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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.

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 (C.) trachomatis, a leading cause of sexually transmitted infections (STIs) worldwide, continues to be a significant public health concern. The majority of infections are asymptomatic and, when left untreated, severe sequelae such as infertility and chronic pelvic pain can occur. Despite decades of research, an effective vaccine remains elusive. This review focuses on the potential of Major Outer Membrane Protein (MOMP)-derived constructs as promising candidates for C. trachomatis vaccination. MOMP, the most abundant protein in the outer membrane of C. trachomatis, has been a focal point of vaccine research over the years due to its antigenic properties. To overcome issues associated with the use of full MOMP as a vaccine antigen, derivative constructs have been studied. As these constructs are often not sufficiently immunogenic, antigen delivery systems or accompanying adjuvants are required. Additionally, several immunization routes have been explored with these MOMP-derived vaccine antigens, and determining the optimal route remains an ongoing area of research. Future directions and challenges in the field of C. trachomatis vaccination are discussed.

BackgroundPublic health organizations have inconsistent recommendations for screening adolescents and young adults for Chlamydia trachomatis and Neisseria gonorrhoeae infections. Guidelines suggest different combinations of anorectal, pharyngeal, and urogenital testing based on age, sex, and sexual activity. Further evaluation of how identity and behaviors impact the anatomic distribution of C. trachomatis and N. gonorrhoeae infection is needed to optimize future screening practices.MethodsWe assessed the positivity of C. trachomatis and N. gonorrhoeae infections at different anatomic sites in a cohort of at-risk sexually active adolescents and young adults aged 12-24 years in New Orleans, Louisiana and Los Angeles, California. Participants were tested for C. trachomatis and N. gonorrhoeae at 3 sites (anorectum, pharynx, and urethral/cervix) every 4 months using self-collected swabs. We stratified anatomic distributions of infection into 4 gender and sexual behavior categories: (1) cisgender men who have sex with men and transgender women (MSMTW); (2) cisgender heterosexual males; (3) cisgender heterosexual females; and (4) gender minorities assigned female at birth.ResultsWhile three-site testing detected all infections, two-site (anorectum and urethra/cervix) testing identified 92%-100% of C. trachomatis or N. gonorrhoeae infections in participants assigned female at birth and cisgender heterosexual males. For MSMTW, two-site anorectal and pharyngeal testing vs single-site anorectal testing increased the proportion of individuals with either infection from 74% to 93%.ConclusionsSexual behavior and gender identity may influence detection of C. trachomatis and N. gonorrhoeae infections at specific anatomic testing sites. Testing guidelines should incorporate sexual behavior and gender identity.Clinical trials registrationNCT03134833.

BackgroundAlthough molecular testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) is highly sensitive, the cost can be prohibitive. Those high costs are amplified when the recommended screening approach is used, which requires separate testing of specimens from 3 anatomic sites (rectal, pharyngeal and urogenital). Although individual molecular testing is standard of care, pooled testing may offer a cost-saving alternative.MethodsUsing the Xpert® CT/NG assay (Cepheid, Sunnyvale, CA) we tested urine, rectal and pharyngeal swabs for CT and NG in a high-risk cohort of participants assigned male at birth who reported sex with other persons who were assigned male at birth. Remnant specimens (0.34 mL from each anatomic site) were combined to perform a single 'pooled' test. We calculated positive and negative percent agreement between the pooled testing results with standard of care Xpert CT/NG test results as the reference.ResultsWe conducted 644 pooled tests. Of those, 598 (92.3%) gave CT and NG results. The CT-positive and -negative percent agreement were 90.1% (95% confidence interval [CI], 80.7-95.9%) and 99.2% (98.1-99.8%), respectively. The NG-positive and -negative percent agreement were 96.2% (95% CI, 86.8-99.5%) and 99.8% (95% CI, 99.0-100%), respectively. Pooled testing identified 4 CT and 1 NG infections that were negative at all anatomic sites by individual testing.ConclusionsThree-site pooled CT and NG testing performs similarly to single anatomic site testing among tests providing a valid result. Future cost analyses should evaluate the cost effectiveness of pooled 3-site testing to determine if such a strategy improves the feasibility and accessibility of molecular sexually transmitted infection testing.

BackgroundCurrent guidelines recommend community-wide mass azithromycin for trachoma, but a targeted treatment strategy could reduce the volume of antibiotics required.MethodsIn total, 48 Ethiopian communities were randomized to mass, targeted, or delayed azithromycin distributions. In the targeted arm, only children aged 6 months to 5 years with evidence of ocular chlamydia received azithromycin, distributed thrice over the following year. The primary outcome was ocular chlamydia at months 12 and 24, comparing the targeted and delayed arms (0-5 year-olds, superiority analysis) and the targeted and mass azithromycin arms (8-12 year-olds, noninferiority analysis, 10% noninferiority margin).ResultsAt baseline, the mean prevalence of ocular chlamydia in the 3 arms ranged from 7% to 9% among 0-5 year-olds and from 3% to 9% among 8-12 year-olds. Averaged across months 12-24, the mean prevalence of ocular chlamydia among 0-5 year-olds was 16.7% (95% confidence interval [CI]: 9.0%-24.4%) in the targeted arm and 22.3% (95% CI: 11.1%-33.6%) in the delayed arm (P = .61). The final mean prevalence of ocular chlamydia among 8-12 year-olds was 13.5% (95% CI: 7.9%-19.1%) in the targeted arm and 5.5% (95% CI: 0.3%-10.7%) in the mass treatment arm (adjusted risk difference 8.5 percentage points [pp] higher in the targeted arm, 95% CI: 0.9 pp-16.1 pp higher).ConclusionsAntibiotic treatments targeted to infected preschool children did not result in significantly less ocular chlamydia infections compared with untreated communities and did not meet noninferiority criteria relative to mass azithromycin distributions. Targeted approaches may require treatment of a broader segment of the population in areas with hyperendemic trachoma.

BackgroundProphylactic administration of doxycycline is regarded as a potential new public health strategy to combat the rising rates of Chlamydia trachomatis infections and syphilis among men who have sex with men. We conducted a survey-based study to evaluate how community members and health care providers in Southern California would perceive doxycycline preexposure/postexposure prophylaxis (PrEP/PEP) to predict its acceptability and identify potential areas of concern.MethodsWe conducted an online cross-sectional survey among community members who identify as men who have sex with men and health care providers with prescribing authority in Southern California to investigate the current attitudes toward doxycycline PrEP/PEP, including their willingness to accept. We analyzed the data using descriptive statistics and binary logistic regression.ResultsAmong 212 enrolled community member participants, 67.5% indicated they would take doxycycline PrEP/PEP if offered by their provider. Higher acceptability was significantly associated with several characteristics, including recent history of bacterial sexually transmitted infection diagnosis and current use of HIV PrEP. For health care providers, 89.5% of 76 enrolled participants expressed willingness to prescribe doxycycline PrEP/PEP to their patients if recommended by the Centers for Disease Control and Prevention, but only 43.4% were willing if not. Both community members and health care providers demonstrated high levels of concern toward possible drug resistance.ConclusionsDoxycycline PrEP/PEP as a preventive strategy against chlamydial infections and syphilis would likely be accepted among community members and health care providers. Clear guidelines from public health officials and further clarification on the strategy's potential impact on developing drug resistance may be necessary to ensure successful implementation.

Sexually transmitted diseases (STDs) are detrimental to the health and economic well-being of society. Consequently, predicting outbreaks and identifying effective disease interventions through epidemiological tools, such as compartmental models, is of the utmost importance. Unfortunately, the ordinary differential equation compartmental models attributed to the work of Kermack and McKendrick require a duration of infection that follows the exponential or Erlang distribution, despite the biological invalidity of such assumptions. As these assumptions negatively impact the quality of predictions, alternative approaches are required that capture how the variability in the duration of infection affects the trajectory of disease and the evaluation of disease interventions. So, we apply a new family of ordinary differential equation compartmental models based on the quantity person-days of infection to predict the trajectory of disease. Importantly, this new family of models features non-exponential and non-Erlang duration of infection distributions without requiring more complex integral and integrodifferential equation compartmental model formulations. As proof of concept, we calibrate our model to recent trends of chlamydia incidence in the U.S. and utilize a novel duration of infection distribution that features periodic hazard rates. We then evaluate how increasing STD screening rates alter predictions of incidence and disability adjusted life-years over a five-year horizon. Our findings illustrate that our family of compartmental models provides a better fit to chlamydia incidence trends than traditional compartmental models, based on Akaike information criterion. They also show new asymptomatic and symptomatic infections of chlamydia peak over drastically different time frames and that increasing the annual STD screening rates from 35% to 40%-70% would annually avert 6.1-40.3 incidence while saving 1.68-11.14 disability adjusted life-years per 1000 people. This suggests increasing the STD screening rate in the U.S. would greatly aid in ongoing public health efforts to curtail the rising trends in preventable STDs.

Objectives:Chlamydia trachomatis infects the urogenital tract and eyes. Anatomical tropism is correlated with serovars which are characterized according to the variation in the major outer membrane proteins encoded by the ompA gene. The aim of the present study was to determine the distribution of C. trachomatis serovars among patients with follicular conjunctivitis in Iran.Materials and Methods:A total of 68 conjunctival specimens from symptomatic adults were studied for the presence of C. trachomatis using polymerase chain reaction (PCR) analysis. Serovars were determined by Omp1 PCR-RFLP analysis.Results:C. trachomatis was detected in 38 (55.9%) of patients with follicular conjunctivitis, with higher C. trachomatis prevalence in the younger age groups. Twenty-six (38.2%) of these patients had a history of urinary tract infection. Four distinct serovars were identified in the conjunctiva samples using molecular genotyping. The most prevalent was serovar E, followed by G, I, and F.Conclusion:Our serovar distribution indicated that chlamydial follicular conjunctivitis usually has a genital source. Genital serovars may cause eye diseases, especially in sexually active adults. On the other hand, conjunctivitis might be the only sign of sexually transmitted infection. Therefore, genotyping C. trachomatis in ocular and genital specimens could be beneficial for acquiring more detailed epidemiological information about the etiology of the disease and monitoring treatment success.

Abstract Background Bacterial sexually transmitted infections (STIs) including Neisseria gonorrhoeae and Chlamydia trachomatis are common in men who have sex with men (MSM). These infections increase the risk of acquiring and transmitting human immunodeficiency virus (HIV) in this key population. Access to MSM in many countries in sub-Saharan Africa remains generally difficult due to discrimination or criminalization of their sexual orientation which could lead to depression and risky sexual practices associated with prevalence. This protocol therefore proposes to undertake a systematic review and meta-analysis of literature on the prevalence of gonococcal and chlamydial infections among MSM in Sub-Saharan Africa. Methods This review which aims to ascertain the pooled prevalence and risk factors of these infections in sub-Saharan Africa’s MSM population will follow the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines. The search strategy will review relevant articles from the following databases: PubMed, Scopus, ISI Web of Science and the Directory of Open Access Journals (DOAJ). Articles screening for eligibility and data extraction will be conducted by two independent reviewers. All discrepancies will be resolved by the third and fourth reviewers. Heterogeneity in studies will be evaluated using the I 2 statistic and where heterogeneity is high and significant, a random effect model will be used to estimate the pooled prevalence. Publication bias will be assessed using the Doi plot. Extracted data will be analysed using MetaXL add-on for Microsoft excel. Data will be presented in tables and graphically presented in forest plots. Discussion In this study, we anticipate being able to systematically determine the prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis among MSM as well as explore possible risk factors associated with prevalence. The outcomes of the systematic review and meta-analyses will serve to support researchers and public health stakeholders in identifying healthcare priorities and in addressing issues pertaining to the overall wellbeing of the MSM community. Systematic review registration PROSPERO CRD42022327095

Abstract Background The prevalence of sexually transmitted infections (STIs) in sub-Saharan Africa is poorly described. We aimed to determine the prevalence of five treatable STIs (Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, Treponema pallidum) in a sample of Gambian women from the general population. Methods Archived specimens from 420 women aged 15 − 69 years living in The Gambia enrolled in a clinical trial of human papilloma virus vaccine schedules were tested in this study. Urine samples were tested for C. trachomatis, N. gonorrhoeae, T. vaginalis and M. genitalium using a commercially available, open-platform multiplex PCR kit. A fragment of the ompA gene was amplified from C. trachomatis-positive samples and sequenced. Serum samples were tested for T. pallidum using the Chembio DPP Syphilis Screen and Confirm test. Results Overall, 41/420 (9.8%) women tested positive for at least one STI. 32 (7.6%), 9 (2.1%), 1 (0.2%), 1 (0.2%) and 0 (0.0%) tested positive for T. vaginalis, C. trachomatis, N gonorrhoeae, M. genitalium and T. pallidum, respectively. ompA gene sequence was available from five C. trachomatis infections: four were genovar D,one was genovar G and one was genovar F. Conclusions STIs are endemic in The Gambia. Monitoring systems should be established.

Abstract Background Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most common notifiable sexually transmitted infections (STIs) in the United States. Because symptoms of these infections often overlap with other urogenital infections, misdiagnosis and incorrect treatment can occur unless appropriate STI diagnostic testing is performed in clinical settings. The objective of this study was to describe STI diagnostic testing and antimicrobial treatment patterns and trends among adolescent and adult men and women with lower genitourinary tract symptoms (LGUTS). Methods We analyzed insurance claims data from the IBM® MarketScan® Research Databases. Patients included were between 14 and 64 years old with LGUTS as determined by selected International Classification of Diseases codes between January 2010 and December 2019. Testing of STIs and relevant drug claims were captured, and distribution of testing patterns and drug claims were described. Results In total, 23,537,812 episodes with LGUTS (87.4% from women; 12.6% from men) were analyzed from 12,341,154 patients. CT/NG testing occurred in only 17.6% of all episodes. For episodes where patients received treatment within 2 weeks of the visit date, 89.3% received treatment within the first 3 days (likely indicating presumptive treatment), and 77.7% received it on the first day. For women with pelvic inflammatory disease and men with orchitis/epididymitis and acute prostatitis, ≤ 15% received CT/NG testing, and around one-half received antibiotic treatment within 3 days. Conclusions Our study revealed low CT/NG testing rates, even in patients diagnosed with complications commonly associated with these STIs, along with high levels of potentially inappropriate presumptive treatment. This highlights the need for timely and accurate STI diagnosis in patients with LGUTS to inform appropriate treatment recommendations.

Aim: Chlamydia trachomatis, is one of the most important sexually transmitted disease (STD) pathogens on a global scale. In this study we aimed to analyze the publication developments with bibliometric methods on C.trachomatis by examining the research articles published between January 1970–December 2021. Material and methods: Herein, a bibliometric design was used to achieve the developments in C. trachomatis research. Research articles published in the Web of Science (WoS) database between January, 1970–December, 2021 were included in the study. The keywords selected for the search were ‘Chlamydia trachomatis, Chlamydia, and C. trachomatis’. Results: The search of the WoS database for C. trachomatis research articles from 1970 to 2021 yielded 8133 results. Of the documents, 5696 were articles. 95.769% were published in Science Citation Index Expanded (SCI-EXPANDED) indexed journals. Most were published in English (94.803%). The articles were mostly from the Infectious Diseases (33.251%) research area. Most of the articles were from the USA. About 51% of the studies had funding organizations, with the United States Department of Health and Human Services provided the most financial support. Most of the articles (n=346, 6.074%) were published in the Journal of Sexually Transmitted Diseases. Although the number of publications seems to be irregular, it has not fallen below 80 articles per year, especially since 1980. The articles were cited 147,672 times (25.93 times per article) and the H-index was 133. Conclusion: STDs are still an important public health problem in almost all parts of the world. We have found that the number of published articles and citations to articles on C. trachomatis has increased rapidly, especially in recent years. However, although the number of publications in developed countries has increased, the number of publications in developing and underdeveloped countries is below the expected level. Since C. trachomatis is a global public health problem, countries with a lower number of publications should be supported financially.

Cong You,1 Mingyi Liao,1 Mei Wang,2 Leran Zhao,3 Longnian Li,1 Xiaoying Ye,1 Tao Yang1 1Department of Dermatology and Venereology; Candidate Branch of National Clinical Research Centre for Skin and Immune Diseases, the First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China; 2Department of Dermatology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, People’s Republic of China; 3Department of Dermatology and Venereology, the General Hospital of Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Tao Yang, Department of Dermatology and Venereology, Candidate Branch of National Clinical Research Centre for Skin and Immune Diseases, the First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China, Tel +8618720732351, Email danny20021068@sina.comPurpose: We investigated the influence of amoxicillin pre-exposure on treatment outcomes, Chlamydia trachomatis (CT) culture, the presence of drug-resistant genes, minimum inhibitory concentrations (MICs), and fractional inhibitory concentrations (FICs) in CT clinical strains. Additionally, we explored the effect of different antimicrobial combinations on CT.Patients and Methods: Clinical data of 62 patients with CT infection were recorded. Of these, 33 had pre-exposure to amoxicillin and 29 did not. Among patients with pre-exposure, 17 received azithromycin and 16 received minocycline. Among the patients without pre-exposure, 15 received azithromycin and 14 received minocycline. All patients underwent microbiological cure follow-ups one month after completing the treatment. 23S rRNA gene mutations, acquisition of tet(M) and tet(C) were detected using reverse transcription PCR (RT-PCR) and PCR, respectively. The MICs and FICs of azithromycin, minocycline, and moxifloxacin, alone or in combination, were determined using the microdilution and checkerboard methods, respectively.Results: More cases of treatment failure occurred in pre-exposed patients, in both treatment groups (P < 0.05). No 23S rRNA gene mutations or tet(M) and tet(C) acquisitions were found. More inclusion bodies were cultured from patients without amoxicillin pre-exposure than from those with pre-exposure (P < 0.0001). The MICs of all antibiotics were higher in pre-exposed patients than in those without pre-exposure (P < 0.01). The FICs of azithromycin plus moxifloxacin were lower than those of the other antibiotic combinations (P < 0.0001). The synergy rate of azithromycin plus moxifloxacin was significantly higher than those of azithromycin plus minocycline and minocycline plus moxifloxacin (P < 0.001). The FICs of all antibiotic combinations were comparable between isolates from the two patient groups (all P > 0.05).Conclusion: Pre-exposure to amoxicillin in CT patients may inhibit CT growth and decrease sensitivity of CT strains to antibiotics. Azithromycin plus moxifloxacin may be a promising treatment regimen for genital CT infections with treatment failure.Keywords: Chlamydia trachomatis, amoxicillin, minimal inhibitory concentrations, fractional inhibitory concentrations, persistent infection

Introduction: One hundred thirty million Chlamydia trachomatis infections are reported worldwide each year. Nineteen serotypes of this pathogen can cause infection in pregnant women and neonates. The distribution of these genotypes in newborns with respiratory infections in Mexico is unknown. Material and methods: We tested 1062 bronchial lavage samples from neonates with respiratory distress syndrome for Chlamydia infection. The diagnosis of Chlamydia was made by plasmid detection with an in-house PCR assay, and genotypes were identified using a PCR-RFLP assay for the ompA gene. Results: The genotyping of 40 strains identified 14 as I/Ia (35%), 13 as E (32.5%), 7 as D (17.5%), 5 as F (12.5%), and 1 as L2 (2.5%). The relative risk analysis showed that genotype D was associated with neonatal sepsis (RR, 5.83; 95% confidence interval [CI], 1.51–25.985; P

IntroductionAmong the different antigens used in the detection of anti-Chlamydia trachomatis antibodies, significant differences in sensitivity and specificity have been observed. Further evaluation of C. trachomatis antigens in antibody detection is urgently needed for the development and application of C. trachomatis serologic assays.MethodsChlamydia trachomatis antigens Pgp3, TmeA, InaC, and HSP60 were selected and used in luciferase immunosorbent assay (LISA). The detection results obtained from well-defined C. trachomatis positive and negative samples were compared with the commercial C. trachomatis ELISA (Mikrogen) for performance evaluation.ResultsPgp3, TmeA, InaC, and HSP60-based LISA showed sensitivity of 92.8, 88.8, 90.4, and 94.4%, and specificity of 99.2, 99.2, 99.2, and 92%, respectively. ROC analysis indicated that Pgp3-based LISA showed similar performance to Mikrogen ELISA (AUC 0.986 vs. 0.993, p = 0.207). Furthermore, four C. trachomatis antigens achieved strong diagnostic efficiency, i.e., positive likelihood ratios [+LR] ≥ 10 in C. trachomatis-infected women and negative likelihood ratios [−LR] ≤ 0.1 in C. trachomatis negative low exposure risk children, but only Pgp3 and TmeA showed strong diagnostic value in general adults. In addition, Pgp3, TmeA, and InaC, but not HSP60, achieved high performance, i.e., both positive predictive value (PPV) and negative predictive value (NPV) ≥ 90.9%, and showed no significant cross-reactivity with anti-Chlamydiapneumoniae.ConclusionThree C. trachomatis species-specific antigens Pgp3, TmeA, and InaC show superior performance in the detection of anti-C. trachomatis antibody, indicating the potential to be used in developing C. trachomatis serologic tests.

Many cellular processes are regulated by ubiquitin-mediated proteasomal degradation. Pathogens can regulate eukaryotic proteolysis through the delivery of proteins with de-ubiquitinating (DUB) activities. The obligate intracellular pathogen Chlamydia trachomatis secretes Cdu1 (ChlaDUB1), a dual deubiquitinase and Lys-acetyltransferase, that promotes Golgi remodeling and survival of infected host cells presumably by regulating the ubiquitination of host and bacterial proteins. Here, we determined that Cdu1’s acetylase but not its DUB activity is important to protect Cdu1 from ubiquitin-mediated degradation. We further identified three C. trachomatis proteins on the pathogen-containing vacuole (InaC, IpaM, and CTL0480) that required Cdu1‘s acetylase activity for protection from degradation and determined that Cdu1 and these Cdu1-protected proteins are required for optimal egress of Chlamydia from host cells. These findings highlight a non-canonical mechanism of pathogen-mediated protection of virulence factors from degradation after their delivery into host cells and the coordinated regulation of secreted effector proteins.

ABSTRACT Chlamydia trachomatis is an obligate intracellular bacterium that is responsible for the most prevalent bacterial sexually transmitted infection. Changes in DNA topology in this pathogen have been linked to its pathogenicity-associated developmental cycle. Here, evidence is provided that the balanced activity of DNA topoisomerases contributes to controlling Chlamydia developmental processes. Utilizing catalytically inactivated Cas12 (dCas12)-based clustered regularly interspaced short palindromic repeats interference (CRISPRi) technology, we demonstrate targeted knockdown of chromosomal topA transcription in C. trachomatis without detected toxicity of dCas12. Repression of topA impaired the developmental cycle of C. trachomatis mostly through disruption of its differentiation from a replicative form to an infectious form. Consistent with this, expression of late developmental genes of C. trachomatis was downregulated, while early genes maintained their expression. Importantly, the developmental defect associated with topA knockdown was rescued by overexpressing topA at an appropriate degree and time, directly linking the growth patterns to the levels of topA expression. Interestingly, topA knockdown had effects on DNA gyrase expression, indicating a potential compensatory mechanism for survival to offset TopA deficiency. C. trachomatis with topA knocked down displayed hypersensitivity to moxifloxacin that targets DNA gyrase in comparison with the wild type. These data underscore the requirement of integrated topoisomerase actions to support the essential developmental and transcriptional processes of C. trachomatis.IMPORTANCEWe used genetic and chemical tools to demonstrate the relationship of topoisomerase activities and their obligatory role for the chlamydial developmental cycle. Successfully targeting the essential gene topA with a CRISPRi approach, using dCas12, in C. trachomatis indicates that this method will facilitate the characterization of the essential genome. These findings have an important impact on our understanding of the mechanisms by which well-balanced topoisomerase functions in adaptation of C. trachomatis to unfavorable growth conditions imposed by antibiotics.

ABSTRACTThe epidemiology of sexually transmitted infections (STIs) is complex due to the coexistence of various pathogens, the variety of transmission modes derived from sexual orientations and behaviors at different ages and genders, and sexual contact hotspots resulting in network transmission. There is also a growing proportion of recreational drug users engaged in high-risk sexual activities, as well as pharmacological self-protection routines fostering non-condom practices. The frequency of asymptomatic patients makes it difficult to develop a comprehensive approach to STI epidemiology. Modeling approaches are required to deal with such complexity. Membrane computing is a natural computing methodology for the virtual reproduction of epidemics under the influence of deterministic and stochastic events with an unprecedented level of granularity. The application of the LOIMOS program to STI epidemiology illustrates the possibility of using it to shape appropriate interventions. Under the conditions of our basic landscape, including sexual hotspots of individuals with various risk behaviors, an increase in condom use reduces STIs in a larger proportion of heterosexuals than in same-gender sexual contacts and is much more efficient for reducing Neisseria gonorrhoeae than Chlamydia and lymphogranuloma venereum infections. Amelioration from diagnostic STI screening could be instrumental in reducing N. gonorrhoeae infections, particularly in men having sex with men (MSM), and Chlamydia trachomatis infections in the heterosexual population; however, screening was less effective in decreasing lymphogranuloma venereum infections in MSM. The influence of STI epidemiology of sexual contacts between different age groups (

ABSTRACTPacific Islanders (PI) are a vulnerable population with a high prevalence of Chlamydia trachomatis (Ct) sexually transmitted infections and remain underrepresented in research. Here, 258 vaginal and 92 paired endocervical samples from women of diverse ethnicities in Fiji were analyzed using metagenomic shotgun sequencing. Using VALENCIA, a sub-community state type (subCST) classifier, 93 (36.04%) vaginal and 38 (41.30%) endocervical microbiomes did not match reference subCSTs. We, therefore, designed four unique subCSTs, IV-D0, IV-D1, IV-D2, and IV-E—differentially dominated by Gardnerella vaginalis, Prevotella spp., and Lactobacillus iners—to improve microbiome classifications. Ct-infected paired endocervical and vaginal microbiomes were significantly more likely to have differential species relative abundance (81.58%) than uninfected pairs (35.84%; adjusted odds ratio, 7.93; 95% confidence interval, 2.93–21.93; P < 0.0001). Among paired microbiomes, the endocervix had a significantly higher alpha diversity and independently a higher alpha diversity for high-risk human papilloma virus (HPV) types compared to low-risk and no HPV. The Ct-infected endocervical network compared to all others had smaller clusters—indicating lower species abundance and decreased weight of interactions among bacterial groups within clusters—and no interactions with potentially beneficial Lactobacillus spp. These data suggest a distinct influence on this network from Ct-infected endocervical cells. Furthermore, the high relative abundance of G. vaginalis and Prevotella spp. may generate polymicrobial biofilms that predispose to and/or promote Ct and possibly HPV persistence and pathogenicity. While these data expand on the existing repertoire of endocervical and vaginal microbiomes and fill in knowledge gaps regarding PIs, prospective studies are needed to define causal associations to develop successful interventions.IMPORTANCEChlamydia 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.

Abstract Early detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) is the key to controlling the spread of these bacterial infections. An important step in developing biosensors involves identifying reliable sensing probes against specific genetic targets for CT and NG. Here, the authors have designed single‐stranded oligonucleotides (ssDNAs) targeting mutually conserved genetic regions of cryptic plasmid and chromosomal DNA of both CT and NG. The 5′‐ and 3′‐ ends of these ssDNAs are differentially functionalized with thiol groups and coupled with gold nanoparticles (AuNP) to develop absorbance‐based assay. The AuNPs agglomerate selectively in the presence of its target DNA sequence and demonstrate a change in their surface plasmon resonance. The optimized assay is then used to detect both CT and NG DNA extracted from 60 anonymized clinical samples with a clinical sensitivity of ∼100%. The limit of detection of the assays are found to be 7 and 5 copies/µL for CT and NG respectively. Furthermore, it can successfully detect the DNA levels of these two bacteria without the need for DNA extraction and via a lateral flow‐based platform. These assays thus hold the potential to be employed in clinics for rapid and efficient monitoring of sexually transmitted infections.

ABSTRACT Infection of the female genital tract by Chlamydia trachomatis can produce severe fibrotic sequelae, including tubal factor infertility and ectopic pregnancy. While infection demonstrably mediates a pro-fibrotic response in host cells, it remains unclear if intrinsic properties of the upper genital tract exacerbate chlamydial fibrosis. The relatively sterile environment of the upper genital tract is primed for a pro-inflammatory response to infection, potentially enhancing fibrosis; however, subclinical C. trachomatis infections still develop fibrosis-related sequelae. Here, we compare infection-associated and steady-state gene expression of primary human cervical and vaginal epithelial cells. In the former, we observe enhanced baseline expression and infection-mediated induction of fibrosis-associated signal factors (e.g., TGFA, IL6, IL8, and IL20), implying predisposition to Chlamydia-associated pro-fibrotic signaling. Transcription factor enrichment analysis identified regulatory targets of YAP, a transcriptional cofactor induced by infection of cervical epithelial cells, but not vaginal epithelial cells. YAP target genes induced by infection include secreted fibroblast-activating signal factors; therefore, we developed an in vitro model involving coculture of infected endocervical epithelial cells with uninfected fibroblasts. Coculture enhanced fibroblast expression of type I collagen, as well as prompting reproducible (albeit statistically insignificant) induction of α-smooth muscle actin. Fibroblast collagen induction was sensitive to siRNA-mediated YAP knockdown in infected epithelial cells, implicating chlamydial YAP activation in this effect. Collectively, our results present a novel mechanism of fibrosis initiated by Chlamydia, wherein infection-mediated induction of host YAP facilitates pro-fibrotic intercellular communication. Chlamydial YAP activation in cervical epithelial cells is thus a determinant of this tissue’s susceptibility to fibrosis.IMPORTANCEChronic or repeated infection of the female upper genital tract by C. trachomatis can lead to severe fibrotic sequelae, including tubal factor infertility and ectopic pregnancy. However, the molecular mechanisms underlying this effect are unclear. In this report, we define a transcriptional program specific to C. trachomatis infection of the upper genital tract, identifying tissue-specific induction of host YAP—a pro-fibrotic transcriptional cofactor—as a potential driver of infection-mediated fibrotic gene expression. Furthermore, we show that infected endocervical epithelial cells stimulate collagen production by fibroblasts and implicate chlamydial induction of YAP in this effect. Our results define a mechanism by which infection mediates tissue-level fibrotic pathology via paracrine signaling and identify YAP as a potential therapeutic target for the prevention of Chlamydia-associated scarring of the female genital tract.

ABSTRACT The occurrence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) is increasing worldwide, particularly in low- and middle-income countries. In cases where most infections are asymptomatic and remain in a coinfection condition. It may cause missed detections or the severe subsequent symptoms. Accurate diagnosis and convenient screening are essential for disease control. However, molecular diagnostics for CT/NG predominantly rely on polymerase chain reaction (PCR)-based detection, which requires special devices and conditions. Here, we developed an isothermal CRISPR-based CT/NG dual-target detection system by pairing recombinase polymerase amplification (RPA) and CRISPR-Cas12a/13a detection. Multiplex RPA can amplify NG and CT simultaneously, and a single-pot reaction with the Cas12a/13a can be performed for further recognizing the amplified target, driving the cleavage of the corresponding fluorescence reporter separately; thus, the signal can be monitored in different channels. This CRISPR-based CT/NG detection system achieved analytical sensitivities of 10° copies/μL for both synthetic CT/NG dsDNA and exhibited no cross-reaction with other species. In tests on 88 clinical samples, our CRISPR-based assay showed excellent agreement with the commercial assay Roche Cobas 4800 (100% accuracy for NG, 94.32% accuracy for CT, and 97.73% accuracy for CT/NG coinfection) and showed higher positive percent agreement, negative percent agreement, and accuracy than those reported for TaqMan PCR in a previous study. In addition, the results of this CRISPR-based system could be acquired within 75 min. Our isothermal diagnostic method with promising performance provides more convenience than PCR-based methods for detection and screening. IMPORTANCE A method for Neisseria gonorrhoeae (NG)/Chlamydia trachomatis (CT) detection is developed using multiplex-recombinase polymerase amplification and Cas12a/Cas13a. This method can detect NG and CT simultaneously with high sensitivity and specificity. This method has great potential to be further developed into larger-scale screening and point-of-care testing (POCT).

Bacterial vaginosis (BV), a dysbiosis of the vaginal microbiota, is a common coinfection with Chlamydia trachomatis (Ct), and BV-associated bacteria (BVAB) and their products have been implicated in aiding Ct evade natural immunity. Here, we determined if a non-optimal vaginal microbiota was associated with a higher genital Ct burden and if metronidazole, a standard treatment for BV, would reduce Ct burden or aid in natural clearance of Ct infection. Cervicovaginal samples were collected from women at enrollment and, if testing positive for Ct infection, at a follow-up visit approximately one week later. Cervical Ct burden was assessed by inclusion forming units (IFU) and Ct genome copy number (GCN), and 16S rRNA gene sequencing was used to determine the composition of the vaginal microbiota. We observed a six-log spectrum of IFU and an eight-log spectrum of GCN in our study participants at their enrollment visit, but BV, as indicated by Amsel’s criteria, Nugent scoring, or VALENCIA community state typing, did not predict infectious and total Ct burden, although IFU : GCN increased with Amsel and Nugent scores and in BV-like community state types. Ct burden was, however, associated with the abundance of bacterial species in the vaginal microbiota, negatively with Lactobacillus crispatus and positively with Prevotella bivia. Women diagnosed with BV were treated with metronidazole, and Ct burden was significantly reduced in those who resolved BV with treatment. A subset of women naturally cleared Ct infection in the interim, typified by low Ct burden at enrollment and resolution of BV. Abundance of many BVAB decreased, and Lactobacillus increased, in response to metronidazole treatment, but no changes in abundances of specific vaginal bacteria were unique to women who spontaneously cleared Ct infection.

Objectives: The aim of this study was to determine the prevalence of Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) among HPV-positive women undergoing colposcopy at the Second Xiangya Hospital of Central South University, Hunan, China. Additionally, we aimed to assess the impact of C. trachomatis or M. genitalium co-infection with HPV on the severity of cervical lesions. Methods: We collected HPV data, cervical cytology results, and demographic information from 439 women attending colposcopy. Cervical swabs were obtained for simultaneous amplification testing (SAT) of C. trachomatis and M. genitalium. Multivariate logistic regression analyses were performed to examine the association between sexually transmitted pathogens and cervical lesions. Results: Among the participants, C. trachomatis was detected in 17 (3.87%) individuals, and M. genitalium in 16 (3.64%) individuals. There was no co-infection of C. trachomatis and M. genitalium. The highest prevalence of M. genitalium was observed in women aged 19–30 years (10.20%; 95% CI, 1.41-18.99%), with a subsequent decline in prevalence with increasing age (Ptrend = 0.014). The most common HPV subtype in our study was HPV52 (30.79%), followed by HPV16 (18.62%), HPV58 (16.95%), and HPV53 (10.02%). Infection with HPV16 (OR = 3.43, 95% CI, 2.13–5.53), HPV31 (OR = 3.70, 95% CI, 1.44–9.50), and HPV33 (OR = 3.71, 95% CI, 1.43–9.67) was associated with an increased severity of cervical lesions, while HPV53 infection was not likely to lead to advanced cervical lesions (OR = 0.45, 95% CI, 0.23–0.89). The leukocyte level in vaginal secretions (P = 0.042) and cervical cytology results (P < 0.001) showed associations with the degree of cervical lesions. However, there was no significant association between C. trachomatis or M. genitalium infection and the severity of cervical lesions, nor with their co-infection with HPV16. Conclusions: There was no correlation between co-infection of Chlamydia trachomatis or Mycoplasma genitalium and the degree of cervical lesions in HPV-positive population in Hunan, China. Our findings emphasized the need to pay more attention to M. genitalium infection among young women. Increased levels of leukocytes in vaginal secretions may be linked to cervical lesions. HPV16, HPV31, and HPV33 in Hunan province, China, may exhibit higher cervical pathogenicity. [ABSTRACT FROM AUTHOR]

Background: Sexually transmitted infections (STIs) like chlamydia, gonorrhea, syphilis, and trichomoniasis contribute significantly to global morbidity and mortality. Researchers are pursuing vaccines for these STIs, and a clinical trial is currently underway for a chlamydia vaccine. However, there is little research available on individuals' willingness to receive chlamydia, gonorrhea, syphilis, and trichomoniasis vaccines. The purpose of this analysis was to map the existing literature we have on individuals' willingness to receive these bacterial/parasitic STI vaccines and understand what information on vaccine acceptability is still needed. Methods: We searched seven databases for literature on STI vaccine acceptability, then conducted title/abstract and full-text reviews to assess eligibility. All reviews and abstractions were conducted blindly by two reviewers, with discrepancies settled by discussion or the input of a third reviewer. Results: Eight of the original 2,259 texts of interest met inclusion criteria. After data abstraction, we found that gonorrhea was the most commonly examined, followed by chlamydia and syphilis. Trichomoniasis vaccine acceptability was not reported. Most texts reported high acceptability, but there did not appear to be data describing how vaccine characteristics affect acceptability. Similarly, while the literature covers a variety of populations, most of the study populations were based out of the United States or Canada and were patrons of healthcare facilities or participants from a larger health intervention study. Therefore, more information is needed on populations outside North America, and on groups with lower healthcare access and utilization. Conclusion: As the incidence of bacterial and parasitic STIs increase, and as we grow nearer vaccines for these illnesses, understanding how likely the public is to accept and receive these vaccines is crucial to their success. While the existing literature describes STI vaccine acceptability in a variety of populations, their overall number is small. More research into STI vaccine acceptability outside of North America, and especially examining how factors like number of doses, timing, and cost influence vaccine acceptability is needed to ensure effective future vaccine rollouts. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis (Ct) remains the most common bacterial sexually transmitted pathogen worldwide, causing significant morbidity particularly among women, including pelvic inflammatory disease, ectopic pregnancy, and infertility. Several vaccines are advancing through pre-clinical and clinical development, and it is likely that one or more vaccines will progress into human efficacy trials soon. In this Perspective, we present a case for considering the challenges of Ct vaccine development through a lens of equity and justice. These challenges include the need to protect against multiple serovars, in both females and males, at multiple anatomic sites, and in resource poor areas of the world. We propose that early consideration of vaccine implementation by conducting community-engaged research will ensure that a scientifically sound chlamydia vaccine promotes equity, justice, and shared-gendered responsibility for STI prevention. [ABSTRACT FROM AUTHOR]

Background: South Africa is among the countries with the highest prevalence of sexually transmitted infections (STIs), including Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). In 2017, there were an estimated 6 million new CT, 4.5 million NG and 71 000 Treponema pallidum infections among South African men and women of reproductive age. Methods: We evaluated STI prevalence and incidence and associated risk factors in 162 women aged 18–33 years old, residing in eThekwini and Tshwane, South Africa who were part of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. Women were randomised to use depot medroxyprogesterone acetate (n = 53), copper intrauterine device (n = 51), or levonorgestrel (n = 58) implant. Lateral vaginal wall swab samples were collected prior to contraceptive initiation and at months one and three following contraceptive initiation for STI testing. Results: There were no significant differences in STI incidence and prevalence across contraceptive groups. At baseline, 40% had active STIs (CT, NG, Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) or herpes simplex virus-2 shedding across all age groups– 18–21 years (46%), 22–25 years (42%) and 26–33 years (29%). The incidence of STIs during follow-up was exceptionally high (107.9/100 women-years [wy]), with younger women (18–21 years) more likely to acquire CT (75.9/100 wy) compared to 26–33 year olds (17.4/100 wy; p = 0.049). TV incidence was higher in the 26–33 year old group (82.7/100 wy) compared to the 18–21 year olds (8.4/100 wy; p = 0.01). Conclusions: Although the study participants received extensive counselling on the importance of condom use, this study highlights the high prevalence and incidence of STIs in South African women, especially amongst young women, emphasising the need for better STI screening and management strategies. [ABSTRACT FROM AUTHOR]

Background: Trachoma, the leading infectious cause of blindness, is caused by the bacterium Chlamydia trachomatis (Ct). Despite enormous disease control efforts and encouraging progress, trachoma remains a significant public health problem in 44 countries. Ethiopia has the greatest burden of trachoma worldwide, however, robust data exploring transmission risk factors and the association between socio-economic status is lacking from some regions. This is the first study to investigate these factors in this South-Eastern region of Oromia, Ethiopia. Methodology/Principal findings: A total of 1211 individuals were enrolled from 247 households in Shashemene Rural district in Oromia Region between 11th April and 25th June 2018, of whom 628 (51.9%) were female and 526 (43.4%) were children aged 1–9 years. Three standardised ophthalmic nurses examined each participant for the presence of active trachoma using the WHO simplified trachoma grading system. Conjunctival swab samples were collected from the upper tarsal conjunctiva of the left eye of each participant. Ct was detected using quantitative PCR. Risk factor data were collected through structured interviews and direct observations. Clinical signs of trachomatous inflammation-follicular among children aged 1–9 (TF1-9) were observed in at least one eye of 106/526 (20.2%) and trachomatous inflammation-intense among children aged 1–9 (TI1-9) were observed in at least one eye of 10/526 (1.9%). We detected Ct by PCR in 23 individuals, of whom 18 (78.3%) were in children aged 1–9 years. Among the 106 children aged 1–9 years with TF, 12 (11.3%) were Ct PCR positive and among 20 children aged 1–9 years with TI, 4 (20.0%) were Ct PCR positive. In a multivariable model, adjusting for household clustering, active trachoma was associated with younger age, the poorest households (aOR = 2.56, 95% CI 1.21–5.51), presence of flies on the face (aOR = 2.87, 95% CI 1.69–6.46), and ocular discharge (aOR = 1.89, 95% CI 1.03–3.24). Pre-school children face washing more than once a day had lower odds of having active trachoma (aOR = 0.59, 95% CI 0.19–0.84). The same was true for washing children's clothing at least once per week (aOR = 0.27, 95% CI 0.33–1.02). Conclusion/Significance: Younger age, personal hygiene in this age group (presence of ocular and nasal discharges, infrequent washing of faces and clothing) and fly-eye contacts are potential risk factors for trachoma in this setting, suggesting that hygiene interventions and environmental improvements are required to suppress transmission to ensure sustained reduction in disease burden Further studies are needed to evaluate these interventions for trachoma control and elimination. Trachoma remains a disease associated with lower socio-economic status, emphasising the need for continued implementation of control measures in addition to poverty reduction interventions in this region. Author summary: Trachoma, caused by ocular Ct, is targeted by the World Health Organization (WHO) for elimination by 2030. The WHO recommends the SAFE strategy to be implemented in all endemic countries. Ethiopia bears the highest trachoma disease burden globally. In Oromia, the biggest region of Ethiopia, the prevalence of trachomatous inflammation-follicular (TF) among children age 1–9 (TF1-9) was >30% in 46% of the 2016 GTMP surveyed districts. We conducted a cross-sectional survey of 247 households in Shashemene Rural district in southeastern region of Oromia to explore risk factors for trachoma in this setting. Prevalence of trachomatous inflammation-follicular (TF) was 9.3% overall and 20.2% among children aged 1–9 years. Ct infection among individuals with active trachoma (TF and/or TI) was 12.7% overall. Seventy-eight percent (18/23) of those with Ct detected were children aged 1–9 years. In this setting, active trachoma was associated with younger age, the poorest households, presence of flies on the face, and ocular discharge, emphasizing the importance of the continued implementation of SAFE strategy in addition to poverty reduction interventions. [ABSTRACT FROM AUTHOR]

Associations of HLA class II alleles with genital chlamydial infection outcomes have been reported, especially HLA DQB1*06. However, the potential role of DQB1*06 in influencing reinfection risk has still not been established. The purpose of this study was to determine whether the association of DQB1*06 with chlamydia reinfection was impacted by any other nearby HLA class II variants that were also associated with reinfection. We used next-generation sequencing to map HLA class II variants spanning the HLA-DQ and -DR loci. DQB1*06 as well as DQB1*04 were confirmed as significant predictors of chlamydia reinfection, when controlling for age and percent African ancestry. SKAT analysis revealed one region each in DRB1, DRB5, DQA2, and three intergenic regions that had variants associated with reinfection. Further analyses of these variants revealed that rs112651494 within DRB5 and an intergenic SNP rs617058 in DRB1:DQA1 were significantly associated with reinfection, but this did not impact the significance of the association of DQB1*06 or DQB1*04 with reinfection. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis is the leading cause of sexually transmitted diseases causing frequent, long-lasting, and often asymptomatic recurrent infections resulting in severe reproductive complications. C. trachomatis is an intracellular Gram-negative bacterium with a biphasic developmental cycle in which extracellular, infectious elementary bodies (EB) alternate with the intracellular replicating reticulate bodies (RB). The outer membrane of EB consists of a tight disulfide cross-linking protein network. The most essential protein is the 42 kDa major outer membrane protein (MOMP) that contributes to the rigid structural integrity of the outer membrane. MOMP is a transmembrane protein with a β-barrel structure consisting of four variable domains (VD) separated by five constant domains. VDIV possesses surface-exposed species-specific epitopes recognized by the immune system and, therefore, functions as a candidate for vaccine development. To analyze the protective contribution of antibodies for a MOMP vaccine, we investigated the specificity and binding characteristics of two monoclonal antibodies (MAb)224.2 and MAb244.4 directed against C. trachomatis serovar D MOMP. By immunoelectron microscopy, we found that both MAb bind to the surface of C. trachomatis EB. By epitope mapping, we characterized the MOMP epitope as linear consisting of 6 amino acids: 322TIAGAGD328. By ELISA it was shown that both antibodies bind with a higher avidity to the chlamydial surface compared to binding to monomeric MOMP, indicating that the antibodies bind divalently to the surface of C. trachomatis EB. Despite strong binding to the chlamydial surface, the antibodies only partially reduced the infectivity. This may be explained by the observation that even though both MAb covered the EB surface, antibodies could not be regularly detected on EB after the uptake into the host cell. • Characterization of MAb to Chlamydia trachomatis MOMP variable domain IV. • The MAb bind to the surface of infectious chlamydiae. • The MAb have high avidity but lack neutralization of infection. • MAb are released upon intracellular uptake. [ABSTRACT FROM AUTHOR]

Sexually transmitted infection (STI) diagnosis is complicated as these infections can present with lower genitourinary tract symptoms (LGUTS) that overlap with other disorders, i.e. urinary tract infections (UTIs). The study's objective was to determine potential missed STI diagnoses from patients presenting with LGUTS in the US between January 2010 and December 2019. The de-identified insurance claims data from the IBM® MarketScan® Research Databases were collected from patients (14–64 years old) who presented with LGUTS, which could be caused by an STI. A 'GAP' cohort was created, consisting of episodes with potentially delayed STI (Chlamydia trachomatis [CT]/Neisseria gonorrhoeae [NG]) treatment. The intention was to capture episodes where an STI was not initially suspected. Four subgroups were defined depending on the treatment received (fluoroquinolone; azithromycin and/or doxycycline; cephalosporins; gentamicin and azithromycin). The GAP cohort consisted of 833,574 LGUTS episodes from the original cohort (23,537,812 episodes). Post-index CT/NG testing was carried out for 4.6% and 5.4% of the episodes from men and women, respectively. There were ≥2 return visits for 16.1% and 15.8% of the episodes from men and women, respectively. A substantial percentage of episodes from men (52.1%) and women (68.3%) were diagnosed with a UTI and/or acute cystitis at the index prior to receiving post-index STI treatment. Other top conditions diagnosed at index for men were dysuria (25.8% of the episodes), orchitis/epididymitis (14.3% of the episodes), and acute prostatitis (10.1% of the episodes), and for women were dysuria (24.2% of the episodes), vaginitis/vulvitis/vulvovaginitis (11.7% of the episodes), and cervicitis (3.3% of the episodes). These findings highlight delayed STI antibiotic treatment and low rates of CT/NG testing, suggesting late STI consideration and suboptimal diagnosis. Additionally, our study illustrates the importance of accurately diagnosing and treating STIs in patients with LGUTS and associated conditions, to avoid antibiotic misuse and complications from delayed administration of appropriate treatment. [ABSTRACT FROM AUTHOR]

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Prevalent cervical HPV infection and high-risk HPV persistence consequences have been extensively investigated in the literature; nevertheless, any causative interrelations of other sexually transmitted bacterial infections (STIs) with cervical HPV infection have not yet been fully elucidated. This study aimed to investigate the possible association of STIs with cervical cytology aberrations and HPV genotyping results in a representative sample of predominantly young Greek women. Liquid-based cytology and molecular detection for bacterial STIs and HPV as well as extended HPV genotyping were simultaneously assessed in cervical samples from 2256 individuals visiting several urban outpatient Gynecology Departments for well-woman visits or cervical screening throughout a 20-month period. All specimens were centrally processed with validated molecular assays. The mean age of the studied women was 37.0 ± 11.7 years; 722 women (33.30%) tested positive for STI (mean age 34.23 ± 10.87 years). A higher mean age (38.34 ± 11.83 years (p < 0.05)) was associated with negative STI testing. Chlamydia trachomatis was detected in 59 individuals (8.2%), Mycoplasma hominis in 156 (21.6%), Mycoplasma genitalium in 14 (1.9%), and Ureaplasma spp. in 555 (76.9%); infections with two bacterial pathogens were identified in 73 samples (10.1%). Cervical HPV was detected in 357 out of 1385 samples with a valid HPV typing result (25.8%). The mean age of HPV-positive women was 32.0 ± 8.4 years; individuals testing HPV-negative were slightly older (N = 1028): 34.4 ± 9.2 (p < 0.05). Among the 1371 individuals with valid results both for bacterial STIs and cervical HPV detection, women with an HPV-positive sample were more likely to harbor an STI (OR: 2.69, 95% CI 2.10–3.46, p < 0.05). Interestingly, bacterial STI positivity illustrated significant heterogeneity between NILM and LSIL cases, with 28.88% of NILM and 46.33% of LSIL cases harboring an STI, respectively (p < 0.05). In brief, in a population with a high prevalence for STIs, especially Ureaplasma spp., an association was documented between bacterial pathogen detection and cervical HPV infection, as well as abnormal cytology; these findings merit further investigation. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis is a strict intracellular human pathogen. It is the main bacterial cause of sexually transmitted infections and the etiologic agent of trachoma, which is the leading cause of preventable blindness. Despite over 100 years since C. trachomatis was first identified, there is still no vaccine. However in recent years, the advancement of genetic manipulation approaches for C. trachomatis has increased our understanding of the molecular pathogenesis of C. trachomatis and progress towards a vaccine. In this mini-review, we aimed to outline the factors related to the developmental cycle phase and specific pathogenesis activity of C. trachomatis in order to focus priorities for future genetic approaches. We highlight the factors known to be critical for developmental cycle stages, gene expression regulatory factors, type III secretion system and their effectors, and individual virulence factors with known impacts. [ABSTRACT FROM AUTHOR]

To determine the prevalence of genital Chlamydia trachomatis (chlamydia) infection, knowledge about chlamydia and experience of previous testing for chlamydia, we carried out a national probability-based survey in emerging adults aged 18–25 years in Croatia in 2021–2022. Participants (n = 1197), members of a national online panel, completed a web-based questionnaire that collected information on socio-demographics, sexual behaviours and knowledge about sexually transmitted infections (STIs). Urine specimens from a sample of sexually experienced participants were self-collected and tested for chlamydia using Cobas 4800 CT/NG test. To achieve broad representativeness of the emerging adult population in the country, we applied post-hoc weighting for gender and age. Multivariable ordinary least squares linear regression was used to determine correlates of knowledge about chlamydia infection and binomial logistic regression to assess correlates of the willingness to test for chlamydia. Among 448 participants who sent in their urine specimens chlamydia prevalence was 2.5% (95% CI 1.2–5.1) in women and 1.0% (0.3–3.2%) in men. A total of 8.0% of women and 4.7% men reported testing for chlamydia prior to the survey. About a quarter of the sample was characterized by not answering correctly any of the six questions related to knowledge about chlamydia, while only 9.6% had five or six correct answers. In the multivariable analysis, significantly higher odds of willingness to test for chlamydia were found in females compared to males (OR = 1.34, p = 0.024), those with better knowledge about the infection (OR = 1.11, p = 0.005), and those with lower religiosity (OR = 0.91, p = 0.017). In conclusion, prevalence of chlamydia in emerging adults in Croatia is considerable. Efforts to control this infection should focus on primary prevention and targeted testing combined with effective case management strategies. [ABSTRACT FROM AUTHOR]

Trachoma is the world's most frequent cause of blindness from an infectious agent. The disease caused by infection is associated with lack of access to sanitation and low hygiene standards. Trachoma is controlled through the Surgery, Antibiotics, Facial cleanliness, and Environmental improvement (SAFE) strategy, which delivers azithromycin (AZM) mass drug administration (MDA) in endemic areas. The putative vector Musca sorbens principally reproduce in human faecal matter left in the environment due to open defecation. Ivermectin (IVM) is on the WHO's essential medicines list and is administered as preventative chemotherapy against two neglected tropical diseases (NTDs)—onchocerciasis, as an annual or bi-annual treatment, and lymphatic filariasis, as an annual treatment in combination with albendazole. Ivermectin has a known inhibitive effect on insects that reproduce in dung. To assess if IVM could be a viable vector control tool against M. sorbens, this study evaluates existing data from trachoma, onchocerciasis and lymphatic filariasis mass drug administration (MDA) operations in Ethiopia. Persistent and recrudescent trachoma in evaluation units (EUs) were examined for whether AZM MDA in EUs was accompanied by IVM MDA, and whether co-administration was associated with greater likelihood of trachoma control. Results show an association suggesting that EUs that received both IVM and AZM MDA benefit from improved control of trachoma in persistent or recrudescent areas, when compared to EUs that received AZM MDA. This initial investigation supports the potential for ivermectin's use to support SAFE. Findings warrant further work to validate ivermectin's impact on M. sorbens reproduction through controlled lab and field-based studies. Author summary: Trachoma is the world's most frequent cause of blindness from an infectious agent. Trachoma is controlled through the Surgery, Antibiotics, Facial cleanliness, and Environmental improvement (SAFE) strategy, which delivers azithromycin (AZM) mass drug administration (MDA) in endemic areas. The putative vector Musca sorbens principally reproduce in human faecal matter left in the environment due to open defecation. Ivermectin (IVM) is on the WHO's essential medicines list, administered against two neglected tropical diseases (NTDs)–onchocerciasis and lymphatic filariasis. Ivermectin has an inhibitive effect on insects reproducing in dung. To assess if IVM could be a viable vector control tool against M. sorbens, this study evaluates existing data from trachoma, onchocerciasis and lymphatic filariasis mass drug administration (MDA) operations in Ethiopia. Persistent and recrudescent trachoma in evaluation units (EUs) were examined for whether AZM MDA in EUs was accompanied by IVM MDA, and whether co-administration could have controlled the putative vector, unintentionally enhancing trachoma control. Results suggest that EUs receiving both IVM and AZM MDA had improved control of trachoma, when compared to EUs that have only received AZM MDA. This initial investigation supports conducting further work into ivermectin's impact on M. sorbens reproduction through controlled lab and field-based studies. [ABSTRACT FROM AUTHOR]

Trichomonas vaginalis is a human infective parasite responsible for trichomoniasis–the most common, non-viral, sexually transmitted infection worldwide. T. vaginalis resides exclusively in the urogenital tract of both men and women. In women, T. vaginalis has been found colonizing the cervix and vaginal tract while in men it has been identified in the upper and lower urogenital tract and in secreted fluids such as semen, urethral discharge, urine, and prostatic fluid. Despite the over 270 million cases of trichomoniasis annually worldwide, T. vaginalis continues to be a highly neglected organism and thus poorly studied. Here we have developed a male mouse model for studying T. vaginalis pathogenesis in vivo by delivering parasites into the murine urogenital tract (MUT) via transurethral catheterization. Parasite burden was assessed ex-vivo using a nanoluciferase-based gene expression assay which allowed quantification of parasites pre- and post-inoculation. Using this model and read-out approach, we show that T. vaginalis can be found within MUT tissue up to 72 hrs post-inoculation. Furthermore, we also demonstrate that parasites that exhibit increased parasite adherence in vitro also have higher parasite burden in mice in vivo. These data provide evidence that parasite adherence to host cells aids in parasite persistence in vivo and molecular determinants found to correlate with host cell adherence in vitro are applicable to infection in vivo. Finally, we show that co-inoculation of T. vaginalis extracellular vesicles (TvEVs) and parasites results in higher parasite burden in vivo. These findings confirm our previous in vitro-based predictions that TvEVs assist the parasite in colonizing the host. The establishment of this pathogenesis model for T. vaginalis sets the stage for identifying and examining parasite factors that contribute to and influence infection outcomes. Author summary: Trichomonas vaginalis is a human infective parasite that is responsible for most common, non-viral, sexually transmitted infection worldwide. Despite the over 270 million cases of T. vaginalis infection reported annually worldwide, the parasite continues to be a highly neglected pathogen and thus poorly studied. Despite several attempts to establish an animal model to study T. vaginalis infection, reliable infection models are lacking. As a result, our understanding of parasitic features that contribute to establishing and maintaining an infection have been determined by growing cultures of parasites and human host cells in the laboratory and testing parasite:host cell interactions in test tubes. Here we describe the development of a mouse model for studying T. vaginalis infection in an animal. We demonstrate that two features of the parasite that affect parasite: host cell interaction in test tubes: (1) its adherence properties and (2) the extracellular vesicles it releases that are taken up by host cells also impact parasite survival in this novel, mice model. The establishment of this animal model for T. vaginalis sets the stage for identifying and examining parasite factors that contribute to and influence infection outcomes. [ABSTRACT FROM AUTHOR]

Sexually transmitted infections (STIs) are hazardous to human health worldwide. STIs have a direct influence on sexual and reproductive health and can increase the chances of HIV. Globally, more than 1 million STIs are acquired every day and the majority are asymptomatic. Approximately, 374 million cases of STIs have been reported annually. The most prevalent STIs include chlamydia, gonorrhoea, syphilis, and trichomoniasis. These STIs are caused by Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum and Trichomonas vaginalis. The major factor that contributes to the susceptibility and prognosis of infectious diseases is genetic variation. Host genes play a huge role in STIs and immune response. The production of host factors is stimulated by a variety of bacteria, viruses and parasites and the host factors can play a role in increasing host vulnerability to infection and pathogen persistence. Genetic variation or polymorphisms within certain host genes can influence the course of pathogen infection and disease progression. Polymorphisms can contribute to changes in gene expression and or changes in the protein structure. which may either contribute to/or protect against infection. This review discusses the role of host genes in influencing the susceptibility of the most prevalent STIs caused by Chlamydia trachomatis, Trichomonas vaginalis, Treponema pallidum and Neisseria gonorrhoeae. We evaluate polymorphisms associated pathogen recognition signalling pathway of these diseases. These polymorphisms may be used as biomarkers to infer risk to specific STIs. [ABSTRACT FROM AUTHOR]

Background: Trachoma is a neglected tropical disease caused by ocular infection with Chlamydia trachomatis, where repeated infections and chronic inflammation can ultimately result in scarring, trichiasis and blindness. While scarring is thought to be mediated by a dysregulated immune response, the kinetics of cytokines and antimicrobial proteins in the tear film have not yet been characterised. Methodology: Pooled tears from a Gambian cohort and Tanzanian cohort were semi-quantitatively screened using a Proteome Profiler Array to identify cytokines differentially regulated in disease. Based on this screen and previous literature, ten cytokines (CXCL1, IP-10, IFN-γ, IL-1β, IL-8, IL-10, IL-12 p40, IL-1RA, IL-1α and PDGF), lysozyme and lactoferrin were assayed in the Tanzanian cohort by multiplex cytokine assay and ELISA. Finally, CXCL1, IP-10, IL-8, lysozyme and lactoferrin were longitudinally profiled in the Gambian cohort by multiplex cytokine assay and ELISA. Results: In the Tanzanian cohort, IL-8 was significantly increased in those with clinically inapparent infection (p = 0.0086). Lysozyme, IL-10 and chemokines CXCL1 and IL-8 were increased in scarring (p = 0.016, 0.046, 0.016, and 0.037). CXCL1, IP-10, IL-8, lysozyme and lactoferrin were longitudinally profiled over the course of infection in a Gambian cohort study, with evidence of an inflammatory response both before, during and after detectable infection. CXCL1, IL-8 and IP-10 were higher in the second infection episode relative to the first (p = 0.0012, 0.044, and 0.04). Conclusions: These findings suggest that the ocular immune system responds prior to and continues to respond after detectable C. trachomatis infection, possibly due to a positive feedback loop inducing immune activation. Levels of CXC chemokines in successive infection episodes were increased, which may offer an explanation as to why repeated infections are a risk factor for scarring. Author summary: The neglected tropical disease trachoma is caused by repeated ocular infections with Chlamydia trachomatis. Progression from infection to inflammation and scarring is thought to be due to a pathogenic immune response. This study aimed to identify new associations between tear proteins and trachoma, and to study how they change over time in those with infection. We found that inflammatory chemokines and the antibacterial enzyme lysozyme were increased in scarring, while IL-8 was increased during infection. In a separate cohort study, the same inflammatory chemokines were found to increase before and after detectable infection, and were higher in repeated infections. [ABSTRACT FROM AUTHOR]

Background Natural clearance of Chlamydia trachomatis in women occurs in the interval between screening and treatment. In vitro, interferon-γ (IFN-γ)–mediated tryptophan depletion results in C. trachomatis clearance, but whether this mechanism occurs in vivo remains unclear. We previously found that women who naturally cleared C. trachomatis had lower cervicovaginal levels of tryptophan and IFN-γ compared to women with persisting infection, suggesting IFN-γ–independent pathways may promote C. trachomatis clearance. Methods Cervicovaginal lavages from 34 women who did (n = 17) or did not (n = 17) naturally clear C. trachomatis were subjected to untargeted high-performance liquid chromatography mass-spectrometry to identify metabolites and metabolic pathways associated with natural clearance. Results In total, 375 positively charged metabolites and 149 negatively charged metabolites were annotated. Compared to women with persisting infection, C. trachomatis natural clearance was associated with increased levels of oligosaccharides trehalose, sucrose, melezitose, and maltotriose, and lower levels of indoline and various amino acids. Metabolites were associated with valine, leucine, and isoleucine biosynthesis pathways. Conclusions The cervicovaginal metabolome in women who did or did not naturally clear C. trachomatis is distinct. In women who cleared C. trachomatis , depletion of various amino acids, especially valine, leucine, and isoleucine, suggests that amino acids other than tryptophan impact C. trachomatis survival in vivo. [ABSTRACT FROM AUTHOR]

Sexually transmitted infections (STIs) are a public health problem worldwide, and current diagnostic methods have certain limitations. In recent years, volatile organic compounds (VOCs) have been studied as an alternative diagnostic method. Due to this, this study aimed to detect, in vaginal swabs and urine samples, VOCs emitted by highly prevalent STIs-causing bacteria (Chlamydia trachomatis, Mycoplasma genitalium, and Neisseria gonorrhoeae) to identify potential biomarkers that allow the detection of these STIs. VOCs detected in urine samples showed a better differentiation of patients with STIs due to C. trachomatis from those not infected, with 2,6-dimethyl-4-heptanone as the volatile compound most related to the presence of this bacterium. Among the VOCs most related to M. genitalium in urine, 4-methyltetradecane and 2-methylpentadecane stood out, while 3,4,4-trimethyl-2-cyclohexen-1-one was the VOC most closely related to N. gonorrhoeae infection. Moreover, C12 alcohols were the main VOC family associated with positive samples in all three bacteria, which could indicate the presence of aldehyde reductases in their metabolism. In contrast, alcohols such as 3-methyl-1-heptanol and 1-octanol, as well as dimethyl esters, were more associated with negative samples and may be useful in ruling out an STI caused by one of these three bacteria. In short, the VOCs identified as potential biomarkers in patients with infection by C. trachomatis, M. genitalium, or N. gonorrhoeae could be used in the early diagnosis of these STIs, quickly interrupting the chain of transmission, especially interesting in asymptomatic patients. Key points: • Sexually transmitted infections are a serious public health problem worldwide. • The study of VOCs in multiple infections is increasing in recent years. • The identification of volatile biomarkers could allow new diagnostic methods. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis (CT) is the most common negative gram bacteria obligate intracellular pathogen that causes sexually transmitted diseases, including ocular trachoma worldwide. the objective was to diagnose genital CT infection among reproductive-age women attending AlBatool Hospital in Mosul-Iraq. including Immuno-chromatographic test and quantitative Polymerase chain reaction (qPCR). A total of 125 females were included in this research, out of which 100 were infertile and 25 were fertile. Endo-cervical swabs were collected from all participants during the study period (July 2022 to September 2022). The immune chromatographic for chlamydia (ICT) and qPCR method was utilized to amplify and quantify chlamydial 16srRNA, known for its high specificity and sensitivity. qPCR is considered an ultrasensitive marker for the detection of CT. and was used to confirm the positive cases identified by ICT. Among the 125 women tested, a total of 12 cases (12%) were found to be positive for CT infection, all positive cases identified through immunographic test showed increased amplicon copy numbers with variable concentrations when analyzed by qPCR, providing strong evidence for the accuracy and reliability of molecular test. Out of the 100 infertile women, 12 were positive for CT infection, while none of the 25 fertile women tested positive. These findings suggest a potential association between CT infection and female infertility. The research demonstrated the utility of quantitative Polymerase chain reaction (qPCR) in diagnosing genital Chlamydia trachomatis infection among reproductive-age women. [ABSTRACT FROM AUTHOR]

This review summarizes and examines research in the area of salpingitis animal modeling in the last 40 years, focusing primarily on Chlamydia trachomatis animal models, which are the most numerous in the literature. Early animal models are examined, followed by a discussion of study parameters and their impact on modeling success, subsequent considerations of fertility measures in modeling, explorations of treatment options, and finally exploring recent directions with a brief discussion of models using other bacterial pathogens. [ABSTRACT FROM AUTHOR]