Effects of azithromycin and doxycycline on the vaginal microbiota of women with urogenital Chlamydia trachomatis infection: a substudy of the Chlazidoxy randomized controlled trial.

OBJECTIVES: Dysbiotic bacterial communities within the vagina are associated with Chlamydia trachomatis infection. We compared the effect of treatment with azithromycin and doxycycline on the vaginal microbiota in a cohort of women with a urogenital C. trachomatis infection randomly assigned to one of these treatments (Chlazidoxy trial). METHODS: We analysed vaginal samples from 284 women (135 in the azithromycin group and 149 in the doxycycline group) collected at baseline and 6 weeks after treatment initiation. The vaginal microbiota was characterized using 16S rRNA gene sequencing and classified into community state types (CSTs). RESULTS: At baseline, 75% (212/284) of the women had a high-risk microbiota (CST-III or CST-IV). A cross-sectional comparison 6 weeks after treatment showed that 15 phylotypes were differentially abundant, but this difference was not reflected at the CST (p 0.772) or diversity level (p 0.339). Between baseline and the 6-week visit, α-diversity (p 0.140) and transition probabilities between CSTs were not significantly different between the groups, and no phylotype was differentially abundant. DISCUSSION: In women with urogenital C. trachomatis infection, the vaginal microbiota does not seem to be affected by azithromycin or doxycycline 6 weeks after treatment. Because the vaginal microbiota remains susceptible to C. trachomatis infection (with CST-III or CST-IV) after antibiotic treatment, women remain at risk of reinfection, which could originate from unprotected sexual intercourse or untreated anorectal C. trachomatis infection. This last consideration advocates for the use of doxycycline instead of azithromycin because of its higher anorectal microbiological cure rate.

Multi-component prime-boost Chlamydia trachomatis vaccination regimes induce antibody and T cell responses and accelerate clearance of infection in a non-human primate model.

It is of international priority to develop a vaccine against sexually transmitted Chlamydia trachomatis infections to combat the continued global spread of the infection. The optimal immunization strategy still remains to be fully elucidated. The aim of this study was to evaluate immunization strategies in a nonhuman primate (NHP) model. Cynomolgus macaques (Macaqua fascicularis) were immunized following different multi-component prime-boost immunization-schedules and subsequently challenged with C. trachomatis SvD in the lower genital tract. The immunization antigens included the recombinant protein antigen CTH522 adjuvanted with CAF01 or aluminium hydroxide, MOMP DNA antigen and MOMP vector antigens (HuAd5 MOMP and MVA MOMP). All antigen constructs were highly immunogenic raising significant systemic C. trachomatis-specific IgG responses. In particularly the CTH522 protein vaccinated groups raised a fast and strong pecificsIgG in serum. The mapping of specific B cell epitopes within the MOMP showed that all vaccinated groups, recognized epitopes near or within the variable domains (VD) of MOMP, with a consistent VD4 response in all animals. Furthermore, serum from all vaccinated groups were able to in vitro neutralize both SvD, SvE and SvF. Antibody responses were reflected on the vaginal and ocular mucosa, which showed detectable levels of IgG. Vaccines also induced C. trachomatis-specific cell mediated responses, as shown by in vitro stimulation and intracellular cytokine staining of peripheral blood mononuclear cells (PBMCs). In general, the protein (CTH522) vaccinated groups established a multifunctional CD4 T cell response, whereas the DNA and Vector vaccinated groups also established a CD8 T cells response. Following vaginal challenge with C. trachomatis SvD, several of the vaccinated groups showed accelerated clearance of the infection, but especially the DNA group, boosted with CAF01 adjuvanted CTH522 to achieve a balanced CD4/CD8 T cell response combined with an IgG response, showed accelerated clearance of the infection.

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.

Doxycycline versus azithromycin for the treatment of anorectal Chlamydia trachomatis infection in women concurrent with vaginal infection (CHLAZIDOXY study): a multicentre, open-label, randomised, controlled, superiority trial.

BACKGROUND: Anorectal infections with Chlamydia trachomatis are commonly found in women. Although the efficacy of doxycycline and azithromycin is comparable in the treatment of urogenital infection, their efficacies toward anorectal infection remain unclear. We therefore aimed to compare a single dose of azithromycin with a 7-day course of doxycycline for the treatment of anorectal C trachomatis infection in women with concurrent vaginal infection. METHODS: We did a multicentre, open-label, randomised, controlled, superiority trial involving four sexually transmitted infection screening centres and three pregnancy termination centres in France. We included sexually active adult women (≥18 years) with a positive C trachomatis vaginal swab who agreed to provide self-collected anorectal swabs for C trachomatis detection. Participants were randomly assigned (1:1), using block sizes of six and eight and stratification by each investigating centre, to orally receive either azithromycin (a single 1-g dose, with or without food) or doxycycline (100 mg in the morning and evening at mealtimes for 7 days [ie, 100 mg of doxycycline twice per day for 7 days]). All laboratory staff who did the bacteriological analyses, but not the participants and the investigators, were masked to the treatment groups. The primary outcome was the microbiological anorectal cure rate defined as a C trachomatis-negative nucleic acid amplification test (NAAT) result in anorectal specimens 6 weeks after treatment initiation among women who had a baseline C trachomatis-positive anorectal NAAT result. The primary analysis was done in the modified intention-to-treat population, with multiple imputation, which included all women who underwent randomisation and had a C trachomatis-positive vaginal and anorectal NAAT result at baseline. Adverse events were reported in all women who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT03532464. FINDINGS: Between Oct 19, 2018, and April 17, 2020, we randomly assigned a total of 460 participants to either the doxycycline group (n=230) or the azithromycin group (n=230). Four (1%) of 460 participants were excluded because they refused to take doxycycline or were found to be ineligible after randomisation. Among the 456 participants, 357 (78%) had a concurrent C trachomatis-positive anorectal NAAT result at baseline; 184 (52%) of 357 were in the doxycycline group and 173 (48%) were in the azithromycin group (ie, the modified intention-to-treat population). Microbiological anorectal cure occurred in 147 (94%) of 156 participants in the doxycycline group (28 missing values) versus 120 (85%) of 142 in the azithromycin group (31 missing values; adjusted odds ratio with imputation of missing values 0·43 [95% CI 0·21-0·91]; p=0·0274). Reported adverse events possibly related to treatment were notified in 53 (12%) of 456 women: 24 (11%) of 228 in the doxycycline group and 29 (13%) of 228 in the azithromycin group. Gastrointestinal disorders were the most frequently occurring, in 43 (9%) of 456 women: 17 (8%) of 228 in the doxycycline group and 26 (11%) of 228 in the azithromycin group. INTERPRETATION: The microbiological anorectal cure rate was significantly lower among women who received a single dose of azithromycin than among those who received a 1-week course of doxycycline. This finding suggests that doxycycline should be the first-line therapy for C trachomatis infection in women. FUNDING: French Ministry of Health. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Spread of clonal genovar E Chlamydia trachomatis among men who have sex with men.

In a previous study, we developed a Multi-Locus VNTRs Analysis (MLVA) typing system, called MLVA-5, for the discrimination of Chlamydia trachomatis genovar E strain. The results suggested the clonal spread of a MLVA-5 type 21 strain among men who have sex with men (MSM). We applied the MLVA-5 typing method on 157 French anorectal genovar E specimens and 19 Swedish specimens collected between 2010 and 2015. A total of 29 MLVA-5 types was obtained, with three predominant types among French samples: 78 specimens belonged to MLVA-5 type 21, two other types, 11 and 13, included 9 and 14 specimens, respectively. In 15 cases, one unique MLVA-5 type was observed for a single patient, 7 of which were new types not previously described. The distribution of MLVA-5 types according to sexual orientation showed that the 7 anorectal specimens from heterosexual patients belonged to 6 genotypes, and the 12 anorectal specimens from bisexual patients comprised eight types. The 95 anorectal specimens from MSM were distributed into 22 types, but 55 (57.9%) of them belonged to MLVA-5 type 21. Among the Swedish specimens from MSM, eight were from MLVA-type 21 (4 urines and 4 anorectal specimens). The results support the hypothesis of the spread of clonal genovar E strain among MSM.

Ongoing evolution of Chlamydia trachomatis lymphogranuloma venereum: exploring the genomic diversity of circulating strains.

Lymphogranuloma venereum (LGV), the invasive infection of the sexually transmissible infection (STI) Chlamydia trachomatis, is caused by strains from the LGV biovar, most commonly represented by ompA-genotypes L2b and L2. We investigated the diversity in LGV samples across an international collection over seven years using typing and genome sequencing. LGV-positive samples (n=321) from eight countries collected between 2011 and 2017 (Spain n=97, Netherlands n=67, Switzerland n=64, Australia n=53, Sweden n=37, Hungary n=31, Czechia n=30, Slovenia n=10) were genotyped for pmpH and ompA variants. All were found to contain the 9 bp insertion in the pmpH gene, previously associated with ompA-genotype L2b. However, analysis of the ompA gene shows ompA-genotype L2b (n=83), ompA-genotype L2 (n=180) and several variants of these (n=52; 12 variant types), as well as other/mixed ompA-genotypes (n=6). To elucidate the genomic diversity, whole genome sequencing (WGS) was performed from selected samples using SureSelect target enrichment, resulting in 42 genomes, covering a diversity of ompA-genotypes and representing most of the countries sampled. A phylogeny of these data clearly shows that these ompA-genotypes derive from an ompA-genotype L2b ancestor, carrying up to eight SNPs per isolate. SNPs within ompA are overrepresented among genomic changes in these samples, each of which results in an amino acid change in the variable domains of OmpA (major outer membrane protein, MOMP). A reversion to ompA-genotype L2 with the L2b genomic backbone is commonly seen. The wide diversity of ompA-genotypes found in these recent LGV samples indicates that this gene is under immunological selection. Our results suggest that the ompA-genotype L2b genomic backbone is the dominant strain circulating and evolving particularly in men who have sex with men (MSM) populations.

A New SNP-Based Genotyping Method for C. psittaci: Application to Field Samples for Quick Identification.

Chlamydia (C.) psittaci is the causative agent of avian chlamydiosis and human psittacosis. In this study, we extracted single-nucleotide polymorphisms (SNPs) from the whole genome sequences of 55 C. psittaci strains and identified eight major lineages, most of which are host-related. A combined PCR/high-resolution melting (HRM) assay was developed to screen for eight phylogenetically informative SNPs related to the identified C. psittaci lineages. The PCR-HRM method was validated on 11 available reference strains and with a set of 118 field isolates. Overall, PCR-HRM clustering was consistent with previous genotyping data obtained by ompA and/or MLST analysis. The method was then applied to 28 C. psittaci-positive samples from animal or human cases. As expected, PCR-HRM typing results from human samples identified genotypes linked to ducks and pigeons, a common source of human exposure, but also to the poorly described Mat116-like genotype. The new genotyping method does not require time-consuming sequencing and allows a quick identification of the source of infection.

Identification of 16S rRNA mutations in Mycoplasma genitalium potentially associated with tetracycline resistance in vivo but not selected in vitro in M. genitalium and Chlamydia trachomatis.

OBJECTIVES: Tetracyclines are widely used for the treatment of bacterial sexually transmitted infections (STIs) and recently have been used successfully for post-exposure prophylaxis of STIs in MSM. We investigated the in vitro and in vivo development of tetracycline resistance in Chlamydia trachomatis and Mycoplasma genitalium and evaluated 16S rRNA mutations associated with acquired resistance in other bacteria. METHODS: In vitro selection of resistant mutants of reference strains of C. trachomatis and M. genitalium was undertaken by serial passage in medium containing subinhibitory concentrations of tetracycline or doxycycline, respectively. The 16S rRNA gene of the two microorganisms was amplified and sequenced at different passages, as were those of 43 C. trachomatis- and 106 M. genitalium-positive specimens collected in France from 2013 to 2019. RESULTS: No tetracycline- or doxycycline-resistant strains of C. trachomatis and M. genitalium, respectively, were obtained after 30 serial passages. The tetracycline and doxycycline MICs were unchanged and analysis of the 16S rRNA gene, the molecular target of tetracyclines, of C. trachomatis and M. genitalium revealed no mutation. No mutation in the 16S rRNA gene was detected in C. trachomatis-positive specimens. However, six M. genitalium-positive specimens harboured a mutation potentially associated with tetracycline resistance without known prior tetracycline treatment for patients. CONCLUSIONS: Tetracyclines did not select in vitro-resistant mutants of C. trachomatis or M. genitalium. However, 16S rRNA mutations either responsible for or associated with tetracycline resistance in other bacteria, including mycoplasma species, were identified in several M. genitalium-positive specimens.

Evaluation of four commercial real-time PCR assays for the detection of lymphogranuloma venereum in Chlamydia trachomatis-positive anorectal samples.

OBJECTIVES: Lymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by Chlamydia trachomatis (CT) genovars L. The identification of LGV is of therapeutic interest because treatment requires 3 weeks of doxycycline compared with 1 week for infection with a non-L strain. The aim of this study was to evaluate the performance of four commercial real-time PCR kits in comparison with the reference methods used for LGV diagnosis by the French National Reference Centre (NRC) for bacterial STIs. METHODS: A total of 215 French CT-positive anorectal specimens collected consecutively in 2017 were used (66 LGV and 149 non-LGV). Among these, 92 were collected from symptomatic men who have sex with men (MSM) and 123 from asymptomatic MSM using pre-exposure prophylaxis. Four commercial assays were evaluated; a single-plex assay RealCycler CHSL kit (Progenie Molecular), tested on all the specimens, and three multiplex kits, the RealCycler Universal ULCGEN (Progenie Molecular), the Allplex Genital Ulcer Assay (Seegene) and the VIASURE Haemophilus ducreyi + CT LGV Real Time PCR Detection kit (CerTest Biotec), tested on the 92 samples from symptomatic MSM. Clinical performance was determined in comparison to the in-house real time PCR targeting the pmpH and the ompA gene sequencing. RESULTS: Overall agreement ranged between 91.3% and 100% (95% CI 83.7-100%) with very good Kappa index values (>0.8). The clinical sensitivities and specificities varied between 91% and 100% (95% CI 80.8-100%), and 97% and 100% (95% CI 87.1-100%), respectively, with some kits performing better than others. DISCUSSION: The four assays showed very good performance for the detection of LGV on anorectal specimens.

Prevalence of lymphogranuloma venereum among anorectal Chlamydia trachomatis-positive MSM using pre-exposure prophylaxis for HIV.

OBJECTIVES: We evaluated the prevalence of lymphogranuloma venereum (LGV) in anorectal Chlamydia trachomatis-positive French men who have sex with men (MSM) using pre-exposure prophylaxis (PrEP) for HIV. Here, we describe the clinical, biological and behavioural characteristics of these patients. METHODS: Laboratories throughout French metropolitan areas performing routine testing for C. trachomatis sent positive anorectal specimens to the National Reference Centre for bacterial STIs for LGV real-time PCR targeting the pmpH gene. Identification of the C. trachomatis genovar was performed by ompA gene sequencing. For each patient, clinical, biological and sexual behaviour data were collected after obtaining written informed consent. RESULTS: In 2017, 486 anorectal C. trachomatis-positive specimens from MSM PrEP users were analysed. A strain of genovar L was detected in 91 cases (18.7%). Patients with LGV were significantly more symptomatic, had more sexual partners and more concurrent syphilis compared with their non-LGV counterparts. OmpA gene sequencing, successful in two-thirds of anorectal C. trachomatis-positive specimens, showed that the LGV cases were mainly of variant L2b (n=33), followed by genovar L2 (n=27) and genetic L2b ompA variants (n=16). In 11 cases, the results indicated the occurrence of genetic exchange between L and non-L genovars. CONCLUSIONS: LGV was diagnosed in 18.7% of anorectal C. trachomatis-positive specimens from French MSM using PrEP. LGV testing should be carried out for MSM diagnosed with chlamydia and with a large number of sexual partners, high-risk practices and anorectal symptoms. These patients should be presumptively treated as having LGV. This is the first surveillance study of LGV among MSM PrEP users and monitoring should continue.

Pelvic inflammatory diseases: Updated French guidelines.

Pelvic inflammatory diseases (PID) must be suspected when spontaneous pelvic pain is associated with induced adnexal or uterine pain (grade B). Pelvic ultrasonography is necessary to rule out tubo-ovarian abscess (TOA) (grade C). Microbiological diagnosis requires endocervical and TOA sampling for molecular and bacteriological analysis (grade B). First-line treatment for uncomplicated PID combines ceftriaxone 1 g, once, IM or IV, doxycycline 100 mg ×2/day, and metronidazole 500 mg ×2/day PO for 10 days (grade A). First-line treatment for complicated PID combines IV ceftriaxone 1-2 g/day until clinical improvement, doxycycline 100 mg ×2/day, IV or PO, and metronidazole 500 mg ×3/day, IV or PO for 14 days (grade B). Drainage of TOA is indicated if the pelvic fluid collection measures more than 3 cm (grade B). Follow-up is required in women with sexually transmitted infections (STIs) (grade C). The use of condoms is recommended (grade B). Vaginal sampling for microbiological diagnosis is recommended 3-6 months after PID (grade C), before the insertion of an intrauterine device (grade B), and before elective termination of pregnancy or hysterosalpingography. When specific bacteria are identified, antibiotics targeted at them are preferable to systematic antibiotic prophylaxis.

Randomized, open-label, multicenter study of azithromycin compared with doxycycline for treating anorectal Chlamydia trachomatis infection concomitant to a vaginal infection (CHLAZIDOXY study).

BACKGROUND: Chlamydia trachomatis can lead to a persistent infection in the lower gastrointestinal tract, suggesting a potential role of autoinoculation of cervical chlamydial infection from the rectal site, contributing to repeat infections. Moreover, around 75% of women with urogenital C. trachomatis have concurrent anorectal infection. Current treatment guidelines for urogenital C. trachomatis infection recommend either a single 1 g dose of azithromycin or doxycycline 100 mg twice daily for 7 days. Doxycycline appears to be more effective in treating anorectal infections as suggested in a population of men who have sex with men, but no randomized controlled trial (RCT) had directly compared azithromycin with doxycycline for the treatment of rectal infections. We propose an open-label RCT to compare the microbial cure obtained with a single 1 g dose of azithromycin versus 100 mg of doxycycline twice daily for 7 days, for the treatment of anorectal C. trachomatis infection concurrent to urogenital infection in women. METHODS AND STUDY DESIGN: A total of 460 women with C. trachomatis urogenital infection will be enrolled in the study. Women will be asked to provide self-collected anorectal swabs and will be randomized to receive either a 1 g single dose of azithromycin or doxycycline 100 mg twice daily for 7 days. Clinical and biological data will be collected and patients will complete questionnaires about their sexual behavior. The primary outcome is the microbial cure rate, defined as a C. trachomatis negative nucleic acid amplification test (NAAT) result in the anorectal specimens 6 weeks after treatment initiation among women with a C. trachomatis positive urogenital and anorectal NAAT result at the baseline. The secondary outcome is autoinoculation from the rectum to the vagina, which will be evaluated based on the number of women with the same C. trachomatis genotype profile that will be identified in an anorectal-positive specimen obtained 6 weeks after treatment initiation and in a vaginal-positive specimen obtained four months after treatment. DISCUSSION: The results of this trial will establish which treatment is more efficacious against anorectal infection and could affect recommendations for the treatment of urogenital C. trachomatis infection, taking into account concurrent anorectal infection. TRIAL REGISTRATION NUMBERS: EudraCT number: 2017-002595-15. CLINICALTRIALS. GOV IDENTIFIER: NCT03532464. Date of registration: May 31, 2018. WORLD HEALTH ORGANISATION INTERNATIONAL CLINICAL TRIALS REGISTRY: NTC03532464. Secondary ID: CHUBX 2016/26. Date of registration: May 09, 2018.

Bacterial sexually transmitted infections in France: recent trends and patients' characteristics in 2016.

Diagnoses of bacterial sexually transmitted infections (STI) have been increasing in France since their resurgence in the late 1990s. This article presents recent epidemiological trends until 2016 and the patients' characteristics. STI surveillance relies on sentinel networks: a clinician-based network RésIST (clinical, biological and behavioural data for early syphilis and gonorrhoea), the lymphogranuloma venereum (LGV) network (clinical, biological and behavioural data for rectal LGV, and the laboratory networks Rénachla and Rénago (demographic and biological data for chlamydial infections and gonorrhoea, respectively). Here we describe trends between 2014 and 2016, using data from diagnostic centres which participated regularly during the study period. The number of early syphilis, gonorrhoea and LGV diagnoses increased between 2014 and 2016, particularly in men who have sex with men. An increase in syphilis and gonorrhoea cases was also observed in heterosexuals. Nevertheless, we observed a drop in 2016 for syphilis and chlamydial infections after two decades of increases. Under-reporting and shortage of benzathine penicillin in 2016 may explain this latest evolution. Regular screening of patients and partners, followed by prompt treatment, remains essential to interrupt STI transmission in a context where human immunodeficiency virus (HIV) prevention has expanded towards biomedical prophylaxis.

Contribution of a multiplex serological test for the preoperative diagnosis of prosthetic joint infection: a prospective study.

BACKGROUND: Prosthetic joint infection (PJI) is a severe complication of orthopaedic surgery. Preoperative diagnosis, although sometimes difficult, is key to choose the relevant treatment. METHODS: We conducted a prospective study aimed at evaluating the diagnostic performance of a multiplex serological test for the pre-operative diagnosis of PJI. Blood samples were collected between 1 July 2016 and 31 July 2017 among patients referred for suspected PJI that occurred at least six weeks prior. Infection diagnosis was confirmed using intraoperative bacteriological cultures during prosthetic exchange. RESULTS: Seventy-one patients were included, with a median age of 73 years (interquartile range [IQR]: 66-81) and 40 (56%) were male. Twenty-six patients had aseptic loosening and 45 patients had PJI. Among the latter, median time since the last surgery was 96 weeks (IQR: 20-324). Intraoperative cultures found Staphylococcus spp, Streptococcus spp or both in 39, 5 and 1 patients, respectively. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 81.8, 95.4, 97.3 and 72.4%, respectively, for all patients and 87.5, 93.5, 94.6 and 85.3%, respectively, for staphylococcal infections. Patients with false negative (FN) results had a significantly lower blood lymphocyte count (p = .045). CONCLUSIONS: Multiplex serological test performed well among patients with chronic staphylococcal prosthetic infection. This approach could contribute to PJI diagnosis especially in patients for whom the pre-operative analysis of joint fluid is not informative.

Vaginal microbiota composition and association with prevalent Chlamydia trachomatis infection: a cross-sectional study of young women attending a STI clinic in France.

OBJECTIVES: New molecular techniques have allowed describing groups of bacterial communities in the vagina (community state types (CST)) that could play an important role in Chlamydia trachomatis (CT) infection. Our aim was to describe the distribution of CST in a population of young women in France. METHODS: A cross-sectional study was carried out in June 2015 among anonymous young women attending a STI clinic in Bordeaux, France. Participants provided a vaginal sample for CT screening and sociodemographic data. CT was diagnosed using the Aptima-combo 2 transcription-mediated-amplification assay. Vaginal microbiota composition was characterised using 16S rRNA gene amplicon sequencing. RESULTS: Microbiota composition and CT status were available for 132 women. CST dominated by Lactobacillus crispatus (CST-I), L. iners (CST-III) and a diversity of anaerobes (CST-IV) represented 37.1%, 38.6% and 22.0% of the sample, respectively. Twenty-one out of 132 women were CT positive. Proportions of CT-positive women were higher for samples belonging to CST-III (21.6%) and CST-IV (17.2%) than to CST-I (8.2%). CONCLUSIONS: Five CST were found in 132 young women from a STI clinic in France. These CSTs were not significantly associated with CT but higher proportions of CT-positive women were found in CST-III and CST-IV, consistent with a previous study in the Netherlands. Though our study lacked statistical power and was cross-sectional, it is a necessary first step to understand the structure of the vaginal microbiota in French women with or without infection before performing in-depth longitudinal studies.

Extra-rectal lymphogranuloma venereum in France: a clinical and molecular study.

OBJECTIVES: To describe a series of extrarectal lymphogranuloma venereum (LGV) cases diagnosed in France. METHODS: Consecutive LGV cases confirmed at the French Reference Centre for chlamydiae with an extrarectal sample from January 2010 to December 2015 were included. The first part of the study consisted of a retrospective case note review and analysis. In a second part, the complete ompA gene sequence of our samples was determined. RESULTS: There were 56 cases overall: 50 cases of genital LGV and six cases of pharyngeal LGV. Subjects were all men, median age 39 years, 27/53 were HIV-positive, 47/51 reported having sex with other men, 43/49 reported multiple sexual partners (a mean 25 in the last 6 months). Median time from symptom onset to diagnosis was 21 days. Subjects most commonly presented with inguinal adenopathy alone (19 of 50 genital cases) and adenopathy with genital ulcer (17 of 50). Three pharyngeal cases were symptomatic. Fever was reported in 11 cases. Inguinal abscess was reported in 22 of 42 cases presenting with lymphadenopathy. Co-infections were frequent: eight cases of syphilis, four non-LGV Chlamydia trachomatis infections, one case of gonorrhoea. Cure was always achieved with doxycycline therapy but prolonged treatment was necessary in eight cases with inguinal abscess. Genotyping according to ompA sequencing showed the co-circulation of genovars L2 (16 of 42 strains successfully typed) and L2b (24 of 42). There was no association between HIV status and disease severity or genovar distribution. CONCLUSION: In the span of 6 years, 56 extrarectal LGV cases were confirmed through genotyping in France. Extrarectal LGV seemed to share a common epidemiological background with rectal disease in terms of affected population and genovar distribution. HIV prevalence was lower than expected.

Early screening for Chlamydia trachomatis in young women for primary prevention of pelvic inflammatory disease (i-Predict): study protocol for a randomised controlled trial.

BACKGROUND: Genital infection with Chlamydia trachomatis (Ct) is the most common bacterial sexually transmitted infection, especially among young women. Mostly asymptomatic, it can lead, if untreated, to pelvic inflammatory disease (PID), tubal factor infertility and ectopic pregnancy. Recent data suggest that Ct infections are not controlled in France and in Europe. The effectiveness of a systematic strategy for Ct screening in under-25 women remains controversial. The main objective of the i-Predict trial (Prevention of Diseases Induced by Chlamydia trachomatis) is to determine whether early screening and treatment of 18- to-24-year-old women for genital Ct infection reduces the incidence of PID over 24 months. METHODS/DESIGN: This is a randomised prevention trial including 4000 eighteen- to twenty-four-year-old sexually active female students enrolled at five universities. The participants will provide a self-collected vaginal swab sample and fill in an electronic questionnaire at baseline and at 6, 12 and 18 months after recruitment. Vaginal swabs in the intervention arm will be analysed immediately for Ct positivity, and participants will be referred for treatment if they have a positive test result. Vaginal swabs from the control arm will be analysed at the end of the study. All visits to general practitioners, gynaecologists or gynaecology emergency departments for pelvic pain or other gynaecological symptoms will be recorded to evaluate the incidence of PID, and all participants will attend a final visit in a hospital gynaecology department. The primary endpoint measure will be the incidence of PID over 24 months. The outcome status (confirmed, probable or no PID) will be assessed by two independent experts blinded to group assignment and Ct status. DISCUSSION: This trial is expected to largely contribute to the development of recommendations for Ct screening in young women in France to prevent PID and related complications. It is part of a comprehensive approach to gathering data to facilitate decision-making regarding optimal strategies for Ct infection control. The control group of this randomised trial, following current recommendations, will allow better documentation of the natural history of Ct infection, a prerequisite to evaluating the impact of Ct screening. Characterisation of host immunogenetics will also allow identification of women at risk for complications. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02904811 . Registered on September 14, 2016. World Health Organisation International Clinical Trials Registry, NCT02904811. AOM, 15-0063 and P150950. Registered on September 26, 2016. A completed Standard Protocol Items : Recommendations for International Trials (SPIRIT) Checklist is available in additional file 1.

Chlamyweb Study II: a randomised controlled trial (RCT) of an online offer of home-based Chlamydia trachomatis sampling in France.

BACKGROUND: The number of cases of Chlamydia trachomatis (Ct) diagnosed has increased in the past 15 years in France as well as in other European countries. This paper reports a randomised controlled trial (RCT) to evaluate whether the offer of home-based testing over the internet increased the number of young people tested for chlamydia compared with the current testing strategy and to estimate the number and risks factors of the infected population. This RCT took place as an element of the Chlamyweb Study-a study aiming to evaluate an intervention (the Chlamyweb Intervention) involving the offer of a free self-sampling kit online to sexually active men and women aged 18-24 years in France. METHODS: Participants in the Chlamyweb RCT (n=11 075) received either an offer of a free self-sampling kit (intervention group) or were invited to be screened in primary care settings (control group). Risks ratios were used to compare screening rates between the intervention and control groups. Risk factors were analysed for infected people in the intervention group. RESULTS: The screening frequency was about three times higher among young people who received a self-sampling kit than those who only received a tailored recommendation to be screened (29.2% vs 8.7%). Although rates of screening among men were lower than among women (23.9% vs 33.9%), the intervention effect was greater among men (adjusted risk ratios (aRR)=4.55 vs aRR=2.94). Ct positivity (6.8%) was similar to that observed in STI clinics. It was higher in women (8.3%) than in men (4.4%). CONCLUSIONS: These results invite us to consider the establishment of a large home-based screening programme, although additional studies including economic assessments are needed to evaluate the most appropriate combination of strategies in the French context. TRIAL REGISTRAION NUMBER: AFFSAPS n° IDRCB 0211-A01000-41; Results.