Proteomic analysis of HeLa cells after stable transfection with the Chlamydia trachomatis CT143 gene.

BACKGROUND: The CT143 protein of Chlamydia trachomatis (Ct) is a key immunodominant antigen and candidate type-III secretion substrate. Although CT143 expression has not been detected in the cytosol of infected cells, it is known to interfere with the physiological behavior of HeLa cells. This study aims to investigate how the CT143 protein affects the protein expression profile of HeLa cells, providing a basis for further research into Ct's pathogenic mechanisms. METHODS: We constructed a stably transfected HeLa cell line, pCD513B-1-CT143-HeLa, and a control cell line, pCD513B-1-HeLa. Protein expression profiles of these cell lines were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins were identified, constructed into a database, and verified using parallel reaction monitoring (PRM). Bioinformatics software facilitated the preliminary analysis of the biological functions of these differential proteins. RESULTS: A total of 221 host proteins were differentially expressed, with 68 upregulated and 153 downregulated. These variations influence the regulation of peptidase activity and are crucial in biological processes such as cell secretion and protease activity. Significant changes were noted in protein processing, alcohol dehydrogenase activity, Aldo-Keto reductase activity, and peptidase regulator activity. Furthermore, alterations were observed in cellular components like the plasma membrane and cell periphery. Pathways involving the hematopoietic system, glycosaminoglycan degradation, retinol metabolism, and cytochrome P450-mediated exogenous drug metabolism were notably affected. Indirect interactions among differentially expressed proteins included three key nodal proteins: C3, IFIT3, and IFIT1. CONCLUSION: The successful construction of a host differential protein expression profile was achieved through stable transfection of HeLa cells with the CT143 gene. The differential proteins identified are implicated in regulating various biological processes such as intracellular signal transduction, cell secretion, protein processing, hydrolysis, and enzyme activity. These findings suggest that the CT143 protein may influence the host cell's biological behavior by altering host protein expression, potentially hindering Ct growth and development.

Identifying the Impact of Chlamydia trachomatis Screening and Treatment on Mother-to-Child Transmission, and Respiratory Neonatal Outcomes in Mexico.

Chlamydia trachomatis (C. trachomatis) screening and treatment in pregnancy allows the opportunity to reduce adverse pregnancy and neonatal outcomes worldwide. Although C. trachomatis infection is easily treated and cured with antibiotics, only some countries have routine pregnancy screening and treatment programs. We therefore evaluated whether just one maternal screening for C. trachomatis is enough to prevent adverse pregnancy and negative neonatal outcomes. Among the 4087 first-time gynecological-obstetric consultations granted at the National Institute of Perinatology in 2018, we selected the study population according to a case-cohort design. Antenatal C. trachomatis screening and treatment interventions were performed on 628 pregnant women using COBAS® TaqMan CT. C. trachomatis DNA was also detected in samples from 157 infants of these mothers. In the maternal cohort, incidence of C. trachomatis infection was 10.5%. The vertical transmission rate was 1.5% for the cohort of mothers who tested positive for C. trachomatis and received treatment, and 29.7% for those with a negative test. By evaluating symptomatic neonatal infection, the hazard rate of perinatal pneumonia was 3.6 times higher in C. trachomatis-positive babies than in C. trachomatis-negative babies. Despite the low rate of mother-to-child transmission in women positive for C. trachomatis, possible maternal infection that is not detected in pregnancy significantly increases the risk of neonatal infection with consequent perinatal pneumonia.

No impact of a positive Chlamydia trachomatis serology on live-birth rate after intra-uterine insemination.

OBJECTIVE: To study the impact of a CT serology on intrauterine insemination (IUI) cumulative live-birth rate (cLBR) in women with documented bilateral tubal patency. DESIGN: Cohort study SUBJECTS: Infertile women with documented bilateral tubal patency and medical indication of IUI matched on the following criteria: woman's age, number of cycles completed and number of motile sperm inseminated (NMSI). EXPOSURE: This retrospective, observational and monocentric cohort study compared women with positive CT serology matched 1:1 to control women with negative CT serology. MAIN OUTCOME MEASURES: Cumulative LBR, rates of clinical pregnancy, spontaneous abortion, biochemical pregnancy. RESULTS: A total of 71 women in the CT positive group were matched to 71 women in the negative CT group, leading to compare 136 cycles per group. No statistically significant difference was observed between groups regarding the demographic and medical characteristics of couples. Cumulative LBR per woman was similar in both groups with 32.4% (n = 23) in the negative serology group Vs 25.4% (n = 18) in the positive CT group (NS). The rates of clinical pregnancy, spontaneous abortion, biochemical pregnancy were comparable between the two groups. CONCLUSION: In a population of infertile women with patent tubes, our study suggests that the serological status for CT has no impact on the IIU cLBR.

Spontaneous Clearance of Chlamydia trachomatis and Its Associated Factors among Women Attending Screening for Chlamydia in Shenzhen, China.

OBJECTIVES: This study aimed to investigate the factors associated with the spontaneous clearance of Chlamydia trachomatis, a phenomenon that, despite a growing body of literature, remains understudied in the context of women in China. METHODS: Spontaneous clearance was defined as the transition from a positive to negative Chlamydia status over time without the use of antichlamydial therapy. Data from 5,935 women aged 18 years and older who participated in the Clinical-Based Health Check program were analyzed. Eligible participants had no history of Neisseria gonorrhoeae infection, pelvic inflammatory disease, recent antibiotic use, or pregnancy and had an interval between the screening and follow-up visits of more than three days. Logistic regression was used to identify factors influencing spontaneous clearance. RESULTS: Spontaneous clearance occurred in 23.9% (50/209) of the participants, typically with a median interval of 27 days. Significant factors included an interval > 45 days, an age > 35 years, the use of an intrauterine device (IUD), and the presence of clue cells. CONCLUSION: Spontaneous clearance of C. trachomatis is significantly affected by age, the interval between two tests, IUD use, and the presence of clue cells. Screening strategies should prioritize women under 35 years of age who do not use IUDs and test negative for clue cells for more effective chlamydia prevention and management.

Exploring the prevalence of chlamydial and gonorrheal infections in pregnant women: a multicenter study in Egypt.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are widespread, treatable sexually transmitted infections (STIs) of global significance, affecting millions annually. Left untreated, they pose significant risks, including pelvic inflammatory disease (PID), infertility, and complications during pregnancy. The U.S. Centers for Disease Control recommends annual chlamydial screening for sexually active women to address these risks. Responding to this global challenge, the World Health Organization (WHO) has formulated a global health sector strategy on sexually transmitted infections, outlining priority actions to strengthen STI responses in countries. However, STI epidemiological studies encounter challenges in developing nations like Egypt due to socio-cultural factors, poverty, and limited diagnostic facilities. In Egypt, STI diagnosis primarily relies on clinical presentations, lacking structured screening programs for CT and NG. This study's main objective is to estimate the prevalence of Chlamydial and gonorrheal infections, advocating for supportive STI strategies in Egypt. Additionally, the study aims to provide a foundation for national prevalence estimates of CT and NG infections. METHODS: A cross-sectional study encompassed five antenatal clinics in different regions of Egypt. A total of 1040 pregnant women attending these clinics were consecutively sampled. Data collection involved structured questionnaires, and urine samples were subjected to the GeneXpert CT/NG qualitative real-time PCR test. RESULTS: The prevalence of CT infections was 0.29% (95% CI, 0.10-0.86%), with no detected NG infections. The three CT-positive cases were distributed across different recruitment centers, with no statistically significant differences observed between infected and non-infected participants. Notably, 40.3% of recruited women reported gynecological symptoms, primarily discharge. Additionally, 9.6% had undergone previous testing for sexually transmitted infections, with 8.2% receiving positive results. CONCLUSIONS: This study provides valuable data on the prevalence of CT and NG infections among pregnant women attending ANC clinics in Egypt. The findings underscore the importance of ongoing surveillance, routine screening, and targeted interventions to ensure the reproductive health and well-being of pregnant women and their infants. Further research is warranted to explore the broader implications of STIs in different populations and to inform evidence-based guidelines for screening and management in diverse settings. TRIAL REGISTRATION: IRB no.: 17,400,017; WHO ERC Protocol Id. A66005.

High rates of Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis, or Trichomonas vaginalis co-infection in people with HIV: a systematic review and meta-analysis.

PURPOSE: People living with HIV (PWH) experience a disproportionate burden of sexually transmitted infections (STIs), leading to more severe health outcomes and increasing the risk of HIV transmission. The presence of untreated STIs can accelerate HIV disease progression, while HIV infection can complicate STI diagnosis and treatment. Despite this interconnectedness, comprehensive data on the global prevalence of specific STIs among PWH remain limited. This systematic review aims to synthesize existing data to provide a more accurate picture of the prevalence of co-infection with Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis or Trichomonas vaginalis in PWH, while also identifying critical knowledge gaps and informing future research priorities. METHODS: We searched databases for eligible studies reporting the prevalence of Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis, or Trichomonas vaginalis among PWH, published from January 1, 2000, to February 1, 2023. From 22,290 identified articles, 127 independent studies meeting the inclusion criteria were included in this meta-analysis. RESULTS: The overall global co-infection prevalence of Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis in PWH, was 4.8% (95%CI: 4.7-5.0%), 0.8% (95%CI: 0.6-0.9%), 2.5% (95%CI: 2.2-2.7%), and 3.0% (95%CI: 2.7-3.3%), respectively. The global prevalence of these four STIs in PWH is high, especially in Africa and Southeast Asia and in MSM and TGW populations. Based on the subgroup analyses, we further found that there was a high prevalence of Treponema pallidum and Chlamydia trachomatis in Southeast Asia and a high infection of Trichomonas vaginalis in the whole of Africa. Treponema pallidum infection was more common in males than females, and Chlamydia trachomatis and Trichomonas vaginalis infections were more common in females than males. Besides, high infection rates of Treponema pallidum, Neisseria gonorrhoeae, and Chlamydia trachomatis were detected in men who have sex with men (MSM) + transgender women (TGW), while high infection rates of Trichomonas vaginalis were found in sex workers and pregnant women. CONCLUSION: The study confirmed high prevalence of four sexually transmitted pathogens in PWH, noting regional, gender, and subpopulation-specific differences. It offered insights for targeted interventions and healthcare strategies. The research underscored the necessity for enhanced data collection and expanded screening/treatment for vulnerable populations and regions.

Chlamydia trachomatis Inc Ct226 is vital for FLI1 and LRRF1 recruitment to the chlamydial inclusion.

The obligate intracellular pathogen, Chlamydia trachomatis, establishes an intracellular niche within a host membrane-derived vacuole called the chlamydial inclusion. From within this inclusion, C. trachomatis orchestrates numerous host-pathogen interactions, in part, by utilizing a family of type III secreted effectors, termed inclusion membrane proteins (Incs). Incs are embedded within the inclusion membrane, and some function to recruit host proteins to the inclusion. Two such recruited host proteins are leucine rich repeat Flightless-1 interacting protein 1 (LRRF1/LRRFIP1) and its binding partner Flightless 1 (FLI1/FLII). Previously, LRRF1 has been shown to interact with Inc protein Ct226/CTL0478. This is the first study to examine interactions of FLI1 with candidate Incs or with LRRF1 during infection. We hypothesized that FLI1 recruitment to the inclusion would be dependent on LRRF1 localization. We demonstrated that FLI1 co-immunoprecipitated with Ct226 but only in the presence of LRRF1. Furthermore, FLI1 localized to the inclusion when LRRF1 was depleted via small interfering RNA, suggesting that FLI1 may have an alternative recruitment mechanism. We further developed a series of CRISPRi knockdown and complementation strains in C. trachomatis serovar L2 targeting ct226 and co-transcribed candidate Incs, ct225 and ct224. Simultaneous knockdown of ct226, ct225, and ct224 prevented localization of both FLI1 and LRRF1 to the inclusion, and only complementation of ct226 restored their localization. Thus, we demonstrated Ct226 is critical for FLI1 and LRRF1 localization to the inclusion. Our results also indicate an LRRF1-independent localization mechanism for FLI1, which likely influence their mechanism(s) of action during chlamydial infection.IMPORTANCEChlamydia trachomatis is a leading cause of both bacterial sexually transmitted infections and preventable infectious blindness worldwide. As an obligate intracellular pathogen, C. trachomatis has evolved multiple ways of manipulating the host to establish a successful infection. As such, it is important to understand host-chlamydial protein-protein interactions as these reveal strategies that C. trachomatis uses to shape its intracellular environment. This study looks in detail at interactions of two host proteins, FLI1 and LRRF1, during chlamydial infection. Importantly, the series of CRISPR inference knockdown and complement strains developed in this study suggest these proteins have both independent and overlapping mechanisms for localization, which ultimately will dictate how these proteins function during chlamydial infection.

Intradermal administration of novel particulate Chlamydia trachomatis vaccine candidates drives protective immune responses.

Chlamydia trachomatis causes the most prevalent bacterial sexually transmitted infection worldwide. Its complex lifecycle and the lack of appropriate antigen delivery vehicles make it difficult to develop an effective C. trachomatis vaccine. Recently, bacterial protein bodies (PBs) have emerged as promising bioparticles for vaccine antigen delivery. By developing a PB-tag for translational fusion, we were able to induce the aggregation of recombinant antigens expressed in Escherichia coli into PBs. Here, we investigated the immunogenicity and efficacy of PBs containing either the C. trachomatis MOMP-derived CTH522-SP or HtrA antigen in mice. Intradermal administration of c-di-AMP-adjuvanted PB-CTH522-SP and PB-HtrA vaccines, produced in an LPS-detoxified E. coli strain, induced antigen-specific cellular immunity, as measured by significant release of IFN-γ and IL17a in draining cervical lymph node and splenic cell cultures. Moreover, significant induction of HtrA-specific IFN-γ expressing CD4+ and CD8+ T cells was detected in the spleens. While immunization with the two PB vaccines led to prominent levels of specific antibodies in both serum and vaginal compartments, only antiserum against PB-CTH522-SP exhibited C. trachomatis-specific neutralization activity. Importantly, intradermal immunization with PB-CTH522-SP significantly reduced bacterial counts following C. trachomatis genital challenge. These data highlight the potential of the PB-based platform for the development of C. trachomatis vaccines.

Extragenital self-collection testing for gonorrhea and chlamydia: A feasibility study for expanding STI screening in the Veterans Health Administration.

OBJECTIVES: Rectal and pharyngeal infections with gonorrhea and chlamydia are of concern because they are associated with higher risk of HIV acquisition. Extragenital screening in asymptomatic persons at high risk may have the potential to reduce the incidence of these sexually transmitted infections (STIs). Several testing platforms are available for the testing of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) using nucleic acid amplification tests (NAATs). Self-collected extragenital samples are currently not approved by the US Food and Drug Administration in any NAAT platform. This study compares the analytical performance of self-collected extragenital specimens to that of clinician-collected specimens. METHODS: We performed a multicenter/multiplatform validation study as a National Veterans Health Administration Pathology and Laboratory Medicine quality improvement project, with 9 different participating sites. Self-collected specimens were obtained at the same time as clinician-collected specimens. Clinician-collected specimens were used as the gold standard to evaluate the sensitivity and specificity of self-collection. RESULTS: A total of 2324 individual tests were analyzed (501 rectal and 661 oropharyngeal). The sensitivity was 94.44% for CT and 100% for NG for rectal specimens, whereas it was 100% for CT and 97.22% for NG for oral specimens. Specificity for oral specimens was 99.85% for CT and 99.36% for NG, whereas for rectal specimens, it was 99% for CT and NG. CONCLUSIONS: Self-collected specimens for extragenital CT/NG testing are highly sensitive and specific, with negative predictive values of 100%. Self-collection has the potential to overcome a major barrier for STI screening by providing an accessible, convenient, and patient-centered alternative.

A novel method for the preparation of reproducible, stable, and non-infectious quality control materials for Chlamydia trachomatis nucleic acid detection.

Chlamydia trachomatis (CT) is a significant sexually transmitted pathogen known to evoke severe complications, including infertility. Nucleic acid amplification tests (NAATs) are recommended by the World Health Organization to detect CT infection. Furthermore, the establishment of methods, performance validation, internal quality control, and external quality assessment for CT NAATs necessitate the utilization of quality control materials (QCs). QCs are specimens or solutions that are analyzed for quality control purposes in a test system. In this study, we established a novel cell line that stably integrates CT amplification target sequences for producing QCs for CT NAATs. Utilizing clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 technology, we integrated the CT plasmid-mediated sequence (comprising the full length of the cryptic plasmid and the major outer membrane protein gene, 9,136 bp) into the MUC4 gene of HEK293T cells. Positive clones were screened through flow cytometric sorting, single-cell culture, and PCR-based identification, followed by the establishment of stable cell lines. These cells were then processed using optimized cell preservation procedures to prepare QCs. The sequence insertion copy number was confirmed by real-time quantitative PCR. This novel CT QCs demonstrate excellent clinical applicability, non-infectiousness, quantifiability, and stability. With an integrated sequence exceeding 9 kb in length, it offers exceptional flexibility for adapting to new kit developments. Furthermore, maintaining a well-defined copy number and stable shelf life, the QCs closely aligns with the quality control requirements of CT NAATs. This study presents an innovative method for preparing QCs for CT nucleic acid detection, making a valuable contribution to improving the performance of CT NAATs.IMPORTANCEUntreated CT infections impose significant burdens on individuals and communities, underscoring the importance of early and accurate testing via CT NAATs for disease control. QCs are instrumental in identifying testing process issues. Hence, we developed a cell line integrating CT-amplified target sequences as readily accessible non-infectious QCs. These QCs boast several advantages: the integration of over 9 kb of CT sequence allows for broad applicability, allowing flexible adaptation to the development of new kits. Confirming the CT sequence copy number provides a reliable basis for QC concentration preparation and kit detection limit evaluation. Optimized preservation protocol enhances QC stability during storage, facilitating convenient shipment to clinical laboratories at ambient temperatures. In summary, our novel CT QCs offer a powerful tool for improving CT NAAT performance and present a fresh perspective on QC preparation for detecting nucleic acids from intracellular parasitic pathogens.

A case of Fitz-Hugh-Curtis syndrome diagnosed by noninvasive metagenomic next-generation sequencing.

OBJECTIVE: Fitz-Hugh-Curtis Syndrome (FHCS) is an inflammation of the liver capsule as a complication of pelvic inflammatory disease (PID) in sexually active women, mostly associated with Chlamydia trachomatis (C. trachomatis) and Neisseria gonorrhoeae. Classically presenting as sharp right upper quadrant pain, usually accompanied salpingitis and ascites. With nonspecific clinical presentation and poor specificity, definitive diagnosis needs tissue biopsy and culture by laparoscopy. CASE REPORT: We report the case of a 22-year-old female with a 2-month history of abdominal pain and distention. Symptomatic relief when supportive treatments were given, with the ultrasound and PET-CT suggested advanced bilateral ovarian cancer. After metagenomic next-generation sequencing (mNGS) detected C. trachomatis in ascitic fluid. Following anti-infective medication, clinical improvement was satisfactory and the patient was discharged. CONCLUSION: FHCS with distention was rare and challenging to diagnose. The mNGS would be a potent, non-invasive pathogen detection method with significant sensitivity and specificity.

Loss in Pluripotency Markers in Mesenchymal Stem Cells upon Infection with Chlamydia trachomatis.

The intracellular pathogen Chlamydia trachomatis can inflict substantial damage on the host. Notably, Chlamydia infection is acknowledged for its precise modulation of diverse host signaling pathways to ensure cell survival, a phenomenon intricately connected to genetic regulatory changes in host cells. To monitor shifts in gene regulation within Chlamydia-infected cells, we employed mesenchymal stem cells (MSCs) as a naïve, primary cell model. Utilizing biochemical methods and imaging, our study discloses that acute Chlamydia infection in human MSCs leads to the downregulation of transcription factors Oct4, Sox2, and Nanog, suggesting a loss of pluripotency markers. Conversely, pluripotency markers in MSCs were sustained through treatment with conditioned medium from infected MSCs. Additionally, there is an augmentation in alkaline phosphatase activity, along with elevated Sox9 and CD44 mRNA expression levels observed during acute infection. A comprehensive screening for specific cell markers using touchdown PCR indicates an upregulation of mRNA for the early chondrogenesis gene Sox9 and a decrease in mRNA for the MSC marker vimentin. Real-time PCR quantification further corroborates alterations in gene expression, encompassing increased Sox9 and CD44 mRNA levels, alongside heightened alkaline phosphatase activity. In summary, the infection of MSCs with C. trachomatis induces numerous genetic deregulations, implying a potential trend towards differentiation into chondrocytes. These findings collectively underscore a targeted impact of Chlamydia on the gene regulations of host cells, carrying significant implications for the final fate and differentiation of these cells.

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.

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.

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.

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.