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Mozambique is making progress towards elimination of trachoma as a public health problem, but in some districts trachomatous inflammation-follicular (TF) prevalence remains above the 5% elimination threshold despite years of various interventions, including antibiotic mass drug administration. To characterize transmission in four districts, we incorporated testing of ocular infection and serology into routine trachoma impact surveys (TIS) in August 2022. We examined residents aged ≥ 1 year for trachoma and collected information on household water, sanitation, and hygiene. Among children aged 1-9 years, we tested conjunctival swabs for Chlamydia trachomatis nucleic acid and dried blood spots for C. trachomatis antibodies. We modeled age-dependent seroprevalence to estimate seroconversion rate (SCR). We examined 4841 children aged 1-9 years. TF prevalence ranged between 1.1 and 6.0% with three districts below the 5% threshold. PCR-confirmed infection prevalence ranged between 1.1 and 4.8%, and Pgp3 seroprevalence ranged between 8.8 and 24.3%. Pgp3 SCR was 1.9 per 100 children per year in the district with the lowest TF prevalence. Two other districts with TF

Chlamydia trachomatis (Ct) is the most common cause of bacterial sexually transmitted infections (STIs) worldwide. Ct infections are often asymptomatic in women, leading to severe reproductive tract sequelae. Development of a vaccine against Chlamydia is crucial. The Chlamydia major outer membrane protein (MOMP) is a prime vaccine antigen candidate, and it can elicit both neutralizing antibodies and protective CD4+ T cell responses. We have previously designed chimeric antigens composed of immunogenic variable regions (VDs) and conserved regions (CDs) of MOMP from Chlamydia muridarum (Cm) expressed into a carrier protein (PorB), and we have shown that these were protective in a mouse model of Cm respiratory infection. Here, we generated corresponding constructs based on MOMP from Ct serovar F. Preliminary structure analysis of the three antigens, PorB/VD1-3, PorB/VD1-4 and PorB/VD1-2-4, showed that they retained structure features consistent with those of PorB. The antigens induced robust humoral and cellular responses in mice with different genetic backgrounds. The antibodies were cross-reactive against Ct, but only anti-PorB/VD1-4 and anti-PorB/VD1-2-4 IgG antibodies were neutralizing, likely due to the antigen specificity. The cellular responses included proliferation in vitro and production of IFN-γ by splenocytes following Ct re-stimulation. Our results support further investigation of the PorB/VD antigens as potential protective candidates for a Chlamydia subunit vaccine.

Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections in the USA and of preventable blindness worldwide. This obligate intracellular pathogen replicates within a membrane-bound inclusion, but how it acquires nutrients from the host while avoiding detection by the innate immune system is incompletely understood. C. trachomatis accomplishes this in part through the translocation of a unique set of effectors into the inclusion membrane, the inclusion membrane proteins (Incs). Incs are ideally positioned at the host-pathogen interface to reprogram host signaling by redirecting proteins or organelles to the inclusion. Using a combination of co-affinity purification, immunofluorescence confocal imaging, and proteomics, we characterize the interaction between an early-expressed Inc of unknown function, Tri1, and tumor necrosis factor receptor-associated factor 7 (TRAF7). TRAF7 is a multi-domain protein with a RING finger ubiquitin ligase domain and a C-terminal WD40 domain. TRAF7 regulates several innate immune signaling pathways associated with C. trachomatis infection and is mutated in a subset of tumors. We demonstrate that Tri1 and TRAF7 specifically interact during infection and that TRAF7 is recruited to the inclusion. We further show that the predicted coiled-coil domain of Tri1 is necessary to interact with the TRAF7 WD40 domain. Finally, we demonstrate that Tri1 displaces the native TRAF7 binding partners, mitogen-activated protein kinase kinase kinase 2 (MEKK2), and MEKK3. Together, our results suggest that by displacing TRAF7 native binding partners, Tri1 has the capacity to alter TRAF7 signaling during C. trachomatis infection.IMPORTANCEChlamydia trachomatis is the leading cause of bacterial sexually transmitted infections in the USA and preventable blindness worldwide. Although easily treated with antibiotics, the vast majority of infections are asymptomatic and therefore go untreated, leading to infertility and blindness. This obligate intracellular pathogen evades the immune response, which contributes to these outcomes. Here, we characterize the interaction between a C. trachomatis-secreted effector, Tri1, and a host protein involved in innate immune signaling, TRAF7. We identified host proteins that bind to TRAF7 and demonstrated that Tri1 can displace these proteins upon binding to TRAF7. Remarkably, the region of TRAF7 to which these host proteins bind is often mutated in a subset of human tumors. Our work suggests a mechanism by which Tri1 may alter TRAF7 signaling and has implications not only in the pathogenesis of C. trachomatis infections but also in understanding the role of TRAF7 in cancer.

BACKGROUND: Promotion of facial cleanliness is recommended for the elimination of blinding trachoma, largely because of observational studies that have found an association between various measures of facial uncleanliness and trachoma. However, when a field grader assesses both facial cleanliness and trachoma, associations may be biased. Assessment of photographs of the face and conjunctiva by masked graders may provide a less biased estimate of the relationship between facial cleanliness and trachoma. METHODS: Face photographs, conjunctival photographs, and conjunctival swabs were obtained on a random sample of 0-9-year-old children from each of 40 communities in Amhara region, Ethiopia. Face photographs were assessed for the presence of seven measures of an unclean face (i.e., wet nasal discharge, dry nasal discharge, wet ocular discharge, dry ocular discharge, food, dust/dirt, and flies) by three independent masked photo-graders. Conjunctival photographs were similarly graded in a masked fashion for signs of clinically active trachoma. Conjunctival swabs were processed for Chlamydia trachomatis DNA. RESULTS: Of 2073 children with complete data, 808 (39%) had evidence of clinically active trachoma, 150 (7%) had evidence of ocular chlamydia infection, and 2524 (91%) had at least one measure of an unclean face. Dry ocular discharge had the strongest association with clinically active trachoma (age- and sex-adjusted prevalence ratio [PR] 1.4, 95% CI 1.2-1.6) and ocular chlamydia infection (PR 1.9, 95%CI 1.3-2.9), although significant associations were observed between each of the measures of facial uncleanliness and trachoma. CONCLUSIONS: Masked assessment of face and conjunctival photographs confirmed prior observational studies that have noted associations between various measures of facial uncleanliness and trachoma. The causal relationship between facial uncleanliness and trachoma is unclear since many features used to measure facial cleanliness (e.g., ocular discharge, nasal discharge, and flies) could be consequences of antecedent ocular chlamydia infection. TRIAL REGISTRATION: NCT02754583, clinicaltrials.gov.

Millions of doses of azithromycin are distributed each year for trachoma, yet the treatment efficacy of a single dose of azithromycin for ocular Chlamydia infection has not been well characterized. In this study, four villages in Niger received a mass azithromycin distribution for trachoma. All 426 children aged 0-5 years residing in the study villages were offered conjunctival swabbing every 6 months to test for ocular Chlamydia trachomatis. Among the children infected with ocular Chlamydia before treatment, 6% (95% CI: 2-15%) tested positive for ocular Chlamydia infection 6 months later, and 15% (95% CI: 7-28%) tested positive 12 months later. The most important predictor of post-treatment ocular Chlamydia infection was pretreatment ocular Chlamydia infection (relative risk: 3.5, 95% CI: 1.3-9.4). Although the 6-monthly monitoring schedule was suboptimal for testing the treatment efficacy of an antibiotic, these findings are nonetheless consistent with high treatment efficacy of a single dose of azithromycin and suggest that additional interventions might be most effective if targeted to those children infected prior to treatment.

BACKGROUND: Neisseria gonorrheae and Chlamydia trachomatis are associated with mucosal inflammation and human immunodeficiency virus 1 (HIV-1) transmission. We assessed levels of inflammatory cytokines in men who have sex with men (MSM) with and without rectal gonorrhea and/or chlamydia in Lima, Peru. METHODS: We screened 605 MSM reporting condomless receptive anal intercourse for rectal N. gonorrheae/C. trachomatis using nucleic acid testing. We identified 101 cases of gonorrhea and/or chlamydia and randomly selected 50 N. gonorrheae/C. trachomatis positive cases and matched 52 negative controls. We measured levels of IL-1β, IL-6, IL-8, and TNF-α in rectal secretions. Tests for HIV-1, rectal N. gonorrheae/C. trachomatis, and mucosal cytokines were repeated after 3 and 6 months. Cytokine levels in cases and uninfected controls were compared using Wilcoxon rank-sum tests and linear regression. RESULTS: MSM with gonorrhea/chlamydia had elevated levels of all cytokines in rectal mucosa compared with matched controls (all P values .05). DISCUSSION: Rectal gonorrhea/chlamydia infection is associated with transient mucosal inflammation and cytokine recruitment. Our data provide proof of concept for rectal sexually transmitted infection screening as an HIV prevention strategy for MSM. Clinical Trials Registration. NCT03010020.

The obligate intracellular bacterium Chlamydia has a unique developmental cycle that alternates between two contrasting cell types. With a hardy envelope and highly condensed genome, the small elementary body (EB) maintains limited metabolic activities yet survives in extracellular environments and is infectious. After entering host cells, EBs differentiate into larger and proliferating reticulate bodies (RBs). Progeny EBs are derived from RBs in late developmental stages and eventually exit host cells. How expression of the chlamydial genome consisting of nearly 1,000 genes governs the chlamydial developmental cycle is unclear. A previous microarray study identified only 29 Chlamydia trachomatis immediate early genes, defined as genes with increased expression during the first hour postinoculation in cultured cells. In this study, we performed more sensitive RNA sequencing (RNA-Seq) analysis for C. trachomatis cultures with high multiplicities of infection. Remarkably, we observed well over 700 C. trachomatis genes that underwent 2- to 900-fold activation within 1 hour postinoculation. Quantitative reverse transcription real-time PCR analysis was further used to validate the activated expression of a large subset of the genes identified by RNA-Seq. Importantly, our results demonstrate that the immediate early transcriptome is over 20 times more extensive than previously realized. Gene ontology analysis indicates that the activated expression spans all functional categories. We conclude that over 70% of C. trachomatis genes are activated in EBs almost immediately upon entry into host cells, thus implicating their importance in initiating rapid differentiation into RBs and establishing an intracellular niche conducive with chlamydial development and growth.

ObjectivePregnant and postpartum women (PPW) in Southern Africa are at increased risk of acquiring HIV and curable sexually transmitted infections (STIs). Oral pre-exposure prophylaxis (PrEP) is safe and effective to use during pregnancy to reduce HIV acquisition and vertical transmission. Point-of-care (POC) STI testing can identify PPW at risk of HIV and facilitate risk-differentiated and person-centred counselling to improve PrEP initiation, persistence and adherence. We evaluated the impact of POC STI testing compared with STI syndromic management on PrEP outcomes among PPW in Cape Town, South Africa.MethodsThe STI and PrEP in Pregnancy Study enrolled PPW without HIV and ≤34 weeks pregnant at their regular antenatal care visit with follow-up after 1 month. PPW were randomised to receive POC STI testing or STI syndromic management. PPW randomised to POC STI testing self-collected vaginal swabs for Chlamydia trachomatis, Neisseria gonorhoeae and Trichomonas vaginalis (Cepheid GeneXpert) testing and were offered same-day treatment if diagnosed. We compared PrEP initiation at baseline, PrEP prescription refill at 1 month (persistence) and adherence through tenofovir-diphosphate detection in dried blood spots by randomisation arm. In a secondary analysis, we evaluated the association between an STI diagnosis (positive STI test or reporting STI symptoms) with PrEP outcomes.ResultsWe enrolled and randomised 268 pregnant women. Twenty-eight per cent of women were diagnosed with ≥1 STI. Overall, 65% of women initiated and 79% persisted on PrEP with no significant differences by randomisation arm. Secondary analysis demonstrated that an STI diagnosis (positive STI test or reporting STI symptoms) was associated with higher PrEP initiation (adjusted relative risk=1.28; 95% CI 1.08 to 1.52), controlling for arm, maternal and gestational age.ConclusionsPOC STI testing was not associated with PrEP initiation or persistence relative to syndromic management. However, improving STI diagnosis by supplementing syndromic management with POC STI testing could improve PrEP initiation among PPW.Trial registration numberNCT03902418; Clinical Trials.gov; 1 April 2019.

BACKGROUND: A rapid and affordable point-of-care test is a priority for Neisseria gonorrhoeae control. WHO and Foundation for Innovative New Diagnostics (FIND) have a target product profile for a non-molecular N gonorrhoeae rapid point-of-care test that requires a clinical sensitivity of greater than 80% and a specificity over 95% to be considered useful in syndromic management; test turnaround time should be 30 min or under, and the test should cost less than US$3. A novel lateral flow assay (LFA) was developed to achieve that profile. METHODS: In this cross-sectional study we evaluated the performance of the novel N gonorrhoeae lateral flow assay (NG-LFA) at the primary health-care level in South Africa. Male patients with urethral discharge syndrome and female patients with vaginal discharge syndrome were recruited from five primary health-care facilities in the Buffalo City Metropolitan Municipality health district of South Africa. First-void urine specimens and nurse-collected vaginal swabs were tested in-facility with the NG-LFA and Xpert CT/NG PCR assay. N gonorrhoeae multi-antigen sequence typing (NG-MAST) was performed on all LFA positive specimens. FINDINGS: Between March 7, and Sept 19, 2022, we enrolled 200 male patients with urethral discharge and 200 female patients with vaginal discharge. The median age of male patients was 24 years (IQR 21-31 years), and the median age of female patients was 25 years (IQR 21-32 years). In addition, 23 male patients and 12 female patients who presented at the facility with a partner notification slip were enrolled of whom one (4%) and five (42%) were symptomatic, respectively. NG-LFA and Xpert results were available for all participants. In urine specimens, NG-LFA sensitivity was 96·1% (Wilson 95% CI 91·2-98·3; 123 LFA-positive among 128 PCR-positive specimens) and 91·7% in vaginal swab specimens (78·2-97·1; 33 LFA-positive among 36 PCR-positive). The specificity was 97·2% in urine specimens (90·4-99·2; 70 LFA-negative among 72 PCR-negative) and 96·3% in vaginal specimens (92·2-98·3; 158 LFA-negative among 164 PCR-negative). In 156 LFA-positive specimens, NG-MAST showed 93 different sequence types. INTERPRETATION: The novel NG-LFA had excellent clinical sensitivity and specificity in symptomatic male and female patients. The test met the optimal requirement for sensitivity and the minimal requirement for specificity specified in the target product profile. NG-LFA could provide an important tool to optimise clinical management and reduce excess antibiotic use in settings without direct access to laboratory testing. FUNDING: Global Antimicrobial Resistance Innovation Fund (GAMRIF) via FIND and National Institutes of Health.

Hallmarks of the developmental cycle of the obligate intracellular pathogenic bacterium Chlamydia are the primary differentiation of the infectious elementary body (EB) into the proliferative reticulate body (RB) and the secondary differentiation of RBs back into EBs. The mechanisms regulating these transitions remain unclear. In this report, we developed an effective novel strategy termed dependence on plasmid-mediated expression (DOPE) that allows for the knockdown of essential genes in Chlamydia. We demonstrate that GrgA, a Chlamydia-specific transcription factor, is essential for the secondary differentiation and optimal growth of RBs. We also show that GrgA, a chromosome-encoded regulatory protein, controls the maintenance of the chlamydial virulence plasmid. Transcriptomic analysis further indicates that GrgA functions as a critical regulator of all three sigma factors that recognize different promoter sets at developmental stages. The DOPE strategy outlined here should provide a valuable tool for future studies examining chlamydial growth, development, and pathogenicity.

Chlamydia trachomatis (Ct) is the most common sexually transmitted bacterium globally. Endocervical and vaginal microbiome interactions are rarely examined within the context of Ct or among vulnerable populations. We evaluated 258 vaginal and 92 paired endocervical samples from Fijian women using metagenomic shotgun sequencing. Over 37% of the microbiomes could not be classified into sub-community state types (subCSTs). We, therefore, developed subCSTs IV-D0, IV-D1, IV-D2, and IV-E-dominated primarily by Gardnerella vaginalis-to improve classification. Among paired microbiomes, the endocervix had a significantly higher alpha diversity and, independently, higher diversity for high-risk human papilloma virus (HPV) genotypes compared to low-risk and no HPV. Ct-infected endocervical networks had smaller clusters without interactions with potentially beneficial Lactobacillus spp. Overall, these data suggest that G. vaginalis may generate polymicrobial biofilms that predispose to and/or promote Ct and possibly HPV persistence and pathogenicity. Our findings expand on the existing repertoire of endocervical and vaginal microbiomes and fill in knowledge gaps regarding Pacific Islanders.

[This corrects the article DOI: 10.3389/fmicb.2023.1154664.].

Background: Men who have sex with men (MSM) are disproportionately affected by sexually transmitted infections (STI) including Neisseria gonorrhoeae (Ng) and Chlamydia trachomatis (Ct). The lack of robust data on STIs among African MSM has limited the development of evidence-based screening strategies. This study aimed at documenting the pooled prevalence of Ng/Ct among MSM in sub-Saharan Africa (SSA). Methods: This systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) 2020 guidelines. Relevant articles from the following databases were searched: PubMed, Scopus, ISI Web of Science, and the Directory of Open Access Journals (DOAJ). Eligible studies reported on the prevalence of Ng/Ct among the MSM population in SSA. Publication bias was assessed using the Hoy tool, Doi plot, and LFK ratio. Due to heterogeneity among studies, subgroup analyses were performed using the MetaXL add-on tool for Microsoft Excel. Results: Of 525 articles screened, 20 were selected for inclusion. Six were cross-sectional, four had a prospective cohort study design, and one was an epidemiological study. The pooled prevalence of Ng/Ct in MSM was 27% (95% CI, 19–39%), with an I2 of 98% signifying heterogeneity among the studies. Subgroup analysis by country revealed South Africa had the highest prevalence (38%). Discussion: Interpretation The high prevalence of Ng/Ct infection among MSM in SSA is of concern. Limitations Due to limited data available on Ng/Ct prevalence, the true prevalence of SSA and its associated risk factors is uncertain. Conclusion: As the first study to systematically review the available literature on STI prevalence among the MSM population in SSA, it showed the burden of Ng/Ct is higher than in other regions, warranting the strengthening of health systems to improve education, testing, and treatment in MSM population. Systematic review registration: PROSPERO CRD42022327095. [ABSTRACT FROM AUTHOR]

Background: Chlamydia trachomatis is a common sexually transmitted disease that is associated with considerable morbidity and harmful sequelae, including pelvic inflammatory disease and infertility. Strategies for prevention and treatment of infertility in women with C. trachomatis infection require further investigation. There is evidence suggesting that vitamin D could be a potential treatment. This study aimed to investigate the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels, chlamydia seropositivity, and the risk of infertility in women. Methods: We conducted this cross-sectional study using 2013–2016 National Health and Nutrition Examination Survey data. Women aged 18–39 years with complete serum 25(OH)D and chlamydia Pgp3Ab multiplex bead/enzyme-linked immunosorbent assay data available were included. The correlation between 25(OH)D level, chlamydia seropositivity, and infertility was evaluated using the weighted chi-squared test and the t-test with multivariate logistic regression and moderation effect models. Results: Among the 1424 women who met our eligibility criteria, the weighted chlamydia seropositivity rate was 36.8%. The 25(OH)D level was significantly lower in the seropositive group compared with seronegative control. (P = 0.009). After adjusting for ethnicity, the effect of 25(OH)D was no longer significant (P = 0.693). Further analysis in the chlamydia-seropositive subset revealed that the vitamin D level was lower in the infertile group (P = 0.024). In an interaction model, 25(OH)D was found to antagonizes the positive relationship between chlamydia and infertility (OR = 0.985, 95% CI: 0.971–0.999, P = 0.040). Conclusion: The serum vitamin D level may be more related to the prognosis in terms of infertility than to the risk of chlamydia infection. This finding may reveal a possible treatment strategy for chlamydia infection. [ABSTRACT FROM AUTHOR]

In Baringo County, Kenya, trachoma remains endemic despite repeated mass drug administration (MDA) efforts, with coverage in one of the wards consistently falling short of world health organization (WHO) targets. The disease is endemic in 12 out of the 47 counties in Kenya. Baringo county is a pastoral conflict, hard to reach area where eight rounds of mass drug administration (MDA) for trachoma have been implemented. In Loyamorok ward, treatment coverage has been below 68% against the WHO recommended threshold of 80%. Community engagements that promote participatory approaches are key to MDA success. In this study, we describe community-based participatory approaches qualitatively developed and implemented during the intervention phase of a study that involved a pre-intervention, intervention and post intervention phases and aimed to address barriers of community participation and access to trachoma MDA. Interviews and focus group discussions were used to identify barriers to community participation in MDA, that included power and gender dynamics, rampant insecurity, community myths and misconceptions, migration in search of water and pastures, vastness and terrain and ineffective teams which resulted to unsupervised swallowing of drugs during MDA campaigns. Stakeholders in trachoma were identified through meetings with national, county and sub-county health management teams. The stakeholders, community members and the research team used the identified barriers to formulate MDA strategies including effective stakeholder engagement, enhanced social mobilization, community awareness creation on trachoma, effective planning and execution of MDA and implementation monitoring of the MDA campaign, all aimed at increasing MDA coverage. Overall MDA coverage in the area increased from 67.6% in 2021 to 87% in 2023 thus meeting the WHO threshold of 80%. The use of community-based, participatory approaches in the development and implementation of data driven strategies has the potential to positively influence MDA coverage for trachoma, and other neglected tropical diseases. Author summary: Trachoma is a disease of the eye and a leading infectious cause of blindness in sub-Saharan Africa. It is caused by a bacterium called Chlamydia trachomatis. It is transmitted by directly or indirectly transferring of eye and nose discharges from people who already have the disease mostly by flies. The disease in controlled by among other things provision of drugs to communities where the disease is endemic through mass drug administration (MDA). For the MDA to be effective, more than 80% of the community members should be reached. In areas where communities record very low access to MDA, there is need to identify barriers and develop strategies to mitigate the same. In this study we describe community-based participatory approaches employed to develop and test implementation strategies aimed at increasing access to trachoma MDA in Loyamorok ward of Baringo county. The results showed an increase in community participation in the subsequent MDA, which could be attributed to the implemented strategies. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis infections are the most common bacterial STIs globally and can lead to serious morbidity if untreated. Development of a killed, whole-cell vaccine has been stymied by coincident epitope destruction during inactivation. Here, we present a prototype Chlamydia vaccine composed of elementary bodies (EBs) from the related mouse pathogen, Chlamydia muridarum (Cm). EBs inactivated by gamma rays (Ir-Cm) in the presence of the antioxidant Mn2+-Decapeptide (DEHGTAVMLK) Phosphate (MDP) are protected from epitope damage but not DNA damage. Cm EBs gamma-inactivated with MDP retain their structure and provide significant protection in a murine genital tract infection model. Mice vaccinated with Ir-Cm (+MDP) exhibited elevated levels of Cm-specific IgG and IgA antibodies, reduced bacterial burdens, accelerated clearance, and distinctive cytokine responses compared to unvaccinated controls and animals vaccinated with EBs irradiated without MDP. Preserving EB epitopes with MDP during gamma inactivation offers the potential for a polyvalent, whole-cell vaccine against C. trachomatis. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Methods Results Conclusions Implications for the Profession Impact Reporting Method Patient Contribution To increase Chlamydia trachomatis screening in adolescents 15–19 years of age from 7.8% to 15% following a 6‐week implementation of universal chlamydia screening at three paediatric primary care (PPC) sites.Pre‐implementation (1 January 2022–19 October 2022) and post‐implementation (20 October 2022–1 June 2023) screening rates were tracked through run charts and compared via Chi‐square testing. Universal opt‐out chlamydia screening with universal urine collection for 15‐ to 19‐year‐old was implemented at well visits, along with patient and staff education, and sexually transmitted infection treatment protocols.Chlamydia trachomatis screening increased from 7.8% to 34.1% with implementation of universal opt‐out chlamydia screening. Proportions of patients screened increased significantly among White individuals, males and privately insured individuals.A universal C. trachomatis screening project can be feasibly implemented in pediatric primary care and successfully increase adolescent chlamydia screening rates.Implementing a universal opt‐out C. trachomatis screening project is feasible in PPC and can help achieve the public health goal of chlamydia identification and treatment.These findings will be impactful for both paediatric primary care and adolescent patients. The universal, opt‐out C. trachomatis screening approach facilitated screening increases, improved equity in screening and led to increased case detection and treatment which has vast significance for those patients.This manuscript is submitted using the SQUIRE 2.0 guidelines for quality improvement reporting.Patient contribution included de‐identified data collection of chlamydia screening rates of eligible adolescents 15–19 years old who attended routine well visits at the three PPC locations. The data were reviewed on a dashboard, then stratified by race, ethnicity, payor and sex assigned at birth. [ABSTRACT FROM AUTHOR]

Purpose: The urinary tract is colonized by microbial communities that impact urinary health. Previous studies have suggested that the bacterial composition of the male urinary microbiota is related to STIs. This study assessed the bacterial composition of the urinary microbiome in South African MSM with and without C. trachomatis. Methods: This study used urine samples from MSM attending care at the King Edward VIII hospital and the Aurum Institute in Durban, South Africa. A total of 200 samples were tested for C. trachomatis infection using the Applied Biosystems™ TaqMan® Assays. Urinary microbiomes of 23 samples were characterized using 16 S rRNA (V3 and V4) gene sequencing on the Illumina MiSeq platform. Results: Bacterial taxonomic analysis showed a high abundance of Streptococcus, Corynebacterium, and Staphylococcus in all the sequenced samples. Moreover, Prevotella and Lactobacillus were detected in urine samples of MSM. Alpha diversity metrics showed a slight increase in microbial diversity in C. trachomatis positive samples; however, this was not significant (ANOVA, P > 0.05). Principal coordinates analysis (PCoA) showed that the microbiome of C. trachomatis infected MSM was not clearly different from those uninfected. Distinct bacterial communities were not detected between positive and negative samples (PERMANOVA F1,22= 1.0284, R2 = 0.047%, P = 0.385). Conclusion: Most microbiome studies on MSM to date have focused on the gut microenvironment. Few studies, however, have provided data regarding the normal composition of the male urethral microbiomes or if these microbiomes are associated with male STIs. This study adds to the growing body of knowledge highlighting the urinary microbiome in MSM. [ABSTRACT FROM AUTHOR]

Background: The objective of this study lies in identifying the dominant genotype of C. trachomatis isolated in Republic of Korea (ROK) between 2017 and 2018. Methods: A total of 504 clinical cervicovaginal swabs from patients were collected and inoculated on McCoy cell monolayers to isolate Chlamydial agents. C. trachomatis isolates were analyzed by sequencing of its ompA gene. Results: A total of 54 C. trachomatis isolates were obtained. The constructed phylogenetic tree revealed the genotypes of isolates are D/Ep6 (48, 88.89%), D/Ep6-like (5, 9.26%), and Ja (1, 1.85%). The C. trachomatis D/Ep6-like have one single nucleotide polymorphism (SNP) compared to C. trachomatis D/Ep6, leading to E870K amino acid change. Conclusions: Phylogenetic analysis demonstrated globally rare C. trachomatis D/Ep6 was dominant in the ROK from 2017 to 2018. Findings in this study act as a keystone, bridging past and present molecular epidemiology of C. trachomatis in context of ROK. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of genital infections (GIs), including sexual transmitted STIs: Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, and opportunistic pathogens that generally do not cause STIs, non-classic STI: Ureaplasma urealyticum, Ureaplasma parvum and Mycoplasma hominis, in women with high-risk oncogenic human papillomavirus (hr-HPV) infection and their association with cervical lesions. Methods: A cross-sectional study was carried out including 231 hr-HPV positive women. Of these, 46 has histologically confirmed cervical intraepithelial neoplasia 3 (CIN3) or more (including CIN3 and cervical cancer lesions-CIN3+). GIs were detected by multiplex real time PCR. Odds ratios (OR) were estimated to explore possible associations between GIs and the presence or absence of CIN3+ lesions. Additionally, we examined associations between sociodemographic, sexual, and clinical characteristics and the presence of GIs. Results: In total, there were 174/231 cases of GIs corresponding to an overall prevalence of 75.3% (95%CI: 69.4–80.4), being non-classic STIs the most common (72.3%) compared to STIs (12.6%). The most prevalent non-classic STI and STI were U. parvum (49.8%) and C. trachomatis (7.4%), respectively. The odds of presenting GIs were 3 times higher in women under 46 years compared to older counterparts (OR: 3.32, 95%CI: 1.74–6.16), and in women with a normal Pap smear with inflammation compared to those without inflammation (OR: 3.31, 95%CI: 1.15–9.77). GIs were equally present in women with and without CIN3+ lesions. Conclusion: We observed an association of GIs with inflammation in the Pap smear, but no association with CIN3+, as some of them are very common and likely part of the normal vaginal flora, suggesting that such infections do not appear to be cofactors in cervical carcinogenesis, although larger prospective studies are needed. [ABSTRACT FROM AUTHOR]

The chlamydial deubiquitinase Cdu1 of the obligate intracellular human pathogenic bacterium Chlamydia trachomatis plays important roles in the maintenance of chlamydial infection. Despite the structural similarities shared with its homologue Cdu2, both DUBs display remarkable differences in their enzymatic activity towards poly-UB chain substrates. Whereas Cdu1 is highly active towards K48- and K63- poly-UB chains, Cdu2 activity is restricted mostly to mono-UB substrates. Here, we shed light on the molecular mechanisms of the differential activity and the substrate specificity of Cdu1 to better understand the cellular processes it is involved in, including infection-related events. We found that the strikingly elevated activity of Cdu1 relative to its paralogue Cdu2 can be attributed to an N-terminally extended α-helix, which has not been observed in Cdu2. Moreover, by employing isothermal titration calorimetry and nuclear magnetic resonance spectroscopy, we demonstrate the differential recognition of K48- and K63-linked poly-UB substrates by Cdu1. Whereas K63-linked poly-UB substrates appear to be recognized by Cdu1 with only two independent ubiquitin interaction sites, up to four different binding interfaces are present for K48-linked ubiquitin chains. Combined, our data suggest that Cdu1 possesses a poly-UB chain directed activity that may enable its function as a multipurpose DUB with a broad substrate specificity. Author summary: As a post-translational modification ubiquitination plays key roles in virtually all cellular processes and is also involved in the host immune response upon infection with intracellular pathogens. Chlamydia trachomatis secretes the two deubiquitinase effector proteins Cdu1 and Cdu2, which can subvert the host cell ubiquitin signaling and play crucial roles during infection. Both deubiquitinases have been shown to display drastic differences in their activity towards poly-ubiquitin chains. We here identified the molecular mechanisms by which the enhanced activity of Cdu1 towards these substrates is mediated. Moreover, we discovered marked differences in the recognition of differently linked poly-ubiquitin chains by Cdu1 and mapped binding sites for the individual ubiquitin moieties. Our study thus provides new insights into the enzymatic mechanisms of chlamydial deubiquitinases, which can be crucial to understand their distinct roles during infection. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Not having an established relationship is associated with an elevated risk of Chlamydia trachomatis (CT) infection, but this might reflect selection into and out of unions. Although union formation and union separation are common events in reproductive age, little is known about changes in CT risk before and after these transitions. Methods We linked Finnish Population Register data to the National Register of Infectious Diseases and used fixed-effects linear probability models that account for all time-invariant confounders to examine changes in women's 6-month CT risk 3 years before and 3 years after entry into first cohabitation (n  = 293 554), non-marital separation (n  = 201 647) or marital separation (n  = 92 232) during 2005–14. Results From 3 years to 1 year before first union formation, the 6-month risk of CT increased slightly, peaking at 1.27% immediately prior to union formation (95% confidence interval 1.22–1.31). It declined sharply following union formation, being only 0.40% (0.34–0.46) 6–12 months after union formation with little changes thereafter. Among women separating from non-marital unions, the risk increased from 0.50% (0.42–0.57) to 1.45% (1.40–1.49) around the time of separation and decreased following separation. The pattern of findings was relatively similar for marital separation, although the observed risks and changes were smaller in magnitude. Conclusions Our results based on longitudinal data and individual fixed-effects models indicate that the period immediately after separation may be causally associated with an elevated risk of CT. This suggests that recently separated women should be identified as a high-risk group for CT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Epidemiological investigations have revealed an important association between infection, inflammation and prostate cancer. Certain bacterial species, such as Klebsiella spp, Escherichia coli, Pseudomonas spp, Proteus mirabilis, Chlamydia trachomatis have been linked to prostate cancer. This study aimed to examine the microbiota; specifically bacterial species that have been linked to prostate infections in the urine of individuals diagnosed with prostate cancer. Results: Sixty-six prostate cancer patients and forty controls provided midstream urine samples. The urine samples were grown on suitable medium, and bacterial isolates were detected by standard microbiological methods. Additionally, the antibiotic sensitivity pattern of the bacterial isolates was analysed. A total of number of 72 bacterial isolates were obtained from the urine of study participants. The results showed the presence of Escherichia coli (50.0%), Pseudomonas aeruginosa (18.1%), Klebsiella spp (15.3%), Staphylococcus aureus (8.3%), Enterobacter spp (4.2%), and Proteus mirabilis (2.8%) in the urine. The most common bacterial species isolated from prostate cancer patients was Escherichia coli, which was susceptible to levofloxacin (100%), tobramycin (91.7%), and amikacin (62.5%). Conclusions: This study's findings established the presence of bacteria previously linked to prostatitis. This report indicates a high prevalence of pro-inflammatory bacteria and uropathogens in the urinary tract of men diagnosed with prostate cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Chlamydia trachomatis testing and treatment strategies have not decreased infection rates, justifying need for a chlamydia vaccine. A murine study showed that a vaccine consisting of major outer membrane protein (MOMP) and polymorphic membrane proteins (Pmps) E, F, G, and H elicited protective immunity; studies on human cellular immune responses to Pmps are sparse. Methods Interferon gamma (IFN-γ) responses to these 5 proteins were measured by ELISPOT in peripheral blood mononuclear cells from women returning for treatment of a positive chlamydia test. Responses were compared in those with spontaneous chlamydia clearance versus persisting infection at baseline and no reinfection versus reinfection at a 3-month follow-up visit. Results IFN-γ response to 1 or more proteins was detected in 39% at baseline and 51.5% at follow-up, most often to PmpE and MOMP. IFN-γ responses to MOMP were detected less often at follow-up versus baseline in women with reinfection, but were maintained in those without reinfection. Women with spontaneous clearance had a higher magnitude of IFN-γ response to PmpE and MOMP. Conclusions IFN-γ responses to these 5 C. trachomatis vaccine candidate proteins were heterogenous and primarily directed against MOMP and PmpE. Spontaneous chlamydia clearance and absence of reinfection may be clinical correlates of protection. [ABSTRACT FROM AUTHOR]

Seminal plasma (SP) is the main vector of C. trachomatis (CT) during heterosexual transmission from male to female. It has immunomodulatory properties and impacts the susceptibility to HIV-1 infection, but its role has not been explored during CT infection. In the female reproductive tract (FRT), CT infection induces cytokine production and neutrophil recruitment. The role of neutrophils during CT infection is partially described, they could be at the origin of the pathology observed during CT infection. During this study, we developed an experimental in vitro model to characterize the impact of CT infection and SP on endocervical epithelial cell immune response in the FRT. We also studied the impact of the epithelial cell response on neutrophil phenotype and functions. We showed that the production by epithelial cells of pro-inflammatory cytokines increased during CT infection. Moreover, the pool of SP as well as individuals SP inhibited CT infection in a dose-dependent manner. The pool of SP inhibited cytokine production in a dose-dependent manner. The pool of SP altered gene expression profiles of infected cells. The culture supernatants of cells infected or not with CT, in presence or not of the pool of SP, had an impact on neutrophil phenotype and functions: they affected markers of neutrophil maturation, activation and adhesion capacity, as well as the survival, ROS production and phagocytosis ability. This study proposes a novel approach to study the impact of the environment on the phenotype and functions of neutrophils in the FRT. It highlights the impact of the factors of the FRT environment, in particular SP and CT infection, on the mucosal inflammation and the need to take into account the SP component while studying sexually transmitted infections during heterosexual transmission from male to female. [ABSTRACT FROM AUTHOR]

Background: Inadequate surgical interventions can lead to serious complications such as tubo-ovarian abscesses in the upper female genital system, often resulting from untreated pelvic inflammatory disease. Pelvic inflammatory disease, caused by infections like Chlamydia trachomatis and Neisseria gonorrhoeae, leads to scarring and adhesions in the reproductive organs, with common risk factors including intrauterine device use and multiple sexual partners. Pelvic inflammatory disease primarily affects sexually active young women and can manifest with varied symptoms, potentially leading to complications like ectopic pregnancy, infertility, and chronic pelvic pain if untreated. Case presentation: This case report presents a unique scenario involving a 17-year-old sexually inactive female who experienced concurrent tubo-ovarian abscess, acute cystitis, and pancolitis following laparoscopic ovarian cystectomy. Pelvic inflammatory disease and its complications are well-documented, but the simultaneous occurrence of acute cystitis and pancolitis in this context is unprecedented in the medical literature. The patient's presentation, clinical course, and management are detailed, highlighting the importance of considering diverse and severe complications in individuals with a history of gynecological surgeries. Conclusions: Our case report highlights the need for healthcare professionals to remain vigilant for atypical presentations of gynecological complications and emphasizes the value of interdisciplinary collaboration for optimal patient care. We encourage further research and awareness to enhance understanding and recognition of complex clinical scenarios associated with gynecological procedures. [ABSTRACT FROM AUTHOR]

Background Increasing rates of macrolide and fluroquinolone resistance in Mycoplasma genitalium (MG) are being reported worldwide with resultant treatment failure. Aim We aimed to determine the level of antibiotic resistance of MG in men who have sex with men (MSM) attending a sexually transmitted infections (STIs) clinic in New Delhi, India. Methods Real-time polymerase chain reaction (PCR) assays targeting MgPa and pdhD genes were performed to detect MG rectal, urogenital or oropharyngeal infections in 180 MSM between January 2022 and June 2023. Macrolide resistance–associated mutations (MRM) and quinolone resistance–associated mutations (QRM) were detected by specific amplification of domain V of 23SrRNA gene and appropriate regions of p arC and gyrA genes respectively followed by sequencing. PCR-based screening for Chlamydia trachomatis (CT) infection was also performed. Results A total of 13 (7.2%) MSM were positive for MG infection. The most common site of infection was anorectum (8/13; 61.5%) followed by the urethra (5/13; 38.5%). None of the patients had infection at both the sites, and no oropharyngeal MG infection was detected. CT infection was detected in 37 (20.6%) MSM. Of the 13 MG-infected MSM, 6 (46.2%) were co-infected with CT. MRM and QRM were found in five (46.2%) and two (15.4%) strains, respectively. Both Quinolone resistance mutation (QRM)-harbouring strains also harboured MRM. All the five MG isolates carried the MRM A2071G. Both the QRM isolates co-harboured the parC and gyrA single-nucleotide polymorphisms. There was no correlation between the presence of antibiotic resistance and co-infection with CT (P = 0.52). Limitation Because all patients in the study were MSM, the high rate of resistance to macrolides and fluoroquinolones could not be extrapolated for non-MSM patients. Conclusion This is a report of an initial survey of antibiotic resistance to MG in a country where its diagnosis and treatment are not routinely available. We found a high prevalence of MG-carrying MRM, QRM and dual-class resistance in MSM in the absence of antibiotic exposure. This study mandates the need for both screening and detection of antimicrobial resistance against MG. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Per- and polyfluoroalkyl substances (PFAS) alter immune function increasing infectious diseases risk. We examined the relationship between PFAS and chlamydia. Methods: A total of 3965 nonpregnant adults ages 18-39 years from the National Nutrition Examination Survey 2003-2016 cycles were included. Poisson regression with robust error variance estimated the prevalence ratio and 95% confidence intervals for the association between PFAS and chlamydia. Ag computationmodelwas used to examine PFASmixtures and chlamydia. Results: In adjusted age and sex-stratifiedmodels, an increase in PFASmixtures by one quintilewas associated with chlamydia in oldermales and younger females. Associationswere not observed before stratification. Conclusions: PFAS exposure associated with higher chlamydia prevalence, but only in stratified models suggesting biological differences by gender and age. However, small sample sizes could have affected the precision of our models. [ABSTRACT FROM AUTHOR]

Background: Chlamydia trachomatis (CT) is a sexually transmitted infection that requires early detection to prevent complications. This study aimed to evaluate the prevalence of CT among asymptomatic women in Spain and investigate the relationship between CT and risk factors associated with sexual practices, as well as factors such as stress and depression. Results: We found that 3.8% of asymptomatic women tested positive for CT. Our findings suggested that having more than five sexual partners increases the risk of sexually transmitted infections (STIs) by 3.87 times when compared with having fewer partners (p = 0.005, OR: 3.87, 95% CI 1.24–11.65). Additionally, 4.5% of participants admitted to using drugs. We found that there was a slightly higher proportion of anxiety and depression among women who tested positive for CT. Conclusions: We aimed to establish a basis for the implementation of screening in asymptomatic women. Early identification and preventive measures are crucial in minimizing the long-term complications and transmission of the disease. Sexual behavior must be recognized as a risk factor, and women's psychological well-being should be given top priority as a vital aspect of their sexual health. [ABSTRACT FROM AUTHOR]

Trachoma is one of the oldest known causes of blindness in humans and it is caused by the intracellular Gram-negative bacterium Chlamydia trachomatis serovars A, B, Ba and C. Its transmission has historically been related to poorness, overcrowded housing and scarce hygiene. We have traced the history of trachoma in Italy in the 19th and 20th centuries, among people living in Italy, those who immigrated to America and the population in the colonies, with a focus on Libya (1912–1943). Trachoma knowledge and perception in Italy and in its colonies was ambiguous during the 19th and 20th centuries. Trachoma was responsible for a great morbidity on both sides of the Mediterranean, in Italy as well as in Libya. Trachoma is still one of the leading infectious causes of preventable blindness worldwide and it was widespread in Italy and the Italian colonies in the first half of the last century. [ABSTRACT FROM AUTHOR]

BackgroundMeeting sex partners online is associated with increased risk of acquiring sexually transmitted infections. We examined whether different venues where men who have sex with men (MSM) meet sex partners was associated with prevalent Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection, and whether prevalence increased during (vs before) the COVID-19 pandemic.MethodsWe conducted a cross-sectional analysis of data from San Diego's 'Good To Go' sexual health clinic from two enrolment periods: (1) March-September 2019 (pre-COVID-19) and (2) March-September 2021 (during COVID-19). Participants completed self-administered intake assessments. This analysis included males aged ≥18 years self-reporting sex with males within 3 months before enrolment. Participants were categorised as (1) meeting new sex partners in-person only (eg, bars, clubs), (2) meeting new sex partners online (eg, applications, websites) or (3) having sex only with existing partners. We used multivariable logistic regression, adjusting for year, age, race, ethnicity, number of sex partners, pre-exposure prophylaxis use and drug use to examine whether venue or enrolment period were associated with CT/NG infection (either vs none).ResultsAmong 2546 participants, mean age was 35.5 (range: 18-79) years, 27.9% were non-white and 37.0% were Hispanic. Overall, CT/NG prevalence was 14.8% and was higher during COVID-19 vs pre-COVID-19 (17.0% vs 13.3%). Participants met sex partners online (56.9%), in-person (16.9%) or only had existing partners (26.2%) in the past 3 months. Compared with having only existing sex partners, meeting partners online was associated with higher CT/NG prevalence (adjusted OR (aOR) 2.32; 95% CI 1.51 to 3.65), while meeting partners in-person was not associated with CT/NG prevalence (aOR 1.59; 95% CI 0.87 to 2.89). Enrolment during COVID-19 was associated with higher CT/NG prevalence compared with pre-COVID-19 (aOR 1.42; 95% CI 1.13 to 1.79).ConclusionsCT/NG prevalence appeared to increase among MSM during COVID-19, and meeting sex partners online was associated with higher prevalence.

Abstract Background Men who have sex with men (MSM) are disproportionately affected by sexually transmitted infections (STI) including Neisseria gonorrhoeae (Ng) and Chlamydia trachomatis (Ct). The lack of robust data on STIs among African MSM has limited the development of evidence-based screening strategies. This study aimed at documenting the pooled prevalence of Ng/Ct among MSM in sub-Saharan Africa (SSA). Methods This systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) 2020 guidelines. Relevant articles from the following databases were searched: PubMed, Scopus, ISI Web of Science, and the Directory of Open Access Journals (DOAJ). Eligible studies reported on the prevalence of Ng/Ct among the MSM population in SSA. Publication bias was assessed using the Hoy tool, Doi plot, and LFK ratio. Due to heterogeneity among studies, subgroup analyses were performed using the MetaXL add-on tool for Microsoft Excel. Results Of 525 articles screened, 20 were selected for inclusion. Six were cross-sectional, four had a prospective cohort study design, and one was an epidemiological study. The pooled prevalence of Ng/Ct in MSM was 27% (95% CI, 19–39%), with an I 2 of 98% signifying heterogeneity among the studies. Subgroup analysis by country revealed South Africa had the highest prevalence (38%). Discussion Interpretation The high prevalence of Ng/Ct infection among MSM in SSA is of concern. Limitations Due to limited data available on Ng/Ct prevalence, the true prevalence of SSA and its associated risk factors is uncertain. Conclusion As the first study to systematically review the available literature on STI prevalence among the MSM population in SSA, it showed the burden of Ng/Ct is higher than in other regions, warranting the strengthening of health systems to improve education, testing, and treatment in MSM population. Systematic review registration PROSPERO CRD42022327095.

Abstract Background Chlamydia trachomatis is a common sexually transmitted disease that is associated with considerable morbidity and harmful sequelae, including pelvic inflammatory disease and infertility. Strategies for prevention and treatment of infertility in women with C. trachomatis infection require further investigation. There is evidence suggesting that vitamin D could be a potential treatment. This study aimed to investigate the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels, chlamydia seropositivity, and the risk of infertility in women. Methods We conducted this cross-sectional study using 2013–2016 National Health and Nutrition Examination Survey data. Women aged 18–39 years with complete serum 25(OH)D and chlamydia Pgp3Ab multiplex bead/enzyme-linked immunosorbent assay data available were included. The correlation between 25(OH)D level, chlamydia seropositivity, and infertility was evaluated using the weighted chi-squared test and the t-test with multivariate logistic regression and moderation effect models. Results Among the 1424 women who met our eligibility criteria, the weighted chlamydia seropositivity rate was 36.8%. The 25(OH)D level was significantly lower in the seropositive group compared with seronegative control. (P = 0.009). After adjusting for ethnicity, the effect of 25(OH)D was no longer significant (P = 0.693). Further analysis in the chlamydia-seropositive subset revealed that the vitamin D level was lower in the infertile group (P = 0.024). In an interaction model, 25(OH)D was found to antagonizes the positive relationship between chlamydia and infertility (OR = 0.985, 95% CI: 0.971–0.999, P = 0.040). Conclusion The serum vitamin D level may be more related to the prognosis in terms of infertility than to the risk of chlamydia infection. This finding may reveal a possible treatment strategy for chlamydia infection.

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.

Abstract 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.

ImportanceIn this study, we developed a correlative approach that combined DNA immunoprecipitation-seq and RNA-seq analyses to define the regulon of the Chlamydia trachomatis transcription factor Euo. We confirmed the proposed role of Euo as a transcriptional repressor of late chlamydial genes but also showed that Euo activates transcription of a subset of midcycle genes and autoregulates its own expression via negative feedback. This study validates and expands the role of Euo as an important developmental regulator in C. trachomatis. In addition, this genome-wide correlative approach can be applied to study transcription factors in other pathogenic bacteria.

Na Li,1,&ast; Yue-xiang Ren,2,&ast; Heng-ming Ye,1,3 Ying Lin,4 Qiang Liu,5 Jiao Wang,1 Ze-fang Ren,1 Lin Xu1,6,7 1The School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Public Health Service Center of Bao’an District, Shenzhen, People’s Republic of China; 4The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 5Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 6School of Public Health, the University of Hong Kong, Hong Kong; 7Institute of Applied Health Research, University of Birmingham, Birmingham, UK&ast;These authors contributed equally to this workCorrespondence: Ze-fang Ren; Lin Xu, School of Public Health, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou, 510080, People’s Republic of China, Tel +0086-20-87332577 ; Tel +0086-20- 87335523, Fax +011-86-20-87332577, Email renzef@mail.sysu.edu.cn; xulin27@mail.sysu.edu.cnPurpose: 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-1β), 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.Keywords: Chlamydia trachomatis, breast cancer, prognosis, pro-inflammatory cytokines

Abstract Background Chlamydia genital infections continue to be a serious health concern globally. Previous studies have reported that Chlamydia trachomatis infection alters the vaginal microbiota of infected women. This study investigated differences in the vaginal microbiome of South African pregnant women living with HIV with and without C. trachomatis infection. Methods This was a cross-sectional study among 385 pregnant women, recruited from the King Edward VIII Hospital in Durban, South Africa. C. trachomatis was detected using the Applied Biosystems™ TaqMan® Assays. A total of 40 samples, 20 C. trachomatis positive and 20 C. trachomatis negative, were selected for sequencing. The sequencing of the vaginal microbiome was performed using the PacBio platform. Statistical analysis was performed on IBM SPSS version 26. Results The prevalence of C. trachomatis infection was 12.2% (47/385). The genus Gardnerella (32.14% vs. 24.02%) and species in the genus Gardnerella (31.97% vs. 24.03%) were more abundant in the C. trachomatis-infected group compared to the uninfected group. Lactobacillus iners were also more abundant in the C. trachomatis-infected women (28.30%) compared to the uninfected women. However, these observed patterns did not reach statistical significance. Discriminant analysis showed that the class Alpha-Proteobacteria; order Bacillales; family Enterococcaceae; the genera Enhydrobacter, Enterococcus, and Parabacteroides; Enterococcus spp.; and Pseudomonas stutzeri significantly contributed to a model separating C. trachomatis-infected women from the uninfected group (p

Introduction: Of the many sexually transmitted pathogens, Chlamydia trachomatis is increasingly being associated with long-term sequelae such as infertility, apart from causing genital tract infections. Many inflammatory responses directed against chlamydial infection can cause tubal damage resulting in infertility. For example, chlamydial heat shock protein 60 (cHSP60) and cHSP10 along with humoral immune response. The aim of our study is to detect the presence of immunoglobulin G (IgG) antibodies against Major Outer Membrane Protein (MOMP), cHSP60, and cHSP10 among female infertility. Methods: A total number of 230 female infertility patients attending the Outpatient Department of Reproductive Medicine, SRIHER, were included in the study. Detailed history documented in the proforma. Serological detection of C. trachomatis IgG antibody against MOMP, cHSP60, and cHSP10 antibody was done by enzyme-linked immunosorbent assay (ELISA). Results: C. trachomatis IgG antibody against MOMP was detected in 15 (6.5%) of 230 females. High seropositivity to cHSP60 antibodies was detected among females of tubal factor infertility (TFI). Our study showed that cHSP60 antibodies (3.4%) were more common than cHSP10 (2.6%). Conclusion: Our study suggest cHSP60 or cHSP10 antibody detection by ELISA along with TFI is helpful for diagnosis and early institution of therapy. The accuracy of TFI prediction could be increased by the detection of anti-MOMP and cHSP60 over cHSP10 among secondary infertility than primary. The most probable reason for high seropositivity among secondary infertility patients may be due to repeated infection and chronicity because of longer active sexual life.

Abstract Introduction Chlamydia trachomatis infection can cause a significant disease burden in high-risk populations. This study aimed to assess the overall prevalence of C. trachomatis infection, and determine the long-term trends and geographic distribution of this infection among female sex workers (FSWs) and men who have sex with men (MSM) in China. Methods The PubMed, Web of Science, CNKI, Wanfang Data and VIP databases were searched from 1 January 1990 through 30 April 2023. Publications in which C. trachomatis infection was detected using nucleic acid amplification tests (NAATs) were included. The Q test and I 2 statistics were used to assess the heterogeneity between studies. A random-effect model was used to estimate the pooled prevalence of C. trachomatis infection. Subgroup, meta-regression, and sensitivity analyses were performed to explore the sources of heterogeneity. Publication bias was evaluated using Egger’s test. Trend analysis of the prevalence was performed using the Jonckheere-Terpstra trend test method. Results Sixty-one studies were eligible for inclusion (including 38 for FSWs and 23 for MSM). The pooled prevalence of C. trachomatis infection was 19.5% (95% CI: 16.4, 23.0) among FSWs and 12.7% (95% CI: 9.2, 17.7) in the rectum, 6.4% (95% CI: 5.3, 7.8) in the urethra and 1.3% (95% CI: 0.8, 2.1) in the oropharynx from MSM in China. The subgroup analyses showed that the sample size, study period, study region, specimen collection type, molecular diagnosis method, and recruitment site could explain some heterogeneity among studies of FSWs, and the publication language, study period, study region, molecular diagnosis method, and specimen collection anatomical site could explain some heterogeneity among studies of MSM. From 1998 to 2004, 2005 to 2009, 2010 to 2015, and 2016 to 2021, the pooled prevalence of C. trachomatis infection among FSWs were 30.3%, 19.9%, 21.4%, and 11.3%, respectively. For MSM, the pooled prevalence from 2003 to 2009, 2010 to 2015, and 2016 to 2022 were 7.8%, 4.7%, and 6.5%, respectively. However, no overall decline in the prevalence of C. trachomatis infection was observed among FSWs (z = -1.51, P = 0.13) or MSM (z = -0.71, P = 0.48) in China. Conclusions The prevalence of C. trachomatis infection was high in these two high-risk populations in China. The findings of this study provide evidence for the formulation of effective surveillance and screening strategies for the prevention and control of C. trachomatis infection among these two specific populations.

Chlamydiae are bacteria that are intriguing and important at the same time. The genus Chlamydia encompasses many species of obligate intracellular organisms: they can multiply only inside the cells of their host organism. Many, perhaps most animals have their own specifically adapted chlamydial species. In humans, the clinically most relevant species is Chlamydia trachomatis, which has particular importance as an agent of sexually transmitted disease. Pigs are the natural host of Chlamydia suis but may also carry Chlamydia abortus and Chlamydia pecorum. C. abortus and possibly C. suis have anthropozoonotic potential, which makes them interesting to human medicine, but all three species bring a substantial burden of disease to pigs. The recent availability of genomic sequence comparisons suggests adaptation of chlamydial species to their respective hosts. In cell biological terms, many aspects of all the species seem similar but non-identical: the bacteria mostly replicate within epithelial cells; they are taken up by the host cell in an endosome that they customize to generate a cytosolic vacuole; they have to evade cellular defences and have to organize nutrient transport to the vacuole; finally, they have to organize their release to be able to infect the next cell or the next host. What appears to be very difficult and challenging to achieve, is in fact a greatly successful style of parasitism. I will here attempt to cover some of the aspects of the infection biology of Chlamydia, from cell biology to immune defence, epidemiology and possibilities of prevention. I will discuss the pig as a host species and the species known to infect pigs but will in particular draw on the more detailed knowledge that we have on species that infect especially humans. [ABSTRACT FROM AUTHOR]

Several reports suggest that intestinal tissue may be a natural niche for Chlamydia trachomatis infection and a reservoir for persistent infections in the human body. Due to the human specificity of the pathogen and the lack of suitable host models, there is limited knowledge on this topic. In our study, we modelled the course of the chlamydial infection in human primary gastrointestinal (GI) epithelial cells originating from patient-derived organoids. We show that GI cells are resistant to apical infection and C. trachomatis needs access to the basolateral membrane to establish an infection. Transmission electron microscopy analysis reveals the presence of both normal as well as aberrant chlamydial developmental forms in the infected cells, suggesting a possible cell-type specific nature of the infection. Furthermore, we show that the plasmid-encoded Pgp3 is an important virulence factor for the infection of human GI cells. This is the first report of C. trachomatis infection in human primary intestinal epithelial cells supporting a possible niche for chlamydial infection in the human intestinal tissue. Author summary: Chlamydial infection has a high global prevalence and is a major health concern. Untreated infections may cause complications and lead to serious health problems, especially in women. Although the infection is usually localized to the genital tract, experiments performed in a mouse infection model as well as the accumulating clinical data suggest that the human gastrointestinal (GI) tract might represent a hidden infection niche and a source of reinfections. In our study, we used the advantages of the organoid technology to model the chlamydial infection in patient-derived primary GI epithelial cells. We were able to show that these cells are resistant to the infection, however, Chlamydia could utilize a basolateral entry route for efficient infection. Chlamydia form either normal or persistent-like developmental forms in these GI epithelial cells. We also showed the importance of the plasmid-mediated virulence in the infection of human GI cells. The results obtained in the GI infection model replicated phenotypes predicted and expected for Chlamydia human intestinal infection, and therefore support a role of the human GI tract as a potential niche for chlamydial infection. [ABSTRACT FROM AUTHOR]

Monitoring trachoma transmission with antibody data requires characterization of decay in IgG to Chlamydia trachomatis antigens. In a 3-year longitudinal cohort in a high-transmission setting, we estimated a median IgG half-life of 3 years and a seroreversion rate of 2.5 per 100 person-years (95% confidence interval, 1.6–3.5). Clinical Trials Registration NCT02754583. [ABSTRACT FROM AUTHOR]