Screening for genital chlamydia infection.
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ABSTRACT:
SUBMITTER: Low N
PROVIDER: S-EPMC6457643 | biostudies-literature | 2016 Sep
REPOSITORIES: biostudies-literature
Publications
Screening for genital chlamydia infection.
Low Nicola N Redmond Shelagh S Uusküla Anneli A van Bergen Jan J Ward Helen H Andersen Berit B Götz Hannelore H
The Cochrane database of systematic reviews 20160913
<h4>Background</h4>Genital infections caused by Chlamydia trachomatis are the most prevalent bacterial sexually transmitted infection worldwide. Screening of sexually active young adults to detect and treat asymptomatic infections might reduce chlamydia transmission and prevent reproductive tract morbidity, particularly pelvic inflammatory disease (PID) in women, which can cause tubal infertility and ectopic pregnancy.<h4>Objectives</h4>To assess the effects and safety of chlamydia screening ver ...[more]
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Project description: Not available
| S-EPMC6483758 | biostudies-literature
Project description:Background and aimsAtherosclerosis is a chronic inflammatory disease, and recent studies have shown that infection at remote sites can contribute to the progression of atherosclerosis in hyperlipidemic mouse models. In this report, we tested the hypothesis that genital Chlamydia infection could accelerate the onset and progression of atherosclerosis.MethodsApolipoprotein E (Apoe-/-) and LDL receptor knockout (Ldlr-/-) mice on a high-fat diet were infected intra-vaginally with Chlamydia muridarum. Atherosclerotic lesions on the aortic sinuses and in the descending aorta were assessed at 8-weeks post-infection. Systemic, macrophage, and vascular site inflammatory responses were assessed and quantified.ResultsCompared to the uninfected groups, infected Apoe-/- and Ldlr-/- mice developed significantly more atherosclerotic lesions in the aortic sinus and in the descending aorta. Increased lesions were associated with higher circulating levels of serum amyloid A-1, IL-1β, TNF-α, and increased VCAM-1 expression in the aortic sinus, suggesting an association with inflammatory responses observed during C. muridarum infection. Genital infection courses were similar in Apoe-/-, Ldlr-/-, and wild type mice. Further, Apoe-/- mice developed severe uterine pathology with increased dilatations. Apoe-deficiency also augmented cytokine/chemokine response in C. muridarum infected macrophages, suggesting that the difference in macrophage response could have contributed to the genital pathology in Apoe-/- mice.ConclusionsOverall, these studies demonstrate that genital Chlamydia infection exacerbates atherosclerotic lesions in hyperlipidemic mouse and suggest a novel role for Apoe in full recovery of uterine anatomy after chlamydial infection.
| S-EPMC8552421 | biostudies-literature
Project description:BACKGROUND:Sexual transmission rates of Chlamydia trachomatis (Ct) cannot be measured directly; however, the study of concordance of Ct infection in sexual partnerships (dyads) can help to illuminate factors influencing Ct transmission. METHODS:Heterosexual men and women with Ct infection and their sex partners were enrolled and partner-specific coital and behavioral data collected for the prior 30 days. Microbiological data included Ct culture, and nucleic acid amplification testing (NAAT), quantitative Ct polymerase chain reaction, and ompA genotyping. We measured Ct concordance in dyads and factors (correlates) associated with concordance. RESULTS:One hundred twenty-one women and 125 men formed 128 dyads. Overall, 72.9% of male partners of NAAT-positive women and 68.6% of female partners of NAAT-positive men were Ct-infected. Concordance was more common in dyads with culture-positive members (78.6% of male partners, 77% of female partners). Partners of women and men who were NAAT-positive only had lower concordance (33.3%, 46.4%, respectively). Women in concordant dyads had significantly higher median endocervical quantitative Ct polymerase chain reaction values (3,032) compared with CT-infected women in discordant dyads (1013 inclusion forming units DNA equivalents per mL; P < 0.01). Among 54 Ct-concordant dyads with ompA genotype data for both members, 96.2% had identical genotypes. CONCLUSIONS:Higher organism load appears associated with concordance among women. Same-genotype chlamydial concordance was high in sexual partnerships. No behavioral factors were sufficiently discriminating to guide partner services activities. Findings may help model coitus-specific transmission probabilities.
| S-EPMC5113142 | biostudies-literature
Project description:Chlamydia spp. productively infect mucosal epithelial cells of multiple anatomical sites, including the conjunctiva, lungs, gastrointestinal (GI) tract, and urogenital tract. We, and others, previously established that chlamydial GI tropism is mediated by distinct chromosomal and plasmid factors. In this study, we describe a genital infection-attenuated Chlamydia muridarum mutant (GIAM-1) that is profoundly and specifically attenuated in the murine genital tract. GIAM-1 infected the murine GI tract similarly to wild-type (WT) Chlamydia muridarum but did not productively infect the lower genital tract of female mice, ascend to infect the upper genital tract, or cause hydrosalpinx. However, GI infection of mice with GIAM-1 elicited a transmucosal immune response that protected against subsequent genital challenge with WT Chlamydia muridarum Collectively, our results demonstrate that chlamydia mutants that are profoundly attenuated for specific organ tissues can be derived and demonstrate that live-attenuated vaccine strains that infect the GI tract, but do not elicit genital tract disease, could be used to protect against chlamydia genital tract infection and disease.IMPORTANCE Chlamydia is the most common sexually transmitted bacterial infection in the United States. Most chlamydia genital infections resolve without serious consequences; however, untreated infection in women can cause pelvic inflammatory disease and infertility. Antibiotics are very effective in treating chlamydia, but most genital infections in both men and women are asymptomatic and go undiagnosed. Therefore, there is a critical need for an effective vaccine. In this work, we show that a mutant chlamydia strain, having substantially reduced virulence for genital infection, colonizes the gastrointestinal tract and produces robust immunity to genital challenge with fully virulent wild-type chlamydia. These results are an important advance in understanding chlamydial virulence and provide compelling evidence that safe and effective live-attenuated chlamydia vaccines may be feasible.
| S-EPMC7642681 | biostudies-literature
Project description:It has been shown that caspase-1, but not its upstream activator, ASC, contributes to oviduct pathology during mouse genital Chlamydia muridarum infection. We hypothesized that this dichotomy is due to the inadvertent absence of caspase-11 in previously used caspase-1-deficient mice. To address this, we studied the independent contributions of caspase-1 and -11 during genital Chlamydia infection. Our results show that caspase-11 deficiency was sufficient to recapitulate the effect of the combined absence of both caspase-1 and caspase-11 on oviduct pathology. Further, mice that were deficient for both caspase-1 and -11 but that expressed caspase-11 as a transgene (essentially, caspase-1-deficient mice) had no significant difference in oviduct pathology from control mice. Caspase-11-deficient mice showed reduced dilation in both the oviducts and uterus. To determine the mechanism by which caspase-11-deficient mice developed reduced pathology, the chlamydial burden and immune cell infiltration were determined in the oviducts. In the caspase-11-deficient mice, we observed increased chlamydial burdens in the upper genital tract, which correlated with increased CD4 T cell recruitment, suggesting a contribution of caspase-11 in infection control. Additionally, there were significantly fewer neutrophils in the oviducts of caspase-11-deficient mice, supporting the observed decrease in the incidence of oviduct pathology. Therefore, caspase-11 activation contributes to pathogen control and oviduct disease independently of caspase-1 activation.
| S-EPMC6652777 | biostudies-literature
Project description:Defining the mechanisms of immunity conferred by the combination of antibody and CD4+ T cells is fundamental to designing an efficacious chlamydial vaccine. Using the Chlamydia muridarum genital infection model of mice, which replicates many features of human C. trachomatis infection and avoids the characteristic low virulence of C. trachomatis in the mouse, we previously demonstrated a significant role for antibody in immunity to chlamydial infection. We found that antibody alone was not protective. Instead, protection appeared to be conferred through an undefined antibody-cellular interaction. Using gene knockout mice and in vivo cellular depletion methods, our data suggest that antibody-mediated protection is dependent on the activation of an effector cell population in genital tract tissues by CD4+ T cells. Furthermore, the CD4+ T cell-secreted cytokine interferon-gamma (IFNγ) was found to be a key component of the protective antibody response. The protective function of IFNγ was not related to the immunoglobulin class or magnitude of the Chlamydia-specific antibody response or to recruitment of an effector cell population to genital tract tissue. Rather, IFNγ appears to be necessary for activation of the effector cell population that functions in antibody-mediated chlamydial immunity. Our results confirm the central role of antibody in immunity to chlamydia reinfection, and demonstrate a key function for IFNγ in antibody-mediated protection.
| S-EPMC5067755 | biostudies-literature
Project description:The T cell response to Chlamydia genital tract infections in humans and mice is unusual in that the majority of antigen-specific CD8 T cells are not restricted by HLA/MHC class I and therefore have been referred to as “unrestricted” or “atypical”. We previously reported that a subset of unrestricted murine Chlamydia-specific CD8 T cells had an unusual cytokine polarization pattern that included IFN-ɣ and IL-13. For this report, we investigated the transcriptome of Chlamydia-specific CD8ɣ13 T cells, comparing them to Chlamydia-specific multifunctional Tc1 clones using gene expression micro array analysis. The molecular study revealed that CD8ɣ13 polarization included IL-5 in addition to IFN-γ and IL-13. Adoptive transfer studies were performed with Tc1 clone and CD8ɣ13 T cell clones to determine whether either influenced bacterial clearance or immunopathology during Chlamydia muridarum (Cm) genital tract infections. To our surprise, an adoptively transferred CD8ɣ13 T cell clone was remarkably proficient at preventing chlamydia immunopathology while the multifunctional Tc1 clone did not enhance clearance or significantly protect from immunopathology. Mapping studies with MHC class I- and class II-deficient splenocytes showed our previously published Chlamydia-specific CD8 T cell clones are MHC class II-restricted. MHC class II-restricted CD8 T cells may play important roles in protection from intracellular pathogens that limit class I antigen presentation or deplete the CD4 T cell compartment.
2020-05-21 | GSE140213 | GEO
Project description:Some members of the genus Chlamydia, including the human pathogen Chlamydia trachomatis, infect multiple tissues, including the genital and gastrointestinal (GI) tracts. However, it is unknown if bacterial targeting to these sites is mediated by multifunctional or distinct chlamydial factors. We previously showed that disruption of individual large clostridial toxin homologs encoded within the Chlamydia muridarum plasticity zone were not critical for murine genital tract infection. Here, we assessed whether cytotoxin genes contribute to C. muridarum GI tropism. Infectivity and shedding of wild-type (WT) C. muridarum and three mutants containing nonsense mutations in different cytotoxin genes, tc0437, tc0438, and tc0439, were compared in mouse genital and GI infection models. One mutant, which had a nonsense mutation in tc0439, was highly attenuated for GI infection and had a GI 50% infectious dose (ID50) that was 1,000 times greater than that of the WT. GI inoculation with this mutant failed to elicit anti-chlamydial antibodies or to protect against subsequent genital tract infection. Genome sequencing of the tc0439 mutant revealed additional chromosomal mutations, and phenotyping of additional mutants suggested that the GI attenuation might be linked to a nonsense mutation in tc0600 The molecular mechanism underlying this dramatic difference in tissue-tropic virulence is not fully understood. However, isolation of these mutants demonstrates that distinct chlamydial chromosomal factors mediate chlamydial tissue tropism and provides a basis for vaccine initiatives to isolate chlamydia strains that are attenuated for genital infection but retain the ability to colonize the GI tract and elicit protective immune responses.
| S-EPMC6013670 | biostudies-literature
Project description:We have previously shown that the time of Chlamydia infection was crucial in determining the chlamydial infectivity and pathogenesis. This study aims to determine whether the time of Chlamydia infection affects the genital tract microbiome. This study analyzed mice vaginal, uterine, and ovary/oviduct microbiome with and without Chlamydia infection. The mice were infected with Chlamydia at either 10:00 am (ZT3) or 10:00 pm (ZT15). The results showed that mice infected at ZT3 had higher Chlamydia infectivity than those infected at ZT15. There was more variation in the compositional complexity of the vaginal microbiome (alpha diversity) of mice infected at ZT3 than those mice infected at ZT15 throughout the infection within each treatment group, with both Shannon and Simpson diversity index values decreased over time. The analysis of samples collected four weeks post-infection showed that there were significant taxonomical differences (beta diversity) between different parts of the genital tract-vagina, uterus, and ovary/oviduct-and this difference was associated with the time of infection. Firmicutes and Proteobacteria were the most abundant phyla within the microbiome in all three genital tract regions for all the samples collected during this experiment. Additionally, Firmicutes was the dominant phylum in the uterine microbiome of ZT3 Chlamydia infected mice. The results show that the time of infection is associated with the microbial dynamics in the genital tract. And this association is more robust in the upper genital tract than in the vagina. This result implies that more emphasis should be placed on understanding the changes in the microbial dynamics of the upper genital tract over the course of infection.
| S-EPMC10238418 | biostudies-literature
Project description:BackgroundEstimating prevalence of Chlamydia trachomatis (CT) worldwide is necessary in designing control programs and allocating health resources. We performed a meta-analysis to calculate the prevalence of CT in the general population.MethodsThe Pubmed and Embase databases were searched for eligible population-based studies from its inception through June 5, 2019. Q test and I2 statistic were used to calculate the heterogeneity between studies. Random effects models were used to pool the prevalence of CT. Meta regression was performed to explore the possible sources of heterogeneity. Publication bias was evaluated using a funnel plot and "trim and fill" method.ResultsTwenty nine studies that reported prevalence of CT infection from 24 countries were identified, including a total population of 89,886 persons. The pooled prevalence of CT among the general population was 2.9% (95% CI, 2.4-3.5%), and females had a higher CT prevalence (3.1, 95% CI, 2.5-3.8%) than males (2.6, 95% CI, 2.0-3.2%) (χ2 = 10.38, P < 0.01). Prevalence of CT was highest in region of America (4.5, 95% CI, 3.1-5.9%), especially in Latin America (6.7, 95% CI, 5.0-8.4%), followed by females in region of Africa (3.8, 95% CI, 0.7-6.9%), while South-East Asia had a lowest CT prevalence 0.8% (95% CI, 0.3-1.3%).ConclusionsThis study provided the updated prevalence of CT among general population worldwide. General population from Latin America, especially females, and women in Africa should be given priority by WHO when design and delivery CT control programs.
| S-EPMC7414538 | biostudies-literature