Clustering of Polymorphic Membrane Protein E Clade in Chlamydia trachomatis Lineages from Men Who Have Sex with Men.

Several Chlamydia trachomatis lineages identified through outer membrane protein A genotyping or multilocus sequence typing have been circulating worldwide among men who have sex with men. In a study in Tokyo, Japan, we demonstrate that such lineages commonly belong to a specific polymorphic membrane protein E clade across genotypes.

Autophagy: the misty lands of Chlamydia trachomatis infection.

Chlamydia are Gram-negative, obligate intracellular bacterial pathogens that infect eukaryotic cells and reside within a host-derived vacuole known as the inclusion. To facilitate intracellular replication, these bacteria must engage in host-pathogen interactions to obtain nutrients and membranes required for the growth of the inclusion, thereby sustaining prolonged bacterial colonization. Autophagy is a highly conserved process that delivers cytoplasmic substrates to the lysosome for degradation. Pathogens have developed strategies to manipulate and/or exploit autophagy to promote their replication and persistence. This review delineates recent advances in elucidating the interplay between Chlamydia trachomatis infection and autophagy in recent years, emphasizing the intricate strategies employed by both the Chlamydia pathogens and host cells. Gaining a deeper understanding of these interactions could unveil novel strategies for the prevention and treatment of Chlamydia infection.

Prevalence of sexually transmitted infections (STIs) among first time visitors at STIs clinic in Hangzhou, China: Assessing the influence of the COVID-19 pandemic.

BACKGROUND: This study assesses the prevalence of sexually transmitted infections (STIs) in first time visitors to the STIs clinic in Hangzhou, China, considering different genders, ages and symptoms. And also explores howthe COVID-19 pandemic has affected on STIs. METHODS: From 2019 to 2023, 27,283 first time visitors were tested for nine distinct STIs, including Human Papillomavirus (HPV), Human Immunodeficiency Virus (HIV), syphilis, Herpes Simplex Virus type 2 (HSV-2), Ureaplasma urealyticum (UU), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Mycoplasma genitalium (MG), and vaginal Candida. RESULTS: Symptomatic male and female visitors showed overall STI-positive rates of 39.27% and 59.20%, respectively(p < .001). The top three pathogens in both genders were HPV (47.56% and 56.71%), UU (29.21% and 56.47%), and HSV-2 (22.41% and 52.94%). Among asymptomatic visitors, the total STI-positive rate was 36.63% in males and 52.03% in females. Age-stratified analysis revealed higher STI rates in visitors ≤ 20 or >50 years, regardless of gender and symptoms. During the COVID-19 pandemic, symptomatic visitors showed lower positive rates for HPV, HIV, syphilis, and HSV-2, while Candida, UU, CT, NG, and multiple infections increased. Among asymptomatic visitors, HPV had the lowest positive rate, while NG and multiple infections increased during the pandemic. CONCLUSION: STI prevalence is notably high, particularly in those aged ≤ 20 and >50 years. It emphasizes the need for enhanced health education, condom use, and vaccination. The COVID-19 pandemic impacting STIs through varied factors, such as reduced sexual activity and clinical service interruption.

Reproductive tract complication risks following Chlamydia trachomatis infections: a long-term prospective cohort study from 2008 to 2022.

Background: The clinical and public health relevance of widespread testing for asymptomatic Chlamydia trachomatis (chlamydia) infections is under debate. To address uncertainties in screening programs, we estimate reproductive tract complication risks following asymptomatic and symptomatic chlamydia infections in a long-term prospective cohort. Methods: A cohort of 5704 reproductive-age women recruited from a chlamydia screening study was followed for up to 14 years. Chlamydia positivity was determined using screening polymerase chain reaction test results, self-reported diagnoses (with/without symptoms), and chlamydia Immunoglobulin G antibodies. Outcome data (pregnancies, pelvic inflammatory disease (PID), ectopic pregnancy, and tubal factor infertility) were collected through self-completed questionnaires. Cox regression calculated adjusted hazard ratios (aHR) with confidence intervals (CI) to compare outcomes between time-updated chlamydia groups since sexual debut. Findings: During 104,612 person-years, 2103 (36.9%) women were chlamydia-positive and 3692 women (64.7%) had been pregnant at least once. Risks for PID, ectopic pregnancy and tubal factor infertility were 1.62 (95% CI 1.20-2.17), 1.84 (95% CI 1.14-2.95) and 2.75 (95% CI 1.53-4.94), compared to chlamydia-negatives. aHRs for PID after symptomatic and asymptomatic infections were 2.29 (95% CI 1.62-3.25) and 1.06 (95% CI 0.66-1.69), respectively. Incidence of PID, ectopic pregnancy and tubal factor infertility after symptomatic chlamydia infection remained low with rates per 1000 person-years of 5.8, 1.9, and 1.8, respectively. Interpretation: We found a significantly higher risk of PID, ectopic pregnancy and tubal factor infertility in chlamydia-positive women compared to chlamydia-negative women, although the overall incidence rates of complications remained low. Symptomatic, but not asymptomatic, chlamydia infections were associated with PID risk, suggesting the largest disease burden of complications is in this group. Funding: The Netherlands Organisation for Health Research and Development (ZonMW Netherlands) and Research Funding from the Ministry of Health, Welfare and Sports.

The Risk of Pelvic Inflammatory Disease in Women Infected With Chlamydia (Chlamydia trachomatis): A Literature Review.

A literature review was undertaken to examine the risk of developing pelvic inflammatory disease (PID) in women infected with Chlamydia trachomatis. A search of OVID Medline and Embase databases was conducted for studies published between 1946 and 26 June 2023. This review looked solely at prospective cohort study designs and searched reference lists of studies selected for inclusion. This literature review confirmed that C. trachomatisis a key factor in the development of PID in women through different pathogenic mechanisms. However, to reach more firm conclusions on the subject, further prospective cohort studies with a larger cohort size and a longer follow-up time are needed.

Distribution of Chlamydia trachomatis ompA-genotypes over three decades in Portugal.

OBJECTIVES: Chlamydia trachomatis is classified into 15 major genotypes, A to L3, based on the diversity of ompA gene. Here, we evaluated and characterised the distribution and diversity of ompA-genotypes over 32 years (1990-2021) in Portugal. METHODS: The collection of the Portuguese National Reference Laboratory for Sexually Transmitted Infections includes 5824 C. trachomatis-positive samples that were successfully ompA-genotyped between 1990 and 2021. An in-depth analysis of ompA-genotypes distribution across the years, as well as by biological sex, age and anatomical site of infection was performed. RESULTS: ompA-genotype E was consistently the most frequently detected across the years, with a median frequency of 34.6%, followed by D/Da (17.6%), F (14.3%) and G (10.7%). The prevalence of lymphogranuloma venereum (LGV) genotypes (mostly L2, 62.0%, followed by L2b, 32.1%) increased since 2016, reaching the highest value in 2019 (20.9%). LGV, G and Da genotypes were associated with biological sex, specifically with being male, and were the most frequent among anorectal specimens (37.7%, 19.4% and 17.7%, respectively). Notably, LGV ompA-genotypes represented 38.9% of the male anorectal specimens since 2016, and were also detected among oropharynx and urogenital samples. ompA-genotype E was the most frequently detected at the oropharynx (28.6%) and urogenital (33.9%) sites during the study period, followed by D/Da (17.4%) and F (16.0%) in the urogenital specimens, and by G (26.1%) and D/Da (25.7%) in oropharynx specimens. Our data also highlight the emergence of the recombinant L2b/D-Da strain since 2017 (representing between 2.0% and 15.5% of LGV cases per year) and the non-negligible detection of ompA-genotype B in urogenital and anorectal specimens. CONCLUSIONS: This study provides a comprehensive landscape of C. trachomatis molecular surveillance in Portugal, highlighting the continued relevance of ompA-genotyping as a complement to rapid LGV-specific detection tests. It also contributes to a deeper understanding of C. trachomatis epidemiology, diversity and pathogenicity.

Tracking Chlamydia and Syphilis in the Detroit Metro Area by Molecular Analysis of Environmental Samples.

This paper describes one of the first studies applying wastewater surveillance to monitor Chlamydia and Syphilis and back-estimate infections in the community, based on bacterial shedding and wastewater surveillance data. Molecular biology laboratory methods were optimized, and a workflow was designed to implement wastewater surveillance tracking Chlamydia and Syphilis in the Detroit metro area (DMA), one of the most populous metropolitan areas in the U.S. Untreated composite wastewater samples were collected weekly from the three main interceptors that service DMA, which collect wastewater and discharge it to the Great Lakes Water Authority Water Resource Recovery Facility. Additionally, untreated wastewater was also collected from street manholes in three neighborhood sewersheds in Wayne, Macomb, and Oakland counties. Centrifugation, DNA extraction, and ddPCR methods were optimized and performed, targeting Chlamydia trachomatis and Treponema pallidum, the causative agents of Chlamydia and Syphilis, respectively. The limit of blank and limit of detection methods were determined experimentally for both targets. Both targets were detected and monitored in wastewater between December 25th, 2023, and April 22nd, 2024. The magnitudes of C. trachomatis and T. pallidum concentrations observed in neighborhood sewersheds were higher as compared to the concentrations observed in the interceptors. Infections of Chlamydia and Syphilis were back-estimated through an optimized formula based on shedding dynamics and wastewater surveillance data, which indicated potentially underreported conditions relative to publicly available clinical data.

Candidate antibody reference reagents for Chlamydia trachomatis serology.

Chlamydia trachomatis (Ct) serology is an important tool for monitoring infection and disease burden but there are currently no formal reference reagents to harmonize results reporting. Our objective was to develop a panel of candidate reference reagents with reactivity against the major outer membrane protein (MOMP) and virulence factor (pgp3) antigens. Plasma packs from females (20-40 years old) were screened against MOMP and pgp3 antigens and selected positive and negative samples pooled to create a panel of candidate antibody reference reagents that were tested in two laboratories. Antigen specificity and internal quality assurance were also evaluated. Suitable candidate materials have been selected to produce Ct reference reagents.

Viability of Chlamydia trachomatis in different anatomical sites - a systematic review & meta-analysis.

BACKGROUND: Modern assays for the detection of Chlamydia trachomatis (CT) rely on nucleic acid amplification testing (NAAT) of DNA or ribosomal RNA. However, it is also known that both viable ("living") & non-viable ("dead") CT can be detected by NAAT. Multiple laboratory techniques to measure CT viability have emerged. METHODS: We searched PubMed, EMBASE, Scopus and Dimensions as well as conference abstracts for entries between January 2000 to May 2023. We included any studies that measured CT viability among NAAT-positive samples. Viability assays include enhanced cell culture, direct fluorescent antibody (DFA), messenger RNA (mRNA) detection via digital droplet PCR (ddPCR), viability PCR (V-PCR) & real-time PCR measuring RNA-to-DNA ratio (RDR) (e.g. InSignia®). A meta-analysis was performed on the proportions of non-viable CT by anatomical site. RESULTS: We screened 31,342 records and included 16 studies in the analysis. The pooled proportions of non-viable CT by site were: 33% (95%CI 19-47%) in rectal swabs (eight studies), 17% (95%CI 7-27%) in cervical swabs (six studies), 15% (95%CI 6-25%) in vaginal swabs (six studies) and 11% (95%CI 9-17%) in urine/urethral swabs (two studies). CONCLUSION: All included studies found that a proportion of NAAT-detected CT is non-viable. The findings have far-reaching implications for screening programs and studies evaluating new STI tests and antimicrobial regimens.

Prevalence of Mycoplasma genitalium and macrolide resistance in rectal and urine samples among men who have sex with men in Sweden.

OBJECTIVES: While Mycoplasma genitalium is reported as a common rectal infection among men who have sex with men (MSM), published data refer predominantly to urethral infections. Currently, most guidelines recommend M. genitalium testing from urine in men with symptomatic, non-gonococcal urethritis. Macrolide resistance-associated mutations (MRMs) among M. genitalium have increased during the last decade especially among MSM. We aim to demonstrate the prevalence and anatomical distribution of M. genitalium infection and MRM in urine and rectal specimens among MSM in Sweden. METHODS: In this cross-sectional study in 2019, paired urine and rectal samples from symptomatic and asymptomatic MSM attending a sexually transmitted infection clinic in the south of Sweden were screened for M. genitalium, presence of MRM, Neisseria gonorrhoeae, Chlamydia trachomatis, HIV and syphilis. RESULTS: The overall prevalence of M. genitalium was 10.5% (64 of 609), rectal samples 7.6% (46 of 609) and urine samples 3.9% (24 of 609) (p=0.007). Among M. genitalium-positive cases, single rectal and single urethral infection was detected in 62.5% (40 of 64) and 28.1% (18 of 64), respectively (p<0.0001). Infection at both sites was seen in 9.4% (6 of 64). The prevalence of MRM was 67.9% (19 of 28). M. genitalium was significantly associated with HIV (OR 2.60, 95% CI 1.14 to 5.88, p=0.02). Among the MSM, 7.4% (45 of 609) were infected with N. gonorrhoeae, 6.7% (41 of 609) with C. trachomatis, 7.1% (43 of 609) with HIV and 0.7% (4 of 609) with syphilis. CONCLUSIONS: In this study, among MSM, most infections with M. genitalium were detected as rectal mono infections. The prevalence of M. genitalium among MSM was almost twofold higher in rectal samples (7.6%) compared with urine samples (3.9%). The prevalence of macrolide resistance was high with no difference between urine and rectal samples.

Interleukin-10 Gene Polymorphisms Modulate the Risk of Infertility in Chlamydia trachomatis Positive Kurdish Women in Erbil Province.

Background: There is evident inter-individual variability in women's responses to Chlamydial infections and reproductive tract problems. Women's genetic variations within the Interleukin-10 (IL-10) gene have been linked to variances in response to Chlamydia trachomatis infection. This study was aimed to demonstrate the profound association of IL-10 with infertility and demonstrate the role of IL-10 (-592 C/A rs1800872) and (-1082 A>G rs1800896) single nucleotide polymorphism (SNPs) gene in the susceptibility and severity of a C. trachomatis infection. Methods: In this evaluation study, serum IL-10 concentration was measured in 134 women diagnosed with infertility and 50 healthy volunteers by enzyme-linked immunosorbent assay (ELISA). The tetra-amplification refractory mutation system-PCR (T-ARMS-PCR) analysis was performed to detect the genotyping of the rs1800872 and rs1800896 SNPs genes. Results: Both female groups were positive for anti-chlamydial IgM antibody, but the intensity of response differed between cases. At the same time, the incidence of genital C. trachomatis by PCR was 46.2% in infertile women. The serum concentration of IL10 was lower in infertile women than healthy participants and higher in infertile C. trachomatis -positive women compared to infertile C. trachomatis-negative in all groups except endometriosis (Endo) infertility. In rs1800872, the CA genotype and C allele are associated with an increased risk for infertility, except in polycystic ovarian syndrome (PCOS), which is an A allele. In the case of rs1800896, the AG genotype and G allele show a greater risk for infertility. Conclusions: Our results confirmed that rs1800872 and rs1800896 gene polymorphisms were associated with an increased risk of C. trachomatis infection.

Insights into Pathogenesis of Trachoma.

Trachoma is the most common infectious cause of blindness worldwide. This review investigates the pathogenesis of trachoma, focusing on its causative agent, transmission pathways, disease progression, and immune responses. Trachoma is caused by serovars A-C of the bacterium Chlamydia trachomatis (Ct). Transmission occurs through direct or indirect exchanges of ocular and nasal secretions, especially in regions with poor hygiene and overcrowded living conditions. The disease is initiated in early childhood by repeated infection of the ocular surface by Ct. This triggers recurrent chronic inflammatory episodes, leading to the development of conjunctival scarring and potentially to trichiasis, corneal opacity, and visual impairment. Exploring the pathogenesis of trachoma not only unveils the intricate pathways and mechanisms underlying this devastating eye disease but also underscores the multifaceted dimensions that must be considered in its management.

Immunity to Sexually Transmitted Bacterial Infections of the Female Genital Tract: Toward Effective Vaccines.

Sexually transmitted infections (STIs) caused by bacterial pathogens Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum present significant public health challenges. These infections profoundly impact reproductive health, leading to pelvic inflammatory disease, infertility, and increased susceptibility to other infections. Prevention measures, including antibiotic treatments, are limited by the often-asymptomatic nature of these infections, the need for repetitive and continual screening of sexually active persons, antibiotic resistance for gonorrhea, and shortages of penicillin for syphilis. While vaccines exist for viral STIs like human papillomavirus (HPV) and hepatitis B virus (HBV), there are no vaccines available for bacterial STIs. This review examines the immune responses in the female genital tract to these bacterial pathogens and the implications for developing effective vaccines against bacterial STIs.

Viral Vector-Based Chlamydia trachomatis Vaccines Encoding CTH522 Induce Distinct Immune Responses in C57BL/6J and HLA Transgenic Mice.

Chlamydia trachomatis remains a major global health problem with increasing infection rates, requiring innovative vaccine solutions. Modified Vaccinia Virus Ankara (MVA) is a well-established, safe and highly immunogenic vaccine vector, making it a promising candidate for C. trachomatis vaccine development. In this study, we evaluated two novel MVA-based recombinant vaccines expressing spCTH522 and CTH522:B7 antigens. Our results show that while both vaccines induced CD4+ T-cell responses in C57BL/6J mice, they failed to generate antigen-specific systemic CD8+ T cells. Only the membrane-anchored CTH522 elicited strong IgG2b and IgG2c antibody responses. In an HLA transgenic mouse model, both recombinant MVAs induced Th1-directed CD4+ T cell and multifunctional CD8+ T cells, while only the CTH522:B7 vaccine generated antibody responses, underscoring the importance of antigen localization. Collectively, our data indicate that distinct antigen formulations can induce different immune responses depending on the mouse strain used. This research contributes to the development of effective vaccines by highlighting the importance of careful antigen design and the selection of appropriate animal models to study specific vaccine-induced immune responses. Future studies should investigate whether these immune responses provide protection in humans and should explore different routes of immunization, including mucosal and systemic immunization.

The Chlamydia effector IncE employs two short linear motifs to reprogram host vesicle trafficking.

Chlamydia trachomatis, a leading cause of bacterial sexually transmitted infections, creates a specialized intracellular replicative niche by translocation and insertion of a diverse array of effectors (Incs [inclusion membrane proteins]) into the inclusion membrane. Here, we characterize IncE, a multifunctional Inc that encodes two non-overlapping short linear motifs (SLiMs) within its short cytosolic C terminus. The proximal SLiM, by mimicking just a small portion of an R-N-ethylmaleimide-sensitive factor adaptor protein receptor (SNARE) motif, binds and recruits syntaxin (STX)7- and STX12-containing vesicles to the inclusion. The distal SLiM mimics the sorting nexin (SNX)5 and SNX6 cargo binding site to recruit SNX6-containing vesicles to the inclusion. By simultaneously binding two distinct vesicle classes, IncE brings these vesicles in close apposition with each other at the inclusion to facilitate C. trachomatis intracellular development. Our work suggests that Incs may have evolved SLiMs to enable rapid evolution in a limited protein space to disrupt host cell processes.

IUSTI Europe position statement on use of DoxyPEP: June 2024.

This position statement is aimed at front-line clinical practitioners and public health authorities in WHO European Region providing services for people wishing to reduce their risk of acquiring sexually transmitted infections (STIs), including HIV.

Impact of STIs on cervical cancer screening: Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae in visual inspection with acetic acid (VIA) positive women in Mozambique.

BACKGROUND: Cervical cancer, primarily from HPV, is prevalent in countries like Mozambique, with HIV individuals at higher risk. The Visual Inspection with Acetic Acid (VIA) screening method can be influenced by STIs like Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). This study examines CT and NG prevalence in HIV-positive and negative women using VIA in Mozambique's DREAM program. METHODS: In this cross-sectional research conducted at a DREAM program facility in Maputo from 01/07/2021 to 31/05/2022, cervical specimens were taken from VIA-positive patients. CT/NG testing was performed using the Cobas® 4800 DNA CT/NG test. Statistical analyses focused on associations and prevalence rates, considering demographic, clinical, and exposure data. RESULTS: Among 117 women, we observed a CT prevalence of 6.8% (8/117) and an NG prevalence of 2.6%(3/117). No significant associations between CT/NG infection rates and factors such as age, HIV status, VIA results, or high-risk HPV (hrHPV) was observed. We found a 47% prevalence of hrHPV infections among participants with cervical lesions; no significant association between hrHPV and CT/NG infections was observed. CONCLUSION: This study highlights the prevalence of CT and NG in VIA-positive women in Mozambique, emphasizing the STI burden and suggesting integration of STI screening in cervical cancer prevention strategies.

Prognostic Value of Anti-Chlamydia Trachomatis IgG in Breast Cancer and the Modification Effects of Pro-Inflammatory Cytokines: A 13-Year Prospective Cohort Study.

Purpose: Chlamydia trachomatis (C. trachomatis) is associated with several gynecological tumors; yet its prognostic role in breast cancer remains unclear. Thus, we investigated the prognostic role of anti-C. trachomatis immunoglobulin G (IgG) in breast cancer patients and the modification effects of pro-inflammatory cytokines. Methods: The serum levels of C. trachomatis IgG and four pro-inflammatory cytokines were measured. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), including product terms to assess the modification effects of pro-inflammatory cytokines on the association between C. trachomatis IgG and breast cancer prognosis. Results: From 2008 to 2018, 1121 breast cancer patients were recruited and followed up until December 31, 2021, with a median follow-up time of 63.91 months (interquartile range: 39.16-90.08 months). Patients positive for C. trachomatis IgG showed HRs of 1.09 (95% CI, 0.67-1.78) for overall survival (OS) and 1.24 (0.87-1.78) for progression-free survival (PFS), compared to those who were negative. These associations became statistically significant in women aged 50 years or younger (HR=1.43, 95% CI=0.79-2.58 for OS; HR=1.79, 95% CI=1.16-2.77 for PFS). Positive C. trachomatis IgG serology was associated with adverse prognostic effects among patients with higher levels of pro-inflammatory cytokines (IL-6, TNF-α, IL-8, and IL-1ß), but with favorable prognostic effects for those with low levels. These interactions were particularly significant in those aged 50 years or younger. Conclusion: In breast cancer patients younger than 50 years of age or with higher levels of pro-inflammatory cytokines, C. trachomatis infection appeared to have a negative prognostic impact. These findings highlight the significance of C. trachomatis in predicting prognosis and personalized therapy for breast cancer patients.

Shifting Grounds-Facilitating Self-Care in Testing for Sexually Transmitted Infections Through the Use of Self-Test Technology: Qualitative Study.

BACKGROUND: Chlamydia remains prevalent worldwide and is considered a global public health problem. However, testing rates among young sexually active people remain low. Effective clinical management relies on screening asymptomatic patients. However, attending face-to-face consultations of testing for sexually transmitted infections is associated with stigmatization and anxiety. Self-testing technology (STT) allows patients to test themselves for chlamydia and gonorrhea without the presence of health care professionals. This may result in wider access to testing and increase testing uptake. Therefore, the sexual health clinic at Odense University Hospital has designed and developed a technology that allows patients to get tested at the clinic through self-collected sampling without a face-to-face consultation. OBJECTIVE: This study aimed to (1) pilot-test STT used in clinical practice and (2) investigate the experiences of patients who have completed a self-test for chlamydia and gonorrhea. METHODS: The study was conducted as a qualitative study inspired by the methodology of participatory design. Ethnographic methods were applied in the feasibility study and the data analyzed were inspired by the action research spiral in iterative processes using steps, such as plan, act, observe, and reflect. The qualitative evaluation study used semistructured interviews and data were analyzed using a qualitative 3-level analytical model. RESULTS: The findings from the feasibility study, such as lack of signposting and adequate information, led to the final modifications of the self-test technology and made it possible to implement it in clinical practice. The qualitative evaluation study found that self-testing was seen as more appealing than testing at a face-to-face consultation because it was an easy solution that both saved time and allowed for the freedom to plan the visit independently. Security was experienced when the instructions balanced between being detail-oriented while also being simple and illustrative. The anonymity and discretion contributed to preserving privacy and removed the fear of an awkward conversation or being judged by health care professionals thus leading to the reduction of intrusive feelings. CONCLUSIONS: Accessible health care services are crucial in preventing and reducing the impact of sexually transmitted infections and STT may have the potential to increase testing uptake as it takes into account some of the barriers that exist. The pilot test and evaluation have resulted in a fully functioning implementation of STT in clinical practice.