RESUMEN
BACKGROUND: Neisseria gonorrhoeae (Ng) causes the sexually transmitted disease gonorrhoea. There are no vaccines and infections are treated principally with antibiotics. However, gonococci rapidly develop resistance to every antibiotic class used and there is a need for developing new antimicrobial treatments. In this study we focused on two gonococcal enzymes as potential antimicrobial targets, namely the serine protease L,D-carboxypeptidase LdcA (NgO1274/NEIS1546) and the lytic transglycosylase LtgD (NgO0626/NEIS1212). To identify compounds that could interact with these enzymes as potential antimicrobials, we used the AtomNet virtual high-throughput screening technology. We then did a computational modelling study to examine the interactions of the most bioactive compounds with their target enzymes. The identified compounds were tested against gonococci to determine minimum inhibitory and bactericidal concentrations (MIC/MBC), specificity, and compound toxicity in vitro. RESULTS: AtomNet identified 74 compounds that could potentially interact with Ng-LdcA and 84 compounds that could potentially interact with Ng-LtgD. Through MIC and MBC assays, we selected the three best performing compounds for both enzymes. Compound 16 was the most active against Ng-LdcA, with a MIC50 value < 1.56 µM and MBC50/90 values between 0.195 and 0.39 µM. In general, the Ng-LdcA compounds showed higher activity than the compounds directed against Ng-LtgD, of which compound 45 had MIC50 values of 1.56-3.125 µM and MBC50/90 values between 3.125 and 6.25 µM. The compounds were specific for gonococci and did not kill other bacteria. They were also non-toxic for human conjunctival epithelial cells as judged by a resazurin assay. To support our biological data, in-depth computational modelling study detailed the interactions of the compounds with their target enzymes. Protein models were generated in silico and validated, the active binding sites and amino acids involved elucidated, and the interactions of the compounds interacting with the enzymes visualised through molecular docking and Molecular Dynamics Simulations for 50 ns and Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA). CONCLUSIONS: We have identified bioactive compounds that appear to target the N. gonorrhoeae LdcA and LtgD enzymes. By using a reductionist approach involving biological and computational data, we propose that compound Ng-LdcA-16 and Ng-LtgD-45 are promising anti-gonococcal compounds for further development.
Asunto(s)
Antibacterianos , Inteligencia Artificial , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/enzimología , Antibacterianos/farmacología , Peptidoglicano/metabolismo , Humanos , Ensayos Analíticos de Alto Rendimiento/métodosRESUMEN
Neisseria gonorrhoeae is a global threat to public health due to the accumulation of antimicrobial resistance mechanisms. ST-1901 is an internationally important sequence type (ST) because of its high incidence and the usual occurrence of chromosomally determined resistance. In this study, we describe the evolution of the ST-1901 and its single locus variants in Rio de Janeiro from 2006 to 2022. We analyzed 82 N. gonorrhoeae isolates according to antimicrobial susceptibility profile, resistance mechanisms, molecular typing, and phylogenetics. Six different single locus variants were detected. Phylogenetic analysis identified five clades, which share similar characteristics. Resistance rates for penicillin and tetracycline decreased due to the lower occurrence of resistance plasmids, but intermediary resistance to penicillin rose. Resistance to ciprofloxacin remained high throughout all clades and the years of the study. Regarding resistance to azithromycin, alterations in mtrR promoter and gene, and 23S rRNA encoding gene rrl were detected, with a notable rise in the incidence of C2611T mutations in more recent years occurring in four of five clades. In contrast, ß-lactam resistance associated penA 34 mosaic was found only in one persisting clade (Clade D), and unique G45D and A39T mutations in mtrR gene and its promoter (Nm-Like) were found only in Clade B. Taken together, these data suggest that ST-1901, a persistently circulating lineage of N. gonorrhoeae in Rio de Janeiro, has undergone changes over the years and may evolve to develop resistance to the current recommended dual therapy adopted in Brazil, namely, ceftriaxone and azithromycin.
Asunto(s)
Antibacterianos , Gonorrea , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae , Filogenia , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/clasificación , Brasil , Antibacterianos/farmacología , Humanos , Gonorrea/microbiología , Gonorrea/epidemiología , Gonorrea/tratamiento farmacológico , Farmacorresistencia Bacteriana/genética , Proteínas Bacterianas/genética , Azitromicina/farmacología , Ciprofloxacina/farmacología , ARN Ribosómico 23S/genética , Proteínas Represoras/genética , Plásmidos/genética , Mutación , Penicilinas/farmacologíaRESUMEN
OBJECTIVE: To estimate the prevalence and factors associated with the detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) in transgender women and travestis in five Brazilian capitals. METHODS: Data were obtained from a cross-sectional study conducted between 2019 and 2021, with participants recruited through Respondent Driven Sampling in São Paulo, Campo Grande, Manaus, Porto Alegre and Salvador. Detection of CT and NG was analyzed at three collection sites (anorectal, oropharyngeal and urethral). Mixed logistic regression models were employed to identify associated factors. RESULTS: A total of 1,297 recruited participants provided biological material to detect these infections. The prevalences of CT, NG and coinfection were 11.5%, 13.3% and 3.6%, respectively. Independent associations with CT infections included past (OR=1.73; 95%CI 1.02-2.95), current (OR=2.13; 95%CI 1.23-3.69), and part-time sex work (OR=2.75; 95%CI 1.60-4.75), as well as lifetime injectable drug use (OR=3.54; 95%CI 1.49-8.40). For NG, associations were observed with lifetime injectable drug use (OR=1.91; 95%CI 1.28-2.84) and sexual orientation, including heterosexual (OR=3.44; 95%CI 1.35-8.82), homosexual (OR=5.49; 95%CI 1.89-15.97), and bisexual (OR=3.21; 95%CI 1.06-9.68). Coinfection was associated with use of illicit drugs in the last 12 months (OR=2.34, 95%CI 1.10-5.00), and younger age was associated with all investigated outcomes. CONCLUSION: Estimated prevalences of CT, NG and co-infection were higher among transgender women and travestis compared to the general population, particularly among younger, individuals engaged in sex work and illicit drug use.
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Infecciones por Chlamydia , Chlamydia trachomatis , Gonorrea , Personas Transgénero , Humanos , Femenino , Brasil/epidemiología , Infecciones por Chlamydia/epidemiología , Estudios Transversales , Adulto , Personas Transgénero/estadística & datos numéricos , Prevalencia , Gonorrea/epidemiología , Adulto Joven , Masculino , Adolescente , Chlamydia trachomatis/aislamiento & purificación , Neisseria gonorrhoeae/aislamiento & purificación , Persona de Mediana Edad , Factores de Riesgo , Coinfección/epidemiologíaRESUMEN
This study aimed to know the opinion of professionals participating in an experiment to implement a pilot for molecular tests to detect Chlamydia trachomatis and Neisseria gonorrhoeae at the Brazilian Unified National Health System (SUS). The detection rate of C. trachomatis and/or N. gonorrhoeae and the factors associated with infection were determined. The strategy included laboratories belonging to the HIV and viral hepatitis viral load network. Testing targeted people who are more vulnerable to sexually transmitted infections and collected urine samples and/or vaginal, endocervical, and/or male urethral swabs. Questionnaires were sent to state managers and laboratory professionals about the implementation of the pilot. Reviews were overall positive. Weaknesses included difficulties changing work processes, lack of human resources, poorly sensitized care professionals, and absence of primary urine tubes, the only input not provided. Strengths included the centralized acquisition of tests, sharing of equipment, and storage of samples at room temperature. Of the 16,177 people who were tested, 1,004 (6.21%) were positive for C. trachomatis; 1,036 (6.4%), for N. gonorrhoeae; and 239 (1.48%), for C. trachomatis/N. gonorrhoeae . Detection of any infection occurred more frequently in young people (≤ 24 vs. > 24 years) (adjOR = 2.65; 95%CI: 2.38-2.96), men (adjOR = 1.95; 95%CI: 1.72-2.21), brown/black individuals (adjOR = 1.06; 95%CI: 1.05-1.11), those in Southeastern Brazil (adjOR = 1.08; 95%CI: 1.02-1.13), and in urethral secretion samples (adjOR = 1.46; 95%CI: 1.41-1.52). Results show the importance of making testing available nationwide, which supported the implementation of a definitive network to detection C. trachomatis/N. gonorrhoeae in SUS.
O objetivo deste estudo foi conhecer a opinião dos profissionais participantes da implantação-piloto de testes moleculares para detecção de Chlamydia trachomatis e Neisseria gonorrhoeae no Sistema Único de Saúde (SUS). Determinou-se a taxa de detecção de C. trachomatis e/ou N. gonorrhoeae e os fatores associados à infecção. A estratégia contou com laboratórios pertencentes à rede de carga viral de HIV e hepatites virais. A testagem teve como público-alvo pessoas mais vulnerabilizadas às infecções sexualmente transmissíveis, com coleta de amostras de urina e/ou swabs vaginal, endocervical e/ou uretral masculino. Questionários foram enviados aos gestores estaduais e profissionais de laboratório sobre a implantação-piloto. De maneira geral, as avaliações foram positivas. Entre as fraquezas, citou-se dificuldades na mudança do processo de trabalho, carência de recursos humanos, pouca sensibilidade de profissionais da assistência e ausência de tubo primário de urina, único insumo não fornecido. Como fortaleza, destaca-se aquisição centralizada de testes, compartilhamento de equipamentos e armazenamento de amostras à temperatura ambiente. Das 16.177 pessoas testadas, 1.004 (6,21%) foram positivas para C. trachomatis, 1.036 (6,4%) para N. gonorrhoeae e 239 (1,48%) para C. trachomatis/N. gonorrhoeae. A detecção de infecção ocorreu mais em pessoas jovens (≤ 24 vs. > 24 anos) (aOR = 2,65; IC95%: 2,38-2,96), do sexo masculino (aOR = 1,95; IC95%: 1,72-2,21), pardas/pretas (aOR = 1,06; IC95%: 1,05-1,11), na Região Sudeste (aOR = 1,08; IC95%: 1,02-1,13) e em amostras de secreção uretral (aOR = 1,46; IC95%: 1,41-1,52). Os resultados deste estudo demonstraram a importância da disponibilização da testagem em âmbito nacional, os quais subsidiaram a implantação da rede definitiva para detecção de C. trachomatis/N. gonorrhoeae no SUS.
El objetivo de este estudio fue conocer la opinión de los profesionales participantes de la implantación piloto de pruebas moleculares para la detección de Chlamydia trachomatis y Neisseria gonorrhoeae en el Sistema Único de Salud brasileño (SUS). Se determinó la tasa de detección de C. trachomatis y/o N. gonorrhoeae y los factores asociados con la infección. En la estrategia participaron laboratorios pertenecientes a la red de carga viral de VIH y hepatitis virales. La prueba tuvo como público objetivo a personas más vulnerables a las infecciones de transmisión sexual, con recolección de muestras de orina y/o swabs vaginal, endocervicales y/o uretral masculino. Se enviaron cuestionarios a los gestores estatales y a los profesionales de laboratorio sobre la implementación piloto. En general, las evaluaciones fueron positivas. Entre las debilidades, se citó las dificultades en el cambio del proceso de trabajo, la falta de recursos humanos, los profesionales de la asistencia poco sensibilizados y la ausencia del contenedor de orina primaria, el único insumo no suministrado. Como fortalezas, se destaca la adquisición centralizada de pruebas, el intercambio de equipos y el almacenamiento de muestras a temperatura ambiente. De las 16.177 personas evaluadas, 1.004 (6,21%) fueron positivas para C. trachomatis, 1.036 (6,4%) para N. gonorrhoeae y 239 (1,48%) para C. trachomatis/N. gonorrhoeae. La detección de alguna infección ocurrió más en personas jóvenes (≤ 24 vs. > 24 años) (aOR = 2,65; IC95%: 2,38-2,96), del sexo masculino (aOR = 1,95; IC95%: 1,72-2,21), parda/negra (aOR = 1,06; IC95%: 1,05-1,11), localizadas en la región Sudeste (aOR = 1,08; IC95%: 1,02-1,13) y en muestras de secreción uretral (aOR = 1,46; IC95%: 1,41-1,52). Los resultados de este estudio demostraron la importancia de la disponibilidad de la prueba a nivel nacional, los cuales subsidiaron la implantación de la red definitiva para detección de C. trachomatis/N. gonorrhoeae en el SUS.
Asunto(s)
Infecciones por Chlamydia , Chlamydia trachomatis , Gonorrea , Neisseria gonorrhoeae , Humanos , Brasil , Infecciones por Chlamydia/diagnóstico , Chlamydia trachomatis/aislamiento & purificación , Chlamydia trachomatis/genética , Neisseria gonorrhoeae/aislamiento & purificación , Neisseria gonorrhoeae/genética , Gonorrea/diagnóstico , Masculino , Femenino , Proyectos Piloto , Adulto , Adulto Joven , Programas Nacionales de Salud , Adolescente , Técnicas de Diagnóstico Molecular/métodosRESUMEN
OBJECTIVE: Monitoring the susceptibility patterns of Neisseria gonorrhoeae is essential for the continuing compliance with current treatment recommendations. Puerto Rico conducts susceptibility tests on N. gonorrhoeae; however, trends on antimicrobial resistance in the island have not been reported since the mid 80's. METHODS: We performed a secondary analysis of a national data repository on the antimicrobial susceptibility of N. gonorrhoeae isolates between 2012 and 2017; a period of time when the CDC recommended a single dose of ceftriaxone and azithromycin for the treatment of uncomplicated gonorrhea. Data on susceptibility to eight antibiotics using the standard disk diffusion method was obtained for 30.0% (84/276) of the samples collected from the Sexually Transmitted Disease clinics in Puerto Rico. We also performed patient demographic analyses linked to resistance. RESULTS: Rates of resistance to ceftriaxone and azithromycin were 0% and 4.0% (2/50), respectively. The percentage of isolates resistant to antimicrobials no longer recommended in Puerto Rico, such as tetracycline, ciprofloxacin, and penicillin, was 86.0% (43/50), 76.0% (38/50), and 38.0% (19/50), respectively. Prevalence of resistant N. gonorrhoeae was higher among men who have sex with men, MSM (79%, 37/47). DISCUSSION: Lack of resistance to ceftriaxone and slow emergence of azithromycin resistance was identified from 2012-2017. It is imperative to continue the surveillance for emerging patterns of resistance, especially for ceftriaxone, as it is part of the current treatment guidelines. Therefore, protocols for culture based surveillance, including sample transport and processing, should be strengthened to ensure quality assured epidemiology of gonococcal resistance in Puerto Rico.
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Antibacterianos , Farmacorresistencia Bacteriana , Gonorrea , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae , Puerto Rico , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/aislamiento & purificación , Humanos , Masculino , Gonorrea/tratamiento farmacológico , Gonorrea/microbiología , Gonorrea/epidemiología , Femenino , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Adulto , Adulto Joven , Azitromicina/farmacología , Azitromicina/administración & dosificación , Ceftriaxona/farmacología , Adolescente , Persona de Mediana EdadRESUMEN
This study presents the synthesis of four series of novel hybrid chalcones (20,21)a-g and (23,24)a-g and six series of 1,3,5-triazine-based pyrimido[4,5-b][1,4]diazepines (28-33)a-g and the evaluation of their anticancer, antibacterial, antifungal, and cytotoxic properties. Chalcones 20b,d, 21a,b,d, 23a,d-g, 24a-g and the pyrimido[4,5-b][1,4]diazepines 29e,g, 30g, 31a,b,e-g, 33a,b,e-g exhibited outstanding anticancer activity against a panel of 60 cancer cell lines with GI50 values between 0.01 and 100 µM and LC50 values in the range of 4.09 µM to >100 µM, several of such derivatives showing higher activity than the standard drug 5-fluorouracil (5-FU). On the other hand, among the synthesized compounds, the best antibacterial properties against N. gonorrhoeae, S. aureus (ATCC 43300), and M. tuberculosis were exhibited by the pyrimido[4,5-b][1,4]diazepines (MICs: 0.25-62.5 µg/mL). The antifungal activity studies showed that triazinylamino-chalcone 29e and triazinyloxy-chalcone 31g were the most active compounds against T. rubrum and T. mentagrophytes and A. fumigatus, respectively (MICs = 62.5 µg/mL). Hemolytic activity studies and in silico toxicity analysis demonstrated that most of the compounds are safe.
Asunto(s)
Chalconas , Isocianatos , Mycobacterium tuberculosis , Chalconas/farmacología , Antifúngicos/farmacología , Staphylococcus aureus , Antibacterianos/farmacología , Azepinas/farmacología , Fluorouracilo , Neisseria gonorrhoeae , Triazinas/farmacologíaRESUMEN
Resistance to antibiotics and antimicrobial compounds is a significant problem for human and animal health globally. The development and introduction of new antimicrobial compounds are urgently needed, and copper oxide nanoparticles (CuO NPs) have found widespread application across various sectors including biomedicine, pharmacy, catalysis, cosmetics, and many others. What makes them particularly attractive is the possibility of their synthesis through biogenic routes. In this study, we synthesized biogenic green tea (GT, Camellia sinensis)-derived CuO NPs (GT CuO NPs) and examined their biophysical properties, in vitro toxicity for mammalian cells in culture, and then tested them against Neisseria gonorrhoeae, an exemplar Gram-negative bacterium from the World Health Organization's Priority Pathogen List. We compared our synthesized GT CuOP NPs with commercial CuO NPs (Com CuO NPs). Com CuO NPs were significantly more cytotoxic to mammalian cells (IC50 of 7.32 µg/mL) than GT CuO NPs (IC50 of 106.1 µg/mL). GT CuO NPs showed no significant increase in bax, bcl2, il6, and il1ß mRNA expression from mammalian cells, whereas there were notable rises after treatment with Com CuO NPs. GT-CuO NPs required concentrations of 0.625 and 3.125 µg/mL to kill 50 and 100% of bacteria, respectively, whereas Com-CuO NPs needed concentrations of 15.625 and 30 µg/mL to kill 50 and 100% of bacteria, and the antibiotic ceftriaxone killed 50 and 100% with 3.125 and 30 µg/mL. Gonococci could be killed within 30 min of exposure to GT CuO NPs and the NPs could kill up to 107 within 1 h. In summary, this is the first report to our knowledge that describes the bioactivity of biogenic CuO NPs against N. gonorrhoeae. Our data suggest that biogenic nanoparticle synthesis has significant advantages over traditional chemical routes of synthesis and highlights the potential of GT-CuO NPs in addressing the challenges posed by multidrug-resistant Neisseria gonorrhoeae infections.
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Antibacterianos , Cobre , Nanopartículas del Metal , Neisseria gonorrhoeae , Neisseria gonorrhoeae/efectos de los fármacos , Humanos , Cobre/química , Cobre/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Nanopartículas del Metal/química , Nanopartículas del Metal/toxicidad , Pruebas de Sensibilidad MicrobianaRESUMEN
In South Africa, basic healthcare centres treat sexually transmitted infections (STIs) using a syndromic approach. In line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, a complete study of all randomised controlled trials and surveillance data relevant to N. gonorrhoeae antibiotic resistance was conducted. To discover papers published between 2002 and 2022, searches were undertaken using PubMed, EMBASE and any other relevant databases. This systematic review extracted a total of 463 articles published between 2002 and 2022 from a variety of online research sources. Seven South African provinces were represented in the studies that were assessed. Mpumalanga and the North West Province did not have any studies that described the identification and monitoring of antimicrobial resistance (AMR). This study presents data obtained from a comprehensive analysis of 2140 isolates, in which we examined the presence of one or more antibiotic resistance. Our findings revealed that out of these samples, 1891 isolates exhibited antimicrobial properties; tetracycline was the antimicrobial resistance that was found the most often (30%), followed by ciprofloxacin (19%) and penicillin (17%). The mean of the isolates was 143, the upper 95% mean was 243, and the standard deviation (SD) was 181.6. All microbiological identification and susceptibility testing processes must be standardised and improved so national organisations can monitor AMR. The nation's health community must address all identified areas of concern to avoid AMR.
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Antibacterianos , Farmacorresistencia Bacteriana , Gonorrea , Neisseria gonorrhoeae , Sudáfrica , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/aislamiento & purificación , Gonorrea/microbiología , Gonorrea/tratamiento farmacológico , Gonorrea/epidemiología , Humanos , Antibacterianos/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: The effective testing of sexually transmitted infections (STIs) requires sampling from potential infection sites. This study aimed to assess the choice, satisfaction, and performance of self-collected samples (SCS) from potential infection sites for STI testing among transgender women in Brazil. METHODS: TransOdara was a multicentric, cross-sectional STI prevalence study conducted in 5 Brazilian cities. Using respondent-driven sampling, 1317 transgender women 18 years or older were recruited. Participants completed interviewer-led questionnaires and provided swab samples from multiple sites (anorectal, oropharyngeal, genital) for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and human papillomavirus (HPV) testing. Participants were given a choice of SCS or provider-collected samples (PCS) at each site. RESULTS: Most participants selected SCS for anorectal (74.9%; 95% confidence interval [CI], 72.4-77.3) and genital (72.7%; 95% CI, 70.2-75.1) sites, whereas fewer chose for oropharyngeal samples (49.8%; 95% CI, 47.0-52.6). For future testing, most participants expressed a preference for SCS for genital (72.2%; 95% CI, 69.5-74.7) and anorectal (70.2%; 95% CI, 67.6-72.7) sites. There was no significant difference in the positive test results for CT and NG between SCS and PCS at anorectal and oropharyngeal sites, or for HPV at anorectal and genital (penile or neovaginal) sites. CONCLUSIONS: This study demonstrated a high level of acceptability and usability of self-sampling for STI testing among transgender women. A preference for SCS was evident at the anorectal and genital sites, and the results of SCS were comparable to those of PCS. The findings suggest that multisite STI testing utilizing self-collection methods as a provided option can be effectively integrated into sexual health services for transgender women.
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Infecciones por Chlamydia , Gonorrea , Infecciones por Papillomavirus , Enfermedades de Transmisión Sexual , Personas Transgénero , Femenino , Humanos , Brasil , Infecciones por Chlamydia/epidemiología , Chlamydia trachomatis , Estudios Transversales , Gonorrea/epidemiología , Neisseria gonorrhoeae , Prevalencia , Enfermedades de Transmisión Sexual/epidemiología , Masculino , AdultoRESUMEN
BACKGROUND: In 2018, the World Health Organization commenced a multi-country validation study of the Cepheid GeneXpert for a range of molecular-based point-of-care (POC) tests in primary care settings. One study arm focused on the evaluation of POC tests for screening 'women at risk' for chlamydia (CT), gonorrhoea (NG) and trichomonas (TV) in four countries - Australia, Guatemala, Morocco and South Africa. METHODS: Study participants completed a pre-test questionnaire which included demographics, clinical information and general questions on POC testing (POCT). Two vaginal swab samples (either self-collected or clinician collected) from each patient were tested on the GeneXpert at the POC and at a reference laboratory using quality-assured nucleic acid amplification tests (NAATs). RESULTS: One thousand three hundred and eighty-three women were enrolled: 58.6% from South Africa, 29.2% from Morocco, 6.2% from Guatemala, and 6.0% from Australia. 1296 samples for CT/NG and 1380 samples for TV were tested by the GeneXpert and the reference NAAT. The rate of unsuccessful tests on the GeneXpert was 1.9% for CT, 1.5% for NG and 0.96% for TV. The prevalence of CT, NG and TV was 31%, 13% and 23%, respectively. 1.5% of samples were positive for all three infections; 7.8% were positive for CT and NG; 2.4% were positive for NG and TV; and 7.3% were positive for CT and TV. Compared to reference NAATs, pooled estimates of sensitivity for the GeneXpert tests were 83.7% (95% confidence intervals 69.2-92.1) for CT, 90.5% (85.1-94.1) for NG and 64.7% (58.1-70.7) for TV (although estimates varied considerably between countries). Estimates for specificity were ≥96% for all three tests both within- and between-countries. Pooled positive and negative likelihood ratios were: 32.7 ([CI] 21.2-50.5) and 0.17 (0.08-0.33) for CT; 95.3 (36.9-245.7) and 0.10 (0.06-0.15) for NG; and 56.5 (31.6-101.1) and 0.35 (0.27-0.47) for TV. CONCLUSION: This multi-country evaluation is the first of its kind world-wide. Positive likelihood ratios, as well as specificity estimates, indicate the GeneXpert POC test results for CT, NG and TV were clinically acceptable for ruling in the presence of disease. However, negative likelihood ratios and variable sensitivity estimates from this study were poorer than expected for ruling out these infections, particularly for TV. TRIAL REGISTRATION: Ethics approval to conduct the ProSPeRo study was granted by the WHO Ethics Review Committee, as well as local ethics committees from all participating countries.
Asunto(s)
Gonorrea , Trichomonas vaginalis , Femenino , Humanos , Trichomonas vaginalis/genética , Chlamydia trachomatis/genética , Gonorrea/diagnóstico , Gonorrea/epidemiología , Guatemala/epidemiología , Marruecos/epidemiología , Sudáfrica/epidemiología , Neisseria gonorrhoeae/genética , Australia , Pruebas en el Punto de AtenciónRESUMEN
BACKGROUND: Sexually transmitted infections (STIs) are a public health problem. The aim of the present study was to assess the prevalence and risk factors associated with at least one STI (Chlamydia trachomatis [CT], Neisseria gonorrhoeae [NG], Trichomonas vaginalis [TV], and Mycoplasma genitalium [MG]) in Brazil. METHODS: A cross-sectional study was conducted using secondary data from the pilot implementation of the National Service for molecular diagnosis of CT, NG, TV, and MG in pregnancy. We obtained Ministry of Health surveillance data from the implementation project. Data encompassing pregnant women aged 15-49 years from public antenatal clinics in Brazil in 2022 were included. RESULTS: A total of 2728 data of pregnant women were analyzed. The prevalence of at least one infection was 21.0% (573), with the highest prevalence in the Southeast region (23.3%) and the lowest in the Center-West region (15.4%). The prevalence of CT was 9.9% (270), NG 0.6% (16), TV 6.7% (184), and MG 7.8% (212). Factors associated with any infection were from 15 to 24 years (AOR = 1.93; 95% CI: 1.58-2.35); reported family income up to US$400 (AOR = 1.79; 95% CI: 1.03-3.34); declared not living maritally with their partners (AOR = 1.90, 95% CI: 1.52-2.37) and had more than one sexual partner in their lifetime (AOR = 2.09, 95% CI: 1.55-2.86). CONCLUSION: This study showed a high prevalence of at least one STI among pregnant women in Brazil, particularly among younger women. It also provides up-to-date national data on CT, NG, TV, and MG infections in this population. These findings underscore the importance of enhancing access to STI screening for young pregnant women within the Brazilian public health system.
Asunto(s)
Infecciones por Chlamydia , Chlamydia trachomatis , Gonorrea , Infecciones por Mycoplasma , Mycoplasma genitalium , Neisseria gonorrhoeae , Complicaciones Infecciosas del Embarazo , Vaginitis por Trichomonas , Trichomonas vaginalis , Humanos , Femenino , Brasil/epidemiología , Embarazo , Adulto , Estudios Transversales , Adolescente , Prevalencia , Adulto Joven , Mycoplasma genitalium/aislamiento & purificación , Factores de Riesgo , Infecciones por Mycoplasma/epidemiología , Infecciones por Mycoplasma/diagnóstico , Gonorrea/epidemiología , Gonorrea/diagnóstico , Neisseria gonorrhoeae/aislamiento & purificación , Trichomonas vaginalis/aislamiento & purificación , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/diagnóstico , Chlamydia trachomatis/aislamiento & purificación , Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/diagnóstico , Vaginitis por Trichomonas/epidemiología , Vaginitis por Trichomonas/diagnóstico , Persona de Mediana Edad , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/diagnósticoRESUMEN
New pyridine-based chalcones 4a-h and pyrazolines 5a-h (N-acetyl), 6a-h (N-phenyl), and 7a-h (N-4-chlorophenyl) were synthesized and evaluated by the National Cancer Institute (NCI) against 60 different human cancer cell lines. Pyrazolines 6a, 6c-h, and 7a-h satisfied the pre-determined threshold inhibition criteria, obtaining that compounds 6c and 6f exhibited high antiproliferative activity, reaching submicromolar GI50 values from 0.38 to 0.45 µM, respectively. Moreover, compound 7g (4-CH3) exhibited the highest cytostatic activity of these series against different cancer cell lines from leukemia, nonsmall cell lung, colon, ovarian, renal, and prostate cancer, with LC50 values ranging from 5.41 to 8.35 µM, showing better cytotoxic activity than doxorubicin. Furthermore, the compounds were tested for antibacterial and antiplasmodial activities. Chalcone 4c was the most active with minimal inhibitory concentration (MIC) = 2 µg/mL against methicillin-resistant Staphylococcus aureus (MRSA), while the pyrazoline 6h showed a MIC = 8 µg/mL against Neisseria gonorrhoeae. For anti-Plasmodium falciparum activity, the chalcones display higher activity with EC50 values ranging from 10.26 to 10.94 µg/mL. Docking studies were conducted against relevant proteins from P. falciparum, exhibiting the minimum binding energy with plasmepsin II. In vivo toxicity assay in Galleria mellonella suggests that most compounds are low or nontoxic.
Asunto(s)
Antibacterianos , Antimaláricos , Antineoplásicos , Chalconas , Pruebas de Sensibilidad Microbiana , Plasmodium falciparum , Pirazoles , Piridinas , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Chalconas/farmacología , Chalconas/síntesis química , Chalconas/química , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Línea Celular Tumoral , Relación Estructura-Actividad , Plasmodium falciparum/efectos de los fármacos , Pirazoles/farmacología , Pirazoles/química , Pirazoles/síntesis química , Piridinas/farmacología , Piridinas/química , Piridinas/síntesis química , Antimaláricos/farmacología , Antimaláricos/síntesis química , Antimaláricos/química , Simulación del Acoplamiento Molecular , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular/efectos de los fármacos , Estructura Molecular , Animales , Relación Dosis-Respuesta a Droga , Neisseria gonorrhoeae/efectos de los fármacosRESUMEN
OBJECTIVES: Regular quality-assured WGS with antimicrobial resistance (AMR) and epidemiological data of patients is imperative to elucidate the shifting gonorrhoea epidemiology, nationally and internationally. We describe the dynamics of the gonococcal population in 11 cities in Brazil between 2017 and 2020 and elucidate emerging and disappearing gonococcal lineages associated with AMR, compare to Brazilian WGS and AMR data from 2015 to 2016, and explain recent changes in gonococcal AMR and gonorrhoea epidemiology. METHODS: WGS was performed using Illumina NextSeq 550 and genomes of 623 gonococcal isolates were used for downstream analysis. Molecular typing and AMR determinants were obtained and links between genomic lineages and AMR (determined by agar dilution/Etest) examined. RESULTS: Azithromycin resistance (15.6%, 97/623) had substantially increased and was mainly explained by clonal expansions of strains with 23S rRNA C2611T (mostly NG-STAR CC124) and mtr mosaics (mostly NG-STAR CC63, MLST ST9363). Resistance to ceftriaxone and cefixime remained at the same levels as in 2015-16, i.e. at 0% and 0.2% (1/623), respectively. Regarding novel gonorrhoea treatments, no known zoliflodacin-resistance gyrB mutations or gepotidacin-resistance gyrA mutations were found. Genomic lineages and sublineages showed a phylogenomic shift from sublineage A5 to sublineages A1-A4, while isolates within lineage B remained diverse in Brazil. CONCLUSIONS: Azithromycin resistance, mainly caused by 23S rRNA C2611T and mtrD mosaics/semi-mosaics, had substantially increased in Brazil. This mostly low-level azithromycin resistance may threaten the recommended ceftriaxone-azithromycin therapy, but the lack of ceftriaxone resistance is encouraging. Enhanced gonococcal AMR surveillance, including WGS, is imperative in Brazil and other Latin American and Caribbean countries.
Asunto(s)
Antibacterianos , Azitromicina , Farmacorresistencia Bacteriana , Gonorrea , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae , Secuenciación Completa del Genoma , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/clasificación , Brasil/epidemiología , Humanos , Gonorrea/microbiología , Gonorrea/epidemiología , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Azitromicina/farmacología , Masculino , Genoma Bacteriano , Femenino , Adulto , Epidemiología Molecular , Adulto Joven , Genómica , ARN Ribosómico 23S/genética , Persona de Mediana Edad , Ceftriaxona/farmacología , Adolescente , Tipificación de Secuencias Multilocus , Cefixima/farmacologíaRESUMEN
BACKGROUND: Little is known about the aetiology of urethral discharge syndrome (UDS) and genital ulcer disease (GUD) in Brazil due to limited access to laboratory tests and treatment based mainly on the syndromic approach. OBJECTIVES: To update Brazilian treatment guidelines according to the current scenario, the first nationwide aetiological study for UDS and GUD was performed. METHODS: Male participants with urethral discharge (UD) and/or genital ulcer (GU) reports were enrolled. Sample collection was performed by 12 sentinel sites located in the five Brazilian regions. Between 2018 and 2020, 1141 UD and 208 GU samples were collected in a Universal Transport Medium-RT (Copan). A multiplex quantitative PCR kit (Seegene) was used to detect UD: Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), M. hominis (MH), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV), Ureaplasma parvum (UP), U. urealyticum (UU) and another kit to detect GU: cytomegalovirus (CMV), Haemophilus ducreyi (HD), herpes simplex virus type 1 (HSV1), herpes simplex virus type 2 (HSV2), lymphogranuloma venereum (LGV), Treponema pallidum (TP) and varicella-zoster virus (VZV). RESULTS: In UD samples, the frequency of pathogen detection was NG: 78.38%, CT: 25.6%, MG: 8.3%, UU: 10.4%, UP: 3.5%, MH: 3.5% and TV: 0.9%. Coinfection was assessed in 30.9% of samples, with 14.3% of NG/CT coinfection. The most frequent pathogen identified in GU was HSV2, present in 40.8% of the samples, followed by TP at 24.8%, LGV and CMV at 1%, and HSV1 at 0.4%. Coinfection of TP/HSV2 was detected in 4.4% of samples. VZV and HD were not detected. In 27.7% of the GU samples, no pathogen was detected. CONCLUSION: This study provided the acquisition of unprecedented data on the aetiology of UDS and GUD in Brazil, demonstrated the presence of a variety of pathogens in both sample types and reaffirmed the aetiologies known to be most prevalent globally.
Asunto(s)
Coinfección , Infecciones por Citomegalovirus , Herpesvirus Humano 1 , Enfermedades de Transmisión Sexual , Trichomonas vaginalis , Masculino , Humanos , Úlcera/complicaciones , Brasil/epidemiología , Coinfección/epidemiología , Coinfección/complicaciones , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/etiología , Chlamydia trachomatis/genética , Herpesvirus Humano 2 , Treponema pallidum , Neisseria gonorrhoeae/genética , Genitales , Infecciones por Citomegalovirus/complicacionesRESUMEN
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: Neisseria gonorrheae and Chlamydia trachomatis are associated with mucosal inflammation and human immunodeficiency virus 1 (HIV-1) transmission. We assessed levels of inflammatory cytokines in men who have sex with men (MSM) with and without rectal gonorrhea and/or chlamydia in Lima, Peru. METHODS: We screened 605 MSM reporting condomless receptive anal intercourse for rectal N. gonorrheae/C. trachomatis using nucleic acid testing. We identified 101 cases of gonorrhea and/or chlamydia and randomly selected 50 N. gonorrheae/C. trachomatis positive cases and matched 52 negative controls. We measured levels of IL-1ß, IL-6, IL-8, and TNF-α in rectal secretions. Tests for HIV-1, rectal N. gonorrheae/C. trachomatis, and mucosal cytokines were repeated after 3 and 6 months. Cytokine levels in cases and uninfected controls were compared using Wilcoxon rank-sum tests and linear regression. RESULTS: MSM with gonorrhea/chlamydia had elevated levels of all cytokines in rectal mucosa compared with matched controls (all P values <.001). Following antibiotic treatment there were no significant differences in cytokine levels at 3- or 6-month follow-up evaluations (all P values >.05). DISCUSSION: Rectal gonorrhea/chlamydia infection is associated with transient mucosal inflammation and cytokine recruitment. Our data provide proof of concept for rectal sexually transmitted infection screening as an HIV prevention strategy for MSM. Clinical Trials Registration. NCT03010020.
Asunto(s)
Infecciones por Chlamydia , Gonorrea , Infecciones por VIH , VIH-1 , Enfermedades del Recto , Minorías Sexuales y de Género , Masculino , Humanos , Homosexualidad Masculina , Gonorrea/diagnóstico , Chlamydia trachomatis , Citocinas , Perú/epidemiología , Neisseria gonorrhoeae , Infecciones por Chlamydia/diagnóstico , Enfermedades del Recto/epidemiología , Membrana Mucosa , Inflamación , Infecciones por VIH/tratamiento farmacológico , PrevalenciaRESUMEN
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
Hematogenous spread of Neisseria gonorrhoeae, a sexually transmitted pathogen, results in disseminated gonococcal disease (DGD), also known as arthritis-dermatitis syndrome, due to the development of skin lesions, tenosynovitis, and arthritis. The most frequently affected population is young adults. We describe the case of an adolescent female who acutely developed skin lesions, arthritis, tenosynovitis, and constitutional symptoms. The causal agent was identified by a culture of vaginal secretion and treated with ceftriaxone for 7 days with complete recovery. It is important to differentiate this clinical picture from other types of arthritis developed in adolescence.
Asunto(s)
Artritis Infecciosa , Gonorrea , Tenosinovitis , Adolescente , Adulto Joven , Humanos , Femenino , Niño , Tenosinovitis/complicaciones , Antibacterianos/uso terapéutico , Gonorrea/complicaciones , Gonorrea/diagnóstico , Gonorrea/tratamiento farmacológico , Neisseria gonorrhoeae , Artritis Infecciosa/diagnósticoRESUMEN
BACKGROUND AND AIM: Gonorrhea is a bacterial infection in the urogenital tract, transmitted by sexual or perinatal contact, caused by Neisseria gonorrhoeae, a gram-negative diplococcus. The present study evaluates the frequency of N. gonorrhoeae in women treated at Hospital Wladimir Arruda in poor area of São Paulo and also verifies the presence of genetic resistance against three antimicrobials of different classes: Tetracycline, Azithromycin and Ciprofloxacin. METHODS: This is an observational and descriptive study with a quantitative approach. Samples were collected at Hospital Escola Wladimir Arruda. The volunteers are women from 16 to 65 years of age. Sociodemographic, gynecological, sexual and health data are collected through a questionnaire, their symptoms/clinical manifestation were requested by the medical records, and then the participant is referred for collection of samples of cervical vaginal smear. The samples were screened for N. gonorrhoeae (dcmH gene) and tested for resistance genes to Tetracycline, Azithromycin and Ciprofloxacin through PCR. RESULTS: In the total of 127 samples analyzed by Real-Time PCR, 23 were positive and correspond to a general prevalence of a gonococcal infection in the studied population of 17% (CI:95%), and the participants were married (43.4%), had active sexual life (56.5%) and did not use any type of condom during sexual intercourse (52.1%). The resistance to the tetM ribosomal gene was found in 14 samples, prevalence of 60% (CI= 95%). CONCLUSIONS: We have described a concerning frequency of N. gonorrhoeae infection in females attended in an outcare patient. Also, most of the strains detected presented resistance to one or more antimicrobials.
Asunto(s)
Antiinfecciosos , Gonorrea , Humanos , Femenino , Gonorrea/epidemiología , Gonorrea/tratamiento farmacológico , Gonorrea/microbiología , Azitromicina/uso terapéutico , Brasil/epidemiología , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Neisseria gonorrhoeae/genética , Ciprofloxacina/uso terapéutico , Tetraciclina , Antiinfecciosos/uso terapéuticoRESUMEN
BACKGROUND: Gonorrhea is not a notifiable disease in Brazil, and the national health information system does not collect data on reported cases or infection prevalence. METHODS: We compiled published data on gonorrhea prevalence in Brazil from cross-sectional surveys and clinical trials between 2000 and 2020. The study entry criteria included a sample size of 50 or more, and Neisseria gonorrhoeae infection detected in urine, urethral, anal, or cervicovaginal specimens using either Nucleic Acid Amplification Test or culture. Gonorrhea prevalence trends between 2000 and 2020 were generated using Spectrum-STI, a statistical trend-fitting model. RESULTS: Forty-five studies with 59 gonorrhea prevalence data points were identified. Fifty data points were for women and represented 21,815 individuals, eight for men encompassing a total of 4,587 individuals, and one for transgender people comprising 345 individuals. The Spectrum-STI estimate for the prevalence of urogenital infection with gonorrhea in women 15-49 in 2020 was 0.63% (95% confidence interval (CI): 0.13-2.23) and was lower than the 1.05% estimated value for 2000 (95% CI: 0.36-2.79). The corresponding figures for men were 0.70% (95% CI: 0.16-2.44) and 1.14% (95% CI: 0.34-3.15). Anal prevalence estimates could not be generated because of insufficient data (three data points). CONCLUSIONS: These results suggest that the overall prevalence of genitourinary gonococcal infections in Brazil is less than 1%. Data on gonorrhea prevalence in men and in populations at increased STI vulnerability are limited.