DNAm scores for serum GDF15 and NT-proBNP levels associate with a range of traits affecting the body and brain.

BACKGROUND: Plasma growth differentiation factor 15 (GDF15) and N-terminal proB-type natriuretic peptide (NT-proBNP) are cardiovascular biomarkers that associate with a range of diseases. Epigenetic scores (EpiScores) for GDF15 and NT-proBNP may provide new routes for risk stratification. RESULTS: In the Generation Scotland cohort (N ≥ 16,963), GDF15 levels were associated with incident dementia, ischaemic stroke and type 2 diabetes, whereas NT-proBNP levels were associated with incident ischaemic heart disease, ischaemic stroke and type 2 diabetes (all PFDR < 0.05). Bayesian epigenome-wide association studies (EWAS) identified 12 and 4 DNA methylation (DNAm) CpG sites associated (Posterior Inclusion Probability [PIP] > 95%) with levels of GDF15 and NT-proBNP, respectively. EpiScores for GDF15 and NT-proBNP were trained in a subset of the population. The GDF15 EpiScore replicated protein associations with incident dementia, type 2 diabetes and ischaemic stroke in the Generation Scotland test set (hazard ratios (HR) range 1.36-1.41, PFDR < 0.05). The EpiScore for NT-proBNP replicated the protein association with type 2 diabetes, but failed to replicate an association with ischaemic stroke. EpiScores explained comparable variance in protein levels across both the Generation Scotland test set and the external LBC1936 test cohort (R2 range of 5.7-12.2%). In LBC1936, both EpiScores were associated with indicators of poorer brain health. Neither EpiScore was associated with incident dementia in the LBC1936 population. CONCLUSIONS: EpiScores for serum levels of GDF15 and Nt-proBNP associate with body and brain health traits. These EpiScores are provided as potential tools for disease risk stratification.

TransOdara study: the challenge of integrating methods, settings and procedures during the COVID-19 pandemic in Brazil.

OBJECTIVE: Sexually transmitted infections (STIs) disproportionately affect transgender women and travestis (TGW), who often lack access to healthcare due to stigma and discrimination. We describe the approach and methodology of a study investigating the prevalence of syphilis, HIV, hepatitis A, B, and C, Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), and human papillomavirus (HPV) among TGW, as well as their knowledge and perceptions regarding syphilis, to better inform policies to curb STIs among this vulnerable population. METHODS: TransOdara was a multicentric, cross-sectional study conducted among TGW in five capital cities from major Brazilian regions between December 2019 and July 2021. Self-identified transgender women and travestis aged >18 years were recruited using respondent-driven sampling after a qualitative formative phase, completed an interviewer-led questionnaire, were offered a physical examination, and were also asked to provide samples from multiple sites to detect various STIs, starting vaccination and treatment when indicated. RESULTS: A total of 1,317 participants were recruited from the five study locations: Campo Grande (n=181, 13.7%), Manaus (n=340, 25.8%), Porto Alegre (n=192, 14.6%), Salvador (n=201, 15.3%), and São Paulo (n=403, 30.6%). The recruitment period varied at each study location due to logistic constraints imposed by the COVID-19 pandemic. CONCLUSION: Despite the enormous challenges posed by the co-occurrence of the COVID-19 pandemic and field work targeting a vulnerable, elusive, and scattered population, the TransOdara project has been effectively implemented. Caveats did not preclude 1,300 TGW from being interviewed and tested, amid a significant epidemic that disrupted health services and research projects in Brazil and worldwide.

Hepatitis A, B and C prevalence among transgender women and travestis in five Brazilian capitals between 2019-2021.

OBJECTIVE: To estimate the prevalence and factors associated with hepatitis A, B, and C in transgender women and travestis's networks, in 5 regions of Brazil. METHODS: This cross-sectional study includedtransgender women and travestis in five Brazilian capitals (Campo Grande, Manaus, Porto Alegre, Salvador, and São Paulo), between December/2019 and July/2021. All samples were subjected to detection of serological markers of hepatitis virus A (HAV), B (HBV), and C (HCV) infections through rapid tests and chemiluminescent microparticle immunoassays. Positive samples in the screening tests were submitted to detect HBV DNA and HCV-RNA by real-time PCR and genotyped by Sanger sequencing. RESULTS: Analysis of 1,317 samples showed network prevalence rates of 69.1%, 25.1%, and 1.5% for HAV, HBV, and HCV exposure, respectively. A high susceptibility rate to HBV infection (35.7%) and low prevalence of vaccine response markers (40%) were also observed. Age greater than 26 years, self-declared black/brown skin color, having only primary education, history of incarceration, and use of a condom in the last sexual intercourse with a casual partner were associated with total anti-HAV. Exposure to HBV was associated with age greater than 26 years, self-declared black/brown, history of being a sex worker, and incarceration. Age > 37 years, history of sexual abuse, and frequent alcohol consumption were associated with hepatitis C infection. CONCLUSION: The highest prevalence of HAV in this population was found in the North and Northeast regions, and the prevalence found was higher than that in the general population, suggesting greater vulnerability. The prevalence of HCV infection in our study was similar to that observed in the general population.

Physical examination for the detection of sexually transmitted infections among transgender women and travestis in Brazil: acceptability and associated factors.

OBJECTIVE: This study aimed to determine the acceptability and factors associated with uptake of a physical examination for the detection of symptomatic sexually transmitted infections (STIs) by transgender women and travestis in Brazil. METHODS: TransOdara was a multi-centric, cross-sectional STI prevalence study conducted among transgender women and travestis in five capital cities (Campo Grande, Manaus, Porto Alegre, Salvador and São Paulo) representing all Brazilian regions, between December 2019 and July 2021. A total of 1,317 self-identified transgender women and travestis aged ≥18 years were recruited using respondent-driven sampling and responded to a standard questionnaire. A medical consultation was offered including a physical examination and collection of samples from multiple sites to detect various STIs. Factors associated with uptake were investigated by reviewing demographic characteristics of participants who gave permission for physical examination (general, genital, and anorectal). RESULTS: Most participants (65.4%, 95% confidence interval - 95%CI 62.7-68.0) gave permission for a general examination (including oropharyngeal), with fewer permitting genital (42.3%, 95%CI 39.6-46.0) or anorectal (42.1%, 95%CI 39.4-44.9) examinations. Overall, 34.4% (95%CI 31.8-37.0) of participants refused all examinations. Participants with STI symptoms were significantly more likely to give permission for full examination than asymptomatic participants (64.3 vs. 37.4%, adjusted odds ratio - AOR=3.6, 95%CI 2.4-5.5). Other factors significantly associated with uptake of a full examination in multivariate analysis included age (AOR=1.5 for ≥25 years), religion (AOR=1.7 for Afro-Brazilian, AOR=1.9 for other religions compared to no religion), and education (AOR=2.0 for higher-level). CONCLUSION: In the context of STI management, this study found limited acceptance of anogenital examinations among transgender women and travestis, with higher acceptance among those with STI symptoms.

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.

Alzheimer's disease genetic pathways impact cerebrospinal fluid biomarkers and imaging endophenotypes in non-demented individuals.

INTRODUCTION: Unraveling how Alzheimer's disease (AD) genetic risk is related to neuropathological heterogeneity, and whether this occurs through specific biological pathways, is a key step toward precision medicine. METHODS: We computed pathway-specific genetic risk scores (GRSs) in non-demented individuals and investigated how AD risk variants predict cerebrospinal fluid (CSF) and imaging biomarkers reflecting AD pathology, cardiovascular, white matter integrity, and brain connectivity. RESULTS: CSF amyloidbeta and phosphorylated tau were related to most GRSs. Inflammatory pathways were associated with cerebrovascular disease, whereas quantitative measures of white matter lesion and microstructure integrity were predicted by clearance and migration pathways. Functional connectivity alterations were related to genetic variants involved in signal transduction and synaptic communication. DISCUSSION: This study reveals distinct genetic risk profiles in association with specific pathophysiological aspects in predementia stages of AD, unraveling the biological substrates of the heterogeneity of AD-associated endophenotypes and promoting a step forward in disease understanding and development of personalized therapies. HIGHLIGHTS: Polygenic risk for Alzheimer's disease encompasses six biological pathways that can be quantified with pathway-specific genetic risk scores, and differentially relate to cerebrospinal fluid and imaging biomarkers. Inflammatory pathways are mostly related to cerebrovascular burden. White matter health is associated with pathways of clearance and membrane integrity, whereas functional connectivity measures are related to signal transduction and synaptic communication pathways.

Methylome-wide studies of six metabolic traits.

Exploring the molecular correlates of metabolic health measures may identify the shared and unique biological processes and pathways that they track. Here, we performed epigenome-wide association studies (EWASs) of six metabolic traits: body mass index (BMI), body fat percentage, waist-hip ratio (WHR), and blood-based measures of glucose, high-density lipoprotein (HDL) cholesterol, and total cholesterol. We considered blood-based DNA methylation (DNAm) from >750,000 CpG sites in over 17,000 volunteers from the Generation Scotland (GS) cohort. Linear regression analyses identified between 304 and 11,815 significant CpGs per trait at P<3.6×10-8, with 37 significant CpG sites across all six traits. Further, we performed a Bayesian EWAS that jointly models all CpGs simultaneously and conditionally on each other, as opposed to the marginal linear regression analyses. This identified between 3 and 27 CpGs with a posterior inclusion probability ≥ 0.95 across the six traits. Next, we used elastic net penalised regression to train epigenetic scores (EpiScores) of each trait in GS, which were then tested in the Lothian Birth Cohort 1936 (LBC1936; European ancestry) and Health for Life in Singapore (HELIOS; Indian-, Malay- and Chinese-ancestries). A maximum of 27.1% of the variance in BMI was explained by the BMI EpiScore in the subset of Malay-ancestry Singaporeans. Four metabolic EpiScores were associated with general cognitive function in LBC1936 in models adjusted for vascular risk factors (Standardised ßrange: 0.08 - 0.12, PFDR < 0.05). EpiScores of metabolic health are applicable across ancestries and can reflect differences in brain health.

A unified framework for estimating country-specific cumulative incidence for 18 diseases stratified by polygenic risk.

Polygenic scores (PGSs) offer the ability to predict genetic risk for complex diseases across the life course; a key benefit over short-term prediction models. To produce risk estimates relevant to clinical and public health decision-making, it is important to account for varying effects due to age and sex. Here, we develop a novel framework to estimate country-, age-, and sex-specific estimates of cumulative incidence stratified by PGS for 18 high-burden diseases. We integrate PGS associations from seven studies in four countries (N = 1,197,129) with disease incidences from the Global Burden of Disease. PGS has a significant sex-specific effect for asthma, hip osteoarthritis, gout, coronary heart disease and type 2 diabetes (T2D), with all but T2D exhibiting a larger effect in men. PGS has a larger effect in younger individuals for 13 diseases, with effects decreasing linearly with age. We show for breast cancer that, relative to individuals in the bottom 20% of polygenic risk, the top 5% attain an absolute risk for screening eligibility 16.3 years earlier. Our framework increases the generalizability of results from biobank studies and the accuracy of absolute risk estimates by appropriately accounting for age- and sex-specific PGS effects. Our results highlight the potential of PGS as a screening tool which may assist in the early prevention of common diseases.

Generation Scotland: an update on Scotland's longitudinal family health study.

PURPOSE: Generation Scotland (GS) is a large family-based cohort study established as a longitudinal resource for research into the genetic, lifestyle and environmental determinants of physical and mental health. It comprises extensive genetic, sociodemographic and clinical data from volunteers in Scotland. PARTICIPANTS: A total of 24 084 adult participants, including 5501 families, were recruited between 2006 and 2011. Within the cohort, 59% (approximately 14 209) are women, with an average age at recruitment of 49 years. Participants completed a health questionnaire and attended an in-person clinic visit, where detailed baseline data were collected on lifestyle information, cognitive function, personality traits and mental and physical health. Genotype array data are available for 20 026 (83%) participants, and blood-based DNA methylation (DNAm) data for 18 869 (78%) participants. Linkage to routine National Health Service datasets has been possible for 93% (n=22 402) of the cohort, creating a longitudinal resource that includes primary care, hospital attendance, prescription and mortality records. Multimodal brain imaging is available in 1069 individuals. FINDINGS TO DATE: GS has been widely used by researchers across the world to study the genetic and environmental basis of common complex diseases. Over 350 peer-reviewed papers have been published using GS data, contributing to research areas such as ageing, cancer, cardiovascular disease and mental health. Recontact studies have built on the GS cohort to collect additional prospective data to study chronic pain, major depressive disorder and COVID-19. FUTURE PLANS: To create a larger, richer, longitudinal resource, 'Next Generation Scotland' launched in May 2022 to expand the existing cohort by a target of 20 000 additional volunteers, now including anyone aged 12+ years. New participants complete online consent and questionnaires and provide postal saliva samples, from which genotype and salivary DNAm array data will be generated. The latest cohort information and how to access data can be found on the GS website (www.generationscotland.org).

Blood-based epigenome-wide analyses of chronic low-grade inflammation across diverse population cohorts.

Chronic inflammation is a hallmark of age-related disease states. The effectiveness of inflammatory proteins including C-reactive protein (CRP) in assessing long-term inflammation is hindered by their phasic nature. DNA methylation (DNAm) signatures of CRP may act as more reliable markers of chronic inflammation. We show that inter-individual differences in DNAm capture 50% of the variance in circulating CRP (N = 17,936, Generation Scotland). We develop a series of DNAm predictors of CRP using state-of-the-art algorithms. An elastic-net-regression-based predictor outperformed competing methods and explained 18% of phenotypic variance in the Lothian Birth Cohort of 1936 (LBC1936) cohort, doubling that of existing DNAm predictors. DNAm predictors performed comparably in four additional test cohorts (Avon Longitudinal Study of Parents and Children, Health for Life in Singapore, Southall and Brent Revisited, and LBC1921), including for individuals of diverse genetic ancestry and different age groups. The best-performing predictor surpassed assay-measured CRP and a genetic score in its associations with 26 health outcomes. Our findings forge new avenues for assessing chronic low-grade inflammation in diverse populations.

Acceptability and Usability of Self-Sampling for the Detection of Sexually Transmitted Infections Among Transgender Women: The TransOdara Multicentric Study in Brazil.

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.

Epigenetic scores of blood-based proteins as biomarkers of general cognitive function and brain health.

BACKGROUND: Epigenetic Scores (EpiScores) for blood protein levels have been associated with disease outcomes and measures of brain health, highlighting their potential usefulness as clinical biomarkers. They are typically derived via penalised regression, whereby a linear weighted sum of DNA methylation (DNAm) levels at CpG sites are predictive of protein levels. Here, we examine 84 previously published protein EpiScores as possible biomarkers of cross-sectional and longitudinal measures of general cognitive function and brain health, and incident dementia across three independent cohorts. RESULTS: Using 84 protein EpiScores as candidate biomarkers, associations with general cognitive function (both cross-sectionally and longitudinally) were tested in three independent cohorts: Generation Scotland (GS), and the Lothian Birth Cohorts of 1921 and 1936 (LBC1921 and LBC1936, respectively). A meta-analysis of general cognitive functioning results in all three cohorts identified 18 EpiScore associations (absolute meta-analytic standardised estimates ranged from 0.03 to 0.14, median of 0.04, PFDR < 0.05). Several associations were also observed between EpiScores and global brain volumetric measures in the LBC1936. An EpiScore for the S100A9 protein (a known Alzheimer disease biomarker) was associated with general cognitive functioning (meta-analytic standardised beta: - 0.06, P = 1.3 × 10-9), and with time-to-dementia in GS (Hazard ratio 1.24, 95% confidence interval 1.08-1.44, P = 0.003), but not in LBC1936 (Hazard ratio 1.11, P = 0.32). CONCLUSIONS: EpiScores might make a contribution to the risk profile of poor general cognitive function and global brain health, and risk of dementia, however these scores require replication in further studies.

Epigenetic Contributions to Clinical Risk Prediction of Cardiovascular Disease.

BACKGROUND: Cardiovascular disease (CVD) is among the leading causes of death worldwide. The discovery of new omics biomarkers could help to improve risk stratification algorithms and expand our understanding of molecular pathways contributing to the disease. Here, ASSIGN-a cardiovascular risk prediction tool recommended for use in Scotland-was examined in tandem with epigenetic and proteomic features in risk prediction models in ≥12 657 participants from the Generation Scotland cohort. METHODS: Previously generated DNA methylation-derived epigenetic scores (EpiScores) for 109 protein levels were considered, in addition to both measured levels and an EpiScore for cTnI (cardiac troponin I). The associations between individual protein EpiScores and the CVD risk were examined using Cox regression (ncases≥1274; ncontrols≥11 383) and visualized in a tailored R application. Splitting the cohort into independent training (n=6880) and test (n=3659) subsets, a composite CVD EpiScore was then developed. RESULTS: Sixty-five protein EpiScores were associated with incident CVD independently of ASSIGN and the measured concentration of cTnI (P<0.05), over a follow-up of up to 16 years of electronic health record linkage. The most significant EpiScores were for proteins involved in metabolic, immune response, and tissue development/regeneration pathways. A composite CVD EpiScore (based on 45 protein EpiScores) was a significant predictor of CVD risk independent of ASSIGN and the concentration of cTnI (hazard ratio, 1.32; P=3.7×10-3; 0.3% increase in C-statistic). CONCLUSIONS: EpiScores for circulating protein levels are associated with CVD risk independent of traditional risk factors and may increase our understanding of the etiology of the disease.

Comprehensive evaluation of smoking exposures and their interactions on DNA methylation.

BACKGROUND: Smoking impacts DNA methylation, but data are lacking on smoking-related differential methylation by sex or dietary intake, recent smoking cessation (<1 year), persistence of differential methylation from in utero smoking exposure, and effects of environmental tobacco smoke (ETS). METHODS: We meta-analysed data from up to 15,014 adults across 5 cohorts with DNA methylation measured in blood using Illumina's EPIC array for current smoking (2560 exposed), quit < 1 year (500 exposed), in utero (286 exposed), and ETS exposure (676 exposed). We also evaluated the interaction of current smoking with sex or diet (fibre, folate, and vitamin C). FINDINGS: Using false discovery rate (FDR < 0.05), 65,857 CpGs were differentially methylated in relation to current smoking, 4025 with recent quitting, 594 with in utero exposure, and 6 with ETS. Most current smoking CpGs attenuated within a year of quitting. CpGs related to in utero exposure in adults were enriched for those previously observed in newborns. Differential methylation by current smoking at 4-71 CpGs may be modified by sex or dietary intake. Nearly half (35-50%) of differentially methylated CpGs on the 450 K array were associated with blood gene expression. Current smoking and in utero smoking CpGs implicated 3049 and 1067 druggable targets, including chemotherapy drugs. INTERPRETATION: Many smoking-related methylation sites were identified with Illumina's EPIC array. Most signals revert to levels observed in never smokers within a year of cessation. Many in utero smoking CpGs persist into adulthood. Smoking-related druggable targets may provide insights into cancer treatment response and shared mechanisms across smoking-related diseases. FUNDING: Intramural Research Program of the National Institutes of Health, Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, Chief Scientist Office of the Scottish Government Health Directorates and the Scottish Funding Council, Medical Research Council UK and the Wellcome Trust.

Impact of the COVID-19 lockdown on the vitamin D status of people in the West of Ireland.

OBJECTIVE: Identify the impact of COVID-19 lockdown restrictions on the vitamin D status of individuals in the west of Ireland. DESIGN: Cross-sectional study. SETTING: Adults who had wintertime serum 25(OH)D analysis completed in Galway University Hospital. PARTICIPANTS: A total of 16,725 participants (2015-2020 (n = 13,449) and 2020-2021 (n = 3276)). Baseline demographics; sex, age, origin of the sample and the date of sample collection. RESULTS: Median serum vitamin D and serum vitamin D3 concentrations were higher in the 5-month period from October-February 2020-2021 (61 nmol/L (± 36-85 nmol/L) and 60 nmol/L (± 34-85 nmol/L)) respectively, than for the corresponding 5-month period (October-February) in 2015-2020 (53 nmol/L (± 32-78 nmol/L) and 51 nmol/L (± 30-77 nmol/L)) respectively. These changes coincided with a decline in the prevalence of deficiency. In the 5-month period October-February 2020-2021, 19.2% of the population were vitamin D deficient (< 30 nmol/L) compared to 22.5% in the corresponding 5-month period in 2015-2020, and 38.1% were vitamin D deficient (< 50 nmol/L) in the 5-month period October-February 2020-2021 compared to 46.6% in the corresponding 5-month period in 2015-2020. Males were more likely to be deficient at both thresholds (p < 0.001). For the total cohort, at the < 30 nmol/L threshold, inpatients (25.5%) and nursing home residents (34.1%) had higher prevalence of deficiency. CONCLUSIONS: Vitamin D levels were higher in the 5-month period of October-February 2020-2021, and this precipitated a decline in deficiency at both thresholds, indicating that lockdown coincided with enhanced vitamin D status. We postulate that it may be attributable to changes in diet and/or supplementation, or increased sun exposure, but further confirmatory studies are required.

Anorectal gonorrhoea and chlamydia among transgender women in Brazil: prevalence and assessment of performance and cost of anorectal infection detection and management approaches.

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.

TransOdara study: the challenge of integrating methods, settings and procedures during the COVID-19 pandemic in Brazil / Estudo TransOdara: o desafio de integrar métodos, contextos e procedimentos durante a pandemia de COVID-19 no Brasil

ABSTRACT Objective Sexually transmitted infections (STIs) disproportionately affect transgender women and travestis (TGW), who often lack access to healthcare due to stigma and discrimination. We describe the approach and methodology of a study investigating the prevalence of syphilis, HIV, hepatitis A, B, and C, Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), and human papillomavirus (HPV) among TGW, as well as their knowledge and perceptions regarding syphilis, to better inform policies to curb STIs among this vulnerable population. Methods: TransOdara was a multicentric, cross-sectional study conducted among TGW in five capital cities from major Brazilian regions between December 2019 and July 2021. Self-identified transgender women and travestis aged >18 years were recruited using respondent-driven sampling after a qualitative formative phase, completed an interviewer-led questionnaire, were offered a physical examination, and were also asked to provide samples from multiple sites to detect various STIs, starting vaccination and treatment when indicated. Results: A total of 1,317 participants were recruited from the five study locations: Campo Grande (n=181, 13.7%), Manaus (n=340, 25.8%), Porto Alegre (n=192, 14.6%), Salvador (n=201, 15.3%), and São Paulo (n=403, 30.6%). The recruitment period varied at each study location due to logistic constraints imposed by the COVID-19 pandemic. Conclusion: Despite the enormous challenges posed by the co-occurrence of the COVID-19 pandemic and field work targeting a vulnerable, elusive, and scattered population, the TransOdara project has been effectively implemented. Caveats did not preclude 1,300 TGW from being interviewed and tested, amid a significant epidemic that disrupted health services and research projects in Brazil and worldwide.

RESUMO Objetivo As infecções sexualmente transmissíveis (IST) afetam desproporcionalmente as mulheres trans e travestis (MTT), que muitas vezes não têm acesso a cuidados de saúde devido ao estigma e à discriminação. Descrevemos a abordagem e a metodologia de um estudo que investigou a prevalência de sífilis, HIV, hepatite A, B e C, Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) e papilomavírus humano (HPV) entre as MTT, bem como seu conhecimento e percepção sobre a sífilis, para melhor as políticas para redução de IST nessa população vulnerável. Métodos: TransOdara foi um estudo multicêntrico, transversal, realizado em cinco capitais das principais regiões brasileiras entre dezembro de 2019 e julho de 2021. Mulheres autoidentificadas como mulheres trans ou travestis, com idade >18 anos, foram recrutadas usando respondent-driven sampling, após uma fase de pesquisa formativa. Responderam a um questionário conduzido por entrevistadoras. Foi oferecida consulta médica, com exame físico, e solicitou-se que fornecessem amostras de vários locais para detectar as IST citadas. Quando indicado e consentido, foram iniciadas a vacinação e o tratamento. Resultados: Foram recrutadas 1.317 participantes nos cinco locais de estudo: Campo Grande (n=181, 13,7%), Manaus (n=340, 25,8%), Porto Alegre (n=192, 14,6%), Salvador (n= =201, 15,3%) e São Paulo (n=403, 30,6%). O período de recrutamento variou em cada local em razão de restrições logísticas impostas pela pandemia de COVID-19. Conclusão: Apesar dos enormes desafios colocados pela ocorrência simultânea da pandemia da COVID-19 e do trabalho de campo dirigido a uma população vulnerabilizada e dispersa, o projeto TransOdara foi eficazmente implementado. As adversidades não impediram que mais de 1.300 mulheres trans e travestis tenham sido entrevistadas e testadas em meio a uma epidemia de tal magnitude que perturbou os serviços de saúde e os projetos de pesquisa no Brasil e no mundo.

Physical examination for the detection of sexually transmitted infections among transgender women and travestis in Brazil: acceptability and associated factors / Realização do exame físico para detecção de infecções sexualmente transmissíveis entre mulheres trans e travestis no Brasil

ABSTRACT Objective This study aimed to determine the acceptability and factors associated with uptake of a physical examination for the detection of symptomatic sexually transmitted infections (STIs) by transgender women and travestis in Brazil. Methods: TransOdara was a multi-centric, cross-sectional STI prevalence study conducted among transgender women and travestis in five capital cities (Campo Grande, Manaus, Porto Alegre, Salvador and São Paulo) representing all Brazilian regions, between December 2019 and July 2021. A total of 1,317 self-identified transgender women and travestis aged ≥18 years were recruited using respondent-driven sampling and responded to a standard questionnaire. A medical consultation was offered including a physical examination and collection of samples from multiple sites to detect various STIs. Factors associated with uptake were investigated by reviewing demographic characteristics of participants who gave permission for physical examination (general, genital, and anorectal). Results: Most participants (65.4%, 95% confidence interval — 95%CI 62.7-68.0) gave permission for a general examination (including oropharyngeal), with fewer permitting genital (42.3%, 95%CI 39.6-46.0) or anorectal (42.1%, 95%CI 39.4-44.9) examinations. Overall, 34.4% (95%CI 31.8-37.0) of participants refused all examinations. Participants with STI symptoms were significantly more likely to give permission for full examination than asymptomatic participants (64.3 vs. 37.4%, adjusted odds ratio — AOR=3.6, 95%CI 2.4-5.5). Other factors significantly associated with uptake of a full examination in multivariate analysis included age (AOR=1.5 for ≥25 years), religion (AOR=1.7 for Afro-Brazilian, AOR=1.9 for other religions compared to no religion), and education (AOR=2.0 for higher-level). Conclusion: In the context of STI management, this study found limited acceptance of anogenital examinations among transgender women and travestis, with higher acceptance among those with STI symptoms.

RESUMO Objective Determinar a aceitabilidade e os fatores associados à realização do exame físico para detecção de infecções sexualmente transmissíveis (IST) sintomáticas em mulheres trans e travestis no Brasil. Métodos: Foram utilizados dados do "TransOdara", estudo transversal de prevalência de IST, realizado em cinco capitais brasileiras (Campo Grande, Manaus, Porto Alegre, Salvador e São Paulo) entre dezembro de 2019 e julho de 2021. As 1.317 mulheres trans e travestis, com idade ≥18 anos, recrutadas por meio do método respondent-driven sampling passaram por entrevistas e responderam a um questionário estruturado. Foi ofertada consulta médica, incluindo realização de exame físico e coleta de amostras de vários locais para detectar diversas IST. Para a análise dos fatores associados à aceitabilidade do exame físico (geral, genital e anorretal), considerou-se as características sociodemográficas das participantes que permitiram a sua realização. Resultados: A maioria (65,4%; intervalo de confiança - IC95% 62,7-68,0) concedeu permissão para o exame geral (incluindo orofaríngeo), com permissão concedida em menor proporção para os exames genitais (42,3%; IC95% 39,6-46,0) ou anorretais (42,1%; IC95% 39,4-44,9). No geral, 34,4% (IC95% 31,8-37,0) delas recusaram todos os exames. As participantes com sintomas de IST foram significativamente mais propensas a conceder permissão para o exame completo do que as participantes assintomáticas (64,3 vs 37,4%, odds ratio ajustado - AOR=3,6, IC95% 2,4-5,5). Os fatores significativamente associados à aceitabilidade do exame completo na análise multivariada incluíram idade (AOR=1,5 para ≥25 anos), religião (AOR=2,0 para afro-brasileiras, AOR=1,9 para outras religiões em comparação com nenhuma religião) e nível de escolaridade (AOR=2,0 para nível superior). Conclusão: No contexto do manejo de IST, nós observamos aceitação limitada de exames anogenitais entre mulheres trans e travestis, com maior aceitação entre aquelas com sintomas de IST.

Hepatitis A, B and C prevalence among transgender women and travestis in five Brazilian capitals between 2019-2021 / Prevalência das hepatites A, B e C entre mulheres trans e travestis em cinco capitais brasileiras entre 2019-2021

ABSTRACT Objective: To estimate the prevalence and factors associated with hepatitis A, B, and C in transgender women and travestis's networks, in 5 regions of Brazil. Methods: This cross-sectional study includedtransgender women and travestis in five Brazilian capitals (Campo Grande, Manaus, Porto Alegre, Salvador, and São Paulo), between December/2019 and July/2021. All samples were subjected to detection of serological markers of hepatitis virus A (HAV), B (HBV), and C (HCV) infections through rapid tests and chemiluminescent microparticle immunoassays. Positive samples in the screening tests were submitted to detect HBV DNA and HCV-RNA by real-time PCR and genotyped by Sanger sequencing. Results: Analysis of 1,317 samples showed network prevalence rates of 69.1%, 25.1%, and 1.5% for HAV, HBV, and HCV exposure, respectively. A high susceptibility rate to HBV infection (35.7%) and low prevalence of vaccine response markers (40%) were also observed. Age greater than 26 years, self-declared black/brown skin color, having only primary education, history of incarceration, and use of a condom in the last sexual intercourse with a casual partner were associated with total anti-HAV. Exposure to HBV was associated with age greater than 26 years, self-declared black/brown, history of being a sex worker, and incarceration. Age > 37 years, history of sexual abuse, and frequent alcohol consumption were associated with hepatitis C infection. Conclusion: The highest prevalence of HAV in this population was found in the North and Northeast regions, and the prevalence found was higher than that in the general population, suggesting greater vulnerability. The prevalence of HCV infection in our study was similar to that observed in the general population.

RESUMO Objetivo: Estimar as prevalências e fatores associados com as hepatites A, B e C em mulheres trans e travestis em cinco regiões do Brasil. Métodos: Estudo transversal com mulheres trans e travestis em cinco capitais brasileiras (Campo Grande, Manaus, Porto Alegre, Salvador e São Paulo), entre dezembro/2019 e julho/2021. As amostras foram submetidas à detecção de marcadores das infecções pelos vírus das hepatites A (HAV), B (HBV) e C (HCV), utilizando-se testes rápidos e quimioluminescência. Amostras positivas foram submetidas à detecção de HBV-DNA e HCV-RNA por PCR em tempo real e genotipadas por sequenciamento de Sanger. Resultados: As análises de 1.317 amostras indicaram taxas de prevalências nas mulheres trans e travestis recrutadas de 69,1%, 24,4% e 1,5% para exposição ao HAV, HBV e HCV, respectivamente. Elevada taxa de suscetibilidade ao HBV (35,7%) e baixa prevalência do marcador vacinal (40,0%) foram observadas. Mostraram-se associadas à presença de anti-HAV: idade maior que 26 anos, autodeclarar-se preta-parda, ter apenas educação básica, história de encarceramento e uso de preservativo na última relação sexual com parceiro casual. Quanto à exposição ao HBV, foi associada a idade maior que 26 anos, cor da pele preto-parda, ter sido profissional do sexo e história de encarceramento. Idade maior de 37 anos, história de abuso sexual e consumo frequente de álcool foram associadas ao HCV. Conclusão: As maiores prevalências de HAV nessa população encontram-se nas regiões Norte e Nordeste. Com relação ao HBV, a prevalência encontrada foi superior à encontrada na população geral, sugerindo maior vulnerabilidade. A prevalência do HCV foi semelhante à encontrada na população geral.

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.