Recent dynamics in Neisseria gonorrhoeae genomic epidemiology in Brazil: antimicrobial resistance and genomic lineages in 2017-20 compared to 2015-16.

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.

Aetiological molecular identification of sexually transmitted infections that cause urethral discharge syndrome and genital ulcer disease in Brazilian men: a nationwide study.

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.

Brazilian Clinical Practice Guidelines for Sexually Transmitted Infections That Cause Urethral Discharge: Assessment According to the AGREE II and Critical Analysis Based on the WHO Recommendations.

BACKGROUND: Sexually transmitted infections (STI) can have severe consequences. In Brazil, case management is recommended by the Clinical Protocol and Therapeutical Guidelines for Comprehensive Care for People with STIs (PCDT-IST). This study assessed the quality of PCDT-IST (2021) and reviewed the main recommendations for the management of STI that cause urethral discharge compared with the World Health Organization (WHO) STI Guidelines. METHODS: The PCDT-IST (2021) quality was independently assessed by 4 appraisers using the Appraisal of Guidelines Research and Evaluation instrument, version II (AGREE II). The PCDT-IST (2021) and the WHO Guidelines for the Management of Symptomatic STI (2021) were compared considering 14 different assessment domains. RESULTS: The PCDT-IST (2021) scores in the AGREE II domains were: Rigor of Development (58%), Applicability (35%), Editorial Independence (38%), Scope and Purpose (78%), Stakeholder Involvement (74%), and Clarity and Presentation (82%). The overall score was 67%, and all appraisers recommended the Brazilian guideline. Regarding the PCDT-IST (2021) and the WHO STI Guidelines (2021) comparation, 10 domains would be relevant for further reviewing the Brazilian recommendations: Diagnostic tests; Etiological approach; Treatment for recurrent urethral discharge; Treatment for urethritis without etiological agent identification; Treatment for gonococcal urethritis; Treatment for chlamydial urethritis; Retreatment for gonococcal infections; Treatment for Mycoplasma genitalium urethritis; Treatment for Trichomonas vaginalis urethritis; 10. Flowcharts. CONCLUSIONS: The PCDT-IST (2021) has a reasonable degree of quality. However, the domains of Applicability, Rigor of Development, and Editorial Independence must be better ensured. The guidelines comparison will help to select key topics that should be addressed with priority in the following national STI guidelines updates.

Genomic epidemiology of Neisseria gonorrhoeae elucidating the gonococcal antimicrobial resistance and lineages/sublineages across Brazil, 2015-16.

OBJECTIVES: Neisseria gonorrhoeae antimicrobial resistance (AMR) surveillance is imperative internationally, but only eight (22.9%) countries in the WHO Region of the Americas reported complete AMR data to the WHO Global Gonococcal Antimicrobial Surveillance Program (WHO GASP) in 2016. Genomic studies are ideal for enhanced understanding of gonococcal populations, including the spread of AMR strains. To elucidate the circulating gonococcal lineages/sublineages, including their AMR determinants, and the baseline genomic diversity among gonococcal strains in Brazil, we conducted WGS on 548 isolates obtained in 2015-16 across all five macroregions in Brazil. METHODS: A total of 548 gonococcal isolates cultured across Brazil in 2015-16 were genome sequenced. AMR was determined using agar dilution and/or Etest. Genome sequences of isolates from Argentina (n = 158) and the 2016 WHO reference strains (n = 14) were included in the analysis. RESULTS: We found 302, 68 and 214 different NG-MAST, MLST and NG-STAR STs, respectively. The phylogenomic analysis identified one main antimicrobial-susceptible lineage and one AMR lineage, which was divided into two sublineages with different AMR profiles. Determination of NG-STAR networks of clonal complexes was shown as a new and valuable molecular epidemiological analysis. Several novel mosaic mtrD (and mtrR and mtrE) variants associated with azithromycin resistance were identified. CONCLUSIONS: We describe the first genomic baseline data to support the Brazilian GASP. The high prevalence of resistance to ciprofloxacin, tetracycline and benzylpenicillin, and the high number of isolates with mosaic penA and azithromycin resistance mutations, should prompt continued and strengthened AMR surveillance, including WGS, of N. gonorrhoeae in Brazil.

Evaluation of seven rapid tests for syphilis available in Brazil using defibrinated plasma panels.

OBJECTIVES: In 2012, the WHO estimated that 6 million new cases of syphilis per year would occur worldwide, including 937 000 in Brazil. Early diagnosis and treatment of syphilis are essential to reduce morbidity and prevent transmission. The availability of rapid tests (RTs) for this diagnosis means that testing can be performed more quickly, as a point-of-care test, even in non-laboratory environments and requires only simple technical training to antibodies detection. The objective of this study was to evaluate the performance and operational aspects of seven commercially available RTs for syphilis in Brazil. METHODS: Seven rapid treponemal tests were evaluated for sensitivity, specificity, accuracy and Kappa value, according to a panel composed of 493 members. The operational performance of the assay was also determined for these tests. RESULTS: The seven RTs showed sensitivity ranging from 94.5% to 100% when compared with the reference tests and specificity of between 91.5% and 100%. All the RTs evaluated presented good operational performance, and only one failed to present the minimum specificity as defined by Brazil's Ministry of Health. CONCLUSION: All the tests presented good operational performance, and the professionals who performed them considered them to be easy to use and interpret. This evaluation is important for making informed choices of tests to be used in the Brazilian Unified Health System.

Effects of 1,3,5-triphenyl-4,5-dihydro-1H-pyrazole derivatives on cell-cycle and apoptosis in human acute leukemia cell lines.

Pyrazoline is an important 5-membered nitrogen heterocycle that has been extensively researched. Ten derivatives were synthesized and tested for antileukemic effects on 2 human acute leukemia cell lines, K562 and Jurkat. The most cytotoxic of these derivatives, compound 21, was chosen for investigation of cytotoxicity mechanisms. The results obtained with selectivity calculations revealed that compound 21 is more selective for acute leukemia (K562 and Jurkat cell lines) than for other tumor cell lines. Moreover, compound 21 was not cytotoxic to normal cell lines, indicating a potential use in clinical tests. Compound 21 caused a significant cell cycle arrest in the S-phase in Jurkat cells and increased the proportion of cells in the sub G0/G1 phase in both cell lines. Cells treated with compound 21 demonstrated morphological changes characteristic of apoptosis in the EB/AO assay, confirmed by externalization of phosphatidylserine by the annexin V - fluorescein isothiocyanate method and by DNA fragmentation. An investigation of cytotoxicity mechanisms suggests the involvement of an intrinsic apoptosis pathway due to mitochondrial damage and an increase in the ratio of mitochondrial Bax/Bcl2. Pyrazoline 21 obeyed Lipinski's "rule of five" for drug-likeness. Based on these preliminary results, the antileukemic activity of compound 21 makes it a potential anticancer agent.

Prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium and risk factors among pregnant women in Brazil: Results from the national molecular diagnosis implementation project.

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.

Apoptotic events induced by maleimides on human acute leukemia cell lines.

Cyclic imides are known for their antitumor activity, especially the naphthalimide derivatives, such as Mitonafide and Amonafide. Recently, we have demonstrated the cytotoxic effect of a series of naphthalimide derivatives against B16F10 melanoma cells. On the basis of this fact, we have developed a study starting from the synthesis of different cyclic imides and the evaluation of their cytotoxic properties on human acute leukemia cells (K562 and Jurkat). Initially, a screening test was conducted to select the compound with the best cytotoxic effect, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. After this selection, structural modifications were performed in the most active compound to obtain five more derivatives. All compounds presented a good cytotoxic effect. The results of cell cycle analysis, fluorescence microscopy, and Annexin V-FITC assay confirmed that the cells observed in the sub-G0/G1 phase were undergoing apoptosis. From this set of results, cyclic imides 8, 10, and 12 were selected for the evaluation of the mechanisms involved in the apoptotic process. The results demonstrate the involvement of the intrinsic pathway of apoptosis, evidenced by the reduction in mitochondrial potential, an increase in the level of AIF protein expression, a decreased level of expression of anti-apoptotic Bcl-2 protein, and an increased level of expression of pro-apoptotic protein Bax in both K562 and Jurkat cells treated with cyclic imides (8, 10, and 12). Furthermore, cyclic imides 8 and 10 caused an increase in the level of Fas expression in Jurkat cells, indicating the additional involvement of the extrinsic apoptosis pathway. The compounds (8, 10, and 12) also caused a decreased level of expression of anti-apoptotic protein survivin. The biological effects observed with these cyclic imide derivatives in this study suggest promising applications against acute leukemia.

Comparison between two portable hemoglobinometers and a reference method to verify the reliability of screening in blood donors.

Portable hemoglobinometers are used to determine hemoglobin level, but there are conflicting reports regarding their accuracy. The aim of this study was to compare results from two portable hemoglobinometers (HemoCue® and Hemo-Control) with an automated hematology analyzer (Sysmex XE-2100D) to determine if the screening of blood donors is reliable. A total of 426 blood donors' samples were studied and on average the Hb content measured in capillary blood samples was higher than that found in venous blood samples. Hemoglobinometers can be employed as a method to screen blood donors, but critical values should be confirmed in an automated hematology analyzer.

Gonorrhea prevalence in adults in Brazil: Spectrum-STI trend estimation, 2000-2020.

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.

Perspectives and challenges for mother-to-child transmission of HIV, hepatitis B, and syphilis in Brazil.

Background: Eliminating mother-to-child transmission (MTCT) of HIV, hepatitis B, and syphilis is a challenge in Brazil. Many policies have been implemented since 1986, but important gaps remain. This study aimed to describe the trends of MTCT in Brazil and evaluate the gaps and perspectives in this scenario. Methods: This is a descriptive study conducted with secondary data publicly available in the information systems of the Brazilian Ministry of Health regarding data on HIV, syphilis, and hepatitis B in pregnant women and children from 2011 to 2021. Results: HIV and hepatitis B have had constant rates over the years in pregnant women, with the detection rates around 2.5/1,000 live birth (LB) and 0.5/1.000LB, respectively. The same did not happen with syphilis, which has shown an increasing line in the last decade. In 2011, the detection rate of syphilis in pregnancy was 4.7/1,000LB, and in 2021 it reached 27.1/1,000LB. Regarding the trends in children, an important decrease was observed in HIV/AIDS (incidence rate from 0.18/1,000 in 2011 to 0.04/1,000 in 2021) and Hepatitis B (incidence rate from 0.9/1,000LB in 2011 to 0.5/1,000LB in 2021). For congenital syphilis, there is a continuous increase, being 3.3/1,000LB in 2011 and 9.9/1,000LB in 2021. Data from the HIV clinical monitoring showed that antiretroviral treatment coverage among pregnant women identified increased slightly between 2011 and 2021, in Brazil, from 92.3% to 94.3%. For syphilis, 82.5% of pregnant women were treated with benzathine penicillin, and 88.7% in 2011. The historical series of hepatitis B vaccination coverage in children has decreased over the years; it was 96% in 2013 and 76% in 2021. Conclusion: These data show many gaps and some perspectives in the MTCT program in Brazil. The country is close to reaching MTCT HIV elimination, but there are many challenges regarding HBV and syphilis. These data can be used to organize the strategies to improve the Brazilian response to MTCT elimination of HIV, hepatitis B, and syphilis.

Assessment of the Accuracy, Usability and Acceptability of a Rapid Test for the Simultaneous Diagnosis of Syphilis and HIV Infection in a Real-Life Scenario in the Amazon Region, Brazil.

We field-assessed the accuracy, acceptability, and feasibility of the SD BIOLINE HIV/Syphilis Duo rapid diagnostic test in three groups: pregnant women, female sex workers (FSW), and men who have sex with men (MSM). Venous blood samples collected in the field were compared with the respective gold standard methods: SD BIOLINE HIV/Syphilis Duo Treponemal Test versus FTA-abs (Wama brand) treponemal laboratory test for syphilis, and SD BIOLINE HIV/Syphilis Duo Test versus the fourth generation Genscreen Ultra HIV Ag-Ag (Bio-Rad brand) laboratory test for HIV. From a total of 529 participants, 397 (75.1%) were pregnant women, 76 (14.3%) FSW and 56 (10.6%) MSM. Sensitivity and specificity parameters of HIV were 100.0% (95% CI: 82.35-100.0%) and 100.0% (95% CI: 99.28-100.0%), respectively. Sensitivity and specificity parameters found for TP antibody detection were 95.00% (95% CI: 87.69-98.62%) and 100.0% (95% CI: 98.18-100.0%), respectively. The SD BIOLINE HIV/Syphilis Duo Test showed high acceptability among participants (85.87%) and health professionals (85.51%), as well as easy usability by professionals (91.06%). The usability of the SD BIOLINE HIV/Syphilis Duo Test kit would not be a barrier to accessing rapid testing, if the product were incorporated into the list of health service supplies.

Detection of HPV DNA in vaginal samples self-collected by women living with HIV treated through the Brazilian public health system: Prevalence and analysis of risk factors.

BACKGROUND: Women living with human immunodeficiency virus (HIV) (WLWH) are more likely to be infected with the oncogenic human papillomavirus (HPV). We assessed the prevalence of high-risk (HR) (16/18/31/33/35/39/45/51/52/56/58/59/68/73/82), probable high-risk (pHR) (26/53/66), and low-risk (LR) (6/11/40/42/43/44/54/61/70) HPV types and their associated risk factors. METHODS: This cross-sectional study of WLWH aged 18-64 years included one laboratory and eight HIV-specialty healthcare facilities in the pilot network. Descriptive statistics were used to assess sociodemographic and behavioral characteristics. Adjusted analyses were conducted to evaluate risk factors associated with HR and/or pHR HPV infection in WLWH. RESULTS: From May/2021 to May/2022, 1,914 (92.5%) WLWH participated in the pilot study and had valid HPV-DNA results of self-collected vaginal samples. The median age of the participants was 45 years, 60.1% had ≥ 9 years of schooling, 80.5% were ≤ 18 years at first sexual intercourse, and 51.7% had > 4 sexual partners throughout life. The prevalence of any HPV type, HR HPV, pHR HPV, and LR HPV was 65.8%, 49.6%, 16.7%, and 40.0%, respectively. Age was inversely associated with pHR and/or HR-HPV (p < 0.001), and education level was inversely associated with HR-HPV (p = 0.003) types. Any HR or pHR was associated with being single (p = 0.029) and exchanging sex for drugs (p = 0.037). CONCLUSIONS: The prevalence of HPV, especially HR HPV, among WLWH is high in Brazil, highlighting the need for HPV screening in this population. Self-collection of vaginal samples is an important strategy for increasing testing access.

Subnational certification of elimination of mother-to-child transmission of HIV and/or syphilis: a Brazilian experience report.

OBJECTIVE: to describe the subnational implementation process of the certification for elimination of mother-to-child transmission of HIV and/or syphilis, its main barriers, challenges and opportunities. METHODS: in 2022, indicators from the last full year for impact targets and the last two full years for process targets, available in national information systems, were evaluated; descriptive reports were analyzed and actions were acknowledged within four thematic axes, according to PAHO/WHO recommendations. RESULTS: 43 municipalities ≥ 100,000 inhabitants were certified, covering 24.6 million inhabitants; one municipality achieved dual elimination (HIV-syphilis), 28 municipalities achieved elimination of HIV and 10 received silver tiers; regarding syphilis, one elimination was observed, along with 4 gold tiers, 13 silver tiers and 4 bronze tiers; a higher number of certifications was identified in the Southeast and South regions. CONCLUSION: barriers and challenges of the process were overcome through tripartite collaboration; the experience provided better integration of surveillance with care and improved actions aimed at preventing mother-to-child transmission. MAIN RESULTS: First experience of the sub-national process of certification of elimination of mother-to-child transmission (MTCT) of HIV and/or syphilis at a global level. In 2022, 43 municipalities ≥ 100,000 inhabitants were certified, covering 24.6 million inhabitants. IMPLICATIONS FOR SERVICES: The experience of sub-national certification of the EMTCT was important in mobilizing the municipalities that engaged in its initiatives, worked to improve the quality of care and surveillance and emerging as the main proponents in the process. PERSPECTIVES: Through this ongoing and dynamic initiative, there is an anticipation of over 100 municipalities and states joining in 2023. Sub-national certification aims to enhance comprehensive care for pregnant women, in order to achieve national certification of EMTCT.

National surveillance of Neisseria gonorrhoeae antimicrobial susceptibility and epidemiological data of gonorrhoea patients across Brazil, 2018-20.

Objectives: To (i) describe the nationwide antimicrobial susceptibility of Neisseria gonorrhoeae (NG) isolates cultured across Brazil in 2018-20 and compare it with NG antimicrobial resistance data from 2015-16, and (ii) present epidemiological data of the corresponding gonorrhoea patients in 2018-20. Methods: Twelve representative sentinel sites cultured NG isolates from men with urethral discharge. Susceptibility to eight antimicrobials was examined using agar dilution method, according to WHO standards. The consenting participants were invited to provide epidemiological data. Results: In total, 633 NG isolates (one isolate per participant) were analysed, and 449 (70.9%) questionnaires were answered. Heterosexual (68.2%) and homosexual (23.1%) sexual orientations were common, and most prevalent types of unprotected sexual intercourse were vaginal insertive (69.9%), oral giving (56.6%) and anal insertive (47.4%). The levels of in vitro NG resistance to ciprofloxacin, tetracycline, benzylpenicillin, azithromycin, cefixime, gentamicin, spectinomycin and ceftriaxone were 67.3%, 40.0%, 25.7%, 10.6%, 0.3%, 0%, 0% and 0%, respectively. Compliance with the recommended first-line ceftriaxone 500 mg plus azithromycin 1 g therapy was high (90.9%). Conclusions: Compared with 2015-16, ciprofloxacin resistance has remained high and azithromycin and cefixime resistance rates have increased in Brazil. Resistance remained lacking to ceftriaxone, gentamicin and spectinomycin, which all are gonorrhoea treatment options. The increasing azithromycin resistance in Brazil and internationally may threaten the future use of azithromycin in dual regimens for treatment of gonorrhoea. Consequently, continued and enhanced quality-assured surveillance of gonococcal AMR, and ideally also treatment failures and including WGS, is imperative in Brazil and worldwide.

Brazilian Protocol for Sexually Transmitted Infections 2020: syphilis diagnostic tests.

The recommendations for diagnostic tests for investigating syphilis are part of the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections and the Technical Manual for Syphilis Diagnosis, published by the Brazilian Ministry of Health. These recommendations were developed based on scientific evidence and discussions with a panel of experts. This article presents direct tests to detect Treponema pallidum in lesions and algorithms that combine treponemal and non-treponemal antibody tests to assist in syphilis diagnosis, with the aim of contributing to the efforts of health service managers and health professionals in qualifying health care. The article also covers the use of non-treponemal tests to investigate neurosyphilis and guidelines for interpreting non-treponemal antibody titers in monitoring the treatment and diagnosis of congenital syphilis, as well as prospects for innovations in diagnosis. The critical role of rapid immunochromatographic treponemal tests for public health and for addressing syphilis is also highlighted. Highlighted excerpt: During the natural evolution of syphilis, activity periods with distinct clinical, immunological, and histopathological characteristics are interspersed with latent periods when there are no signs or symptoms, making access to tests critical for early diagnosis.

Brazilian Protocol for Sexually Transmitted Infections, 2020: infections that cause urethral discharge.

This article approaches infections that cause urethral discharge. This theme is part of the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Ministry of Health of Brazil in 2020. These guidelines were prepared based on scientific evidence and validated in discussions with experts. Urethritis can cause severe and even irreversible health damage when not properly treated, or when the microorganism develops antimicrobial resistance. It is noteworthy that the high levels of antimicrobial resistance grown by pathogens that cause urethritis comprises a global emergency in public health. This article presents epidemiological and clinical aspects, recommendations on diagnostic and treatment, and strategies for surveillance, prevention, and control actions for infections that cause urethral discharge, to contribute to managers' and health professionals' care qualification. Associated factors with urethritis are: young age, low socioeconomic level, multiple partnerships or new sexual partnership, history of STI, irregular use of condoms, and lack of access to adequate diagnosis and treatment.

[Brazilian Protocol for Sexually Transmitted Infections 2020: syphilis diagnostic tests]. / Protocolo Brasileiro para Infecções Sexualmente Transmissíveis 2020: testes diagnósticos para sífilis.

The recommendations for diagnostic tests for investigating syphilis are part of the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections and the Technical Manual for Syphilis Diagnosis, published by the Brazilian Ministry of Health. These recommendations were developed based on scientific evidence and discussions with a panel of experts. Aiming to contribute to the efforts of health service managers and health professionals in qualifying health care, this article presents the use of direct tests to detect Treponema pallidum in lesions, as well as algorithms that combine treponemal and non-treponemal antibody tests to assist in the diagnosis of syphilis. The article also covers use of non-treponemal tests to investigate neurosyphilis and guidelines for interpreting non-treponemal antibody titers in monitoring treatment and diagnosis of congenital syphilis, as well as prospects for innovations in diagnosis. The important role of rapid immunochromatographic treponemal tests for public health and for addressing syphilis is also highlighted.

As recomendações de testes diagnósticos para investigação da sífilis compõem o Protocolo Clínico e Diretrizes Terapêuticas para Atenção Integral às Pessoas com Infecções Sexualmente Transmissíveis e o Manual Técnico para Diagnóstico de Sífilis, publicados pelo Ministério da Saúde do Brasil. Tais recomendações foram elaboradas com base em evidências científicas e discussões com painel de especialistas. Visando contribuir com gestores e profissionais de saúde na qualificação da assistência, este artigo apresenta o uso dos exames diretos para detecção de Treponema pallidum em lesões, assim como algoritmos que combinam testes imunológicos treponêmicos e não treponêmicos para auxiliar no diagnóstico da sífilis. O artigo também apresenta o uso dos testes não treponêmicos para investigação de neurossífilis e orientações para interpretação do título dos anticorpos não treponêmicos no monitoramento do tratamento e diagnóstico de sífilis congênita, bem como as perspectivas futuras de inovações em diagnóstico. Ressalta-se, além disso, o importante papel dos testes rápidos imunocromatográficos treponêmicos para a saúde pública e o enfrentamento da sífilis.

Las recomendaciones de las pruebas de diagnóstico de sífilis forman parte del Protocolo Clínico y Directrices Terapéuticas para la Atención Integral a las Personas con Infecciones de Transmisión Sexual y del Manual Técnico para el Diagnóstico de Sífilis, publicados por el Ministerio de Salud de Brasil. Estos documentos fueron preparados en base a la evidencia científica y discusiones con especialistas. Con el objetivo de contribuir con los administradores y profesionales de la salud pública en la calificación de la atención, este artículo presenta el uso de pruebas directas para la detección de Treponema pallidum en lesiones, además de algoritmos que combinan pruebas treponémicas y no treponémicas para ayudar al diagnóstico. También se presentan las pruebas no treponémicas para investigar la neurosífilis y orientaciones para la interpretación de títulos de anticuerpos no treponémicos para monitorear la respuesta al tratamiento y diagnosticar la sífilis congénita, así como las perspectivas futuras para las innovaciones diagnósticas. También se enfatiza el uso de pruebas inmunocromatográficas treponémicas rápidas como una herramienta importante para la salud pública y para el enfrentamiento de la sífilis.

[Brazilian Protocol for Sexually Transmitted Infections 2020: infections that cause urethral discharge]. / Protocolo Brasileiro para Infecções Sexualmente Transmissíveis 2020: infecções que causam corrimento uretral.

This article approach infections that cause urethral discharge, theme which is part of the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Ministry of Health of Brazil in 2020. These guidelines were prepared based on scientific evidence and validated in discussions with experts. When urethritis is not treated correctly, or when the microorganism develops antimicrobial resistance, it can cause serious and even irreversible health damage. It is noteworthy that the high levels of antimicrobial resistance developed by pathogens that causes urethritis comprises a global emergency in public health. This article presents epidemiological and clinical aspects, recommendations on diagnostic and treatment, and strategies for surveillance, prevention and control actions of infections that cause urethral discharge, with the purpose of contributing with managers and health professionals to care qualification.

Este artigo aborda as infecções que causam corrimento uretral, tema que compõe o Protocolo Clínico e Diretrizes Terapêuticas para Atenção Integral às Pessoas com Infecções Sexualmente Transmissíveis, publicado pelo Ministério da Saúde do Brasil em 2020. Tal documento foi elaborado com base em evidências científicas e validado em discussões com especialistas. As uretrites, quando não tratadas de maneira correta, ou quando o microrganismo desenvolve resistência ao tratamento empregado, podem causar danos graves e até irreversíveis à saúde. Os níveis de resistência antimicrobiana que esses agentes têm desenvolvido são considerados uma emergência global em saúde pública. Neste artigo, são apresentados aspectos epidemiológicos e clínicos, recomendações sobre diagnóstico e tratamento e estratégias para as ações de vigilância, prevenção e controle das infecções que causam corrimento uretral, com a finalidade de contribuir com gestores e profissionais de saúde para a qualificação da assistência.

El artículo trata de las infecciones que causan secreción uretral, tema que hace parte del Protocolo Clínico y Directrices Terapéuticas para Atención Integral a Personas con Infecciones de Transmisión Sexual, publicado por el Ministerio de Salud de Brasil en 2020. Dicho documento se elaboró con base en evidencias científicas y se validó en discusiones con expertos. Las uretritis, cuando no tratadas correctamente o cuando el microorganismo desarrolla resistencia al tratamiento, puede ocasionar daños graves a la salud. Los niveles de resistencia antimicrobiana que estos agentes desarrollan son considerados una emergencia de salud pública. En este artículo, se presentan aspectos epidemiológicos y clínicos, recomendaciones para el diagnóstico y tratamiento y estrategias para acciones de monitoreo epidemiológico, prevención y control de las infecciones que causan secreción uretral, a fin de contribuir con gestores y personal de salud para la cualificación de la asistencia.

Gonorrhea prevalence in adults in Brazil: Spectrum-STI trend estimation, 2000-2020

ABSTRACT 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.