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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.

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.].

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]

Objective: To evaluate the impact of screening and treating asymptomatic pregnant women for Chlamydia (C.) trachomatis and Neisseria (N.) gonorrhoeae infections on the frequency of preterm birth or low birthweight infants in Botswana. Design: Non‐randomised, cluster‐controlled trial. Setting: Four antenatal care clinics in Gaborone, Botswana. Population: Pregnant women aged ≥15 years, attending a first antenatal care visit, ≤27 weeks of gestation and without urogenital symptoms were eligible. Methods: Participants in the intervention clinics received screening (GeneXpert®, Cepheid) during pregnancy and at the postnatal visit. Participants in the standard‐of‐care clinics received screening at the postnatal visit only. We used multivariable logistic regression and post‐estimation predictive margins analysis. Post‐hoc analysis was conducted among sub‐samples stratified by parity. Main outcome measures: Preterm birth (<37 weeks of gestation) and low birthweight (<2500 g). Results: After controlling for parity, hypertension, antenatal care visits and clinic site, the predicted prevalence of preterm birth or low birthweight was lower in the intervention arm (11%) compared with the standard‐of‐care arm (16%) (adjusted odds ratio [aOR] 0.59; 95% confidence interval [CI] 0.28–1.24). In post‐hoc analysis, the intervention was more effective than the standard‐of‐care (aOR 0.20; 95% CI 0.07–0.64) among nulliparous participants. Conclusion: A C. trachomatis and N. gonorrhoeae infection screening and treatment intervention among asymptomatic pregnant women may have reduced preterm birth or low birthweight outcomes, but results were not statistically significant. Post‐hoc analysis found that the intervention reduced adverse outcomes among nulliparous participants. [ABSTRACT FROM AUTHOR]

There is no vaccine against the major global pathogen Chlamydia trachomatis ; its different serovars cause trachoma in the eye or chlamydia in the genital tract. We did a clinical trial administering CTH522, a recombinant version of the C trachomatis major outer membrane molecule, in different dose concentrations with and without adjuvant, to establish its safety and immunogenicity when administered intramuscularly, intradermally, and topically into the eye, in prime-boost regimens. CHLM-02 was a phase 1, double-blind, randomised, placebo-controlled trial at the National Institute for Health Research Imperial Clinical Research Facility, London, UK. Participants were healthy men and non-pregnant women aged 18–45 years, without pre-existing C trachomatis genital infection. Participants were assigned into six groups by the electronic database in a pre-prepared randomisation list (A–F). Participants were randomly assigned (1:1:1:1:1) to each of the groups A–E (12 participants each) and 6 were randomly assigned to group F. Investigators were masked to treatment allocation. Groups A–E received investigational medicinal product and group F received placebo only. Two liposomal adjuvants were compared, CAF01 and CAF09b. The groups were intramuscular 85 μg CTH522-CAF01, or placebo on day 0 and two boosters or placebo at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (A); intramuscular 85 μg CTH522-CAF01, two boosters at day 28 and 112 with additional topical ocular administration of CTH522, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (B); intramuscular 85 μg CTH522-CAF01, two boosters at day 28 and 112 with additional intradermal administration of CTH522, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (C); intramuscular 15 μg CTH522-CAF01, two boosters at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (D); intramuscular 85 μg CTH522-CAF09b, two boosters at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (E); intramuscular placebo (F). The primary outcome was safety; the secondary outcome (humoral immunogenicity) was the percentage of trial participants achieving anti-CTH522 IgG seroconversion, defined as four-fold and ten-fold increase over baseline concentrations. Analyses were done as intention to treat and as per protocol. The trial is registered with ClinicalTrials.gov , NCT03926728 , and is complete. Between Feb 17, 2020 and Feb 22, 2022, of 154 participants screened, 65 were randomly assigned, and 60 completed the trial (34 [52%] of 65 women, 46 [71%] of 65 White, mean age 26·8 years). No serious adverse events occurred but one participant in group A2 discontinued dosing after having self-limiting adverse events after both placebo and investigational medicinal product doses. Study procedures were otherwise well tolerated; the majority of adverse events were mild to moderate, with only seven (1%) of 865 reported as grade 3 (severe). There was 100% four-fold seroconversion rate by day 42 in the active groups (A–E) and no seroconversion in the placebo group. Serum IgG anti-CTH522 titres were higher after 85 μg CTH522-CAF01 than 15 μg, although not significantly (intention-to-treat median IgG titre ratio groups A–C:D=5·6; p=0·062), with no difference after three injections of 85 μg CTH522-CAF01 compared with CTH522-CAF09b (group E). Intradermal CTH522 (group C) induced high titres of serum IgG anti-CTH522 neutralising antibodies against serovars B (trachoma) and D (urogenital). Topical ocular CTH522 (group B) at day 28 and 112 induced higher total ocular IgA compared with baseline (p<0·001). Participants in all active vaccine groups, particularly groups B and E, developed cell mediated immune responses against CTH522. CTH522, adjuvanted with CAF01 or CAF09b, is safe and immunogenic, with 85 μg CTH522-CAF01 inducing robust serum IgG binding titres. Intradermal vaccination conferred systemic IgG neutralisation breadth, and topical ocular administration increased ocular IgA formation. These findings indicate CTH522 vaccine regimens against ocular trachoma and urogenital chlamydia for testing in phase 2, clinical trials. The EU Horizon Program TRACVAC. [ABSTRACT FROM AUTHOR]

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

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

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

Chlamydial infections are one of the most common sexually transmitted bacterial infections worldwide, which is related to serious consequences for the mental, sexual, and reproductive health of women and men. The infection is commonly asymptomatic; consequently, screening programs for infection control have been introduced in some countries. The detection methods of Chlamydia trachomatis infections have evolved since the establishment of the first gold-standard detection method in the 1970s, the culture assay. Over the decades, many efforts were made to find methods with a higher sensitivity, until the 1990s, when, as a result of advances in molecular biology, nucleic acid amplification tests came into use with more sensitivity, and, currently, there are several available with which to detect infection. Therefore, herein, we will review the main methods used for CT detection and the differences between them, in terms of targets, infections that can be detected, sensitivity, and specificity. We will focus on some of the FDA-approved CT detection tests and highlight the major advantages and superiority of using molecular biology techniques. In addition, we will examine the larger challenges and limitations of the methods currently in use and discuss how they might be surpassed. Moreover, in this review, we will describe the next step to carry out after testing positive for CT infection. [ABSTRACT FROM AUTHOR]

The association between human papillomavirus (HPV) and other sexually transmitted infections (STIs) in anal lesions still remains unclear. Aim of the study was to evaluate the prevalence of simultaneous infection of HPV and Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis in individuals screened for HPV anal infection. A total of 507 anal samples were tested for both anal HPV and STIs: 16% resulted positive for one or more non‐HPV STIs. Specifically, C. trachomatis, M. genitalium, and N. gonorrhoeae were detected in 8%, 5%, and 4% of cases, respectively. Two groups were considered, including a positive STI group and a negative STI group. The prevalence of HPV was similar in patients in both groups: high risk (HR)‐HPV and low risk (LR)‐HPV were 67% and 53% versus 62% (p = 0.361) and 54% (p = 0.864) of patients, respectively. However, HPV 16, 18, 35, 51, 59, and 69 were significantly more frequent in patients tested positive for other STIs versus HPV infection alone (p < 0.05). No significant differences between the two groups were observed in vaccination coverage, 28% versus 32% (p = 0.463), and HIV status, 86% versus 84% (p = 0.658). The study shows that the overall HPV status is not directly correlated to other STIs in the investigated population, except for certain HPV types, including HR‐HPV 16, reinforcing the urge for a greater vaccination coverage. [ABSTRACT FROM AUTHOR]

Background: Chlamydia trachomatis infection is a significant cause of follicular conjunctivitis worldwide, particularly in regions where trachoma is endemic. Aim of the work: This study investigates the prevalence, clinical significance, and molecular diagnosis of Chlamydia trachomatis in patients with follicular conjunctivitis, shedding light on important demographic and clinical associations identifying knowledge gaps and proposing avenues for future research and public health interventions. Methodology: Forty patients presenting with follicular conjunctivitis at Ain Shams University hospitals, Egypt. Conjunctival scraping samples were collected, and DNA extraction was performed for amplification targeting the 16S rRNA gene of Chlamydia trachomatis by conventional PCR. Results: The key finding is that 75% of conjunctival samples tested positive for the presence of the C. trachomatis 16S rRNA gene. Significant associations were found between PCR positivity and demographic characteristics such as gender (P < 0.005) with an equal distribution of 20 males and 20 females and age (P = 0.021) ranged from 18 to 64 years, with a median age of 26 years. Clinical symptoms were also strongly associated with positive PCR results (P < 0.005) including redness, foreign body sensation, irritation, itching, tearing, burning sensation, and blurred vision, along with unilateral and/or bilateral site of infection. Conclusion: These results underscore the clinical significance of C. trachomatis in follicular conjunctivitis and stress the necessity for targeted interventions and public health initiatives. Future efforts should focus on the development of a rapid, simple, and cost-effective diagnostic test to curtail the spread of C. trachomatis infection and targeting its proper management. [ABSTRACT FROM AUTHOR]

Inspired by the broad spectrum of antimicrobial activity exhibited by Magainins and SMAP‐28, and based on their chemical structures, several linear peptides were designed and synthesized with the aim of achieving peptides possessing promising anti‐chlamydial activity with lower cytotoxicity towards human normal cell lines. We found these peptides to be cytotoxic against human normal cell lines, except for one designated as DJ‐7, which was utilized in subsequent experiments, while the others were excluded. Peptide DJ‐7 was readily synthesized using standard Fmoc‐SPPS, and its anti‐chlamydial activity was investigated against HeLa cells (ATCC CCL‐2) infected with Chlamydia trachomatis L2 (ATCC VR‐902B) at MOI 1 for 2 hours, followed by treatment with increasing concentrations of peptide DJ‐7 (15–60 μg/mL). Microscopic examination revealed a significant reduction in the total number of bacterial inclusions in cells by around 50 % and 80 % after treatment with 15 μg/mL (5.5 μM) and 30 μg/mL (11 μM) of peptide DJ‐7, respectively, compared to control untreated infected cells. The impact of peptide DJ‐7 treatment on the development of infectious C. trachomatis serovar L2 progeny was investigated, demonstrating a significant decrease in infectious chlamydia after treatment with peptide DJ‐7. This suggests that chlamydia failed to complete its typical developmental cycle, indicating that peptide DJ‐7 exhibits anti‐chlamydial properties, by disrupting the normal bacterial development process. Our results indicate that peptide DJ‐7 is a promising lead peptide for further development as a potential anti‐chlamydial agent. [ABSTRACT FROM AUTHOR]

Epstein–Barr virus (EBV) is a major cause of infectious mononucleosis (IM), characterized by fever, fatigue, sore throat, lymphadenopathy, atypical lymphocytosis, and elevated liver enzymes. However, ascites is a rare complication associated with IM. We present a rare case of IM with ascites and peritonitis in a patient who underwent a peritoneal biopsy. A 20‐year‐old woman presented with fatigue and abdominal distension. Laboratory examination revealed atypical lymphocytes in peripheral blood (54%) and elevated liver enzymes. EBV serological tests revealed a recent primary infection (EBV VCA IgM 1:160). Computed tomography revealed moderate ascites and peritonitis. Adenocarcinoma was suspected based on the ascites' cytology. Considering possible complications of IM and adenocarcinoma, a laparoscopic biopsy was performed. Histological findings of biopsy specimens from the peritoneum, omentum, and fimbria of the fallopian tube demonstrated severe inflammatory cell infiltration and focal aggregation of large EBV‐encoded RNA‐1 (EBER1)‐positive B cells, mimicking EBV‐positive polymorphous B‐cell lymphoproliferative disorder. Furthermore, intracytoplasmic inclusion bodies of Chlamydia trachomatis were observed by immunohistochemistry. Real‐time polymerase chain reaction detected C. trachomatis in cervical secretions. Two months after laparoscopy, ascites decreased, and the diagnosis was IM‐associated peritonitis with C. trachomatis infection. IM should be considered as a differential diagnosis in young patients with ascites. [ABSTRACT FROM AUTHOR]

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 < 0.05). Conclusion: The organisms and taxa that significantly contributed to separating the vaginal microbiota of C. trachomatis-infected women from the uninfected women in this study cohort have not been previously observed in association with C. trachomatis infection or the vaginal microbiota. Future studies in larger cohorts that will investigate the role of these microorganisms in C. trachomatis infection and the vaginal microbiota are required. [ABSTRACT FROM AUTHOR]

Chlamydiae are a large group of obligate endosymbionts of eukaryotes that includes the Chlamydiaceae family, comprising several animal pathogens. Among Chlamydiaceae, Chlamydia trachomatis causes widespread ocular and urogenital infections in humans. Like many bacterial pathogens, all Chlamydiae manipulate host cells by injecting them with type III secretion effector proteins. We previously characterized the C. trachomatis effector CteG, which localizes at the host cell Golgi and plasma membrane during distinct phases of the chlamydial infectious cycle. Here, we show that CteG is a Chlamydiaceae-specific effector with over 60 homologs phylogenetically categorized into two distinct clades (CteG I and CteG II) and exhibiting several inparalogs and outparalogs. Notably, cteG I homologs are syntenic to C. trachomatis cteG, whereas cteG II homologs are syntenic among themselves but not with C. trachomatis cteG. This indicates a complex evolution of cteG homologs, which is unique among C. trachomatis effectors, marked by numerous events of gene duplication and loss. Despite relatively modest sequence conservation, nearly all tested CteG I and CteG II proteins were identified as type III secretion substrates using Yersinia as a heterologous bacterial host. Moreover, most of the type III secreted CteG I and CteG II homologs were delivered by C. trachomatis into host cells, where they localized at the Golgi region and cell periphery. Overall, this provided insights into the evolution of bacterial effectors and revealed a Chlamydiaceae family of type III secreted proteins that underwent substantial divergence during evolution while conserving the capacity to localize at specific host cell compartments. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis (CT) is a sexually transmitted infection that can lead to adverse reproductive health outcomes. CT prevalence estimates are primarily derived from screening using nucleic acid amplification tests (NAATs). However, screening guidelines in the United States only include particular subpopulations, and NAATs only detect current infections. In contrast, seroassays identify past CT infections, which is important for understanding the public health impacts of CT, including pelvic inflammatory disease and tubal factor infertility. Older seroassays have been plagued by low sensitivity and specificity and have not been validated using a consistent reference measure, making it challenging to compare studies, define the epidemiology of CT, and determine the effectiveness of control programs. Newer seroassays have better performance characteristics. This narrative review summarizes the "state of the science" for CT seroassays that have been applied in epidemiologic studies and provides practical considerations for interpreting the literature and employing seroassays in future research. [ABSTRACT FROM AUTHOR]

Introduction: Chlamydia trachomatis, a gram-negative obligate intracellular bacterium, commonly causes sexually transmitted infections (STIs). Little is known about C. trachomatis transmission within the host, which is important for understanding disease epidemiology and progression. Methods: We used RNA-bait enrichment and whole-genome sequencing to compare rectal, vaginal and endocervical samples collected at the same time from 26 study participants who attended Fijian Ministry of Health and Medical Services clinics and tested positive for C. trachomatis at each anatomic site. Results: The 78 C. trachomatis genomes from participants resolved into two major clades of the C. trachomatis phylogeny (the "prevalent urogenital and anorectal" clade and "non-prevalent urogenital and anorectal" clade). For 21 participants, genome sequences were almost identical in each anatomic site. For the other five participants, two distinct C. trachomatis strains were present in different sites; in two cases, the vaginal sample was a mixture of strains. Discussion: The absence of large numbers of fixed SNPs between C. trachomatis genomes within many of the participants could indicate recent acquisition of infection prior to the clinic visit without sufficient time to accumulate significant genetic variation in different body sites. This model suggests that many C. trachomatis infections may be resolved relatively quickly in the Fijian population, possibly reflecting common prescription or over-the-counter antibiotics usage. [ABSTRACT FROM AUTHOR]

Musca sorbens (Diptera: Muscidae) flies are thought to be vectors of the blinding eye disease trachoma, carrying the bacterium Chlamydia trachomatis (Ct) between the eyes of individuals. While their role as vectors has been convincingly demonstrated via randomised controlled trials in The Gambia, studies of fly-borne trachoma transmission remain scant and as such our understanding of their ability to transmit Ct remains poor. We examined fly-eye contact and caught eye-seeking flies from 494 individuals (79% aged ≤9 years) in Oromia, Ethiopia. Ct-carrying flies (harbouring Ct DNA) were found to cluster spatially in and nearby to households in which at least one resident had Ct infection. Fly-eye contact was positively associated with the presence of trachoma (disease), lower human body weight and increased human body temperature. Studies of laboratory-reared M. sorbens indicated that Ct is found both externally and internally following feeds to Ct culture, with scanning electron microscopy revealing how Ct bodies can cling to fly hairs (setae). Testing for Ct on field-caught M. sorbens found fly 'bodies' (thorax, wings and abdomen) to consistently test positive for Ct while legs and heads were infrequently Ct-positive. These studies strongly support the role of M. sorbens as vectors of trachoma and highlight the need for improved understanding of fly-borne trachoma transmission dynamics and vector competence. Author summary: Trachoma is a blinding eye disease caused by an infection of the eye by the bacterium Chlamydia trachomatis (Ct). Trachoma is responsible for vision impairment or blindness in 1.8 million people and is the leading infectious cause of blindness worldwide. The presence of flies around the eyes of young children is a common feature of life in trachoma endemic communities worldwide. This fly is most often Musca sorbens, an understudied species thought to transmit Ct. In order to understand more about Musca sorbens flies and their relationship with Ct, the researchers studied 247 households in the Oromia region of Ethiopia, where there is known to be a lot of trachoma. The authors found evidence of Ct on flies and that flies in households containing children with Ct infection were much more likely themselves to be carrying Ct, adding to evidence that M. sorbens flies contribute to transmission of the bacterium. They also found that children who weigh less and currently have trachoma were more likely to have flies land on their face. Should further studies clearly elucidate a role for M. sorbens as vectors of trachoma, controlling fly populations or preventing fly-eye contact may become an important aspect of trachoma disease control. [ABSTRACT FROM AUTHOR]

Background: Among the most commonly known causes of hematospermia are infections in the genitourinary tract, but no study exists that has comprehensively investigated hematospermia in patients with acute epididymitis. Objectives: To assess the impact of hematospermia in patients with acute epididymitis and its association with clinical, microbiological, and semen parameters. Materials and methods: Since May 2007, a total of 324 sexually active patients with acute epididymitis were recruited in a prospective cohort study. Patients received a comprehensive medical and sexual history, and clinical, sonographic, laboratory, and microbiological diagnostics. Antibiotic therapy was given according to European Association of Urology guidelines. Semen analysis was offered 14 days after the first presentation and initiation of therapy. Since 2013, a separate control group of 56 patients presenting with isolated hematospermia (= no other urogenital symptoms) was prospectively recruited, and differences between the groups were statistically evaluated. Results: Of 324 patients with acute epididymitis, 50 patients (15%) had self‐reported hematospermia. This occurred with a median of 24 h before the onset of scrotal symptoms and was associated with significantly elevated prostate‐specific antigen levels compared to 274 patients without hematospermia (3.1 vs. 1.8 ng/ml, p < 0.01). The two most common etiological pathogens were Escherichia coli and Chlamydia trachomatis, and the bacterial spectrum was comparable in both epididymitis subgroups (p = 0.859). Semen analysis at 14 days still showed hematospermia in 24% of patients associated with massive leukocytospermia. Compared to the hematospermia control group, the two epididymitis subgroups showed significantly increased inflammation markers (pH, leukocytes, and elastase), reduced sperm concentration, and reduced levels of alpha‐glucosidase and zinc (always p < 0.01). Discussion and conclusion: In sexually active patients who develop acute epididymitis, self‐reported hematospermia is evident in 15% of patients as early as one day before the onset of scrotal symptoms. Conversely, none of the 56 patients presenting with isolated hematospermia developed epididymitis within the next 4 weeks. [ABSTRACT FROM AUTHOR]

Objective: Tubal ectopic pregnancy (EP) is a leading cause of maternal morbidity and mortality. Studies have suggested that infection‐induced inflammatory responses are major risk factors for EP. The aim of the present study was to find an association between MMP2 and CD63 gene variants and risk of EP during Chlamydia trachomatis infection in an Indian population. Methods: Fallopian tube samples of 120 EP and 120 tubal ligation women were collected. C. trachomatis was detected by PCR. The genotyping of MMP2 (rs17859882 G/T, rs7201A/C) and CD63(rs2231464 C/T, rs376086542 A/G) gene variants was done by qualitative real‐time PCR using allelic discrimination method (VIC‐ and FAM‐labeled). Results: The frequency of GG or GT genotype of MMP2 G/T polymorphism (rs17859882) was 66.6% in infected EP and 36.7% in uninfected EP and 22% in tubal ligation controls (P < 0.0001), while the frequency of AC or CC genotype of MMP2 A/C polymorphism (rs7201) was 66.6% in infected EP and 20.6% in uninfected EP and 13.5% in tubal ligation controls (P < 0.0001). The frequency of CT or TT genotype of CD63 C/T polymorphism (rs2231464) was 74% in infected EP and 21.8% in uninfected EP and 11.8% tubal ligation controls (P < 0.0001), while the frequency of AG or GG genotype of CD63 A/G polymorphism (rs376086542) was 48.1% in infected EP and 41.3% in uninfected EP and 18.6% tubal ligation controls (P < 0.0001). Conclusions: The present study revealed a strong association between the presence of gene variants MMP2 (rs17859882 G/T, rs7201A/C) and CD63 (rs2231464 C/T, rs376086542 A/G) and risk of tubal EP during C. trachomatis infection. Synopsis: MMP2 and CD63 genetic variants are significantly linked with increased susceptibility of tubal ectopic pregnancy during Chlamydia trachomatis infection. [ABSTRACT FROM AUTHOR]

Background: Sexually transmitted infections (STIs) are a public health problem. The aim of the present study was to assess the prevalence and risk factors associated with at least one STI (Chlamydia trachomatis [CT], Neisseria gonorrhoeae [NG], Trichomonas vaginalis [TV], and Mycoplasma genitalium [MG]) in Brazil. Methods: A cross‐sectional study was conducted using secondary data from the pilot implementation of the National Service for molecular diagnosis of CT, NG, TV, and MG in pregnancy. We obtained Ministry of Health surveillance data from the implementation project. Data encompassing pregnant women aged 15–49 years from public antenatal clinics in Brazil in 2022 were included. Results: A total of 2728 data of pregnant women were analyzed. The prevalence of at least one infection was 21.0% (573), with the highest prevalence in the Southeast region (23.3%) and the lowest in the Center‐West region (15.4%). The prevalence of CT was 9.9% (270), NG 0.6% (16), TV 6.7% (184), and MG 7.8% (212). Factors associated with any infection were from 15 to 24 years (AOR = 1.93; 95% CI: 1.58–2.35); reported family income up to US$400 (AOR = 1.79; 95% CI: 1.03–3.34); declared not living maritally with their partners (AOR = 1.90, 95% CI: 1.52–2.37) and had more than one sexual partner in their lifetime (AOR = 2.09, 95% CI: 1.55–2.86). Conclusion: This study showed a high prevalence of at least one STI among pregnant women in Brazil, particularly among younger women. It also provides up‐to‐date national data on CT, NG, TV, and MG infections in this population. These findings underscore the importance of enhancing access to STI screening for young pregnant women within the Brazilian public health system. Synopsis: This study showed a high prevalence of bacterial STI among pregnant women in Brazil, particularly among younger women with low income and multiple partners. [ABSTRACT FROM AUTHOR]

Pre-exposure prophylaxis (PrEP) use may be associated with risk compensation. We enrolled and provided PreP to sexual and gender minorities (SGM) in Abuja, Nigeria between April 2018 and May 2019. Behavioral information and samples for urogenital and anorectal Chlamydia trachomatis and Neisseria gonorrhoeae sexually transmitted infections (STIs) were collected at baseline. Blood samples for PrEP assay and self-reported adherence were collected at three-monthly follow-up visits. STIs were detected using Aptima Combo2 assay. We estimated the odds ratios (ORs) of PCR-diagnosed bacterial STIs and self-reported behavioral outcomes (condomless anal intercourse [CAI] and concurrent sexual relationships) with conditional logistic regression. Of 400 SGM who initiated PrEP, 206 were eligible for analysis, and had a median age of 24 years (IQR 22–27). In multivariable analysis, participants in the PrEP period had decreased odds of CAI (adjusted OR: 0.49, 95% CI 0.28, 0.84). PrEP use was not associated with risk compensation. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis (CT) is the leading cause of bacterial sexually transmitted diseases worldwide, which can cause diseases such as pelvic inflammatory disease, and cervical and fallopian tube inflammation, and poses a threat to human health. Rosmarinic acid (RosA) is an active ingredient of natural products with anti-inflammatory and immunomodulatory effects. This study aimed to investigate the role of RosA in inhibiting autophagy-regulated immune cells-CD8+ T cells via the Ras/Raf/MEK/ERK signaling pathway in a CT-infected mouse model. Mice were inoculated with CT infection solution vaginally, and the mechanistic basis of RosA treatment was established using H&E staining, flow cytometry, immunofluorescence, transmission electron microscopy, and western blot. The key factors involved in RosA treatment were further validated using the MEK inhibitor cobimetinib. Experimental results showed that both RosA and the reference drug azithromycin could attenuate the pathological damage to the endometrium caused by CT infection; flow cytometry showed that peripheral blood CD8+ T cells increased after CT infection and decreased after treatment with RosA and the positive drug azithromycin (positive control); immunofluorescence showed that endometrial CD8 and LC3 increased after CT infection and decreased after RosA and positive drug treatment; the results of transmission electron microscopy showed that RosA and the positive drug azithromycin inhibited the accumulation of autophagosomes; western bolt experiments confirmed the activation of autophagy proteins LC3Ⅱ/Ⅰ, ATG5, Beclin-1, and p62 after CT infection, as well as the inhibition of Ras/Raf/MEK/ERK signaling. RosA and azithromycin inhibition of autophagy proteins activates Ras/Raf/MEK/ERK signaling. In addition, the MEK inhibitor cobimetinib attenuated RosA's protective effect on endometrium by further activating CD8+ T cells on a CT-induced basis, while transmission electron microscopy, immunofluorescence, and western blots showed that cobimetinib blocked ERK signals activation and further induced phagocytosis on a CT-induced basis. These data indicated that RosA can activate the Ras/Raf/MEK/ERK signaling pathway to inhibit autophagy, and RosA could also regulate the activation of immune cells-CD8+T cells to protect the reproductive tract of CT-infected mice. • RosA has a therapeutic effect on CT-induced reproductive tract infection in mice. • RosA can activate the Ras/Raf/MEK/ERK signaling pathway to inhibit autophagy, and can also regulate the activation of immune cells-CD8+T cells to protect the reproductive tract of CT-infected mice. • Natural compound RosA could inhibit inflammation caused by reproductive tract infection. [ABSTRACT FROM AUTHOR]

Background Photography could be used to train individuals to diagnose trachomatous inflammation—follicular (TF) as trachoma prevalence decreases and to ensure accurate field TF grading in trachoma prevalence surveys. We compared photograph and field TF grading and determined the acceptability and feasibility of eyelid photography to community members and trachoma survey trainers. Methods A total of 100 children ages 1–9 y were examined for TF in two Maasai villages in Tanzania. Two images of the right everted superior tarsal conjunctiva of each child were taken with a smartphone and a digital single-lens reflex (DSLR) camera. Two graders independently graded all photos. Focus group discussions (FGDs) were conducted with community members and Tropical Data trainers. Results Of 391 photos, one-fifth were discarded as ungradable. Compared with field grading, photo grading consistently underdiagnosed TF. Compared with field grading, DSLR photo grading resulted in a higher prevalence and sensitivity than smartphone photo grading. FGDs indicated that communities and trainers found photography acceptable and preferred smartphones to DSLR in terms of practicalities, but image quality was of paramount importance for trainers. Conclusions Photography is acceptable and feasible, but further work is needed to ensure high-quality images that enable accurate and consistent grading before being routinely implemented in trachoma surveys. [ABSTRACT FROM AUTHOR]

A new Italian intersociety position statement on the prevention of ophthalmia neonatorum was published in 2023. In this document, attention was paid to the indications for the screening of gonococcal and chlamydial infections during pregnancy according to the international and national guidelines for the prevention of sexually transmitted infections (STIs). We conducted an observational retrospective study to assess whether the current guidelines for the prevention of STIs are being followed correctly. From February to August 2022, 2507 women nearing childbirth were enrolled. Among them, 42.4% received a swab for Chlamydia and only 0.5% for gonococcus. Concerning the geographical area of origin, most of the screened women came from Western Europe. None of the women who received gonococcal swabs and only 105 women out of 1062 screened for Chlamydia were under 25 years of age. Overall, only seven swabs were positive for Chlamydia, while none were positive for gonococcus. Concerning the age, geographical area of origin, and medical history of the women with a positive screening for Chlamydia, all were over 25 years old, six were from Western Europe, one was from South America, and none had other STIs. Although monocentric in nature, this study shows that the guidelines are not being followed correctly. [ABSTRACT FROM AUTHOR]

We applied lymphogranuloma venereum (LGV) clinical case criteria to a cohort of 1381 Veterans positive for HIV and Chlamydia trachomatis (CT) from 2016 from 2023 and analyzed variables to ascertain risk factors for LGV and factors associated with the use of standard treatment regimens. In total, 284/1381 (20.6%) met the criteria for LGV. A total of 179/284 (63%) were probable cases, and 105/284 (37%) were possible cases (those meeting clinical criteria but with concurrent sexually transmitted infections (STI) associated with LGV-like symptoms). None had confirmatory CT L1–L3 testing. A total of 230 LGV cases (81%) presented with proctitis, 71 (25%) with ulcers, and 57 (20.1%) with lymphadenopathy. In total, 66 (23.2%) patients had >1 symptom of LGV. A total of 43 (15%) LGV cases were hospitalized. Primary risk factors for LGV were male birth sex (p = 0.004), men who have sex with men (p < 0.001), and the presence of STIs other than gonorrhea or syphilis (p = 0.011). In total, 124/284 (43.7%) LGV cases received standard recommended treatment regimens. Probable cases were more likely to receive standard treatment than possible cases (p = 0.003). We report that 20.6% of CT cases met clinical criteria for LGV among HIV-infected Veterans and that less than half of cases received recommended treatment regimens, indicating that LGV is likely underestimated and inadequately treated among this US population. [ABSTRACT FROM AUTHOR]

Background: A systematic review on acceptability, feasibility, equity and resource use was conducted as part of updating recommendations from the Public Health Agency of Canada on prenatal screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). Methods: Information sources, including MEDLINE® All, Embase and Cochrane CENTRAL (January 2003-January 2021) electronic databases were searched for studies that assessed acceptability, feasibility, equity and resource use of screening for CT or NG in pregnant persons aged =12 years. The Risk of Bias Assessment Tool for Non-Randomized Studies was used for quality assessment and a narrative synthesis was prepared. Results: Of the 1,386 records identified, nine observational studies (approximately 5,000 participants) and three economic evaluations met the inclusion criteria. In general, pregnant persons and healthcare providers accepted screening. Most pregnant persons and partners supported universal testing for CT. Pregnant persons preferred non-invasive sampling Methods. Inequities in feasibility (accessibility to screening) exist in certain populations. Studies have shown that targeted screening can miss cases. Screening all pregnant persons for CT has net cost savings compared to no screening. Limitations include not identifying eligible literature on acceptability of prenatal screening for NG among partners of pregnant persons and some studies with increased risk populations that restrict the generalizability of the findings highlighting areas for future research. Conclusion: Prenatal screening for CT and NG is generally acceptable among pregnant persons and healthcare providers. Evidence has shown that targeted screening can miss cases. The findings were included when updating PHAC's recommendations on prenatal screening for CT and NG. This work was presented at the Society of Obstetricians and Gynaecologists of Canada's 2024 Annual Clinical and Scientific Conference in Edmonton, Alberta. [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.

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

BACKGROUND: Current guidelines recommend annual community-wide mass administration of azithromycin for trachoma. Targeting treatments to those most likely to be infected could reduce the amount of unnecessary antibiotics distributed. METHODS: In a cluster-randomized trial conducted from 1 November 2010 through 8 November 2013, 48 Ethiopian communities previously treated with annual mass azithromycin distributions for trachoma were randomized in equal numbers to (1) annual azithromycin distributions targeted to children aged 0-5 years, (2) annual azithromycin distributions targeted to households with a child aged 0-5 years found to have clinically active trachoma, (3) continued annual mass azithromycin distributions to the entire community, or (4) cessation of treatment. The primary outcome was the community prevalence of ocular chlamydia infection among children aged 0-9 years at month 36. Laboratory personnel were masked to treatment allocation. RESULTS: The prevalence of ocular chlamydia infection among children aged 0-9 years increased from 4.3% (95% confidence interval [CI], .9%-8.6%) at baseline to 8.7% (95% CI, 4.2%-13.9%) at month 36 in the age-targeted arm, and from 2.8% (95% CI, .8%-5.3%) at baseline to 6.3% (95% CI, 2.9%-10.6%) at month 36 in the household-targeted arm. After adjusting for baseline chlamydia prevalence, the 36-month prevalence of ocular chlamydia was 2.4 percentage points greater in the age-targeted group (95% CI, -4.8% to 9.6%; P = .50; prespecified primary analysis). No adverse events were reported. CONCLUSIONS: Targeting azithromycin treatment to preschool children was no different than targeting azithromycin to households with a child with clinically active trachoma. Neither approach reduced ocular chlamydia over the 3-year study. CLINICAL TRIALS REGISTRATION: NCT01202331.

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.

Abstract Background Tubal factor infertility (TFI) is common in sub-Saharan Africa and often secondary to pelvic inflammatory disease (PID). Anaerobes associated with bacterial vaginosis (BV) are also found in PIDs widely dominated by Chlamydia trachomatis (C. trachomatis), whose role in TFI is better demonstrated than that of BV. Objectives To determine the prevalence of BV and C. trachomatis and to investigate the association between BV, C. trachomatis and TFI. Methods We included 137 patients treated for infertility between January 2020 and November 2021. Cases were defined as women with infertility aged 18-45 years presenting with TFI (n = 52), and controls as infertile women in the same age groups without TFI (n = 85). Data on social habits, life style and infertility parameters were collected, and we performed screening for BV and C. trachomatis. Multiple regression was used to measure associations. Results The prevalence of BV and C. trachomatis was 42.3% (58/137) and 23.4% (32/137), respectively. BV (61.5% vs 30.6%, p

Abstract Background Genital infection with Chlamydia trachomatis (C. trachomatis) is a major public health issue worldwide. It can lead to cervicitis, urethritis, and infertility. This study was conducted to determine the characteristics of genital C. trachomatis infection among women attending to the infertility and gynecology clinics. Methods Endocervical swabs were collected from 8,221 women for C. trachomatis nucleotide screening and genotyping, while serum samples were collected for C. trachomatis pgp3 antibody determination using luciferase immunosorbent assays. Results High C. trachomatis DNA prevalence (3.76%) and seroprevalence (47.46%) rates were found, with genotype E (27.5%) being the most prevalent. C. trachomatis omp1 sense mutation was associated with cervical intraepithelial neoplasia (CIN) (odds ratio [OR] = 6.033, 95% confidence interval [CI] = 1.219–39.185, p = 0.045). No significant differences in C. trachomatis seroprevalence rates were observed between women with detectable C. trachomatis DNA in the infertility and routine physical examination groups (86.67% vs. 95%, p > 0.05); however, among women with negative C. trachomatis DNA, the former group had a markedly higher seroprevalence than the latter group (56.74% vs. 20.17%, p

Chlamydia trachomatis is a clinically important bacterium that infects epithelial cells of the genitourinary and respiratory tracts and the eye. These differentiated cells are in a quiescent growth state and have a surface organelle called a primary cilium, but the standard Chlamydia cell culture infection model uses cycling cells that lack primary cilia. To investigate if these differences are relevant, we performed infections with host cells that have a primary cilium. We found that C. trachomatis caused progressive loss of the primary cilium that was prevented by disrupting Aurora A (AurA), HDAC6 or calmodulin, which are components of the cellular cilia disassembly pathway. Stabilization of the primary cilium by targeting this pathway caused a large reduction in infectious progeny although there were no changes in chlamydial inclusion growth, chlamydial replication or the ultrastructural appearance of dividing and infectious forms (RBs and EBs, respectively). Thus, the presence of a primary cilium interfered with the production of infectious EBs at a late step in the developmental cycle. C. trachomatis infection also induced quiescent cells to re-enter the cell cycle, as detected by EdU incorporation in S-phase, and Chlamydia-induced cilia disassembly was necessary for cell cycle re-entry. This study therefore describes a novel host-pathogen interaction in which the primary cilium limits a productive Chlamydia infection, and the bacterium counteracts this host cell defense by activating the cellular cilia disassembly pathway. Author summary: In this study, we describe a novel tussle between the pathogenic bacterium Chlamydia trachomatis and its infected host cell. This interaction is centered on the primary cilium, which is a protrusion on the cell surface that is important for many cellular functions. While the primary cilium is present on cells infected by Chlamydia during a natural infection, it is absent from dividing cells used to study Chlamydia infections in cell culture. We found that Chlamydia infection caused loss of the primary cilium by activating the cellular cilia disassembly machinery and induced a quiescent host cell to re-enter the cell cycle. Furthermore, we showed that the presence of a primary cilium severely inhibited the production of infectious chlamydial progeny. Thus, the host cell uses the primary cilium to restrict a productive infection, while Chlamydia induces cilia disassembly as a countermeasure. This host-pathogen interaction could be unique to Chlamydia, but it could also have been missed for other intracellular bacteria and viruses, which are commonly studied in cells that lack a primary cilium. This work could lead to new antimicrobial approaches targeting the primary cilium. [ABSTRACT FROM AUTHOR]