A Narrative Review on Spontaneous Clearance of Urogenital Chlamydia trachomatis: Host, Microbiome, and Pathogen-Related Factors.

ABSTRACT: Chlamydia trachomatis (CT) is the most commonly reported sexually transmitted infection in the United States. Untreated urogenital infection in women can result in adverse sequelae such as pelvic inflammatory disease and infertility. Despite national screening and treatment guidelines, rates continue to rise; because most infections are asymptomatic, the actual prevalence of CT infection is likely significantly higher than reported. Spontaneous clearance of CT in women (in the absence of antibiotic treatment) has been described in multiple epidemiologic studies. Given the serious consequences and high prevalence of CT infection, there is growing interest in understanding this phenomenon and factors that may promote CT clearance in women. Spontaneous CT clearance is likely the result of complex interactions between CT, the host immune system, and the vaginal microbiota (i.e., the communities of bacteria inhabiting the vagina), which has been implicated in CT acquisition. Herein, we briefly review current literature regarding the role of each of these factors in spontaneous CT clearance, identify knowledge gaps, and discuss future directions and possible implications for the development of novel interventions that may protect against CT infection, facilitate clearance, and prevent reproductive sequelae.

Stand up to better pay attention, sit down to better subtract: a new perspective on the advantage of cognitive-motor interactions.

The Stroop task and subtraction rely on the different cognitive processes and cerebral regions, but both these cognitive functions interact with posture. The study of cognitive-motor interactions falls under the concept of sharing resources, implying that resources for processing are limited. Researchers try to understand this interaction by constructing dual task (DT) paradigms. None have investigated the Stroop and subtraction tasks in three inherently simple postures in two groups of young adults. This study aimed to test whether a given posture benefits a given cognitive function when cognitive and postural tasks are not overly demanding and are underpinned by common cerebral structures. This study presents the results of 60 healthy young adults performing a subtraction task in three postures (sitting, standing, and walking) and 57 healthy young adults performing the Stroop task in the same three postures. Our results showed that performance at the Stroop task, in terms of number of correct answers and interference, are better while standing or even walking compared to sitting while subtraction is better sitting compared to standing and walking. Moreover, static postural parameters did not vary when in DT compared to single task. This means that there was no additional cost on posture when achieving the cognitive activity simultaneously. The absence of impact of the DT on postural parameters in static postures and the changes in the gait pace when walking suggest that cognitive tasks can be achieved in various postures, without being too costly on posture.

State-of-the-Art Review: Neurosyphilis.

We review key concepts in the diagnosis, treatment, and follow-up of individuals with neurosyphilis. We describe the epidemiology of syphilis in the United States, highlight populations that are markedly affected by this infection, and attempt to estimate the burden of neurosyphilis. We describe the cardinal clinical features of early and late (tertiary) neurosyphilis and characterize the clinical significance of asymptomatic neurosyphilis in the antibiotic era. We review the indications for cerebrospinal fluid (CSF) examination and the performance characteristics of different CSF assays including treponemal and lipoidal antibodies, white cell count, and protein concentration. Future biomarkers and the role of imaging are briefly considered. We review preferred and alternative treatments for neurosyphilis and evidence for their use, including evidence for the use of enhanced intramuscular benzathine penicillin G to supplement intravenous penicillin.

A patient with secondary syphilis following incomplete treatment of primary infection.

Syphilis is a bacterial infection caused by Treponema pallidum and is primarily transmitted via skin-to-skin or mucosal contact during sexual encounters, or through vertical transmission during pregnancy. Cases continue to rise globally across various demographic groups despite effective treatment and prevention interventions. We discuss the case of a 28-year-old cisgender man who presented with secondary syphilis 1 month after being inadequately treated for primary syphilis. Individuals can present with symptoms and signs of syphilis to clinicians of various subspecialties due to diverse clinical presentation. All health-care providers should be able to identify the common and less common manifestations of this infection, and adequate treatment and follow-up are crucial to preventing serious sequelae. Novel biomedical prevention interventions, such as doxycycline post-exposure prophylaxis, are on the horizon.

Bacterial Vaginosis and Spontaneous Clearance of Chlamydia trachomatis in the Longitudinal Study of Vaginal Flora.

BACKGROUND: Up to 26% of urogenital Chlamydia trachomatis infections spontaneously resolve between detection and treatment. Mechanisms governing natural resolution are unknown. We examined whether bacterial vaginosis (BV) was associated with greater chlamydia persistence versus spontaneous clearance in a large, longitudinal study. METHODS: Between 1999 and 2003, the Longitudinal Study of Vaginal Flora followed reproductive-age women quarterly for 1 year. Baseline chlamydia screening and treatment were initiated after ligase chain reaction testing became available midstudy, and unscreened endocervical samples were tested after study completion. Chlamydia clearance and persistence were defined between consecutive visits without chlamydia-active antibiotics (n = 320 persistence/n = 310 clearance). Associations between Nugent score (0-3, no BV; 4-10, intermediate/BV), Amsel-BV, and chlamydia persistence versus clearance were modeled with alternating and conditional logistic regression. RESULTS: Of chlamydia cases, 48% spontaneously cleared by the next visit (310/630). Nugent-intermediate/BV was associated with higher odds of chlamydia persistence (adjusted odds ratio [aOR] = 1.89; 95% confidence interval [CI], 1.30-2.74), and the findings were similar for Amsel-BV (aOR 1.39; 95% CI, .99-1.96). The association between Nugent-intermediate/BV and chlamydia persistence was stronger in a within-participant analysis of 67 participants with both clearance/persistence intervals (aOR = 4.77; 95% CI, 1.39-16.35). BV symptoms did not affect any results. CONCLUSIONS: BV is associated with greater chlamydia persistence. Optimizing the vaginal microbiome may promote chlamydia clearance.

Association of Pregnancy and HIV Status With Molecular-Bacterial Vaginosis in Indian Women.

BACKGROUND: Bacterial vaginosis (BV) is a highly prevalent disorder of the cervicovaginal microbiota. Molecular-BV may put women at increased risk for adverse reproductive and obstetric outcomes. We investigated the association of HIV and pregnancy on the vaginal microbiota and associations with molecular-BV in women of reproductive age from Pune, India. SETTING: We studied vaginal samples from N = 170 women, including N = 44 nonpregnant HIV seronegative, N = 56 pregnant seronegative, N = 47 nonpregnant women with HIV (WWH), and N = 23 pregnant WWH, and collected data on clinical, behavioral, and demographic factors. METHODS: We used 16S rRNA gene amplicon sequencing to characterize the composition of the vaginal microbiota. We classified the vaginal microbiota of these women into community state types based on bacterial composition and relative abundance and further categorized them into molecular-BV versus Lactobacillus -dominated states. To determine associations between pregnancy and HIV status with outcome of molecular-BV, logistic regression models were used. RESULTS: There was a high prevalence of molecular-BV (30%) in this cohort. We found that pregnancy was associated with decreased odds of molecular-BV (adjusted OR = 0.35, 95% CI: 0.14 to 0.87), while HIV was associated with increased odds of molecular-BV (adjusted OR = 2.76, 95% CI: 1.33 to 5.73), even when controlling for multiple relevant factors such as age, number of sexual partners, condom use, and douching. CONCLUSION: Larger and longitudinal studies are needed to further characterize molecular-BV and the vaginal microbiota in pregnant women and WWH and relate these factors to infectious, reproductive, and obstetric outcomes. In the long term, these studies may lead to novel microbiota-based therapeutics to improve women's reproductive and obstetric health.

The Utility of Biomarkers in the Clinical Management of Syphilis: A Systematic Review.

BACKGROUND: Routinely available laboratory tests for Treponema pallidum remain suboptimal for diagnostic, prognostic, predictive, and monitoring purposes. Biomarkers with enhanced performance characteristics can improve diagnostic confidence and facilitate management. We conducted a systematic review to examine the utility of biomarkers in the diagnosis and management of syphilis. METHODS: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses to identify articles for inclusion and independently reviewed them for eligibility and study quality using a 3-stage procedure. The search, conducted by a senior library informationist, used PubMed, Embase, Cochrane Library, and Scopus and included any study published before May 2022. RESULTS: Of the 111 studies identified, 31 (27.9%) were included in our review. Most studies were cross-sectional or prospective. The data were strikingly heterogeneous examining a variety of biomarkers across different syphilis stages, using different methodologies and definitions of treatment success. Available publications chiefly focused on diagnosing various syphilis stages, neurosyphilis and congenital syphilis, serological cure, the serofast state, and reinfection. CONCLUSIONS: Despite increasing attempts to identify novel biomarkers, we found limited evidence to support the use of any biomarker in clinical decision making at this time; the syphilis biomarker literature is heterogenous and lacks measurement of clinically meaningful end points. We recommend the formation of a working group to set priorities for syphilis biomarker research and to guide future study of clinically meaningful biomarkers.

Nonpublication and Selective Outcome Reporting of Oral Health Trials.

Less than one-quarter of oral health trials are registered in a public registry. However, no study has assessed the extent of study publication and selective outcome reporting bias in the field of oral health. We identified oral health trials registered between 2006 and 2016 in ClinicalTrials.gov. We assessed whether results of early discontinued trials, trials having an unknown status, and completed trials had been published and, among published trials, whether outcomes differed between the registered record and the corresponding publication. We included 1,399 trials, of which 81 (5.8%) were discontinued, 247 (17.7%) had an unknown status, and 1,071 (76.6%) were completed. The registration was prospective for 719 (51.9%) trials. Over half the registered trials were unpublished (n = 793, 56.7%). To explore the association between trials publication and characteristics of trials, we performed a multivariate logistic regression analysis. Trials conducted in the United States (P = 0.003) or Brazil (P < 0.001) were associated with increased odds of publication, whereas trials registered prospectively (P = 0.001) and industry-sponsored trials (P = 0.02) were associated with decreased odds. Among the 479 published trials with completed status, the primary outcomes of 215 (44.9%) articles differed from that registered. Major discrepancies consisted of the introduction of a new primary outcome in the published article (196 [91.2%]) and the transformation of a registered secondary outcome into a primary outcome (112 [52.1%]). In the remaining 264 (55.1%) trials, primary outcomes did not differ from that registered, but 141 (53.4%) had been registered retrospectively. Our study highlights the high rate of nonpublication and selective outcome reporting in the field of oral health. These results could alert sponsors, funders, authors of systematic reviews, and the oral health research community at large to combat the nondisclosure of trial results.

Vaginal Candida albicans: High Frequency of in Vitro Fluconazole Resistance in a Select Population-A Brief Note.

Among clinician-ordered vaginal cultures positive for Candida albicans , 30% exhibited fluconazole resistance. Resistance did not reliably predict future susceptibility. Prospective studies to verify associations with demographic and clinical factors as well as to correlate in vitro resistance with treatment response and longitudinal resistance patterns are needed.

Douching cessation and molecular bacterial vaginosis: a reanalysis of archived specimens.

OBJECTIVES: Observational studies demonstrate an association between vaginal douching and bacterial vaginosis (BV) characterised by Gram stain. We sought to describe the effect of a douching cessation intervention on the composition and structure of the vaginal microbiota and molecular-BV, a state defined by low levels of Lactobacillus spp evaluated by molecular tools. METHODS: 33 women self-collected mid-vaginal swabs twice weekly (982 samples) during a douching observation phase (4 weeks) followed by a douching cessation phase (12 weeks) in a 2005 single crossover pilot study conducted in Baltimore, Maryland. Vaginal microbiota were characterised by 16S rRNA gene amplicon sequencing (V3-V4) and clustered into community state types (CSTs). Conditional logistic regression modelling allowed each participant to serve as their own control. Wilcoxon signed-rank tests were used to evaluate changes in microbiota between phases. Broad-range qPCR assays provided estimates of bacterial absolute abundance per swab in a subsample of seven participants before and after douching. A piecewise linear mixed effects model was used to assess rates of change in bacterial absolute abundance before and after douching. RESULTS: There was no statistically significant change in the odds of molecular-BV versus Lactobacillus-dominated CSTs comparing the douching cessation interval to douching observation (adjusted OR 1.77, 95% CI 0.89 to 3.55). Removal of L. iners-dominated CST III from the outcome did not affect the results. There were no significant changes in the relative abundance of four Lactobacillus spp and no meaningful changes in other taxa investigated. There was no significant change in bacterial absolute abundance between a participant's sample collected 3 days prior to and following douching (p=0.46). CONCLUSIONS: In this pilot study, douching cessation was not associated with major changes in vaginal microbiota. Douching cessation alone may not durably shift the vaginal microbiota and additional interventions may be needed to restore optimal vaginal microbiota among those who douche.

Enacted Sexual Minority Stigma, Psychological Distress, and Sexual and Drug Risk Behaviors Among Urban Men Who Have Sex with Men (MSM).

Urban Black men who have sex with men (MSM) bear a disproportionate burden of HIV and syphilis in the U.S. Experiences of enacted sexual minority stigma and psychological distress among these men may be associated with HIV/STI sexual and drug risk behaviors. The objective was to determine the associations between enacted sexual minority stigma, psychological distress, and sexual and drug risk behaviors. In an urban prospective cohort study, survey measures assessed past 3-month exposure to enacted sexual minority stigma, psychological distress, and sexual and drug risk behaviors. Multivariable logistic regression models were utilized for hypothesis testing. The Black MSM (N = 140) reported the following: 22.1% experiences of enacted sexual minority stigma, 39% high levels of psychological distress, 48.6% > 1 sex partner, 8.6% transactional sex, and 6% injection drug use (IDU). In models adjusted for age and education, enacted sexual minority stigma significantly increased the odds of reporting > 1 sex partner, transactional sex, and IDU. Adjusting additionally for homelessness, the association between enacted sexual minority stigma and transactional sex remained significant. Adding psychological distress to this model showed a significant association between psychological distress and transactional sex, while the association was no longer significant for transactional sex. These findings highlight some of the complex psycho-social relationships that may be associated with sexual and drug risk behaviors among Black MSM placing them at increased risk for HIV and syphilis.

RESUMEN: Hombres urbanos de raza Negra que tienen sexo con hombres (HSH) sobrellevan una carga desproporcionada de VIH y sífilis en los EE.UU. Experiencias de estigma efectivo de minoría sexual y angustia psicológica entre estos hombres pudiese ser asociado con conductas sexuales de riesgo VIH/ITS y drogas. El objetivo era determinar las asociaciones entre un estigma efectivo de minoría sexual, angustia psicológica, y comportamientos sexuales y de riesgo de drogas. En un estudio de cohortes prospectivo urbano, las medidas de la encuesta evaluada en los últimos tres meses de exposición al estigma efectivo, angustia psicológica, y sus conductas sexuales y comportamientos riesgoso de drogas. Modelos de regresión logística multivariante se utilizaron para la prueba de hipótesis. Los HSH de raza negra (N = 140) reportaron lo siguiente: 22.1% experiencias de estigma efectivo, 39% niveles altos de angustia psicológica, 48.6% y > 1 pareja sexual, 8.6% sexo transaccional, y 6% uso de drogas inyectables (UDI). En modelos ajustados a edad y educación, un estigma efectivo de minoría sexual aumentó de manera significante las probabilidades de reportar y > 1 pareja sexual, sexo transaccional, y UDI. Ajustando adicionalmente para personas sin vivienda, la asociación entre estigma efectivo de minoría sexual y sexo transaccional permaneció significante. La adición de angustia psicológica al modelo mostró una asociación significativa entre angustia psicológica y sexo transaccional, mientras que la asociación ya no era significativa para el sexo transaccional. Estos resultados destacan algunas de las complejas relaciones psicosociales que pudiesen estar asociadas con conductas sexuales y de riesgo de drogas entre HSH de raza negra, poniéndolos a mayor riesgo de contraer VIH y sífilis.

Lactobacillus-dominance and rapid stabilization of vaginal microbiota in combined oral contraceptive pill users examined through a longitudinal cohort study with frequent vaginal sampling over two years.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: R01-AI089878.

Is better selective attention while standing possible without cost on postural sway?

While it is known that posture and cognition interact, the mechanism of this interaction is still uncertain. This interaction falls under the concept of sharing resources, implying that resources for processing are limited. Many studies were conducted to understand this interaction; however, none have investigated the attention network task (ANT) in two common static postures in young adults. The purpose of this study was to test whether a given posture benefits the components of attention without dual-task (DT) cost, when cognitive and postural tasks are not overly demanding. This study presents the results of 37 healthy young adults performing the ANT in two postural conditions. Our results showed ANT performance with faster reaction times while standing than sitting without cost on postural parameters. This study raises the question of the contribution of posture variations in daily life. Knowledge gained from this research may lead to a better understanding of the interaction between posture and attention. Using "simple" postures, we aim to show that posture might facilitate the achievement of the cognitive activity.

Psychological distress and adherence to anti-retroviral therapy or pre-exposure prophylaxis regimens among Urban Black gay and bisexual men (MSM).

BACKGROUND: Urban Black gay, and bisexual men (MSM) bear a disproportionate burden of HIV in the U.S. Mental health is a barrier to adherence to both antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP). The objective was to determine the association between psychological distress and ART or PrEP adherence among urban Black MSM. METHODS: Using data from a four-year prospective cohort study, adherence to ART was defined as > 95% and PrEP was defined as > 80% of doses taken in the past 30 days. Psychological distress measures included difficulty sleeping; feeling anxious; suicidality; feeling sad or depressed; feeling sick, ill, or not well in the past 3 months; high (vs. low) overall psychological distress was classified as above the median value. Associations were examined using Chi-square, Fisher's exact tests, and logistic regression. RESULTS: Among 165 Black MSM, 44.2% (73) reported high psychological distress. 65.3% (47/72) of participants living with HIV and 39.8% (37/93) of HIV negative participants were ART or PrEP adherent, respectively. Education was significantly associated with PrEP adherence (p = 0.038). Non-injection drug use in the past 3 months (p = 0.008), difficulty sleeping (p = 0.010), feeling anxious (p = 0.003), and feeling sad or depressed (p < 0.001), and overall psychological distress (p < 0.001) were significantly associated with ART adherence. High psychological distress was significantly associated with a reduced odds of ART adherence (aOR 0.23; 95% CI = 0.08-0.70) adjusting for age and non-injection drug use. CONCLUSIONS: Increased psychological distress was significantly associated with ART nonadherence and may represent an important barrier to viral suppression.

Safety and efficacy of a biodegradable implant releasing tenofovir alafenamide for vaginal protection in a macaque model.

OBJECTIVES: To advance the initiative of ending the global epidemic, long-lasting HIV protection is needed through sustained release of antiretroviral drugs for months to years. We investigated in macaques the safety and efficacy of biodegradable polycaprolactone implants releasing tenofovir alafenamide for HIV pre-exposure prophylaxis (PrEP). METHODS: Implants were administered subcutaneously in the arm using a contraceptive trocar. Efficacy against vaginal simian-HIV (SHIV) infection was investigated in six pigtailed macaques that received two tenofovir alafenamide implants (0.35 mg/day), one in each arm, for a total release rate of tenofovir alafenamide at 0.7 mg/day. Macaques were exposed to SHIV twice weekly for 6 weeks. Statistical analyses were used to compare outcome with eight untreated controls. Histological assessments were performed on skin biopsies collected near implantation sites. RESULTS: Median (range) tenofovir diphosphate level in PBMCs was 1519 (1068-1898) fmol/106 cells. All macaques with tenofovir alafenamide implants were protected against vaginal SHIV infection. In contrast, 7/8 controls were infected after a median of 4 SHIV exposures (P = 0.0047). Histological assessment of tissues near tenofovir alafenamide implant sites showed inflammation and necrosis in 5/6 animals, which were not evident by visual inspection. CONCLUSIONS: We demonstrated complete protection against vaginal SHIV infection with two implants releasing a total of 0.7 mg of tenofovir alafenamide per day. We also identified tenofovir diphosphate concentrations in PBMCs associated with complete vaginal protection. Consistent with previous findings, we observed adverse local toxicity and necrosis near the tenofovir alafenamide implant site. Improved tenofovir alafenamide implants that are safe and maintain high efficacy have the potential to provide long-lasting protection against vaginal HIV infection.

Summary of the Fourth Annual American Sexually Transmitted Diseases Association Workshop on Improving Sexually Transmitted Infection Control Efforts Through Cross-Sector Collaboration.

ABSTRACT: 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.