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Background: Chlamydia trachomatis is the causative agent of the most prevalent bacterial sexually transmitted infections globally. Whole genome sequencing is essential for molecular Chlamydia surveillance; however, its application is hampered by the pathogen's low abundance in clinical specimens and the expensive labor-intensive nature of existing enrichment methodologies for Chlamydia., Methods: We developed a targeted whole genome amplification tool termed SWITCH by integrating phi29 DNA polymerase-mediated amplification with meticulously designed primer sets to enrich the C trachomatis genome, followed by whole genome sequencing. This method underwent evaluation through testing synthetic and clinical specimens., Results: SWITCH demonstrated robust ability to achieve up to 98.3% genomic coverage of C trachomatis from as few as 26.4 genomic copies present in synthetic specimens, and it exhibited excellent performance across diverse C trachomatis serovars. Utilizing SWITCH, we directly generated 21 Chlamydia genomes from 26 clinical samples, enabling us to gain insights into the genetic relationships and phylogeny of current Chlamydia strains circulating in the country. Remarkably, this study marked the first instance of generating Chinese Chlamydia genomes directly from clinical samples., Conclusions: SWITCH represents a practical cost-efficient approach to enrich the Chlamydia genome directly from clinical specimens, offering an efficient avenue for molecular surveillance of Chlamydia., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Chlamydia trachomatis (CT) is a sexually transmitted infection that can lead to adverse reproductive health outcomes. CT prevalence estimates are primarily derived from screening using nucleic acid amplification tests (NAATs). However, screening guidelines in the United States only include particular subpopulations, and NAATs only detect current infections. In contrast, seroassays identify past CT infections, which is important for understanding the public health impacts of CT, including pelvic inflammatory disease and tubal factor infertility. Older seroassays have been plagued by low sensitivity and specificity and have not been validated using a consistent reference measure, making it challenging to compare studies, define the epidemiology of CT, and determine the effectiveness of control programs. Newer seroassays have better performance characteristics. This narrative review summarizes the "state of the science" for CT seroassays that have been applied in epidemiologic studies and provides practical considerations for interpreting the literature and employing seroassays in future research., Competing Interests: Potential conflicts of interest. L. E. M. has received research materials and research funding from Hologic, Inc, and Nabriva Therapeutics, as well as an honorarium from Health Advances. C. M. K. has received donations of study collection kits and reagents from Hologic, Inc, for research studies outside the submitted work. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Detection of anti-Chlamydia trachomatis (Ctr) antibodies is compromised by cross-reactivity and poor sensitivity of classic Ctr-antigens. We discovered 48 strongly reactive peptide antigens of Ctr-specific B-cell epitopes from 21 immunodominant proteins. In this study, we review the utility of peptide assays for diagnosis of Ctr infections. By combining many of these Ctr-specific B-cell epitopes from several proteins in separate or mixed multipeptide assays, they achieved vastly superior assay sensitivity and specificity over standard enzyme-linked immunosorbent assays. Such multipeptide assays eliminate cross-reactivities (false positives) and correct for stochastic gaps in antibody responses (false negatives). More importantly, we developed and validated a novel microarray platform in which hundreds of peptides from many proteins are spotted in a single reaction well. This offers the possibility of high-throughput screening of many candidate peptides for routine serological fingerprinting of Ctr infections. Discovery of optimal sets of antibody responses that associate with clinical pelvic inflammatory disease (PID) may identify diagnostically useful PID biomarker antigens., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Chlamydia trachomatis (CT), the most common bacterial sexually transmitted infection worldwide, has been widely researched for its involvement in many disease pathologies in the reproductive tract, including pelvic inflammatory disease, ectopic pregnancy, and tubal factor infertility. Recent findings, through the efforts to understand the pathogenesis of CT, suggest that CT can induce the process of epithelial-to-mesenchymal transition (EMT) through epigenetic changes in the epithelium of the female reproductive tract. This literature review aims to analyze the evidence for CT's ability to promote EMT and to pinpoint the areas that merit further investigation., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Pelvic inflammatory disease (PID) is a syndrome that causes substantial morbidity, including chronic pelvic pain, to women globally. While limited data are available from low- and middle-income countries, national databases from the United States and Europe suggest that PID incidence may be decreasing but the rate of decrease may differ by the etiologic cause. Recent studies of women with PID have reported that fewer than half of women receiving a diagnosis of PID have gonococcal or chlamydial infection, while Mycoplasma genitalium, respiratory pathogens, and the constellation of bacteria associated with bacterial vaginosis may account for a substantial fraction of PID cases. The clinical diagnosis of PID is nonspecific, creating an urgent need to develop noninvasive tests to diagnose PID. Advances in serologic testing for Chlamydia trachomatis and Neisseria gonorrhoeae could advance epidemiologic studies, while the development of vaccines against these sexually transmitted pathogens could affect incident PID and associated morbidity., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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 article, 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., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Pelvic inflammatory disease (PID) results from ascension of sexually transmitted pathogens from the lower genital tract to the uterus and/or fallopian tubes in women, with potential spread to neighboring pelvic organs. Patients may present acutely with lower abdominal or pelvic pain and pelvic organ tenderness. Many have subtle symptoms or are asymptomatic and present later with tubal factor infertility, ectopic pregnancy, or chronic pelvic pain. Neisseria gonorrhoeae and Chlamydia trachomatis are the 2 most commonly recognized PID pathogens. Their ability to survive within host epithelial cells and neutrophils highlights a need for T-cell-mediated production of interferon γ in protection. Data indicate that for both pathogens, antibody can accelerate clearance by enhancing opsonophagocytosis and bacterial killing when interferon γ is present. A study of women with N. gonorrhoeae- and/or C. trachomatis-induced PID with histologic endometritis revealed activation of myeloid cell, cell death, and innate inflammatory pathways in conjunction with dampening of T-cell activation pathways. These findings are supported by multiple studies in mouse models of monoinfection with N. gonorrhoeae or Chlamydia spp. Both pathogens exert multiple mechanisms of immune evasion that benefit themselves and each other at the expense of the host. However, similarities in host immune mechanisms that defend against these 2 bacterial pathogens instill optimism for the prospects of a combined vaccine for prevention of PID and infections in both women and men., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: To assess the prevalence of Chlamydia psittaci, Chlamydia pneumoniae, and Chlamydia trachomatis in ocular adnexa lymphoma (OAL) determined by molecular testing in different countries and the potential association of Chlamydia infection with mucosa-associated lymphoid tissue (MALT) histotype by performing a systematic review and meta-analysis., Methods: Electronic databases were searched for studies assessing the presence of Chlamydia in OAL. Pooled prevalence of the three Chlamydia species was calculated in each country. An odds ratio was calculated for the association between Chlamydia and MALT histotype, with a significant P < .05., Results: Thirty-seven studies with 1,188 OALs were included. Pooled prevalence of C psittaci, C pneumoniae, and C trachomatis by country was done. Chlamydia infection was significantly associated with MALT histotype (odds ratio, 2.183; P = .027)., Conclusions: The involvement of C psittaci in OAL is highly variable, with the highest prevalence in Italy and Korea. Chlamydia is associated with MALT histotype., (© American Society for Clinical Pathology, 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen worldwide. Here, we determined the ability of a C. trachomatis recombinant major outer membrane protein (rMOMP) vaccine to elicit cross-serogroup protection., Methods: Female C3H/HeN mice were vaccinated by mucosal and systemic routes with C. trachomatis serovar D (UW-3/Cx) rMOMP and challenged in the ovarian bursa with serovars D (UW-3/Cx), D (UCI-96/Cx), E (IOL-43), or F (N.I.1). CpG-1826 and Montanide ISA 720 were used as adjuvants., Results: Immune responses following vaccination were more robust against the most closely related serovars. Following a genital challenge (as determined by number of mice with positive vaginal cultures, number of positive cultures, number of inclusion forming units recovered, and number of days with positive cultures) mice challenged with C. trachomatis serovars of the same complex were protected but not those challenged with serovar F (N.I.1) from a different subcomplex. Females were caged with male mice. Based on fertility rates, number of embryos, and hydrosalpinx formation, vaccinated mice were protected against challenges with serovars D (UW-3/Cx), D (UCI-96/Cx), and E (IOL-43) but not F (N.I.1)., Conclusions: This is the first subunit vaccine shown to protect mice against infection, pathology, and infertility caused by different C. trachomatis serovars., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Competing Interests: Competing interests: None declared.

Study Question: Can Chlamydia be found in the testes of infertile men?, Summary Answer: Chlamydia can be found in 16.7% of fresh testicular biopsies and 45.3% of fixed testicular biopsies taken from a selection of infertile men., What Is Known Already: Male chlamydial infection has been understudied despite male and female infections occurring at similar rates. This is particularly true of asymptomatic infections, which occur in 50% of cases. Chlamydial infection has also been associated with increased sperm DNA damage and reduced male fertility., Study Design, Size, Duration: We collected diagnostic (fixed, n = 100) and therapeutic (fresh, n = 18) human testicular biopsies during sperm recovery procedures from moderately to severely infertile men in a cross-sectional approach to sampling., Participants/materials, Setting, Methods: The diagnostic and therapeutic biopsies were tested for Chlamydia-specific DNA and protein, using real-time PCR and immunohistochemical approaches, respectively. Serum samples matched to the fresh biopsies were also assayed for the presence of Chlamydia-specific antibodies using immunoblotting techniques., Main Results and the Role of Chance: Chlamydial major outer membrane protein was detected in fixed biopsies at a rate of 45.3%. This was confirmed by detection of chlamydial DNA and TC0500 protein (replication marker). C. trachomatis DNA was detected in fresh biopsies at a rate of 16.7%, and the sera from each of these three positive patients contained C. trachomatis-specific antibodies. Overall, C. trachomatis-specific antibodies were detected in 72.2% of the serum samples from the patients providing fresh biopsies, although none of the patients were symptomatic nor had they reported a previous sexually transmitted infection diagnosis including Chlamydia., Limitations, Reasons for Caution: No reproductively healthy male testicular biopsies were tested for the presence of Chlamydia DNA or proteins or Chlamydia-specific antibodies due to the unavailability of these samples., Wider Implications for the Findings: Application of Chlamydia-specific PCR and immunohistochemistry in this human male infertility context of testicular biopsies reveals evidence of a high prevalence of previously unrecognised infection, which may potentially have a pathogenic role in spermatogenic failure., Study Funding/competing Interest(s): Funding for this project was provided by the Australian NHMRC under project grant number APP1062198. We also acknowledge assistance from the Monash IVF Group and Queensland Fertility Group in the collection of fresh biopsies, and the Monash Health and co-author McLachlan (declared equity interest) in retrieval and sectioning of fixed biopsies. E.M. declares an equity interest in the study due to financing of fixed biopsy sectioning. All other authors declare no conflicts of interest., Trial Registration Number: N/A., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.)

Background: Pelvic inflammatory disease (PID) is common among women of reproductive age and can be complicated by tuboovarian abscess (TOA), which is a serious and potentially life-threatening disease. However, recent mortality rates from PID on hospital admission and the short-term therapeutic usefulness of initial treatment for Chlamydia trachomatis remain unknown., Methods: Using the Diagnosis Procedure Combination database, we identified patients who were diagnosed with PID on admission from July 2010 to March 2016 in Japan. We excluded patients who were pregnant, had cancer, or had missing data. Propensity score-adjusted analyses were performed to compare short-term outcomes between patients administered initial treatment for C. trachomatis and those without this treatment. The primary outcome was surgical intervention (laparotomy, laparoscopic surgery, and/or drainage procedure) during hospitalization., Results: In total, 27841 eligible patients were identified. Of these patients, 2463 (8.8%) had TOA on admission. Mortality during hospitalization was 0.56% and 0.28% in the groups without and with TOA, respectively. Propensity score matching created 6149 pairs. A significant difference was observed in the primary outcome between those receiving initial treatment for C. trachomatis and the control group after propensity score matching (11.5% vs 13.4%; risk difference, -1.9%; 95% confidence interval, -3.1 to -0.7). The group that received initial treatment for C. trachomatis also had a significantly lower mortality rate., Conclusions: In this retrospective nationwide study, initial treatment for C. trachomatis among hospitalized patients diagnosed with PID had clinical benefits in terms of improved short-term outcomes., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Vaginal symptoms are a leading cause of primary care visits for women. Individuals exhibiting symptoms often receive laboratory testing based on clinic-specific standards of care. Thus, women seen at a family practice clinic might only receive a vaginitis workup, whereas those seen at a sexually transmitted diseases clinic could be more likely to receive only sexually transmitted infection (STI) testing., Methods: The likelihood of STIs was assessed in women from whom samples were tested for vaginitis using a molecular diagnostic assay. Positivity rates for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis DNA, detected using the BD MAX CT/GC/TV assay, were calculated. Concordance between the BD MAX Vaginal Panel and the BD MAX CT/GC/TV assay for detection of T. vaginalis was determined., Results: Women with bacterial vaginosis alone or with concurrent Candida spp infections had high rates of coinfection with sexually transmitted infections (24.4%-25.7%); samples from women who were negative for vaginitis had significantly lower positivity rates (7.9%; P < .001). Trichomonas vaginalis results were concordant between the BD MAX Vaginal Panel and the BD MAX CT/GC/TV assay in 559 of 560 samples tested., Conclusions: These data suggest, as have other studies, that women with vaginitis symptoms may be at risk for an STI. Molecular testing could provide broad diagnostic coverage for symptomatic women and improve patient management, regardless of the type of clinic in which patients are treated.

Background: World Health Organization (WHO) recommendations for starting and stopping mass antibiotic distributions are based on a clinical sign of trachoma, which is indirectly related to actual infection with the causative agent, Chlamydia trachomatis., Methods: This study aimed to understand the effect of SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) interventions on ocular chlamydia in Amhara, Ethiopia, by describing the infection prevalence in a population-based sample of children aged 1-5 years. Trachoma surveys were conducted in all districts of Amhara, from 2011 to 2015 following approximately 5 years of SAFE. Ocular swabs were collected from randomly selected children to estimate the zonal prevalence of chlamydial infection. The Abbott RealTime polymerase chain reaction assay was used to detect C. trachomatis DNA., Results: A total of 15632 samples were collected across 10 zones of Amhara. The prevalence of chlamydial infection in children aged 1-5 years was 5.7% (95% confidence interval, 4.2%-7.3%; zonal range, 1.0%-18.5%). Chlamydial infection and trachomatous inflammation-intense (TI) among children aged 1-9 years were highly correlated at the zonal level (Spearman correlation [r] = 0.93; P < .001), while chlamydial infection and trachomatous inflammation-follicular were moderately correlated (r = 0.57; P = .084)., Conclusions: After 5 years of SAFE, there is appreciable chlamydial infection in children aged 1-5 years, indicating that transmission has not been interrupted and that interventions should continue. The sign TI was highly correlated with chlamydial infection and can be used as a proxy indicator of infection.

The potential was modelled of molecular rapid diagnostic tests (RDTs) that target agents of sexually transmitted diseases (STDs) to contribute to a reduction in the exposure risk for sexually active populations who prefer condom-free high-risk contacts. The biostatistical approach is exemplified by considering the use of a PCR-based RDT for Chlamydia trachomatis and Neisseria gonorrhoeae in a population of German men having sex with men. We modelled the exposure risk as risk of sexual contact with individuals infected by a STD in spite of multiple RDTs having been conducted to identify STDs that could lead to avoidance of an infectious sexual contact. The risk for a given specific disease is influenced by the diagnostic accuracy of all diagnostic tests conducted. The simulation showed a reduction in exposure risk through conducting the selected PCR-based RDT as a strategy to prevent infections with C. trachomatis and N. gonorrhoeae in comparison with unprotected sexual contact of >97% for C. trachomatis and ≥96% for N. gonorrhoeae. Reliable knowledge of the performance characteristics of the diagnostic tests applied is essential for a thorough risk assessment based on such diagnostic approaches., Significance and Impact of the Study: A low-threshold use of molecular rapid diagnostic tests in settings where risky sexual activity is undertaken with deliberate non-use of condoms is modelled. Such an approach might contribute to a considerable reduction in the exposure risk if positively tested individuals are excluded from unprotected sexual intercourse. Protective effects are influenced by the prevalence of the disease and the performance characteristics of the applied tests. Precise knowledge of the performance characteristics of the test assays employed are prerequisites of a reliable risk assessment. The modelling approach is of particular use for preventive health experts., (© 2018 The Society for Applied Microbiology.)

Background: Chlamydia trachomatis is the most common reportable infection in the United States and can cause pelvic inflammatory disease (PID) and tubal factor infertility (TFI)., Methods: We created life tables to estimate the "lifetime" risk of chlamydia diagnosis among women aged 15-34 years in King County, Washington, between 1992 and 2014. We estimated the lifetime risk of chlamydia-associated PID and TFI incorporating published estimates of the risk of sequelae., Results: There were 51464 first chlamydia diagnoses in 1992-2014. For women born between 1980 and 1984, the lifetime risk of chlamydia diagnosis was 19.8% overall and 14.0% for non-Hispanic white, 64.9% for non-Hispanic black, and 32.6% for Hispanic women. The cumulative risk of chlamydia by age 24 increased overall from 13.9% to 17.3% among women born between 1975 and 1994 but declined among non-Hispanic black women, among whom risk by age 24 declined from 57.3% among women born between 1980 and 1984 to 38.6% among women born between 1990 and 1994. The lifetime risk of chlamydia-associated PID among women born between 1980 and 1984 ranged from 0.33% to 1.14%. Among non-Hispanic white, non-Hispanic black, and Hispanic women, the lifetime risk of chlamydia-associated TFI was 0.04%, 0.20%, and 0.10%, respectively., Conclusions: Over 60% of non-Hispanic black women had at least 1 chlamydia diagnosis by age 34 in the birth cohorts most affected, a risk almost 5 times that in non-Hispanic whites. An estimated 1 in 500 non-Hispanic black women develops chlamydia-associated TFI. More effective control measures are needed.

We present AAI-profiler, a web server for exploratory analysis and quality control in comparative genomics. AAI-profiler summarizes proteome-wide sequence search results to identify novel species, assess the need for taxonomic reclassification and detect multi-isolate and contaminated samples. AAI-profiler visualises results using a scatterplot that shows the Average Amino-acid Identity (AAI) from the query proteome to all similar species in the sequence database. Taxonomic groups are indicated by colour and marker styles, making outliers easy to spot. AAI-profiler uses SANSparallel to perform high-performance homology searches, making proteome-wide analysis possible. We demonstrate the efficacy of AAI-profiler in the discovery of a close relationship between two bacterial symbionts of an omnivorous pirate bug (Orius) and a thrip (Frankliniella occidentalis), an important pest in agriculture. The symbionts represent novel species within the genus Rosenbergiella so far described only in floral nectar. AAI-profiler is easy to use, the analysis presented only required two mouse clicks and was completed in a few minutes. AAI-profiler is available at http://ekhidna2.biocenter.helsinki.fi/AAI.

Objectives: Antimicrobial susceptibility data for Chlamydia trachomatis are lacking. Methodologies for susceptibility testing in C. trachomatis are not well-defined, standardized or performed routinely owing to its intracellular growth requirements. We sought to develop an assay for the in vitro susceptibility testing of C. trachomatis isolates from two patient cohorts with different clinical outcomes., Methods: Twenty-four clinical isolates (11 from persistently infected and 13 from successfully treated patients) were overlaid with media containing two-fold serial dilutions of azithromycin or doxycycline. After incubation, aliquots were removed from the stock inoculum (SI) and each antimicrobial concentration for total RNA extraction, complementary DNA generation and real-time PCR. The MIC was defined as the lowest antimicrobial concentration where a 95% reduction in transcription was evident in comparison with the SI for each isolate., Results: MICs of azithromycin were comparable for isolates from the two patient groups (82% ≤ 0.25 mg/L for persistently infected and 100% ≤ 0.25 mg/L for successfully treated patients). Doxycycline MICs were at least two-fold lower for isolates from the successfully treated patients (53.9% ≤ 0.064 mg/L) than for the persistently infected patients (100% ≥ 0.125 mg/L) (P = 0.006, Fisher's exact test). Overall, 96% of isolates gave reproducible MICs when re-tested., Conclusions: A reproducible assay was developed for antimicrobial susceptibility testing of C. trachomatis. MICs of azithromycin were generally comparable for the two different patient groups. MICs of doxycycline were significantly higher in the persistently infected patients. However, interpretation of elevated MICs in C. trachomatis is extremely challenging in the absence of breakpoints, or wild-type and treatment failure MIC distribution data.

Background: Anal sex is a common sexual behavior among women that increases their risk of acquiring rectal infection with Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC)., Methods: We estimated the frequency and positivity of rectal CT and GC tests for women aged 15-60 years performed by a large US commercial laboratory between November 2012 and September 2015. We also estimated the frequency and positivity of pharyngeal and genital specimens also performed on the same date. Among women with a positive CT or GC result, we estimated the frequency and positivity of recommended repeat testing within 12 months., Results: Of 5499 women who had rectal CT and GC tests, positivity was 10.8%. On the same date, approximately 80% also had genital CT tests, genital GC tests, and pharyngeal GC tests, while 40% had pharyngeal CT tests. Rectal CT or GC infection was associated with genital CT or GC infection, but 46.5% of rectal CT and GC infections would not have been identified with genital testing alone. Among women with a rectal CT or GC infection, only 20.0% had a recommended repeat rectal test. Of those who had a repeat test, 17.7% were positive., Conclusions: Testing women for rectal CT and GC was infrequent, but positive tests were often found in women with negative genital tests. Most women with positive rectal tests were not retested. Interventions are needed to increase extragenital CT and GC testing of at-risk women., (Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Understanding the relationship between the levonorgestrel (LNG)-releasing intrauterine system (IUS) and sexually transmitted infections (STIs) is increasingly important as use of the LNG-IUS grows to include women at higher risk for STIs. This study assessed the impact of the LNG-IUS on development of Chlamydia trachomatis pelvic inflammatory disease, using a baboon model., Methods: Baboons with and those without the LNG-IUS were cervically inoculated with C. trachomatis and monitored daily, and cervical and fallopian tube swab specimens were collected weekly for C. trachomatis quantitation by nucleic acid amplification testing and culture. Vaginal swab specimens were collected for cytokine analysis, and serum samples were obtained for detection of C. trachomatis antibodies., Results: The LNG-IUS resulted in an increased C. trachomatis burden in the cervix, with the bacterial burden in the LNG-IUS group diverging from that in the non-LNG-IUS group by 6 weeks after infection. One of 7 baboons in the non-LNG-IUS group and 2 of 6 in the LNG-IUS group developed pelvic inflammatory disease, while 3 animals in each group met criteria suggestive of pelvic inflammatory disease. LNG-IUS increased baseline interleukin 8 levels but failed to further upregulate interleukin 8 during infection. In LNG-IUS recipients, early perturbations in the interleukin 1β axis corresponded to decreased C. trachomatis clearance and increased T-helper type 2 immune responses., Conclusion: LNG-IUS use results in delayed clearance of C. trachomatis and might alter the reproductive tract immune environment., (© The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: There is uncertainty around whether the risks of pelvic inflammatory disease (PID) differ following Chlamydia trachomatis (chlamydia) and Neisseria gonorrhoeae (gonorrhea) infection. We quantified the risk of PID associated with chlamydia and gonorrhea infection and subsequent repeat infections in a whole-population cohort., Methods: A cohort of 315123 Western Australian women, born during 1974-1995, was probabilistically linked to chlamydia and gonorrhea testing records and to hospitalizations and emergency department presentations for PID from 2002 to 2013. Time-updated survival analysis was used to investigate the association between chlamydia and gonorrhea testing, and positivity, and risk of PID., Results: Over 3199135 person-years, 120748 women had pathology test records for both chlamydia and gonorrhea, 10745 chlamydia only, and 653 gonorrhea only. Among those tested, 16778 (12.8%) had ≥1 positive chlamydia test, 3195 (2.6%) ≥1 positive gonorrhea test, and 1874 (1.6%) were positive for both. There were 4819 PID presentations (2222 hospitalizations, 2597 emergency presentations). Adjusting for age, Aboriginality, year of follow-up, health area, and socioeconomic status, compared to women negative for chlamydia and gonorrhea, the relative risk (adjusted incidence rate ratio) of PID was 4.29 (95% confidence interval [CI], 3.66-5.03) in women who were both chlamydia and gonorrhea positive; 4.54 (95% CI, 3.87-5.33) in those only gonorrhea positive; and 1.77 (95% CI, 1.61-1.94) in those only chlamydia positive., Conclusions: Gonorrhea infection conferred a substantially higher risk than chlamydia of hospitalization or emergency department presentation for PID. The emergence of gonorrhea antimicrobial resistance may have a serious impact on rates of PID and its associated reproductive health sequelae., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Chlamydia trachomatis (Ctr) is a bacterial pathogen that causes ocular, urogenital and lymph system infections in humans. It is highly abundant and among its serovars, E, F and D are most prevalent in sexually transmitted disease. However, the number of publicly available genome sequences of the serovars E and F, and thereby our knowledge about the molecular architecture of these serovars, is low. Here we sequenced the genomes of six E and F clinical isolates and one E lab strain, in order to study the genetic variance in these serovars. As observed before, the genomic variation inside the Ctr genomes is very low and the phylogenetic placement in comparison to publicly available genomes is as expected by ompA gene serotyping. However, we observed a large InDel carrying four to five open reading frames in one clinical E sample and in the E lab strain. We have also observed substantial variation on nucleotide and amino acid levels, especially in membrane proteins and secreted proteins. Furthermore, these two groups of proteins are also target for recombination events. One clinical F isolate was genetically heterogeneous and revealed the highest differences on nucleotide level in the pmpE gene., (© FEMS 2017.)

A reliable overview of data on the prevalence of Chlamydia trachomatis (CT) in Russia is lacking and needed. All the available data on CT prevalence were analyzed in a systematic literature review on CT prevalence in Russia, strengthened with data from the multicenter study among 1263 people in the second-largest Russian megalopolis, St. Petersburg, testing for CT DNA in urethral, anal, cervical and prostate samples. A total of 10 articles met the inclusion criteria. The overall average prevalence of genital CT infections in Russian populations ranged from 2.9% to 33%. Risk factors included being symptomatic (P = 0.004; in men P < 0.001), being younger than 30 years (P = 0.001) and being a man who has sex with men (MSM) (P = 0.0084). Main limitations included the lack of studies in MSM. CT prevalence was higher in the groups where urethral and prostate secretion samples were pooled (5.2%-7.3% vs 3.2% in the urethra only). The data on CT prevalence in a range of Russian populations are analyzed and reported. Prostate secretions represent an additional sampling material for the study of CT infection in men. CT detection in some settings in St. Petersburg yielded levels of reliability comparable with internationally available tests. The initiation of screening programs for Chlamydia infections in Russia should be considered., (© FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Chlamydia trachomatis (hereafter CT) is Gram-negative, obligate intracellular pathogen. It causes the world's most common non-viral sexually transmitted disease. India is home to the world's greatest burden of infectious diseases, yet information on prevalence rates of CT is scarce. This article systematically reviews the literature for the prevalence rates and testing methods in India. A total of 27 studies were included. Four main patients groups (symptomatic women, infertile women, pregnant women and asymptomatic population groups) could be identified with varying rates of CT (0.1%-32% using PCR, 2.4%-75% using ELISA serology). Most of the studies originated from urban settings, 11 of them from New Delhi. In-house PCR was the most common diagnostic technique used generating the following ranges in prevalence for the four group studies: symptomatic women 10%-50%, pregnant women 0.1%-2.5% and asymptomatic populations 0.9%-24.5%. The rates among infertile women were 9%-68% based on serology results. The prevalence rates featured in this paper are in line with other locations across the Indian subcontinent. This review highlights the extreme heterogeneity in the limited studies available in India on CT and the need for standardized guidelines for diagnosis and management of CT in India. The availability of resources should be considered in the formulation of recommendations., (© FEMS 2017.)

Chlamydia trachomatis (Ct) is the most common cause of bacterial sexually transmitted infection and infectious cause of blindness (trachoma) worldwide. Understanding the spatial distribution of Ct infection may enable us to identify populations at risk and improve our understanding of Ct transmission. In this study, we sought to investigate the spatial distribution of Ct infection and the clinical features associated with high Ct load in trachoma-endemic communities on the Bijagós Archipelago (Guinea Bissau). We collected 1507 conjunctival samples and corresponding detailed clinical data during a cross-sectional population-based geospatially representative trachoma survey. We used droplet digital PCR to estimate Ct load on conjunctival swabs. Geostatistical tools were used to investigate clustering of ocular Ct infections. Spatial clusters (independent of age and gender) of individuals with high Ct loads were identified using local indicators of spatial association. We did not detect clustering of individuals with low load infections. These data suggest that infections with high bacterial load may be important in Ct transmission. These geospatial tools may be useful in the study of ocular Ct transmission dynamics and as part of trachoma surveillance post-treatment, to identify clusters of infection and thresholds of Ct load that may be important foci of re-emergent infection in communities., (© FEMS 2017.)

Background.: Testing on indication of self-reported anal sex or symptoms is used to manage anorectal Chlamydia trachomatis (chlamydia) and Neisseria gonorrhoeae (gonorrhea) infections in women. Little is known about the impact of another testing strategy, routine universal anorectal screening with respect to chlamydia and gonorrhea prevalence and risk factors., Methods.: All women (n = 1012) aged ≥16 years attending our sexually transmitted infection clinic in 2015 were offered routine universal screening. In total, 19.5% (n = 185) of women had an indication (reported anal sex or symptoms), 72.5% (n = 689) did not have an indication, and 8.0% (n = 76) had missing information on indication. Logistic regression analyses were used to identify determinants associated with anorectal chlamydia and gonorrhea., Results.: Of all women who visited our clinic, 94% (n = 950) participated in the study. Overall anorectal chlamydia/gonorrhea positivity was 13.4% (n = 127)/1.3% (n = 12). Self-reported anal sex and anal symptoms were independently associated with anorectal gonorrhea (odds ratios [ORs], 3.3 [95% confidence interval {CI}, 1.01-10.7] and 14.5 [95% CI, 2.8-75.0], respectively), but not with anorectal chlamydia. Of all anorectal chlamydia/gonorrhea cases, 72% (n = 92)/33% (n = 4) were diagnosed in women without an indication, of which 19% (n = 19)/0% (n = 0) were anorectal only. For women with missing indication, this was 7% (n = 9)/8% (n = 1) and 44% (n = 4)/100% (n = 1)., Conclusions.: Anorectal screening in women without an indication is feasible and highly acceptable. Selective testing on indication could be an appropriate control strategy for anorectal gonorrhea, as few infections would be missed. In contrast, selective testing is a suboptimal control strategy for anorectal chlamydia, as we found a high prevalence in women both with and without indication for anorectal testing, along with a substantial amount of anorectal-only infections., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Effectiveness of human papillomavirus (HPV) vaccines in the context of both guidelines, which recommend vaccination at 14 years and modest vaccine coverage, is poorly documented., Methods: Residual specimens from females aged <25 years undergoing chlamydia testing were collected, together with demographic, sexual behavior, and vaccine status data. Human pappilomavirus genotypes were determined using the PapilloCheck test system. We compared vaccine type (VT; types 6, 11, 16, 18) prevalence according to vaccination status and identified factors associated with VT prevalence., Results: Of 3736 eligible samples, 822 were from vaccinated women according to immunization record, 1021 from women self-reporting vaccination, and 1893 from unvaccinated women. Adjusted vaccine effectiveness for confirmed vaccinated compared with unvaccinated women was 95.93% (95% confidence interval [CI] = 90.22-98.32) against VT HPV and 38.37% (95% CI = 12.68-56.51) against cross-reactive genotypes (HPV 31, 33, 45), respectively. Vaccine type HPV prevalence was significantly lower (0.61%) among confirmed-vaccinated women than among those who self-reported vaccination or unvaccinated women (1.76% and 15.0%, respectively). Factors associated with prevalent VT in multivariable analysis were vaccine status, positive Chlamydia trachomatis and ≥4 partners in the preceding year., Conclusion: Our study demonstrates evidence of high effectiveness of HPV prophylactic vaccines at an individual level, supporting that wider implementation will help to reduce cervical cancer and precursors incidence., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

In this study, we examined whether the proportion of tubal factor infertility (TFI) that is attributable to Chlamydia trachomatis, the population excess fraction (PEF), can be estimated from serological data using finite mixture modeling. Whole-cell inclusion immunofluorescence serum antibody titers were recorded among infertile women seen at St. Michael's Hospital in Bristol, United Kingdom, during the period 1985-1995. Women were classified as TFI cases or controls based on laparoscopic examination. Finite mixture models were used to identify the number of component titer distributions and the proportion of serum samples in each, from which estimates of PEF were derived. Four titer distributions were identified. The component at the highest titer was found only in samples from women with TFI, but there was also an excess of the second-highest titer component in TFI cases. Minimum and maximum estimates of the PEF were 28.0% (95% credible interval: 6.9, 50.0) and 46.8% (95% credible interval: 23.2, 64.1). Equivalent estimates based on the standard PEF formula from case-control studies were 0% and over 65%. Finite mixture modeling can be applied to serological data to obtain estimates of the proportion of reproductive damage attributable to C. trachomatis Further studies using modern assays in contemporary, representative populations should be undertaken., (© The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Both yaws and trachoma are endemic in several countries in the Pacific. In co-endemic countries there may be potential synergies between both control programmes., Methods: We undertook a cluster randomised trachoma and yaws seroprevalence survey of children in the Western Division of Fiji. Children were examined for skin lesions consistent with active yaws. A dried blood spot was collected which was tested using the Treponema pallidum particle agglutination (TPPA) test and an ELISA to detect antibodies against Pgp3., Results: A total of 607 children from 305 households across 23 villages were recruited into the survey. On skin examination, no child had clinical evidence of yaws, and the TPPA assay was negative in all children (0%, 95% CI 0.0-0.6). The seroprevalence of Pgp3 antibodies was 20.9% (95% CI 17.8-24.6%)., Discussion: In this study there was neither clinical nor serological evidence that transmission of yaws was ongoing. The Pgp3 seroprevalence pattern was consistent with either low level transmission of ocular Chlamydia trachomatis or exposure to C. trachomatis in the birth canal which is consistent with a survey conducted in the same region in 2013. These data suggest neither yaws nor ocular chlamydia infection are a significant public health problem in the Western Division of Fiji., (© The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Pelvic inflammatory disease (PID) is a leading cause of both tubal factor infertility and ectopic pregnancy. Chlamydia trachomatis is an important risk factor for PID, but the proportion of PID cases caused by C. trachomatis is unclear. Estimates of this are required to evaluate control measures., Methods: We consider 5 separate methods of estimating age-group-specific population excess fractions (PEFs) of PID due to C. trachomatis, using routine data, surveys, case-control studies, and randomized controlled trials, and apply these to data from the United Kingdom before introduction of the National Chlamydia Screening Programme., Results: As they are informed by randomized comparisons and national exposure and outcome estimates, our preferred estimates of the proportion of PID cases caused by C. trachomatis are 35% (95% credible interval [CrI], 11%-69%) in women aged 16-24 years and 20% (95% CrI, 6%-38%) in women aged 16-44 years in the United Kingdom. There is a fair degree of consistency between adjusted estimates of PEF, but all have wide 95% CrIs. The PEF decreases from 53.5% (95% CrI, 15.6%-100%) in women aged 16-19 years to 11.5% (95% CrI, 3.0%-25.7%) in women aged 35-44 years., Conclusions: The PEFs of PID due to C. trachomatis decline steeply with age by a factor of around 5-fold between younger and older women. Further studies of the etiology of PID in different age groups are required., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.)

Genital inflammation associated with sexually transmitted infections increases susceptibility to human immunodeficiency virus (HIV), but it is unclear whether the increased risk can reduce the efficacy of pre-exposure prophylaxis (PrEP). We investigated whether coinfection of macaques with Chlamydia trachomatis and Trichomonas vaginalis decreases the prophylactic efficacy of oral emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF). Macaques were exposed to simian/human immunodeficiency virus (SHIV) vaginally each week for up to 16 weeks and received placebo or FTC/TDF pericoitally. All animals in the placebo group were infected with SHIV, while 4 of 6 PrEP recipients remained uninfected (P= .03). Oral FTC/TDF maintains efficacy in a macaque model of sexually transmitted coinfection, although the infection of 2 macaques signals a modest loss of PrEP activity., (Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Unlabelled: Rapid, sensitive and specific isothermal nucleic acid amplification methods of Chlamydia trachomatis (C. trachomatis) and Neisseria gonorrhoeae (N. gonorrhoeae) have been developed based on cross-priming amplification (CPA). The amplicon of CPA can be detected by a disposable amplicon cross-contamination proof device. The whole assay takes 1-1·5 h from amplification to read out. Ten fold serial dilutions of quantified plasmids were used to test the CPA assay sensitivities, with the detection limits of 45 copies per reaction and 65 copies per reaction for C. trachomatis and N. gonorrhoeae respectively. The specificities of CPA assays for C. trachomatis and N. gonorrhoeae were tested by using total DNA extracted from nine other bacterial strains, and no cross-reactivity was detected. Eighty clinical cervical or vaginal swab specimens were tested by both CPA and real-time polymerase chain reaction (PCR) with the consistencies of 98·75% (79/80) and 97·5% (78/80) for C. trachomatis and N. gonorrhoeae respectively. Using real-time PCR as a reference standard, the clinical sensitivity (positive) and specificity (negative) of CPA was found to be 98·15% (53/54) and 100% (26/26) for C. trachomatis, and 93·75% (30/32) and 100% (48/48) for N. gonorrhoeae. Eight swab specimens tested positive for both C. trachomatis and N. gonorrhoeae simultaneously by real-time PCR and CPA assay. This study demonstrated that CPA is an affordable and accessible assay for C. trachomatis and N. gonorrhoeae detection, with high sensitivity and specificity., Significance and Impact of the Study: Rapid and specific detection of the sexually transmitted pathogens Chlamydia trachomatis (C. trachomatis) and Neisseria gonorrhoeae (N. gonorrhoeae) would enable early treatment and management of their spread. Here, for the first time, a user friendly DNA isothermal amplification method named cross-priming amplification (CPA), was used to test C. trachomatis and N. gonorrhoeae with high sensitivity and specificity. The results indicate that CPA has great potential for improving C. trachomatis and N. gonorrhoeae diagnostics which could be particularly advantageous in resource-limited areas., (© 2016 The Society for Applied Microbiology.)

Lymphogranuloma venereum (LGV) has emerged as an important cause of proctitis and proctocolitis in men who have sex with men; classical inguinal presentation is now increasingly uncommon. We report summary findings of an extensive literature review on LGV clinical presentation, diagnosis, and treatment that form the evidence base for the 2015 Centers for Disease Control and Prevention treatment guidelines for sexually transmitted diseases. Proctitis and proctocolitis are now the most commonly reported clinical manifestations of LGV, with symptoms resembling those of inflammatory bowel disease. Newer molecular tests to confirm LGV infection are sensitive and specific, but are generally restricted to research laboratory or public health settings. Doxycycline (100 mg twice daily for 21 days) remains the treatment of choice for LGV. Patients with rectal chlamydial infection and signs or symptoms of proctitis should be tested for LGV, or if confirmatory testing is not available, should be treated empirically with a recommended regimen to cover LGV infection., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

In preparation for the 2015 Centers for Disease Control and Prevention (CDC) Sexually Transmitted Diseases (STD) Treatment Guidelines, the CDC convened an advisory group in 2013 to examine recent abstracts and published literature addressing the epidemiology, diagnosis, and management of STDs. This article summarizes the key questions, evidence, and recommendations for the diagnosis and management of uncomplicated Chlamydia trachomatis (CT) infection in adolescents and adults that were considered in development of the 2015 CDC STD Treatment Guidelines. The evidence reviewed primarily focused on CT infection risk factors in women, clinical significance of oropharyngeal CT detection, acceptability and performance of CT testing on self-collected specimens in men, performance of CT point-of-care tests, efficacy of recommended and investigational CT infection treatments, and timing of test of cure following CT infection treatment in pregnant women., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Progestin-based contraception may impact women's susceptibility to sexually transmitted infection. We evaluated the effect of the levonorgestrel intrauterine system (LNG-IUS) on cervical persistence of Chlamydia trachomatis (CT) in a baboon model. Female olive baboons (Papio anubis) with or without an LNG-IUS received CT or sham inoculations. CT was detected in cervical epithelium with weekly nucleic acid amplification testing (NAAT) and culture. Presence of the LNG-IUS was associated with prolonged persistence of CT. Median time to post-inoculation clearance of CT as detected by NAAT was 10 weeks (range 7-12) for animals with an LNG-IUS and 3 weeks (range 0-12) for non-LNG-IUS animals (P = 0.06). Similarly, median time to post-inoculation clearance of CT by culture was 9 weeks (range 3-12) for LNG-IUS animals and 1.5 weeks (range 0-10) for non-LNG-IUS animals (P = 0.04). We characterized the community structure of the vaginal microbiota with the presence of the LNG-IUS to determine if alterations in CT colonization dynamics were associated with changes in vaginal commensal bacteria. Vaginal swabs were collected weekly for microbiome analysis. Endocervical CT infection was not correlated with alterations in the vaginal microbiota. Together, these results suggest that LNG-IUS may facilitate CT endocervical persistence through a mechanism distinct from vaginal microbial alterations., (© FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Expedited Partner Therapy (EPT) is the practice of treating the partners of patients with sexually transmitted infections by providing medications for the patient to deliver to his or her sexual partner (s) without direct clinical assessment of the partner(s). EPT is an evidence-based option that can augment existing partner management strategies. For military health care providers, questions still loom as to the pragmatic medical, legal, and ethical uncertainties of EPT use in military populations. These issues, in addition to the absence of an explicit Department of Defense EPT policy may dissuade military clinicians from fully employing EPT to prevent reinfection and inhibit additional disease transmission in their patients. To advance the notion that EPT could not only be an efficient but also a vital measure to decrease the high sexually transmitted disease burden, this report highlights existing approaches utilized by military providers to treat partners of patients diagnosed with chlamydia and/or gonorrhea, benefits of using EPT in military populations, and specific challenges of implementing an EPT program. This report asserts that now is the time to "push the conversation" on the use of EPT as a viable choice for military providers., (Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.)

Chlamydia trachomatis is an important human pathogen causing both ocular and sexually transmitted disease. Recently, we identified CT135 as an important virulence determinant in a mouse infection model. Results from CEL 1 digestion assays and sequencing analyses indicated that CT135 was much more polymorphic in high in vitro passage reference serovars than it was in clinical strains that had undergone limited passaging. Herein, we used targeted next-generation sequencing of the CT134-135 locus, from reference strains and clinical isolates, enabling accurate discovery of single nucleotide polymorphisms and other population genetic variations. Our results indicate that CT134 is stable in all C. trachomatis serovars examined. In contrast, CT135 is highly polymorphic in high-passaged reference ocular and non-LGV genital serovars, with the majority of the mutations resulting in gene disruption. In low-passaged ocular clinical isolates, CT135 was frequently disrupted, whereas in genital clinical isolates CT135 was intact in almost all instances. When a serovar K isolate, with an intact CT134 and CT135, was subjected to serial passage in vitro CT134 remained invariable, while numerous gene interrupting mutations rapidly accumulated in CT135. Collectively, our data indicate that, for genital serovars, CT135 is under strong positive selection in vivo, and negative selection in vitro., (© FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The role of organism load in Chlamydia trachomatis infection is not well understood. We conducted a systematic review to investigate the epidemiology of C. trachomatis organism load in human genital chlamydia infection., Methods: Embase, PubMed, and Medline databases were searched for literature published through August 2014. English-language publications that quantified load in humans were eligible. Participant characteristics and laboratory data were extracted., Results: A total of 737 records were identified, and 29 publications involving 40 883 participants were included. In women, load was highest for cervical swabs and lowest for urine specimens. In men, load was highest for rectal swabs and similar for urethral swabs and urine specimens. Evidence of any association between load and age, serovar, risk of transmission, hormone levels, and concurrent sexually transmitted infections was inconsistent. Eight of 9 culture-based studies found an association between load and signs and symptoms, in contrast with only 3 of 8 nucleic acid amplification test (NAAT)-based studies (P = .03)., Conclusion: Chlamydia organism load varies by specimen type and site of sampling, and viable chlamydia organism load may be a more important indicator of severity of infection than total load measured by NAAT., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Knowledge about genital Chlamydia trachomatis (CT) infections in the Pacific is limited. In this study we investigated CT infection in Samoan women., Methods: We recruited women having unprotected sex aged 18 to 29 years from 41 Samoan villages. They completed a questionnaire and provided a urine sample for CT testing by PCR. Associations between CT infection and possible risk factors were explored using logistic regression., Results: Altogether, 239 women were recruited; 86 (36.0%; weighted estimate of prevalence: 41.9%; 95% CI: 33.4-50.5%) were positive for CT infection. A higher proportion of women aged 18 to 24 were positive (54/145; 37.2%) than those aged 25 to 29 (32/94; 34.0%; p=0.20). Being single (OR 1.92; 95% CI: 1.02-3.63) and having two or more lifetime sexual partners (OR 3.02; 95% CI: 1.19-7.67) were associated with CT infection; 27.6% of those with one lifetime partner were positive. Participants who had a previous pregnancy were less likely to be positive (OR 0.49; 95% CI: 0.27-0.87). Primiparous and multiparous women were less likely to be positive than nulliparous women (OR 0.54; 95% CI: 0.30-0.99 and OR 0.46; 95% CI: 0.24-0.89, respectively)., Conclusions: The prevalence of CT infection in these Samoan women is very high. Further studies, including investigating the prevalence of CT infection in men, and strategies for sustainable control are needed., (© The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Chlamydia trachomatis is suspected of causing female infertility. It is the most widespread sexually transmitted infection with an estimated general prevalence of ~5-10% with a peak in younger individuals. C. trachomatis infection is more prevalent among lower social classes., Objective: In this study, the association between age, gender, social status and testing and positive rates is investigated in the age group 15-24 years., Design: Case-control study linked to data from Statistics Denmark., Methods: Data from the Department of Microbiology, Hvidovre University Hospital, Copenhagen were used and included 21887 people tested by general practitioners (GPs) and 3177 people tested at a venereological clinic. The age range was 15-24 years in 2011. These data were linked with the parental educational status delivered by Statistics Denmark, which also delivered a matched control group. The data were analysed using a case-control design., Results: Testing was more frequent in the following groups: age range 20-24 years, females and patients with higher parental educational status. About 87.3% of patient had been tested by GPs. Positive rates were highest among males at the general practice constituting 17.1% versus females 10.6%, younger individuals and patients with lower parental educational status., Conclusions: The C. trachomatis testing pattern and positive rates highlight a need for a greater focus on males, younger patients and individuals with a lower social status., (© The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Trachoma, caused by repeated infections with ocular Chlamydia trachomatis, is targeted for elimination using multiple annual rounds of mass drug administration (MDA) in endemic communities. Infection rates do not decline as expected in some communities, leading to concerns about azithromycin resistance., Methods: After 3 yearly MDAs in 32 communities in Tanzania, 107 children were identified 1 year later with infection. All were provided MDA again, and 90 were seen again at 2 months, of whom 30 had infection. Chlamydia trachomatis isolates were obtained before and after MDA in 15 paired samples and were tested for antimicrobial susceptibility. The infectious load of C. trachomatis before MDA was determined in 30 children who had infection at both times and 60 whose infection cleared., Results: The median load was 8.6 genome copies per polymerase chain reaction in the consistently infected, and 8.4 in those whose infection cleared (P = .86). For the consistently infected, the average minimum inhibitory concentration was 0.26 µg/mL for azithromycin before and 0.20 µg/mL after MDA. All isolates had minimum inhibitory concentration ≤0.50 µg/mL., Conclusions: There is no evidence that continued infection after MDA was due either to resistance to azithromycin or to a heavier load of organism before treatment. Other potential causes of persistent infection need to be evaluated.

Objectives: To evaluate the performance of the Hologic Gen-Probe (San Diego, CA) PANTHER system., Methods: The performance of PANTHER was compared with the Hologic Gen-Probe TIGRIS and/or Roche (Indianapolis, IN) COBAS AMPLICOR systems through testing of patient specimens and the spiked-urine matrix., Results: After discrepant resolution, PANTHER demonstrated a 99.3% (95% confidence interval [CI], 96.0%-99.9%) positive and 100% (98.5%-100.0%) negative agreement for Chlamydia trachomatis (CT) and 100% (96.6%-100.0%) positive and 100% (98.6%-100.0%) negative agreement for Neisseria gonorrhoeae (NG) for all male, female, unsexed, and NG-spiked female urine specimens combined. For other specimen types collectively, the PANTHER demonstrated 100% (95% CI, 90.6%-100.0%) positive and 100% (88.3%-100.0%) negative agreement for CT and 90.9% (62.8%-98.4%) positive and 100% (93.5%-100.0%) negative agreement for NG. Analytical sensitivity of the PANTHER in urine matrix was similar to the TIGRIS system., Conclusions: The PANTHER system provides an excellent new addition to options for detecting CT and NG, is appropriate for testing urine samples, and will facilitate high-throughput testing in the clinical laboratory.

Background: Sexually transmitted bacterial rectal infections are objective markers of HIV risk behavior. Quantifying HIV risk among men who have sex with men (MSM) who have had these infections can inform prevention efforts. We measured HIV risk among MSM who have and those who have not been diagnosed with rectal Chlamydia trachomatis (CT) and/or rectal Neisseria gonorrhoeae (GC)., Methods: HIV incidence among a cohort of 276 HIV-negative MSM diagnosed with rectal CT and/or GC in New York City sexually transmitted disease (STD) clinics was compared to HIV incidence among HIV-negative MSM without these infections. Matches against the citywide HIV/AIDS registry identified HIV diagnoses from STD clinics, and by other providers. Cox proportional hazards models were used to explore factors associated with HIV acquisition among MSM with rectal infections., Results: HIV-negative MSM with rectal infections (>70% of which were asymptomatic) contributed 464.7 person-years of follow-up. Among them, 31 (11.2%) were diagnosed with HIV, of whom 14 (45%) were diagnosed by non-STD clinic providers. The annual HIV incidence was significantly higher among MSM with rectal infections (6.67%; 95% confidence interval [CI], 4.61%-9.35%) than among MSM without rectal infections (2.53%; 95% CI, 1.31%-4.42%). Black race (hazard ratio, 4.98; 95% CI, 1.75-14.17) was associated with incident HIV among MSM with rectal CT/GC., Conclusions: One in 15 MSM with rectal infections was diagnosed with HIV within a year, a higher risk than for MSM without rectal infections. Such data have implications for screening for rectal STD, and may be useful for targeting populations for risk-reduction counseling and other HIV prevention strategies, such as preexposure prophylaxis.

Background: Previous studies identified specific Chlamydia trachomatis strains circulating among men who have sex with men (MSM). This study investigates whether distinct C. trachomatis strains circulate among subpopulations within the MSM community., Methods: Participants were recruited at the sexually transmitted infection clinic of the Public Health Service of Amsterdam from 2008 to 2009. C. trachomatis samples were typed using multilocus sequence typing. Epidemiological and clinical data were derived from questionnaires and patient records., Results: Typing of 277 samples from 260 MSM identified distinct C. trachomatis strains circulating concurrently over time. Men with lymphogranuloma venereum (LGV)-inducing strains were more likely to be infected with human immunodeficiency virus, more often had a history of STI, and had a higher frequency of risky sexual behavior. No such associations were found for non-LGV-inducing strains. MSM infected with heterosexual-associated strains were often younger (P = .04) and more often reported sex with women (P = .03), compared with men infected with MSM-associated strains., Conclusions: With the exception of LGV-inducing strains, no evidence was found that different C. trachomatis strains circulated in distinct subpopulations of MSM. This indicates that no separate transmission networks for C. trachomatis among MSM existed. However, younger MSM and bisexuals were more often infected with heterosexual-associated C. trachomatis strains.

In disease control or elimination programs, diagnostics are essential for assessing the impact of interventions, refining treatment strategies, and minimizing the waste of scarce resources. Although high-performance tests are desirable, increased accuracy is frequently accompanied by a requirement for more elaborate infrastructure, which is often not feasible in the developing world. These challenges are pertinent to mapping, impact monitoring, and surveillance in trachoma elimination programs. To help inform rational design of diagnostics for trachoma elimination, we outline a nonparametric multilevel latent Markov modeling approach and apply it to 2 longitudinal cohort studies of trachoma-endemic communities in Tanzania (2000-2002) and The Gambia (2001-2002) to provide simultaneous inferences about the true population prevalence of Chlamydia trachomatis infection and disease and the sensitivity, specificity, and predictive values of 3 diagnostic tests for C. trachomatis infection. Estimates were obtained by using data collected before and after mass azithromycin administration. Such estimates are particularly important for trachoma because of the absence of a true "gold standard" diagnostic test for C. trachomatis. Estimated transition probabilities provide useful insights into key epidemiologic questions about the persistence of disease and the clearance of infection as well as the required frequency of surveillance in the post-elimination setting.

Objectives: Using a statistical modelling approach, our study aim is to determine reliable age-related estimates of the risk of all-cause tubal factor infertility (TFI) following past or current chlamydial infection in women in Scotland., Method: Using data from several sources, a Markov-Chain Monte Carlo model was used to estimate the age-related risk of TFI given genital chlamydia infection at any time. The analysis is based on the probability of a woman ever having chlamydial infection, ever having TFI and ever having a previous chlamydial infection given a diagnosis of TFI. The model was programmed and evaluated using WinBugs14., Results: By the age 44 years, the overall risk of a woman having at least a single chlamydial infection is estimated at 42.9% (95% credible interval 30.0, 59.0%). The risk of a woman having TFI increased from 0.5% in those aged 16-19 years to 0.8% in those aged 40-44. The overall estimated probability of TFI, based on lifetime infertility, given a past or current chlamydial infection, is relatively consistent across all five age groups from 16-44 years, being 0.9% among those aged 25-29 and 1.4% in those aged 35-39; The estimates were found to be sensitive to the definition of infertility, with the estimate increasing from 1.3% in the youngest age group to 2.8% and 4.5% for 24-month primary infertility and primary or secondary infertility, respectively., Conclusions: At the population level, the likelihood of all-cause TFI in those with past or current chlamydial infection is low. These findings have relevance both at the policy level, in the development of control programmes, and also at an individual level, particularly for clinicians supporting women undergoing testing or with a positive diagnosis.

The development of a plasmid-based genetic transformation protocol for Chlamydia trachomatis provides the basis for the detailed investigation of the function of the chlamydial plasmid and its individual genes or coding sequences (CDS). In this study we constructed a plasmid vector with CDS6 deleted (pCDS6KO) from the original Escherichia coli/C. trachomatis shuttle vector pGFP::SW2. pCDS6KO was transformed into a clinical isolate of C. trachomatis from Sweden that is plasmid-free (C. trachomatis SWFP-). Penicillin-resistant transformants expressing the green fluorescent protein were selected. These transformants did not stain with iodine, indicating that this property is regulated by CDS6 or its gene product. In addition, mature inclusions of C. trachomatis SWFP- transformed by pCDS6KO displayed an identical morphological phenotype to the untransformed plasmid-free recipient host. In this phenotype the morphology of inclusions was altered with the chlamydiae lining the periphery of the inclusion leaving a 'hole' in the centre. These green fluorescent inclusions appear 'doughnut-shaped' with an empty centre when examined under blue light, giving rise to a characteristic 'black hole' phenotype. Our study demonstrates the power of the new genetic system for investigating chlamydial gene function using gene deletion technology., (© 2013 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.)

Aim: To develop and evaluate an in-house reverse hybridization technique for Chlamydia trachomatis genotype identification., Methods and Results: The evaluation of the developed and optimized reverse hybridization method on reference strains showed the specific detection of all genotypes. This technique showed its ability to type one inclusion-forming unit of C. trachomatis genotype E and equivalent sensitivity to the Cobas TaqMan assay. It was also able to detect mixed infections in vitro. Application of the reverse hybridization method on 38 isolated C. trachomatis strains and their respective swabs allowed the detection of six urogenital genotypes D, E, F, G, H and K and one trachoma genotype B. Genotype E was the most prevalent, detected in 73% of the swab samples. Mixed infections were detected in 26% of swab cases., Conclusion: The reverse hybridization technique is simple and does not require specialized instruments. It is powerful in the diagnosis of mixed infections and is suitable for use in epidemiological studies., Significance and Impact of the Study: This technique allowed rapid C. trachomatis genotype identification., (© 2012 The Authors Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.)

This study compared the performance of Chlamydia trachomatis testing using 2 methods: the BD ProbeTec Chlamydia trachomatis Q(x) Amplified DNA Assay (CTQ) on the BD Viper System with XTR technology (CTQ assay) and the Hybrid Capture (HC) 2 assay. A total of 1,054 Surepath and ThinPrep specimens were tested for C trachomatis nucleic acids using the CTQ assay and the HC2 assay. For positive and discrepant C trachomatis test results, confirmatory test for C trachomatis was performed using a reverse transcriptase-polymerase chain reaction. Of 1,054 liquid-based gynecologic cytology samples tested for C trachomatis using both assays, 1,041 tested negative on both. In 6 (0.57%) samples, findings were discordant. The CTQ assay and the HC2 assay had sensitivity rates of 100% and 66.7%, respectively, with comparable specificity (99.9%). The positive predictive values were 92.3% and 88.9% with the CTQ and HC2 assays, respectively. In this study, the CTQ assay was found to be more sensitive than the HC2 assay in detecting chlamydial infection; the CTQ assay also demonstrated a higher positive predictive value.

Background: Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), and Trichomonas vaginalis (TV) are sexually transmitted infections (STIs) associated with nongonococcal urethritis (NGU). We assessed their predictors and persistence after treatment., Methods: We analyzed data from an NGU treatment trial among symptomatic heterosexual men aged 16-45 years from STI clinics. Nucleic acid amplification tests detected CT, MG, and TV at baseline and at 1 and 4 weeks after therapy. Associations between variables and STI detection were investigated., Results: Among 293 participants, 44% had CT, 31% had MG, and 13% had TV at baseline. In multivariate analysis, CT infection was associated with young age and STI contact. Young age was also associated with MG, and having ≥ 1 new partner was negatively associated with TV. We detected persistent CT in 12% and MG in 44% of participants at 4 weeks after therapy, which were associated with signs and symptoms of NGU. Persistent CT was detected in 23% of participants after azithromycin treatment vs 5% after doxycycline treatment (P = .011); persistent MG was detected in 68% of participants after doxycycline vs 33% after azithromycin (P = .001). All but 1 TV infection cleared after tinidazole., Conclusions: Persistent CT and MG after treatment of NGU are common, and were associated with clinical findings and drug regimen.