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Chlamydia is a group of zoonotic diseases caused by Chlamydiaceae spp., which carries high potential risks for animal welfare, public health and animal husbandry. The application of effective vaccines for livestock is still one of the major important tools of managing Chlamydia infection. In this study, the main characteristics of the currently available Russian commercial inactivated whole-cell mono-, polyvalent, and combination vaccines for the prevention of either a single Chlamydia infection (monoinfection) or multi-pathogen infection in livestock, cattle, small ruminants, pigs, farm birds, and fur animals are briefly reviewed. All of the vaccines are inactivated, absolutely safe for the immunization of target livestock and naive untreated contacting animals in the same herd and produce no documented serious vaccine-related complications. Since chlamydia has not yet been eradicated in the world, the infection persists in nature and can be transmitted from infected livestock, wild, domestic animals, and migratory birds to unprotected farm animals. Thus, the availability of effective and safe chlamydia vaccines remains an important aspect for the prevention and control over Chlamydia infection in Russian Federation and worldwide. [ABSTRACT FROM AUTHOR]

We applied lymphogranuloma venereum (LGV) clinical case criteria to a cohort of 1381 Veterans positive for HIV and Chlamydia trachomatis (CT) from 2016 from 2023 and analyzed variables to ascertain risk factors for LGV and factors associated with the use of standard treatment regimens. In total, 284/1381 (20.6%) met the criteria for LGV. A total of 179/284 (63%) were probable cases, and 105/284 (37%) were possible cases (those meeting clinical criteria but with concurrent sexually transmitted infections (STI) associated with LGV-like symptoms). None had confirmatory CT L1–L3 testing. A total of 230 LGV cases (81%) presented with proctitis, 71 (25%) with ulcers, and 57 (20.1%) with lymphadenopathy. In total, 66 (23.2%) patients had >1 symptom of LGV. A total of 43 (15%) LGV cases were hospitalized. Primary risk factors for LGV were male birth sex (p = 0.004), men who have sex with men (p < 0.001), and the presence of STIs other than gonorrhea or syphilis (p = 0.011). In total, 124/284 (43.7%) LGV cases received standard recommended treatment regimens. Probable cases were more likely to receive standard treatment than possible cases (p = 0.003). We report that 20.6% of CT cases met clinical criteria for LGV among HIV-infected Veterans and that less than half of cases received recommended treatment regimens, indicating that LGV is likely underestimated and inadequately treated among this US population. [ABSTRACT FROM AUTHOR]

Sexually transmitted infections (STIs) are socially significant diseases and require close attention due to the multifactorial causes that influence their spread. In 2012–2022, the Russian Federation maintained a downward trend in the incidence of STIs (from 267.6 to 91.3 cases per 100 thousand population), established since 1998 in all age groups. In 2022, compared to 2012, the incidence rates decreased: syphilis — by 42.7%; gonococcal infection — by 77.7%; trichomoniasis — by 75.8%; chlamydial infections — by 72.1%; anogenital herpetic infection — by 51.2%; anogenital (venereal) warts — by 36.5%. But at the same time, in 2021 and 2022, there was an increase in the incidence of syphilis and gonococcal infection: compared to 2019, the increase in the incidence of syphilis was 25.9%, and that of gonococcal infection — 5.2%. The increase in the incidence of syphilis was largely due to an increase in this indicator in the Central (from 18.1 to 37.3 cases per 100 thousand population) and Northwestern (from 14.5 to 16.2 cases per 100 thousand population) federal districts ( FO). An increase in the incidence of gonococcal infection in 2022 compared to 2019 was observed in the Central (+26.3%), Northwestern (+31.2%) and Ural (+27.6%) Federal Districts.

Abstract The uterus is a unique mucosal site where immune responses are balanced to be permissive of a fetus, yet protective against infections. Regulation of natural killer (NK) cell responses in the uterus during infection is critical, yet no studies have identified uterine-specific factors that control NK cell responses in this immune-privileged site. We show that the constitutive expression of IFNε in the uterus plays a crucial role in promoting the accumulation, activation, and IFNγ production of NK cells in uterine tissue during Chlamydia infection. Uterine epithelial IFNε primes NK cell responses indirectly by increasing IL-15 production by local immune cells and directly by promoting the accumulation of a pre-pro-like NK cell progenitor population and activation of NK cells in the uterus. These findings demonstrate the unique features of this uterine-specific type I IFN and the mechanisms that underpin its major role in orchestrating innate immune cell protection against uterine infection.

The uterus is a unique mucosal site where immune responses are balanced to be permissive of a fetus, yet protective against infections. Regulation of natural killer (NK) cell responses in the uterus during infection is critical, yet no studies have identified uterine-specific factors that control NK cell responses in this immune-privileged site. We show that the constitutive expression of IFNε in the uterus plays a crucial role in promoting the accumulation, activation, and IFNγ production of NK cells in uterine tissue during Chlamydia infection. Uterine epithelial IFNε primes NK cell responses indirectly by increasing IL-15 production by local immune cells and directly by promoting the accumulation of a pre-pro-like NK cell progenitor population and activation of NK cells in the uterus. These findings demonstrate the unique features of this uterine-specific type I IFN and the mechanisms that underpin its major role in orchestrating innate immune cell protection against uterine infection. Synopsis: IFNε promotes the accumulation, activation and IFNγ production of NK cells in the uterus through both IL-15-dependent and -independent mechanisms. IFNε-mediated NK cell responses protect against Chlamydia FRT infections. IFNε is produced exclusively by reproductive tract epithelial cells and acts in the uterus to increase IL-15 production by myeloid cells. IFNε and IL-15 production in the uterus increases NK cell haematopoiesis in the bone marrow, increasing NK cell numbers systemically, and NK cell accumulation in the uterus. IFNε acts directly on pre-pro NK cell progenitors in the uterus, promoting their accumulation. IL-15 has no effect on this population. Local production of IFNε in the uterus is required for optimal NK cell activation during infection and IFNε directly increases NK cell CD69 expression ex vivo. IL-15 production downstream of IFNε is responsible for promoting NK cell IFNγ production and cytolytic activity. IFNε and IL-15 co-stimulate and are required in concert for full NK cell function. IFNε promotes the accumulation, activation and IFNγ production of NK cells in the uterus through both IL-15-dependent and -independent mechanisms. IFNε-mediated NK cell responses protect against Chlamydia FRT infections. [ABSTRACT FROM AUTHOR]

Background: Chlamydia trachomatis (CT) is one of the most prevalent sexually transmitted infections, causing genital tract infections and infertility. Defensins have an immunomodulatory function and play an important role in sperm maturation, motility, and fertilization. DEFB126 is present on ejaculated spermatozoa and is essential for them to pass through the female reproductive tract. The purpose of the study was to determine the frequency of the 2-nt deletion of the DEFB126 (rs11467417) in Iranian infertile males with a recurrent history of CT. Methods: Semen samples of 1080 subfertile males were investigated. Among patients who had CT-positive results, sperm DNA from 50 symptomatic and 50 asymptomatic patients were collected for the DEFB126 genotype analysis. Additionally, a control group comprising 100 DNA samples from individuals with normal spermogram and testing negative for CT was included in the study. The PCR-sequencing for detecting the 2-nt deletion of the second exon of the DEFB126 was performed. Results: The Chi-squared test comparing all three groups revealed no significant difference across the different genotypes. Moreover, no significant difference between the symptomatic and asymptomatic groups was seen. However, analysis within CT-positive patients and controls demonstrated significant difference between the frequencies of homozygous del/del. Conclusion: The higher frequency of the 2-nt deletion of the DEFB126 in CT- positive patients suggests that the occurrence of mutations in the DEFB-126 may cause the impairment of the antimicrobial activity of the DEFB126 protein and consequently makes individuals more susceptible to infections such as CT. [ABSTRACT FROM AUTHOR]

Prospective mothers who are at risk of aortic problems face difficulties. AOD may indicate aortic disease in certain pregnant women. Refer them to a tertiary care facility for delivery treatment and pregnancy monitoring. Current medications must not cause birth defects or teratogenicity. In the second and third trimesters, several medications may induce foetal central nervous system toxicity. Pregnant women change medically and physically to help their child. All organs are affected by these post-conception changes. Extra oxygen is required during a normal pregnancy. This is due to a 15% rise in metabolic rate and a 20% increase in oxygen demand. Tidal volume has increased minute ventilation by 40-50%, but respiratory rate has risen. Hyperventilation by the mother raises arterial pO2, decreases pCO2, and lowers serum bicarbonate to 18-22 mmol/l. With early pregnancy insulin-secreting beta-cell hyperplasia, insulin sensitivity and secretion increase, followed by insulin resistance. Early experiences and exposures have long been researched in the developmental sciences to see how they impact later development in individuals and among people. They contend that healthy development does not begin at birth. Pregnant and non-pregnant women are both affected by ischemic heart disease. Hypertension, high cholesterol, high triglycerides, diabetes, obesity, smoking, and inactivity are all risk factors for ischemic heart disease. When the embryo implants outside the uterus, this is known as an ectopic pregnancy. Despite the fact that stomach pain and vaginal bleeding are frequent, only half of women experience them. The pain might be minor, severe, or unbearable. Ectopic pregnancies account for fewer than 2% of all pregnancies worldwide. Ectopic pregnancies may occur as a consequence of chlamydia infection, smoking, tubal ligation, infertility, or assisted reproductive technology. [ABSTRACT FROM AUTHOR]

We applied lymphogranuloma venereum (LGV) clinical case criteria to a cohort of 1381 Veterans positive for HIV and Chlamydia trachomatis (CT) from 2016 from 2023 and analyzed variables to ascertain risk factors for LGV and factors associated with the use of standard treatment regimens. In total, 284/1381 (20.6%) met the criteria for LGV. A total of 179/284 (63%) were probable cases, and 105/284 (37%) were possible cases (those meeting clinical criteria but with concurrent sexually transmitted infections (STI) associated with LGV-like symptoms). None had confirmatory CT L1–L3 testing. A total of 230 LGV cases (81%) presented with proctitis, 71 (25%) with ulcers, and 57 (20.1%) with lymphadenopathy. In total, 66 (23.2%) patients had >1 symptom of LGV. A total of 43 (15%) LGV cases were hospitalized. Primary risk factors for LGV were male birth sex (p = 0.004), men who have sex with men (p < 0.001), and the presence of STIs other than gonorrhea or syphilis (p = 0.011). In total, 124/284 (43.7%) LGV cases received standard recommended treatment regimens. Probable cases were more likely to receive standard treatment than possible cases (p = 0.003). We report that 20.6% of CT cases met clinical criteria for LGV among HIV-infected Veterans and that less than half of cases received recommended treatment regimens, indicating that LGV is likely underestimated and inadequately treated among this US population.

India has one of the largest numbers of men who have sex with men (MSM) globally; however, geographic data on sexually transmitted infection (STI) prevalence and associations with sexual behavior are limited. Six-hundred and eight MSM in Chennai and Mumbai underwent screening for a behavioral trial and were assessed for bacterial STIs (syphilis, chlamydia, gonorrhea), HIV, and past-month self-reported condomless anal sex (CAS). Mumbai (37.8%) had a greater prevalence of any STI than Chennai (27.6%) (prevalence ratio [PR] = 1.37, 95% CI: 1.09, 1.73). This pattern also emerged for gonorrhea and chlamydia separately but not syphilis. Conversely, Mumbai MSM reported lower rates of CAS (mean = 2.2) compared to Chennai MSM (mean = 14.0) (mean difference = -11.8, 95% CI: -14.6, -9.1). The interaction of city by CAS on any STI prevalence (PR = 2.09, 95% CI: 1.45, 3.01, p

ObjectivesRectal douching/enema (RD) is a common practice among men who have sex with men (MSM) in preparation for sex. RD can break down the rectal mucosal barrier and potentially affect the rectal microbiome. The objective of this study was to understand if RD is associated with acquiring rectal infections (RI) with rectal gonorrhoea (NG) and/or chlamydia (CT).MethodsFrom 2013 to 2015, 395 adult HIV-uninfected MSM were enrolled in a randomised controlled study for pre-exposure prophylaxis (PrEP) adherence with routine sexual risk survey and testing. Using data from this cohort, baseline differences by RI were assessed using Pearson's χ² and Wilcoxon-Mann-Whitney test. Association between RD and RI was modelled using multivariable logistic regression adjusted for potential confounders (sexual behaviour, substance use and age) selected a priori. Effect modification by number of male partners and sensitivity analysis to rule out reverse causality were also conducted.ResultsOf 395 participants, 261 (66%) performed RD and 133 (33%) had at least one NG/CT RI over 48 weeks. Number of condomless anal receptive sex (med: 4, p

BackgroundPre-exposure prophylaxis (PrEP) is an effective method for reducing HIV incidence among at-risk populations. However, concerns exist over the potential for an increase in STIs following PrEP initiation. The objective of this study is to compare the STI incidence before and after PrEP initiation within subjects among a cohort of men who have sex with men in Los Angeles, California.MethodsThe present study used data from patients who initiated PrEP services at the Los Angeles LGBT Center between October 2015 and October 2016 (n=275). A generalised linear mixed model was used with a case-crossover design to determine if there was a significant difference in STIs within subjects 365 days before (before-PrEP period) and 365 days after PrEP initiation (after-PrEP period).ResultsIn a generalised linear mixed model, there were no significant differences in urethral gonorrhoea (P=0.95), rectal gonorrhoea (P=0.33), pharyngeal gonorrhoea (P=0.65) or urethral chlamydia (P=0.71) between periods. There were modest increases in rectal chlamydia (rate ratio (RR) 1.83; 95% CI 1.13 to 2.98; P=0.01) and syphilis diagnoses (RR 2.97; 95% CI 1.23 to 7.18; P=0.02).ConclusionsThere were significant increases in rectal chlamydia and syphilis diagnoses when comparing the periods directly before and after PrEP initiation. However, only 28% of individuals had an increase in STIs between periods. Although risk compensation appears to be present for a segment of PrEP users, the majority of individuals either maintain or decrease their sexual risk following PrEP initiation.

Chlamydia trachomatis, a parasitic intracellular bacterium, is a major human pathogen that causes millions of trachoma, sexually transmitted infections, and pneumonia cases worldwide. Previously, peptidomimetic inhibitors consisting of a hydrophobic dipeptide derivative exhibited significant inhibitory effects against chlamydial growth. Based on this finding, this study showed that both bortezomib (BTZ) and ixazomib (IXA), anticancer drugs characterized by proteasome inhibitors, have intensive inhibitory activity against Chlamydia. Both BTZ and IXA consisted of hydrophobic dipeptide derivatives and strongly restricted the growth of Chlamydia (BTZ, IC50 = 24 nM). In contrast, no growth inhibitory effect was observed for other nonintracellular parasitic bacteria, such as Escherichia coli. BTZ and IXA appeared to inhibit chlamydial growth bacteriostatically via electron microscopy. Surprisingly, Chlamydia-infected cells that induced a persistent infection state were selectively eliminated by BTZ treatment, whereas uninfected cells survived. These results strongly suggested the potential of boron compounds based on hydrophobic dipeptides for treating chlamydial infections, including persistent infections, which may be useful for future therapeutic use in chlamydial infectious diseases. [ABSTRACT FROM AUTHOR]

This review analyzes scientific data and systematized information regarding microbiological aspects and pathogenesis of chlamydia infection. Chlamydia are obligate intracellular microorganisms that are sensitive to any human cells where energy parasitism is possible: various types of epithelium, fibrocytes, histiocytes, glial and muscle cells, squamous epithelium of the meninges and eyeball, neurons, monocytes, macrophages. Structure, chemical composition and enzymatic activity of Chlamydia closely resemble those in Gram-negative bacteria, as they retain their morphological identity throughout the life cycle, possess cell wall, ribosomes, DNA, RNA, biochemical elements of glycolysis, tissue respiration, peptose production being sensitive to some broad-spectrum antibiotics, and are able to vegetative form division. In recent decades, the pathogenesis and clinical symptoms of chlamydial lesions in the urogenital tract, nervous, cardiovascular, musculoskeletal and bronchopulmonary systems have been actively studied, and new approaches and treatment schemes for chlamydia-infected patients are still developing. Over many decades, Chlamydia infection has been an important and urgent problem, not only due to its high prevalence, but also because of high rate of complications negatively affecting populational health and related demographic parameters. Chlamydia causes multiple diseases resulting in chronization of inflammatory process in all human organs and systems, and affects reproduction of population. Mandatory statistical recording of chlamydiosis cases introduced as early as in 1994 in the Russian Federation does not reflect the actual incidence rate. A rise in number of inflammatory diseases of the upper respiratory tract caused by Chlamydia undoubtedly increases its etiological importance, but data regarding etiopathogenetic role of Chlamydia in ENT pathology are ambiguous and contradictory. Available publications describe a large range of variation in rate of detected Chlamydia due to poor awareness of doctors about the microbiological properties of chlamydia, pathogenetic and clinical features of clinical signs of this infection, and lack of common and clear understanding on the algorithms for identifying and treating chlamydiosis. Since the majority of chlamydia-associated nosological forms are asymptomatic, knowing pathogenetic features of related will allow to prevent the spread of the infection and reduce subsequent socio-economic consequences.

ObjectivesHIV studies and risk assessments among men who have sex with men (MSM) frequently use self-reported STI history as a proxy for true STI history. The objective of our study was to assess the validity of self-reported STI history through comparison with laboratory-confirmed biomedical results.MethodsData were analysed for MSM attending the Los Angeles LGBT Center (the Center) from August 2011 to July 2015. We identified 10 529 unique MSM who received testing for chlamydia, gonorrhoea and/or syphilis and had a later visit in which they self-reported their STI history to a clinic counsellor during a risk assessment.ResultsMSM who had an STI in the past year self-reported their STI history with 51%-56% accuracy, and MSM who had an STI more than a year ago self-reported their STI history with 65%-72% accuracy. Among MSM with any positive STIs at the Center, black/African-American and Hispanic MSM were more likely to inaccurately self-report their positive results for gonorrhoea (adjusted OR (aOR): 1.48, 95% CI 1.09 to 2.01; aOR: 1.39, 95% CI 1.14 to 1.70). Additionally, HIV-positive MSM were more likely to inaccurately self-report their positive results for gonorrhoea (aOR: 1.63, 95% CI 1.22 to 2.18) and/or syphilis (aOR: 2.19, 95% CI 1.08 to 4.47).ConclusionsThis is the first study that attempts to evaluate the validity of self-reported STI history among MSM. We found that self-reported STI history may not be an appropriate proxy for true STI history in certain settings and minority populations. Clinical guidelines and research studies that rely on self-reported STI history will need to modify their recommendations in light of the limited validity of these data.

Background: We reviewed studies on the prevalence of Chlamydia infection as a risk factor for developing cervical cancer in a meta-analysis studies published in that subject area. Methods: Cochrane Library and PubMed databases were systematically searched for articles (observational and randomized controlled trials) published from 2008-2018. A meta-analysis of studies was performed to analyse the association between chlamydia infection and cervical cancer. Results: Five articles were included in the final analysis (N=5271). All five articles were case-control studies, of which three studies sampled from population-based registries. All studies involved with sexually active women with minimum 15 years old. Three studies reported the association of C. trachomatis infection cervical cancers, two other studies reported C. trachomatis-HPV co-infection in association with cervical cancer. Result showed C. trachomatis has an overall prevalence of 31.9%, pooled OR 1.96, 95% CI 1.05 to 3.67, OR 2.13, 95% CI 1.78 to 2.54 among cervical cancer. There was a mild publication bias detected at 3.0 effect estimation. Heterogeneity detected from clinical and methodological diversities particularly from C. trachomatis-HPV co-infection subgroup analysis, including sampling bias, geographical strain diversity, and different outcome endpoint measured. Conclusion: C. trachomatis infection was significantly associated with the development of cervical cancer. Co-infection of C. trachomatis-HPV with cervical cancer is plausibly sound but temporality of C. trachomatis-HPV with the development of cervical cancer need to be proven in future prospective cohort studies.

The use of systemic enzyme therapy in combination with antibiotics in the treatment of urogenital chlamydia infection in patients of both sexes proved to improve the therapeutic efficacy and to reduce the risk of the side effects.

ObjectivesDisclosure of sexually transmitted infections (STI)/HIV diagnoses to sexual partners is not mandated by public health guidelines in Mexico. To assess the feasibility of couples-based STI/HIV testing with facilitated disclosure as a risk-reduction strategy within female sex workers' (FSW) primary partnerships, we examined STI/HIV test result disclosure patterns between FSWs and their primary, non-commercial male partners in two Mexico-US border cities.MethodsFrom 2010 to 2013, 335 participants (181 FSWs and 154 primary male partners) were followed for 24 months. At semiannual visits, participants were tested for STIs/HIV and reported on their disclosure of test results from the previous visit. Multilevel logistic regression was used to identify individual-level and partnership-level predictors of cumulative (1) non-disclosure of ≥1 STI test result and (2) non-disclosure of ≥1 HIV test result within couples during follow-up.ResultsEighty-seven percent of participants reported disclosing all STI/HIV test results to their primary partners. Non-disclosure of ≥1 STI test result was more common among participants who reported an STI diagnosis as part of the study (adjusted OR=3.05, 95% CI 1.13 to 8.25), while non-disclosure of ≥1 HIV test result was more common among participants in longer-duration partnerships (AOR=1.15 per year, 95% CI 1.03 to 1.28). Drug use before/during sex within partnerships was associated with non-disclosure of both STI (AOR=5.06, 95% CI 1.64 to 15.62) and HIV (AOR=4.51, 95% CI: 1.32 to 15.39) test results.ConclusionsSTI/HIV test result disclosure was highly prevalent within FSWs' primary partnerships, suggesting couples-based STI/HIV testing with facilitated disclosure may be feasible for these and potentially other high-risk, socially marginalised couples.

Ectopic pregnancies (EPs) are potentially fatal if not recognized early. Evidence of an association with chlamydial infection in South East Asia is lacking. This case-control study aims to (i) compare chlamydial infection in women with EP to women who delivered a full-term pregnancy, (ii) investigate classical factors associated with EP, and (iii) investigate rupture status in EP. Seventy-two women with a confirmed diagnosis of EP and sixty-nine who delivered a full-term pregnancy in a tertiary hospital in Malaysia were recruited from November 2019 to January 2022. Demographic and relevant clinical data and intraoperative findings were documented. Blood samples for testing IgG levels of chlamydia were obtained. Women with EP were more likely to have tested positive for chlamydia than those with a full-term delivery (34.7% vs. 13.0%, AOR = 4.18, 95% CI = 1.67–10.48, p = 0.002). The majority did not have the classic risk factors associated with EP. An amount of 52.8% presented with a ruptured EP, with 84.2% of ruptures occurring after six weeks of gestation. An amount of 44.2% had an estimated blood loss of more than 500 cc, with 20% losing more than 1500 cc of blood. The prevalence of prior chlamydial infection in women with EP is significant enough to necessitate a review of early pregnancy care.

BackgroundGeosocial networking applications (GSN apps) used for meeting sexual partners have become increasingly popular with men who have sex with men (MSM) since 2009. The current study aimed to determine if self-identified HIV-negative, MSM clinic attendees who used GSN apps have an increased incidence of sexually transmitted infections (STI) compared to self-identified HIV-negative, MSM attendees who met sexual partners via in-person venues, such as bars or clubs or through MSM-specific hook-up websites.MethodsData were collected between August 2011 and January 2013 on all self-identified HIV-negative, MSM clients visiting the L.A. Gay & Lesbian Center for STI screening. A total of 7184 individuals tested for STIs and self-reported behaviours on drug use and social networking methods to meet sexual partners. Multivariate logistic regression models were used to analyse the results.ResultsIndividuals who used GSN apps for meeting sexual partners had greater odds of testing positive for gonorrhoea (OR: 1.25; 95% CI 1.06 to 1.48) and for chlamydia (OR: 1.37; 95% CI 1.13 to 1.65) compared to individuals who met partners through in-person methods only. There were no significant differences in syphilis and HIV incidence between those who met partners via in-person venues only, on the internet or through GSN apps.ConclusionsThe present study concludes that sexual health clinic MSM attendees who are meeting on GSN apps are at greater risk for gonorrhoea and chlamydia than MSM attendees who meet in-person or on the internet. Future interventions should explore the use of these novel technologies for testing promotion, prevention and education.

Abstract Background Genital C. trachomatis infection may cause pelvic inflammatory disease (PID) that can lead to tubal factor infertility (TFI). Understanding the pathogenesis of chlamydial complications including the pathophysiological processes within the female host genital tract is important in preventing adverse pathology. MicroRNAs regulate several pathophysiological processes of infectious and non-infectious etiologies. In this study, we tested the hypothesis that the miRNA profile of single and repeat genital chlamydial infections will be different and that these differences will be time dependent. Thus, we analyzed and compared differentially expressed mice genital tract miRNAs after single and repeat chlamydia infections using a C. muridarum mouse model. Mice were sacrificed and their genital tract tissues were collected at 1, 2, 4, and 8 weeks after a single and repeat chlamydia infections. Histopathology, and miRNA sequencing were performed. Results Histopathology presentation showed that the oviduct and uterus of reinfected mice were more inflamed, distended and dilated compared to mice infected once. The miRNAs expression profile was different in the reproductive tissues after a reinfection, with a greater number of miRNAs expressed after reinfection. Also, the number of miRNAs expressed each week after chlamydia infection and reinfection varied, with weeks eight and one having the highest number of differentially expressed miRNAs for chlamydia infection and reinfection respectively. Ten miRNAs; mmu-miR-378b, mmu-miR-204-5p, mmu-miR-151-5p, mmu-miR-142-3p, mmu-miR-128-3p, mmu-miR-335-3p, mmu-miR-195a-3p, mmu-miR-142-5p, mmu-miR-106a-5p and mmu-miR-92a-3p were common in both primary chlamydia infection and reinfection. Pathway analysis showed that, amongst other functions, the differentially regulated miRNAs control pathways involved in cellular and tissue development, disease conditions and toxicity. Conclusions This study provides insights into the changes in miRNA expression over time after chlamydia infection and reinfection, as well as the pathways they regulate to determine pathological outcomes. The miRNAs networks generated in our study shows that there are differences in the focus molecules involved in significant biological functions in chlamydia infection and reinfection, implying that chlamydial pathogenesis occurs differently for each type of infection and that this could be important when determining treatments regime and disease outcome. The study underscores the crucial role of host factors in chlamydia pathogenesis.

Chlamydia trachomatis, a parasitic intracellular bacterium, is a major human pathogen that causes millions of trachoma, sexually transmitted infections, and pneumonia cases worldwide. Previously, peptidomimetic inhibitors consisting of a hydrophobic dipeptide derivative exhibited significant inhibitory effects against chlamydial growth. Based on this finding, this study showed that both bortezomib (BTZ) and ixazomib (IXA), anticancer drugs characterized by proteasome inhibitors, have intensive inhibitory activity against Chlamydia. Both BTZ and IXA consisted of hydrophobic dipeptide derivatives and strongly restricted the growth of Chlamydia (BTZ, IC50 = 24 nM). In contrast, no growth inhibitory effect was observed for other nonintracellular parasitic bacteria, such as Escherichia coli. BTZ and IXA appeared to inhibit chlamydial growth bacteriostatically via electron microscopy. Surprisingly, Chlamydia-infected cells that induced a persistent infection state were selectively eliminated by BTZ treatment, whereas uninfected cells survived. These results strongly suggested the potential of boron compounds based on hydrophobic dipeptides for treating chlamydial infections, including persistent infections, which may be useful for future therapeutic use in chlamydial infectious diseases.

We report the complete genome sequence of the Chlamydia psittaci АМК-16, recovered from the aborted caprine fetus during a case of chlamydia infection. This 1,152,497-bp genome with 7,552-bp cryptic plasmid provides novel insights into the genetic diversity of chlamydia agent strains particularly those causing the infection in small ruminants., Competing Interests: The authors declare no conflict of interest.

Background: This case provides a rare case of Chlamydia Trachomatis presenting with ascites and granulomatous peritonitis. Case: A 23-year old gravida 0 presented as a new patient to her gynecologist with complaints of irregular menses. A pelvic ultrasound showed ascites and the ovaries appeared heterogenous with irregular borders. A CA125 was 432. The patient was taken to the operating room by gynecologic oncology for a diagnostic laparoscopy. Biopsies were taken and final pathology resulted as “diffuse granulomatous inflammation.” Post-operatively, the etiology remained unknown. The patient was brought back to the office for more testing. She tested positive for Chlamydia and was diagnosed with pelvic inflammatory disease. Conclusion: When encountering granulomatous pathology, Chlamydia Trachomatis is a rare etiology however it should be included on the differential diagnosis.

Introduction. Pipe and peritoneal factors are important causes of infertility and inflammatory diseases of the pelvic organs (PID). It is well known that Neisseria gonorrhoeae and Chlamydia trachomatis are etiologic agents of pelvic inflammation leading to infertility. There is a very limited number of publications about which representatives of sexually transmitted infections (STIs) or other microorganisms can be found in the fallopian tubes during reconstructive plastic surgery. Knowledge in this area is necessary for the proper selection of antibiotic therapy during and after operations. The purpose of our study is to determine the microbial landscape of the contents of the fallopian tubes in infertile patients with a tubal peritoneal infertility factor diagnosed during laparoscopy and normal uterine tubes. Materials and methods. 22 women with infertility were included in the study. 12 of them (the main group) had tubal peritoneal pathology, 10 women had no pathology of the fallopian tubes (control group). The average age of patients in the first group was 25 years (20-29), in the control group - 31 years (20-36). For all women, laparoscopy was part of the infertility survey. In the 1 st group, the changes in the fallopian tubes according to the type of fibrosis, hydrosalpinx or adhesions in the region of the periampulal or fimbrial part were identified. During laparoscopy, the fallopian tubes were washed with 2-4 ml of saline immediately after laparoscopic and laparoscopic instruments. Through the lateral trocar, the material was taken from the fallopian tubes using a bacteriological loop to perform bacteriological inoculation. Identification of the DNA of the pathogens was carried out by the polymerase chain reaction method according to the instructions. Identification and sensitivity determination of the isolated cultures was performed using an automatic bacteriological analyzer Vitek 2 Compact 30. Results. In all women without an identification of STIs and PID in the history and absence of abnormalities of the fallopian tubes in laparoscopy (control group), we did not find any microorganisms in the fallopian tubes. We did not detect C. trachomatis, N. gonorrhoeae or Trichomonas vaginalis in the fallopian tubes. However, we found twice Ureaplasma urealyticum in the fallopian tubes (16.7%), while in the control group this microorganism was also detected once. An important feature of salpingitis is extensive tissue remodeling, leading to chronic effects, such as scarring and obstruction, during which STIs and other microorganisms are eliminated by the immune system. In this study, we identified twice in the fallopian tubes of U. urealyticum. Perhaps U. urealyticum persists after antibiotic therapy and selective elimination of the main pathogens, since certain antibiotics affect the cell wall that is absent in this microorganism.

Chlamydia trachomatis is an obligate intracellular bacterium with a distinctive biphasic developmental cycle that alternates between two distinct cell types; the extracellular infectious elementary body (EB) and the intracellular replicating reticulate body (RB). Members of the genus Chlamydia are dependent on the formation and degradation of protein disulfide bonds. Moreover, disulfide cross-linking of EB envelope proteins is critical for the infection phase of the developmental cycle. We have identified in C. trachomatis a homologue of the Disulfide Bond forming membrane protein Escherichia coli (E. coli) DsbB (hereafter named CtDsbB) and—using recombinant purified proteins—demonstrated that it is the redox partner of the previously characterised periplasmic oxidase C. trachomatis Disulfide Bond protein A (CtDsbA). CtDsbA protein was detected in C. trachomatis inclusion vacuoles at 20 h post infection, with more detected at 32 and similar levels at 44 h post infection as the developmental cycle proceeds. As a redox pair, CtDsbA and CtDsbB largely resemble their homologous counterparts in E. coli; CtDsbA is directly oxidised by CtDsbB, in a reaction in which both periplasmic cysteine pairs of CtDsbB are required for complete activity. In our hands, this reaction is slow relative to that observed for E. coli equivalents, although this may reflect a non-native expression system and use of a surrogate quinone cofactor. CtDsbA has a second non-catalytic disulfide bond, which has a small stabilising effect on the protein’s thermal stability, but which does not appear to influence the interaction of CtDsbA with its partner protein CtDsbB. Expression of CtDsbA during the RB replicative phase and during RB to EB differentiation coincided with the oxidation of the chlamydial outer membrane complex (COMC). Together with our demonstration of an active redox pairing, our findings suggest a potential role for CtDsbA and CtDsbB in the critical disulfide bond formation step in the highly regulated development cycle. [ABSTRACT FROM AUTHOR]

Sexually transmitted infections (STIs) remain a worldwide problem and a severe threat to public health. The purpose of this study was to compare Aptima® Assays (Hologic®) and the Allplex™ STI Essential Assay (Seegene®) for the simultaneous detection of Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis and Mycoplasma genitalium in clinical practice. The Aptima® assays (Hologic®) are based on a transcription-mediated amplification (TMA) method. The Allplex™ STI Essential assay (Seegene®) is based on a multiplex Real-Time PCR (RT-PCR) method. A total of 622 clinical samples from different anatomical sites were tested using both methods. A total of 88 (14.1%) and 66 (10.6%) positive samples were found for any of the TMA assays used and for the RT-PCR assay, respectively. Aptima® assays showed a slightly higher rate of positive results for all pathogens except for T. vaginalis, the results of which were similar to those obtained with Allplex™. The most commonly detected pathogen was C. trachomatis (37 samples; 5.9% using TMA assays) and the anatomical site with the highest prevalence of microorganisms was a non-urogenital site, the pharynx (27 positive samples; 4.3%). Using the Aptima® assays as reference method, the comparison showed that the average specificity of multiplex RT-PCR was 100.0% for the four pathogens. However an average sensitivity of 74.5% was observed, showing 95.2% (CI95%; 93.6–96.9) of overall concordance (κ = 0.80). In conclusion, the Aptima® assays show a higher sensitivity on a wide range of sample types compared to the Allplex™ assay. [ABSTRACT FROM AUTHOR]

Recent findings have suggested an association between pubic hair grooming and self-reported history of sexually transmitted infection (STI), specifically gonococcal infection (GC), chlamydial infection (CT), or human immunodeficiency virus (HIV). We evaluated the association between self-reported extreme grooming and laboratory-confirmed prevalence of GC/CT. Between April 2017 and April 2018, we enrolled English-speaking, adult, female students at a large, Midwestern university who presented on-campus for STI testing. Participants completed a questionnaire on demographics and sexual and grooming behaviors, which was linked to their GC/CT test results based on nucleic acid amplification testing. We defined extreme grooming as removal of all pubic hair either at least weekly in the past 12 months or ≥6 times in the past 30 days. We used two separate logistic regression models to determine whether odds of GC/CT varied by extreme groomer status for either time interval. In the study sample of 214 women, prevalence of GC/CT was 9.8%. Nearly all participants (98.1%) reported ever grooming; 53.6% were extreme groomers in the past year and 18% in the past month. Extreme grooming was not associated with prevalent GC/CT in the past year (odds ratio [OR] = 0.8; 95% confidence interval [CI]: 0.3–1.9; adjusted OR = 0.7; 95% CI: 0.3–2.0) or in the past month (OR = 0.5; 95% CI: 0.1–2.0; aOR = 0.4; 95% CI: 0.1–1.9). Pubic hair grooming was common among female university students attending for STI testing. Findings do not support pubic hair grooming as an STI risk factor in this population. [ABSTRACT FROM AUTHOR]

Background: Trachoma is a progressive blinding disease initiated by infection of the conjunctiva with Chlamydia trachomatis. Repeated infections are thought to cause chronic inflammation, which drives scarring, leading to in-turning of the eyelids. The relationship between C. trachomatis, clinical inflammation and scarring development in children is not fully understood due to a paucity of longitudinal studies with infection data at frequent follow-up. Methods and findings: This longitudinal cohort study took place in northern Tanzania. Children aged 6–10 years at baseline were eligible for inclusion. Participants were visited every three months for four years. Clinical signs and conjunctival swabs for C. trachomatis detection by qPCR were collected at each time-point. Conjunctival photographs from baseline and final time-points were graded and compared side-by-side to determine scarring incidence and progression. Of the 666 children enrolled in the study, outcome data were obtained for 448. Scarring progression was detected in 103/448 (23%) children; 48 (11%) of which had incident scarring and 55 (12%) had progression of existing scarring. Scarring was strongly associated with increasing episodes of trachomatous papillary inflammation (TP). Weaker associations were found between episodes of C. trachomatis infection and follicular trachoma (TF) with scarring progression in unadjusted models, which were absent in multivariable analysis after adjusting for inflammation (multivariable results: C. trachomatis p = 0.44, TF p = 0.25, TP p = <0.0001, age p = 0.13, female sex p = 0.05). Individuals having TP at 30% or more of the time-points they were seen had an odds ratio of 7.5 (95%CI = 2.7–20.8) for scarring progression relative to individuals without any TP detected during the study period. Conclusions: These data suggest that the effect of infection on scarring progression is mediated through papillary inflammation, and that other factors contributing to the development of inflammation, in addition to C. trachomatis infection, may be important in driving conjunctival scarring progression in children. The addition of TP as a measure in trachoma control programs would provide an indication of the future risk of developing scarring sequelae. [ABSTRACT FROM AUTHOR]

Chlamydial-induced cystitis in the koala (Phascolarctos cinereus) is currently treated by antibiotics. However, while reducing the chlamydial load, this treatment can also lead to gastrointestinal complications and death. Development of alternative treatments, such as a therapeutic chlamydial vaccine, are hindered by the lack of detailed understanding of the innate immune response to chlamydial clearance and disease regression during antibiotic treatment. Through clinical, microbiological and transcriptomic approaches, disease regression, bacterial clearance and innate immune responses were mapped in koalas with signs of chlamydial-induced cystitis while receiving anti-chlamydial antibiotics. Significant reduction in the signs of cystitis were observed during and post antibiotic treatment. This was observed as a thinning of the bladder wall and complete reversal of urinary incontinence. Transcriptomic analysis before treatment, at the end of treatment and prior to release identified significant down-regulation of specific genes involved in 21 biological pathways. Of these, the chemokine receptor signalling and NOD-like receptor signalling pathways where identified as important markers of inflammation. Specific genes within these pathways (NCF1 and NOX2) were significantly down-regulated, suggesting a decrease in reactive oxygen species production. Through the monitoring of specific clinical and transcriptomic markers, these findings allow detailed profiling of the clinical response to therapeutic vaccination in koalas with current signs of disease. This also adds to our understanding of innate immune responses to chlamydial infections and indicates that chlamydial-induced cystitis in the koala is linked to the regulation of reactive oxygen pathways. [ABSTRACT FROM AUTHOR]

Background: Trachoma, caused by Chlamydia trachomatis, remains the leading infectious cause of blindness worldwide. Persistence and progression of the resulting clinical disease appears to be an immunologically mediated process. Azithromycin, which is distributed at the community level for trachoma control, has immunomodulatory properties. We investigated the impact of one round of oral azithromycin on conjunctival immune responses, C. trachomatis infection and clinical signs three- and six- months post treatment relative to three pre-treatment time-points. Methodology: A cohort of children aged 6 to 10 years were recruited from a trachoma endemic region of northern Tanzania and were visited five times in a 12-month period. They were examined for clinical signs of trachoma and conjunctival swabs were collected for laboratory analysis. C. trachomatis infection was detected and the expression of 46 host genes was quantified using quantitative PCR. All community members were offered azithromycin treatment immediately after the six-month timepoint according to international guidelines. Findings: The prevalence of C. trachomatis infection and inflammatory disease signs were significantly reduced three- and six- months post-mass drug administration (MDA). C. trachomatis infection was strongly associated with clinical signs at all five time-points. A profound anti-inflammatory effect on conjunctival gene expression was observed 3 months post-MDA, however, gene expression had largely returned to pre-treatment levels of variation by 6 months. This effect was less marked, but still observed, after adjusting for C. trachomatis infection and when the analysis was restricted to individuals who were free from both infection and clinical disease at all five time-points. Interestingly, a modest effect was also observed in individuals who did not receive treatment. Conclusion: Conjunctival inflammation is the major clinical risk factor for progressive scarring trachoma, therefore, the reduction in inflammation associated with azithromycin treatment may be beneficial in limiting the development of potentially blinding disease sequelae. Future work should seek to determine whether this effect is mediated directly through inhibition of pro-inflammatory intracellular signalling molecules, through reductions in concurrent, sub-clinical infections, and/or through reduction of infection exposure. [ABSTRACT FROM AUTHOR]

Introduction: Response rates in health research are declining, and low response rates could result in biased outcomes when population characteristics of participants systematically differ from the non-respondents. Few studies have examined key factors of non-response beyond demographic characteristics, such as behavioral and psychological factors. The aim of the current study was to identify predictors of non-response and loss to follow-up in a longitudinal sexual health study. Materials and methods: A longitudinal cohort study (iMPaCT) was conducted from November 2016 to July 2018 among heterosexual STI clinic visitors aged 18–24 years. At four different time points in one year, data was collected on sexual behavior, psychological determinants and chlamydia infections. The national STI surveillance database provided data on demographic, behavioral and sexual health-related characteristics for non-respondents. Predictors of non-response at baseline and of loss to follow-up were identified using multivariable logistic regression analyses. Results: In total, 13,658 STI clinic visitors were eligible to participate, of which 1,063 (8%) participated. Male gender, low/medium education level, young age (≤ 20 years) and having a non-Dutch migration background were significant predictors of non-response at baseline. Furthermore, non-respondents at baseline were more likely to report STI-related symptoms, to have been notified by a partner, to have had condomless sex, and to have had ≤ 2 partners in the past six months, compared to participants. Psychological predictors of loss to follow-up differed between STI clinic regions, but low perceived importance of health at baseline was associated with loss to follow-up in all regions. The baseline chlamydia positivity rate was significantly higher in the non-respondents (17%) compared to the participants (14%), but was not a predictor of loss to follow-up. Discussion: Targeted recruitment aimed at underrepresented groups in the population based on demographic, behavioral and psychological characteristics, might be necessary to decrease loss to follow-up, and to prevent non-response bias in health research. [ABSTRACT FROM AUTHOR]

Background: The world is witnessing mass displacement of populations which could impact global efforts to eliminate neglected tropical diseases such as trachoma. On the African continent, South Sudan has experienced high levels of population displacement. Population based baseline trachoma surveys were conducted among refugee camps in two Sudanese localities hosting South Sudanese refugee populations to determine whether the SAFE strategy was warranted. Methodology/Principal findings: Cross-sectional, multi-stage, cluster-random surveys were conducted within refugee camps in each of two Sudanese localities, Al Salam and Al Jabalain. For survey sampling, multiple camps within each locality were combined to form the sampling frame for that locality. Household water, sanitation and hygiene indicators were assessed, and trachoma signs were graded by trained and certified graders. The prevalence of trachomatous inflammation-follicular (TF) in children aged one to nine years was 15.7% (95%CI: 12.1–20.2) in Al Salam and 10.6% (95%CI: 7.9–14.0) in Al Jabalain. The prevalence of trachomatous trichiasis (TT) in those 15 years above was 2.9% (95%CI: 1.8–4.8) in Al Salam and 5.0% (95%CI: 3.8–6.6) in Al Jabalain. The presence of water and sanitation was high in both survey units. Conclusion/ Significance: Sudan has made progress in reducing the prevalence of trachoma within the country; however, the presence of over one million refugees from a neighboring trachoma hyper-endemic country could impact this progress. These surveys were the first step in addressing this important issue. The results demonstrate that at least three years of mass drug administration with azithromycin and tetracycline is needed in addition to the provision of TT surgical services. Additionally, it highlights that non-endemic or formerly endemic localities may have to adopt new strategies to provide services for refugee populations originating from hyper-endemic regions to ensure elimination of trachoma as a public health problem for all populations. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis infections are the leading cause of sexually transmitted infections of bacterial origin. Lower genital tract infections are often asymptomatic, and therefore left untreated, leading to ascending infections that have long-term consequences on female reproductive health. Human pathology can be recapitulated in mice with the mouse adapted strain C. muridarum. Eight years into the post-genetic era, significant advances to expand the Chlamydia genetic toolbox have been made to facilitate the study of this important human pathogen. However, the need for additional tools remains, especially for C. muridarum. Here, we describe a new set of spectinomycin resistant E. coli-Chlamydia shuttle vectors, for C. trachomatis and C. muridarum. These versatile vectors allow for expression and localization studies of Chlamydia effectors, such as Inc proteins, and will be instrumental for mutant complementation studies. In addition, we have exploited the differential expression of specific Chlamydia genes during the developmental cycle to engineer an omcA: :gfp fluorescent transcriptional reporter. This novel tool allows for monitoring RB to EB conversion at the bacterial level. Spatiotemporal tracking of GFP expression within individual inclusions revealed that RB to EB conversion initiates in bacteria located at the edge of the inclusion and correlates with the time post initiation of bacterial replication and inclusion size. Comparison between primary and secondary inclusions potentially suggests that the environment in which the inclusions develop influences the timing of conversion. Altogether, the Chlamydia genetic tools described here will benefit the field, as we continue to investigate the molecular mechanisms underlying Chlamydia-host interaction and pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Chlamydia trachomatis causes the most prevalent bacterial Sexual Transmitted Infection. In pregnant women, untreated chlamydial infections are associated with abortions, premature rupture of membranes, postpartum endometritis, low birth weight and transmission to the newborn. In Córdoba, Argentina, there is little knowledge about the prevalence of Chlamydia trachomatis in women in their third trimester of pregnancy, so, the aim of this study was to evaluate Chlamydia trachomatis prevalence and genotypes present in Cordovan pregnant women with different age and socioeconomic status. Methods and findings: Design: prospective study. Settings: Women population from Cordoba city, Argentina. Population: Pregnant women having 35 to 37 weeks of gestation. Methods: Five hundred and nine cervical swabs were collected. Each sample was subjected to DNA extraction and PCR for Chlamydia trachomatis using primers NRO/NLO and CTP1/CTP2. Positives samples were sequenced to determine genotype. Main outcome measures: Demographic data of the patients were collected to detect a population at risk for this infection. Results: A prevalence of 6.9% (35/509) for Chlamydia trachomatis infection was detected, with 32/295 and 3/214 from pregnant women with low or better economic resources respectively (p = 0,0001). Results showed a significantly increased rate of 11.6% (30/258) in women under 25 years compared with 2% (5/251) in patients over that age (p = 0,00003). Genotype E was the most prevalent. Conclusions: With these results, we can say that pregnant women under 25 years old and low economic resources are one of the populations in which the screening programs of Chlamydia trachomatis should focus. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis is the most common cause of bacterial sexually transmitted infection, responsible for millions of infections each year. Despite this high prevalence, the elucidation of the molecular mechanisms of Chlamydia pathogenesis has been difficult due to limitations in genetic tools and its intracellular developmental cycle. Within a host epithelial cell, chlamydiae replicate within a vacuole called the inclusion. Many Chlamydia–host interactions are thought to be mediated by the Inc family of type III secreted proteins that are anchored in the inclusion membrane, but their array of host targets are largely unknown. To investigate how the inclusion membrane proteome changes over the course of an infected cell, we have adapted the APEX2 system of proximity-dependent biotinylation. APEX2 is capable of specifically labeling proteins within a 20 nm radius in living cells. We transformed C. trachomatis to express the enzyme APEX2 fused to known inclusion membrane proteins, allowing biotinylation and purification of inclusion-associated proteins. Using quantitative mass spectrometry against APEX2 labeled samples, we identified over 400 proteins associated with the inclusion membrane at early, middle, and late stages of epithelial cell infection. This system was sensitive enough to detect inclusion interacting proteins early in the developmental cycle, at 8 hours post infection, a previously intractable time point. Mass spectrometry analysis revealed a novel, early association between C. trachomatis inclusions and endoplasmic reticulum exit sites (ERES), functional regions of the ER where COPII-coated vesicles originate. Pharmacological and genetic disruption of ERES function severely restricted early chlamydial growth and the development of infectious progeny. APEX2 is therefore a powerful in situ approach for identifying critical protein interactions on the membranes of pathogen-containing vacuoles. Furthermore, the data derived from proteomic mapping of Chlamydia inclusions has illuminated an important functional role for ERES in promoting chlamydial developmental growth. [ABSTRACT FROM AUTHOR]

Chlamydia is a common pathogen that can causes serious complications in the reproductive system and eyes. Lack of vaccine and other effective prophylactic measures coupled with the largely asymptomatic nature and unrare clinical treatment failure calls for development of new antichlamydials, particularly selective antichlamydials without adverse effects on humans and the beneficial microbiota. We previously reported that benzal-N-acylhydrazones (BAH) can inhibit chlamydiae without detectable adverse effects on host cells and beneficial lactobacilli that dominate the human vaginal microbiota among reproductive-age women. However, the antichlamydial mechanism of BAH is not known. Whereas 4 single nucleotide polymorphisms (i.e., SNP1-4) were identified in a rare Chlamydia variant with a low level of BAH resistance, termed MCR, previous studies failed to establish a causal effect of any particular SNP(s). In the present work, we performed recombination to segregate the four SNPs. Susceptibility tests indicate that the R51G GrgA allele is both necessary and sufficient for the low level of BAH resistance. Thus, the Chlamydia-specific transcription factor GrgA either is a direct target of BAH or regulates BAH susceptibility. We further confirm an extremely low rate of BAH resistance in Chlamydia. Our findings warrant exploration of GrgA as a therapeutic and prophylactic target for chlamydial infections. [ABSTRACT FROM AUTHOR]

Background: Online testing for sexually transmitted infections has a lower unit cost than testing in clinical services and economic analysis has focused on the cost per test and cost per diagnosis in clinics and online. However, online services generate new demand for testing and shift activity between services, requiring system-level analysis to effectively predict cost-effectiveness. Methods and findings: Routinely collected, anonymised, retrospective data on sexual health service activity from all specialist services (clinic and online) within an inner London sexual health economy were collated and harmonised to generate a complete dataset of individual level clinic attendances. Clinic activity and diagnoses were coded using nationally standardised codes assigned by clinicians. Costs were taken from locally or regionally agreed sexual health tariffs. The introduction of online services changed patterns of testing. In an inner London sexual health economy, online STI testing increased total number of tests, the total cost of testing and total diagnoses while slightly reducing the average cost per diagnosis. Two years after the introduction of online services 37% of tests in the were provided online and total diagnoses increased. The positivity of online services is generally lower than that in clinics but varies between contexts. Where the positivity ratio between clinic and online is less than the cost ratio, online services will reduce cost per diagnosis. In this analysis, areas with different classifications as urban and rural had different clinic/online positivity ratios changing the cost effectiveness between areas. Even after the introduction of online services, simple STI testing activity continues in clinics and providers should consider online-first options where clinically appropriate. Conclusions: Online services for STI testing are not ‘stand alone’. They change STI testing behaviour with impacts on all elements of the sexual health economy. Planning, development and monitoring of such services should reference the dynamic nature of these systems and the role of online services within them. [ABSTRACT FROM AUTHOR]

This study aimed to estimate the prevalence of chlamydial trachomatis (CT) infection and explore its risk factors among patients attending sexual and reproductive health clinics in Shenzhen, China. We collected demographic and clinical information from attendees (aged 18–49). CT and Neisseria gonorrhoeae (NG) infection was determined by nucleic acid amplification test (NAAT) on self-collected urine specimens. Of 1,938 participants recruited, 10.3% (95% confidence interval [CI]: 9.6%-11.0%) tested positive for CT. Prevalence was similar between men (10.6% [85/804]; 95% CI, 9.5%–11.7%) and women (10.1% [115/1134]; 95% CI: 9.2%–11.0%). Being 18–25 years old (adjusted odds ratio [aOR] = 2.52; 95%CI:1.35–4.71), never tested for CT before (aOR = 2.42; 95%CI: 1.05–5.61) and infected with NG(aOR = 3.87; 95%CI: 2.10–7.10) were independently associated with CT infection. We found that CT infection is prevalent among patients attending sexual and reproductive health clinics in Shenzhen, China. A comprehensive program including CT screening, surveillance and treatment is urgently needed. [ABSTRACT FROM AUTHOR]

We evaluated the current prevalence of gonococcal cervicitis among pregnant women in institutes that either do or do not routinely screen for gonococcal infection in Japan. We requested 2,330 obstetrical facilities to provide information on Neisseria gonorrhoeae cervicitis in pregnant women. A total of 1,876 (80.5%) of them responded. The universal screening test for gonococcal cervicitis, involving nucleic acid amplification for all pregnant women, was performed in 281 institutes (13.9% of institutes across Japan). The total rate of pregnant women with gonococcal cervicitis was 1.3% in the institutes performing the screening test during pregnancy, while it was only 0.2% (p < 0.01) in those not performing it. This suggests that 84% of infected women may have been missed in the institutes that do not routinely perform the screening test for gonococcal cervicitis. It may be time to examine the cost-effectiveness of providing gonococcal screening for all pregnant women in Japan. [ABSTRACT FROM AUTHOR]

Background: Program decision-making for trachoma elimination currently relies on conjunctival clinical signs. Antibody tests may provide additional information on the epidemiology of trachoma, particularly in regions where it is disappearing or elimination targets have been met. Methods: A cluster-randomized trial of mass azithromycin distribution strategies for trachoma elimination was conducted over three years in a mesoendemic region of Niger. Dried blood spots were collected from a random sample of children aged 1–5 years in each of 24 study communities at 36 months after initiation of the intervention. A multiplex bead assay was used to test for antibodies to two Chlamydia trachomatis antigens, Pgp3 and CT694. We compared seropositivity to either antigen to clinical signs of active trachoma (trachomatous inflammation—follicular [TF] and trachomatous inflammation—intense [TI]) at the individual and cluster level, and to ocular chlamydia prevalence at the community level. Results: Of 988 children with antibody data, TF prevalence was 7.8% (95% CI 6.1 to 9.5) and TI prevalence was 1.6% (95% CI 0.9 to 2.6). The overall prevalence of antibody positivity to Pgp3 was 27.2% (95% CI 24.5 to 30), and to CT694 was 23.7% (95% CI 21 to 26.2). Ocular chlamydia infection prevalence was 5.2% (95% CI 2.8 to 7.6). Seropositivity to Pgp3 and/or CT694 was significantly associated with TF at the individual and community level and with ocular chlamydia infection and TI at the community level. Older children were more likely to be seropositive than younger children. Conclusion: Seropositivity to Pgp3 and CT694 correlates with clinical signs and ocular chlamydia infection in a mesoendemic region of Niger. Trial registration: ClinicalTrials.gov . [ABSTRACT FROM AUTHOR]

Infections of stratified epithelia contribute to a large group of common diseases, such as dermatological conditions and sexually transmitted diseases. To investigate how epithelial structure affects infection dynamics, we develop a general ecology-inspired model for stratified epithelia. Our model allows us to simulate infections, explore new hypotheses and estimate parameters that are difficult to measure with tissue cell cultures. We focus on two contrasting pathogens: Chlamydia trachomatis and Human papillomaviruses. Using cervicovaginal parameter estimates, we find that key infection symptoms can be explained by differential interactions with the layers, while clearance and pathogen burden appear to be bottom-up processes. Cell protective responses to infections (e.g. mucus trapping) generally lowered pathogen load but there were specific effects based on infection strategies. Our modeling approach opens new perspectives for 3D tissue culture experimental systems of infections and, more generally, for developing and testing hypotheses related to infections of stratified epithelia. [ABSTRACT FROM AUTHOR]

Chlamydia pneumoniae is one of the two major species of the Chlamydiaceae family that have a profound effect on human health. C. pneumoniae is linked to a number of severe acute and chronic diseases of the upper and lower respiratory tract including pneumonia, asthma, bronchitis and infection by the pathogen might play a role in lung cancer. Following adhesion, Chlamydiae secrete effector proteins into the host cytoplasm that modulate the actin cytoskeleton facilitating internalization and infection. Members of the conserved TarP protein family comprise such effector proteins that polymerize actin, and in the case of the C. trachomatis TarP protein, has been shown to play a critical role in pathogenesis. In a previous study, we demonstrated that, upon bacterial invasion, the C. pneumoniae TarP family member CPn0572 is secreted into the host cytoplasm and recruits and associates with actin via an actin-binding domain conserved in TarP proteins. We have now extended our analysis of CPn0572 and found that the CPn0572 actin binding and modulating capability is more complex. With the help of the fission yeast system, a second actin modulating domain was identified independent of the actin binding domain. Microscopic analysis of HEp-2 cells expressing different CPn0572 deletion variants mapped this domain to the C-terminal part of the protein as CPn0572536-755 binds F-actin in vitro and colocalizes with aberrantly thickened actin cables in vivo. Finally, microscopic and bioinformatic analysis revealed the existence of a vinculin binding sequence in CPn0572. Our findings contribute to the understanding of the function of the TarP family and underscore the existence of several actin binding domains and a vinculin binding site for host actin modulation. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is an important contributor to morbidity and mortality in American Indian communities. The Strong Heart Study (SHS) was initiated in response to the need for population based estimates of cardiovascular disease in American Indians. Previous studies within SHS have identified correlations between heart disease and deficiencies in mannose binding lectin (MBL), a motif recognition molecule of the innate immune system. MBL mediates the immune response to invading pathogens including Chlamydia pneumoniae (Cp), which has also been associated with the development and progression of CVD. However, a link between MBL2 genotype and Cp in contributing to heart disease has not been established. To address this, SHS collected baseline Cp antibody titers (IgA and IgG) and MBL2 genotypes for common functional variants from 553 individuals among twelve participating tribes. A single nucleotide polymorphism (SNP) in the promoter, designated X/Y, correlated significantly with increased Cp IgG titer levels, whereas another promoter SNP (H/L) did not significantly influence antibody levels to Cp. Two variants within exon 1 of MBL2, the A and B alleles, also displayed significant association with Cp antibody titers. Some MBL2 genotypes were absent from the population, suggesting linkage disequilibrium may be operating within the SHS cohort. Additional factors, such as increasing age and socioeconomic status, were also associated with increased Cp IgG antibody titers. This study demonstrates that MBL2 genotype associates with immune reactivity to C. pneumoniae in the SHS cohort. Thus, MBL2 may contribute to the progression of cardiovascular disease (CVD) among American Indians indirectly through pathogen interactions in addition to its previously defined roles. [ABSTRACT FROM AUTHOR]

Problem: Chlamydia trachomatis infections are often associated with acute syndromes including cervicitis, urethritis, and endometritis, which can lead to chronic sequelae such as pelvic inflammatory disease (PID), chronic pelvic pain, ectopic pregnancy, and tubal infertility. As epithelial cells are the primary cell type productively infected during genital tract Chlamydia infections, we investigated whether Chlamydia has any impact on the integrity of the host epithelial barrier as a possible mechanism to facilitate the dissemination of infection, and examined whether TLR3 function modulates its impact. Method of study: We used wild-type and TLR3-deficient murine oviduct epithelial (OE) cells to ascertain whether C. muridarum infection had any effect on the epithelial barrier integrity of these cells as measured by transepithelial resistance (TER) and cell permeability assays. We next assessed whether infection impacted the transcription and protein function of the cellular tight-junction (TJ) genes for claudins1-4, ZO-1, JAM1 and occludin via quantitative real-time PCR (qPCR) and western blot. Results: qPCR, immunoblotting, transwell permeability assays, and TER studies show that Chlamydia compromises cellular TJ function throughout infection in murine OE cells and that TLR3 deficiency significantly exacerbates this effect. Conclusion: Our data show that TLR3 plays a role in modulating epithelial barrier function during Chlamydia infection of epithelial cells lining the genital tract. These findings propose a role for TLR3 signaling in maintaining the integrity of epithelial barrier function during genital tract Chlamydia infection, a function that we hypothesize is important in helping limit the chlamydial spread and subsequent genital tract pathology. [ABSTRACT FROM AUTHOR]

Chlamydia pecorum is responsible for causing ocular infection and disease which can lead to blindness in koalas (Phascolarctos cinereus). Antibiotics are the current treatment for chlamydial infection and disease in koalas, however, they can be detrimental for the koala’s gastrointestinal tract microbiota and in severe cases, can lead to dysbiosis and death. In this study, we evaluated the therapeutic effects provided by a recombinant chlamydial major outer membrane protein (MOMP) vaccine on ocular disease in koalas. Koalas with ocular disease (unilateral or bilateral) were vaccinated and assessed for six weeks, evaluating any changes to the conjunctival tissue and discharge. Samples were collected pre- and post-vaccination to evaluate both humoral and cell-mediated immune responses. We further assessed the infecting C. pecorum genotype, host MHC class II alleles and presence of koala retrovirus type (KoRV-B). Our results clearly showed an improvement in the clinical ocular disease state of all seven koalas, post-vaccination. We observed increases in ocular mucosal IgA antibodies to whole C. pecorum elementary bodies, post-vaccination. We found that systemic cell-mediated immune responses to interferon-γ, interleukin-6 and interleukin-17A were not significantly predictive of ocular disease in koalas. Interestingly, one koala did not have as positive a clinical response (in one eye primarily) and this koala was infected with a C. pecorum genotype (E’) that was not used as part of the vaccine formula (MOMP genotypes A, F and G). The predominant MHC class II alleles identified were DAb*19, DAb*21 and DBb*05, with no two koalas identified with the same genetic sequence. Additionally, KoRV-B, which is associated with chlamydial disease outcome, was identified in two (29%) ocular diseased koalas, which still produced vaccine-induced immune responses and clinical ocular improvements post-vaccination. Our findings show promise for the use of a recombinant chlamydial MOMP vaccine for the therapeutic treatment of ocular disease in koalas. [ABSTRACT FROM AUTHOR]

Koalas (Phascolarctos cinereus) have suffered severe declines in the northern extent of their range due to a variety of threats, including habitat destruction, trauma from cars and dogs, climate change and importantly, disease. The most significant pathogen in koalas is Chlamydia pecorum, which causes inflammation and fibrosis at mucosal sites, resulting in blindness, infertility and death in severe cases. Chlamydia treatment can be problematic in koalas as the response to treatment is often poor in chronic cases and antimicrobial choice is limited. Thus, chlamydial disease is a severely threatening process for koala conservation. We investigated the short and long-term clinical outcomes for 167 koalas with Chlamydia that underwent capture, telemetric monitoring and intensive veterinary management as part of a large-scale population management program in South East Queensland. Chlamydia treatments included the standard regimen of daily subcutaneous chloramphenicol injections (60mg/kg) for 14 to 28-days, and a variety of non-standard regimens such as topical antimicrobials only (for ocular disease), surgical treatment only (for bilateral reproductive tract disease), and other antimicrobials/treatment lengths. To assess these regimens we analysed clinical records, field monitoring data and swab samples collected from the urogenital tract and ocular conjunctiva. Overall, in contrast to other studies, treatment was generally successful with 86.3% of treated koalas released back into the wild. The success of treatment rose to 94.8% however, when the standard treatment regimen was employed. Further, 100% of koalas that were also treated with surgical ovariohysterectomy (n = 12) remained healthy for a median of 466 days of post-treatment monitoring, demonstrating the benefits of surgical treatment. Previous studies reported 45-day chloramphenicol regimens, but the shorter standard regimen still achieved microbiological cure and reduces the risk of negative sequelae associated with treatment and/or captivity and treatment costs. Despite these positive clinical outcomes, alternatives to chloramphenicol are warranted due to its decreasing availability. [ABSTRACT FROM AUTHOR]

Background: Seroprevalence surveys of Chlamydia trachomatis (CT) antibodies are promising for estimating age-specific CT cumulative incidence, however accurate estimates require improved understanding of antibody response to CT infection. Methods: We used GUMCAD, England’s national sexually transmitted infection (STI) surveillance system, to select sera taken from female STI clinic attendees on the day of or after a chlamydia diagnosis. Serum specimens were collected from laboratories and tested anonymously on an indirect and a double-antigen ELISA, both of which are based on the CT-specific Pgp3 antigen. We used cross-sectional and longitudinal descriptive analyses to explore the relationship between seropositivity and a) cumulative number of chlamydia diagnoses and b) time since most recent chlamydia diagnosis. Results: 919 samples were obtained from visits when chlamydia was diagnosed and 812 during subsequent follow-up visits. Pgp3 seropositivity using the indirect ELISA increased from 57.1% (95% confidence interval: 53.2–60.7) on the day of a first-recorded chlamydia diagnosis to 89.6% (95%CI: 79.3–95.0) on the day of a third or higher documented diagnosis. With the double-antigen ELISA, the increase was from 61.1% (95%CI: 53.2–60.7) to 97.0% (95%CI: 88.5–99.3). Seropositivity decreased with time since CT diagnosis on only the indirect assay, to 49.3% (95%CI: 40.9–57.7) two or more years after a first diagnosis and 51.9% (95%CI: 33.2–70.0) after a repeat diagnosis. Conclusion: Seropositivity increased with cumulative number of infections, and decreased over time after diagnosis on the indirect ELISA, but not on the double-antigen ELISA. This is the first study to demonstrate the combined impact of number of chlamydia diagnoses, time since diagnosis, and specific ELISA on Pgp3 seropositivity. Our findings are being used to inform models estimating age-specific chlamydia incidence over time using serial population-representative serum sample collections, to enable accurate public health monitoring of chlamydia. [ABSTRACT FROM AUTHOR]

Background: Validation of elimination of trachoma as a public health problem is based on clinical indicators, using the WHO simplified grading system. Chlamydia trachomatis (Ct) infection and anti-Ct antibody responses (anti-Pgp3) have both been evaluated as alternative indicators in settings with varying levels of trachoma. There is a need to evaluate the feasibility of using tests for Ct infection and anti-Pgp3 antibodies at scale in a trachoma-endemic country and to establish the added value of the data generated for understanding transmission dynamics in the peri-elimination setting. Methodology/Principal findings: Dried blood spots for serological testing and ocular swabs for Ct infection testing (taken from children aged 1–9 years) were integrated into the pre-validation trachoma surveys conducted in the Northern and Upper West regions of Ghana in 2015 and 2016. Ct infection was detected using the GeneXpert PCR platform and the presence of anti-Pgp3 antibodies was detected using both the ELISA assay and multiplex bead array (MBA). The overall mean cluster-summarised TF prevalence (the clinical indicator) was 0.8% (95% CI: 0.6–1.0) and Ct infection prevalence was 0.04% (95%CI: 0.00–0.12). Anti-Pgp3 seroprevalence using the ELISA was 5.5% (95% CI: 4.8–6.3) compared to 4.3% (95%CI: 3.7–4.9) using the MBA. There was strong evidence from both assays that seropositivity increased with age (p<0.001), although the seroconversion rate was estimated to be very low (between 1.2 to 1.3 yearly events per 100 children). Conclusions/Significance: Infection and serological data provide useful information to aid in understanding Ct transmission dynamics. Elimination of trachoma as a public health problem does not equate to the absence of ocular Ct infection nor cessation in acquisition of anti-Ct antibodies. [ABSTRACT FROM AUTHOR]

Background: In the UK, people of black Caribbean (BC) ethnicity continue to be disproportionately affected by bacterial sexually transmitted infections (STIs) and Trichomonas vaginalis (TV). We systematically reviewed evidence on the association between bacterial STIs/TV and ethnicity (BC compared to white/white British (WB)) accounting for other risk factors; and differences between these two ethnic groups in the prevalence of risk factors associated with these STIs, sexual healthcare seeking behaviours, and contextual factors influencing STI risk. Methods: Studies presenting relevant evidence for participants aged ≥14 years and living in the UK were eligible for inclusion. A pre-defined search strategy informed by the inclusion criteria was developed. Eleven electronic databases were searched from the start date to September-October 2016. Two researchers independently screened articles, extracted data using a standardised proforma and resolved discrepancies in discussion with a third researcher. Descriptive summaries of evidence are presented. Meta-analyses were not conducted due to variation in study designs. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. Results: Of 3815 abstracts identified, 15 articles reporting quantitative data were eligible and included in the review. No qualitative studies examining contextual drivers of STI risk among people of BC ethnicity were identified. Compared to the white/WB ethnic group, the greater STI/TV risk among BCs was partially explained by variations in socio-demographic factors, sexual behaviours, and recreational drug use. The prevalence of reporting early sexual debut (<16 years), concurrency, and multiple partners was higher among BC men compared to white/WB men; however, no such differences were observed for women. People of BC ethnicity were more likely to access sexual health services than those of white/WB ethnicity. Conclusions: Further research is needed to explore other drivers of the sustained higher STI/TV prevalence among people of BC ethnicity. Developing holistic, tailored interventions that address STI risk and target people of BC ethnicity, especially men, could enhance STI prevention. [ABSTRACT FROM AUTHOR]

Background: Men who have sex with men (MSM) and who engage in condomless anal intercourse with casual partners are at high risk of acquiring sexually transmitted infections (STIs), but reliable epidemiological data are scarce. Studies on HIV pre-exposure prophylaxis (PrEP) enrol MSM who indicate that they engage in behaviour that puts them at high risk of acquiring HIV. Because they also screen for STIs at regular intervals, these studies may serve as a valuable source to estimate incidence rates of STIs in this subpopulation of MSM. Methods: We systematically searched for trials and observational studies of PrEP in MSM that reported data on the incidence of STIs during the study period. Incidence rates were calculated as events per 100 person-years (py) with 95% confidence intervals (CI). Data from individual studies were pooled building subgroups along study types and geography. We performed sensitivity analyses, including data only from studies that met pre-defined quality criteria. Results: Twenty-four publications on 20 studies were included. The majority of studies reported that sexual behaviour and/or STI incidence remained stable or decreased during the study period. For syphilis, incidence rates ranged from 1.8/100py to 14.9/100py, the pooled estimate was 9.1/100py (95%-CI: 7.7–10.9). Incidence rates for gonorrhoea and chlamydia of any site ranged from 13.3/100py to 43.0/100py and 15.1/100py to 48.5/100py, respectively. Considering only studies that met the criteria for sensitivity analysis yielded pooled estimates of 39.6/100py (95%-CI: 32.9–47.6) and 41.8/100py (95%-CI: 33.9–51.5), respectively. The overall estimate for hepatitis C incidence was 1.3/100py (95%-CI: 1.0–1.8). Conclusions: Despite partly heterogeneous results, the data depict high incidence rates of STIs among MSM who engage in higher-risk sexual behaviours such as condomless sex with casual partners. This subpopulation of MSM requires access to STI screening at close intervals. By offering access to structures that provide regular STI monitoring and prompt treatment, PrEP may not only decrease HIV incidence but also have beneficial effects in decreasing the burden of STIs. [ABSTRACT FROM AUTHOR]