among women of reproductive age. Its etiology and associated risk factors are not entirely understood. Here we examined the association between BV and at-risk alcohol consumption in women attending 2 sexually transmitted infection (STI) clinics in Baltimore, MD. METHODS This was a retrospective cross-sectional analysis using data from first clinic visits from 2011-2016. At-risk alcohol use was defined as heavy episodic ("binge") drinking within the last 30 days or a self-report of having had vaginal or anal sex in the context of alcohol consumption. Pearson χ2 test and Student t test were used to assess baseline associations. Log binomial models were used to estimate prevalence ratios (PRs) before and after adjustments for potential confounding factors. RESULTS Of the 10,991 women included in the analysis, 2173 (19.7%) met the clinical diagnostic criteria for BV. Having had vaginal or anal sex in the context of alcohol consumption was associated with an increased risk of BV (PR, 1.25; 95% confidence interval, 1.13-1.37), as was binge drinking (PR, 1.15; 95% confidence interval, 1.04-1.27) after adjustment for confounders. CONCLUSIONS In this population, at-risk alcohol consumption was associated with an increased risk of BV. The mechanisms remain uncertain. Future prospective studies are needed to verify and evaluate causality in these associations.

There is an urgent need for innovative methods to reduce transmission of bloodborne pathogens like HIV and HCV among people who inject drugs (PWID). We investigate if PWID who acquire non-pathogenic bloodborne viruses like anelloviruses and pegiviruses might be at greater risk of acquiring a bloodborne pathogen. PWID who later acquire HCV accumulate more non-pathogenic viruses in plasma than matched controls who do not acquire HCV infection. Additionally, phylogenetic analysis of those non-pathogenic virus sequences reveals drug use networks. Here we find first in Baltimore and confirm in San Francisco that the accumulation of non-pathogenic viruses in PWID is a harbinger for subsequent acquisition of pathogenic viruses, knowledge that may guide the prioritization of the public health resources to combat HIV and HCV., Spread of bloodborne infections, such as HCV and HIV, is a problem, particularly amongst people who inject drugs (PWID). Here, the authors describe and then confirm in observational PWID cohorts that those with more non-pathogenic viruses in plasma were more likely later to acquire HCV than PWID who had fewer of these non-pathogenic viruses.

Intravaginal boric acid (IBA) represents one of the only options available to treat azole-resistant vulvovaginal candidiasis (VVC) and is included as part of multiple national guidelines (including the United Kingdom and the United States) for the treatment of VVC or recurrent bacterial vaginosis. Novel products using IBA are under development for treatment and suppression of VVC and bacterial vaginosis. Use of over-the-counter or clinician-prescribed IBA in reproductive-aged women is already widespread and may increase further if drug resistance in VVC rises. However, IBA is not a Food and Drug Administration-approved drug, and safety data are sparse. Given these factors, it is important to understand the currently available data on the safety of IBA use. Herein, we set out to synthesize human and animal data (converting, where appropriate, dose and serum values to standard units to facilitate comparison) to answer 2 key questions: (1) What are the data on the safety of IBA use for women? and (2) What are the data on the safety of IBA use in pregnancy? We find that, despite gaps, available data suggest IBA use is safe, at least when used in doses commonly described in the literature as being prescribed by clinicians. Information on harms in pregnancy is limited, and data remain insufficient to change current guidelines, which recommend IBA avoidance in pregnancy.

Background Pelvic inflammatory disease (PID) leads to long-term reproductive consequences for cisgender women. Bacterial vaginosis (BV) and behavioral factors may play a role in PID pathogenesis. We assessed associations between BV, behavioral factors, and incident PID. Methods We analyzed participants (N = 2956) enrolled in the National Institutes of Health Longitudinal Study of Vaginal Flora, a cohort of nonpregnant cisgender women followed quarterly for 12 months. PID was defined by at least 1 of the following: cervical motion tenderness, uterine tenderness, or adnexal tenderness (160 cases). We tested associations between BV (measured using Nugent and Amsel criteria) and PID at the subsequent visit. Sociodemographic factors, sexual behaviors, and Chlamydia trachomatis (CT), untreated at baseline and concurrent with BV, were covariates in Cox proportional hazards models. Adjusting for the few Neisseria gonorrhoeae and Trichomonas vaginalis cases did not alter results. Results In multivariable modeling, Nugent-BV (adjusted hazard ratio [aHR], 1.53 [95% confidence interval {CI}, 1.05–2.21]), symptomatic Amsel-BV (aHR, 2.15 [95% CI, 1.23–3.75]), and vaginal douching (aHR, 1.47 [95% CI, 1.03–2.09]) were associated with incident PID. Conclusions BV was associated with incident PID in a large prospective cohort, controlling for behavioral factors and sexually transmitted infections (STIs). Larger studies on how BV, STIs, behaviors, and host responses interactively affect PID risk are needed.

ObjectivesCurrent guidelines recommend screening sexually active persons with HIV (PWH) for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) at least annually. Yet, screening rates in many HIV clinics remain low. In this study, we estimated the number needed to screen (NNS) to detect a NG and/or CT infection at each anatomic site among different subpopulations of PWH. NNS provides a concrete, practical measure to aid in assessing the practical impact of screening.Methods We included adults in care at three HIV Research Network sites in 2011–2014. Restricting to first tests within each year, annual NNS was defined as number of persons tested divided by number positive. We computed urogenital and extragenital NNS by age and risk group (women, men who have sex with women (MSW) and men who have sex with men (MSM)).Results A total of 16 864 NG/CT tests were included. Among patients aged ≤25 years, urogenital NNS was similar among women (15 (95% CI 6 to 71)), MSW (21 (95% CI 6 to 167)) and MSM (20 (95% CI 12 to 36)). Over 25, urogenital NNS increased to a greater extent for women (363 (95% CI 167 to 1000)) and MSW (160 (95% CI 100 to 333)) than MSM (46 (95% CI 38 to 56)). The increase for women versus MSM >25 remained significant (p25 years and pharyngeal NNS values were 8 (95% CI 5 to 13) and 20 (95% CI 16 to 24).ConclusionsThese findings suggest the importance of regular, at least annual NG/CT screening, particularly extragenital, of HIV positive MSM of all ages. They provide some support for age-based cutoffs for women and MSW (eg, universal screening for those aged ≤25 and targeted screening for those aged >25 years).

BackgroundWhether human immunodeficiency virus (HIV) infection impacts gut microbial α-diversity is controversial. We reanalyzed raw 16S ribosomal RNA (rRNA) gene sequences and metadata from published studies to examine α-diversity measures between HIV-uninfected (HIV–) and HIV-infected (HIV+) individuals.MethodsWe conducted a systematic review and individual level meta-analysis by searching Embase, Medline, and Scopus for original research studies (inception to 31 December 2017). Included studies reported 16S rRNA gene sequences of fecal samples from HIV+ patients. Raw sequence reads and metadata were obtained from public databases or from study authors. Raw reads were processed through standardized pipelines with use of a high-resolution taxonomic classifier. The χ2 test, paired t tests, and generalized linear mixed models were used to relate α-diversity measures and clinical metadata.ResultsTwenty-two studies were identified with 17 datasets available for analysis, yielding 1032 samples (311 HIV–, 721 HIV+). HIV status was associated with a decrease in measures of α-diversity (P < .001). However, in stratified analysis, HIV status was associated with decreased α-diversity only in women and in men who have sex with women (MSW) but not in men who have sex with men (MSM). In analyses limited to women and MSW, controlling for HIV status, women displayed increased α-diversity compared with MSW.ConclusionsOur study suggests that HIV status, sexual risk category, and gender impact gut microbial community α-diversity. Future studies should consider MSM status in gut microbiome analyses.

Meta-analysis is a practical and powerful analytic tool that enables a unified statistical inference across the results from multiple studies. Notably, researchers often report the results on multiple related markers in each study (eg, various α-diversity indices in microbiome studies). However, univariate meta-analyses are limited to combining the results on a single common marker at a time, whereas existing multivariate meta-analyses are limited to the situations where marker-by-marker correlations are given in each study. Thus, here we introduce two meta-analysis methods, multi-marker meta-analysis (mMeta) and adaptive multi-marker meta-analysis (aMeta), to combine multiple studies throughout multiple related markers with no priori results on marker-by-marker correlations. mMeta is a statistical estimator for a pooled estimate and its SE across all the studies and markers, whereas aMeta is a statistical test based on the test statistic of the minimum P-value among marker-specific meta-analyses. mMeta conducts both effect estimation and hypothesis testing based on a weighted average of marker-specific pooled estimates while estimating marker-by-marker correlations non-parametrically via permutations, yet its power is only moderate. In contrast, aMeta closely approaches the highest power among marker-specific meta-analyses, yet it is limited to hypothesis testing. While their applications can be broader, we illustrate the use of mMeta and aMeta to combine microbiome studies throughout multiple α-diversity indices. We evaluate mMeta and aMeta in silico and apply them to real microbiome studies on the disparity in α-diversity by the status of human immunodeficiency virus (HIV) infection. The R package for mMeta and aMeta is freely available at https://github.com/hk1785/mMeta.

Unique compositional and functional features of the cervicovaginal microbiota have been associated with protection against and risk for sexually transmitted infections (STI). In men, our knowledge of the interaction between the penile microbiota and STI is less developed. The current state of our understanding of these microbiota and their role in select STIs is briefly reviewed, along with strategies that leverage existing findings to manipulate genital microbiota and optimize protection against STIs. Finally, we focus on major research gaps and present a framework for future studies.

IntroductionMany US women report same sex behaviour, yet data on risk factors and STIs in women who have sex with women (WSW), women who have sex with both men and women (WSB) and how these compare to women who have sex with men only (WSM) remain limited. Here we compared self-identified WSW, WSB and WSM attending two STI clinics in Baltimore, Maryland.MethodsThis was a retrospective analysis using a database of first clinic visits 2005–2016. WSW and WSB were compared with an age-matched random sample of WSM. Proportions were compared using the χ2 test. Acute STI (aSTI) was defined as gonorrhoea (Neisseria gonorrhoeae, GC), chlamydia (Chlamydia trachomatis, CT), trichomonas (Trichomonas vaginalis, TV) or early syphilis. Logistic regression was used to assess aSTI predictors. CT testing was not uniformly done, so a sensitivity analysis removing CT from the aSTI definition was conducted.ResultsVisits from 1095 WSW, 1678 WSB and 2773 WSM were analysed. WSB had equal or higher test positivity for all STIs except urogenital chlamydia, had more sexual partners, were more likely to engage in transactional sex and were more likely to report drug use and binge drinking than WSM (p≤0.01). WSW had lower test positivity for urogenital GC and CT than WSM or WSB, but comparable test positivity for TV, higher reported binge drinking and comparable reported substance use as WSM. Younger age and cocaine use predicted STI diagnosis only in WSM.ConclusionsWSB in these clinics bear an equal or higher burden of most STIs, have more partners and report more substance use than WSM. WSW carry a lower, but still substantial burden of STIs, and many report substance use. Factors predicting STI diagnosis differ between WSW, WSB and WSM suggesting that tailored STI prevention and testing approaches are needed in these groups.

A retrospective chart review characterized clinicians' use of maintenance intravaginal boric acid for women with recurrent vulvovaginal candidiasis or bacterial vaginosis. Average length of use was 13 months with high patient satisfaction and few adverse events. Prospective studies are needed to evaluate the efficacy of maintenance boric acid for these conditions.

Summary Background & aims Women with bacterial vaginosis (BV) have increased risk of sexually transmitted infections and other adverse health outcomes. Based on the composition of their vaginal microbiota, women can broadly be classified into low-Lactobacillus (termed molecular-BV) and Lactobacillus-dominated profiles. Our objective was to determine the association between dietary macronutrient intake and molecular-BV. Methods In a cross-sectional study of 104 reproductive-age women, dietary intake data were obtained using the Block Brief 2000 food frequency questionnaire. Vaginal microbiota composition was characterized by sequencing amplicons of the 16S rRNA gene V3–V4 regions and clustering into community state types (CST). Logistic regression was used to determine the association of macronutrient intake with molecular-BV (low-Lactobacillus vs. Lactobacillus-dominated CSTs combined). Results Participants had a median age of 25.9 (interquartile range: 21.9–29.6), 58% were white (30% black), 51% overweight/obese and 52% on hormonal contraception. In multivariable models, diets richer in fiber were inversely associated with molecular-BV (adjusted odds ratio: 0.49 per standard deviation increase in energy-adjusted fiber intake, 95% confidence interval: 0.24–0.99; p = 0.049). Conclusions Our results indicate that diets richer in fiber were associated with lower odds of molecular-BV. Further studies are needed to confirm these findings and to test whether increasing fiber intake can modulate the microbiota towards a more optimal Lactobacillus-dominant profile.

Background Bacterial vaginosis (BV) is characterized by low-Lactobacilli and increased anaerobes. BV can be determined by clinical assessment (Amsel’s criteria) or microscopy (Nugent scoring); molecular methods are also under study. We investigated concordance between Amsel-BV, Nugent-BV and low-Lactobacillus vaginal microbiota identified via 16S rRNA gene sequencing. Methods Vaginal swabs and clinical data were collected from women enrolled in a longitudinal study. Amsel’s criteria were determined clinically and Nugent scoring (Nugent-BV=7–10, intermediate=4–6) was determined by microscopy. Vaginal microbiota were characterized using 16S rRNA gene sequencing and categorized into 7 community state types (CSTs): 4 dominated by Lactobacillus spp. (CST I, II, III and V), and 3 by Streptococcus spp. (CST VI), Bifidobacterium spp. (CST VII), or a variety of anaerobes (CST IV). Results 110 samples, ∼10 from each CST, were selected. 5.5% (n=6) had Amsel-BV, 32.7% (n=36) Nugent-BV, and 36.4% (n=40) had low-Lactobacillus CSTs (IV, VI, VII); 8.2% had symptoms. Among Amsel-BV samples, 83.3% had Nugent-BV, 16.7% had intermediate Nugent score and all were CST IV. 86.1% of women with Nugent-BV and 85% of women with low-Lactobacillus CSTs did not have Amsel-BV. 22.2% of those with Nugent-BV did not have low-Lactobacillus CSTs; of these 50% were CST III (L. iners-dominated). 46.7% of CST-III had a vaginal pH ≥4.5, and 13.3% had a Nugent BV score. 22 samples had a vaginal pH≥4.5 and a normal Nugent score: 45.5% were in CST III, 9.1% in low-Lactobacillus CSTs. 30.6% women with Nugent-BV had a vaginal pH Conclusion Nugent score and low-Lactobacillus CST were concordant. L. iners-dominated CSTs often had normal Nugent scores and high pH. Among mostly asymptomatic women, a large proportion with low-Lactobacillus CSTs did not have Amsel-BV. Future studies assessing long term clinical outcomes will be needed to determine whether molecular methods provide added actionable or prognostic information. Disclosure No significant relationships.

Background Despite widespread use, the effect of hormonal contraception (HC) on the vaginal microbiota (VMB) is understudied. We compared VMB in a longitudinal observational study of women during intervals on and off HC. Methods Women stopping and starting any form of HC and women off HC (controls) collected vaginal swabs twice-weekly for 2 weeks prior to 7 study visits over 2 years. 16S rRNA gene sequencing was conducted, and the VMB was categorized into 7 community state types (CSTs): 4 dominated by Lactobacillus spp, and 3 by Streptococcus spp (CST VI), Bifidobacterium spp (CST VII), or a variety of anaerobes (CST IV). Mixed effects logistic regression models assessed differences in CST proportions. Bayesian double exponential random effects models estimated differences between stability indices within HC and control subjects (measured by median Jensen-Shannon distance [MJSD] from the subject’s own centroid and from the centroid of CST I [L. crispatus-dominated]). Results 4185 samples from 105 women (73 HC, 32 controls) were available for analysis. The VMB was more stable in women on HC as compared to controls (MJSD 0.16 vs 0.22, p Conclusion Women on HC have more stable, Lactobacillus-dominated VMB than controls. There is increased VMB stability after 3 months of HC use. Further assessment by HC type is currently being integrated into the analysis. Disclosure No significant relationships.

The incidence of syphilis is increasing. Syphilitic proctitis involving the rectal mucosa often presents with pain on defecation, rectal bleeding, or ulceration. We present a case of asymptomatic syphilitic proctitis diagnosed upon a routine screening colonoscopy.

Objectives Bacterial vaginosis (BV), a clinical condition characterized by decreased vaginal Lactobacillus spp., is difficult to treat. We examined associations between micronutrient intake and a low-Lactobacillus vaginal microbiota as assessed by molecular methods (termed “molecular-BV”). Methods This cross-sectional analysis utilized data collected at the baseline visit of the Hormonal Contraception Longitudinal Study, a cohort of reproductive-aged women followed over 2 years while initiating or ceasing hormonal contraception (HC). The Block Brief 2000 Food Frequency Questionnaire was administered and micronutrient intakes were ranked. Vaginal microbiota composition was assessed using 16S rRNA gene amplicon sequencing and clustered into community state types (CSTs) based on the types and relative abundance of bacteria detected. Associations between the lowest estimated quartile intake of nutrients and having a low-Lactobacillus CST (molecular-BV) were evaluated by logistic regression. Separate models were built for each nutrient controlling for age, body mass index, behavioral factors, HC use and total energy intake. We also conducted a literature review of existing data on associations between micronutrient intakes and BV. Results Samples from 104 women were included in this analysis. Their mean age was 25.8 years (SD 4.3), 29.8% were African American, 48.1% were using HC, and 25% had molecular-BV. In adjusted multivariable analyses, the lowest quartile of betaine intake was associated with an increased odds of molecular-BV (aOR 9.2, p value Conclusions This is the first study to assess the association between estimated micronutrient intake and molecular-BV. Lower energy-adjusted intake of betaine was associated with an increased risk of molecular-BV. Betaine might have direct effects on the vaginal microenvironment or may be mediated through the gut microbiota. Additional research is needed to determine reproducibility of this finding and whether improved intake of select micronutrients such as betaine decreases the risk of BV and its sequelae.

ObjectivesNeisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) increase the risk of HIV transmission among men who have sex with men (MSM). Diagnosis of NG/CT may provide an efficient entry point for prevention of HIV through the delivery of pre-exposure prophylaxis (PrEP); however, the additional population-level impact of targeting PrEP to MSM diagnosed with NG/CT is unknown.DesignAn agent-based simulation model of NG/CT and HIV cocirculation among MSM calibrated against census data, disease surveillance reports and the US National HIV Behavioral Surveillance study.SettingBaltimore City, Maryland, USA.InterventionsPrEP implementation was modelled under three alternative scenarios: (1) PrEP delivery at NG/CT diagnosis (targeted delivery), (2) PrEP evaluation at NG/CT screening/testing and (3) PrEP evaluation in the general community (untargeted).Main outcomeThe projected incidence of HIV after 20 years of PrEP delivery under two alternatives: when equal numbers of MSM are (1) screened for PrEP or (2) receive PrEP in each year.ResultsAssuming 60% uptake and 60% adherence, targeting PrEP to MSM diagnosed with NG/CT could reduce HIV incidence among MSM in Baltimore City by 12.4% (95% uncertainty range (UR) 10.3% to 14.4%) in 20 years, relative to no PrEP. Expanding the coverage of NG/CT screening (such that individuals experience a 50% annual probability of NG/CT screening and evaluation for PrEP on NG/CT diagnosis) can further increase the impact of targeted PrEP to generate a 22.0% (95% UR 20.1% to 23.9%) reduction in HIV incidence within 20 years. When compared with alternative implementation scenarios, PrEP evaluation at NG/CT diagnosis increased impact of PrEP on HIV incidence by 1.5(95% UR 1.1 to 1.9) times relative to a scenario in which PrEP evaluation happened at the time of NG/CT screening/testing and by 1.6 (95% UR 1.2 to 2.2) times relative to evaluating random MSM from the community.ConclusionsTargeting MSM infected with NG/CT increases the efficiency and effectiveness of PrEP delivery. If high levels of sexually transmitted infection screening can be achieved at the community level, NG/CT diagnosis may be a highly effective entry point for PrEP initialisation.

Ocular syphilis, a form of neurosyphilis, has been increasingly diagnosed in the United States. This case series summarizes the course of 6 patients recently diagnosed with ocular syphilis, emphasizing the varied sociodemographic factors and the wide range of symptoms and outcomes that are seen in patients with this disease.

Many individuals remain sexually active into their eighth decade. Surveillance data suggest that rates of sexually transmitted infections in older patients are increasing. We compared demographics, risk behaviors, and predictors of acute infections in patients 50 years and older versus younger patients attending sexually transmitted disease clinics in Baltimore, Maryland. This was a retrospective study from a large electronic database of visits to two urban sexually transmitted disease clinics between 2005 and 2010. Proportions were compared using the Chi square test. Logistic regression was used to assess predictors of acute sexually transmitted infections in older versus younger groups. It was found that patients over 50 were more likely than younger patients to report never using condoms (32.6% [CI 0.31–0.34] versus 24.1% [CI 0.23–0.25]). The overall prevalence of acute sexually transmitted infections was 18.1% (CI 0.17–0.19) in older and 25.8% (CI 0.25–0.27) in younger patients. Older women were more likely to be diagnosed with trichomoniasis (21.5% [CI 18.6–24.5] versus 13.1% [CI 11.5–14.8]). Black race was predictive of having an acute sexually transmitted infections in younger men (OR 2.2 [CI 1.47–3.35]) and women (OR 2.7 [CI 1.34–5.30]) but not in older men (OR 1.2 [CI 0.79–1.73]) or women (OR 1.2 [CI 0.43–3.15]). Older age was associated with a decreased risk of acute STI diagnosis in younger men and older women only, while having had sex for money or drugs in the past month was predictive only in younger women. Reporting symptoms and increasing numbers of sexual partners in the last six months was predictive of acute sexually transmitted infection diagnosis in all age groups. Older patients seeking care at sexually transmitted disease clinics engage in important risk behaviors. Race, a factor predictive of acute sexually transmitted infections in younger patients is not a significant predictor of sexually transmitted infections in older persons.

After reaching a nadir at the turn of the century, syphilis rates in the United States have increased since 2000. Treponema pallidum may disseminate to the central nervous system within hours to days after inoculation. In this review, we focus on knowledge gaps and areas of controversy in neurosyphilis epidemiology, diagnosis, and management. Modern estimates of the prevalence of neurosyphilis are hindered by the lack of consistent reporting data and are based on relatively small retrospective cohort studies. The various diagnostic modalities for neurosyphilis have significant limitations. Although several novel biomarkers for neurosyphilis have been evaluated, none to date have found a place in clinical practice. The role of a cerebrospinal fluid examination in patients without neurological symptoms continues to be an area of controversy, whereas the data for the use of antibiotic regimens other than intravenous aqueous or intramuscular procaine penicillin for the treatment of neurosyphilis are limited. As syphilis incidence continues to increase unabated in many countries around the world, it is critical to address these gaps of knowledge.

Background The impact of antibiotics on the composition of the vaginal microbiota (VMB) is poorly defined. We analyzed the VMB of women before and after the use of antibiotics. Methods We used samples from a cohort of reproductive-aged women who submitted vaginal swabs and clinical data over a 2-year period. 16S rRNA gene sequencing was conducted, and VMB was categorized into 7 community state types (CSTs): four dominated by Lactobacillus spp. and three low in Lactobacillus, dominated by Streptococcus spp. (CST VI), Bifidobacterium spp. (CST VII), or comprising a variety of anaerobes (CST IV). CSTs were further categorized as Lactobacillus-dominated (LD) or non-Lactobacillus-dominated (NLD). We compared paired vaginal samples collected within 48 hours prior to and 48 hours after completion of antibiotics in 40 women (N = 10 systemic metronidazole, N = 6 vaginal metronidazole, N = 5 trimethoprim-sulfamethoxazole, N = 9 amoxicillin, N = 5 azithromycin, N = 5 other), to time-matched samples in 56 controls. Exact logistic regression was used to evaluate the impact of antibiotics on LD status controlling for baseline CST, race, menses, and hormonal contraceptive use. Results Women who received antibiotics were 25 times more likely to be in an LD state after antibiotics compared with those who did not receive antibiotics (p = 0.0017). NLD to LD transitions occurred almost exclusively in patients receiving metronidazole. Of 13 women who began in NLD (N = 12 in CST IV) and then received metronidazole, 84.6% (N = 11) transitioned to LD (CST III, L. iners-dominated). Of 7 women who started in an NLD state and received non-nitroimidazole antibiotics, only two (receiving clindamycin or amoxicillin) transitioned to an LD state. None of the 20 women who began in a LD state transitioned to a non-LD state after antibiotics. 12 controls were in an NLD state at baseline, of these 11 remained NLD at the second time point. 44 controls started in an LD state and all remained in LD at the second time point. Conclusion In the short term, metronidazole results in a transition of the VMB from a NLD to a L. iners-dominated state. There was little impact of non-nitroimidazole antibiotics on the VMB. Studies assessing longer-term impact of antibiotics on the composition of the VMB are needed. Disclosures All authors: No reported disclosures.

A diverse array of microbes colonizes the human intestine. In this review, we seek to outline the current state of knowledge on what characterizes a 'healthy' or 'normal' intestinal microbiome, what factors modify the intestinal microbiome in the healthy state and how the intestinal microbiome affects normal host physiology.What constitutes a 'normal' or 'healthy' intestinal microbiome is an area of active research, but key characteristics may include diversity, richness and a microbial community's resilience and ability to resist change. A number of factors, including age, the host immune system, host genetics, diet and antibiotic use, appear to modify the intestinal microbiome in the normal state. New research shows that the microbiome likely plays a critical role in the healthy human immune system and metabolism.It is clear that there is a complicated bidirectional relationship between the intestinal microbiota and host which is vital to health. An enhanced understanding of this relationship will be critical not only to maximize and maintain human health but also to shape our understanding of disease and to foster new therapeutic approaches.

The US Centers for Disease Control and Prevention (CDC) issued a clinical advisory late last year on ocular syphilis. Between December 2014 and March 2015, 12 cases of ocular syphilis were reported from two US cities, San Francisco and Seattle.1 Subsequent case finding identified more than 200 cases reported over the last 2 years from 20 states. Whether this is the result of one or more oculotropic strains (neuroinvasive strains have been described)2 or enhanced case detection due to, for example, the increasing use of the reverse sequence algorithm for syphilis screening, is unclear. In Maryland, to date, following the release of the advisory, 13 cases have been identified through careful record reviews with 9 (70%) of the 13 presenting as late ocular syphilis (personal communication Elisabeth Liebow and Alexandra Goode, Maryland Department of Health and Mental Hygiene). If this increasing case detection is the result of a circulating strain, the strain has been circulating for a while. Irrespective of the cause of this observed increase in the number of cases of ocular syphilis, there are several important yet unanswered clinical questions: what is the relationship between ocular and neurosyphilis? How does HIV impact ocular syphilis and this relationship? Is a lumbar puncture (LP) necessary for the evaluation of patients suspected of having ocular syphilis? What is the best treatment of ocular syphilis? Other issues to clarify include the relationship of ocular syphilis presentation to stage of syphilis infection, the risk of ocular syphilis in serofast patients, and whether ocular syphilis in patients with a previous record of treatment represents recrudescence or reinfection. Several studies have tried to address one or more of these questions. All of these studies suffered from a small sample size that limited their power to draw meaningful conclusions. In this issue, Tsuboi et al …

Introduction Mycoplasma genitalium (MG) is a sexually transmitted infection (STI) associated with urethritis in men and cervicitis and pelvic inflammatory disease (PID) in women. Azithromycin (AZ) resistance in MG, resulting in treatment failure is an issue. We compared molecular assays for detection of MG in females; a prospective cohort of adolescents with PID and a retrospective group of women at a STD clinic. We tested vaginal samples for AZ resistance with the SpeeDX assay, a real-time PCR, which detects MG and 23S rRNA AZ resistance mutations. Methods For the prospective study, SpeeDX results were compared to 16S rRNA and pdhD real-time PCR assays, and the Aptima MG ASR assay. Samples consisted of dry transported vaginal swab samples (n=116); expressed in water. For the retrospective study we evaluated vaginal samples (n=289) stored in liquid Amies media. Nucleic acid extraction was performed utilising the Roche MagNA Pure LC robot according to manufacturer instructions. The SpeeDX assay was performed according to manufacturer instructions. For the retrospective study, results were compared to the 2 real-time PCR assays for the 16S rRNA gene and pdhD gene. Results For the prospective study, a gold standard of 3 of 4 positive tests defined a true positive. The 16S PCR had 100% sensitivity (10/10) and 100% specificity (106/106) Kappa=1 [95% CI: 1–1], while SpeeDX PCR displayed 90% sensitivity (9/10) and 99% specificity (105/106) Kappa=0.89 [95% CI: 0.74–1]. The pdhD PCR had 100% sensitivity (10/10) and 100% specificity (106/106) Kappa=1. The Aptima MG assay had 90% sensitivity (9/10) and 94% specificity (100/106) Kappa=0.69 [0.46–0.91]. The SpeeDX 23S rRNA mutation rate was 50% (5/10). For the retrospective group, no Aptima MG was done because of transport media. A gold standard of 2 of 3 positive tests defined a true positive. The 16S PCR was 84% sensitive (21/25) and 100% specific (264/264) Kappa=0.91 [0.813–0.997]. The SpeeDX was 92% sensitive (23/25) and 99% specificity (262/264) Kappa=0.91 [0.833–0.997]. The pdhD PCR was 96% sensitive (24/25) and 99% specific (261/264) Kappa=0.91 [0.833–0.997]. The SpeeDX AZ resistance was 36% (9/25). Conclusion: More prospective evaluation studies are required; all assays performed well. The SpeeDX PCR compared well to two real-time PCRs and the Aptima MG assay. High AZ resistance was observed. The SpeeDX assay is potentially useful for MG diagnosis and for detection of resistance to AZ

The healthy vaginal microbiota is typically characterized by the predominance of Lactobacillus species (including L. crispatus, L. jensenii, L. gasseri , and L. iners ). These bacteria are thought to protect against pathogens through a variety of mechanisms, including competitive inhibition, secretion of bacteriocins (substances that inhibit the growth of bacteria), and the production of lactic acid, which lowers the vaginal pH and has immunomodulatory effects ( 1 ). Consequently, vaginal dysbiosis is currently defined by the presence of polymicrobial bacterial populations with reduced or absent lactobacilli. This low-lactobacillus state characterizes bacterial vaginosis, a clinical condition that is a common cause of vaginal symptoms in reproductive-aged women ( 2 ). Decreased bacterial diversity in the gut has been linked to a number of pathologic conditions ( 3 ), whereas increased vaginal bacterial diversity has been associated with a variety of poor patient outcomes including preterm birth and the acquisition and spread of sexually transmitted infections ( 4 , 5 ). On page 938 of this issue, Klatt et al. ( 6 ) add to this list a decrease in the efficacy of the vaginal antiretroviral gel tenofovir to prevent HIV acquisition.

Background The near-universal prevalence of electronic health records (EHRs) has made the utilization of clinical decision support systems (CDSS) an integral strategy for improving the value of laboratory ordering. Few studies have examined the effectiveness of nonintrusive CDSS on inpatient laboratory utilization in large academic centres. Methods Red blood cell folate, hepatitis C virus viral loads and genotypes, and type and screens were selected for study. We incorporated the appropriate indications for these labs into text that accompanied the laboratory orders in our hospital's EHR. Providers could proceed with the order without additional clicks. An interrupted time-series analysis was performed, and the primary outcome was the rate of tests ordered on all inpatient medicine floors. Results The rate of folate tests ordered per monthly admissions showed no significant level change at the time of the intervention with only a slight decrease in rate of 0.0109 (P = .07). There was a 43% decrease in the rate of hepatitis C virus tests per monthly admissions immediately after the intervention with a decrease of 0.0135 tests per monthly admissions (P = .02). The rate of type and screens orders per patient days each month had a significant downward trend by 0.114 before the intervention (P = .04) but no significant level change at the time of the intervention or significant change in rate after the intervention. Discussion Our study suggests that nonintrusive CDSS should be evaluated for individual laboratory tests to ensure only effective alerts continue to be used so as to avoid increasing EHR fatigue.