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Among 73 women presenting to a sexually transmitted infection (STI) clinic in Birmingham, Alabama for reported sexual contact to a chlamydia-infected partner, Chlamydia trachomatis was detected in genital specimens in 24 (32.8%), less often in women reporting prior chlamydial infection ( P = 0.001). Most women (93.2%) were C. trachomatis seropositive.

To prepare for the development of the 2021 Centers for Disease Control and Prevention (CDC) sexually transmitted infections treatment guidelines, the CDC convened a committee of expert consultants in June 2019 to discuss recent abstracts and published literature on the epidemiology, diagnosis, and management of sexually transmitted infections.This paper summarizes the key questions, evidence, and recommendations for the diagnosis and management of uncomplicated Chlamydia trachomatis (CT) infections in adolescents and adults that were reviewed and discussed for consideration in developing the guidelines. The evidence reviewed mostly focused on efficacy of doxycycline and azithromycin for urogenital, rectal, and oropharyngeal CT infection, CT risk factors in women, performance of CT nucleic acid amplification tests on self-collected meatal specimens in men, and performance of newer CT point-of-care tests.

Mycoplasma genitalium is an important sexually transmitted pathogen affecting both men and women. Its extremely slow growth in vitro and very demanding culture requirements necessitate the use of molecular-based diagnostic tests for its detection in clinical specimens. The recent availability of U.S. Food and Drug Administration (FDA)-cleared commercial molecular-based assays has enabled diagnostic testing to become more widely available in the United States and no longer limited to specialized reference laboratories. Advances in the knowledge of the epidemiology and clinical significance of M. genitalium as a human pathogen made possible by the availability of molecular-based testing have led to updated guidelines for diagnostic testing and treatment that have been published in various countries. This review summarizes the importance of M. genitalium as an agent of human disease, explains the necessity of obtaining a microbiological diagnosis, describes currently available diagnostic methods, and discusses how the emergence of antimicrobial resistance has complicated treatment alternatives and influenced the development of diagnostic tests for resistance detection, with an emphasis on developments over the past few years.

Background Nearly 14% of US women report any lifetime infertility which is associated with healthcare costs and psychosocial consequences. Tubal factor infertility (TFI) often occurs as a result of sexually transmitted diseases and subsequent pelvic inflammatory disease. We sought to evaluate for and describe potential racial disparities in TFI and in vitro fertilization (IVF) prevalence. Methods Records of women aged 19-42 years in our retrospective cohort from two US infertility clinics were reviewed. We calculated TFI prevalence, IVF initiation prevalence, and prevalence ratios (PR), with 95% confidence intervals for each estimate, overall and by race. Results Among 660 infertile women, 110 (16.7%; 95% confidence interval [CI] 13.8-19.5%) had TFI which was higher in black compared to white women (30.3% [33/109] vs. 13.9% [68/489]; PR 2.2 [95% CI 1.5-3.1]). For women with TFI, IVF was offered to similar proportions of women by race (51.5% [17/33] versus 52.9% [36/68] for black versus white women); however, fewer black than white women with TFI started IVF (6.7% [1/15] versus 31.0% [9/29]; PR 0.2 [95% CI 0-1.0]), although the difference was not statistically different. Conclusions TFI prevalence was two-fold higher among black than white women seeking care for infertility. Among women with TFI, data suggested a lower likelihood of black women starting IVF than white women. Improved sexually transmitted disease prevention and treatment might ameliorate disparities in TFI.

Background Chlamydia trachomatis (Ct) infection ascending to the upper genital tract can cause infertility. Direct association of genetic variants as contributors is challenging because infertility may not be diagnosed until years after infection. Investigating the intermediate trait of ascension bridges this gap. Methods We identified infertility genome-wide association study (GWAS) loci using deoxyribonucleic acid from Ct-seropositive cisgender women in a tubal factor infertility study and Ct-infected cisgender women from a longitudinal pelvic inflammatory disease cohort with known fertility status. Deoxyribonucleic acid and blood messenger ribonucleic acid from 2 additional female cohorts with active Ct infection and known endometrial infection status were used to investigate the impact of infertility single-nucleotide polymorphisms (SNPs) on Ct ascension. A statistical mediation test examined whether multiple infertility SNPs jointly influenced ascension risk by modulating expression of mediator genes. Results We identified 112 candidate infertility GWAS loci, and 31 associated with Ct ascension. The SNPs altered chlamydial ascension by modulating expression of 40 mediator genes. Mediator genes identified are involved in innate immune responses including type I interferon production, T-cell function, fibrosis, female reproductive tract health, and protein synthesis and degradation. Conclusions We identified Ct-related infertility loci and their potential functional effects on Ct ascension.

In men with nongonococcal urethritis (NGU), clinicians and patients rely on clinical cure to guide the need for additional testing/treatment and when to resume sex, respectively; however, discordant clinical and microbiological cure outcomes do occur. How accurately clinical cure reflects microbiological cure in specific sexually transmitted infections (STIs) is unclear.Men with NGU were tested for Neisseria gonorrhoeae, Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Trichomonas vaginalis, urethrotropic Neisseria meningitidis ST-11 clade strains, and Ureaplasma urealyticum (UU). Men received azithromycin 1 g and returned for a 1-month test-of-cure visit. In MG infections, we evaluated for the presence of macrolide resistance-mediating mutations (MRMs) and investigated alternate hypotheses for microbiological treatment failure using in situ shotgun metagenomic sequencing, phylogenetic analysis, multilocus sequence typing analyses, and quantitative PCR.Of 280 men with NGU, 121 were included in this analysis. In the monoinfection group, 52 had CT, 16 had MG, 7 had UU, 10 had mixed infection, and 36 men had idiopathic NGU. Clinical cure rates were 85% for CT, 100% for UU, 50% for MG, and 67% for idiopathic NGU. Clinical cure accurately predicted microbiological cure for all STIs, except MG. Discordant results were significantly associated with MG-NGU and predominantly reflected microbiological failure in men with clinical cure. Mycoplasma genitalium MRMs, but not MG load or strain, were strongly associated with microbiological failure.In azithromycin-treated NGU, clinical cure predicts microbiological cure for all STIs, except MG. Nongonococcal urethritis management should include MG testing and confirmation of microbiological cure in azithromycin-treated MG-NGU when MRM testing is unavailable.

Mycoplasma genitalium (MG) infection, a sexually transmitted infection (STI), causes cervicitis and may cause reproductive sequelae and adverse pregnancy outcomes. Some MG-infected women report dysuria, a symptom frequently attributed to urinary tract infection (UTI). Given potential MG-associated morbidity and the likelihood that UTI treatment would be ineffective in eradicating MG, an improved understanding of MG infection frequency and clinical significance in young women reporting dysuria is needed. We conducted MG testing on stored urogenital specimens collected in a pilot study on frequency of STIs in young women presenting to an emergency department for dysuria evaluation and performed a literature review on MG infection frequency in women reporting dysuria. Among 25 women presenting for dysuria evaluation in our pilot study, 6 (24.0%) had MG detected and one-third had co-infection with chlamydia and one-third with trichomoniasis; half with MG detected did not receive an antibiotic with known efficacy against MG, while the other half received azithromycin. In five studies identified in the literature review, dysuria was reported by 7%–19% of women and MG detected in 5%–22%. MG infection is common in young women with dysuria and empiric UTI treatment may not be effective against MG. Studies evaluating the clinical significance of MG infection in women reporting dysuria are needed.

BackgroundChlamydial infection is associated with tubal factor infertility (TFI); however, assessment of prior chlamydial infection and TFI is imperfect. We previously evaluated a combination of serological assays for association with TFI. We now describe the chlamydial contribution to TFI using a newer Chlamydia trachomatis Pgp3 enhanced serological (Pgp3) assay.MethodsIn our case-control study of women 19–42 years old with hysterosalpingogram-diagnosed TFI (cases) and non-TFI (controls) in two U.S. infertility clinics, we assessed possible associations and effect modifiers between Pgp3 seropositivity and TFI using adjusted odds ratios (aOR) with 95% confidence intervals (CI) stratified by race. We then estimated the adjusted chlamydia population attributable fraction (aPAF) with 95% CI of TFI.ResultsAll black (n=107) and 618 of 620 non-black women had Pgp3 results. Pgp3 seropositivity was 25.9% (19.3–33.8%) for non-black cases, 15.2% (12.3–18.7%) for non-black controls, 66.0% (95% CI 51.7–77.8%) for black cases, and 71.7% (59.2–81.5%) for black controls. Among 476 non-black women without endometriosis (n=476), Pgp3 was associated with TFI (aOR 2.6 [1.5– 4.4]), adjusting for clinic, age, and income; chlamydia TFI aPAF was 19.8% (95% CI 7.7–32.2%) in these women. Pgp3 positivity was not associated with TFI among non-black women with endometriosis nor among black women (regardless of endometriosis).ConclusionsAmong non-black infertile women without endometriosis in these clinics, 20% of TFI was attributed to chlamydia. Better biomarkers are needed to estimate chlamydia TFI PAF, especially in black women.

BACKGROUND Chlamydia trachomatis (CT) infection remains highly prevalent, and young women are disproportionately affected. Most CT-infected women are asymptomatic, and their infection often goes unrecognized and untreated. We hypothesized that testing for active CT infection with molecular diagnostics and obtaining a reported history of CT infection underestimate the prevalence of current and past CT infection, and incorporating serum CT antibody testing in addition to these other prevalence measures would generate more accurate estimates of the prevalence of CT infection in asymptomatic young women. METHODS We enrolled 362 asymptomatic women aged 16 to 29 years at 4 different clinical settings in Birmingham, AL, between August 2016 and January 2020 and determined the prevalence of CT infection based on having 1 or more of the following prevalence measures: an active urogenital CT infection based on molecular testing, reported prior CT infection, and/or being CT seropositive. Multivariable regression analysis was used to determine predictors of the prevalence of CT infection after adjustment for participant characteristics. RESULTS The prevalence of CT infection was 67.7% (95% confidence interval, 62.6%-72.5%). Addition of CT antibody testing to the other individual prevalence measures more than doubled the CT infection prevalence. Non-Hispanic Black race, reported prior gonorrhea, and reported prior trichomoniasis predicted a higher prevalence of CT infection. CONCLUSIONS More than half of women were unaware of ever having CT infection, suggesting many were at risk for CT-associated reproductive complications. These data reinforce the need to adhere to chlamydia screening guidelines and to increase screening coverage in those at risk.

Background Antimicrobial resistance in Mycoplasma genitalium (MG), a cause of urethritis, is a growing concern. Yet little is known about the geographic distribution of MG resistance in the United States or about its associated clinical outcomes. We evaluated the frequency of MG among men with urethritis, resistance mutations, and posttreatment symptom persistence. Methods We enrolled men presenting with urethritis symptoms to 6 US sexually transmitted disease (STD) clinics during June 2017–July 2018; men with urethritis were eligible for follow-up contact and, if they had persistent symptoms or MG, a chart review. Urethral specimens were tested for MG and other bacterial STDs. Mutations in 23S ribosomal ribonucleic acid (rRNA) loci (macrolide resistance–associated mutations [MRMs]) and in parC and gyrA (quinolone-associated mutations) were detected by targeted amplification/Sanger sequencing. Results Among 914 evaluable participants, 28.7% (95% confidence interval [CI], 23.8–33.6) had MG. Men with MG were more often Black (79.8% vs 66%, respectively), Conclusions MG infection was common among men with urethritis; the MRM prevalence was high among men with MG. Persistent symptoms following treatment were frequent among men both with and without MG.

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 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.

BACKGROUND African Americans have the highest rates of Chlamydia trachomatis (CT) infection in the United States and also high reinfection rates. The primary objective of this study was to develop a Bayesian model to predict the probability of CT reinfection in African American women using immunogenetic data. METHODS We analyzed data from a cohort of CT-infected African American women enrolled at the time they returned to a clinic in Birmingham, AL, for the treatment of a positive routine CT test result. We modeled the probability of CT reinfection within 6 months after treatment using logistic regression in a Bayesian framework. Predictors of interest were presence or absence of an HLA-DQB1*06 allele and CT-specific CD4+ IFN-γ response, both of which we had previously reported were independently associated with CT reinfection risk. RESULTS Among 99 participants evaluated, the probability of reinfection for those with a CT-specific CD4+ IFN-γ response and no HLA-DQB1*06 alleles was 14.1% (95% credible interval [CI], 3.0%-45.0%), whereas the probability of reinfection for those without a CT-specific CD4+ IFN-γ response and at least one HLA-DQB1*06 allele was 61.5% (95% CI, 23.1%-89.7%). CONCLUSIONS Our model demonstrated that presence or absence of an HLA-DQB1*06 allele and CT-specific CD4+ IFN-γ response can have an impact on the predictive probability of CT reinfection in African American women.

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

We used the Food and Drug Administration-cleared Aptima Mycoplasma genitalium assay to evaluate for M. genitalium infection among young women without urogenital symptoms presenting to a community-based emergency department in Birmingham, Alabama, between August 2016 to August 2019 for evaluation of nongynecological concerns. M. genitalium was detected in 23 (14.8%) of 155 women.

Advancing the understanding of pelvic inflammatory disease (PID) requires access to advanced diagnostic approaches for evaluating reproductive sequelae of sexually transmitted infections (STIs). Current limitations of clinical criteria and advanced imaging technologies for diagnosing reproductive sequelae make diagnosis and surveillance of PID a challenge. We summarize and comment on major challenges in diagnostic evaluation of reproductive sequelae: limited point-of-care clinical diagnostic options for reproductive sequelae, economic and geographical obstacles to accessing state-of-the-art diagnostics, an expanding list of STIs that may cause reproductive sequelae and the complexities in evaluating them, and the need for coordinated research efforts to systematically evaluate biomarkers with gold-standard, well-defined specimens and associated clinical data. The future use of biomarkers in readily accessible mucosal or blood-derived specimens as a noninvasive approach to determining STI etiologies may be fruitful and requires more research. Biomarkers under consideration include cytokines, STI-specific antibody responses, and mRNA transcriptional profiles of inflammatory markers.

Chlamydia trachomatis (CT) causes pelvic inflammatory disease, which may result in tubal factor infertility (TFI) in women. Serologic assays may be used to determine the proportion of women with and without TFI who have had previous CT infection and to generate estimates of infertility attributable to chlamydia. Unfortunately, most existing CT serologic assays are challenged by low sensitivity and sometimes specificity for prior CT infection, however they are currently the only available tests available to detect prior CT infection. Modeling methods such as finite mixture modeling may be a useful adjunct to quantitative serologic data to obtain better estimates of CT-related infertility. In this paper, we review CT serological assays, including the use of antigens preferentially expressed during upper genital tract infection, and suggest future research directions. These methodologic improvements coupled with creation of new biomarkers for previous CT infection should improve our understanding of chlamydia’s contribution to female infertility.Chlamydia trachomatis (CT) is the most common sexually transmitted bacteria in the world[1]. In CT-infected women who go untreated, approximately 17% develop pelvic inflammatory disease (PID), inflammation of upper genital tract structures, and this may result in chronic sequelae, including ectopic pregnancy and tubal factor infertility (TFI)[2]. In the United Kingdom, it has been estimated that CT causes approximately 35% of PID cases in women under 25 years of age and 20% in aged 16-44 years[2, 3]. Other PID-associated pathogens include Neisseria gonorrhoeae, Mycoplasma genitalium, and bacterial vaginosis-associated bacteria [4]. The majority of symptomatic PID cases have no pathogen identified[2, 4, 5]. Further, many PID cases remain undiagnosed due to atypical or absent symptoms [2-4]. There is good evidence from a longitudinal cohort study of 1884 women with PID that the persistence of fallopian tube pathology (adhesions/scarring) can cause infertility in women – tubal factor infertility (TFI)[5]. Only women with PID who have macroscopic fallopian tube inflammation (salpingitis) are at risk of TFI, which is present in some but not all diagnosed PID[2, 5]. A dose response relationship has been observed with more severe macroscopic salpingitis and more PID episodes leading to a greater risk for adverse reproductive outcomes, especially for CT infection[2, 5, 6]. There is also evidence that upper genital tract CT infection may also impair fertility in the absence of tubal pathology, this is reviewed elsewhere in this supplement by Horner et al

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.

Chlamydia trachomatis is an obligate intracellular bacterium. C. trachomatis infection is the most prevalent bacterial sexually transmitted infection and can lead to pelvic inflammatory disease and infertility in women. There is no licensed vaccine for C. trachomatis prevention, in part due to gaps in our knowledge of C. trachomatis-specific immune responses elicited during human infections. Previous investigations of the antibody response to C. trachomatis have identified immunodominant antigens and antibodies that can neutralize infection in cell culture. However, epitope-specific responses to C. trachomatis are not well characterized, and the impact of these antibodies on infection outcome is unknown. We recently developed a technology called deep sequence-coupled biopanning that uses bacteriophage virus-like particles to display peptides from antigens and affinity select against human serum IgG. Here, we used this technology to map C. trachomatis-specific antibodies in groups of women with defined outcomes following C. trachomatis infection: (i) C. trachomatis negative upon presentation for treatment (“spontaneous resolvers”), (ii) C. trachomatis negative at a 3-month follow-up visit after treatment (“nonreinfected”), and (iii) C. trachomatis positive at a 3-month follow-up after treatment (“reinfected”). This analysis yielded immunodominant epitopes that had been previously described but also identified new epitopes targeted by human antibody responses to C. trachomatis. We focused on human antibody responses to the C. trachomatis variable domain 4 serovar-conserved region of the major outer membrane protein (VD4-MOMP), a previously described immunodominant epitope. All three groups of women produced IgG to the VD4-MOMP, suggesting that detection of serum antibodies to VD4-MOMP in women with urogenital C. trachomatis infection is not associated with protection against reinfection. IMPORTANCEC. trachomatis infection is the most common bacterial sexually transmitted infection, and infection in women can lead to pelvic inflammatory disease and infertility. No licensed vaccine exists to prevent C. trachomatis infection, and investigations of the natural immune response may inform the design of targeted vaccines for C. trachomatis. Our study fills a gap in knowledge regarding the epitope specificity of antibody responses that are elicited in response to C. trachomatis infection in women. We identified several new B cell epitopes for C. trachomatis antigens and confirmed B cell epitopes that have been identified by other methods. Our finding that women produce antibodies to the VD4-MOMP regardless of infection outcome provides insight into vaccine development, suggesting that vaccines targeting VD4-MOMP may need to elicit higher-titer antibody responses than natural infection imparts or that additional vaccine targets should be pursued in the future.

Class Mollicutes includes organisms in the genera Mycoplasma and Ureaplasma. They are prokaryotes that lack a cell wall and are among the smallest known living organisms both in cellular dimension and genome size. At least 17 different species inhabit the mucosae of the respiratory and urogenital tracts of humans, several of which are pathogenic in a variety of clinical illnesses. Their fastidious nature and often slow growth in vitro has hampered understanding of their roles as agents of human disease. Mycoplasma hominis and Ureaplasma spp. have been recognized as causes of various pelvic inflammatory syndromes in women and systemic illnesses in immunocompromised persons, and U. urealyticum has been identified as a potential cause of urethritis in men. The appreciation of Mycoplasma genitalium as an important cause of inflammatory urogenital syndromes in men and women has come about over the past decade as a result of the advancement of molecular methods for its detection. Development of resistance to macrolides and fluoroquinolones in M. genitalium has made management of these infections more challenging. This review provides an update on the epidemiology, pathogenesis, disease spectrum, diagnosis, and treatment of urogenital and/or systemic infections caused by these organisms. This review contains 1 figure, 2 tables and 97 references Key Words: Antimicrobial Resistance, Inflammation, Mycoplasma, Pelvic Inflammatory Disease, Sexually Transmitted Infections, Ureaplasma

The class Mollicutes includes organisms in the genera Mycoplasma and Ureaplasma. They are prokaryotes that lack a cell wall, and are among the smallest known living organisms in both cellular dimensions and genome sizes. At least 17 different species inhabit the mucosae of the respiratory and urogenital tracts of humans, several of which are pathogenic in a variety of clinical illnesses. Their fastidious nature and often slow growth in vitro have hampered understanding of their roles as agents of human disease. Mycoplasma pneumoniae is an important cause of community acquired respiratory infections that occur endemically and epidemically worldwide in persons of all ages and ranges in severity from mild to life-threatening. Molecular-based laboratory techniques have resulted in increased understanding of the pathogenesis and epidemiology M. pneumoniae infections as well as improved means for laboratory detection. Resistance of M. pneumoniae to macrolide antimicrobials has emerged worldwide over the past several years, complicating treatment strategies. This review contains 2 figures, 1 table and 58 references Key Words: Antimicrobial Resistance, Ciliated respiratory epithelium, Community Acquired Pneumonia, Cytadherence, Mycoplasma pneumoniae, Reinfections

A longstanding challenge facing MD-PhD students and other dual-degree medical trainees is the loss of clinical knowledge that occurs during the non medical phases of training. Academic medical institutions nationwide have developed continued clinical training and exposure to maintain clinical competence; however, quantitative assessment of their usefulness remains largely unexplored. The current study therefore sought to both implement and optimize an online game platform to support MD-PhD students throughout their research training. Sixty three current MD-PhD students completing the PhD research phase of training were enrolled in an institutionally-developed online game platform for 2 preliminary and 4 competition rounds of 3-4 weeks each. During preliminary game rounds, we found that participation, though initially high, declined precipitously throughout the duration of each round, with 37 students participating to some extent. Daily reminders were implemented in subsequent rounds, which markedly improved player participation. Average participation in competition rounds exceeded 35% (23/63) active participants each round, with trending improvement in scores throughout the duration of PhD training. Both player participation and progress through the research phase of the MD-PhD program correlated positively with game performance and therefore knowledge retention and/or acquisition. Coupled with positive survey-based feedback from participants, our data therefore suggest that gamification is an effective tool for MD-PhD programs to combat loss of clinical knowledge during research training.

T cell phenotypes involved in the immune response to Chlamydia trachomatis (CT) have not been fully elucidated in humans. We evaluated differences in T cell phenotypes between CT-infected women and CT-seronegative controls and investigated changes in T cell phenotype distributions after CT treatment and their association with reinfection. We found a higher expression of T cell activation markers (CD38(+)HLA-DR(+)), T helper type 1 (Th1)- and Th2-associated effector phenotypes (CXCR3(+)CCR5(+) and CCR4(+), respectively), and T cell homing marker (CCR7) for both CD4(+) and CD8(+) T cells in CT-infected women. At follow-up after treatment of infected women, there were a lower proportion of CD4(+) and CD8(+) T cells expressing these markers. These findings suggest a dynamic interplay of CD4(+) and CD8(+) T cells in CT infection, and once the infection is treated, these cell markers return to basal expression levels. In women without reinfection a significantly higher proportion of CD8(+) T cells co-expressing CXCR3 with CCR5 or CCR4 at follow-up was detected compared to women with reinfection, suggesting they might play some role in adaptive immunity. Our study elucidated changes in T cell phenotypes during CT infection and after treatment, broadening our understanding of adaptive immune mechanisms in human CT infections.

Chlamydia trachomatis elementary body enzyme-linked immunosorbent assay (ELISA) was used to investigate serum anti-CT immunoglobulin G1 (IgG1; long-lived response) and immunoglobulin G3 (IgG3; short-lived response indicating more recent infection) from treatment (enrollment) and 6-month follow-up visits in 77 women previously classified as having spontaneous resolution of chlamydia. Of these women, 71.4% were IgG1+IgG3+, consistent with more recent chlamydia resolution. 15.6% were IgG3− at both visits, suggesting absence of recent chlamydia. Using elementary body ELISA, we demonstrated approximately 1 in 6 women classified as having spontaneous resolution of chlamydia might have been exposed to C. trachomatis but not infected. Further, we classified their possible infection stage.

We evaluated the prevalence of Mycoplasma genitalium co-infection in 302 chlamydia-infected women seen at a sexually transmitted disease clinic in Birmingham, Alabama. M. genitalium co-infection was detected in 22 (7.3%). No participant characteristics predicted co-infection. Among co-infected women, M. genitalium was detected again in 6 of 21 (28.6%) women returning for a 3-month follow-up visit after azithromycin treatment.

Background Mycoplasma genitalium (MG) is an emerging cause of urethritis. Although an FDA-approved MG diagnostic test is now available in the U.S., syndromic management of urethritis remains widespread. Little is known about the geographic distribution of MG resistance in the U.S. and associated clinical outcomes. We evaluated the frequency of MG among men with urethritis, antimicrobial susceptibility of MG, and post-treatment symptom persistence. Methods We enrolled men presenting with urethritis symptoms to 6 U.S. STD clinics during June 2017–July 2018. Participants with urethritis confirmed on stained urethral smear were eligible for a follow-up phone call 14–17 days post-enrollment and chart review. Urethral specimens were tested locally for N. gonorrhoeae and C. trachomatis. CDC tested specimens for MG and T. vaginalis. MG resistance mutations were detected by targeted amplification/Sanger sequencing of 23S rRNA loci (macrolide resistance mutations [MRM]) and parC and gyrA (quinolone resistance mutations). Results Among 914 participants with evaluable MG results, MG was detected in 28.7% (95% CI 23.8–33.6). Men with MG were more often black (79.8% vs 66%), Conclusion MG was common among men with urethritis and MRM prevalence high. Persistent symptoms were frequent among men with and without MG. Many participants with macrolide-resistant MG experienced symptom persistence and returned to clinic for evaluation. Disclosure No significant relationships.

Background African Americans have the highest rates of Chlamydia trachomatis (CT) infection in the U.S., nearly six-fold higher than Caucasians. Even after controlling for sociodemographic factors, African American women have higher CT infection rates, suggesting immunogenetic factors could influence infection risk. The primary objective of this study is to develop a Bayesian model to predict CT reinfection in African American women. Methods We are using data from a study cohort of CT-infected women who were enrolled when they returned to a STD clinic in Birmingham, AL, USA, for treatment of a positive screening urogenital CT nucleic acid amplification test. They had repeat urogenital CT NAAT performed at enrollment and 3- and 6-month follow-up visits. We modeled the probability of CT reinfection within 6 months after treatment using conditional logistic regression in a Bayesian framework and weakly informative priors. Primary predictors of interest were immunogenetic risk factors specified by the presence of at least one HLA-DQB1*06 allele and absence of a CT-specific CD4+ IFN-γ response. Additional predictors evaluated include the modifying effects of unprotected sex and concomitant bacterial vaginosis (BV). Results To date, we have evaluated 75 participants for whom complete data were available. Modeling both HLA-DQB1*06 and a CT-specific CD4+ IFN-γ response performed best for expected predictive accuracy of CT reinfection within 6 months after treatment. Under this model, the probability of reinfection for those with a CT-specific CD4+ IFN-γ response and no HLA-DQB1*06 alleles was 23.1% (95% CI: 7.6%–47.5%), whereas probability of reinfection for those without a CT-specific CD4+ IFN-γ response and at least one HLA-DQB1*06 allele was 75.0% (95% CI: 52.5%–89.1%). Conclusion Our model evaluating immunogenetic factors predicting CT reinfection demonstrated that presence of an HLA-DQB1*06 allele and absence of a CT-specific CD4+ IFN-γ response may be a significant predictor in African American women. Disclosure No significant relationships.

Background Our recent case-control study explored the Chlamydia trachomatis population attributable fraction (PAF) for tubal factor infertility (TFI) using an elementary body enzyme-linked immunosorbent serological assay (EB-ELISA) or a commercially available (Medac) major outer membrane protein ELISA to measure prior chlamydial infection. We examined data from this study using a Pgp3 enhanced ELISA (Pgp3). Methods In this study of women with TFI by hysterosalpingogram (cases) and non-TFI infertility (controls) in two U.S. infertility clinics, we assessed anti-C. trachomatis seropositivity by Pgp3. We then assessed the association between chlamydia seropositivity and TFI using adjusted odds ratios (aOR) along with 95% confidence intervals (CI) stratified by race. Finally, the adjusted chlamydia TFI PAF (aPAF) and 95% CI based on the Pgp3 assay were estimated. Results All black (n=107) and 618 of 620 non-black women had Pgp3 results. Seropositivity frequency by Pgp3 was 66% (95% CI 52–80%) for black cases, 72% (60–83%) for black controls, 26% (19–33%) for non-black cases, and 15% (12–18%) for non-black controls. Pgp3 was not associated with TFI among black women (aOR 1.1 [95% CI 0.4–3.3]). Among non-black women, Pgp3 seropositivity was associated with TFI (aOR 1.8 [95% CI 1.1–3.0]) adjusting for clinic, age, income, trichomonas, and endometriosis. Using Pgp3 and adjusting for the same variables, chlamydia TFI aPAF was 12% (95% CI 1–22%) in non-black women. Conclusion Among non-black women, Pgp3 ELISA seropositivity was associated with TFI. Assays to estimate chlamydia TFI PAF merit further investigation, especially in black women. Chlamydial TFI may be prevented in all women by early identification and treatment of chlamydia. Disclosure No significant relationships.

Mycoplasma genitalium (MG) infection is a sexually transmitted infection that causes up to 25% of nongonococcal urethritis (NGU). MG strains carrying genetic markers of antimicrobial resistance that may affect treatment outcomes are increasingly recognized as a public health concern. We present two cases of persistent MG NGU with strains carrying both macrolide and quinolone resistance-associated mutations that were eradicated successfully by an extended course of minocycline.

© 2018 Elsevier Ltd Genital Chlamydia trachomatis infection is the most commonly diagnosed sexually transmitted infection. Trachoma is caused by ocular infection with C trachomatis and is the leading infectious cause of blindness worldwide. New serological assays for C trachomatis could facilitate improved understanding of C trachomatis epidemiology and prevention. C trachomatis serology offers a means of investigating the incidence of chlamydia infection and might be developed as a biomarker of scarring sequelae, such as pelvic inflammatory disease. Therefore, serological assays have potential as epidemiological tools to quantify unmet need, inform service planning, evaluate interventions including screening and treatment, and to assess new vaccine candidates. However, questions about the performance characteristics and interpretation of C trachomatis serological assays remain, which must be addressed to advance development within this field. In this Personal View, we explore the available information about C trachomatis serology and propose several priority actions. These actions involve development of target product profiles to guide assay selection and assessment across multiple applications and populations, establishment of a serum bank to facilitate assay development and evaluation, and development of technical and statistical methods for assay evaluation and analysis of serological findings. The field of C trachomatis serology will benefit from collaboration across the public health community to align technological developments with their potential applications.

Little is known about whether Chlamydia trachomatis can be sexually transmitted between women or how often it occurs in women who have sex with women (WSW). We investigated Chlamydia trachomatis prevalence and serum Chlamydia trachomatis-specific antibody responses among African American WSW who reported a lifetime history of sex only with women (exclusive WSW) (n = 21) vs. an age-matched group of women reporting sex with women and men (WSWM) ( n = 42). Participants completed a survey, underwent a pelvic examination in which a cervical swab was collected for Chlamydia trachomatis nucleic acid amplification testing (NAAT), and had serum tested for anti- Chlamydia trachomatis IgG1 and IgG3 antibodies using a Chlamydia trachomatis elementary body-based ELISA. No exclusive WSW had a positive Chlamydia trachomatis NAAT vs. 5 (11.9%) WSWM having a positive Chlamydia trachomatis NAAT ( p = 0.16). Compared with WSWM, WSW were significantly less likely to be Chlamydia trachomatis seropositive (7 [33.3%] vs. 29 [69%], p = 0.007). Among Chlamydia trachomatis seropositive women, all were seropositive by IgG1, and the magnitude of Chlamydia trachomatis-specific IgG1 responses did not differ in Chlamydia trachomatis-seropositive WSW vs. WSWM. In conclusion, Chlamydia trachomatis seropositivity was relatively common in exclusive African American WSW, though significantly less common than in African American WSWM.

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.

Chlamydia trachomatis (CT) infections remain highly prevalent. CT reinfection occurs frequently within months after treatment, likely contributing to sustaining the high CT infection prevalence. Sparse studies have suggested CT reinfection is associated with a lower organism load, but it is unclear whether CT load at the time of treatment influences CT reinfection risk. In this study, women presenting for treatment of a positive CT screening test were enrolled, treated and returned for 3- and 6-month follow-up visits. CT organism loads were quantified at each visit. We evaluated for an association of CT bacterial load at initial infection with reinfection risk and investigated factors influencing the CT load at baseline and follow-up in those with CT reinfection. We found no association of initial CT load with reinfection risk. We found a significant decrease in the median log10 CT load from baseline to follow-up in those with reinfection (5.6 CT/ml vs. 4.5 CT/ml; P = 0.015). Upon stratification of reinfected subjects based upon presence or absence of a history of CT infections prior to their infection at the baseline visit, we found a significant decline in the CT load from baseline to follow-up (5.7 CT/ml vs. 4.3 CT/ml; P = 0.021) exclusively in patients with a history of CT infections prior to our study. Our findings suggest repeated CT infections may lead to possible development of partial immunity against CT.

Chlamydia trachomatis infection (chlamydia) is the most prevalent sexually transmitted bacterial infection and causes significant reproductive morbidity in women. Little is known about how immunity to chlamydia develops in women, though animal models of chlamydia indicate that T-helper type 1 (Th1) responses are important for chlamydia clearance and protective immunity, whereas T-helper type 2 (Th2) responses are associated with persisting infection. In chlamydia-infected women, whether the predominant immune response is Th1- or Th2-polarizing remains controversial. To determine the cytokine profiles elicited by peripheral blood mononuclear cells (PBMCs) from chlamydia-infected women, we stimulated PBMCs with C. trachomatis elementary bodies and recombinant C. trachomatis Pgp3 and measured supernatant levels of select cytokines spanning Th1- and Th2-polarizing responses. We found that stimulated PBMCs from chlamydia-infected women secreted cytokines that indicate strong Th1-polarizing responses, especially interferon-gamma, whereas Th2-polarizing cytokines were expressed at significantly lower levels. In chlamydia-infected women, the predominant cytokine responses elicited on stimulation of PBMCs with C. trachomatis antigens were Th1-polarizing, with interferon-gamma as the predominant cytokine.

Chlamydia trachomatis serological assays with improved sensitivity over commercially available assays are needed to evaluate the burden of C. trachomatis infection and the effectiveness of prevention efforts. We evaluated the performance of a C. trachomatis outer membrane complex protein B (OmcB) enzyme-linked immunosorbent assay (ELISA) in the detection of anti- C. trachomatis antibody responses in C. trachomatis -infected women.