RESUMEN
STI prophylaxis using doxycycline is discussed internationally for persons at high risk of STIs (Doxy-PEP). Doxy-PEP would probably have limited effect on gonorrhoea due to resistance to tetracyclines. Doxy-PEP may reduce the incidence of chlamydia and syphilis, but would not reduce the number of complicated infections. Further studies are needed on the effects of intermittent antibiotic use on the microbiome or antibiotic resistance in general.
Asunto(s)
Antibacterianos , Infecciones por Chlamydia , Doxiciclina , Gonorrea , Enfermedades de Transmisión Sexual , Humanos , Doxiciclina/administración & dosificación , Doxiciclina/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Gonorrea/tratamiento farmacológico , Gonorrea/prevención & control , Enfermedades de Transmisión Sexual/prevención & control , Infecciones por Chlamydia/prevención & control , Infecciones por Chlamydia/tratamiento farmacológico , Sífilis/tratamiento farmacológico , Sífilis/prevención & control , Profilaxis Antibiótica , Farmacorresistencia BacterianaRESUMEN
Chlamydia trachomatis (Ct) is the most common cause for bacterial sexually transmitted infections (STIs) worldwide with a tremendous impact on public health. With the aim to unravel novel targets of the chlamydia life cycle, we screen a compound library and identify 28 agents to significantly reduce Ct growth. The known anti-infective agent pentamidine-one of the top candidates of the screen-shows anti-chlamydia activity in low concentrations by changing the metabolism of host cells impairing chlamydia growth. Furthermore, it effectively decreases the Ct burden upon local or systemic application in mice. Pentamidine also inhibits the growth of Neisseria gonorrhea (Ng), which is a common co-infection of Ct. The conducted compound screen is powerful in exploring antimicrobial compounds against Ct in a medium-throughput format. Following thorough in vitro and in vivo assessments, pentamidine emerges as a promising agent for topical prophylaxis or treatment against Ct and possibly other bacterial STIs.
Asunto(s)
Infecciones por Chlamydia , Chlamydia trachomatis , Modelos Animales de Enfermedad , Pentamidina , Animales , Chlamydia trachomatis/efectos de los fármacos , Infecciones por Chlamydia/tratamiento farmacológico , Infecciones por Chlamydia/microbiología , Infecciones por Chlamydia/prevención & control , Pentamidina/farmacología , Ratones , Humanos , Antibacterianos/farmacología , Femenino , Evaluación Preclínica de Medicamentos , Gonorrea/tratamiento farmacológico , Gonorrea/microbiología , Neisseria gonorrhoeae/efectos de los fármacos , Células HeLaRESUMEN
To begin to optimize the immunization routes for our reported PLGA-rMOMP nanovaccine [PLGA-encapsulated Chlamydia muridarum (Cm) recombinant major outer membrane protein (rMOMP)], we compared two prime-boost immunization strategies [subcutaneous (SC) and intramuscular (IM-p) prime routes followed by two SC-boosts)] to evaluate the nanovaccine-induced protective efficacy and immunogenicity in female BALB/c mice. Our results showed that mice immunized via the SC and IM-p routes were protected against a Cm genital challenge by a reduction in bacterial burden and with fewer bacteria in the SC mice. Protection of mice correlated with rMOMP-specific Th1 (IL-2 and IFN-γ) and not Th2 (IL-4, IL-9, and IL-13) cytokines, and CD4+ memory (CD44highCD62Lhigh) T-cells, especially in the SC mice. We also observed higher levels of IL-1α, IL-6, IL-17, CCL-2, and G-CSF in SC-immunized mice. Notably, an increase of cytokines/chemokines was seen after the challenge in the SC, IM-p, and control mice (rMOMP and PBS), suggesting a Cm stimulation. In parallel, rMOMP-specific Th1 (IgG2a and IgG2b) and Th2 (IgG1) serum, mucosal, serum avidity, and neutralizing antibodies were more elevated in SC than in IM-p mice. Overall, the homologous SC prime-boost immunization of mice induced enhanced cellular and antibody responses with better protection against a genital challenge compared to the heterologous IM-p.
Asunto(s)
Anticuerpos Antibacterianos , Vacunas Bacterianas , Infecciones por Chlamydia , Chlamydia muridarum , Citocinas , Ratones Endogámicos BALB C , Animales , Femenino , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Chlamydia muridarum/inmunología , Citocinas/metabolismo , Infecciones por Chlamydia/prevención & control , Infecciones por Chlamydia/inmunología , Ratones , Anticuerpos Antibacterianos/sangre , Inyecciones Intramusculares , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Proteínas de la Membrana Bacteriana Externa/inmunología , Proteínas de la Membrana Bacteriana Externa/genética , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Inmunización Secundaria , Modelos Animales de Enfermedad , Inmunogenicidad Vacunal , Inyecciones Subcutáneas , Nanopartículas/administración & dosificación , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/administración & dosificación , Eficacia de las Vacunas , Células TH1/inmunología , NanovacunasRESUMEN
Chlamydia trachomatis (Ct) is the most common sexually transmitted bacterial infection worldwide, potentially leading to severe pathologies including pelvic inflammatory disease, ectopic pregnancy, and tubal infertility if left untreated. Current strategies, including screening and antibiotics, have limited effectiveness due to high rates of asymptomatic cases and logistical challenges. A multiepitope prophylactic vaccine could afford long-term protection against infection. Immunoinformatic analyses were employed to design a multiepitope Chlamydia vaccine antigen. B- and T-cell epitopes from five highly conserved and immunogenic Ct antigens were predicted and selected for the vaccine design. The final construct, adjuvanted with cholera toxin A1 subunit (CTA1), was further screened for immunogenicity. CTA1-MECA (multiepitope Chlamydia trachomatis antigen) was identified as antigenic and nonallergenic. A tertiary structure was predicted, refined, and validated as a good quality model. Molecular docking exhibited strong interactions between the vaccine and toll-like receptor 4 (TLR4). Additionally, immune responses consistent with protection including IFN-γ, IgG + IgM antibodies, and T- and B-cell responses were predicted following vaccination in an immune simulation. Expression of the construct in an Escherichia coli expression vector proved efficient. To further validate the vaccine efficacy, we assessed its immunogenicity in mice. Immunization with CTA1-MECA elicited high levels of Chlamydia-specific antibodies in mucosal and systemic compartments.
Asunto(s)
Anticuerpos Antibacterianos , Vacunas Bacterianas , Infecciones por Chlamydia , Chlamydia trachomatis , Epítopos de Linfocito B , Epítopos de Linfocito T , Simulación del Acoplamiento Molecular , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/genética , Infecciones por Chlamydia/prevención & control , Infecciones por Chlamydia/inmunología , Animales , Chlamydia trachomatis/inmunología , Epítopos de Linfocito T/inmunología , Ratones , Anticuerpos Antibacterianos/inmunología , Anticuerpos Antibacterianos/sangre , Epítopos de Linfocito B/inmunología , Epítopos de Linfocito B/genética , Femenino , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/química , Antígenos Bacterianos/genética , Simulación por Computador , Epítopos/inmunología , Humanos , Receptor Toll-Like 4/inmunología , Receptor Toll-Like 4/metabolismo , Toxina del Cólera/inmunología , Toxina del Cólera/genética , Modelos Animales de EnfermedadAsunto(s)
Vacunas Bacterianas , Infecciones por Chlamydia , Chlamydia trachomatis , Humanos , Chlamydia trachomatis/inmunología , Infecciones por Chlamydia/inmunología , Infecciones por Chlamydia/prevención & control , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Femenino , Anticuerpos Antibacterianos/sangre , Adolescente , MasculinoRESUMEN
OBJECTIVE: To evaluate the effect of preexposure prophylaxis (PrEP) initiation on bacterial sexually transmitted infection (STI) occurrence (overall; chlamydia; gonorrhea; syphilis), in MSM. DESIGN: Systematic review and meta-analysis. METHODS: Systematic searches were performed in PubMed, Embase, and Scopus without language restrictions until 1 February 2023. We sought studies reporting data for the estimation of incidence rate ratios (IRR), prevalence ratios or cumulative incidence ratios (the latter in equal time periods before and after PrEP initiation) regarding bacterial STI occurrence. Separate analyses were performed overall for any STI, syphilis, chlamydia and gonorrhea (overall; rectal; urethral; pharyngeal for the two latter conditions); ratios greater than unity denoted increase in STI occurrence after PrEP initiation. RESULTS: Twenty-three eligible studies with 11â776 participants (age range: 18-71âyears) with a median follow-up of 12âmonths were included. Overall, PrEP initiation was associated with a significant increase in the occurrence of any STI (pooled effect size: 1.15, 95% confidence interval (CI): 1.04-1.26), any gonorrhea (pooled effect size: 1.17, 95% CI: 1.02-1.34), any chlamydia (pooled effect size: 1.31, 95% CI: 1.09-1.58) and rectal chlamydia (pooled effect size: 1.31, 95% CI: 1.05-1.64), whereas a borderline increase was found in urethral chlamydia (pooled effect size: 1.25, 95% CI: 0.99-1.60, P â=â0.064). Changes in pharyngeal chlamydia and site-specific gonorrhea occurrence did not reach statistical significance. Syphilis showed virtually no change after PrEP initiation (pooled effect size: 0.99, 95% CI: 0.72-1.37). CONCLUSION: These results highlight the need for more comprehensive, accessible STI testing to tackle bacterial STI infections in PrEP users.
Asunto(s)
Gonorrea , Infecciones por VIH , Homosexualidad Masculina , Profilaxis Pre-Exposición , Enfermedades Bacterianas de Transmisión Sexual , Adolescente , Adulto , Anciano , Humanos , Persona de Mediana Edad , Adulto Joven , Infecciones por Chlamydia/prevención & control , Infecciones por Chlamydia/epidemiología , Gonorrea/epidemiología , Gonorrea/prevención & control , Infecciones por VIH/prevención & control , Infecciones por VIH/epidemiología , Incidencia , Prevalencia , Enfermedades Bacterianas de Transmisión Sexual/epidemiología , Enfermedades Bacterianas de Transmisión Sexual/prevención & control , Sífilis/epidemiología , Sífilis/prevención & controlRESUMEN
OBJECTIVES: Although oral pre-exposure prophylaxis (PrEP) for HIV is being rolled out in West Africa, data on sexually transmitted infections (STIs) in PrEP users are scarce. We assessed the prevalence, incidence and determinants of bacterial STIs in men who have sex with men (MSM) taking PrEP in Burkina Faso, Côte d'Ivoire, Mali and Togo. METHODS: A prospective cohort study among MSM initiating PrEP as part of a comprehensive HIV prevention package was conducted between 2017 and 2021 in community-based clinics in the four study countries. Molecular screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) was performed at months 0, 6 and 12. Serological testing for syphilis was performed every 3 months over the first year of follow-up. Determinants of CT and/or NG incidence were identified using Poisson generalised linear mixed models. RESULTS: A total of 598 participants with a median age of 24.7 years were included. Prevalence of CT and/or NG was 24.4% (95% CI 21.0 to 28.1), 22.4% (95% CI 18.4 to 26.8) and 29.0% (95% CI 24.2 to 34.1) at months 0, 6 and 12, respectively. The prevalence of syphilis ranged from 0.2% (95% CI 0.0 to 0.9) at month 0 to 0.8% (95% CI 0.2 to 2.4) at month 12. Ninety incident CT and/or NG infections occurred during a total follow-up time of 280.6 person-years (incidence rate 32.1 per 100 person-years, 95% CI 25.8 to 39.4). Three incident syphilis infections were detected during a total follow-up time of 459.7 person-years (incidence rate 0.7 per 100 person-years, 95% CI 0.1 to 1.9). CT and/or NG incidence was associated with condomless insertive anal sex (adjusted incidence rate ratio 1.96, 95% CI 1.04 to 3.71, p=0.038). CONCLUSIONS: CT and NG were frequent but syphilis was very infrequent in MSM using HIV PrEP in West Africa. HIV programme managers should integrate STI services into PrEP programmes.
Asunto(s)
Infecciones por Chlamydia , Gonorrea , Infecciones por VIH , Homosexualidad Masculina , Profilaxis Pre-Exposición , Sífilis , Humanos , Masculino , Gonorrea/epidemiología , Gonorrea/prevención & control , Homosexualidad Masculina/estadística & datos numéricos , Estudios Prospectivos , Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/prevención & control , Adulto , Sífilis/epidemiología , Sífilis/prevención & control , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Incidencia , Adulto Joven , Prevalencia , África Occidental/epidemiologíaRESUMEN
We have demonstrated previously that TNF-α-producing CD8+ T cells mediate chlamydial pathogenesis, likely in an antigen (Ag)-specific fashion. Here we hypothesize that inhibition of Ag-specific CD8+ T cell response after immunization and/or challenge would correlate with protection against oviduct pathology induced by a protective vaccine regimen. Intranasal (i.n.) live chlamydial elementary body (EB), intramuscular (i.m.) live EB, or i.n. irrelevant antigen, bovine serum albumin (BSA), immunized animals induced near-total protection, 50% protection, or no protection, respectively against oviduct pathology following i.vag. C. muridarum challenge. In these models, we evaluated Ag-specific CD8+ T cell cytokine response at various time-periods after immunization or challenge. The results show protective efficacy of vaccine regimens correlated with reduction of Ag-specific CD8+ T cell TNF-α responses following i.vag. chlamydial challenge, not after immunization. Depletion of CD4+ T cells abrogated, whereas adoptive transfer of Ag-specific CD4+ T cells induced the significant reduction of Ag-specific CD8+ T cell TNF-α response after chlamydial challenge. In conclusion, protective anti-chlamydial vaccine regimens induce Ag-specific CD4+ T cell response that mediate early inhibition of pathogenic CD8+ T cell response following challenge and may serve as a predictive biomarker of protection against Chlamydia -induced chronic pathologies.
Asunto(s)
Vacunas Bacterianas , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Infecciones por Chlamydia , Animales , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD4-Positivos/inmunología , Infecciones por Chlamydia/inmunología , Infecciones por Chlamydia/prevención & control , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Femenino , Ratones , Modelos Animales de Enfermedad , Factor de Necrosis Tumoral alfa/metabolismo , Chlamydia muridarum/inmunologíaRESUMEN
Pre-exposure prophylaxis (PrEP) use may be associated with risk compensation. We enrolled and provided PreP to sexual and gender minorities (SGM) in Abuja, Nigeria between April 2018 and May 2019. Behavioral information and samples for urogenital and anorectal Chlamydia trachomatis and Neisseria gonorrhoeae sexually transmitted infections (STIs) were collected at baseline. Blood samples for PrEP assay and self-reported adherence were collected at three-monthly follow-up visits. STIs were detected using Aptima Combo2 assay. We estimated the odds ratios (ORs) of PCR-diagnosed bacterial STIs and self-reported behavioral outcomes (condomless anal intercourse [CAI] and concurrent sexual relationships) with conditional logistic regression. Of 400 SGM who initiated PrEP, 206 were eligible for analysis, and had a median age of 24 years (IQR 22-27). In multivariable analysis, participants in the PrEP period had decreased odds of CAI (adjusted OR: 0.49, 95% CI 0.28, 0.84). PrEP use was not associated with risk compensation.
Asunto(s)
Profilaxis Pre-Exposición , Conducta Sexual , Minorías Sexuales y de Género , Humanos , Profilaxis Pre-Exposición/estadística & datos numéricos , Nigeria , Masculino , Femenino , Adulto , Minorías Sexuales y de Género/estadística & datos numéricos , Adulto Joven , Gonorrea/prevención & control , Infecciones por Chlamydia/prevención & control , Enfermedades de Transmisión Sexual/prevención & controlRESUMEN
BackgroundPre-exposure prophylaxis (PrEP) effectively prevents HIV, but its association with sexually transmitted infections (STIs) has raised concerns about risk compensation, potentially impacting the expansion of PrEP programmes.AimWe examined the relationship between PrEP and the incidence of chlamydia, gonorrhoea and syphilis.MethodsIn this prospective cohort study, we compared STI rates before and after PrEP initiation among users in the capital region of Denmark (2019-2022), calculating incidence rate ratios adjusted for age and testing frequency (aIRR). To pinpoint when increases began, we plotted weekly STI rates, adjusting the timeline to correspond with PrEP initiation.ResultsThe study included 1,326 PrEP users with a median age of 35 years. The STI incidence rate per 100,000 person-years rose from 35.3 before to 81.2 after PrEP start, with an aIRR of 1.35 (95%â¯CI: 1.18-1.56). Notably, this increase preceded PrEP initiation by 10-20 weeks. Specific aIRR for chlamydia, gonorrhoea and syphilis were 1.23 (95%â¯CI:â¯1.03-1.48), 1.24 (95%â¯CI: 1.04-1.47) and 1.15 (95%â¯CI: 0.76-1.72), respectively. In subanalyses for anatomical sites aIRR was 1.26 (95%â¯CI: 1.01-1.56) for rectal chlamydia and 0.66 (95%â¯CI: 0.45-0.96) for genital gonorrhoea.ConclusionWe found a 35% increase in STI incidence associated with PrEP use. It started before PrEP initiation, challenging the assumption that PrEP leads to risk compensation. Instead, the data suggest that individuals seek PrEP during periods of heightened sexual risk-taking. Consequently, PrEP programmes should include sexual health consultations, STI testing, treatment and prevention strategies to prevent HIV and improve sexual health.
Asunto(s)
Infecciones por Chlamydia , Gonorrea , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Enfermedades de Transmisión Sexual , Sífilis , Masculino , Humanos , Adulto , Gonorrea/epidemiología , Gonorrea/prevención & control , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Sífilis/epidemiología , Homosexualidad Masculina , Estudios Prospectivos , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/prevención & control , Dinamarca/epidemiología , Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/prevención & controlRESUMEN
Chlamydia trachomatis is an obligate intracellular pathogen responsible for the most prevalent bacterial sexually transmitted disease globally. The high prevalence of chlamydial infections underscores the urgent need for licensed and effective vaccines to prevent transmission in populations. Bacterial outer membrane vesicles (OMVs) have emerged as promising mucosal vaccine carriers due to their inherent adjuvant properties and the ability to display heterologous antigens. In this proof-of-concept study, we evaluated the immunogenicity of Salmonella OMVs decorated with C. trachomatis MOMP-derived CTH522 or HtrA antigens in mice. Following a prime-boost intranasal vaccination approach, two OMV-based C. trachomatis vaccines elicited significant humoral responses specific to the antigens in both systemic and vaginal compartments. Furthermore, we demonstrated strong antigen-specific IFN-γ and IL17a responses in splenocytes and cervical lymph node cells of vaccinated mice, indicating CD4+ Th1 and Th17 biased immune responses. Notably, the OMV-CTH522 vaccine also induced the production of spleen-derived CD8+ T cells expressing IFN-γ. In conclusion, these results highlight the potential of OMV-based C. trachomatis vaccines for successful use in future challenge studies and demonstrate the suitability of our modular OMV platform for intranasal vaccine applications.
Asunto(s)
Infecciones por Chlamydia , Vacunas , Femenino , Animales , Ratones , Chlamydia trachomatis , Linfocitos T CD8-positivos , Antígenos Bacterianos , Salmonella , Inmunidad , Vacunas Bacterianas , Infecciones por Chlamydia/prevención & control , Anticuerpos Antibacterianos , Proteínas de la Membrana Bacteriana ExternaRESUMEN
OBJECTIVE: To evaluate the impact of screening and treating asymptomatic pregnant women for Chlamydia (C.) trachomatis and Neisseria (N.) gonorrhoeae infections on the frequency of preterm birth or low birthweight infants in Botswana. DESIGN: Non-randomised, cluster-controlled trial. SETTING: Four antenatal care clinics in Gaborone, Botswana. POPULATION: Pregnant women aged ≥15 years, attending a first antenatal care visit, ≤27 weeks of gestation and without urogenital symptoms were eligible. METHODS: Participants in the intervention clinics received screening (GeneXpert®, Cepheid) during pregnancy and at the postnatal visit. Participants in the standard-of-care clinics received screening at the postnatal visit only. We used multivariable logistic regression and post-estimation predictive margins analysis. Post-hoc analysis was conducted among sub-samples stratified by parity. MAIN OUTCOME MEASURES: Preterm birth (<37 weeks of gestation) and low birthweight (<2500 g). RESULTS: After controlling for parity, hypertension, antenatal care visits and clinic site, the predicted prevalence of preterm birth or low birthweight was lower in the intervention arm (11%) compared with the standard-of-care arm (16%) (adjusted odds ratio [aOR] 0.59; 95% confidence interval [CI] 0.28-1.24). In post-hoc analysis, the intervention was more effective than the standard-of-care (aOR 0.20; 95% CI 0.07-0.64) among nulliparous participants. CONCLUSION: A C. trachomatis and N. gonorrhoeae infection screening and treatment intervention among asymptomatic pregnant women may have reduced preterm birth or low birthweight outcomes, but results were not statistically significant. Post-hoc analysis found that the intervention reduced adverse outcomes among nulliparous participants.
Asunto(s)
Infecciones por Chlamydia , Chlamydia trachomatis , Gonorrea , Recién Nacido de Bajo Peso , Neisseria gonorrhoeae , Complicaciones Infecciosas del Embarazo , Nacimiento Prematuro , Humanos , Femenino , Embarazo , Nacimiento Prematuro/prevención & control , Nacimiento Prematuro/epidemiología , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/prevención & control , Gonorrea/epidemiología , Gonorrea/diagnóstico , Gonorrea/prevención & control , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/prevención & control , Complicaciones Infecciosas del Embarazo/diagnóstico , Adulto , Chlamydia trachomatis/aislamiento & purificación , Botswana/epidemiología , Neisseria gonorrhoeae/aislamiento & purificación , Recién Nacido , Adulto Joven , Atención Prenatal/métodos , Tamizaje Masivo/métodos , Antibacterianos/uso terapéutico , AdolescenteRESUMEN
Murine research has revealed a significant role for antibody responses in protection against Chlamydia reinfection. To explore potential humoral immune markers of protection elicited by Chlamydia trachomatis (CT) antigens in humans in the context of presumed clinical correlates of protection, we used both an IgG1-based ELISA and a conventional total IgG ELISA to evaluate antibody responses. We evaluated responses to five CT outer membrane proteins (PmpE, PmpF, PmpG, PmpH, and MOMP), along with other promising CT antigens (Pgp3 and HSP60), negative control antigens (RecO and AtpE), and CT elementary bodies (EBs) in sera from a well-characterized cohort of 60 women with different CT infection outcomes, including two outcomes that are likely clinical correlates of protective immunity: spontaneous resolution of infection and absence of reinfection after treatment. Furthermore, we used a flow cytometry-based assay to measure antibody-mediated phagocytosis by neutrophils in these sera. Results demonstrated that IgG1 ELISA displayed higher sensitivity than conventional total IgG ELISA in assessing antibody responses to CT EBs and antigens. Pgp3 IgG1 ELISA exhibited the highest sensitivity compared to IgG1 ELISA incorporating CT EBs or other antigens, confirming Pgp3 IgG1 ELISA as an ideal assay for CT antibody detection. Most (95%) sera from women with CT infection outcomes exhibited antibody-mediated phagocytosis of CT EBs, which was significantly correlated with IgG1 antibody responses to MOMP, Pgp3, HSP60, and PmpF. However, neither IgG1 responses to CT antigens and EBs nor antibody-mediated phagocytosis were associated with clinical correlates of protection. These findings suggest that neither CT IgG1 antibody detection nor antibody-mediated phagocytosis will be useful as immune correlates of protection against CT infection in humans.
Asunto(s)
Infecciones por Chlamydia , Vacunas , Humanos , Femenino , Animales , Ratones , Chlamydia trachomatis , Formación de Anticuerpos , Reinfección , Antígenos Bacterianos , Infecciones por Chlamydia/prevención & control , Infecciones por Chlamydia/diagnóstico , Anticuerpos Antibacterianos , Inmunoglobulina G , FagocitosisRESUMEN
BACKGROUND: Guidelines recommend screening for Neisseria gonorrhoeae and Chlamydia trachomatis at three anatomical sites (urethra, anus, and pharynx) every 3 months (3 × 3) in men who have sex with men (MSM) and transgender women taking HIV pre-exposure prophylaxis (PrEP). We present the first randomised controlled trial to compare the effect of screening versus non-screening for N gonorrhoeae and C trachomatis on the incidence of these infections in MSM and transgender women taking PrEP. METHODS: A multicentre, randomised, controlled trial of 3 × 3 screening for N gonorrhoeae and C trachomatis versus non-screening was done among MSM and transgender women taking PrEP in five HIV reference centers in Belgium. Participants attended the PrEP clinics quarterly for 12 months. N gonorrhoeae and C trachomatis was tested at each visit in both arms, but results were not provided to the non-screening arm, if asymptomatic. The primary outcome was incidence rate of N gonorrhoeae and C trachomatis infections in each arm, assessed in the per-protocol population. Non-inferiority of the non-screening arm was proven if the upper limit of the 95% CI of the incidence rate ratio (IRR) was lower than 1·25. This trial is registered with ClinicalTrials.gov, NCT04269434, and is completed. FINDINGS: Between Sept 21, 2020, and June 4, 2021, 506 participants were randomly assigned to the 3 × 3 screening arm and 508 to the non-screening arm. The overall incidence rate of N gonorrhoeae and C trachomatis was 0·155 cases per 100 person-days (95% CI 0·128-0·186) in the 3 × 3 screening arm and 0·205 (95% CI 0·171-0·246) in the non-screening arm. The incidence rate was significantly higher in the non-screening arm (IRR 1·318, 95% CI 1·068-1·627). Participants in the non-screening arm had a higher incidence of C trachomatis infections and symptomatic C trachomatis infections. There were no significant differences in N gonorrhoeae infections. Participants in the non-screening arm consumed significantly fewer antimicrobial drugs. No serious adverse events were reported. INTERPRETATION: We failed to show that non-screening for N gonorrhoeae and C trachomatis is non-inferior to 3 × 3 screening in MSM and transgender women taking PrEP in Belgium. However, screening was associated with higher antibiotic consumption and had no effect on the incidence of N gonorrhoeae. Further research is needed to assess the benefits and harms of N gonorrhoeae and C trachomatis screening in this population. FUNDING: Belgian Health Care Knowledge Centre.
Asunto(s)
Infecciones por Chlamydia , Gonorrea , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Personas Transgénero , Masculino , Humanos , Femenino , Neisseria gonorrhoeae , Homosexualidad Masculina , Chlamydia trachomatis , Profilaxis Pre-Exposición/métodos , Incidencia , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Infecciones por VIH/tratamiento farmacológico , Gonorrea/diagnóstico , Gonorrea/epidemiología , Gonorrea/prevención & control , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/prevención & controlRESUMEN
BACKGROUND: The presence of untreated sexually transmitted infections (STIs) significantly increases the chance of acquiring HIV. In Brazil, testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) among Pre-Exposure Prophylaxis (PrEP) users is insufficient, and syndromic treatment is a priority in clinical practice. Multi-site testing for CT/NG improves thescreening of asymptomatic cases and ensures timely treatment. Therefore, it is essential for HIV prevention. This study aims to test the importance of two-site testing for better screening of these pathogens and to determine whether the presence of symptoms is an indicator of CT/NG infection. METHODS: This is a cross-sectional study carried out in four public infectious diseases clinics in São Paulo State, Brazil between January of 2022 and March of 2023. All participants had an anal swab and a first-pass or mid-stream urine collected for CT/NG analysis by Polymerase chain reaction (PCR). Data about sociodemographic, sexual behavioural and clinical aspects were collected. Pathway analysis was used to examine the direct and indirect relationships between variables according to the theoretical model. RESULTS: We screened 171 PrEP users which had two samples collected, resulting in 342 samples. Comparing the anatomic sites, the urine samples showed lower sensitivity for CT and NG than anal samples. Gonorrhoea was directly linked to lower age (ß= -0.161, p = 0.001). Time of PrEP use was directly associated with CT infection (ß = 0.202; p = 0.042) and inversely associated with dysuria (ß= -0.121, p = 0.009). Lower occurrence of yellow-green secretion was linked to detection of CT (ß= -0.089, p = 0.005) and NG (ß= -0.048, p = 0.002) infections. Foul-smelling discharge was directly associated with CT (ß = 0.275, p = 0.004) and NG (ß = 0.295, p = 0.037) infection. CONCLUSION: The symptoms are a bad indicator of CT and NG infection, and the screening must be done in more than one site since most of the positive results would be missed if only urines were tested. In the case of testing only one anatomical site, specifically the urethra, the CT/NG incidence and prevalence would be underestimated. The two-sites testing improves detection rates of CT/NG, and PrEP follow-up benefits people offering STI testing.
Asunto(s)
Infecciones por Chlamydia , Gonorrea , Infecciones por VIH , Profilaxis Pre-Exposición , Enfermedades de Transmisión Sexual , Humanos , Neisseria gonorrhoeae , Chlamydia trachomatis , Brasil/epidemiología , Estudios Transversales , Gonorrea/epidemiología , Gonorrea/prevención & control , Gonorrea/diagnóstico , Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/prevención & control , Infecciones por Chlamydia/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , PrevalenciaRESUMEN
BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are the 2 most common sexually transmitted infections (STIs) in the United States. The Centers for Disease Control and Prevention regularly publishes and updates STI Treatment Guidelines. The purpose of this study was to measure and compare treatment rates for CT and GC among public and private providers. METHODS: Data from multiple sources, including electronic health records and Medicaid claims, were linked and integrated. Cases observed during 2016-2020 were defined based on positive laboratory results. We calculated descriptive statistics and odd ratios based on characteristics of providers and patients, stratifying by public versus private providers. Univariate logistic regression models were used to examine the factors associated with recommended treatment. RESULTS: Overall, we found that 82.2% and 63.0% of initial CT and GC episodes, respectively, received Centers for Disease Control and Prevention-recommended treatment. The public STI clinic treated more than 90% of CT and GC cases consistently across the 5-year period. Private providers were significantly less likely to treat first episodes for CT (79.6%) and GC (53.3%; P < 0.01). Other factors associated with a higher likelihood of recommended treatment included being male, being HIV positive, and identifying as Black or multiracial. Among GC cases, 10.8% received nonrecommended treatment; all CT cases with treatment occurred per guidelines. CONCLUSIONS: Although these treatment rates are higher than previous studies, there remain significant gaps in STI treatment that require intervention from public health.
Asunto(s)
Infecciones por Chlamydia , Gonorrea , Enfermedades de Transmisión Sexual , Humanos , Masculino , Estados Unidos/epidemiología , Femenino , Neisseria gonorrhoeae , Chlamydia trachomatis , Gonorrea/tratamiento farmacológico , Gonorrea/epidemiología , Gonorrea/prevención & control , Infecciones por Chlamydia/tratamiento farmacológico , Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/prevención & control , Enfermedades de Transmisión Sexual/prevención & control , Estudios de Cohortes , PrevalenciaRESUMEN
BACKGROUND: Expedited partner therapy prescription remains low and highly variable throughout the United States, leading to frequent reinfections with Chlamydia trachomatis and Neisseria gonorrhoeae . We examined provider counseling on expedited partner therapy before and after an electronic smart tool-based initiative. METHODS: In this quasi-experimental interrupted time-series study, we implemented an initiative of electronic smart tools and education for expedited partner therapy in March 2020. We reviewed the records of patients with chlamydia and/or gonorrhea at an urban, academic obstetrics and gynecology clinic in the preimplementation (March 2019-February 2020) and postimplementation (March 2020-February 2021) groups. Descriptive statistics and an interrupted time-series model were used to compare the percent of expedited partner therapy offered by clinicians to patients in each group. RESULTS: A total of 287 patient encounters were analyzed, 155 preintervention and 132 postintervention. An increase in expedited partner therapy counseling of 13% (95% confidence interval [CI], 2%-24%) was observed before the intervention (27.1% [42 of 155]) versus after the intervention (40.2% [53 of 132]). Significant increases in provider counseling were seen for patients who were single (15%; 95% CI, 3%-26%), 25 years or older (21%; 95% CI, 6%-37%), receiving public insurance (15%; 95% CI, 3%-27%), seen by a registered nurse (18%; 95% CI, 4%-32%), or seen for an obstetrics indication (21%; 95% CI, 4%-39%). No difference was seen in patients' acceptance of expedited partner therapy ( P = 1.00). CONCLUSIONS: A multicomponent initiative focused on electronic smart tools is effective at increasing provider counseling on expedited partner therapy. Further research to understand patient perceptions and acceptance of expedited partner therapy is critical.
Asunto(s)
Infecciones por Chlamydia , Gonorrea , Humanos , Estados Unidos , Infecciones por Chlamydia/tratamiento farmacológico , Infecciones por Chlamydia/prevención & control , Infecciones por Chlamydia/epidemiología , Parejas Sexuales/psicología , Trazado de Contacto , Gonorrea/tratamiento farmacológico , Gonorrea/prevención & control , Gonorrea/epidemiología , Chlamydia trachomatis , ConsejoRESUMEN
OBJECTIVES: We aimed to determine the prevalence of anorectal Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) among transgender women in Brazil, and to assess the performance and costs of various approaches for the diagnosis and management of anorectal NG/CT. METHODS: TransOdara was a multicentric, cross-sectional STI prevalence study among 1317 transgender women conducted in five capital cities representing all Brazilian regions. Participants aged >18 years were recruited using respondent-driven sampling (RDS), completed an interviewer-led questionnaire, offered an optional physical examination and given choice between self-collected or provider-collected samples for NG/CT testing. Performance and cost indicators of predetermined management algorithms based on the WHO recommendations for anorectal symptoms were calculated. RESULTS: Screening uptake was high (94.3%) and the estimated prevalence of anorectal NG, CT and NG and/or CT was 9.1%, 8.9% and 15.2%, respectively. Most detected anorectal NG/CT infections were asymptomatic (NG: 87.6%, CT: 88.9%), with a limited number of participants reporting any anorectal symptoms (9.1%). Of those who permitted anal examination, few had clinical signs of infection (13.6%). Sensitivity of the tested algorithms ranged from 1.4% to 5.1% (highest for treatment based on the reported anorectal discharge or ulcer and receptive anal intercourse (RAI) in the past 6 months) and specificity from 98.0% to 99.3% (highest for treatment based on the reported anorectal discharge with clinical confirmation or report of RAI). The estimated cost-per-true case of anorectal NG/CT infection treated varied from lowest providing treatment for anorectal discharge syndrome based on the reported RAI ($2.70-4.28), with algorithms including clinical examinations decreasing cost-effectiveness. CONCLUSIONS: High prevalence of mostly asymptomatic anorectal NG and CT was observed among Brazilian transgender women. Multi-site NG/CT screening should be offered to transgender women. Where diagnostic testing capacity is limited, syndromic management for those presenting with anorectal symptoms is recommended.
Asunto(s)
Infecciones por Chlamydia , Enfermedades Gastrointestinales , Gonorrea , Personas Transgénero , Humanos , Femenino , Masculino , Gonorrea/diagnóstico , Gonorrea/epidemiología , Gonorrea/prevención & control , Brasil/epidemiología , Prevalencia , Estudios Transversales , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/prevención & control , Neisseria gonorrhoeae , Chlamydia trachomatis , Homosexualidad MasculinaRESUMEN
The Pgp3 subunit vaccine elicits immune protection against Chlamydia trachomatis infection, but additional adjuvants are still required to enhance its immunoprotective efficacy. Flagellin can selectively stimulate immunity and act as an adjuvant. In this research, the FliC-Pgp3 recombinant was successfully expressed and purified. Tri-immunization with the FliC-Pgp3 vaccine in Balb/C mice induced rapid and persistent germinal center B-cell response and Tfh differentiation, promoting a significantly higher IgG antibody titer compared to the Pgp3 group. FliC-Pgp3 immunization primarily induced Th1-type cellular immunity, leading to higher levels of IFN-γ, TNF-α, and IL-2 secreted by CD4+ T cells than in Pgp3-vaccinated mice. Chlamydia muridarum challenge results showed that FliC-Pgp3-vaccinated mice exhibited more rapid clearance of Chlamydia muridarum colonization in the lower genital tract, ensuring a lower hydrosalpinx rate and cumulative score. Histological analysis showed reduced dilation and inflammatory infiltration in the oviduct and uterine horn of FliC-Pgp3-vaccinated mice compared to the PBS and Pgp3 control. Importantly, tri-immunization with FliC-Pgp3 effectively activated CD4+ T cells and dendritic cells, as confirmed by the adoptive transfer, resulting in better immune protection in recipient mice. In summary, the novel FliC-Pgp3 chimeric is hoped to be a novel vaccine with improved immunoprotection against Chlamydia muridarum.
Asunto(s)
Infecciones por Chlamydia , Chlamydia muridarum , Animales , Ratones , Proteínas Bacterianas , Antígenos Bacterianos , Infecciones por Chlamydia/patología , Infecciones por Chlamydia/prevención & control , Inmunización , Vacunas Sintéticas , Adyuvantes InmunológicosRESUMEN
Understanding the global burden of sexually transmitted infections (STIs) is fundamental to being able to address and control these infections and the health harms they cause. The World Health Organization has renewed its global health sector strategy for the prevention and control of STIs. Reducing STIs remains an integral part of HIV prevention and of sexual and reproductive health programs. Data to measure and describe the global burden continue to improve, with systematic reviews and modeling providing global and regional data for the major STIs. Although substantial gaps remain, as many countries have limited data, the measures available demonstrate the scale of the problem for the main curable STIs, gonorrhea, chlamydia, syphilis, and trichomoniasis; the most common viral STIs, human papillomavirus and genital herpes; the interrelation between STIs and HIV; and the substantially unequal burden of these infections globally and among key populations. Regional and global trends in these infections are affected by population changes; the impact and availability of interventions, such as vaccination; changing behaviors that alter the dynamics of STI transmission; and the role of international travel in promulgating STIs in an increasingly interconnected world.