Haematopoietic innate interleukin 17A production drives immunopathology in female mouse genital Chlamydia muridarum infection.

Chlamydia trachomatis infection is the leading cause of bacterial urogenital infection and has been demonstrated to drive inflammation and scarring of the reproductive tract. Recent studies have identified key triggers of proinflammatory adaptive immune responses driven by innate leukocytes and epithelia driving immunopathology. Utilizing chimeric mouse models, we investigated the definitive source and role of IL17 and IL17 signalling receptors during early Chlamydia muridarum infection of the female urogenital tract. Bone marrow transplants from wild-type (WT) and IL17A-/- mice to recipients demonstrated equivocal infection kinetics in the reproductive tract, but interestingly, adoptive transfer of IL17A-/- immune cells to WT recipients resulted in no infertility, suggesting a haematopoietic (as opposed to tissue) source of IL17 driving immunopathology. To further delineate the role of IL17 in immunopathology, we infected WT and IL17 receptor A (IL17RA)-/- female mice and observed a significant reduction in immunopathology in IL17RA-/- mice. WT bone marrow transplants to IL17RA-/- recipient mice prevented hydrosalpinx, suggesting signalling through IL17RA drives immunopathology. Furthermore, early chemical inhibition of IL17 signalling significantly reduced hydrosalpinx, suggesting IL17 acts as an innate driver of disease. Early during the infection, IL17 was produced by γδ T cells in the cervico-vagina, but more importantly, by neutrophils at the site of infertility in the oviducts. Taken together, these data suggest innate production of IL17 by haematopoietic leukocytes drives immunopathology in the epithelia during early C. muridarum infection of the female reproductive tract.

CLINICAL EFFICACY OF TREATMENT OF WOMEN WITH CHRONIC RECURRENT UROGENITAL CHLAMYDIA INFECTION.

OBJECTIVE: Aim: To to increase the efficacy of the treatment of women diagnosed with complicated urogenital chlamydia infection based on the study of the immune status, clinical and pathogenetic features of the course, development and implementation of pathogenetically substantiated therapy methods. PATIENTS AND METHODS: Materials and methods: Laboratory diagnostics of chlamydia infection was conducted with the use of direct immunofluorescence, enzyme immunoassay and cytological method. The dynamics of clinical symptoms was studied in the patients of Group I (64 women) who received Wobenzym in combination with Doxycycline and Group II (64 women) who were treated with conventional therapy (CT). RESULTS: Results: Clinical effectiveness of the treatment of women in Groups I and II was analyzed. The treatment according to our developed method was well tolerated by all the patients. No manifestations of the disease exacerbation which could be associated with the inclusion of these drugs in the comprehensive treatment were noted. The insignificant effectiveness of our treatment in the examined patients with complicated urogenital chlamydia infection in Groups I and II was distributed as follows: only 1 (1.56%) woman (Group I) had an insignificant improvement in clinical manifestations after the treatment according to our method. An insignificant improvement in the clinical manifestations after the treatment with conventional therapy (Group II) was observed in 4 women constituting 6.25%. Unfortunately, a small percentage of women in Groups I and II with no changes in clinical symptoms after the treatment was observed. In particular, the absence of treatment effectiveness was noted in 3 (4.69%) women after the application of our method and in 6 women (9.38%) who were treated by the conventional therapy. Therefore, these women were prescribed an additional course of treatment. CONCLUSION: Conclusions: The dynamics of clinical symptoms was found to be significantly more pronounced and fast in the patients of Group I compared to the patients in Group II who were treated with conventional therapy.

Antichlamydia antibodies and sperm quality among male partners of infertile couples ins Nigeria.

Background: The impact of Chlamydia trachomatis on semen quality has been studied with varied results. Aim: To determine the prevalence of antichlamydial antibodies and their relationship with sperm quality among male partners of infertile couples in Enugu, South-East Nigeria. Materials and Methods: It was a cross-sectional study of infertile male partners of couples attending infertility clinics at the University of Nigeria Teaching Hospital (UNTH) Ituku-Ozalla, Enugu, Nigeria. Their sera were assayed for antichlamydial antibodies, and semen analysis and culture were done for each participant. Results: Two hundred and eighty-two (282) male partners of infertile couples were studied. Infertility was commoner among participants aged 40 years or more (45.1%) and was mainly of the "primary type" (62.1%). Antichlamydia antibody was detected in 156 (55.3%) participants and was significantly associated with sperm quality (P = 002; OR = 2.294; 95% CI = 1.36-3.88). Overall, 81 (28.7%) had abnormal sperm quality. The sperm count, progressive motility, and vitality were significantly lower in participants with abnormal sperm quality than those with normal sperm quality (P < 0.001) while morphology, volume, and liquefaction time did not differ significantly (P > 0.05). Staphylococcus aureus was the predominant organism isolated from culture (122/282, 43.3%) while Streptococcus species were the least (4/262, 1.4%). There was significantly more Staphylococcus aureus isolated from the semen of participants that were seropositive to antichlamydial antibodies than those that were seronegative (80/156, 51.3% vs. 42/126, 33.3%; OR = 2.105; 95% CI = 1.30-3.42; P = 0.003). Conclusion: The prevalence of antichlamydial antibodies among male partners of infertile couples in Enugu, Nigeria is high and there is a significant association with sperm quality, sperm count, and bacterial isolates in seminal culture. Male partners of infertile couples in Enugu should be screened for antichlamydial antibodies and appropriate treatment offered wherever indicated. There is a need for increased public awareness and advocacy campaigns on the impact of Chlamydia infection on male factor infertility. This primary preventive measure may help in reducing the burden of Chlamydia infection and male factor infertility.

Comparison of the patterns of chlamydia and gonorrhoea at the oropharynx, anorectum and urethra among men who have sex with men.

OBJECTIVE: Chlamydia and gonorrhoea are common sexually transmitted infections that infect the oropharynx, anorectum and urethra in men who have sex with men (MSM). This study aimed to examine the pattern of infection at more than one site (multisite) for chlamydia and gonorrhoea among MSM. METHODS: This was a retrospective study of MSM attending the Melbourne Sexual Health Centre for the first time between 2018 and 2019. We included MSM aged ≥16 years who had tested for Neisseria gonorrhoeae and Chlamydia trachomatis at all three sites (oropharynx, anorectum and urethra). We compared infections that occurred at a single site (termed single-site infection) and those that occurred at more than one site (termed multisite infections). RESULTS: Of the 3938 men who were tested for chlamydia and gonorrhoea, 498/3938 men (12.6%, 95% CI 11.5% to 13.6%) had chlamydia at any site, of whom 400/498 (80.3%, 95% CI 78.9% to 81.2%) had single-site chlamydia infection, and 98/498 (19.7%, 95% CI 16.2% to 23.1%) had multisite infections. A similar proportion of men had gonorrhoea at any site (447/3938, 11.4%, 95% CI 10.3% to 12.2%), but among these 447 men, single-site infection was less common (256/447, 57.3%, 95% CI 52.6% to 61.7%, p<0.001) and multisite infection (191/447, 42.7%, 95% CI 38.2% to 47.3%, p<0.001) was more common than chlamydia. There were also marked differences by anatomical site. Urethral infection commonly occurred as single sites (75/122, 61.5%, 95% CI 52.8% to 70.1%) for chlamydia but uncommonly occurred for gonorrhoea (12/100, 12.0%, 95% CI 5.6% to 18.3%, p<0.001). In contrast, anorectal infection uncommonly occurred as multisite infection for chlamydia (98/394, 24.9%, 95% CI 20.6% to 29.1%) but was common (184/309, 59.5%, 95% CI 54.0% to 64.9%, p<0.001) for gonorrhoea. CONCLUSIONS: The markedly different pattern of site-specific infection for chlamydia and gonorrhoea infections among the same MSM suggests significant differences in the transmissibility between anatomical sites and the duration of each infection at each site.

Use of healthcare reimbursement data to monitor bacterial sexually transmitted infection testing in France, 2006 to 2020.

BackgroundDiagnoses of bacterial sexually transmitted infections (STIs) have increased in France since the 2000s. The main strategy to control STI transmission is recommending/facilitating access to condom use, testing, and antibiotic treatments.AimThis study analyses the evolution of STI testing in the private sector in France from 2006 to 2020.MethodsNational health insurance reimbursement data were used to determine numbers and rates of individuals aged ≥ 15 years tested for diagnoses of chlamydia, gonorrhoea and syphilis in the private sector in France and to describe their evolution from 2006 to 2020.ResultsUpward tendencies in testing were observed from 2006 to 2019 for all three STIs. The highest testing rates were identified in people aged 25‒29-years old. The observed testing-increase from 2017 to 2019 was twice as high in young people (< 25 years old) as in older people. In 2019, chlamydia, gonorrhoea and syphilis testing rates were respectively 45.4 (+ 21% since 2017), 41.3 (+ 60%), and 47.2 (+ 22%) per 1,000 inhabitants. For all STIs combined, the number of tested individuals decreased by 37% between March and April 2020 during the first COVID-19 epidemic wave and lockdown in France.ConclusionImprovements found in STI testing rates may have resulted from better awareness, especially among young people and health professionals, of the importance of testing, following prevention campaigns. Nevertheless, testing levels remain insufficient considering increasing diagnoses. In 2020, the COVID-19 pandemic had a considerable impact on STI testing. Partner notification and offering diverse testing opportunities including self-sampling are essential to control STI epidemics particularly in exposed populations.

Bortezomib Eliminates Persistent Chlamydia trachomatis Infection through Rapid and Specific Host Cell Apoptosis.

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.

Epididymitis rates in Australian hospitals 2009-2018: ecological analysis.

OBJECTIVES: To investigate rates of acute epididymitis diagnosed in Australian hospital settings. METHODS: Yearly hospital admission and emergency department (ED) rates of epididymitis as primary diagnoses were calculated for 15-44-year-old men for three states (Victoria, New South Wales, Queensland) from 2009 to 2014 using population denominators. Zero inflated Poisson regression models were used to analyse variation in rates by year, age, and residential area. Additionally, we investigated national epididymitis admission trends from 2009 to 2018 using generalised linear models. RESULTS: Between 2009 and 2014, there was a total of 7375 admissions and 17 281 ED presentations for which epididymitis was the main reason for care. Most epididymitis diagnoses (94.0% in admissions, 99.7% in EDs) were without abscess, and 2.5% of admissions were for chlamydial epididymitis. Almost a quarter (23.3%) of epididymitis diagnosed in EDs resulted in hospital admission. In 2014, the epididymitis rate per 100 000 men was 38.7 in admissions and 91.9 in EDs. Comparing 2014 with 2009, the overall epididymitis diagnosis rate increased in admissions by 32% (adjusted incident rate ratio (aIRR) 1.32, 95% CI 1.20 to 1.44) and in ED attendances by 40% (aIRR 1.40, 95% CI 1.31 to 1.49). By age, the highest rates were among men 35-44 years in admissions and men 15-24 years in EDs. National admission rates of epididymitis during 2009-2018 showed a similar pattern. CONCLUSION: Rates of epididymitis diagnosis in hospital admission and ED presentations increased. Different age-related rates in these settings suggest a different aetiology or differential severity by age group.

High prevalence of coinfection of azithromycin-resistant Mycoplasma genitalium with other STIs: a prospective observational study of London-based symptomatic and STI-contact clinic attendees.

OBJECTIVES: Azithromycin treatment of Chlamydia trachomatis (CT) may not be adequate to treat concomitant Mycoplasma genitalium (MG) infection, and particularly if MG has macrolide resistance-associated mutations (MG-MRAMs). We estimated prevalence of coinfections of CT with MG carrying MRAM, and risk factors for MG-MRAM among a sexual health clinic population. STUDY DESIGN AND SETTING: Among symptomatic and STI-contact clinic attendees in London, prevalence of CT-MG coinfection and MG-MRAM were estimated using nucleic acid amplification testing and Sanger sequencing, respectively, and their associated risk factors analysed using logistic regression. RESULTS: MG prevalence was 7.5% (23/307), 17.3% (30/173), and 11.4% (8/70) in females, men who have sex with women (MSW) and men who have sex with men (MSM), respectively; MG coinfection in CT-infected participants represented 28.0% (7/25), 13.5% (5/37), 0.0% (0/0), respectively. Presence of MG-MRAM was 39.1% (9/23) in female swabs, 70.0% (21/30) in MSW urine and 83.3% (5/6) in MSM rectal swabs. In multivariate analyses, coinfection with another STI was strongly associated with MG-MRAM (OR: 7.19; 95% CI: 2.4 to 21.5). CONCLUSION: A significant proportion of participants in our study of symptomatic patients and STI contacts were infected with macrolide-resistant MG, suggesting that testing for MG and MRAM, for MG positives, might be clinically useful. The findings also suggest services explore potential benefits of testing CT positive samples for MG in these patient groups. Where MG testing is not available, potential high rates of MG coinfection should be borne in mind when considering azithromycin in the treatment of CT among STI contacts and symptomatic patients.

Characterising HIV and STIs among transgender female sex workers: a longitudinal analysis.

OBJECTIVES: Though highly vulnerable to HIV and STIs, transgender female sex workers (TFSWs) are understudied in the US HIV and STI response. This study examined the correlates of laboratory-confirmed STIs among a cohort of 62 TFSWs followed over the course of 1 year and explored associations between specimen site and self-reported engagement in insertive and receptive anal intercourse. METHODS: Participants completed an interviewer-administered computer-assisted personal interview at baseline, 3-, 6-, 9- and 12-month visits where self-administered anal swabs and urine samples for gonorrhea, chlamydia and trichomoniasis were also collected. HIV testing was conducted at baseline, 6-month and 12-month visits. RESULTS: Baseline HIV prevalence was 40.3% with no HIV seroconversions over follow-up. Baseline prevalence of gonorrhea, chlamydia and trichomoniasis was 9.7%, 17.7% and 14.5%, respectively. In the multivariable regression modelling, recent arrest was significantly associated with testing positive for any STI (adjusted risk ratio (RR) 1.77; 95% CI: 1.10 to 2.84). Insertive anal sex with clients was associated with increased risk of testing positive for an STI via urine specimen (RR 3.48; 95% CI: 1.14 to 10.62), while receptive anal sex was not significantly associated with specimen site. CONCLUSION: Our findings confirm a high prevalence of STIs among TFSWs and highlight the importance of addressing structural drivers such as criminal justice involvement as well as the need to ensure screening for STIs at all anatomical sites regardless of self-reported sites of potential exposure. More research is needed to better understand HIV and STI vulnerabilities and appropriate interventions for TFSWs in the USA.

Evidence of changing sexual behaviours and clinical attendance patterns, alongside increasing diagnoses of STIs in MSM and TPSM.

BACKGROUND: Due to rising numbers of STI diagnosis and increasing prevalence of antimicrobial resistance, we explored trends in STI testing frequency and diagnoses, alongside sexual decision making and attitudes concerning condom use and HIV pre-exposure prophylaxis (PrEP) at a large urban UK sexual health clinic. METHODS: We examined 66 528 electronic patient records covering 40 321 attendees between 2016 and 2019, 3977 of whom were men who have sex with men or trans persons who have sex with men (MSM/TPSM). We also explored responses from MSM/TPSM attendees sent an electronic questionnaire between November 2018 and 2019 (n=1975) examining behaviours/attitudes towards PrEP. We measured trends in STI diagnoses and sexual behaviours including condomless anal intercourse (CAI), using linear and logistic regression analyses. RESULTS: Tests resulting in gonorrhoea, chlamydia or syphilis diagnoses increased among MSM/TPSM from 13.5% to 18.5% between 2016 and 2019 (p<0.001). The average MSM/TPSM STI testing frequency increased from 1.5/person/year to 2.1/person/year (p=0.017). Gay MSM/TPSM had the highest proportions of attendances resulting in diagnoses, increasing from 15.1% to 19.6% between 2016 and 2019 (p<0.001) compared with bisexual/other MSM/TPSM increasing from 6.9% to 14.5% (p<0.001), alongside smaller but significant increases in non-MSM/TPSM from 5.9% to 7.7% (p<0.001).The proportion of MSM/TPSM clinic attendees reporting CAI in the previous 3 months prior to at least one appointment in a given year increased significantly from 40.6% to 45.5% between 2016 and 2019 (p<0.0001) and average number of partners from 3.8 to 4.5 (p=0.002). Of 617 eligible questionnaire responses, 339/578 (58.7%) HIV-negative and 29/39 (74.4%) HIV-positive MSM/TPSM indicated they would be more likely to have CAI with someone on PrEP versus not on PrEP. 358/578 (61.9%) HIV-negative respondents said that PrEP use would make them more likely to have CAI with HIV-negative partners. CONCLUSION: Rising numbers of STI diagnoses among MSM/TPSM are not attributable to increased testing alone. Increased CAI and number of partners may be attributable to evolving sexual decision making among PrEP users and their partners. Proportionally, bisexual/other MSM/TPSM have the steepest increase in STI diagnoses.

Aetiology and prevalence of mixed-infections and mono-infections in non-gonococcal urethritis in men: a case-control study.

OBJECTIVES: Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) cause the majority of non-gonococcal urethritis (NGU). The role of Ureaplasma urealyticum (UU) in NGU is unclear. Prior case-control studies that examined the association of UU and NGU may have been confounded by mixed infections and less stringent criteria for controls. The objective of this case-control study was to determine the prevalence and aetiology of mixed infections in men and assess if UU monoinfection is associated with NGU. METHODS: We identified 155 men with NGU and 103 controls. Behavioural and clinical information was obtained and men were tested for Neisseria gonorrhoeae and CT, MG, UU and Trichomonas vaginalis (TV). Men who were five-pathogen negative were classified as idiopathic urethritis (IU). RESULTS: Twelve per cent of NGU cases in which a pathogen was identified had mixed infections, mostly UU coinfections with MG or CT; 27% had IU. In monoinfected NGU cases, 34% had CT, 17% had MG, 11% had UU and 2% had TV. In controls, pathogens were rarely identified, except for UU, which was present in 20%. Comparing cases and controls, NGU was associated with CT and MG monoinfections and mixed infections. UU monoinfection was not associated with NGU and was almost twice as prevalent in controls. Men in both the case and control groups who were younger and who reported no prior NGU diagnosis were more likely to have UU (OR 0.97 per year of age, 95% CI 0.94 to 0.998 and OR 6.3, 95% CI 1.4 to 28.5, respectively). CONCLUSIONS: Mixed infections are common in men with NGU and most of these are UU coinfections with other pathogens that are well-established causes of NGU. UU monoinfections are not associated with NGU and are common in younger men and men who have never previously had NGU. Almost half of NGU cases are idiopathic.

Assessment of rectal Chlamydia trachomatis viable load in women by viability-PCR.

OBJECTIVES: In recent years, studies have demonstrated frequent rectal Chlamydia trachomatis (CT) detection in women, irrespective of reported anal sex or rectal symptoms. However, the clinical relevance and public health implication of rectal CT detection in women remain under debate. Therefore, evaluating CT viability may provide more insight into the relevance of standard routine nucleic acid amplification test (NAAT)-positive results. METHODS: In this cross-sectional explorative study, a convenience sample of female patients at our STI clinic aged 18 years or older, diagnosed with vaginal and/or rectal CT, were invited to participate. On return for treatment, rectal CT-diagnosed women were instructed to self-collect rectal swab samples before being treated. Standard COBAS 4800 CT/NG routine NAAT testing was applied for CT diagnosis. Rectal viable CT load was evaluated by using viability-PCR (V-PCR). RESULTS: 53 women with rectal CT were included in this study; 86.8% (46/53) had a quantifiable rectal total CT load. Of women with quantifiable samples, 52.2% (24/46) had viable CT detected from rectal swabs by V-PCR, with a mean rectal viable CT load of 3.31 log10 CT/mL (range 1.16-6.22). No statistically significant difference (p=0.73) was observed in the mean rectal viable CT load of women with an indication for rectal testing (n=9) and without (n=15), 3.20 log10 CT/mL (range 2.06-4.36) and 3.38 log10 CT/mL (range 1.16-6.22), respectively. CT culture yielded positive test results from rectal swabs in 22.6% (12/53) of rectal CT NAAT-diagnosed women. Of women with viable rectal CT by V-PCR (n=24), 50% (12/24) were positive by CT culture. CONCLUSIONS: Overall, the detection of high rectal viable CT loads in this study indicates that rectal CT in some women might represent a currently ongoing infection rather than just the presence of remnant DNA from dead bacteria or only contamination from an active vaginal CT infection.

How to increase chlamydia testing in primary care: a qualitative exploration with young people and application of a meta-theoretical model.

OBJECTIVE: The objective of this study was to explore young people's perspectives barriers to chlamydia testing in general practice and potential intervention functions and implementation strategies to overcome identified barriers, using a meta-theoretical framework (the Behaviour Change Wheel (BCW)). METHODS: Twenty-eight semistructured individual interviews were conducted with 16-24 year olds from across the UK. Purposive and convenience sampling methods were used (eg, youth organisations, charities, online platforms and chain-referrals). An inductive thematic analysis was first conducted, followed by thematic categorisation using the BCW. RESULTS: Participants identified several barriers to testing: conducting self-sampling inaccurately (physical capability); lack of information and awareness (psychological capability); testing not seen as a priority and perceived low risk (reflective motivation); embarrassment, fear and guilt (automatic motivation); the UK primary care context and location of toilets (physical opportunity) and stigma (social opportunity). Potential intervention functions raised by participants included education (eg, increase awareness of chlamydia); persuasion (eg, use of imagery/data to alter beliefs); environmental restructuring (eg, alternative sampling methods) and modelling (eg, credible sources such as celebrities). Potential implementation strategies and policy categories discussed were communication and marketing (eg, social media); service provision (eg, introduction of a young person's health-check) and guidelines (eg, standard questions for healthcare providers). CONCLUSIONS: The BCW provided a useful framework for conceptually exploring the wide range of barriers to testing identified and possible intervention functions and policy categories to overcome said barriers. While greater education and awareness and expanded opportunities for testing were considered important, this alone will not bring about dramatic increases in testing. A societal and structural shift towards the normalisation of chlamydia testing is needed, alongside approaches which recognise the heterogeneity of this population. To ensure optimal and inclusive healthcare, researchers, clinicians and policy makers alike must consider patient diversity and the wider health issues affecting all young people.

Prevalence and persistence of Chlamydia trachomatis-specific antibodies after occasional and recurrent infections.

OBJECTIVES: Population-based Chlamydia trachomatis seroepidemiological studies help to identify trends in chlamydia infection. However, an improved understanding of the antibody response to infection is required when using serology to estimate cumulative incidence. Thus, the objectives of this longitudinal, retrospective, biobank-based study were to assess the appearance and persistence of C. trachomatis major outer membrane protein (MOMP)-specific serum IgG antibodies after infection and to evaluate the role of antibodies in providing protective immunity against recurrent infection. METHODS: Data of notified C. trachomatis infections in Finland were obtained from the National Infectious Diseases Register. Serum samples were acquired from the Finnish Maternity Cohort. 411 women with single chlamydia infection and 62 women with recurrent infections, and for whom suitable paired serum samples were available, were included in the study. Antibody appearance, persistence after infection and the impact of recurrent infections were evaluated. IgG antibodies specific for MOMP were measured from serum using an ELISA method. RESULTS: Anti-C. trachomatis MOMP-specific IgG antibodies were detected in 65.5% (269/411) of women within 3 months of notification of infection. In the absence of recurrent infection, seroprevalence declined to 34.5% (142/411) 3-10 years after the initial infection. The serum antibody levels at baseline correlated positively with seroprevalence at follow-up. Reinfection boosted the humoral immune response by increasing seroprevalence and the serum antibody levels. Seroprevalence within 3 months after first notification of infection was 65.5% (19/29) in women who were later diagnosed with recurrent infection, comparable with women with single notification of infection (65.5%, 269/411). CONCLUSIONS: Approximately one-third of women with single notification of chlamydia infection remain seropositive 3-10 years after the initial infection. The concentration of antibodies remained stable during the follow-up. Recurrent infection boosted the humoral immune response, but reinfection occurred despite the presence of pre-existing antibodies.

A unique insight into the MiRNA profile during genital chlamydial infection.

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.

Standardisation is necessary in urogenital and extragenital Chlamydia trachomatis bacterial load determination by quantitative PCR: a review of literature and retrospective study.

OBJECTIVES: Pathogen load has been linked to disease severity in patients infected with HIV, resulting in international standards to adequately and reproducibly quantify load. Chlamydia trachomatis (CT) load has been inconsistently linked to disease severity since extensive differences exist in quantification methods (14 methods in 28 articles). Differences include normalisation for human cell load due to CT's intracellular nature, despite the inability to distinguish inflammatory cells from epithelial cells with molecular techniques. We compared the human cell load in CT-positive men and women at the genital and anal site to a CT-negative control group to estimate the impact of inflammatory cells in these samples. METHODS: 188 women (tested at genital and anal site) and 519 men (207 tested at the anal site and 312 tested at the urogenital site) were included from our STI-clinic in the Netherlands. Specimens were self-collected vaginal swabs, anal swabs and urine samples. Quantitative-PCR targeting the HLA-gene quantified human cell load. Mann-Whitney-U-test was used for statistical analyses. RESULTS: The genital cell load had a similar range and median (6.5 log10) between CT-negative and CT-positive women . The urogenital cell load was significantly higher than the anal cell load (median 3.6 log10). The anal cell load was significantly higher in men with- than without anal CT infection (median 4.5 versus 3.9 respectively). The anal cell load is significantly higher in CT-positive men than in women. Both Neisseria gonorrhoeae-co-infections and reported anal intercourse significantly increased the human cell load in anal samples. CONCLUSION: Standardisation in CT load studies is necessary as current studies show 14 different quantification methods in 28 studies . In this study we demonstrate the inappropriateness of normalising the CT load for the human cell load using molecular techniques, as the presence of inflammatory cells cannot be excluded.

[Health risk factors in the family-members of chlamydiosis patients]. / Faktory riska dlia zdorov'ia chlenov semei s ochagom khlamidiinoi infektsii.

AIM: To study the characteristics of health state in family-members of ENT-patients with identified Chlamydia infection. METHODS: We have examined 245 members of 87 families of otorhinolaryngological patients with verified (44 families) and without (44 families) Chlamydia infection. Laboratory methods of the research included the identification of the following types: Chlamydia trachomatis and Chlamydophila pneumoniae. Chlamydia diagnostics involved both direct immune fluorescence and immune enzyme analyses as well as polymerase chain reaction. Health state in ENT-patient family-members has been evaluated by the complex method based on the special questionnaire for every family-member aimed at determining the health category, the calculation of health average coefficient for each family member followed by the determination of family identity with some definite health category. RESULTS: in the families of otorhinolaryngological patients with verified Chlamydia infection there have been revealed considerably more family-members with acute and chronic pathology of different organs and systems associated with functional disorders. The health status of family members of ENT patients with respiratory Chlamydia was significantly worse than in families of patients with negative laboratory results for Chlamydia, which was manifested by a much smaller number of healthy family members and a large number of people with risk factors for health.

Effect of rectal douching/enema on rectal gonorrhoea and chlamydia among a cohort of men who have sex with men on HIV pre-exposure prophylaxis.

OBJECTIVES: Rectal 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). METHODS: From 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. RESULTS: Of 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<0.001), male partners (med:6, p<0.001) and substance use (any of methamphetamine/hallucinogens/dissociative/poppers) (p<0.001) were associated with increased odds of RI. Controlling for potential confounders, odds of prevalent RI were 3.59 (p<0.001, 95% CI 1.90 to 6.78) and incident RI 3.87 (p=0.001, 95% CI 1.78 to 8.39) when douching weekly or more compared with not douching. MSM with more than six male partners had 5.34 (p=0.002, 95% CI 1.87 to 15.31) increased odds of RI when douching weekly or more compared with not douching. CONCLUSION: Rectal hygiene with RD is a common practice (66%) among HIV-uninfected MSM on PrEP in this study, which increases the odds of acquiring rectal NG and/or CT independent of sexual risk behaviour, substance use and other factors. This suggests interventional approaches targeting rectal hygiene products and practices could reduce sexually transmitted infections.

Patterns of prevalent HPV and STI co-infections and associated factors among HIV-negative young Western Cape, South African women: the EVRI trial.

OBJECTIVE: To estimate the prevalence and describe the patterns of concurrent human papillomavirus (HPV) and STIs and associated factors among HIV-negative young Western Cape, South African women participating in the Efficacy of HPV Vaccine to Reduce HIV Infection (EVRI) trial. METHODS: HIV-negative women aged 16-24 years old were enrolled in the EVRI trial (NCT01489527) and randomised to receive the licensed four-valent HPV vaccine or placebo. At study entry, participants were clinically evaluated for five STIs: herpes simplex virus type 2 (HSV-2), chlamydia, gonorrhoea, syphilis and disease-causing HPV genotypes (6/11/16/18/31/33/35/39/45/51/52/56/58/59/68). Demographic and sexual history characteristics were compared among women with STI co-infections, single infection and no infection using Pearson χ2 and Mann-Whitney tests. ORs were calculated to evaluate factors associated with STI co-infection prevalence. RESULTS: Among 388 young women, STI co-infection prevalence was high: 47% had ≥2 concurrent STIs, 36% had a single STI and 17% had none of the five evaluated STIs. HPV/HSV-2 (26%) was the most prevalent co-infection detected followed by HPV/HSV-2/Chlamydia trachomatis (CT) (17%) and HPV/CT (15%). Co-infection prevalence was independently associated with alcohol use (adjusted OR=2.01, 95% CI 1.00 to 4.06) and having a sexual partner with an STI (adjusted OR=6.96, 95% CI 1.53 to 30.08). CONCLUSIONS: Among high-risk young women from underserved communities such as in Southern Africa, a multicomponent prevention strategy that integrates medical and behavioural interventions targeting both men and women is essential to prevent acquisition of concurrent STI infections and consequent disease. TRIAL REGISTRATION NUMBER: NCT01489527; Post-results.

Impact of expedited partner therapy (EPT) implementation on chlamydia incidence in the USA.

OBJECTIVES: The diagnosis and treatment of Chlamydia trachomatis infection is important in preventing persistent or recurrent infection. Expedited partner therapy (EPT) is the favoured and supported method for STI treatment of the Centers for Disease Control and Prevention when the provider cannot be assured that all recent sexual partner(s) will seek therapy. EPT is legally permissible in 38 states and is endorsed by healthcare organisations to decrease the rates of chlamydia and gonorrhoea infection. Our study investigated the impact of EPT legal status (permissible, potentially allowable or prohibited) on C. trachomatis infection rates for each state. METHODS: Our ecological study modelled the number of reported chlamydia cases from 2000 to 2013 as a function of year, legal status and the interaction between year and legality. We used a negative binomial regression model that included state fixed effects (including the District of Columbia) to account for both the repeated measures per state and state-specific characteristics that could not be measured for inclusion in this study. The lagged number of C. trachomatis cases was included as a covariate and each state's total population for a given year was included in the model as an exposure parameter. States were designated Y (EPT permissible), N (EPT prohibited) and M (EPT potentially allowable), and the legal status of each state could vary over time. RESULTS: Each legal category saw an increase in the incidence rate of C. trachomatis infection, but on average, the incidence rate for states with prohibitive EPT legislation grew significantly faster over time compared with the rate for the states where EPT was permissible. The average increase in predicted incidence rates per year for states with Y, N and M legal status were 14.1 (95% CI (12.0 to 16.2)), 17.5 (95% CI (15.9 to 19.2)) and 16.8 (95% CI (15.0 to 18.6)) cases per 100 000 persons per year, respectively, when controlling for state-specific effects. CONCLUSIONS: Our model suggests that a lack of EPT legislation is associated with an increase in STI rates. States with potentially allowable EPT legislation as of 2013 (n=8) should consider permitting EPT as a component of a multipronged strategy for treatment of sexual partners to prevent C. trachomatis infection.