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Objectives: We aimed to investigate the early natural history of Trichomonas vaginalis in men recently testing positive for this infection by a nucleic acid amplification test (NAAT). We hypothesised that 50% of men would spontaneously resolve their infection (in the absence of treatment) on repeat T. vaginalis NAAT., Methods: Men ages ≥18 years at the Jefferson County Health Department Sexual Health Clinic testing positive for T. vaginalis by NAAT during standard-of-care (SOC) within the past 30 days and presenting to the clinic for treatment were approached. At enrolment, participants completed a questionnaire, provided urine for repeat T. vaginalis NAAT, and were treated with 2 g oral metronidazole. Those with a repeat positive enrolment NAAT were seen for a 4-week test-of-cure (TOC) visit. At TOC, men provided urine for repeat NAAT. We determined the proportion of men with spontaneous resolution of T. vaginalis and evaluated predictors of spontaneous resolution. In those with a repeat positive enrolment T. vaginalis NAAT, we evaluated the proportion with persistent infection at TOC as a secondary outcome., Results: Between October 2021 and January 2023, 53 men with a recent positive SOC T. vaginalis NAAT were approached; 37 (69.8%) participated. The mean participant age was 32.9 years (SD 9.9); all identified as Black. The majority (97.3%) reported sex with women only; 35.1% reported sex with >1 partner in the last month. At enrolment, 26/37 (70.3%) had a repeat positive T. vaginalis NAAT in the absence of treatment after an average of 8.4 days (SD 5.9). Sexual partner gender, number of recent sexual partners, genital symptoms, unprotected sex with any partner and recent antibiotic use were not associated with spontaneous resolution. Of the 26 men attending a TOC visit, 17 (65.4%) returned and all except one (94.1%) were cured., Conclusion: Most men do not spontaneously clear T. vaginalis infection during early repeat testing., Competing Interests: Competing interests: OVG has received research grant support from NIH, Abbott Molecular, Gilead Sciences, Visby and Moderna, served on a scientific advisory board for Scynexis, and done consulting for El Sevier, GSK, Abbott Molecular and Thermo Fisher for which she received honoraria. CAM has received research grant support to her institution from NIH/NIAID, Lupin Pharmaceuticals, Gilead Sciences, Visby Medical and Abbott Molecular. She also reports honorarium and/or consulting fees from Scynexis, Cepheid, BioNTech, BioMed Diagnostics, Visby Medical, Elsevier, UpToDate, Abbott Molecular and Roche. All other authors have no relevant interests to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Van Gerwen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Abstract: This study assessed feasibility of male partner referral by Trichomonas vaginalis -infected women. Of 93 women approached, only 20 enrolled. Only 1 male partner contacted the study but was unable to be reached for scheduling. Other public health interventions are necessary to engaged T. vaginalis -infected women and their male partners in care., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

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., Competing Interests: Competing interests: CAM has received research grant support to her institution from NIH/NIAID, Lupin Pharmaceuticals, Gilead Sciences, Visby Medical and Abbott Molecular. CAM also reports honorarium and/or consulting fees from Scynexis, Cepheid, BioNTech, BioMed Diagnostics, Visby Medical, Elsevier, UpToDate, Abbott Molecular and Roche. OTVG has received research grant support to her institution from NIH/NIAID, Lupin Pharmaceuticals, Gilead Sciences and Abbott Molecular and has served on a scientific advisory board for Scynexis. KJG has received research grant support to his institution from NIH/NIAID and Lupin Pharmaceuticals. The other authors have no competing interests to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite more than 60 years of research, the etiology of bacterial vaginosis (BV) remains controversial. In this pilot study, we used shotgun metagenomic sequencing to characterize vaginal microbial community changes before the development of incident BV (iBV)., Methods: A cohort of African American women with a baseline healthy vaginal microbiome (no Amsel criteria, Nugent score 0-3 with no Gardnerella vaginalis morphotypes) were followed for 90 days with daily self-collected vaginal specimens for iBV (≥2 consecutive days of a Nugent score of 7-10). Shotgun metagenomic sequencing was performed on select vaginal specimens from 4 women, every other day for 12 days before iBV diagnosis. Sequencing data were analyzed through Kraken2 and bioBakery 3 workflows, and specimens were classified into community state types. Quantitative polymerase chain reaction was performed to compare the correlation of read counts with bacterial abundance., Results: Common BV-associated bacteria such as G. vaginalis , Prevotella bivia , and Fannyhessea vaginae were increasingly identified in the participants before iBV. Linear modeling indicated significant increases in G. vaginalis and F . vaginae relative abundance before iBV, whereas the relative abundance of Lactobacillus species declined over time. The Lactobacillus species decline correlated with the presence of Lactobacillus phages. We observed enrichment in bacterial adhesion factor genes on days before iBV. There were also significant correlations between bacterial read counts and abundances measured by quantitative polymerase chain reaction., Conclusions: This pilot study characterizes vaginal community dynamics before iBV and identifies key bacterial taxa and mechanisms potentially involved in the pathogenesis of iBV., Competing Interests: Conflict of Interest and Sources of Funding: C.A.M. is a consultant for Scynexis, Cepheid, and BioNTech. She has received research funding support from National Institutes of Health/National Institute of Allergy and Infectious Diseases, Lupin Pharmaceuticals, Abbott Molecular, and Gilead, as well as honoraria from Visby, Elsevier, Abbott Molecular, Scynexis, Roche, and Cepheid. This work was supported by the National Institute of Allergy and Infectious Diseases (grants K23AI106957 and R01AI146065 to C.A.M. and R01AI118860 to A.J.Q. and C.M.T.), National Science Foundation (grant 2018936 to C.M.T.), National Center for Advancing Translational Sciences (grant UL1TR003096 to the University of Alabama–Birmingham Center for Clinical and Translational Science), and an American Sexually Transmitted Diseases Association Small Project Assistance award (to J.H.E.)., (Copyright © 2023 American Sexually Transmitted Diseases Association. All rights reserved.)

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 >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., Competing Interests: Competing interests: CAM has received research grant support from NIH/NIAID, Lupin Pharmaceuticals, Gilead Sciences, Visby Medical, and Abbott Molecular; is a consultant for Lupin Pharmaceuticals, BioNTech, Scynexis, and Cepheid; and has received honoraria from Visby Medical, Elsevier, Abbott Molecular, Cepheid, Roche Diagnostics, and Lupin Pharmaceuticals. OTVG has received research grant support from NIH/NIAID, Lupin Pharmaceuticals, Gilead Sciences, and Abbott Molecular and has served on a scientific advisory board for Scynexis. KJG has received research grant support from NIH/NIAID and Lupin Pharmaceuticals. The other authors have no competing interests to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the 2 most frequently reported notifiable sexually transmitted infections (STIs) in the United States, and Trichomonas vaginalis (TV), although not a notifiable disease, is the most common curable non-viral STI worldwide. Women bear a disproportionate burden of these infections and testing is necessary to identify infections. Although vaginal swabs are the recommended sample type, the specimen most often used among women is urine. The objective of this meta-analysis was to assess the diagnostic sensitivity of commercially available assays for vaginal swabs vs urine specimens from women., Methods: A systematic search of multiple databases from 1995 through 2021 identified studies that (1) evaluated commercially available assays, (2) presented data for women, (3) included data obtained from the same assay on both a urine specimen and a vaginal swab from the same patient, (4) used a reference standard, and (5) were published in English. We calculated pooled estimates for sensitivity and the corresponding 95% CIs for each pathogen as well as odds ratios for any difference in performance., Results: We identified 28 eligible articles with 30 comparisons for CT, 16 comparisons for NG, and 9 comparisons for TV. Pooled sensitivity estimates for vaginal swabs and urine, respectively, were 94.1% and 86.9% for CT, 96.5% and 90.7% for NG, and 98.0% and 95.1% for TV (all P values <.001)., Conclusions: Evidence from this analysis supports the Centers for Disease Control and Prevention's recommendation that vaginal swabs are the optimal sample type for women being tested for chlamydia, gonorrhea, and/or trichomoniasis., (© 2023 Annals of Family Medicine, Inc.)

Objective: Data on the prevalence and etiology of infertility in Africa are limited. Secondary infertility is particularly common, defined as the inability of a woman to conceive for at least one year following a full-term pregnancy. We describe a prospective study conducted in Cameroon designed to test the hypothesis of an association between common treatable sexually transmitted infections (STI): Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Mycoplasma genitalium (MG), and Trichomonas vaginalis (TV) and secondary infertility in women., Methods: In this case-control study, we enrolled women in Fako Division, Cameroon between November 2017 and December 2018 with secondary infertility (cases) or current pregnancy (controls). We conducted a baseline survey to collect sociodemographic, and sexual and medical history information. Nucleic acid amplification testing using Aptima (Hologic, San Diego, CA, US) was performed on endocervical swabs for CT, NG, MG, and TV. Multivariable logistic regression was used to assess the relationship between active STI and secondary infertility., Results: A total of 416 women were enrolled: 151 cases and 265 controls. Compared to controls, cases were older (median age 32 vs 27 years) and had more lifetime sexual partners (median 4 vs 3) (p<0.001). Cases were more likely to report dyspareunia, abnormal menses, prior miscarriage, and ectopic pregnancy (all p<0.05). STI positivity was not significantly different among cases and controls (2.7% vs 5.4% for CT, 1.3% vs 2.9% for NG, 6.0% vs 7.0% for MG, respectively), with the exception of TV which was more common in pregnant controls (0.7% vs 5%; p = 0.02)., Conclusion: Study findings did not support an association between active STI and secondary infertility in Cameroon. Given high rates of pre-existing tubal damage, routine STI screening and treatment in younger women may be more impactful than costly STI testing during infertility assessments., Competing Interests: The authors have declared that no competing interests exist.

Objective: Syphilis rates among women in the USA more than doubled between 2014 and 2018. We sought to identify correlates of syphilis among women enrolled in the Women's Interagency HIV Study (WIHS) to inform targeted interventions., Methods: The retrospective cross-sectional analysis of secondary data included women with HIV or at-risk of HIV who enrolled in the multisite US WIHS cohort between 1994 and 2015. Syphilis screening was performed at baseline. Infection was defined serologically by a positive rapid plasma reagin test with confirmatory treponemal antibodies. Sociodemographic and behavioural characteristics stratified by baseline syphilis status were compared for women enrolled during early (1994-2002) and recent (2011-2015) years. Multivariable binomial modelling with backward selection (p>0.2 for removal) was used to model correlates of syphilis., Results: The study included 3692 women in the early cohort and 1182 women in the recent cohort. Syphilis prevalence at enrolment was 7.5% and 3.7% in each cohort, respectively (p<0.01). In adjusted models for the early cohort, factors associated with syphilis included age, black race, low income, hepatitis C seropositivity, drug use, HIV infection and >100 lifetime sex partners (all p<0.05). In the recent cohort, age (adjusted prevalence OR (aPOR) 0.2, 95% CI 0.1 to 0.6 for 30-39 years; aPOR 0.5, 95% CI 0.2 to 1.0 for 40-49 years vs ≥50 years), hepatitis C seropositivity (aPOR 2.1, 95% CI 1.0 to 4.1) and problem alcohol use (aPOR 2.2, 95% CI 1.1 to 4.4) were associated with infection., Conclusions: Syphilis screening is critical for women with HIV and at-risk of HIV. Targeted prevention efforts should focus on women with hepatitis C and problem alcohol use., Competing Interests: Competing interests: Dr. Van Der Pol receives research support, consulting fees and/or honorarium from the following: Abbott Molecular, BD Diagnostics, Binx Health, BioFire Diagnostics, Hologic, Rheonix, Roche and SpeeDx; Dr. Marrazzo receives research support and/or consulting fees from BD Diagnostics, Gilead, and BioFire Diagnostics. Dr. Adimora has received research funding from Gilead and consulting fees from Merck, Viiv, and Gilead. Dr. Sheth has received research grants from Gilead sciences unrelated to the published work. As a group, we have no other conflicts of interest to report., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chlamydia trachomatis is a common bacterial sexually transmitted infection that can persist or recur after antibiotic treatment. Universal screening for chlamydia in pregnancy is recommended to prevent adverse birth outcomes. Single-dose oral azithromycin has been the first-line therapy for chlamydia in pregnancy since 2006., Objective: In the setting of limited data and rising sexually transmitted infection rates in the United States, our goal was to document rates and risk factors for persistent or recurrent chlamydia after azithromycin treatment in pregnancy., Study Design: This retrospective cohort study included pregnancies with urogenital chlamydia and follow-up testing in women who delivered at an Alabama facility between November 2012 and December 2017. Pregnancies with prescribed azithromycin therapy and repeat chlamydia testing ≥21 days later were included. Chlamydia trachomatis nucleic acid amplification testing was performed on genital swab or urine samples. Descriptive characteristics and birth outcomes were compared for categories stratified by repeat test results: persistence (+ +), recurrence (+ - +), or clearance (+ -). Logistic regression models were used to identify demographic and clinical risk factors for persistent or recurrent chlamydia in pregnancy., Results: Among 810 women with 840 pregnancies with repeat chlamydia testing after azithromycin treatment, 114 (14%) had persistence and an additional 72 (9%) had recurrence later in pregnancy. The median time to repeat testing was 30 days (interquartile range, 24-49 days). Concomitant gonorrhea or syphilis in pregnancy was independently associated with persistent or recurrent chlamydia (adjusted odds ratio, 1.6; 95% confidence interval, 1.1-2.4)., Conclusion: Persistent or recurrent chlamydia after azithromycin treatment was detected in nearly 1 in 4 pregnancies with repeat testing in our urban center, highlighting the importance of performing a test of cure and ensuring partner therapy to reduce recurrent chlamydia risk., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Nucleic acid amplification testing (NAAT) is the preferred method to detect Chlamydia trachomatis and Neisseria gonorrhoeae, but information regarding performance of currently available assays is needed. This study evaluated the performance of the Aptima Combo 2, GeneXpert, cobas4800, and ProbeTec Q (CTQ/GCQ) to detect chlamydia and gonorrhea in pharyngeal, rectal, and urine specimen., Methods: Adult male patients seen at an urban human immunodeficiency virus clinic in Birmingham, Alabama who reported sex with men (men who have sex with men) and no antibiotic use in the past 30 days were enrolled between November 2014 and December 2016. Following a baseline survey, rectal and initial void urine specimens were self-collected. A composite infection standard was used, where 1 assay was compared with 3 others to determine sensitivity and specificity estimates for rectal and urine samples. Two pharyngeal samples were clinician-collected for chlamydia and gonorrhea testing and both had to be positive to be considered a true positive., Results: Among the 181 men enrolled into the study, 15.5% and 7.2% had at least 1 positive chlamydia and gonorrhea result at any site, respectively. Among all 4 assays, chlamydia sensitivity rates ranged from 82% to 96% among rectal samples. Rectal gonorrhea sensitivity estimates ranged from 67% to 99%. The GCQ assay was less sensitive in detecting rectal gonorrhea compared with the other assays (P = 0.02)., Conclusions: More than 80% of chlamydia and gonorrhea infections would have been missed with urine-only screening, highlighting the importance in using NAATs to detect chlamydia and gonorrhea infections among men who have sex with men.

Objective: The epidemiology of bacterial vaginosis (BV) favours sexual transmission of BV-associated bacteria. We examined incubation period and risk factors for incident BV (iBV) in a prospective study of women who have sex with women (WSW)., Methods: Using daily self-collected vaginal swabs, WSW with normal vaginal microbiota (no Amsel criteria and a Nugent score of 0-3) were followed for 90 days or until iBV (Nugent score 7-10 on at least 2-3 consecutive days). Daily diaries of sexual activity and menses were completed. Time to iBV was estimated. Accounting for differing lengths of follow-up and age, rates of sexual activities (per 100 person-days (pd)) were compared according to iBV status. The relationship between menses and iBV was also investigated., Results: Of the 36 WSW, the mean age was 30 years (SD 8) and 92% were African American. The probability of iBV at 30 and 60 days was 20% (SD 7%) and 36% (SD 8%), respectively; 14 (39%) developed iBV by 90 days. In WSW with iBV versus those without iBV, the relative rate of any sexual activity prior to iBV was 40% higher (20.4 vs 14.6 per 100 pd; p=0.010), sex with a woman was 38% higher (14.3 vs 10.3 per 100 pd; p=0.038), digital-vaginal sex was 57% higher (14.3 vs 9.1 per 100 pd; p=0.005) and digital-anal sex was 5.6 times higher (2.9 vs 0.5 per 100 pd; p<0.001). iBV was more likely for those WSW with menses in the prior 2 days as compared with those without recent menses (HR 3.4; p=0.029). Sexual activity occurred in 93% WSW at a median of 4 days (95% CI 2 to 6) prior to iBV., Conclusion: iBV was common and associated with sexual activity in this cohort of predominantly African American WSW. An incubation period of 4 days is consistent with other bacterial STIs., Competing Interests: Competing interests: CAM has been a consultant for Lupin Pharmaceuticals and BioFire Diagnostics. She has also received honoraria from Roche Diagnostics and Cepheid. JRS has been a consultant for and received research support from Lupin Pharmaceuticals, Hologic/GenProbe, BD Diagnostics, Cepheid, Quidel, Symbiomix, StarPharma and Toltec., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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

Background: Mycoplasma genitalium (MG) is a sexually transmitted pathogen associated with inflammatory syndromes in men and women. Macrolides and fluoroquinolones are recommended MG treatments. The frequency of MG strains with macrolide resistance-associated mutations (MRMs) and quinolone resistance-associated mutations (qRMs) is increasing worldwide, however these data are sparse in populations in the United States., Methods: We investigated the prevalence of MG infections with MRMs and qRMs and MG infection concordance within African American couples in Birmingham, AL. We used a real-time polymerase chain reaction to detect MG and identify MRMs. quinolone resistance-associated mutations were detected using traditional polymerase chain reactions amplifying regions in gyrA, gyrB, parC, and parE. The MG concordance in couples was evaluated by MG positivity and MG genotypes., Results: Oral, anal, urine, and/or vaginal specimens were tested from 116 couples. Twenty-eight (12.1%) participants comprising 22 couples tested MG-positive (11.2% in men and 12.9% in women). Macrolide resistance-associated mutations were detected in 17 (60.7%) MG-positive participants, with gender-specific resistance rates of 69.2% for men and 53.3% for women. quinolone resistance-associated mutations were detected in 3 (11.1%) MG-positive participants, all of whom also had MRMs. By MG positivity status, 27.3% of couples were concordant. If MG strain genotypes are also considered, then concordance was 20.0%., Conclusions: Among heterosexual African Americans with MG infection, about 60% had strains with MRMs and 11% had strains with both MRMs and qRMs, highlighting the potential for MG treatment failure to not only macrolides, but also quinolones. These findings may help to guide clinicians in MG testing and treatment decisions in the United States.

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

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

We tested for Mycoplasma genitalium in 157 HIV-infected men. Urogenital and rectal prevalence were 10.8% and 6.4%. Macrolide resistance mutations were detected in 70.6% and 80% of urogenital and rectal samples, and fluoroquinolone resistance mutations in 26.7% and 40%, respectively.

Urethral swabs are the samples of choice for point-of-care Gram stain testing to diagnose Neisseria gonorrhoeae infection and nongonococcal urethritis (NGU) in men. As an alternative to urethral swabs, meatal swabs have been recommended for the collection of urethral discharge to diagnose N. gonorrhoeae and Chlamydia trachomatis infection in certain populations by nucleic acid amplification testing (NAAT), as they involve a less invasive collection method. However, as meatal swabs could be sampling a reduced surface area and result in fewer collected epithelial cells compared to urethral swabs, the adequacy of meatal swab specimens to collect sufficient cellular material for Gram stain testing remains unknown. We enrolled 66 men who underwent either urethral or meatal swabbing and compared the cellular content and Gram stain failure rate. We measured the difference in swab cellular content using the Cepheid Xpert CT/NG sample adequacy control crossing threshold (SAC CT ) and determined the failure rate of Gram stain smears (GSS) due to insufficient cellular material. In the absence of discharge, meatal smears were associated with a significant reduction in cellular content ( P = 0.0118), which corresponded with a GSS failure rate significantly higher than that for urethral swabs (45% versus 3%, respectively; P < 0.0001). When discharge was present, there was no difference among results from urethral and meatal swabs. Therefore, if GSS testing is being considered for point-of-care diagnosis of N. gonorrhoeae infection or NGU in men, meatal swabs should be avoided in the absence of a visible discharge., (Copyright © 2017 American Society for Microbiology.)

Background: Better cardiovascular health is associated with lower cardiovascular disease risk., Methods and Results: We determined the association between cardiovascular health and healthcare utilization and expenditures in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. We included 6262 participants ≥65 years with Medicare fee-for-service coverage for the year after their baseline study visit in 2003-2007. Cardiovascular health at baseline was assessed using the American Heart Association's Life's Simple 7 (LS7) metric, which includes 7 factors: cigarette smoking, physical activity, diet, body mass index, blood pressure, cholesterol, and glucose. Healthcare utilization and expenditures were ascertained using Medicare claims in the year following baseline. Overall, 17.2%, 31.1%, 29.0%, 16.4% and 6.4% of participants had 0 to 1, 2, 3, 4, and 5 to 7 ideal LS7 factors, respectively. The multivariable-adjusted relative risk (95% confidence interval [CI]) for having any inpatient and outpatient encounters comparing participants with 5 to 7 versus 0 to 1 ideal LS7 factors were 0.55 (0.39, 0.76) and 1.00 (0.98, 1.02), respectively. Among participants with 0 to 1 and 5 to 7 ideal LS7 factors, mean inpatient expenditures were $3995 and $1250, respectively, mean outpatient expenditures were $5166 and $2853, respectively, and mean total expenditures were $9147 and $4111, respectively. After multivariable adjustment, the mean (95% CI) cost difference comparing participants with 5 to 7 versus 0 to 1 ideal LS7 factors was -$2551 (-$3667, -$1435) for inpatient, -$2410 (-$3089, -$1731) for outpatient, and -$5016 (-$6577, -$3454) for total expenditures., Conclusions: Better cardiovascular health is associated with lower risk for inpatient encounters and lower inpatient and outpatient healthcare expenditures., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Endothelial dysfunction has been shown to be predictive of subsequent cardiovascular events and death. Through a mechanism that is incompletely understood, increased dietary salt intake promotes endothelial dysfunction in healthy, salt-resistant humans. The present study tested the hypothesis that dietary salt-induced transforming growth factor (TGF)-β promoted endothelial dysfunction and salt-dependent changes in blood pressure (BP). Sprague-Dawley rats that received diets containing 0.3% NaCl [low salt (LS)] or 8.0% NaCl [high salt (HS)] were treated with vehicle or SB-525334, a specific inhibitor of TGF-β receptor I/activin receptor-like kinase 5, beginning on day 5. BP was monitored using radiotelemetry in four groups of rats (LS, LS + SB-525334, HS, and HS + SB-525334) for up to 14 days. By day 14 of the study, mean daytime systolic BP and mean pulse pressure of the HS group treated with vehicle was greater than those in the other three groups; mean daytime systolic BP and pulse pressure of the HS + SB-525334 group did not differ from the LS and LS + SB-525334-treated groups. Whereas mean systolic BP, mean diastolic BP, and mean arterial pressure did not differ among the groups on the seventh day of the study, endothelium-dependent vasorelaxation was impaired specifically in the HS group; treatment with the activin receptor-like kinase 5 inhibitor prevented the dietary HS intake-induced increases in phospho-Smad2 (Ser(465/467)) and NADPH oxidase-4 in endothelial lysates and normalized endothelial function. These findings suggest that HS-induced endothelial dysfunction and the development of salt-dependent increases in BP were related to endothelial TGF-β signaling.

The amount of Na(+) and K(+) in the diet promotes significant changes in endothelial cell function. In the present study, a series of in vitro and in vivo experiments determined the role of Na(+) and K(+) in the regulation of two pleckstrin homology domain-containing intracellular signaling molecules, phospholipase C (PLC)-γ1 and epithelial and endothelial tyrosine kinase/bone marrow tyrosine kinase on chromosome X (Bmx), and agonist-generated Ca(2+) signaling in the endothelium. Extracellular K(+) concentration regulated the levels of activated PLC-γ1, Bmx, and carbachol-stimulated intracellular Ca(2+) mobilization in human endothelial cells. Additional experiments confirmed that high-conductance Ca(2+)-activated K(+) channels and phosphatidylinositol 3-kinase mediated these effects. The content of Na(+) and K(+) in the diet also regulated Bmx levels in endothelial cells and activated PLC-γ1 levels in rats in vivo. The effects of dietary K(+) on Bmx were more pronounced in rats fed a high-salt diet compared with rats fed a low-salt diet. These experiments elucidated an endothelial cell signaling mechanism regulated by electrolytes, further demonstrating an integral relationship between endothelial cell function and dietary Na(+) and K(+) content.

Previous studies have demonstrated that an increase in dietary NaCl (salt) intake stimulated endothelial cells to produce transforming growth factor-β (TGF-β). The intent of the present study was to determine the functional significance of increased TGF-β on endothelial cell function. Young Sprague-Dawley rats were fed diets containing 0.3 or 8.0% NaCl for 2 days before treatment with a specific inhibitor of the TGF-β receptor I/activin receptor-like kinase 5 kinase, or vehicle for another 2 days. At day 4 of study, endothelial phosphorylated Smad2 (S465/467) increased and phosphatase and tensin homologue deleted on chromosome 10 (PTEN) levels decreased in the high-salt-treated rats. In addition, phosphorylated Akt (S473) and phosphorylation of the endothelial isoform of NO synthase (NOS3) at S1177 increased. Treatment with the TGF-β receptor I/activin receptor-like kinase 5 inhibitor reduced Smad2 phosphorylation to levels observed in rats on the low-salt diet and prevented the downstream signaling events induced by the high-salt diet. In human umbilical vein endothelial cells, reduction in PTEN levels increased phosphorylated Akt and NOS3. Treatment of macrovascular endothelial cells with TGF-β1 increased phosphorylated NOS3 and the concentration of NO metabolites in the medium but had no effect on either of these variables in cells pretreated with small interfering RNA directed against PTEN. Thus, during high salt intake, an increase in TGF-β directly promoted a reduction in endothelial PTEN levels, which in turn regulated Akt activation and NOS3 phosphorylation. This effect closes a feedback loop that potentially mitigates the effect of TGF-β on the vasculature.

The objective of this review was to provide a synthesis of the evidence on the effect of dietary salt and potassium intake on population blood pressure, cardiovascular disease, and mortality. Dietary guidelines and recommendations are outlined, current controversies regarding the evidence are discussed, and recommendations are made on the basis of the evidence. Designed search strategies were used to search various databases for available studies. Randomized trials of the effect of dietary salt intake reduction or increased potassium intake on blood pressure, target organ damage, cardiovascular disease, and mortality were included. Fifty-two publications from January 1, 1990, to January 31, 2013, were identified for inclusion. Consideration was given to variations in the search terms used and the spelling of terms so that studies were not overlooked, and search terms took the following general form: (dietary salt or dietary sodium or [synonyms]) and (dietary potassium or [synonyms]) and (blood pressure or hypertension or vascular disease or heart disease or chronic kidney disease or stroke or mortality or [synonyms]). Evidence from these studies demonstrates that high salt intake not only increases blood pressure but also plays a role in endothelial dysfunction, cardiovascular structure and function, albuminuria and kidney disease progression, and cardiovascular morbidity and mortality in the general population. Conversely, dietary potassium intake attenuates these effects, showing a linkage to reduction in stroke rates and cardiovascular disease risk. Various subpopulations, such as overweight and obese individuals and aging adults, exhibit greater sensitivity to the effects of reduced salt intake and may gain the most benefits. A diet that includes modest salt restriction while increasing potassium intake serves as a strategy to prevent or control hypertension and decrease cardiovascular morbidity and mortality. Thus, the body of evidence supports population-wide sodium intake reduction and recommended increases in dietary potassium intake as outlined by current guidelines as an essential public health effort to prevent kidney disease, stroke, and cardiovascular disease., (Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Increased dietary Na intake and decreased dietary K intake are associated with higher blood pressure. It is not known whether the dietary Na:K ratio is associated with all-cause mortality or stroke incidence and whether this relationship varies according to race. Between 2003 and 2007, the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort enrolled 30 239 black and white Americans aged 45 years or older. Diet was assessed using the Block 98 FFQ and was available on 21 374 participants. The Na:K ratio was modelled in race- and sex-specific quintiles for all analyses, with the lowest quintile (Q1) as the reference group. Data on other covariates were collected using both an in-home assessment and telephone interviews. We identified 1779 deaths and 363 strokes over a mean of 4·9 years. We used Cox proportional hazards models to obtain multivariable-adjusted hazard ratios (HR). In the highest quintile (Q5), a high Na:K ratio was associated with all-cause mortality (Q5 v. Q1 for whites: HR 1·22; 95 % CI 1·00, 1·47, P for trend = 0·084; for blacks: HR 1·36; 95 % CI 1·04, 1·77, P for trend = 0·028). A high Na:K ratio was not significantly associated with stroke in whites (HR 1·29; 95 % CI 0·88, 1·90) or blacks (HR 1·39; 95 % CI 0·78, 2·48), partly because of the low number of stroke events. In the REGARDS study, a high Na:K ratio was associated with all-cause mortality and there was a suggestive association between the Na:K ratio and stroke. These data support the policies targeted at reduction of Na from the food supply and recommendations to increase K intake.

Objective: In the United States, kidney dysfunction is prevalent in almost 30% of HIV-infected patients and is an independent predictor of mortality. Proteinuria and elevated serum cystatin C (eCysC) are used as markers of kidney disease in the general population; however, the prevalence of these markers in HIV-infected adolescents is largely unknown., Methods: This study includes 304 HIV-infected adolescents from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort, an observational study of adolescents recruited from 13 US cities. Clinical and demographic characteristics of participants were evaluated as correlates of proteinuria, a urine protein to creatinine ratio of ≥200 mg/g. Select univariate predictors were assessed to determine the association with urinary protein excretion and serum cystatin C in multivariable linear regression models and proteinuria and eCysC (eCysC ≥ 75th percentile) in multivariable logistic regression models., Results: Overall, 19.1% of the participants had proteinuria, whereas 23.7% had an eCysC. Low CD4 T-lymphocyte counts (<200 cells/mm) were significantly associated with a greater urine protein to creatinine ratio in linear models and with proteinuria in logistic regression models. CD4 T-lymphocyte counts <500 cells/mm were significantly associated with a greater serum cystatin C concentration in linear models and with eCysC in logistic regression models., Conclusions: Proteinuria among HIV-infected adolescents in the REACH cohort was approximately 2-fold greater than healthy US adolescents. Both proteinuria and eCysC are associated with CD4 T-lymphocyte counts. Further studies investigating early markers of kidney disease and the association with immune status and inflammation in HIV-infected adolescents are needed.

A common renal complication of multiple myeloma is "myeloma kidney," a condition also known as cast nephropathy. The renal lesions (casts) are directly related to the production of monoclonal immunoglobulin free light chains (FLCs), which coprecipitate with Tamm-Horsfall glycoprotein (THP) in the lumen of the distal nephron, obstructing tubular fluid flow. Here, we report that analysis of the binding interaction between FLCs and THP demonstrates that the secondary structure and key amino acid residues on the complementarity-determining region 3 (CDR3) of FLCs are critically important determinants of the molecular interaction with THP. The findings permitted development of a cyclized competitor peptide that demonstrated strong inhibitory capability in the binding of FLCs to THP in vitro. When used in a rodent model of cast nephropathy, this cyclized peptide construct served as an effective inhibitor of intraluminal cast formation and prevented the functional manifestations of acute kidney injury in vivo. These experiments provide proof of concept that intraluminal cast formation is integrally involved in the pathogenesis of acute kidney injury from cast nephropathy. Further, the data support a clinically relevant approach to the management of renal failure in the setting of multiple myeloma.

Aging promotes endothelial dysfunction, defined as a reduction in bioavailable nitric oxide (NO) produced by the endothelial isoform of nitric oxide synthase (NOS3). This enzyme is critically regulated by phosphorylation by protein kinase B (Akt), which in turn is regulated by the lipid phosphatase, PTEN. The present series of studies demonstrated a reduction in bioavailable NO as the age of rats increased from 1 to 12 months. At 12 months of age, rats no longer demonstrated increases in phosphorylated NOS3 in response to high dietary salt intake. Endothelial cell levels of PTEN increased with age and became refractory to change with increased salt intake. In contrast to the reduction in NO production, endothelial cell production of transforming growth factor-ß (TGF-ß) relative to NO increased progressively with age. In macrovascular endothelial cells, PTEN was regulated in a dose-dependent fashion by TGF-ß, which was further regulated by extracellular [KCl]. When combined with prior studies, the present series of experiments suggested an integral role for PTEN in endothelial cell pathobiology of aging and an important mitigating function of TGF-ß in endothelial PTEN regulation. The findings further supported a role for diet in affecting vascular function through the production of TGF-ß and NO.

Background: Among obese adults, sodium intake has been associated with cardiovascular disease. Few data are available on sodium intake and albuminuria, a marker of kidney damage and risk factor for cardiovascular disease., Objective: We examined the relation between dietary sodium and potassium intakes and the ratio of sodium to potassium (Na/K) with albuminuria by BMI in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study (n = 30,239 adults aged ≥45 y)., Design: A modified Block 98 food-frequency questionnaire was used for dietary assessment in 21,636 participants, and nutritional variables were categorized by sex-specific quintiles. Normal weight, overweight, and obese were defined as BMI (in kg/m(2)) categories of 18.5-24.9, 25-29.9, and ≥30, respectively. Albuminuria was defined as a ratio (mg/g) of urinary albumin to creatinine of ≥30., Results: The prevalences of albuminuria were 11.5%, 11.6%, and 16.0% in normal-weight, overweight, and obese participants, respectively. The multivariable-adjusted ORs for albuminuria in a comparison of the highest with the lowest quintile of Na/K intake (≥1.12 to <0.70 for men and ≥1.07 to <0.62 for women) were 0.89 (95% CI: 0.65, 1.22), 1.08 (95% CI: 0.85, 1.36), and 1.28 (95% CI: 1.02, 1.61) in normal-weight, overweight, and obese participants, respectively. The highest quintile of dietary sodium was associated with an increased OR for albuminuria in obese participants (OR: 1.44; 95% CI: 1.00, 2.07) but not in normal-weight or overweight participants. Dietary potassium was not associated with albuminuria., Conclusion: In obese adults, higher dietary Na/K and sodium intakes were associated with albuminuria.

One of the major attendant complications of multiple myeloma is renal injury, which contributes significantly to morbidity and mortality in this disease. Monoclonal immunoglobulin free light chains (FLCs) are usually directly involved, and tubulointerstitial renal injury and fibrosis are prominent histologic features observed in myeloma. The present study examined the role of monoclonal FLCs in altering the nuclear factor κ light chain enhancer of activated B cells (NF-κB) activity of renal epithelial cells. Human proximal tubule epithelial cells exposed to 3 different human monoclonal FLCs demonstrated Src kinase-dependent activation of the NF-κB pathway, which increased production of monocyte chemoattractant protein-1 (MCP-1). Tyrosine phosphorylation of inhibitor of κB kinases (IKKs) IKKα and IKKβ and a concomitant increase in inhibitor of κB (IκB) kinase activity in cell lysates were observed. Time-dependent, Src kinase-dependent increases in serine and tyrosine phosphorylation of IκBα and NF-κB activity were also demonstrated. Proteasome inhibition partially blocked FLC-induced MCP-1 production. These findings fit into a paradigm characterized by FLC-induced redox-signaling events that activated the canonical and atypical (IKK-independent) NF-κB pathways to promote a proinflammatory, profibrotic renal environment.