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Key Points Chlamydia spp. are obligate intracellular pathogens that are important causes of human and animal diseases. Chlamydiae share a common developmental cycle in which they alternate between the extracellular, infectious elementary body and the intracellular, non-infectious reticulate body. Chlamydiae use several redundant mechanisms to enter host cells and to establish their intracellular membrane bound niche — the inclusion. Chlamydiae deliver effector proteins into the inclusion membrane and into host cells to promote replication and survival. Chlamydiae encode a unique set of T3SS effectors, the inclusion membrane proteins (Incs), which are inserted into the inclusion membrane where they may function as structural determinants of the membrane or as scaffolds to interface with various cell pathways in the host. Recent studies have solved the 'chlamydial anomaly' and reveal that Chlamydia spp. do synthesize peptidoglycan and use an atypical mechanism of cell division. The recent major advances in chlamydial genetics open the door for the development of tools and avenues of research that were not previously accessible to this historically intractable pathogen. Chlamydia spp. are intracellular bacteria that depend on the host for their metabolic requirements, while hiding from host immune defences. In this Review, Elwell, Mirrashidi and Engel detail the molecular mechanisms that enable these pathogens to shape and thrive in their niche in host cells. Chlamydia spp. are important causes of human disease for which no effective vaccine exists. These obligate intracellular pathogens replicate in a specialized membrane compartment and use a large arsenal of secreted effectors to survive in the hostile intracellular environment of the host. In this Review, we summarize the progress in decoding the interactions between Chlamydia spp. and their hosts that has been made possible by recent technological advances in chlamydial proteomics and genetics. The field is now poised to decipher the molecular mechanisms that underlie the intimate interactions between Chlamydia spp. and their hosts, which will open up many exciting avenues of research for these medically important pathogens.

ABSTRACT Chlamydiae are pathogenic intracellular bacteria that cause a wide variety of diseases throughout the globe, affecting the eye, lung, coronary arteries and female genital tract. Rather than by direct cellular toxicity, Chlamydia infection generally causes pathology by inducing fibrosis and scarring that is largely mediated by host inflammation. While a robust immune response is required for clearance of the infection, certain elements of that immune response may also damage infected tissue, leading to, in the case of female genital infection, disease sequelae such as pelvic inflammatory disease, infertility and ectopic pregnancy. It has become increasingly clear that the components of the immune system that destroy bacteria and those that cause pathology only partially overlap. In the ongoing quest for a vaccine that prevents Chlamydia-induced disease, it is important to target mechanisms that can achieve protective immunity while preventing mechanisms that damage tissue. This review focuses on mouse models of genital Chlamydia infection and synthesizes recent studies to generate a comprehensive model for immunity in the murine female genital tract, clarifying the respective contributions of various branches of innate and adaptive immunity to both host protection and pathogenic genital scarring. This review summarizes mouse model studies that significantly contributed to our current understanding of the protective and pathogenic immune responses taking place during genital Chlamydia infections.

ABSTRACT Chlamydia trachomatis is the most commonly reported sexually transmitted infection in the United States. The high prevalence of infection and lack of a vaccine indicate a critical knowledge gap surrounding the host's response to infection and how to effectively generate protective immunity. The immune response to C. trachomatis is complex, with cells of the adaptive immune system playing a crucial role in bacterial clearance. Here, we discuss the CD4+ and CD8+ T cell response to Chlamydia, the importance of antigen specificity and the role of memory T cells during the recall response. Ultimately, a deeper understanding of protective immune responses is necessary to develop a vaccine that prevents the inflammatory diseases associated with Chlamydia infection. Here, the authors review the functions by which T cells limit Chlamydia trachomatis infections as well as the ways this pathogen inhibits T cell immunity.

This presentation will honor the distinguished career of Julius Schachter, PhD, whose untimely passing due to COVID-19 in December 2020 left a major gap in the STD/HIV field. We will review the career highlights of our eminent colleague in the field of chlamydia microbiology, novel diagnostics, epidemiology, and their application to national and international program policies for chlamydia prevention.

BackgroundReinfection after treatment for chlamydia is common and increases the risk of reproductive complications, particularly for women. Australian guidelines recommend retesting at 3 months after chlamydia treatment to identify reinfection. There are limited data about chlamydia retesting in Australia’s mainstream primary care setting, general practice. We investigated retesting patterns among young people treated for chlamydia infection in regional Australian general practice clinics during 2010–2015.MethodsChlamydia testing and attendance data for 16–29-year-olds attending 128 regional general practices were collected for a chlamydia testing intervention trial. Rates of retesting within recommended timeframes (defined as 6-weeks-6-months after an individual’s first positive chlamydia test) were calculated. We examined factors associated with retesting using logistic regression models adjusting for patient sex and age-group and clustered by clinic.ResultsA total of 2357 individuals (68.7% female) with a first positive chlamydia result formed the study population. In the following 6-weeks-6-months, 26.5% (95% CI 24.3–28.7) re-attended and were retested; 11.9% had a positive retest and positivity at retest was higher for males (19.2%, 95%CI 14.1–25.6) than females (10%, 95%CI 9.3–15.0). A further 39.1% (95% CI 36.1–42.2) re-attended but were not retested and 34.4% (95% CI 31.7–37.2) did not re-attend. Multivariable analysis showed that retesting was more likely for women (adjusted odds ratio (AOR) 2.23, 95% CI 1.79–2.79) and in intervention clinics (AOR 1.33; 95%CI 1.07–1.64,) and that individuals aged 20–24 years were less likely (AOR 0.73; 95%CI 0.59–0.92) to be retested than 16–19-year-olds.ConclusionsRates of retesting within recommended timeframes were low and there were missed opportunities for retesting. Age and sex differences in retesting and clinics highlight the need for processes within clinics and patient focused strategies to promote reattendance and retesting. High reinfection rates further highlight the importance of retesting for timely reinfection detection and treatment.

BackgroundPharyngeal Chlamydia trachomatis (CT) in women might possibly contribute to autoinoculation to own genital or rectal site and transmission to sexual partners. Isolated pharyngeal CT (without concurrent anogenital CT) is most relevant as this is not coincidentally treated with concurrent anogenital infections. By comparing different testing scenarios, this study aims to inform testing policy and practice.MethodsSurveillance data in women from all Dutch STI clinics between 2008 and 2017 were used (n=541,945 consultations). The pharyngeal CT positivity rate was compared between routine universal testing (>85% tested pharyngeally per clinic-year) and selective testing (5–85%). Missed cases were calculated by extrapolating the proportion positive found by routine universal testing to all selectively tested women. Multivariable generalized estimating equations analyses were used to assess independent risk factors for pharyngeal CT.ResultsRoutine universal oropharyngeal testing was performed in 9.5% (51,293/541,945) of all consultations in women. Pharyngeal CT positivity was lower using routine universal testing (2.4%, 95%CI 2.2–2.5, 1,081/45,774) compared to selective testing (2.9%, 95%CI 2.8–3.0, 3,473/121,262, P<0.001). Hypothetically, selective testing would have missed 64.4% (95%CI 63.5%-65.3%, 6363/9879) of the estimated total of pharyngeal CT cases. The proportion isolated pharyngeal CT was comparable between routinely universally tested women (22.9%) and selectively tested women (20.4%, P=0.07). When using risk factors independently associated with pharyngeal CT as testing indicators, 79.6% of women would be tested finding 80.6% infections.ConclusionNo optimal testing scenario was found for pharyngeal CT, in which only a selection of high-risk women needs to be tested to find most pharyngeal CT cases. The relative low prevalence of isolated pharyngeal CT assessed in this large study and probably limited clinical and public health impact of pharyngeal CT in women do not provide support for routine universal testing.

BackgroundMasturbation is a common sexual practice and saliva is often used as a lubricant. To date, research into the role of oropharynx and saliva in the transmission of Chlamydia trachomatis is limited. We developed three deterministic, population-level, susceptible-infected- susceptible compartmental models to explore the role saliva as a lubricant for both solo and partnered masturbation plays in the transmission of Chlamydia trachomatis at multiple anatomical sites among men who have sex with men (MSM).MethodsOur first model did not include masturbation but included the basic transmission routes (anal sex, oral-penile sex, rimming, kissing and sequential sexual practices) we have previously validated in a published transmission model (Model 1). In model 2, we considered masturbation as a transmission route in addition to Model 1. We used data from five different local and international studies to calibrate the model. We evaluated the model 1 and 2 using the Root Mean Squared Error (RMSE) and then evaluated the magnitude of the effect using Cohen’s d statistic.ResultsModel 2 had significantly higher RMSE values than model 1 (p-value <0.01) for all five datasets, and in four datasets the effect size was large (Cohen’s d > 0.8). Using the five data sets, model 2 generated an incidence of chlamydia caused by masturbation from 3.9% (95%CI 2.0 to 6.8) to 7.8% (95%CI 4.3 to 15.6) which was primarily due to solo masturbation (estimates of 3.5% (95%CI 1.7 to 6.1) to 7.1% (95%CI 4.0 to 13.1)) with little contribution from partnered masturbation (estimates of 0.3% (95%CI 0.0 to 1.5) to 0.7% (95%CI 0.1 to 4.0)).ConclusionsOur model suggests that saliva use as a lubricant for solo/partnered masturbation plays a negligible a role in chlamydia transmission in MSM.

We report avian Chlamydia abortus pneumonia in an immunocompetent elderly patient in the Netherlands after environmental exposure to wild aquatic birds, including seabirds. New molecular surveillance studies are needed in wild and captive birds, as well as increased awareness to establish occurrence, clinical manifestations, and geographic distribution of this rare zoonotic disease.

Screening for bacterial STIs, in particular chlamydia, is common in high income countries using a variety of different approaches. However, recent reductions in funding for STI treatment services in several countries highlight the need to ensure that investment in screening remains appropriate and cost-effective. The evidence base for chlamydia screening suggests that it can reduce the incidence of pelvic inflammatory disease but with several caveats, and it remains unclear whether screening represents good value for money. In particular, the opportunity cost of choosing screening over other sexual health interventions requires consideration. Harms have been poorly characterised but need to be addressed when measuring the potential value of a screening program. Overall, the evidence for broad population based screening is limited and new approaches are needed to reduce the morbidity and reproductive sequelae associated with bacterial STIs.DisclosureNo significant relationships.

BackgroundSpontaneous resolution (clearance) of Chlamydia trachomatis (CT) infections can occur between diagnosis by nucleic acid amplification assays (NAAT) and treatment. Moreover, viability polymerase chain reaction (V-PCR) techniques showed that part of non-resolved NAAT positives represent non-viable CT. This may impact clinic policies aiming to restrict antibiotic treatment (i.e. to viable CT only). We followed 560 CT diagnosed women to assess the proportion without viable CT at follow-up, and associated risk factors.MethodsVaginal (vCT) or rectal (rCT) NAAT positive adult women, negative for HIV, syphilis and Neisseria gonorrhoeae, who not recently used antibiotics, were included at three STI outpatient-clinics (Netherlands, 2016–2017; FemCure). At clinic-diagnosis women were (a) vCT positive, rCT untested (n=351), (b) vCT, rCT positive (n=155), (c) vCT positive, rCT negative (n=25), (d) vCT negative, rCT positive (n=29). After a median of 8 [IQR:7–12] days, before treatment, samples were tested using NAAT and V-PCR. We present percentages of women without viable CT at follow-up, and tested which factors (group [a-d], age, education, non-western-background, symptoms, anal/vaginal sex, sexpartners) were associated, using logistic regression.ResultsAt follow-up, percentages of women NAAT negative at both anatomic sites were 5.4% (a), 0.6% (b), 32.0% (c), and 27.6% (d). Percentages of women without viable CT (i.e. NAAT negative or NAAT positive and V-PCR undetectable) at both anatomic sites were 9.4% (33/351, a), 3.9% (6/155, b), 52.0% (13/25, c), and 41.4% (12/29, d). Alongside group (p<0.001), older age was independently associated (odds ratio: 1.07 per year (95%CI: 1.01–1.13; p=0.029) with lack of viable CT.ConclusionLess than ten percent of STI-clinic women diagnosed with vaginal and rectal CT (or were rectally untested) did not have viable CT one week after diagnosis (when they return for treatment). Yet, this percentage was higher in women with single vaginal or rectal infection and in older women; this may affect treatment-choices.DisclosureNo significant relationships.