OBJECTIVES:Chlamydia trachomatis (chlamydia) infection has a variable course; most infections resolve but some lead to reproductive complications. Behavioural, immunological and host genetic factors likely influence risk. We aimed to identify predictors of complications in persons with and without chlamydia and develop prediction models for risk stratification. METHODS:We analysed data from a long-term cohort of Dutch individuals registered as female in municipal registries and previously screened for chlamydia, including demographic, behavioural, chlamydia-infection and serology variables, and 24 single nucleotide polymorphisms (SNPs). We constructed SNP sets capturing shared biological pathways. Using multivariable Cox regression, we developed and internally validated composite and outcome-specific models for reproductive complications (pelvic inflammatory disease (PID), ectopic pregnancy and tubal factor infertility) stratified by chlamydia status. Model performance was assessed. Point-based risk scores were derived from final models, estimating 15-year risks. Thresholds assessed the proportion classified as high risk and the proportion of outcomes captured. RESULTS:Among the 5704 participants (35 523 and 66 511 person-years in chlamydia-positive and chlamydia-negative groups), 7.1% and 5.4% experienced reproductive complications, respectively. Across outcomes, predictors included behavioural, sociodemographic and immune-related genetic factors, with most identified SNPs known to be involved in immune pathways. Model discrimination was modest (area under the curve ~0.65). Using a ≥15% predicted risk threshold, 54% of chlamydia-positive individuals were classified as high risk of reproductive complications, capturing 75% of composite outcomes (positive predictive value (PPV) 9.7%). For PID, 27% were classified as high risk, capturing 39% of cases (PPV 6.9%), and for ectopic pregnancy, 1.7% were classified as high risk, capturing 10% of cases (PPV 11.8%). CONCLUSIONS:Prediction models integrating behavioural, sociodemographic and host genetic factors showed modest performance, with better classification for chlamydia-positive individuals and PID than for ectopic pregnancy. Individual-level risk stratification is unlikely to be clinically useful, supporting population-level or group-level targeting of prevention and care.
Background:The global impact of sexually transmitted infections (STIs) significantly affects low- and middle-income countries (LMIC). Iin Kenya, where access to STI diagnostics is limited, effective diagnostic solutions are critically needed. Nucleic acid amplification tests are considered the laboratory gold standard for detecting pathogens such as Chlamydia trachomatis and Neisseria gonorrhoeae due to their high sensitivity and specificity. However, these methods typically require centralized laboratories, trained personnel, and longer turnaround times. FlashDx is a near-point-of-care molecular diagnostic platform designed to address these challenges by integrating automated sample processing and multiplex pathogen detection within a compact system suitable for decentralized use. Objective:The primary aim of this study is to validate the performance of the FlashDx STI multiplex assay for detecting STIs including Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, Mycoplasma hominis, and Ureaplasma species compared with the reference Conformité Européenne In-Vitro Diagnostic (CE-IVD)-D dual real-time polymerase chain reaction (rtPCR) from Mikrogen. Methods:We propose a comparative cross-sectional study conducted with up to 400 young pre-exposure prophylaxis (PrEP) users aged between 15 years and 55 years at the Kenya Medical Research Institute Center for Microbiology Research Care and Training Program research site in Kisumu, Kenya. Urine samples were collected and analyzed using the FlashDx STI multiplex chip-based assay to detect 6 STIs, with results confirmed by the CE-IVD-D certified Mikrogen assay in the Netherlands. Participants were recruited in Kisumu, Kenya, from existing HIV prevention programs and sexual health services. Diagnostic performance will be assessed by calculating sensitivity, specificity, positive predictive value, and negative predictive value with 95% CIs. Descriptive and epidemiological analyses will summarize participant characteristics, behavioral risk factors, and the prevalence of STI infections within the cohort. Epidemiological data generated will include prevalence rates for all 6 STIs, providing an overview of STI prevalence with external validation to ensure accuracy and reliability. Results:The study was funded by Microbe & Lab, with in-kind contributions from the Kenya Medical Research Institute (KEMRI) Centre for Microbiology Research (CMR) Research Care and Training Program (RCTP). Data collection was conducted between April 2025 and June 2025 at the KEMRI research site in Kisumu, Kenya. A total of 400 participants were recruited for the study. The study is currently in the data analysis phase. Statistical evaluation of the diagnostic performance of the FlashDx STI multiplex assay is being carried out. In parallel, epidemiological analyses are being conducted. Final results and associated epidemiological findings are expected to be completed and prepared for publication in the summer of 2026. Conclusions:The findings from this study are expected to show the FlashDx STI multiplex assay as an effective point-of-care system for diagnosing 6 common STIs in settings such as Kenya. By demonstrating its usability, accuracy, and reliability, the FlashDx assay could be considered for broader implementation in clinical settings across Kenya and other LMIC.
Cervical cancer remains one of the most common malignancies among women worldwide, and treatment of locally advanced disease is often associated with substantial toxicity that negatively affects the quality of life. Therefore, strategies aimed at improving survival while minimizing treatment-related side effects are essential. Emerging evidence suggests that the gut and vaginal microbiomes influence cervical carcinogenesis, treatment response, and treatment-related adverse effects. This narrative review aims to summarize current evidence regarding the role of the gut and vaginal microbiomes in locally advanced cervical cancer and explores their potential clinical implications, including interactions with immunological mechanisms. Dysbiosis has been associated with chronic inflammation, impaired antitumor immune responses, reduced treatment efficacy, and increased toxicity, whereas a beneficial microbial composition appears to support improved therapeutic outcomes and reduced toxicity. In addition, microbiome-targeted interventions, including probiotics, show promise in modulating microbial composition, optimizing treatment outcomes, and mitigating treatment-related toxicity. Longitudinal studies integrating analyses of both the gut and vaginal microbiomes with immune infiltrates, patient-reported outcomes, and clinical treatment results are essential to clarify the therapeutic potential of microbiome-targeted interventions in personalized cervical cancer care. Particular attention should be given to interactions between the microbiome and immunotherapy, as immune checkpoint inhibitors are increasingly being incorporated into treatment strategies for locally advanced disease.
The epidemiology of Chlamydia trachomatis (CT) in Kenya is not well understood. We conducted a systematic review and meta-analysis of CT prevalence using PubMed, Embase, and Kenyan databases (Jan 2000–June 2024). Included studies had laboratory-confirmed CT and were peer-reviewed. Populations were categorized by sex/gender and STI vulnerability. A random-effects model was used to account for heterogeneity. Of 198 records, 51 studies (32,559 participants) were included. CT prevalence was reported for 18 studies on males, 36 on females, and four on the general population. Pooled prevalence was 5.8
The global impact of sexually transmitted infections (STIs) significantly affects low- and middle-income countries (LMICs)In Kenya, where access to STI diagnostics is limited, effective diagnostic solutions are critically needed. The primary aim of this study is to validate the performance of FlashDx STI multiplex assay, in detecting STIs including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV), Mycoplasma Genitalium (MG), Mycoplasma Hominis (MH) and Ureaplasma Species (US) compared to the CE-IVD-D Golden Standard dual rtPCR of Mikrogen (CT and NG). Epidemiological data generated will include prevalence rates for all 6 STIs, providing an overview of STI prevalence with external validation to ensure accuracy and reliability. We propose to conduct a comparative cross-sectional study with up to 400 young PrEP users aged between 15 and 30 at the Kenya Medical Research Institute Center for Microbiology Research Research Care and Training Program research site in Kisumu Kenya. Urine samples will be collected and analyzed using the FlashDx STI multiplex chip-based assay to detect six STIs, with results confirmed by the CE-IVD-D certified Mikrogen assay in the Netherlands. It is anticipated that the FlashDx STI multiplex assay will demonstrate high sensitivity and specificity in detecting CT and NG. The study will provide prevalence rates for all six STIs (CT, NG, TV, MG, USP and MH) offering a comprehensive overview of STI prevalence in this high-risk population The findings from this study are expected to show the FlashDx STI multiplex assay as an effective POC system for diagnosing six common STIs in settings such as Kenya. By demonstrating its usability, accuracy, and reliability, the FlashDx assay could be considered for broader implementation in clinical settings across Kenya and other LMICs. This could significantly improve STI diagnosis and treatment, ultimately reducing the burden of STIs and their associated complications in these regions. In addition to providing insights into the prevalence of CT and NG, this study will also offer valuable estimates for other STIs relevant to female reproductive health. KEMRI Ethical approval registration: KEMRI/SERU/CMR/P00291/5102
Persistent high-risk Human Papillomavirus infection is the primary factor in cervical carcinogenesis. However, other host-related features are believed to play a role as well. Recent research suggests that the vaginal microbiome and the immune microenvironment play a significant role in the acquisition and persistence of Human Papillomavirus infection, as well as in the regression or progression of cervical intraepithelial lesions. Studies in this emerging field describe factors associated with this interaction, though the precise nature remains incompletely understood. In this narrative review, we aim to summarize the current literature on the topic and propose hypotheses and recommendations for future research and treatment strategies.
IntroductionPopulation-based Chlamydia trachomatis (CT) serology studies help evaluate the effectiveness of CT-control strategies. Determinants of CT seropersistence over time are largely unknown, but may include host genetic factors. This study aims to assess seropositivity, map antibody trajectories, and identify determinants of seropositivity and seropersistence.MethodsWe analyzed anti-chlamydial immunoglobulin G levels in serum of women of reproductive age who participated in a prospective cohort and CT screening study. CT history was determined using screening results and self-reported diagnoses from sexual debut onward. We assessed seropersistence for n = 1,405 participants with samples at baseline and after six years, and seropositivity for n = 2,997 participants with baseline samples. Multivariable logistic regression identified demographic, behavioral, and host single nucleotide polymorphism (SNP) factors associated with seropersistence and seropositivity.ResultsAmong seropositive women at baseline, 42.0% (n = 118/281) were seropositive at follow-up. Seropersistence was more often found in women who reported treated asymptomatic and symptomatic CT infections as compared to those who did not (aOR: 3.74, 95%CI: 1.75-8.15 and 4.79, 95%CI: 2.42-9.47, respectively). Other associated factors were higher baseline antibody titers, carrying SNPs in TLR2 (aOR: 3.06, 95%CI: 1.31-7.36) and TLR9 (2.09, 95%CI: 1.09-4.08) genes and practical education (aOR: 3.16, 95%CI: 1.56-6.64). Seropositivity (24.9%, n = 748/2,997) was associated with a CCR5 deletion (aOR: 0.65, 95%CI: 0.42-0.99).ConclusionsCT seropersistence was more often found in women who reported treated CT infections as compared to women who did not report having had a CT infection or receiving treatment for it. Genetic predisposition and behavioral factors are linked to diversity in seropersistence patterns.
What is the prevalence of an unfavourable vaginal microbiome among women experiencing Recurrent Implantation Failure (RIF) compared with controls? The prevalence of an unfavourable vaginal microbiome among women experiencing RIF was significantly lower than the prevalence in the control group (21% versus 53%, p = 0.001). Infertility affects one in six couples and is recognised as a global health issue by the World Health Organisation. Although Medical Assisted Reproduction (MAR) offers successful treatment for most couples, 4-10% will experience Repeated Implantation Failure, a condition termed RIF. Increasing research sheds light on this clinical phenomenon, however a widely accepted definition is lacking. Furthermore, a multifactorial pathogenesis is considered, including disruption of the vaginal microbiome with a relatively low load of Lactobacillus and a high load of Proteobacteria, Gardnerella Vaginalis or Lactobacillus Jensenii leading to decreased pregnancy chances. This stratification is reflected in the receptIVFity test. RIF-patients and control subjects were recruited in a single-centre University observational cohort study between 2019 and 2024. RIF was defined as consecutive implantation failure of three high quality embryos, based on the Gardner grading scale, or ten embryos without quality criterion. Women referred because of a severe male factor, bilateral tubal pathology or preimplantation genetic testing (PGT) for hereditary disorders without concurrent subfertility were recruited as a control group. Clinical characteristics and vaginal swabs were collected 5-8 days after the LH-peak in natural cycles. The vaginal microbiome was analysed using the IS-Pro based ReceptIVFity test (ARTPred, Amsterdam, the Netherlands). For the composition of the vaginal microbiome a previously described algorithm characterized the microbiome as either high, medium, or low implantation potential. Means were compared by the independent t-test and categorical variables by the chi-square test with SPSS 28.0. P-value <0.05 was considered statistically significant. The clinical characteristics showed that women with RIF (n = 81) were older (33.5 years vs 30.2 years, p < 0.001) in comparison with the control subjects (n = 32). No significant differences were found in BMI, ethnicity and smoking habits. In the RIF-patients, the most common cause of infertility was male factor (44%), followed by female factor (28%), and an unknown factor (28%). In the control subjects the highest reason for referral to our centre was PGT (78%), followed by severe male factor (16%) and tubal pathology (6%). When compared to the control subjects, RIF-patients had a lower prevalence of an unfavourable vaginal microbiome (low profile, 21% vs 53% respectively, p = 0.001). However, the composition differs. In subjects with an unfavourable vaginal microbiome, the relative abundance of Lactobacillus Crispatus is lower in women experiencing RIF compared to control subjects (18% vs 54%, p = 0.119). Moreover, the relative abundance of Proteobacteria is higher among RIF-patients with an unfavourable vaginal microbiome compared to control subjects (14% vs 4%, p = 0.040). There is no widely accepted definition of RIF which makes the group heterogeneous. Furthermore, since genetic testing for aneuploidy was not performed, it cannot be ruled out that an embryo factor instead of an endometrial factor caused RIF. The findings show that the vaginal microbiome is more often unfavourable for implantation in control subjects compared to RIF-patients. Thus the question remains if an aberrant microbiome contributes to RIF. Yes
Chlamydia species, a group of obligate intracellular Gram-negative bacteria, affect humans, livestock, companion animals, and wildlife, with infections ranging from asymptomatic to severe depending on host species and strain. Diagnosis can be difficult due to mild lesions or co-infections. Because Chlamydiaceae infect multiple hosts, a One Health approach, integrating human, animal, and environmental health is essential for effective control and prevention. C. trachomatis remains endemic in many regions, while Chlamydia pneumoniae is implicated in community-acquired pneumonia. C. abortus threatens livestock and people in pastoralist communities. Other species, including C. caviae, C. felis, C. muridarum, C. pecorum, and C. psittaci, cause high morbidity in animals, and many are zoonotic, posing risks to humans through cross-species transmission. Closely related Chlamydia-like bacteria also pose emerging threats in both human and animal populations. In Africa, diverse ecosystems facilitate frequent cross-species contacts that can drive disease emergence. Rapid urbanization, population growth, and widespread poverty increase transmission, while political instability and food insecurity reduce public health responses. As the continent faces a disproportionate burden of emerging and re-emerging infections, strengthening surveillance and targeted interventions is crucial. This review examines current knowledge on the transmission dynamics and public health implications of Chlamydiaceae species in African settings.
Serology routinely serves as a diagnostic tool to confirm Chlamydia infections in humans. Particularly in delayed settings, such as post-outbreak scenarios where the acute phase of infection has subsided, serology is invaluable. Multiple studies, nonetheless, indicate deficiencies in specificity and sensitivity of current chlamydial antibody detection assays. Incorporation of multiple antigens per target is known to improve the accuracy of chlamydial serological assays. We, therefore, used the recomLine test (Mikrogen diagnostics) on serological samples of two cohorts, as it is the only commercially available test allowing detection of antibodies against three human pathogenic Chlamydia species (C. trachomatis, C. pneumoniae and C. psittaci) using multiple antigens per target. The first cohort (n = 156; samples collected between 2008 and 2022 during a C. trachomatis screening initiative) comprised women from the Netherlands (NL) with past exposure to C. trachomatis, while the second cohort (n = 44; samples collected in 2018 in a health examination survey) consisted of Belgian citizens (BE) with occupational or recreational exposure to chickens, representing a risk population for C. psittaci. The test indicated a statistically equivalent C. pneumoniae seroprevalence in both cohorts (39.10% in NL and 34.09% in BE; p = 0.337). As expected C. trachomatis seroprevalence was significantly higher (p < 0.001) in the Dutch cohort (48.72%), as compared to the Belgian cohort (4.55%). Lastly, C. psittaci seroprevalence did not significantly differ between the two groups (2.27% in BE and 1.92% in NL; p = 0.633), even though a higher prevalence was expected for the Belgian cohort. This prompts us to question whether the Belgian cohort truly constituted a C. psittaci risk population or whether the recomLine test is susceptible to cross-reaction of species-specific antibodies, thereby increasing C. psittaci prevalence in the Dutch cohort. We advocate for the development of affordable, highly sensitive antibody detection assays that can effectively distinguish between chlamydial species, addressing the increasing demand for enhanced serological testing methodologies.
Background The clinical and public health relevance of widespread testing for asymptomatic Chlamydia trachomatis (chlamydia) infections is under debate. To address uncertainties in screening programs, we estimate reproductive tract complication risks following asymptomatic and symptomatic chlamydia infections in a long-term prospective cohort. Methods A cohort of 5704 reproductive-age women recruited from a chlamydia screening study was followed for up to 14 years. Chlamydia positivity was determined using screening polymerase chain reaction test results, self-reported diagnoses (with/without symptoms), and chlamydia Immunoglobulin G antibodies. Outcome data (pregnancies, pelvic inflammatory disease (PID), ectopic pregnancy, and tubal factor infertility) were collected through self- completed questionnaires. Cox regression calculated adjusted hazard ratios (aHR) with confidence intervals (CI) to compare outcomes between time-updated chlamydia groups since sexual debut. Findings During 104,612 person-years, 2103 (36.9%) women were chlamydia-positive and 3692 women (64.7%) had been pregnant at least once. Risks for PID, ectopic pregnancy and tubal factor infertility were 1.62 (95% CI 1.20-2.17), - 2.17), 1.84 (95% CI 1.14-2.95) - 2.95) and 2.75 (95% CI 1.53-4.94), - 4.94), compared to chlamydia-negatives. aHRs for PID after symptomatic and asymptomatic infections were 2.29 (95% CI 1.62-3.25) - 3.25) and 1.06 (95% CI 0.66-1.69), - 1.69), respectively. Incidence of PID, ectopic pregnancy and tubal factor infertility after symptomatic chlamydia infection remained low with rates per 1000 person-years of 5.8, 1.9, and 1.8, respectively. Interpretation We found a significantly higher risk of PID, ectopic pregnancy and tubal factor infertility in chlamydiapositive women compared to chlamydia-negative women, although the overall incidence rates of complications remained low. Symptomatic, but not asymptomatic, chlamydia infections were associated with PID risk, suggesting the largest disease burden of complications is in this group. Copyright (c) 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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.
Chlamydia psittaci, Chlamydia gallinacea, and Chlamydia abortus are the most common Chlamydia spp. in chickens and have a confirmed or suggested zoonotic potential. No recent data are available on their prevalence and impact in the Belgian chicken industry or in the recreational chicken branch. Therefore, a cross-sectional epidemiological study was executed where samples were collected from both factory-farmed and backyard chickens. More specifically, pharyngeal chicken swabs were obtained from 20 chicken farms, 5 chicken abattoirs, and 38 different backyard locations and were analyzed using species-specific Polymerase Chain Reactions (PCRs) for the presence of the three avian Chlamydia spp. To investigate their zoonotic potential, samples were simultaneously collected from 54 backyard chicken caretakes and 37 professional chicken caretakers or abattoir employees and analyzed using species-specific PCRs as well. This study confirmed the presence of DNA of all three Chlamydia species in both the chicken industry and backyard settings. Chlamydia psittaci was the most prevalent in the industry chickens (11.0%), whereas Chlamydia gallinacea was the dominant species in the backyard chickens (14.5%). Chlamydia abortus infections were more common in the commercial chickens (9.0%) compared to the backyard chickens (2.6%). The DNA of all three species was also detected in humans (3.9% Chlamydia psittaci, 2.9% Chlamydia gallinacea, and 1.0% Chlamydia abortus).
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Background:Chlamydia trachomatis (CT), a Gram-negative intracellular bacterium, is differentiated into three biovars associated with distinct clinical syndromes, ranging from trachoma, the world's cause of preventable blindness, to the most common sexually transmitted infection. This variability underscores CT's significant impact on public health, particularly in low-resource settings. In Kenya, where the demographic is predominantly younger, the burden of CT remains poorly understood and potentially underestimated. Objectives:This study aimed to assess the prevalence of both sexually transmitted and ocular CT across various regions and populations within Kenya. Eligibility criteria:Articles on CT population testing and laboratory detection, from 2014 to date, in English or Swahili only. Sources of evidence:Electronic databases of PubMed and Google Scholar were used. Design:A scoping review. Charting methods:This study conducted a systematic scoping review, following Arksey and O'Malley's framework and adhering to PRISMA guidelines for scoping reviews (PRISMA-ScR). Results:This study incorporates findings from 19 original studies on sexually transmitted CT and seven on ocular CT. CT prevalence for four identified populations: sexually active females 2%-13%, men who have sex with men 1.3%-51%, pregnant women 2.5%-14.9% and other population groups 2.8%-16.4%. By contrast, studies on ocular CT, all performed in rural settings, found prevalence surpassing the WHO's 10% threshold primarily amongst children and mothers. Conclusion:The variability in CT prevalence across different demographics and geographical regions emphasizes the impact of socio-economic, environmental and diagnostic factors on disease transmission and detection. The insights gained here can serve as a foundation for evidence-based health policies and interventions aimed at mitigating the burden of CT in Kenya.
The urogenital microbiota is increasingly gaining recognition as a significant contributor to reproductive health. Recent studies suggest that microbiota can serve as predictors for fertility treatment outcomes. Our objective was to investigate the degree of similarity in microbial composition between patient-collected urine and vaginal samples in a subfertile population. We enrolled women of reproductive age (20–44 years) diagnosed with subfertility and requiring in vitro fertilization (IVF) or IVF with intracytoplasmic sperm injection (IVF-ICSI) treatment. They self-collected both mid-stream urine samples and vaginal swabs before commencing the IVF or IVF-ICSI procedure. All samples were analysed using the intergenic spacer profiling (IS-pro) technique, a rapid clinical microbiota analysis tool. The main outcome measures were the degree of similarity of microbial composition between the two different, but simultaneously collected, samples. Our findings revealed a high correlation (R squared of 0.78) in microbiota profiles between paired urine and vaginal samples from individual patients. Nevertheless, the urinary microbiota profiles contained fewer species compared to the vaginal microbiota, resulting in minor but distinguishable differences. Furthermore, different subfertility diagnoses appeared to be associated with differences in microbial profiles. A noteworthy observation was the exclusive presence of Escherichia coli (E. coli) in both samples of women diagnosed with male factor subfertility. In conclusion, since urinary microbiota profiles seem to represent a diluted version of the vaginal microbiota, vaginal microbiome sampling to predict fertility treatment outcome seems preferable. To enhance the success of fertility treatments, further research is needed to gain deeper insights into a putative causal role of microbiota in the mechanisms of subfertility.