Thyroid hormone profile is related to prognosis in acute decompensation of cirrhosis.

Objective: To investigate the prognostic significance of thyroid hormone profile in patients hospitalized for decompensated cirrhosis. Subjects and methods: Prospective cohort study that included 119 subjects. All subjects were evaluated at admission and followed for 90 days. TSH, fT3, fT4 were measured within 24 hours of hospitalization. Results: Higher fT4 and lower fT3 levels were observed among Child-Pugh C patients as compared to Child-Pugh A and B, and in those with acute-on-chronic liver failure (ACLF). Lower fT3/fT4 ratio was observed in those with ascites, infections, ACLF, and in Child-Pugh C. Ninety-day mortality was 26.9% and it was independently associated with higher Model for End-stage Liver Disease (MELD) and TSH, and lower fT3/fT4 ratio in multivariate analysis. A new prognostic model including MELD, TSH and fT3/fT4 ratio was devised. The areas under the receiver operating characteristic curves for MELD, fT3/fT4 ratio, TSH (µIU/mL), and the new model for predicting 90-day mortality were 0.847 ± 0.041, 0.841 ± 0.039, 0.658 ± 0.062, and 0.899 ± 0.031, respectively. The 90-day survival was 31.6% in patients with values of the predictive model ≥ -0.77 and 93.5% for values < -0.77 (P < 0.001). Conclusions: Thyroid hormone profile was strongly associated with worse outcomes in patients with cirrhosis and might represent promising prognostic tools that can be incorporated in clinical practice.

Prevalence of chlamydia and gonorreheae among transgender women and travestis in five Brazilian capitals, 2019-2021.

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.

ACE2 and TMPRSS2 expression in patients before, during, and after SARS-CoV-2 infection.

During the SARS-CoV-2 pandemic angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) were constantly under the scientific spotlight, but most studies evaluated ACE2 and TMPRSS2 expression levels in patients infected by SARS-CoV-2. Thus, this study aimed to evaluate the expression levels of both proteins before, during, and after-infection. For that, nasopharyngeal samples from 26 patients were used to measure ACE2/TMPRSS2 ex-pression via qPCR. Symptomatic patients presented lower ACE2 expression levels before and after the infection than those in asymptomatic patients; however, these levels increased during SARS-CoV-2 infection. In addition, symptomatic patients presented higher expression levels of TMPRSS2 pre-infection, which decreased in the following periods. In summary, ACE2 and TMPRSS2 expression levels are potential risk factors for the development of symptomatic COVID-19, and the presence of SARS-CoV-2 potentially modulates those levels.

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.

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.

HPV-DNA test access based on self-collection of vaginal samples from women living with HIV/AIDS: pilot implementation in Brazil / Autocoleta vaginal por mulheres vivendo com HIV/AIDS para testagem de HPV-DNA: implantação piloto no Brasil

Introduction: Women living with HIV/AIDS have a higher frequency of anogenital neoplasms resulting from human papillomavirus (HPV) infection. The World Health Organization recommends that cervical cancer screening uses molecular tests that amplify viral genetic material, such as HPV-DNA. In addition to collection by health professionals, self-collection of vaginal samples is a useful tool for expanding access to testing. Objective: To describe the results of the pilot study that evaluated the acceptability of self-collection of vaginal samples and the applicability of offering HPV-DNA tests with self-collection of vaginal samples for women living with HIV/AIDS in Brazil. Methods: Descriptive cross-sectional study involving women living with HIV/AIDS treated in eight HIV-specialty healthcare facilities distributed in all regions of the country from May 2021 to May 2022 and a central laboratory. Vaginal self-collection was offered, and participants were interviewed about sociodemographic data and impressions of self-collection. Results: In total, 1,919 women living with HIV/AIDS with an average age of 45 years participated in the study. Some type of HPV was detected in 66% (1,267) of cases. The majority (71.9%) said they preferred self-collection to sample collection by health care professionals. Only 53.8% of participants underwent cytology at the appropriate frequency, as recommended by the protocol. Conclusion: The results may support the implementation of molecular biology tests to detect HPV in women living with HIV/AIDS, including the possibility of vaginal self-collection, promoting increased access to cervical cancer screening. (AU)

Introdução: Mulheres vivendo com HIV/AIDS possuem maior frequência de neoplasias anogenitais decorrentes da infecção pelo papilomavírus humano (HPV). A Organização Mundial da Saúde recomenda que o rastreio de câncer do colo do útero seja utilizado por testes moleculares que amplificam o material genético viral, como o HPV-DNA. Além da coleta por profissionais da saúde, a autocoleta de amostras vaginais consiste em uma ferramenta útil para ampliação do acesso à testagem. Objetivo: Descrever os resultados do estudo piloto que avaliou a aceitabilidade da autocoleta de amostra vaginal e aplicabilidade da oferta de testes HPV-DNA com autocoleta de amostras vaginais para mulheres vivendo com HIV/AIDS no Brasil. Métodos: Estudo transversal descritivo envolvendo mulheres vivendo com HIV/AIDS atendidas em oito serviços ambulatoriais distribuídos em todas as regiões do país no período de maio/2021 a maio/2022 e um laboratório central. Realizou-se a oferta de autocoleta vaginal e uma entrevista com as participantes sobre dados sociodemográficos e impressões da autocoleta. Resultados: No total, 1.919 mulheres vivendo com HIV/AIDS com média de 45 anos participaram do estudo. Houve detecção de algum tipo de HPV em 66% (1.267) dos casos. A maioria (71,9%) afirmou preferir a autocoleta à coleta de amostras por profissionais da saúde. Apenas 53,8% das participantes realizaram citologia na periodicidade adequada, conforme recomendação do protocolo. Conclusão:Os resultados poderão apoiar a implementação dos testes de biologia molecular para detecção de HPV em mulheres vivendo com HIV/AIDS, incluindo a possibilidade de autocoleta vaginal, promovendo a ampliação do acesso ao rastreamento de câncer do colo do útero. (AU)

Failure in syndromic management due to drug-resistant Mycoplasma genitalium in Florianópolis, South Brazil / Falha no manejo sindrômico devido a Mycoplasma genitalium resistente em Florianópolis, Sul do Brasil

Introduction: Mycoplasma genitalium is a bacterium associated with sexually transmitted infections that can cause urethritis in men and complications in women, including preterm birth. Increasing macrolide resistance in M. genitalium poses challenges to treatment efficacy. Objective: To present a case of treatment failure of urethritis caused by macrolide-resistant M. genitalium. Case report: This case report describes a 20-year-old man with persistent urethral symptoms despite azithromycin treatment, wherein M. genitalium harbored the A2058G mutation in the 23S rRNA. Subsequent treatment with moxifloxacin resolved symptoms and cleared M. genitalium. Conclusion: The study highlights the importance of resistance testing to guide antimicrobial therapy and emphasizes the need for updated treatment guidelines in Brazil. (AU)

Introdução:Mycoplasma genitalium é uma bactéria associada a infecções sexualmente transmissíveis, que pode causar uretrite em homens e complicações em mulheres, incluindo nascimento prematuro. O aumento da resistência aos macrolídeos em M. genitalium coloca desafios à eficácia do tratamento. Objetivo: Apresentar um caso de falha terapêutica de uretrite causada por M. genitalium resistente aos macrolídeos. Relato de caso: Este relato de caso descreve um homem de 20 anos com sintomas uretrais persistentes, apesar do tratamento com azitromicina, em que M. genitalium possuía a mutação A2058G no rRNA 23S. O tratamento subsequente com moxifloxacino resolveu os sintomas e eliminou M. genitalium. Conclusão: O estudo destacou a importância dos testes de resistência para orientar a terapia antimicrobiana e enfatizou a necessidade de atualizar as diretrizes de tratamento no Brasil. (AU)

Detection of Trichomonas vaginalis by Allplex™ STI Essential Assay (Seegene) in clinical samples from the Brazilian public health system users.

The failures in Trichomonas vaginalis (TV) infection diagnosis leave more than half of cases unidentified. In this report, urine and vaginal discharge samples were analyzed by wet mount, culture examination, and real-time PCR by Allplex™ (Seegene®) kit, in a population assisted by the Brazilian Public Health System. From 747 samples, 2.81% were positive for TV in wet mount and culture, and 3.88% by Allplex™. Samples kept at - 80 ºC for 22 months did not impair the PCR technique. The sensitivity for wet mount, culture, and Allplex™ was 72, 100, and 100%, respectively. Allplex™ technique showed highest detection of TV.

Prevalence of chlamydia and gonorreheae among transgender women and travestis in five Brazilian capitals, 2019-2021 / Prevalências de clamídia e gonorreia entre mulheres trans e travestis de cinco capitais brasileiras, 2019-2021

ABSTRACT 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.

RESUMO Objetivo: Estimar as prevalências e os fatores associados à detecção de Chlamydia trachomatis (CT) e Neisseria gonorrhoeae (NG) em mulheres trans e travestis em cinco capitais brasileiras. Métodos: Os dados vieram de um estudo transversal, realizado entre 2019 e 2021, com pessoas recrutadas por RDS (respondent driven sampling) em São Paulo, Campo Grande, Manaus, Porto Alegre e Salvador. Analisou-se a detecção de CT e NG, em três sítios de coleta (anorretal, orofaríngeo e uretral). Para identificação dos fatores associados empregaram-se modelos logísticos com efeitos mistos. Resultados: Forneceram material biológico para detecção dessas infecções 1.297 participantes recrutadas. As prevalências de CT, NG e coinfecção foram, respectivamente, 11,5, 13,3 e 3,6%. Foram independentemente associados à detecção para CT: trabalho sexual no passado (odds ratio — OR=1,73; intervalos de confiança para 95% — IC95% 1,02-2,95), no momento atual (OR=2,13; IC95% 1,23-3,69) e como atividade parcial (OR=2,75; IC95% 1,60-4,75) e uso de drogas injetáveis na vida (OR=3,54; IC95% 1,49-8,40). Para NG: uso de drogas injetáveis na vida (OR=1,91; IC95% 1,28-2,84) e orientação sexual - heterossexuais (OR=3,44; IC95% 1,35-8,82), homossexuais (OR=5,49; IC95% 1,89-15,97) e bissexuais (OR=3,21; IC95% 1,06-9,68). Para coinfecção: uso de drogas nos últimos 12 meses (OR=2,34; IC95% 1,10-5,00). Ser mais jovem foi associada a todos os desfechos investigados. Conclusão: As prevalências estimadas de CT, NG e de coinfecção foram desproporcionalmente mais elevadas entre as mulheres trans e travestis se comparadas à população geral, especialmente entre as mais jovens, que exerciam trabalho sexual e faziam uso de drogas.

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.

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 Surveillance of SARS-CoV-2 in Healthcare Workers: A Critical Sentinel Group for Monitoring the SARS-CoV-2 Variant Shift.

SARS-CoV-2 genome surveillance is important for monitoring risk groups and health workers as well as data on new cases and mortality rate due to COVID-19. We characterized the circulation of SARS-CoV-2 variants from May 2021 to April 2022 in the state of Santa Catarina, southern Brazil, and evaluated the similarity between variants present in the population and healthcare workers (HCW). A total of 5291 sequenced genomes demonstrated the circulation of 55 strains and four variants of concern (Alpha, Delta, Gamma and Omicron-sublineages BA.1 and BA.2). The number of cases was relatively low in May 2021, but the number of deaths was higher with the Gamma variant. There was a significant increase in both numbers between December 2021 and February 2022, peaking in mid-January 2022, when the Omicron variant dominated. After May 2021, two distinct variant groups (Delta and Omicron) were observed, equally distributed among the five Santa Catarina mesoregions. Moreover, from November 2021 to February 2022, similar variant profiles between HCW and the general population were observed, and a quicker shift from Delta to Omicron in HCW than in the general population. This demonstrates the importance of HCW as a sentinel group for monitoring disease trends in the general population.

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

ABSTRACT 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.

GyrB in silico mining in 27 151 global gonococcal genomes from 1928-2021 combined with zoliflodacin in vitro testing of 71 international gonococcal isolates with different GyrB, ParC and ParE substitutions confirms high susceptibility.

OBJECTIVES: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global threat and novel treatment alternatives are imperative. Herein, susceptibility to the novel antimicrobial zoliflodacin, currently in a global Phase 3 randomized controlled clinical trial for gonorrhoea treatment, was investigated by screening for zoliflodacin GyrB target mutations in publicly available gonococcal genomes and, where feasible, determination of the associated zoliflodacin MIC. METHODS: The European Nucleotide Archive was queried using the search term 'Taxon: 485'. DNA sequences from 27 151 gonococcal isolates were analysed and gyrB, gyrA, parC and parE alleles characterized. RESULTS: GyrB amino acid alterations were rare (97.0% of isolates had a wild-type GyrB sequence). GyrB V470L (2.7% of isolates) was the most prevalent alteration, followed by S467N (0.12%), N. meningitidis GyrB (0.092%), V470I (0.059%), Q468R/P (0.015%), A466T (0.0074%), L425I + L465I (0.0037%), L465I (0.0037%), G482S (0.0037%) and D429V (0.0037%). Only one isolate (0.0037%) carried a substitution in a resistance-associated GyrB codon (D429V), resulting in a zoliflodacin MIC of 8 mg/L. None of the other detected gyrB, gyrA, parC or parE mutations caused a zoliflodacin MIC outside the wild-type MIC distribution. CONCLUSIONS: The zoliflodacin target GyrB was highly conserved among 27 151 global gonococcal isolates cultured in 1928-2021. The single zoliflodacin-resistant clinical isolate (0.0037%) was cultured from a male patient in Japan in 2000. Evidently, this strain has not clonally expanded nor has the gyrB zoliflodacin-resistance mutation disseminated through horizontal gene transfer to other strains. Phenotypic and genomic surveillance, including gyrB mutations, of zoliflodacin susceptibility are imperative.

In vitro selection of Neisseria gonorrhoeae unveils novel mutations associated with extended-spectrum cephalosporin resistance.

The emergence of Neisseria gonorrhoeae strains resistant to extended-spectrum cephalosporins (ESCs) is a worldwide concern because this class of antibiotics represents the last empirical treatment option for gonorrhea. The abusive use of antimicrobials may be an essential factor for the emergence of ESC resistance in N. gonorrhoeae. Cephalosporin resistance mechanisms have not been fully clarified. In this study, we mapped mutations in the genome of N. gonorrhoeae isolates after resistance induction with cefixime and explored related metabolic pathways. Six clinical isolates with different antimicrobial susceptibility profiles and genotypes and two gonococcal reference strains (WHO F and WHO Y) were induced with increasing concentrations of cefixime. Antimicrobial susceptibility testing was performed against six antimicrobial agents before and after induction. Clinical isolates were whole-genome sequenced before and after induction, whereas reference strains were sequenced after induction only. Cefixime resistance induction was completed after 138 subcultures. Several metabolic pathways were affected by resistance induction. Five isolates showed SNPs in PBP2. The isolates M111 and M128 (ST1407 with mosaic penA-34.001) acquired one and four novel missense mutations in PBP2, respectively. These isolates exhibited the highest minimum inhibitory concentration (MIC) for cefixime among all clinical isolates. Mutations in genes contributing to ESC resistance and in other genes were also observed. Interestingly, M107 and M110 (ST338) showed no mutations in key determinants of ESC resistance despite having a 127-fold increase in the MIC of cefixime. These findings point to the existence of different mechanisms of acquisition of ESC resistance induced by cefixime exposure. Furthermore, the results reinforce the importance of the gonococcal antimicrobial resistance surveillance program in Brazil, given the changes in treatment protocols made in 2017 and the nationwide prevalence of sequence types that can develop resistance to ESC.

Genetic diversity and antimicrobial resistance of invasive, noninvasive and colonizing group B Streptococcus isolates in southern Brazil.

Introduction: Group B Streptococcus (GBS) is a human commensal bacterium that is also associated with infection in pregnant and non-pregnant adults, neonates and elderly people. Gap Statement: The authors hypothesize that knowledge of regional GBS genetic patterns may allow the use of prevention and treatment measures to reduce the burden of streptococcal disease. Aim: The aim was to report the genotypic diversity and antimicrobial sensitivity profiles of invasive, noninvasive urinary and colonizing GBS strains, and evaluate the relationships between these findings. Methodology: The study included consecutive and non-duplicated GBS isolates recovered in southern Brazil from 2015 to 2017. We performed multiple-locus variable-number tandem repeat analysis (MLVA) and PCR analyses to determine capsular serotypes and identify the presence of the resistance genes mefA/E, ermB and ermA/TR, and also antibiotic susceptibility testing. Results: The sample consisted of 348 GBS strains, 42 MLVA types were identified, and 4 of them represented 64 % of isolates. Serotype Ia was the most prevalent (42.2 %) and was found in a higher percentage associated with colonization, followed by serotypes V (24.4 %), II (17.8 %) and III (7.8 %). Serotype V was associated with invasive isolates and serotypes II and III with noninvasive isolates, without significant differences. All isolates were susceptible to penicillin. GBS 2018/ hvgA was observed in 17 isolates, with 11 belonging to serogroup III. The Hunter-Gaston diversity index was calculated as 0.879. The genes mefA/E, erm/B and erm/A/TR were found in 45, 19 and 46 isolates. Conclusion: This report suggests that the circulating GBS belong to a limited number of genetic lineages. The most common genotypes were Ia/MT12 and V/MT18, which are associated with high resistance to macrolides and the presence of the genes mefA/E and ermA/TR. Penicillin remains the antibiotic of choice. Implementation of continuous surveillance of GBS infections will be essential to assess GBS epidemiology and develop accurate GBS prevention, especially strategies associated with vaccination.

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.

Spectinomycin, gentamicin, and routine disc diffusion testing: An alternative for the treatment and monitoring of multidrug-resistant Neisseria gonorrhoeae?

INTRODUCTION: Neisseria gonorrhoeae is a major concern of public health due to its extraordinary capacity to develop and acquire resistance to different antimicrobials used to treat gonorrhoea. Limited treatment options and uncontrolled transmission have raised the need to assess the antimicrobial susceptibility profile of the isolates and to establish affordable alternatives for laboratory diagnosis. OBJECTIVES: This study aimed to (i) determine the susceptibility profile of 336 clinical isolates of N. gonorrhoeae to ceftriaxone, azithromycin, ciprofloxacin, spectinomycin and gentamicin by the gold standard agar dilution method; (ii) assess the agreement among agar dilution and disc diffusion results for ciprofloxacin, azithromycin, ceftriaxone, spectinomycin and gentamicin. RESULTS: All isolates were susceptible to ceftriaxone and spectinomycin. The levels of resistance to azithromycin and ciprofloxacin were 3.9% and 35.1%, respectively. Intermediate susceptibility to gentamicin was observed in 19.4% of isolates. There was 100% agreement between methods for spectinomycin and ceftriaxone, 99.7% for ciprofloxacin, and 85.7% for azithromycin. For gentamicin, there was 86.3% agreement between agar dilution and disc diffusion, resulting in intermediate susceptible by one method and susceptible by the other method, defined as minor errors. The discordance among agar dilution and disc diffusion results is acceptable for ciprofloxacin, ceftriaxone and spectinomycin as per CLSI M23-Ed4. CONCLUSIONS: Spectinomycin and gentamicin can be considered in some cases as options for the treatment of gonorrhoea in Brazil. Disc diffusion can be an alternative method in routine testing with comparable accuracy to agar dilution.