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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.

Chlamydia trachomatis is the leading cause of sexually transmitted infections that may progress to pelvic inflammatory disease and infertility. No effective vaccine exists for Chlamydia, nor are there biomarkers available that readily predict disease progression. In this cross-sectional pilot study, we recruited symptomatic and asymptomatic women with C. trachomatis (CT) infection and asymptomatic, uninfected control women from an urban sexually transmitted disease clinic to determine if there were differences in microRNA (miRNA) expression. Infected women with signs and/or symptoms (CTSS) have distinct miRNA profiles compared to asymptomatic infected women (CTNS). In the CTSS group, miR-142 and -147 showed 2.2- to 6.9-fold increases in expression. In the CTNS group, miR-449c, -6779, -519d, -449a, and -2467 showed 3.9- to 9.0-fold increases in expression. In the CTNS group, cyclins and cell cycle regulation and IL-17 pathways were likely downregulated, while the same signaling pathways were upregulated in the CTSS group. In addition, in the CTSS group, additional inflammatory pathways associated with TNFR1 and IL-8 appear to be upregulated. The miRNA expression patterns differ between CT-infected symptomatic and asymptomatic women, and these differences may warrant further study.

In this phase 2 study, single oral doses of gepotidacin were ≥95% effective for bacterial eradication in culture-proven uncomplicated urogenital gonorrhea. New antibiotics for drug-resistant Neisseria gonorrhoeae are urgently needed. With additional evaluation, gepotidacin may provide an alternative therapeutic option., Background In this phase 2 study, we evaluated the efficacy and safety of oral gepotidacin, a novel triazaacenaphthylene bacterial type II topoisomerase inhibitor, for the treatment of uncomplicated urogenital gonorrhea. Methods Adult participants with suspected urogenital gonorrhea were enrolled and completed baseline (day 1) and test-of-cure (days 4–8) visits. Pretreatment and posttreatment urogenital swabs were collected for Neisseria gonorrhoeae (NG) culture and susceptibility testing. Pharyngeal and rectal swab specimens were collected if there were known exposures. Participants were stratified by gender and randomized 1:1 to receive a 1500-mg or 3000-mg single oral dose of gepotidacin. Results The microbiologically evaluable population consisted of 69 participants, with NG isolated from 69 (100%) urogenital, 2 (3%) pharyngeal, and 3 (4%) rectal specimens. Microbiological eradication of NG was achieved by 97%, 95%, and 96% of participants (lower 1-sided exact 95% confidence interval bound, 85.1%, 84.7%, and 89.1%, respectively) for the 1500-mg, 3000-mg, and combined dose groups, respectively. Microbiological cure was achieved in 66/69 (96%) urogenital infections. All 3 failures were NG isolates that demonstrated the highest observed gepotidacin minimum inhibitory concentration of 1 µg/mL and a common gene mutation. At the pharyngeal and rectal sites, 1/2 and 3/3 NG isolates, respectively, demonstrated microbiological cure. There were no treatment-limiting adverse events for either dose. Conclusions This study demonstrated that single, oral doses of gepotidacin were ≥95% effective for bacterial eradication of NG in adult participants with uncomplicated urogenital gonorrhea. Clinical Trials Registration NCT02294682.

At a clinic in Indianapolis, Indiana, USA, we observed an increase in Neisseria gonorrhoeae-negative men with suspected gonococcal urethritis who had urethral cultures positive for N. meningitidis. We describe genomes of 2 of these N. meningitidis sequence type 11 complex urethritis isolates. Clinical evidence suggests these isolates may represent an emerging urethrotropic clade.

ObjectivesChlamydia trachomatis(CT) andMycoplasma genitalium(MG) cause the majority of non-gonococcal urethritis (NGU). The role ofUreaplasma urealyticum(UU) in NGU is unclear. Prior case–control studies that examined the association of UU and NGU may have been confounded by mixed infections and less stringent criteria for controls. The objective of this case–control study was to determine the prevalence and aetiology of mixed infections in men and assess if UU monoinfection is associated with NGU.MethodsWe identified 155 men with NGU and 103 controls. Behavioural and clinical information was obtained and men were tested forNeisseria gonorrhoeaeand CT, MG, UU andTrichomonas vaginalis(TV). Men who were five-pathogen negative were classified as idiopathic urethritis (IU).ResultsTwelve per cent of NGU cases in which a pathogen was identified had mixed infections, mostly UU coinfections with MG or CT; 27% had IU. In monoinfected NGU cases, 34% had CT, 17% had MG, 11% had UU and 2% had TV. In controls, pathogens were rarely identified, except for UU, which was present in 20%. Comparing cases and controls, NGU was associated with CT and MG monoinfections and mixed infections. UU monoinfection was not associated with NGU and was almost twice as prevalent in controls. Men in both the case and control groups who were younger and who reported no prior NGU diagnosis were more likely to have UU (OR 0.97 per year of age, 95% CI 0.94 to 0.998 and OR 6.3, 95% CI 1.4 to 28.5, respectively).ConclusionsMixed infections are common in men with NGU and most of these are UU coinfections with other pathogens that are well-established causes of NGU. UU monoinfections are not associated with NGU and are common in younger men and men who have never previously had NGU. Almost half of NGU cases are idiopathic.

Background Persistent NGU occurs when symptoms persist after empiric NGU treatment and has been associated with Mycoplasma genitalium (MG) infection. The prevalence and etiology of persistent NGU in men remains largely unknown. Methods Within the Idiopathic Urethritis Men’s Project cohort study, we recruited men with NGU. NGU was diagnosed by the presence of urethritis signs and/or symptoms and urethral Gram stain with ≥5 PMN/HPF. Men were treated with 1 gm azithromycin and returned for a 1-month test-of-cure visit. At the test-of-cure visit, men were asked about post-treatment symptom outcomes and partner treatment. A first-catch urine specimen was obtained at both visits for five-pathogen testing for Neisseria gonorrhoeae (NG),Chlamydia trachomatis (CT), MG, Trichomonas vaginalis (TV), and Ureaplasma urealyticum (UU). NG-positive cases were excluded and five-pathogen-negative cases were classified as idiopathic urethritis (IU). Post-treatment symptom outcomes were: (1) resolved, (2) resolved then recurred, or (3) persisted unchanged. Results One hundred twenty-four men are included in this study. The median age was 28, 52% were African American, and 86% self-identified as heterosexual. All men reported urethral symptoms and 98% had a discharge on exam at baseline. Symptoms resolved completely in 91 (73%) men. Symptoms resolved then recurred or persisted unchanged in 12 (10%) and 21 (17%) men, respectively. Excluding men with untreated partners (N = 9, 28%), a different pathogen was identified in 5 (50%) and 4 (25%) men with recurrent and persistent symptoms, respectively. In men with the same pathogen identified (N = 15), 53% were IU, 33% were MG, 7% were CT, and 7% were UU. Conclusion Persistent NGU occurs in approximately 25% of azithromycin-treated men and is related to a new infection in up to 50% of cases. In men with persistent symptoms and the same infection identified at the test-of-cure visit, MG and IU comprised 86% of cases, which suggests that MG and IU-associated organisms may be resistant to azithromycin. Disclosure No significant relationships.

Background Syndromic management remains the standard nongonococcal urethritis (NGU) treatment approach. Whether pathogen-specific signs/symptoms inform treatment decisions remains unclear. We identified men with single- and mixed-pathogen NGU and assessed for the presence of pathogen-specific signs or symptoms to improve syndromic management. Methods As part of an ongoing cohort study (the Idiopathic Urethritis Men’s Project [IUMP]), we recruited men with NGU. NGU was diagnosed by signs and/or symptoms of urethritis, and a urethral Gram stain with ≥5 neutrophils per high-power field without evidence of gram negative intracellular diplococci. Participants underwent a clinical history and physical exam, which documented specific self-reported symptoms and clinician observed signs. Single- and mixed-infections were identified by NAAT testing of first-catch urine for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Trichomonas vaginalis (TV), and Ureaplasma urealyticum (UU); five-pathogen-negative cases were classified as idiopathic urethritis (IU). Results One hundred fifty-five men with NGU are included in this analysis. The median age was 28 (range 18–63), 101 (65%) were African American, and 135 (87%) self-identified as heterosexual. The most commonly reported symptom was urethral discharge (92%), followed by burning/tingling (37%), and dysuria (28%). Over half of these men reported more than one symptom (58%). Single-pathogen NGU was detected in 99 (64%) men, mixed-pathogen in 14 (9%), and IU in 42 (27%). For single pathogen NGU, 53 (34%) had CT, 26 (17%) had MG, 3 (2%) had TV, and 17 (11%) had UU. We compared single-pathogen NGU, mixed-infection and IU for differences in signs or symptoms and found no pathogen-specific differences. Conclusion In men with NGU, no pathogen-specific signs and symptoms were identified that could inform treatment decisions. Pathogen-specific point-of-care tests are needed. Disclosure No significant relationships.

Background The ability to quantify the organism load of Chlamydia trachomatis (CT) using a commercial assay could expand insights from epidemiological studies. This approach can be applied to routine diagnostic testing, and multiple specimen types. Approximate CT organism load was determined in urine from men with NGU, with and without co-infections, by comparing the results from each positive sample to a set of CT standards using the Abbott Realtime m2000 (m2000) platform. Methods Urine specimens, collected from men participating in the Idiopathic Urethritis Men’s Project (IUMP), were tested on the m2000 for CT. Additional testing included Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis, and Ureaplasma urealyticum. Standards were prepared by diluting CT elementary bodies (EB) into the collection device at six concentrations. CT organism load was determined by comparing the instrument generated delta cycle (DC) value from each CT positive urine to the standard curve. Calculated means were compared by t-test (p Results Two hundred and six men were tested for CT and 83 (40.3%) were positive. The DC values for 81/83 (97.3%) CT positive samples fell within the range of the standard curve. The mean DC value was 12.15 (range 0.19–16.96) which equated to a mean CT organism load of 1.4×106 EB/ml urine (range 2.22×102-9.97×106). There was no difference between the mean organism load in specimens from men who did and did not have co-infections with other STIs, 2.04×106 versus 1.38×106 EB/ml, (p≥0.05). Conclusion CT load determination can be performed on urine specimens using the m2000. This could facilitate straightforward load determination in settings where routine testing is performed. In men with NGU, the CT organism load is high and no difference in CT load was observed in men with CT mono-infections and men co-infected with CT and other STIs. Disclosure No significant relationships.

BACKGROUND. Rectal infection with Chlamydia trachomatis (CT) is frequent in women who deny receptive anal sex and is thought to arise from autoinoculation of the rectum from vaginal secretions. An alternate hypothesis is that oral sex inoculates and establishes gastrointestinal tract infection. Distinguishing these hypotheses is difficult in women. In men, autoinoculation is unlikely and heterosexual men frequently perform oral sex, but rarely participate in receptive anal exposure behaviors. METHODS. We enrolled high-risk men with and without nongonococcal urethritis (NGU) who presented to a sexually transmitted infection clinic in Indianapolis, Indiana. Urine and rectal swabs were collected and tested for urogenital and rectal CT, Neisseria gonorrhoeae (NG), and Mycoplasma genitalium (MG). Men completed surveys concerning symptoms, sexual orientation, and detailed recent and lifetime oral and anal sexual behaviors. RESULTS. Rectal CT was detected in 2/84 (2.4%) heterosexual men who reported cunnilingus, but no lifetime receptive anal behaviors. All of the men who denied receptive anal behaviors were negative for rectal NG and MG. In homosexual and bisexual men, rectal CT prevalence was high (9.7%) and rectal NG (4.8%) and MG (4.8%) were also detected. CONCLUSIONS. We detected rectal CT infections in heterosexual men who reported cunnilingus but denied receptive anal behaviors. Oral sex may be a risk factor for rectal CT infection via oral inoculation of the gastrointestinal tract. SUMMARY. We observed a low incidence of rectal C. trachomatis infection in heterosexual men.

BACKGROUND Sexual transmission rates of Chlamydia trachomatis (Ct) cannot be measured directly; however, the study of concordance of Ct infection in sexual partnerships (dyads) can help to illuminate factors influencing Ct transmission. METHODS Heterosexual men and women with Ct infection and their sex partners were enrolled and partner-specific coital and behavioral data collected for the prior 30 days. Microbiological data included Ct culture, and nucleic acid amplification testing (NAAT), quantitative Ct polymerase chain reaction, and ompA genotyping. We measured Ct concordance in dyads and factors (correlates) associated with concordance. RESULTS One hundred twenty-one women and 125 men formed 128 dyads. Overall, 72.9% of male partners of NAAT-positive women and 68.6% of female partners of NAAT-positive men were Ct-infected. Concordance was more common in dyads with culture-positive members (78.6% of male partners, 77% of female partners). Partners of women and men who were NAAT-positive only had lower concordance (33.3%, 46.4%, respectively). Women in concordant dyads had significantly higher median endocervical quantitative Ct polymerase chain reaction values (3,032) compared with CT-infected women in discordant dyads (1013 inclusion forming units DNA equivalents per mL; P < 0.01). Among 54 Ct-concordant dyads with ompA genotype data for both members, 96.2% had identical genotypes. CONCLUSIONS Higher organism load appears associated with concordance among women. Same-genotype chlamydial concordance was high in sexual partnerships. No behavioral factors were sufficiently discriminating to guide partner services activities. Findings may help model coitus-specific transmission probabilities.

Antibiotic-resistant Neisseria gonorrhoeae has prompted the development of new therapies. Zoliflodacin is a new antibiotic that inhibits DNA biosynthesis. In this multicenter, phase 2 trial, zoliflodacin was evaluated for the treatment of uncomplicated gonorrhea.We randomly assigned eligible men and women who had signs or symptoms of uncomplicated urogenital gonorrhea or untreated urogenital gonorrhea or who had had sexual contact in the preceding 14 days with a person who had gonorrhea to receive a single oral dose of zoliflodacin (2 g or 3 g) or a single 500-mg intramuscular dose of ceftriaxone in a ratio of approximately 70:70:40. A test of cure occurred within 6±2 days after treatment, followed by a safety visit 31±2 days after treatment. The primary efficacy outcome measure was the proportion of urogenital microbiologic cure in the microbiologic intention-to-treat (micro-ITT) population.From November 2014 through December 2015, a total of 179 participants (167 men and 12 women) were enrolled. Among the 141 participants in the micro-ITT population who could be evaluated, microbiologic cure at urogenital sites was documented in 55 of 57 (96%) who received 2 g of zoliflodacin, 54 of 56 (96%) who received 3 g of zoliflodacin, and 28 of 28 (100%) who received ceftriaxone. All rectal infections were cured in all 5 participants who received 2 g of zoliflodacin and all 7 who received 3 g, and in all 3 participants in the group that received ceftriaxone. Pharyngeal infections were cured in 4 of 8 participants (50%), 9 of 11 participants (82%), and 4 of 4 participants (100%) in the groups that received 2 g of zoliflodacin, 3 g of zoliflodacin, and ceftriaxone, respectively. A total of 84 adverse events were reported: 24 in the group that received 2 g of zoliflodacin, 37 in the group that received 3 g of zoliflodacin, and 23 in the group that received ceftriaxone. According to investigators, a total of 21 adverse events were thought to be related to zoliflodacin, and most such events were gastrointestinal.The majority of uncomplicated urogenital and rectal gonococcal infections were successfully treated with oral zoliflodacin, but this agent was less efficacious in the treatment of pharyngeal infections. (Funded by the National Institutes of Health and Entasis Therapeutics; ClinicalTrials.gov number, NCT02257918 .).

Summary Contact precautions may have an adverse effect on a patient's hospital experience and the delivery of care. This case–control study compared patient satisfaction scores between 70 patients isolated for MRSA and 139 non-isolated patients. Based on an adjusted analysis, there was no difference in patient satisfaction between the two groups. Age and educational status were found to affect patient satisfaction.

Use of multilocus sequence typing may help identify new strains in at-risk populations., Chlamydia trachomatis causes a high number of sexually transmitted infections worldwide, but reproducible and precise strain typing to link partners is lacking. We evaluated multilocus sequence typing (MLST) for this purpose by detecting sequence types (STs) concordant for the ompA genotype, a single-locus typing standard. We tested samples collected during April 2000–October 2003 from members of established heterosexual partnerships (dyads) in the Indianapolis, Indiana, USA, area who self-reported being coital partners within the previous 30 days. C. trachomatis DNA from 28 dyads was tested by MLST; sequences were aligned and analyzed for ST and phylogenetic relationships. MLST detected 9 C. trachomatis STs, 4 unique to Indianapolis; STs were identical within each dyad. Thirteen unique strains were identified; 9 (32%) dyads harbored novel recombinant strains that phylogenetically clustered with strains comprising the recombinants. The high rate of novel C. trachomatis recombinants identified supports the use of MLST for transmission and strain diversity studies among at-risk populations.

A randomized, double-blind study comparing single-dose chlamydia therapies of oral rifalazil (25 mg) and azithromycin (1 g) was conducted in 82 women with uncomplicated genital Chlamydia trachomatis infection. The microbiologic cure rate of C. trachomatis with rifalazil ( n = 33) was 84.8% at the visit on day 22 to 26 (test-of-cure visit), versus 92.1% with azithromycin ( n = 38), and the number of treatment failures in each group was 5 and 3, respectively. The difference in cure rate was −7.3%, with a lower limit of the 95% confidence interval (95% CI) of −22.5, and thus, noninferiority was not established at the prespecified margin (lower limit of CI of −15%). The overall treatment-emergent adverse event (TEAE) and treatment-related TEAE rates were lower in the rifalazil group (68% and 55%) than in the azithromycin group (71% and 62%), respectively. Subjects classified as treatment failures at day 22 to 26 had a lower mean plasma concentration of rifalazil at the visit on day 8 to 12 than those classified as treatment cures, but this difference was not significant; however, the levels were similar for both groups at the visit on day 22 to 26. A single 25-mg dose of rifalazil was well tolerated and eradicated C. trachomatis in most of these women with uncomplicated genital C. trachomatis infection. (The study was registered at clinicaltrials.gov under registration no. NCT01631201).

To avoid positive results attributable to residual DNA, the Centers for Disease Control and Prevention recommends avoiding repeat testing with nucleic-acid based tests within 3 weeks after treatment of chlamydial (Chlamydia trachomatis [CT]) or gonococcal (Neisseria gonorrhoeae [GC]) infection. We retrospectively analyzed the duration of detectable DNA from a longitudinal cohort of adolescent women after diagnosis and treatment of infection with CT, GC, or Trichomonas vaginalis (TV).Vaginal swabs were obtained weekly from young women for up to 12 weeks (observation period) after treatment of CT, GC and TV infections. Swabs were tested using a commercially available first generation nucleic acid amplification test (NAAT) for CT and GC, and a laboratory developed NAAT for TV. Kaplan-Meier statistics were used to estimate median time to the first negative DNA-based polymerase chain reaction (PCR) result.Observation periods were available for analysis for 195, 82 and 102 treatments for CT, GC, and TV infection, respectively. Median time to a first negative PCR result for CT, GC, and TV was 9 (range 0-84), 6 (0-76), and 7 (0-84) days, and by day 21, 89%, 95%, and 85% were negative, respectively.Data from this retrospective analysis indicate that greater than 85% of these young women did not have detectable CT, GC, or TV DNA by day 21 post-treatment. This data may be useful to clinicians for patient management and post-treatment testing purposes.

Background. Recent studies have raised concern about efficacy of azithromycin for Chlamydia trachomatis infection. Research investigating new antibiotic regimens for chlamydia has been sparse, especially regimens that may reduce adherence difficulties with the recommended twice-daily doxycycline regimen. Methods. We conducted a randomized, double-blind, double-dummy, active-controlled, multicenter trial with the objective of evaluating the safety and efficacy of WC2031 (doxycycline hyclate delayed-release 200-mg tablet) orally once daily for 7 days versus Vibramycin (doxycycline hyclate capsule) 100 mg orally twice daily for 7 days for treatment of uncomplicated urogenital chlamydia. Men and nonpregnant women aged 19–45 years with a urogenital chlamydial diagnosis or a sexual partner with chlamydia were eligible. The primary outcome was microbial cure by nucleic acid amplification testing at day 28. Noninferiority of WC2031 was inferred if the lower limit of the 95% confidence interval (CI) of the difference in cure rates was >�10%. Results. A total of 495 subjects were randomized. The modified intent-to-treat (mITT) population with evaluable efficacy consisted of 323 subjects. Baseline patient characteristics did not differ between the mITT groups. Microbial cure rates for WC2031 were 95.5% (95% CI, 92.3–98.8) versus 95.2% (95% CI, 92.0–98.4) for Vibramycin (95% CI for the difference in cure rates, �4.3% to 4.9%). Types of adverse events were comparable. Nausea and vomiting occurred less frequently with WC2031 than with Vibramycin (13% vs 21% and 8% vs 12%, respectively). Conclusions. WC2031 was noninferior to Vibramycin for uncomplicated urogenital chlamydia treatment, better tolerated, and demonstrated comparable safety. WC2031 could improve treatment adherence over twice-daily Vibramycin.

Background Mycoplasma genitalium (MG) causes symptomatic nonchlamydial, nongonococcal urethritis in men, and cervicitis, pelvic inflammatory disease and infertility in women. We aimed to determine: prevalence and concordance of MG infection within heterosexual partnerships; MG detection by sample site in infected subjects; symptom association with MG infection; frequency of co-infection with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV); and risk factors associated with MG infection and concordance. Methods Data from two partnership studies were combined; both enrolled sexually active heterosexual couples between the ages of 14–24 years who were at high risk for CT, between April 10, 2000 and September 29, 2003 at a sexually transmitted infection (STI) clinic in Indianapolis, IN. MG was detected by nucleic acid amplification from specimens stored at −70°C for up to 48 months. MG was sought in urine and urethra in men and urine, vagina, and cervix in women. Symptoms evaluated were dysuria, discharge in men and discharge, dysuria, abdominal pain in women. Symptom association with MG infection was analyzed by Chi-square test and logistic regression was used for associations of demographic, behavioral and biologic factors with MG concordance. Results Microbiologic data were available from 200 men and 217 women, and demographic information from 188 men and 201 women in partnerships. 43/217 dyads contained an individual with MG infection, and both individuals were infected in 11/43 (26%) partnerships (concordant). In men and women MG detection was highest in urine (10%, 9%) specimens. Prevalence of MG was 14% in women and10% in men. Most infected men (79%) and women (62%) were African American. Mean age at first sex was 14 years for both genders. CT was the most frequent co-infection in both MG infected men (32%) and women (52%). MG infection without co-infection was associated with penile discharge in men (57%) P = 0.18. No symptoms in women were indicative of MG infection, and no demographic, behavioral or biologic factors were statistically associated with MG concordance. Conclusion The prevalence of MG was substantial. Concordance in partnerships was 26%, less than observed with CT (~70%) in this study. Our study is limited due to small numbers of subjects with MG infection. Disclosures All authors: No reported disclosures.

Background. Some screening and treatment programs implemented to control Chlamydia trachomatis genital infections and their complications have shown initial reductions in infection prevalence, followed by increases to preprogram levels or higher. One hypothesis is that treatment shortens duration of infection, attenuates development of protective immunity, and thereby, increases risk of reinfection. Methods. A literature review was undertaken to assess evidence supporting the concept of protective immunity,its characteristics, and its laboratory correlates in human chlamydial infection. The discussion is organized around key questions formulated in preparation for the Chlamydia Immunology and Control Expert Advisory Meeting held by the Centers for Disease Control and Prevention in April 2008. Results. Definitive human studies are not available, but cross-sectional studies show that chlamydia prevalence,organism load, and concordance rates in couples decrease with age, and organism load is lower in those with repeat infections, supporting the concept of protective immunity. The protection appears partial and can be overcome after reexposure, similar to what has been found in rodent models of genital infection. No data are available to define the duration of infection required to confer a degree of immunity or the time course of immunity after resolution of untreated infection. In longitudinal studies involving African sex workers, a group presumed to have frequent and ongoing exposure to chlamydial infection, interferon-g production by peripheral blood mononuclear cells in response to chlamydial heat-shock protein 60 was associated with low risk of incident infection.In cross-sectional studies, relevant T helper 1-type responses were found in infected persons, paralleling the studies in animal models. Conclusions. The data support the concept that some degree of protective immunity against reinfection develops after human genital infection, although it appears, at best, to be partial. It is likely that factors besides population levels of immunity contribute to trends in prevalence observed in screening and treatment programs.Future studies of protective immunity in humans will require longitudinal follow-up of individuals and populations,frequent biological and behavioral sampling, and special cohorts to help control for exposure.

Purpose: To examine associations between depressive symptoms and dyad-level sexual risk behavior in young heterosexual dyads with sexually transmitted infection (STI). Methods: Chlamydia-positive 14-24-year-old, heterosexually active outpatients and their opposite-sex partners completed an assessment that included demographics, past and recent STI risk behaviors, and the Beck Depression Inventory (BDI). Participants in the top 25% of BDI scores within gender were categorized as depressed. Variables were created to identify dyads in which the female or male partner was depressed, as well as a measure of concordance of depression between partners. Dyad-level STI risk variables were created from the STI risk characteristics reported by each dyad member, and associations between these and the depression variables were analyzed. Results: The 130 dyads were comprised of young men and women at high STI risk. One-third of dyads had at least one depressed partner. Dyads in which the female partner was depressed had greater partner age difference, greater total number of lifetime partners, and one or more partners reporting substance use within 2 hours before sex, compared with dyads in which the female partner was not depressed. Dyads in which the male partner was depressed were more likely than the nondepressed-male dyads to report substance use before sex. All dyads in which both partners were depressed reported substance use before sex. Conclusions: In young, chlamydia-infected, heterosexual dyads, depressive symptoms, especially in women, is related to increased dyad-level STI risk, including greater partner age difference, more partners, and substance use before sex.

Purpose Mycoplasma genitalium is a possible sexually transmitted pathogen and its study among the adolescent age group has been limited. In this longitudinal study, the epidemiology, natural history, and associated clinical findings of M. genitalium among adolescents in a primary care setting were explored. Methods A sample of 383 young women (14–17 years of age) and 117 male partners provided sexual behavior data and urogenital samples for polymerase chain reaction testing to detect M. genitalium , Chlamydia trachomatis , and other sexually transmitted infections. Women were tested quarterly for up to 27 months and, during every other quarter, tested weekly. The presence of any signs or symptoms of infection among the female subjects was also documented. Results Cumulatively, 13.6% (52/383) of women tested positive for M. genitalium . All women with M. genitalium , except one, were sexually experienced. M. genitalium was associated with number of sexual partners ( p C. trachomatis infection ( p M. genitalium was more likely among male partners of M. genitalium -positive women ( p M. genitalium cases had infection lasting over 8 weeks. M. genitalium was not associated with the presence of clinical signs or symptoms of infection. Conclusions Findings support sexual transmissibility of M. genitalium and add to understanding of M. genitalium natural history and clinical findings.

Background Trichomonas vaginalis infection is a sexually transmitted infection (STI) linked with reproductive health complications. However, few data exist concerning the epidemiologic profile of this pathogen in adolescent women, a group at high risk for other STIs. Methods Our objective was to describe the prevalence, incidence, natural history, and response to treatment of T. vaginalis infection in adolescent women. Women 14-17 years old were followed for up to 27 months. Vaginal swab samples were obtained during quarterly clinic visits and were self-obtained weekly during 12-week diary collection periods. The weekly samples were tested quarterly. Infections were identified by polymerase chain reaction and were treated with 2.0 g of oral metronidazole. Analysis was performed on the subset of participants who returned for at least 1 quarterly clinic visit. Results T. vaginalis infection was identified in 6.0% (16/268) of the participants at enrollment. Overall, 23.2% (57/245) of the participants with at least 3 months of follow-up had at least 1 infection episode; 31.6% (18/57) experienced multiple episodes. Seventy-two incident infection episodes were diagnosed. When treatment was not documented, weekly samples from participants were positive for up to 12 consecutive weeks. After treatment, T. vaginalis DNA was undetectable within 2 weeks in all but 3 participants. Conclusions The incidence of T. vaginalis infection is high among adolescent women; untreated infections may last undetected for 3 months or longer. Reinfection is common. Treatment with oral metronidazole is effective, and T. vaginalis DNA disappears rapidly after treatment.

Trichomonas vaginalis infection is estimated to be the most widely prevalent nonviral sexually transmitted infection in the world. Wet-mount microscopy is the most common diagnostic method, although it is less sensitive than culture. The OSOM Trichomonas Rapid Test (Genzyme Diagnostics, Cambridge, Mass.) (referred to here as OSOM) is a new point-of-care diagnostic assay for T. vaginalis that uses an immunochromatographic capillary flow (dipstick) assay and provides results in 10 min. The purpose of this study was to determine the test characteristics of OSOM compared to those of a composite reference standard (CRS) comprised of wet-mount microscopy and T. vaginalis culture. This multicenter cross-sectional study enrolled sexually active women ≥18 years of age who presented with symptoms of vaginitis, exposure to T. vaginalis , or multiple sexual partners. Vaginal-swab specimens were obtained for T. vaginalis culture, wet mount, and rapid testing. The prevalence of T. vaginalis in this sample was 23.4% (105 of 449) by the CRS. The sensitivity and specificity of OSOM vaginal-swab specimens were 83.3 and 98.8%, respectively, while wet mount had a sensitivity and specificity of 71.4 and 100%, respectively, compared to the CRS. OSOM performed significantly better than wet mount ( P = 0.004) and detected T. vaginalis in samples that required 48 to 72 h of incubation prior to becoming culture positive. The performance of the rapid test was not affected by the presence of coinfections with chlamydia and gonorrhea. The OSOM Trichomonas Rapid Test is a simple, objective test that can be expected to improve the diagnosis of T. vaginalis , especially where microscopy and culture are unavailable.

The intent of this introductory chapter is to review the nature and extent of the human burden of chlamydial disease and its complications and to describe the diseases and complications that are all too familiar to everyone involved in the clinical care of patients and in the larger public health efforts to control the chlamydial infections. Chlamydia causes substantial and important veterinary disease, but the author has mainly considered the human pathogens C. pneumoniae and C. trachomatis and the ability of different C. trachomatis serovars to cause diseases as distinct as ocular trachoma and sexually transmitted infections. A primary end point in human vaccine trials directed against genital disease might well be reduction in clinically apparent pelvic inflammatory disease (PID) rather than a reduction in infection acquisition; rate of incident infection, bacterial load, and infection duration may serve as secondary outcomes. The chapter focuses on infections caused by C. trachomatis and C. pneumoniae, since they are the common chlamydial infections in humans. Frequent treatment failures related to antibiotic resistance are not evident clinically. Several chronic diseases have been putatively linked to C. pneumoniae, including asthma and atherosclerosis. The major challenges to progress toward worldwide public health goals of reducing the burden of sequelae caused by C. trachomatis infections relate to the common clinical themes of prolonged infection, repeated infection, scarring complications of infection, and their underlying biological mechanisms.

Background Repeated Chlamydia trachomatis infections are common among young sexually active women. The relative frequency of reinfection and antibiotic treatment failure is undefined. Methods Adolescent women enrolled in a longitudinal cohort had behavioral and sexually transmitted infection assessments performed every 3 months, including amplification tests for C. trachomatis, ompA genotyping, and interviews and diary entries to document sex partner-specific coitus and event-specific condom use. Repeated infections were classified as reinfection or treatment failure by use of an algorithm. All infections for which treatment outcomes were known were used to estimate the effectiveness of antibiotic use. Results We observed 478 episodes of infection among 210 study participants; 176 women remained uninfected. The incidence rate was 34 episodes/100 woman-years. Of the women who were infected, 121 experienced 1 repeated infections, forming 268 episode pairs; 183 pairs had complete data available and were classified using the algorithm. Of the repeated infections, 84.2% were definite, probable, or possible reinfections; 13.7% were probable or possible treatment failures; and 2.2% persisted without documented treatment. For 318 evaluable infections, we estimated 92.2% effectiveness of antibiotic use. Conclusions Most repeated chlamydial infections in this high-incidence cohort were reinfections, but repeated infections resulting from treatment failures occurred as well. Our results have implications for male screening and partner notification programs and suggest the need for improved antibiotic therapies.

To determine the recurrence rate of chlamydial infections, we initially screened an urban population of 1308 sexually active female adolescents for chlamydial infection at the urethral and endocervical sites; these young women were followed and had additional examinations for infection. Chlamydial infection was documented by tissue culture in 31.1% (407) of them at some time during the study. After appropriate antibiotic treatment, 68.3% (278/407) returned for test-of-cure cultures within 3 months of their initial infection; of those 278, a total of 254 had sterile cultures. These patients were followed to determine the recurrence rate of chlamydial infections. Of these 254 patients, 177 (69.7%) had one or more follow-up visits; 38.4% (68/177) had a recurrent chlamydial infection. The majority of recurrent infections were documented within 9 months of the initial infection. Recurrent infections with the same serovar were frequent, suggesting reinfection by untreated partners or possible relapse of the initial chlamydial infection. This high rate of recurrent infection suggests that female adolescents should be rescreened frequently for genitourinary chlamydial infections.

Although interferon-gamma has been associated with control of chlamydial infections in mice, no direct evidence links it to human chlamydial infections. Therefore, interferon-gamma was assayed by ELISA in endocervical secretions and plasma of women cultured for Chlamydia trachomatis. Women with positive endocervical chlamydial cultures had increased levels of interferon-gamma in endocervical secretions (6.7 +/- 2.8, mean +/- SE, n = 47) compared with uninfected women (1.4 +/- 0.4, n = 52) (P = .002). Interferon was also present in secretions of women with gonorrhea. Higher levels were seen in secretions from older women with positive chlamydial cultures. Interferon levels in secretions did not correlate with simultaneous plasma levels, the number of organisms recovered in tissue culture, or clinical correlates of inflammation. These data suggest that interferon-gamma is present at the site of chlamydial infection; however, further experiments are needed to determine whether interferon is specifically involved in protection or is a nonspecific indicator of inflammation.

Objectives To determine the safety and effectiveness of single-dose rifalazil, a new rifamycin, for the treatment of nongonococcal urethritis (NGU). Study design Randomized, double-blind trial comparing rifalazil, 2.5, 12.5 or 25 mg, with 1.0 g azithromycin for the treatment of NGU. One hundred and seventy men were evaluated for Chlamydia trachomatis, Ureaplasma urealyticum, and Mycoplasma genitalium infection before therapy and 2- and 5-weeks posttreatment. Results C. trachomatis, M. genitalium, and U. urealyticum were present in 42%, 24%, and 28% of subjects, respectively. Microbiologic eradication of C. trachomatis with rifalazil 25 mg at 2- and 5- weeks was 85% and 83%, respectively. Rifalazil was ineffective in eradicating M. genitalium and U. urealyticum. Overall clinical cure rates at 2- and 5-weeks were 86% (95% CI 67-96) and 59% (39-78) in the rifalazil-treated 25 mg group, and 77% (56-91) and 63% (41-81) in the azithromycin-treated group. Conclusions Rifalazil was well tolerated and eradicates C. trachomatis but not M. genitalium and U. ureaplasma in men with NGU.

Objective: To understand gender differences in sexual behaviours in response to genitourinary symptoms. Methods: 473 (239 female and 234 male) subjects were enrolled at an STD clinic regardless of symptoms or infection status. Subjects completed a 30 day calendar recall interview of genitourinary symptoms, coital activity, sexual partners, and condom use. Results: Of the total of 473 participants, 261 (55%) reported symptoms (61% women and 39% men). STI prevalence was 73% and 75% for symptomatic women and men, respectively. For black women the probability of coitus was decreased in the presence of vaginal discharge (OR 0.64, 95% CI 0.47 to 0.89). No change in coital activity was seen in non-black women in the presence of vaginal discharge. Having vaginal discharge did increase the likelihood of condom use by their partners (OR 2.48, 95% CI 1.05 to 5.88), if coitus occurred. Urethral discharge was not associated with coitus or condom use in men. However, in men, dysuria was associated with increased likelihood of condom use (OR 4.25, 95% CI 1.57 to 11.56) if coitus occurred. Conclusion: Black women altered both coital activity and condom use behaviours in response to vaginal discharge. In contrast, non-black women did not modify coital activity. Men increased condom use when having dysuria but did not alter coital activity. Changes in sexual behaviours may alter the risk of STI transmission independent of interactions with the healthcare system. STI education and prevention programmes need to better understand these gender and racial differences in developing effective strategies to reduce STI transmission.

Reinfection of treated index subjects by untreated partners accounts for 14% to 30% of incident bacterial sexually transmitted infections (STIs).1-3 Treatment of sex partners through partner notification is a cornerstone of STI prevention efforts and reduces the risk of reinfection in index subjects.2 Partner notification is the process whereby the index patients (i.e., patient referral) or healthcare provider (i.e., provider referral) notify the sex partner of potential exposure and encourage them to seek treatment. The goals of partner notification are to ensure timely treatment of infected sex partners, to reduce potential for sequelae, and to prevent reinfection of the treated index patient and infection of other sexual contacts. Major shortcomings of partner notification are low rates of partner contact and treatment, partner noncompliance in seeking care after notification, and difficulties in identifying and contacting nonregular partners.4-8 An alternative to traditional partner notification is patient-delivered partner treatment (PDPT) in which infected index subjects deliver appropriate medication to partners. Several studies have shown that PDPT is well accepted by index subjects and effective in preventing repeated chlamydia and gonorrhea infections.9-12 PDPT is often prescribed by individual clinicians13 and is routinely used in some public health settings.9,14 Although PDPT appears to be a useful clinical strategy for partner treatment, some important limitations are the absence of diagnostic testing of the partner for other STIs before receiving treatment and missed opportunities for partner counseling and education.15 Conceptually, PDPT is an extension of “epidemiologic” partner treatment. The Centers of Disease Control and Prevention recommends initial presumptive treatment (ie, without confirmation of infection) of sexual contacts of infected index patients followed by diagnostic testing. Possible coinfections can also be treated presumptively. 16 Studies conducted in a number of high and low sexually transmitted disease (STD) prevalence settings have documented high rates of coinfection with Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) (range, 9–67%)17-21 and with Trichomonas vaginalis (TV).22-24 Alternatively, diagnostic testing can be used with subsequent treatment of any additional infections. Epidemiologic partner treatment is generally safe and cost-effective because sexual partners have a high likelihood of infection.25,26 In common with other forms of epidemiologic treatment, PDPT is likely associated with overtreatment of a substantial number of uninfected partners. This study was designed to examine the prevalence of CT, GC, and TV in partners of index subjects infected with CT, GC and/or CT, and TV. We also examined the prevalence of infections in partners of uninfected STI clinic clients with the hypothesis that these partners may be a part of sexual network with high STI prevalence, and therefore at high risk for infection even if the index patient is uninfected.

Chlamydia trachomatis is a human pathogen causing trachoma, urogenital disease, and lymphogranuloma venereum (LGV). A family of nine polymorphic membrane protein genes ( pmpA to pmpI ), resembling autotransporter proteins, has recently been discovered in C. trachomatis. pmp genes are large and predicted to be outer membrane proteins. We hypothesized that they would contain useful nucleotide sequence variability for epidemiologic studies. Since sequence information is available only for serovars D and L2, we sought to determine the amount of diversity within an individual pmp gene among serovars. We used restriction fragment length polymorphism (RFLP) analysis as a primary screen to assess the amount of sequence divergence among the pmp genes for serovars A to L3 of C. trachomatis . RFLP analysis showed little variation for some of the genes, such as pmpA , but substantial variation in others, such as pmpI. pmpH and pmpE yielded RFLP patterns that clustered the 15 serovars into ocular, urogenital, and LGV groups, and both proteins have been localized to the outer membrane. Therefore, we chose to sequence pmpE , pmpH , and pmpI from each of the 15 serovars. Evolutionary analysis showed three distinct divergence patterns. PmpI was least variable, resulting in an ambiguous evolutionary pattern. PmpE showed a high degree of diversity in the ocular strains compared to the other strains. Finally, the evolution of PmpH shows three groups that reflect disease groups, suggesting this protein may play a role in pathogenesis.

Screening for chlamydial and gonococcal infection has been strongly recommended for all sexually active women under the age of 26. Advances in the ability to detect infection by nucleic acid detection techniques have improved access to screening methods in routine clinical practices. To meet the increasing demand for testing, a high-throughput system is desirable. We evaluated the performance of the Hybrid Capture 2 CT/GC (HC2) assay with the Digene Rapid Capture System (HC2-RCS). The results of HC2-RCS for endocervical samples from 330 women were compared to those of culture and the COBAS Amplicor PCR. For detection of chlamydial infection, HC2-RCS had a sensitivity and a specificity similar to those of PCR ( P > 0.5) and an improved sensitivity compared to that of culture ( P = 0.007). For identification of gonococcal infections, all assays performed similarly ( P > 0.5). The performance of HC2-RCS was also compared to that of the manual HC2 format (HC2-M) with these samples and with 911 endocervical samples collected previously. The performance of HC2-RCS was equivalent to that of HC2-M; the overall concordance rates for the detection of chlamydia and gonorrhea were 99.7% (κ = 0.97) and 99.8% (κ = 0.97), respectively. When the HC2 assay was performed with a semiautomated system application designed for high throughput, it demonstrated high sensitivity and a high specificity for detection of both Chlamydia trachomatis and Neisseria gonorrhoeae .

Background Recent studies report that treatment failure rates for single-dose azithromycin for urogenital chlamydia in females may be as high as 8%. There has been sparse research investigating new antibiotics for chlamydia, especially those that may reduce adherence difficulties with the CDC recommended doxycycline regimen (100 mg orally twice daily for 7 days). Methods The safety and efficacy of WC2031 (doxycycline hyclate delayed-release 200 mg tablet) orally once daily for 7 days vs Vibramycin (doxycycline hyclate capsule) 100 mg orally twice daily for 7 days for the treatment of uncomplicated urogenital chlamydia was evaluated in a randomised, double-blind, double-dummy, active-controlled, multicenter study. Males and nonpregnant females ages 19–45 with a confirmed diagnosis of urogenital chlamydia C trachomatis at baseline. Non-inferiority of WC2031 was inferred if the lower limit of the 95% CI of the difference in cure rates was >-10%. Safety was studied through clinical evaluation and laboratory tests. Results 495 subjects were randomised at 41 study sites. The mITT population with evaluable efficacy consisted of 323 (65%) subjects (156 in the WC 2031 group and 167 in the Vibramycin group). Baseline characteristics did not differ by group: median age 23, 61% female, 58% African American vs 36% Caucasian vs 7% other race, and 21% Hispanic ethnicity. The microbiological cure rate (95% CI) for the WC2031 group was 95.5 % (92.3 to 98.8) vs 95.2% (92.0 to 98.4) for the Vibramycin group; the 95% CI for the difference in cure rates between treatments was (−4.3% to 4.9%). Types of adverse events were comparable between treatment groups. The WC 2031 group had less nausea and vomiting (13% vs 21% and 8% vs 12%). Conclusions WC2031 was non-inferior to Vibramycin for treatment of uncomplicated urogenital chlamydia, was better tolerated, and demonstrated comparable safety. The once daily dosing of WC2031 may improve treatment adherence compared with twice daily doxycycline.

Synthetic peptides and murine monoclonal antibodies were used to map cross-reactive chlamydial epitopes. A species-specific epitope in the central region of variable sequence region 4 abuts the amino-terminal end of a B-serogroup-specific or F/G-serogroup-specific epitope, which in turn abuts known serovar-specific epitopes. The carboxyl-terminal portion of variable sequence region 4 (residues 297 to 314) comprises a region of end-to-end B-cell epitopes in some serovars of the B and F/G serogroups.

1. The pharmacokinetics of didanosine, trimethoprim, and sulphamethoxazole were evaluated in ten HIV seropositive asymptomatic patients as single agents and upon coadministration of single doses. 2. Using a randomized, balanced incomplete block crossover study with at least a 1-week washout period between successive treatments, each patient under fasting conditions received four of the following five treatments: 200 mg didanosine as a single agent; 200 mg trimethoprim + 1000 mg sulphamethoxazole; 200 mg trimethoprim + 200 mg didanosine; 1000 mg sulphamethoxazole + 200 mg of didanosine and; 200 mg trimethoprim + 1000 mg sulphamethoxazole + 200 mg didanosine. 3. Serial blood and urine samples were collected following the administration of each treatment. Plasma and urine samples were analyzed using high-pressure liquid chromatography (h.p.l.c.)/ultraviolet assays specific for unchanged didanosine, trimethoprim and/or sulphamethoxazole. 4. Percent urinary recovery (%UR) and renal clearance (CLR) emerged as consistently affected parameters, being decreased in the case of didanosine (35%, P = 0.016) and trimethoprim (32%, P = 0.019) and increased in the case of sulphamethoxazole (39%, P = 0.079), when all three agents were coadministered. The magnitude of the changes in didanosine CLR and %UR values was no greater when both trimethoprim and sulphamethoxazole were coadministered vs when each single agent was given with didanosine, suggesting that any effect was not additive. 5. Other key parameters such as Cmax, AUC, and t1/2 for didanosine (1309.9 ng ml-1, 1796.9 ng ml-1 h, and 1.61 h, respectively), trimethoprim (1.96 micrograms ml-1, 22.86 micrograms ml-1 h, and 9.03 h, respectively) or sulphamethoxazole (58.62 micrograms ml-1, 799.7 micrograms ml-1 h and 9.84 h, respectively) were not affected when didanosine was coadministered with either trimethoprim (didanosine: 1751.9 ng ml-1, 2158.0 ng ml-1 h, and 1.28 h; trimethoprim: 1.81 micrograms ml-1, 28.89 micrograms ml-1 h, and 11.4 h), sulphamethoxazole (didanosine: 1279.3 ng ml-1, 1793.2 ng ml-1 h, and 1.61 h; sulphamethoxazole: 53.57 micrograms ml-1, 732.1 micrograms ml-1 h, and 8.95 h), or the combination of trimethoprim and sulphamethoxazole (didanosine: 1283.7 ng ml-1, 1941.8 ng ml-1 h, and 1.38 h; trimethoprim: 1.59 micrograms ml-1, 26.68 micrograms ml-1 h, and 11.3 h; sulphamethoxazole: 59.48 micrograms ml-1, 760.9 micrograms ml-1 h, and 9.47 h). 6. Because the observed differences in CLR and %UR are small and not considered to be clinically relevant, it is not necessary to alter the dosing regimens of didanosine, trimethoprim or sulphamethoxazole when administered in combination to HIV seropositive patients.

The major outer membrane proteins (MOMPs) of human Chlamydia trachomatis serovars exhibit four regions of variable amino acid sequences (VS1 to VS4) harboring serovar-specific B-cell epitopes. Antibody responses to these epitopes may contribute to acquired protection against human chlamydial infection. MOMP B-cell epitopes defined by 22 different serovar-specific or bispecific murine monoclonal antibodies were localized with synthetic peptides representing the four VS regions of seven genital serovars (D, Da, E, F, G, H, and K). Serovar F possessed two distinct serovar-specific epitopes, located in VS2 and VS4, while serovar K possessed three distinct serovar-specific epitopes, located in VS1, VS2, and VS4. Serovar D- and serovar Da-specific epitopes were located in VS1. Regardless of whether the serovar was from the B (serovars D, Da, and E), C (serovars H and K), or F-G (serovars F and G) serogroup, all serovar-specific epitopes were found in three discrete subgroups of MOMPs. These subregions comprised all central portion of VS1, residues 70 to 77; the amino-terminal half of VS2, residues 139 to 149; and the carboxyl-terminal third of VS4, residues 305 to 315. Monoclonal antibodies to each of these subregions neutralized infectivity in standard HaK cell culture assays. These findings are relevant to the development of an MOMP or MOMP subunit vaccine.