Chlamydia trachomatis Genital Tract Infections: When Host Immune Response and the Microbiome Collide

© 2016 Genital infections with Chlamydia trachomatis continue to be a major health problem worldwide. While some individuals clear their infection (presumed to be the result of an effective Th1/interferon-γ response), others develop chronic infections and some are prone to repeat infections. In females in particular, chronic asymptomatic infections are common and can lead to pelvic inflammatory disease and infertility. Recent studies suggest that the genital tract microbiota could be a significant factor and explain person-to-person variation in C. trachomatis infections. One hypothesis suggests that C. trachomatis can use its trpBA genes to rescue tryptophan from indole, which is a product of anaerobic members of the genital tract microbiota. Women with particular microbiota types, such as seen in bacterial vaginosis, have increased numbers of anaerobes, and this would enable the chlamydia in these individuals to overcome the host's interferon-γ attempts to eliminate it, resulting in more repeat and/or chronic infections

Systemic antibody response to Chlamydia Trachomatis infection in patients either infected or reinfected with different Chlamydia serovars

© 2017 Indian Journal of Medical Microbiology | Published by Wolters Kluwer - Medknow. Introduction: Chlamydia trachomatis is the etiological agent for the most prevalent bacterial sexually transmitted infection in both developed and developing countries. The aim of present study was to characterize the antibody response between two groups of individuals, having either a single C. trachomatis infection and or repeated infections. Material and Methods: Current study consisted of two groups, one with an initial Chlamydia infection and a second with repeated infections. A titre based estimation of specific serum (IgG and IgA) levels using ELISA were performed, which further validated by western blot. In vitro neutralizing ability of each patient's serum against both homologous and heterologous strains was also determined. Results: Individuals infected with one of the C. trachomatis serovars D, E or K exhibited a strong systemic antibody response as characterized by ELISA and western blot. These individuals may have developed at least some level of protection as they only represented single infection. By comparison, individuals infected with serovar D, E or F that exhibited low systemic antibody response often presented repeated C. trachomatis infections, suggesting an association with poor immune response. An in vitro neutralizing level of 60-90% was observed in the human sera against homologous serovar D and two heterologous C. trachomatis serovars E and K, compared to <40% against heterologous serovars F. Conclusion: Individuals infected with serovars D and K showed a potential association between circulating antibody response and re-infection risk. While the patients infected with serovars E showed a disconnection between systemic antibody response and re-infection risk

A retrospective cohort study examining STI testing and perinatal records demonstrates reproductive health burden of chlamydia and gonorrhea.

Adverse reproductive health outcomes, such as pelvic inflammatory disease, ectopic pregnancy, and tubal factor infertility, have been associated with Chlamydia trachomatis and Neisseria gonorrhoea infections. These reproductive health outcomes could be complemented by measuring subsequent pregnancies to assess impact on fertility. The study design was a cohort study of women in Queensland (QLD), Australia, using data linkage methods to link chlamydia and/or gonorrhea testing records (including an unexposed group undergoing full blood count tests) (2000 and 2005) with the QLD Perinatal Registry (2000 to 2013). The cohort included 132 962 women, with 69 533 records of pregnancies. Women in the exposed group, with no prior pregnancy, had a reduced odds of a pregnancy during the follow up of the study (20 year old (at 2005) aOR 0.91 95% CI 0.87-0.95, and 25 year old aOR 0.71 95% CI 0.68-0.75). Women in the exposed group with a prior pregnancy had increased odds of pregnancy during the follow up of the study (20 year old (at 2005) aOR 1.72 95% CI 1.59-1.86, and 25 year old aOR 1.35 95% CI 1.26-1.45). Our data provides further evidence at a population level of the significant impact on reproductive outcomes associated with chlamydia and gonorrhea

A cohort study of Chlamydia trachomatis treatment failure in women: A study protocol

Background: Chlamydia trachomatis is the most commonly diagnosed bacterial sexually transmitted infection in the developed world and diagnosis rates have increased dramatically over the last decade. Repeat infections of chlamydia are very common and may represent re-infection from an untreated partner or treatment failure. The aim of this cohort study is to estimate the proportion of women infected with chlamydia who experience treatment failure after treatment with 1 gram azithromycin.Methods/design: This cohort study will follow women diagnosed with chlamydia for up to 56 days post treatment. Women will provide weekly genital specimens for further assay. The primary outcome is the proportion of women who are classified as having treatment failure 28, 42 or 56 days after recruitment. Comprehensive sexual behavior data collection and the detection of Y chromosome DNA and high discriminatory chlamydial genotyping will be used to differentiate between chlamydia re-infection and treatment failure. Azithromycin levels in high-vaginal specimens will be measured using a validated liquid chromatography - tandem mass spectrometry method to assess whether poor azithromycin absorption could be a cause of treatment failure. Chlamydia culture and minimal inhibitory concentrations will be performed to further characterize the chlamydia infections. Discussion: Distinguishing between treatment failure and re-infection is important in order to refine treatment recommendations and focus infection control mechanisms. If a large proportion of repeat chlamydia infections are due to antibiotic treatment failure, then international recommendations on chlamydia treatment may need to be re-evaluated. If most are re-infections, then strategies to expedite partner treatment are necessary. © 2013 Hocking et al.; licensee BioMed Central Ltd

In vitro susceptibility of recent Chlamydia trachomatis clinical isolates to the CtHtrA inhibitor JO146

© 2015 Institut Pasteur. The present study aimed to establish if a previously identified Chlamydia trachomatis HtrA (CtHtrA) inhibitor, JO146, is effective against currently circulating clinical isolates to validate if CtHtrA is a clinically relevant target for future therapeutic development. Inhibition of CtHtrA during the middle of the chlamydial replicative cycle until the completion of the cycle resulted in loss of infectious progeny for six unique clinical isolates representing different serovars. This supports the potential for CtHtrA to be a clinically relevant target for development of new therapeutics and suggests the importance of further investigation of JO146 as a lead compound

Detection of Chlamydia trachomatis mRNA using digital PCR as a more accurate marker of viable organism

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Spontaneous resolution of urogenital Chlamydia trachomatis (CT) without treatment has previously been described, but a limitation of these reports is that DNA or RNA-based amplification tests used do not differentiate between viable infection and non-viable DNA. We modified a previously published CT mRNA detection (omp2) method to differentiate between viable infection and non-viable DNA in a sample of CT DNA PCR positive women. We modified a CT mRNA detection (omp2) method from reverse transcriptase qPCR (RTqPCR) to digital PCR (dPCR) and evaluated it in samples from CT DNA positive women. Firstly, CT infected McCoy B cells treated with azithromycin in vitro identified detectable mRNA levels disappeared <2 days, while DNA persisted up to 6 days. We used 55 self-collected vaginal swabs from a cohort of women diagnosed as DNA positive for chlamydia obtained pre- and 7 days of post-azithromycin treatment. Concordance with DNA results was higher for dPCR than RTqPCR (74.5% versus 65.5%). At visit 1, there was a strong linear relationship between DNA and mRNA (r = 0.9, p < 0.000); 24 samples had both mRNA and DNA detected (82.8%) and 5 had only DNA detected with a potential false positive proportion of 17.2% (95%CI: 5.8, 35.8). At visit 2, there was poor correlation between DNA and mRNA (r = 0.14, p = 0.55); eight specimens had only DNA detected (42.1%; 95%CI: 20.25, 66.50) and one had mRNA detected. DNA detection methods alone may detect non-viable DNA. Consideration should be given to further develop mRNA assays as ancillary tests to improve detection of viable chlamydia

Trends in chlamydia and gonorrhea positivity among heterosexual men and men who have sex with men attending a large urban sexual health service in Australia, 2002-2009

<p>Abstract</p> <p>Background</p> <p>To determine whether chlamydia positivity among heterosexual men (MSW) and chlamydia and gonorrhea positivity among men who have sex with men (MSM), are changing.</p> <p>Methods</p> <p>Computerized records for men attending a large sexual health clinic between 2002 and 2009 were analyzed. Chlamydia and gonorrhea positivity were calculated and logistic regression used to assess changes over time.</p> <p>Results</p> <p>17769 MSW and 8328 MSM tested for chlamydia and 7133 MSM tested for gonorrhea. In MSW, 7.37% (95% CI: 6.99-7.77) were chlamydia positive; the odds of chlamydia positivity increased by 4% per year (OR = 1.04; 95% CI: 1.01-1.07; p = 0.02) after main risk factors were adjusted for. In MSM, 3.70% (95% CI: 3.30-4.14) were urethral chlamydia positive and 5.36% (95% CI: 4.82-5.96) were anal chlamydia positive; positivity could not be shown to have changed over time. In MSM, 3.05% (95% CI: 2.63-3.53) tested anal gonorrhea positive and 1.83% (95% CI: 1.53-2.18) tested pharyngeal gonorrhea positive. Univariate analysis found the odds of anal gonorrhea positivity had decreased (OR = 0.93; 95% CI: 0.87-1.00; p = 0.05), but adjusting for main risk factors resulted in no change. Urethral gonorrhea cases in MSM as a percentage of all MSM tested for gonorrhea also fell (p < 0.001).</p> <p>Conclusions</p> <p>These data suggest that chlamydia prevalence in MSW is rising and chlamydia and gonorrhea prevalence among MSM is stable or declining. High STI testing rates among MSM in Australia may explain differences in STI trends between MSM and MSW.</p

Sexually transmitted infections: challenges ahead.

: WHO estimated that nearly 1 million people become infected every day with any of four curable sexually transmitted infections (STIs): chlamydia, gonorrhoea, syphilis, and trichomoniasis. Despite their high global incidence, STIs remain a neglected area of research. In this Commission, we have prioritised five areas that represent particular challenges in STI treatment and control. Chlamydia remains the most commonly diagnosed bacterial STI in high-income countries despite widespread testing recommendations, sensitive and specific non-invasive testing techniques, and cheap effective therapy. We discuss the challenges for chlamydia control and evidence to support a shift from the current focus on infection-based screening to improved management of diagnosed cases and of chlamydial morbidity, such as pelvic inflammatory disease. The emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae is globally recognised. We review current and potential future control and treatment strategies, with a focus on novel antimicrobials. Bacterial vaginosis is the most common vaginal disorder in women, but current treatments are associated with frequent recurrence. Recurrence after treatment might relate to evidence that suggests sexual transmission is integral to the pathogenesis of bacterial vaginosis, which has substantial implications for the development of effective management approaches. STIs disproportionately affect low-income and middle-income countries. We review strategies for case management, focusing on point-of-care tests that hold considerable potential for improving STI control. Lastly, STIs in men who have sex with men have increased since the late 1990s. We discuss the contribution of new biomedical HIV prevention strategies and risk compensation. Overall, this Commission aims to enhance the understanding of some of the key challenges facing the field of STIs, and outlines new approaches to improve the clinical management of STIs and public health.<br/

Chlamydial clinical isolates show subtle differences in persistence phenotypes and growth in vitro

Urogenital Chlamydia trachomatis infection is the most common sexually transmitted bacterial infection throughout the world. While progress has been made to better understand how type strains develop and respond to environmental stress in vitro, very few studies have examined how clinical isolates behave under similar conditions. Here, we examined the development and persistence phenotypes of several clinical isolates, to determine how similar they are to each other, and the type strain C. trachomatis D/UW-3/Cx. The type strain was shown to produce infectious progeny at a higher magnitude than each of the clinical isolates, in each of the six tested cell lines. All chlamydial strains produced the highest number of infectious progeny at 44 h post-infection in the McCoy B murine fibroblast cell line, yet showed higher levels of infectivity in the MCF-7 human epithelial cell line. The clinical isolates were shown to be more susceptible than the type strain to the effects of penicillin and iron deprivation persistence models in the MCF-7 cell line. While subtle differences between clinical isolates were observed throughout the experiments conducted, no significant differences were identified. This study reinforces the importance of examining clinical isolates when trying to relate in vitro data to clinical outcomes, as well as the importance of considering the adaptations many type strains have to being cultured in vitro.</jats:p

The experience of providing young people attending general practice with an online risk assessment tool to assess their own sexual health risk

<p>Abstract</p> <p>Background</p> <p>Targeted chlamydia screening has been advocated to reduce chlamydia associated reproductive sequelae. General practitioners are well positioned to play a major role in chlamydia control. The primary aim of this pilot study was to measure the effect of offering an online sexual health assessment tool, <it>Youth Check Your Risk</it>, on chlamydia testing rates among young people attending general practices. The secondary aim was to test the acceptability of the tool among general practitioners and young people.</p> <p>Methods</p> <p>General practitioners at three practices in Melbourne, Australia, referred patients aged 16 to 24 years to <it>Youth Check Your Risk </it><url>http://www.checkyourrisk.org.au</url> for use post-consultation between March to October 2007. The proportion of young people tested for chlamydia before and during the implementation of the tool was compared. Acceptability was assessed through a structured interviewer-administered questionnaire with general practitioners, and anonymous online data provided by <it>Youth Check Your Risk </it>users.</p> <p>Results</p> <p>The intervention did not result in any significant increases in the proportion of 16 to 24 year old males (2.7% to 3.0%) or females (6.3% to 6.4%) tested for chlamydia. A small increase in the proportion of 16 to 19 year old females tested was seen (4.1% to 7.2%). Of the 2997 patients seen during the intervention phase, 871 (29.1%) were referred to <it>Youth Check Your Risk </it>and 120 used it (13.8%). Major reasons for low referral rates reported by practitioners included lack of time, discomfort with raising the issue of testing, and difficulty in remembering to refer patients.</p> <p>Conclusion</p> <p>Offering an online sexual risk assessment tool in general practice did not significantly increase the proportion of young people tested for chlamydia, with GPs identifying a number of barriers to referring young people to <it>Youth Check Your Risk</it>. Future interventions aimed at increasing chlamydia screening in general practice with the aid of an online risk assessment tool need to identify and overcome barriers to testing.</p