RESUMO
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 25â29-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.
Assuntos
COVID-19 , Infecções por Chlamydia , Gonorreia , Infecções por HIV , Infecções Sexualmente Transmissíveis , Sífilis , Adolescente , Adulto , Idoso , Antibacterianos , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/prevenção & controle , Controle de Doenças Transmissíveis , Atenção à Saúde , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Infecções por HIV/epidemiologia , Humanos , Pandemias , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Sífilis/epidemiologiaRESUMO
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.
Assuntos
Infecções por Mycoplasma , Mycoplasma genitalium , Minorias Sexuais e de Gênero , Chlamydia trachomatis/genética , França , Homossexualidade Masculina , Humanos , Masculino , Mutação , Mycoplasma genitalium/genética , Prevalência , RNA Ribossômico 16S/genética , Resistência a Tetraciclina/genéticaRESUMO
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.
Assuntos
Chlamydia trachomatis/isolamento & purificação , Infecções por HIV/prevenção & controle , Homossexualidade Masculina/estatística & dados numéricos , Linfogranuloma Venéreo/microbiologia , Doenças Retais/microbiologia , Adolescente , Adulto , Idoso , Chlamydia trachomatis/genética , França/epidemiologia , Humanos , Linfogranuloma Venéreo/diagnóstico , Linfogranuloma Venéreo/epidemiologia , Linfogranuloma Venéreo/psicologia , Masculino , Pessoa de Meia-Idade , Profilaxia Pré-Exposição , Doenças Retais/diagnóstico , Doenças Retais/epidemiologia , Doenças Retais/psicologia , Reto/microbiologia , Parceiros Sexuais , Adulto JovemRESUMO
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.
Assuntos
Heterossexualidade/estatística & dados numéricos , Homossexualidade Masculina/estatística & dados numéricos , Programas de Rastreamento/métodos , Vigilância da População/métodos , Doenças Bacterianas Sexualmente Transmissíveis/epidemiologia , Adulto , Feminino , França/epidemiologia , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Humanos , Linfogranuloma Venéreo/diagnóstico , Linfogranuloma Venéreo/epidemiologia , Masculino , Vigilância de Evento Sentinela , Doenças Bacterianas Sexualmente Transmissíveis/diagnóstico , Sífilis/diagnóstico , Sífilis/epidemiologiaRESUMO
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.
Assuntos
Chlamydia trachomatis/genética , Linfogranuloma Venéreo/epidemiologia , Linfogranuloma Venéreo/microbiologia , Doenças Faríngeas/microbiologia , Doenças Retais/microbiologia , Adulto , Antibacterianos/uso terapêutico , Proteínas da Membrana Bacteriana Externa/genética , Chlamydia trachomatis/isolamento & purificação , Coinfecção/diagnóstico , Coinfecção/epidemiologia , Coinfecção/microbiologia , Coinfecção/virologia , Doxiciclina/uso terapêutico , França/epidemiologia , Genótipo , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Linfadenopatia/diagnóstico , Linfadenopatia/epidemiologia , Linfadenopatia/microbiologia , Linfogranuloma Venéreo/complicações , Linfogranuloma Venéreo/diagnóstico , Masculino , Pessoa de Meia-Idade , Doenças Faríngeas/epidemiologia , Faringe/microbiologia , Prevalência , Doenças Retais/epidemiologia , Reto/microbiologia , Estudos Retrospectivos , Análise de Sequência de DNA , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/microbiologia , Adulto JovemRESUMO
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.
Assuntos
Infecções por Chlamydia/epidemiologia , Microbiota , Vagina/microbiologia , Adolescente , Instituições de Assistência Ambulatorial , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/isolamento & purificação , Estudos Transversais , DNA Bacteriano/genética , Feminino , França/epidemiologia , Humanos , Lactobacillus/classificação , Lactobacillus/isolamento & purificação , Prevalência , RNA Ribossômico 16S/genética , Adulto JovemRESUMO
OBJECTIVES: In recent years, the internet has widely facilitated Chlamydia trachomatis home-sampling. In France (2012), the Chlamyweb Study evaluated an intervention (Chlamyweb) involving home-based self-sampling via the internet. One element of the study consisted of a randomised controlled trial (RCT), which is reported in detail elsewhere. The focus of this paper, however, is on describing the Chlamyweb Intervention and reporting on the non-RCT element of the evaluation of that intervention by the Chlamyweb Study. This involves (1) describing the design and roll-out of the Chlamyweb Intervention, (2) comparing the socio-behavioural profiles of the participants in the intervention with a nationally representative general population sample and (3) examining the factors that influence the acceptance and return of a self-sampling kit supplied to participants in the course of the intervention. METHODS: Self-sampling kits were offered to sexually active people aged 18-24â years living on the mainland French. Participants' characteristics were compared with the general population to describe recruited and participant populations. Multivariate analyses by conditional logistic regression were performed to determine factors that were predictors of kit acceptation and use. RESULTS: 7215 people aged 18-24â years were included. Compared with the general population, Chlamyweb reached larger proportions of women, younger people and people with several partners in the previous year. 3372 (46.7%) agreed to receive a self-sampling kit and 2084 (61.8%) returned it, with more women doing so than men. The participation rate was associated with age, place of birth, occupational status, number of partners and condom use, differently for men and women. CONCLUSION: The offer of easy-to-use, self-sampling kits free of charge appeared to be a logistically feasible strategy for testing in France and reached a large and diverse population including individuals who have limited access to the traditional healthcare system. TRIAL REGISTRATION NUMBER: AFFSAPS n° IDRCB 0211-A01000-41; pre-results.
Assuntos
Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/isolamento & purificação , Internet , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Kit de Reagentes para Diagnóstico/estatística & dados numéricos , Projetos de Pesquisa , Autocuidado , Adolescente , Feminino , França , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Parceiros Sexuais , Manejo de Espécimes , Adulto JovemRESUMO
BACKGROUND: The number of cases of Chlamydia trachomatis (Ct) diagnosed has increased in the past 15â 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=11â 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.
Assuntos
Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/isolamento & purificação , Internet , Programas de Rastreamento/métodos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Análise Custo-Benefício , Feminino , França , Humanos , Masculino , Manejo de Espécimes , Adulto JovemRESUMO
These 5 cases of atypical inflammatory lymphogranula venereum (LGV) serovar L2b presenting initially with edema and persistent painful ulceration illustrate that clinical manifestations of LGV in the current outbreak in men who have sex with men reflect the influence of both the serovars virulence and the host immune system and are not confined to proctitis. L2b serovar could have a particular high virulence profile, and the need for awareness of LGV as a cause of genital ulceration is crucial.
Assuntos
Chlamydia trachomatis/imunologia , Homossexualidade Masculina/estatística & dados numéricos , Linfogranuloma Venéreo/microbiologia , Úlcera/microbiologia , Adulto , Chlamydia trachomatis/patogenicidade , Edema/diagnóstico , Edema/imunologia , Edema/microbiologia , Genitália Masculina/microbiologia , Genitália Masculina/patologia , Humanos , Sistema Imunitário , Linfogranuloma Venéreo/diagnóstico , Linfogranuloma Venéreo/patologia , Masculino , Pessoa de Meia-Idade , Proctite/diagnóstico , Proctite/microbiologia , Proctite/patologia , Sorogrupo , Úlcera/diagnóstico , Úlcera/patologia , VirulênciaRESUMO
We describe a change in the molecular epidemiology of Chlamydia trachomatis strains involved in an outbreak of rectal lymphogranuloma venereum in France during January 2010-April 2015. Until 2012, the C. trachomatis L2b strain predominated; however, starting in 2013, most cases involved the L2 strain. We also identified 4 genetic L2b ompA variants.
Assuntos
Chlamydia trachomatis/classificação , Surtos de Doenças , Linfogranuloma Venéreo/epidemiologia , Linfogranuloma Venéreo/microbiologia , Proteínas da Membrana Bacteriana Externa/genética , Chlamydia trachomatis/genética , Coinfecção , França/epidemiologia , Variação Genética , Genótipo , Infecções por HIV , História do Século XXI , Homossexualidade Masculina , Humanos , Linfogranuloma Venéreo/história , Linfogranuloma Venéreo/transmissão , Masculino , Estudos RetrospectivosRESUMO
We retrospectively analyzed 1802 nonrectal Chlamydia trachomatis-positive specimens to determine if the L strains responsible for rectal Lymphogranuloma venereum in men who have sex with men could spread to the heterosexual population. No evidence for Lymphogranuloma venereum transmission among heterosexuals in France was observed in 2013. L2b strains seem to be restricted to the men who have sex with men population.
Assuntos
Chlamydia trachomatis/isolamento & purificação , Linfogranuloma Venéreo/microbiologia , Proctite/microbiologia , Adolescente , Adulto , Feminino , França/epidemiologia , Genitália/microbiologia , Heterossexualidade , Homossexualidade Masculina , Humanos , Linfogranuloma Venéreo/epidemiologia , Linfogranuloma Venéreo/transmissão , Masculino , Estudos Retrospectivos , Minorias Sexuais e de Gênero , Especificidade da Espécie , Adulto JovemRESUMO
BACKGROUND: Calcaneal osteomyelitis is difficult to manage and requires a multidisciplinary approach. The aim of this study was to describe the characteristics and outcomes of calcaneal osteomyelitis, and to determine prognostic factors. METHODS: This was an observational and retrospective study including all patients presenting with calcaneal osteomyelitis referred to a tertiary referral centre between January 2005 and December 2010. RESULTS: Forty-two patients (mean age 50.7 y, range 22-89 y) were included. Fifteen were female. The mean duration of follow-up was 20 months (range 12-48 months). Twenty-six (62%) were post-traumatic osteomyelitis and 16 (38%) were secondary to neurological damage (sensitivity or motor impairment). All patients underwent surgical management with bone curettage and appropriate antibiotic therapy. Staphylococcus aureus was the most commonly isolated bacterium and was found in 29 patients. Polymicrobial samples were observed in 29 patients. Pseudomonas aeruginosa was associated with calcaneal osteomyelitis secondary to neurological damage (n = 7; 44% p = 0.045). Twenty-eight patients (66.7%) healed without the need to resort to amputation. The mean time to healing was 29 weeks with a range of 4-144 weeks. Relapse of bone infection occurred in 17 patients (40.5%). Seven patients (16.7%) required amputations. Favourable prognostic factors for healing without amputation were an American Society of Anesthesiologists (ASA) score < 2 (p < 10(-4)), post-traumatic calcaneal osteomyelitis (p = 0.001), age < 65 y (p = 0.02), absence of neuropathy (p = 0.005), and absence of diabetes mellitus (p = 0.02). CONCLUSIONS: Calcaneal osteomyelitis is characterized by frequent relapse with delayed wound healing. Clinicians should take into account the impact of older age, as well as co-morbidities such as diabetes mellitus or the presence of neuropathy, during the routine management of patients with this difficult-to-treat bone infection.
Assuntos
Infecções Bacterianas/diagnóstico , Infecções Bacterianas/patologia , Calcâneo/patologia , Osteomielite/diagnóstico , Osteomielite/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/cirurgia , Curetagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteomielite/tratamento farmacológico , Osteomielite/cirurgia , Prognóstico , Pseudomonas aeruginosa/isolamento & purificação , Recidiva , Estudos Retrospectivos , Staphylococcus aureus/isolamento & purificação , Centros de Atenção Terciária , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
The possible systemic infectious consequences of prosthetic joint infections (PJI) are poorly documented in the literature. We assessed the frequency of postoperative prosthetic hip and knee infections leading to bacteremia and investigated their associated factors among patients treated between 2005 and 2009. Among 633 patients with PJI, 62 (9.8%) also had positive blood cultures (95% confidence interval (CI) 7.5-12.1). After complete investigations, the prosthesis was considered as the direct cause of bacteremia in 14 cases (2.2%; 95% CI 1.1-3.4). In the conditional logistic regression analysis, PJI leading to bacteremia was more frequently observed in cases of relapses of a prior PJI (adjusted odds ratio (aOR) 7.3, p = 0.07) and in patients with a C-reactive protein value upon admission ≥ 180 mg/l (aOR 4.5, p = 0.04). None of the 8 bacteremic patients treated with surgical debridement and prosthetic retention were cured from joint infection. These preliminary results raise concerns about the fact that debridement with prosthetic retention may not be an appropriate option in the context of PJI leading to bacteremia, contrary to PJI resulting from hematogenous seeding.
Assuntos
Bacteriemia/etiologia , Bacteriemia/patologia , Osteoartrite/complicações , Osteoartrite/patologia , Infecções Relacionadas à Prótese/complicações , Infecções Relacionadas à Prótese/patologia , Idoso , Proteína C-Reativa/análise , Estudos de Casos e Controles , Desbridamento , Feminino , Articulação do Quadril/patologia , Humanos , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Osteoartrite/cirurgia , Infecções Relacionadas à Prótese/cirurgia , Estudos RetrospectivosRESUMO
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.
Assuntos
Infecções por Chlamydia , Microbiota , Infecções Urinárias , Feminino , Humanos , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Doxiciclina/farmacologia , Doxiciclina/uso terapêutico , Chlamydia trachomatis/genética , RNA Ribossômico 16S/genética , Estudos Transversais , Infecções por Chlamydia/tratamento farmacológico , Infecções por Chlamydia/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Vagina/microbiologia , Infecções Urinárias/tratamento farmacológicoRESUMO
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.
Assuntos
Chlamydia trachomatis , Leucócitos Mononucleares , Animais , Feminino , Vacinação , Imunização , Primatas , Adjuvantes Imunológicos , Adjuvantes Farmacêuticos , Imunoglobulina GRESUMO
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.
Assuntos
Azitromicina , Infecções por Chlamydia , Adulto , Antibacterianos , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/tratamento farmacológico , Chlamydia trachomatis , Doxiciclina/uso terapêutico , Feminino , Humanos , GravidezRESUMO
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.
Assuntos
Infecções por Chlamydia/diagnóstico , Chlamydia trachomatis/isolamento & purificação , Linfogranuloma Venéreo/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Doenças Retais/diagnóstico , Infecções por Chlamydia/complicações , Infecções por Chlamydia/microbiologia , Humanos , Linfogranuloma Venéreo/complicações , Masculino , Minorias Sexuais e de GêneroRESUMO
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.