Abstract in English:

ABSTRACT Background: Chronic Hepatitis B Virus (HBV) infection remains a major global health burden, affecting approximately 296 million individuals worldwide and leading to significant morbidity and mortality due to cirrhosis and Hepatocellular Carcinoma (HCC). Although Nucleos(t)ide Analogues (NAs) such as Tenofovir Disoproxil Fumarate (TDF) and Entecavir (ETV) effectively suppress HBV replication, their comparative efficacy in reducing HCC risk remains controversial. Methods: This retrospective cohort study analyzed HBV-monoinfected patients treated with either TDF or ETV at a tertiary hospital in southern Brazil between 2014 and 2021. Patients with co-infections (HIV, HCV), prior HCC diagnosis, liver transplantation, or others antiviral treatments, like lamivudine e/ou alfainterferon, were excluded. Data on demographics, treatment regimens, disease progression, and HCC incidence were extracted from institutional databases. Statistical analyses included Fisher’s exact test and Poisson regression to determine Relative Risk (RR) and 95 % Confidence Intervals (95 % CIs). Results: Of the 127 included patients, 66 (52 %) received TDF and 61 (48 %) received ETV. Over a 7-year follow-up period, 10 patients developed HCC – 8 in the ETV group (13.1 %) and 2 in the TDF group (3 %). In the raw analysis, TDF use was associated with a significantly lower risk of HCC progression (RR = 0.23, p = 0.057, 95 % CI: 0.05–1.046). After adjusting for the variable’s cirrhosis/advanced fibrosis and age in the multivariate analysis, this association lost statistical significance (RR = 0.33, p = 0.18, 95 % CI: 0.068–1.685). This indicates that the apparent protective effect of tenofovir may have been influenced by these variables and may have limited the statistical power of the adjusted model. Patients receiving ETV had a higher prevalence of advanced liver disease, including cirrhosis (64.7 % vs. 35.3 %, p < 0.05), hepatic encephalopathy (7 % vs. 2.4 %, p < 0.05), and portal hypertension (12.5 % vs. 3.4 %, p < 0.05). The incidence rate of HCC was 1.12 per 100 person-years (to be interpreted with caution due to limited follow-up data). Conclusion: Treatment with TDF was associated with a lower risk of HCC compared to ETV in the bivariate analysis, but this association lost significance in the multivariate analysis. These findings suggest that the initially observed protective effect of TDF against hepatic carcinogenesis may have been partially explained by confounding factors (cirrhosis/advanced fibrosis and age), as well as reflecting the limited sample size. Further studies are warranted to provide a more robust comparative evaluation of antiviral therapies.

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ABSTRACT Background: Kidney Transplant Recipients (KTRs) face increased COVID-19 risks due to immunosuppression, which may affect vaccine response. This study evaluates the impact of Mycophenolate Sodium (MPS) versus Azathioprine (AZA) on anti-SARS-CoV-2 humoral and cellular kinetics after ChAdOx1 vaccination. Methods: In this prospective, observational study, 89 KTRs who seroconverted post-vaccination were grouped based on maintenance immunosuppression (MPS: n = 51; AZA: n = 38). Anti-SARS-CoV-2 IgG titers, neutralizing antibody activity, and cellular immunity assessed by the Interferon-Gamma (IFN-γ) release were measured at screening and 1-, 3-, 6-, and 12-months post-transplant. Linear regression and generalized estimating equations assessed group and time effects. Results: At baseline, IgG titers were 12,059.2 AU/mL (MPS) and 14,369.3 AU/mL (AZA), with both groups experiencing a decline at month 1 (9483.9 AU/mL and 11,023.5 AU/mL, respectively). By month 12, titers stabilized at 11,626.8 AU/mL (MPS) and 13,851.4 AU/mL (AZA; p = 0.286). Neutralizing activity was initially higher with AZA (0.924 vs. 0.764 at baseline; p = 0.006) but converged by month 3 (0.937 vs. 0.871; p = 0.161). Booster doses significantly enhanced neutralizing activity by 0.175 over 12 months. Positive cellular immunity was inferior in the MPS group at screening (4.2% vs. 15.8 %; p = 0.171) and M1 (13.3% vs. 27.8 %; p = 0.266), but similar in the following visits. Conclusions: AZA provided a transient early advantage in immunity responses against SARS-CoV-2, but long-term humoral and cellular kinetics were comparable. Booster doses are essential for sustaining immunity in KTRs, emphasizing the need for tailored vaccination strategies. These findings may inform clinical decisions during pandemics.

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ABSTRACT Background: Early recognition of septic shock is crucial for improving outcomes in children with sepsis. This study aimed to compare the predictive performance of the Pediatric Risk of Mortality-III (PRISM-III), Phoenix Sepsis Score (PSS), and pediatric Sequential Organ Failure Assessment (pSOFA) scores for septic shock in Vietnamese children. Methods: A cross-sectional study was conducted on 86 children aged 2-months to 15-years with sepsis (including 23 with septic shock) admitted to a pediatric intensive care unit. Septic shock classification was performed independently and single – blinded to score calculations to minimize assessment bias. The PSS and pSOFA were calculated using the worst parameters within the first 6-hours, and PRISM-III within the first 24 hours of admission. Discriminatory ability was assessed by the Area Under the Receiver Operating Characteristic Curve (AUROC). Multivariable logistic regression and calibration analyses were performed. Calibration results should be interpreted cautiously due to the small sample size. Results: The PSS showed the highest AUROC (0.867, 95 % CI: 0.777–0.931), followed by PRISM-III (0.826, 95 % CI: 0.729–0.899) and pSOFA (0.791, 95 % CI: 0.690–0.871); pairwise comparisons were not statistically significant. The PSS demonstrated the highest sensitivity (95.7 %) and negative predictive value (97.6 %), while PRISM-III had the highest specificity (90.5 %) and positive predictive value (70.0 %). In multivariable analysis, both PSS (Odds Ratio, OR = 2.78) and PRISM-III (OR = 1.23) were independent predictors of septic shock. Conclusions: The PSS and PRISM-III provide complementary value. A two-step approach using the sensitive PSS for initial screening and the specific PRISM III for confirmation may enhance early septic shock recognition in resource-limited settings.

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Abstract Introduction The analysis of COVID-19 mortality revealed that the Brazilian population was critically impacted by the pandemic. However, many knowledge gaps remain regarding COVID-19 morbidity in the country. This article aims to analyze the consequences of the coronavirus disease on health situation of the Brazilian population. Methods This was a cross-sectional epidemiological online survey using an electronic questionnaire between July and December 2023. The sampling method used was the virtual Respondent Driven Sampling (RDS). Changes in socioeconomic conditions were assessed in the post-pandemic period. Anti-COVID-19 vaccination coverage, prevalence of SARS-CoV-2 infection were estimated, as well as of sequelae lasting three months or more (Long COVID) among confirmed cases. Associations of Long COVID with self-reported heath status, sleep disorders, and depressive symptoms were analyzed. Results The sample included 3805 individuals 18-years or older. Regarding vaccination, 61.5 % (95 % CI: 58.0 %-65.0 %) stated they had received 3‒4 doses. In the post-pandemic period, 41.6 % faced financial difficulties. Prevalence of confirmed SARS-CoV-2 infection was 40.2 %, 6.4 % of respondents reported having had COVID-19, although not confirmed by test, and 15.3 % did not know if they had been infected with the coronavirus. Among those infected, 32.0 % (95 % CI: 28.8 %-35.3 %) reported Long COVID, 21.4 % reported a COVID-19-related illness, and 5.2 % needed and obtained hospitalization. Long COVID was associated with worsening self-rated health, sleep disorders, feelings of depression and 27.7 % were unable to perform their usual activities for one month or more. Conclusion The results of this study showed that Brazil was severely affected by the COVID-19 pandemic, both in terms of mortality and morbidity. The availability of timely post-pandemic data, as presented in this study, may be highly relevant to inform public policies aimed at promoting healthy behaviors, controlling NCDs, improving mental health care, and supporting specialized care for Long COVID within the public health system.

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Abstract The COVID-19 pandemic highlighted the urgent need for rapid and accurate SARS-CoV-2 detection. Current diagnostic methods often suffer from discomfort, slow results, and limited accuracy in early infection stages. This study proposes a solution: a noninvasive, rapid, and accurate detection approach for point-of-care settings using a metal-oxide-sensor-based electronic nose. This innovative electronic nose uses an array of off-the-shelf gas sensors. These sensors detect and analyze the volatile organic compounds present in saliva and exhaled breath, which change based on the presence of the SARS-CoV-2 virus. We evaluated the discriminatory power of the electronic nose using a suite of machine learning algorithms, specifically K-Nearest Neighbors (KNN), Support Vector Machine (SVM), Neural Networks (NN), and Random Forest, to differentiate between SARS-CoV-2 infected and non-infected samples. Accuracy metrics ranged from 76% to 89% for exhaled breath samples and from 75% to 86% for saliva samples. Optimal accuracy was achieved with the KNN algorithm, yielding an Area Under the Curve (AUC) of 0.861 (95% CI 0.825‒0.897) for saliva and 0.895 (95% CI 0.850‒0.940) for exhaled breath. These results support the feasibility and proof-of-concept performance of a low-cost electronic nose for SARS-CoV-2 detection in a real-world hospital cohort.

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Abstract Introduction Post-COVID-19 condition, refers to one or multiple symptoms that continue for several weeks or months following the COVID-19 infection. This study aims to assess the factors associated with post-COVID-19 condition in the Brazilians regions of Paraiba and Rio de Janeiro. Understanding this factor is crucial to public policies and improving care for high-risk individuals. Methods This is a multicenter, retrospective case-control study. Cases were classified as individuals experiencing persistent symptoms for over 12-weeks following a confirmed COVID-19 diagnosis, whereas controls were those who recovered. Data on sociodemographic characteristics, medical history, lifestyle factors, and vaccination status were gathered, and logistic regression was used to analyze the relationship between these variables and the onset of post-COVID-19 condition. Results Of the 1.350 participants, 734 were cases and 616 were controls, with a 54% frequency of post-COVID-19 condition. The study found significant associations between the syndrome and female sex (OR = 2.09; 95% CI 1.6‒2.74), middle age (OR = 2.03; 95% CI 1.31‒3.15 for 40- to 60-years) and over 60 (OR=1.84; 95% CI 1.06‒3.2), white people (OR = 1.41; 95% CI 1.07‒1.86), hypercholesterolemia (OR = 1.66; 95% CI 1.18‒2.32), chronic lung diseases (OR = 5.60; 95% CI 1.18‒26.65), mental illness such as anxiety and panic disorder (OR = 2.52; 95% CI 1.64‒3.87), family history of long COVID syndrome (OR = 2.07; 95% CI 1.45‒2.97), hospitalization (OR = 5.89; 95% CI 3.92‒8.86) and good pre-COVID health perception (OR = 0.69; 95% CI 0.53‒0.9). Conclusions The findings reinforce the importance of identifying groups more frequently affected by post-COVID-19 condition and supporting follow-up strategies aimed at mitigating its impact on individuals and health services.

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Abstract Introduction Access to health services may affect PrEP uptake, adherence, and persistance, especially among persons affected by structural inequities. We assessed the HIV incidence and factors associated with PrEP non-adherence among men who have sex with men (MSM) and transgender women in Brazil, focusing on potential racial disparities. Material and methods ImPrEP was a prospective, single-arm, open-label, PrEP implementation study that enrolled 9509 MSM and transgender women in Brazil, Mexico and Peru (February 2018 ‒ June 2021). Participants received oral PrEP with tenofovir disoproxil fumarate and emtricitabine at the enrollment visit and quarterly thereafter. This analysis was restricted to data from 14 HIV/STI clinics in 11 cities from Brazil. We calculated the HIV incidence per 100 person-years using the Poisson model according to race. We used adjusted logistic regression models to identify factors associated with PrEP non-adherence (medication possession rate < 0.6) for White and Black/Pardo participants separately. Trial registration: UTN U1111-1217-6021 Results Of 3928 participants, 1868 (47.6%) self-identified as White, 1410 (35.9%) Pardo, 595 (15.1%) Black, 42 (1.1%) Asian, and 12 (0.3%) Indigenous. PrEP non-adherence was higher among Black (26.2%) and Pardo (24.2%) compared to White (18.7%) participants (p < 0.0001). Among participants with PrEP non-adherence, HIV incidence was higher among Black (2.16 [95% CI: 0.54‒8.63]) than Pardo (1.49 [95% CI: 0.48‒4.62]) and White (1.00 [95% CI 0.25‒4.01]). In multivariable models, participants aged 18‒30 years, self-identifying as transgender women, and reporting lower number of sex partners had increased odds of PrEP non-adherence among White and Black/Pardo participants. Lower education and transactional sex were associated with increased odds of PrEP non-adherence among Black/Pardo, but not among White participants. Conclusions Higher HIV incidence and PrEP non-adherence among racially and ethnically marginalized groups, such as Black and Pardo Brazilians, highlights the impact of structural racism on health outcomes. The implementation of public policies to reduce racial and social inequities in HIV prevention must be prioritized in Brazil.

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Abstract Introduction Insidious myocarditis due to Chagas disease evolves with low inflammatory potential. Determining biomarkers can help find individuals at risk for Heart Failure (HF) or arrhythmias. This study aimed to evaluate the role of serum cytokines and myocardial tissue Doppler imaging as prognostic markers of Chagas myocarditis. Methods This longitudinal study was carried out in a prospective cohort in which adults living with Chagas disease who had no HF were followed up for 10-years. Tissue Doppler imaging was performed, and inflammatory cytokines were measured. Kaplan-Meier survival analysis, unadjusted and adjusted survival analyses for some variables by Cox regression and multivariate binary logistic regression analysis were performed for the primary and total outcomes. Results This study found that IL1-B and IL-13 were associated with primary and total events (p = 0.015 and p = 0.013 and p = 0.013 and 0.042, respectively). In the adjusted analysis, IL1-B and IL-13 remained associated with primary events, with p = 0.027 and p = 0.030, respectively, and IL1-B with total events (p = 0.022). In the logistic regression analysis, IL-5 independently predicted total events (p = 0.023). We found a significant association between tissue Doppler imaging variables and primary outcomes. Conclusion Identifying IL-5, IL1-B and IL-13 as probable independent predictors of events at an early stage of Chagas disease is a significant milestone to the understanding of this pathology evolution. Also, several tissue Doppler parameters were important as prognosis predictors.

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Abstract Survivors of Coronavirus Disease (COVID-19) frequently report persistent symptoms and reduced exercise capacity after hospital discharge. Simple, accessible methods to assess exertional performance in this population are urgently needed. We conducted a prospective observational study to evaluate exertional capacity using the six-Minute Step Test (6MST) in adults who had been hospitalized for COVID-19 at a referral center in Paraíba, Brazil. Participants were assessed six months after discharge using clinical evaluation, spirometry, standardized questionnaires (mMRC - modified Medical Research Council, SF-12 - Short Form-12), chest computed tomography and 6MST. The primary outcome was the number of steps completed on the 6MST. Performance was compared with normative values. Multivariable regression was used to identify predictors of poor exertional performance. Among 102 eligible participants, 88 (86.3%) completed the 6MST. The mean number of steps was 132.8 ± 30.9. 37.8% performed below the predicted threshold for healthy individuals; 10% fell below the 10th percentile. In the final multivariable model (R2 Ajdjusted = 0.39), older age, female sex, greater post-COVID-19 dyspnea (mMRC), and lower Mental Component Scores (MCS-12) were independently associated with lower step counts. The 6MST is a feasible tool for identifying exertional impairment in COVID-19 survivors. Reduced performance was common, particularly among older women and those with residual dyspnea or poorer mental health. These findings support the use of the 6MST to triage patients for post-COVID-19 rehabilitation.

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Abstract Introduction Antiretroviral drug resistance poses a challenge to therapy efficacy. Although Integrase Strand Transfer Inhibitors (INSTIs) have a high genetic barrier to resistance, few studies in Brazil have focused on INSTI resistance. This study aimed to assess HIV mutations associated with INSTI resistance in vertically infected children in Maranhão and Pernambuco, Brazil. Methods We conducted a retrospective analysis of antiretroviral resistance profiles in paediatric patients with virological failure receiving care through the Brazilian Unified Health System. Data on viral load, CD4+/CD8+ T-cell counts, and medication dispensing were obtained from Ministry of Health databases (SISGENO, SISCEL, and SICLOM). HIV-1 integrase sequences were analysed. Phylogenetic analysis (IQ-TREE) was used to identify subtypes and recombinants. Resistance-associated mutations were determined using the Stanford HIV Drug Resistance Database. Results Thirty-one paediatric patients (median age = 12-years) were included. Mean CD4+ count was 999 cells/mm³, and median viral load was 19,235 copies/mL. Subtype B and INSTI resistance mutations were detected in 74.5 % and 64.5 % of patients, respectively. High resistance rates to raltegravir (70.9 %) were observed, highlighting the importance of genotypic monitoring. Conclusion A high frequency of INSTI resistance-associated mutations was identified, indicating the need for continued surveillance in this population.

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Abstract Background Tuberculosis (TB) remains a major public health concern globally and in Brazil. Although ambulatory treatment is recommended for most patients, hospitalizations still occur due to severe clinical presentations, social vulnerability, or treatment complications. Methods We conducted a retrospective, observational study of TB-related hospitalizations at a regional referral tertiary public hospital in São Paulo, Brazil, from 2013 to 2022. Medical records were reviewed to collect epidemiological, clinical, laboratory, and microbiological data. Results Among 197 hospitalizations for TB, 73.1% were male, with a mean age of 41.8 years. TB-HIV coinfection was identified in 55.3% of cases, with 83.5% of these patients having CD4+ T-cell counts ≤ 200 cells/mm3. Malnutrition (40.1%), smoking (64.0%), alcohol use (51.6%), and illicit drug use (58.1%) were common. Pulmonary TB occurred in 48.7%, while 29.4% had extrapulmonary TB and 21.8% disseminated forms. Diagnostic confirmation was achieved in 74.1%, including bacilloscopy, culture, molecular test, ADA and biopsy. The main reason for hospitalization was diagnostic work-up (74.1%), with a median symptom duration of 3.6 months. ICU care was required in 23.8% of cases. In-hospital mortality was 17.3%, and significant risk factors included malnutrition and thrombocytopenia. Conclusions In this high-burden setting, TB hospitalizations were associated with social vulnerability, HIV coinfection, and delayed diagnosis. The high frequency of severe presentations highlights the importance of early detection and access to molecular testing. Improved integration between outpatient care and hospital services may reduce the need for hospitalization and improve outcomes.

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Abstract Introduction Retention to antiretroviral therapy (ART) is critical for controlling HIV/AIDS and reducing mortality rates worldwide. In Brazil, although ART is widely accessible, challenges remain in retaining individuals on treatment over time. This study aims to analyze trends in ART retention from 2014 to 2022, addressing gaps in current national data. Methods This is a population-based, cross-sectional study, that utilized data from the Brazilian national ART monitoring system to assess retention rates at 6-, 12-, 24-, 36-, 48-, and 60-months post-ART initiation. The analysis included individuals aged 15-years or older, with retention defined as no more than a 28-day delay in drug distribution. Descriptive analyses of retention from 2014 to 2022 were conducted using R version 4.0 (R Core Team, 2020) and SPSS version 21 (IBM Corp.) Results The study observed over 3.4 million ART distributions, revealing that retention rates steadily declined over time, with the lowest rates observed at 60-months (71% in 2022). Men had consistently higher retention rates compared to women (79% vs. 73% in 2022). Lower retention was found among younger age groups (74% in 2022), indigenous populations (67% in 2022), individuals with lower education levels (72% in 2022), and those residing in northern (74% in 2022) regions of Brazil. Conclusions The study highlights considerable retention challenges, particularly after extended periods on ART, with notable disparities across demographic and regional groups. The findings suggest the need of interventions to improve ART retention, especially among vulnerable populations, to reach the 95-95-95 targets in Brazil. The introduction of multi-month drug dispensing and other strategies implemented during the COVID-19 pandemic may have helped stabilize retention rates in recent years.

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Abstract This study aimed to investigate the microbial community structure and the presence of Antibiotic-Resistant Bacteria (ARB), Antibiotic Resistance Genes (ARGs), and antimicrobial residues in an urban stream adjacent to an informal settlement in Brazil. Water samples collected during the winter of 2021 (n = 7) were analysed using culture-dependent and -independent methods. Microbial community structure was assessed by 16S rRNA sequencing, while bacterial isolates were characterized by Chlorhexidine Minimum Inhibitory Concentration (CHX-MIC) and whole-genome sequencing. Free carbapenemase ARGs were screened by conventional PCR and selected antimicrobial residues were quantified by UHPLC-MS/MS. The bacterial community was dominated by phyla Firmicutes, Bacteroidota, Proteobacteria, Campylobacterota, Actinobacteriota, and Patescibacteria. Abundant (> 5%) families included Ruminococcaceae, Prevotellaceae, Moraxellaceae, and Arcobacteraceae, associated with faecal contamination and antimicrobial resistance. Urban stream bacterial isolates (31/66) belonged mainly to the genera Aeromonas, Citrobacter, Escherichia, Serratia, Chryseobacterium, Elizabethkingia with a high percentage of phenotypic resistance to third-generation cephalosporin and carbapenems. WGS of some isolates (16/31) revealed the co-production of ESBL and carbapenemase ARGs as well as Inc-type plasmids, efflux pumps and virulence genes. CHX-MICs ranged from 0.5 to 128 mg/L, with Klebsiella pneumoniae and Serratia marcescens showing the highest values and harboring qac genes and IncHI2 plasmids, respectively. Azithromycin, ceftriaxone, levofloxacin, and chlorhexidine were detected at up to 2.39, 1.18, 0.14, and 0.43 mg/L, respectively. Notably, ceftriaxone-positive water samples also contained ARB and free ARGs (blaNDM, blaKPC, blaVIM). These findings highlight urban streams as reservoirs of ARB, ARGs, and antimicrobial residues, stressing the urgent need for local water treatment to mitigate antimicrobial resistance and public health risks.

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Abstract Objective To estimate the costs associated with the hospitalization of patients with Severe Acute Respiratory Infection (SARI) due to SARS-CoV-2 in a university hospital affiliated with the Brazilian Unified Health System (SUS) in 2020 and 2021. Methods A bottom-up micro-costing approach was used to conduct a cost analysis based on data from a hospital clinical cohort. Patients with confirmed diagnoses of COVID-19 and SARI, admitted to general wards or intensive care units (with or without mechanical ventilation), were included. Healthcare activities were categorized as hospitalization, ventilation, hemodialysis, nutrition, medications, and laboratory tests. Costs were calculated based on individualized consumption of supplies and procedures, also considering the annualized cost of equipment. Comparisons were made between micro-costing and macro-costing (based on the Hospital Admission Authorizations - AIH). Results A total of 627 patients were analyzed. The total cost was R$ 5,824,366.73 (Int$ 2,307,593.80) when healthcare professionals were excluded and R$19,437,731.25 (Int$ 7,701,161.35) when they were included. Medications accounted for the largest share (52.79%). Micro-costing was 1.7-times higher than macro-costing for hospital costs alone and 2.3-times higher when professional costs were included. Multivariate analysis identified length of hospital stay as the main factor associated with increased costs, while age, sex, and referral origin showed no significant association. Conclusion This study reveals the substantial economic impact of COVID-19-related hospitalizations in high-complexity care settings. It also highlights the importance of improving financing models for the SUS, particularly given the discrepancies between actual costs and federal reimbursement values. These findings contribute to the development of public policies and response strategies for future health emergencies.

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Abstract Background Dolutegravir-based antiretroviral therapy has improved virologic outcomes in people living with HIV; however, its effects on Health-Related Quality of Life (HRQoL), particularly among individuals with prior antiretroviral failure, remain insufficiently characterized. We aimed to compare HRQoL in people living with HIV initiating dolutegravir-based regimens, with or without previous antiretroviral failure. Methods This multicenter study was conducted across 15 Brazilian HIV centers. Participants completed the RAND-36 questionnaire at baseline and after 12-months of dolutegravir-based therapy. HRQoL changes were assessed within groups and compared between groups using change scores over time. Results A total of 439 participants were included in the longitudinal analysis, of whom 373 had no prior therapeutic failure and 66 had previous antiretroviral failure. Among participants with prior failure, significant improvements were observed in role-emotional functioning (Δ = 17.17; p = 0.010), social functioning (Δ = 10.79; p = 0.008), and pain (Δ = 10.66; p = 0.024), whereas HRQoL remained stable among individuals switching therapy without prior failure. Between-group comparisons demonstrated significantly greater improvements in role-emotional functioning, social functioning, pain, and general health among individuals with prior therapeutic failure. Conclusions Switching to dolutegravir-based therapy was associated with stable HRQoL among individuals on suppressive regimens and with significant improvements among those with prior antiretroviral failure. These findings support the relevance of psychosocial and patient-reported outcomes in the evaluation of treatment response in people living with HIV.

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Abstract Background Sexually Transmitted Infections (STIs) are major causes of male urethritis and genital ulcer disease, with increasing concern about antimicrobial resistance, particularly in Neisseria gonorrhoeae. This study aimed to describe the etiological profile of male urethritis and genital ulcer disease and to evaluate the antimicrobial resistance profile of Neisseria gonorrhoeae isolates in a medium-sized Brazilian city. Methods To address the study objectives, a descriptive study was conducted among men aged 18-years or older presenting with urethral discharge and/or genital ulcers at STI reference services in Ribeirão Preto, São Paulo State, Brazil. Urethral and ulcer swabs were analyzed using molecular assays to identify etiological agents. Antimicrobial susceptibility testing of N. gonorrhoeae isolates was performed by determining minimum inhibitory concentrations according to international standards. Results A total of 144 samples were obtained from 134 men (mean age: 29-years), including 126 urethral samples and 18 genital ulcer disease samples. Neisseria gonorrhoeae was detected in 108 urethral samples (85.7 %), while Chlamydia trachomatis was identified in 45 (35.7 %), frequently in coinfections. Among genital ulcer disease cases, herpes simplex virus type 2 was detected in 7 cases (38.9 %), Treponema pallidum in 6 (33.3 %), and no pathogen was identified in 4 cases (22.2 %). Antimicrobial susceptibility testing was successfully performed in 95 Neisseria gonorrhoeae isolates, showing resistance rates of 71.7 % to ciprofloxacin, 43.5 % to tetracycline, and 26.1 % to penicillin, with complete susceptibility to ceftriaxone and cefixime. Coinfection with Chlamydia trachomatis and Neisseria gonorrhoeae occurred in 35 samples (28 %). Conclusions Neisseria gonorrhoeae and Chlamydia trachomatis are the leading causes of male urethritis, whereas herpes simplex virus type 2 and Treponema pallidum predominate among cases of genital ulcer disease. The high prevalence of ciprofloxacin resistance reinforces the need for continuous antimicrobial resistance surveillance and supports current guidelines recommending ceftriaxone as first-line therapy.

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Abstract Background Candidemia is a severe healthcare-associated infection with persistently high mortality, particularly in critically ill patients. Beyond host severity, inadequate implementation of recommended management strategies may substantially influence outcomes. Methods This retrospective observational study included adult patients with at least one episode of candidemia in a Brazilian tertiary hospital between 2018 and 2024. Clinical, microbiological, and therapeutic variables were analyzed, including adherence to an eight-item candidemia care bundle. In-hospital mortality was the primary outcome. Univariate, multivariate logistic regression, and Kaplan-Meier survival analyses were performed. Results Among 136 patients (mean age 62.4-years), 87.5% required ICU admission. Overall mortality reached 76.5%. Candida albicans (32.4%) and the C. parapsilosis complex (29.4%) were the most frequent species. Non-optimal treatment (OR = 5.52; p = 0.031) and failure to remove the central venous catheter (OR = 6.60; p = 0.004) were independent predictors of death. Catheter removal significantly improved survival (p < 0.001). Survivors showed greater adherence to the care bundle (3.66 vs. 1.98 items; p = 0.001) and more frequent Infectious Diseases consultation (50%vs. 28.8%; p = 0.027). Mortality did not differ between catheter-drawn and peripheral blood cultures. Conclusions In this cohort, candidemia mortality was strongly associated with failure in early vascular source control and poor adherence to recommended management, underscoring quality of care as a key determinant of survival.

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Abstract Lung cancer is the most common Non-AIDS-Defining Cancer (NADC) and a leading cause of cancer-related death in People Living With HIV (PLWH). Despite antiretroviral therapy, PLWH are at higher risk of developing cancer compared to the general population. This increased susceptibility reflects a combination of immunosuppression, chronic inflammation, smoking, and direct oncogenic effects of HIV proteins. Tat, gp120, and Nef modulate cell cycle control, apoptosis, epithelial-mesenchymal transition, angiogenesis, and immune evasion. Persistent HIV reservoirs in lung tissue (mainly effector memory CD4⁺ T-cells and alveolar macrophages) sustain local immune dysregulation. Extracellular vesicles carrying viral proteins or nucleic acids activate oncogenic pathways, while HIV integration disrupts tumor suppressor genes such as PTEN and induces epigenetic silencing of regulators like P16INK4a. These alterations, together with oxidative stress, promote a pro-tumorigenic microenvironment. A deeper understanding of these mechanisms may enable early biomarker identification and the design of targeted preventive and therapeutic strategies for lung cancer in PLWH.

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Abstract Rapid, syndromic molecular panels and high throughput sequencing have transformed the diagnostic landscape for sepsis, respiratory, gastrointestinal, and central nervous system infections, but their value in routine practice depends on how they are integrated with conventional microbiology and antimicrobial stewardship. This review synthesises recent high-quality evidence to propose a pragmatic three-tier hybrid framework. Tier 1 comprises syndrome specific rapid panels that provide organism and selected resistance markers within hours, primarily to accelerate early escalation or de-escalation rather than to replace culture. Tier 2 positions reflex culture and targeted adjunct tests as the non-negotiable specificity anchor, confirming molecular hits, distinguishing infection from colonisation or contamination, generating phenotypic susceptibility data and supplying isolates for infection prevention and public health surveillance. Tier 3 reserves targeted or metagenomic sequencing for a small, clinically critical subset of high suspicion, panel negative and culture negative cases, where additional breadth can realistically change management. Across sepsis/BSI, pneumonia, gastrointestinal infection and CNS disease, available data indicate that clinical benefit is driven less by any individual technology and more by disciplined implementation: clear indications, explicit reflex rules, close linkage to antimicrobial stewardship and systematic audit of key performance indicators such as time-to-targeted therapy, spectrum of antimicrobial use and cost per additional actionable diagnosis. The proposed tiered, syndrome wise algorithms provide a transferable conceptual scaffold that can be adapted to local resources, allowing laboratories in both high and low resource settings to introduce advanced diagnostics without abandoning culture-based anchors or stewardship accountability.

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Abstract T-cell exhaustion, a well-characterized phenomenon, has historically been studied in the context of viral and oncological diseases. However, its relevance to chronic bacterial infections has only recently garnered attention. This review summarizes emerging evidence suggesting that bacterial pathogens can induce immune exhaustion through a variety of mechanisms. Additionally, we explore how bacterial biofilms, immune-privileged niches, and regulatory T-cell expansion contribute to persistent immune dysfunction. The article further examines the consequences of immune exhaustion, including secondary infections, antibiotic resistance, and microbiome dysbiosis, which are often underappreciated aspects of chronic immune impairment. Therapeutic strategies targeting these exhaustion pathways, such as immune checkpoint blockade, metabolic reprogramming, and microbiome modulation, are also discussed. We emphasize the need to consider chronic bacterial infections not as static conditions but as dynamic processes that interact with and suppress the immune system. Thus, understanding the mechanisms behind immune exhaustion highlights the importance of developing therapies that restore immune function, rather than solely relying on traditional antimicrobial treatments.

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ABSTRACT John Cunningham Virus (JCV) and BK Virus (BKV) are the most extensively studied Human Polyomaviruses (HPyVs), primarily associated with Progressive Multifocal Leukoencephalopathy (PML) and BKV Nephropathy (BKVN), respectively. While co-infection with these viruses has been documented in the same disease, simultaneous manifestation in distinct pathologies has not been previously reported. We present the first documented case of concurrent PML and Polyomavirus Nephropathy (PVN) due to reactivation of two different HPyVs, offering new insights into the clinical spectrum of HPyV-related diseases.

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ABSTRACT Paradoxical inflammatory reactions, similar to Immune Reconstitution Inflammatory Syndrome (IRIS) in HIV, have been occasionally reported in leprosy, tuberculosis, certain immunosuppressive conditions, and Para-coccidioidomycosis (PCM), among others. This report presents the clinical data and outcomes of two PCM cases in which the patients developed a severe inflammatory reaction following antifungal therapy, with subsequent improvement after adjunctive corticosteroid use. Both patients were adults with acute/subacute PCM who experienced clinical worsening after starting liposomal amphotericin B, with fever, anasarca, jaundice, and exacerbation of pre-existing symptoms. After excluding other infections, intravenous hydrocortisone was administered, resulting in rapid improvement. Corticosteroids were tapered after two to three weeks, and both patients continued outpatient follow-up while receiving itraconazole. Few similar PCM cases have been described in the literature, and they reported comparable outcomes. Its exact mechanism remains unclear, but may be immune-mediated. Reporting additional cases is essential to better establish the true incidence of this reaction and to strengthen the evidence supporting the benefit of corticosteroids as an adjunctive therapy.

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ABSTRACT A 25-year-old healthy woman was admitted to our hospital with fever and abdominal pain. Abdominal contrast-enhanced computed tomography revealed a fluid collection with foamy gas formation extending from both rectus abdominis muscles to the subcutaneous tissue. Antimicrobial therapy with meropenem (3 g/day), clindamycin (1800 mg/day), and daptomycin (300 mg/day) was initiated as empiric therapy. Subcutaneous abscess culture revealed gram-positive cocci, which was identified as Anaerococcus tetradius. Histopathological examination of the necrotic tissue showed skeletal muscle necrosis. On the basis of these findings, the patient was diagnosed with Non-Clostridial Gas Gangrene (NCGG) due to A. tetradius. We report a novel case of NCGG caused by A. tetradius following a cesarean section in an immunocompetent patient. Although A. tetradius has been detected in clinical specimens, cases of human infections are extremely rare. Clinicians should consider A. tetradius infection as a complication of a cesarean section.

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ABSTRACT The rate of congenital syphilis remains low in developed countries, as most women with syphilis are routinely screened and treated during pregnancy. We report here the case of a 3-month-old boy, with fever that lasted 15-days referred to the emergency department of tertiary care paediatric center. He had no history and had never travelled. Examination showed severe pallor, slight forehead bulging and large isolated hepatomegaly. Blood tests found: anaemia, elevated C-reactive protein and hyperlymphocytosis. Echocardiography found an intracardiac mass on the posterior wall of the right atrium extending to the origin of the superior vena cava. Cardiac MRI confirmed that mass. The Treponemal Hemagglutination Assay (TPHA) and non-treponemal test (Venereal Disease Research Laboratory, VDRL) were highly positive. Prolonged antibiotic therapy with penicillin G resulted in good clinical evolution, disappearance of lymphocytosis and total disappearance of the mass at 20-months’ follow-up.

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ABSTRACT Objectives: NOVA and DENOVA scores were developed to guide endocarditis risk assessment in Enterococcus faecalis Bacteremia (EfB), but some of their criteria may be open to interpretation. We aimed to evaluate their inter-rater reliability and feasibility. Methods: Thirty-two physicians from four specialties involved in the management of endocarditis independently evaluated eight EfB patient records using the NOVA and DENOVA scores. Each score was applied eight times per case. Inter-rater reliability was measured with Krippendorff’s alpha, and agreement with Fleiss’ Kappa. Completion time was also recorded. Results: No record received identical scores from all raters. NOVA showed low inter-rater reliability (α = 0.37), while DENOVA reached moderate levels (α = 0.49). High agreement was found for extreme score values, but agreement dropped markedly for intermediate values. Among score items, Auscultation of murmur (A) and Valve disease (V) had the highest reliability (α > 0.8), while Duration of symptoms (D) and Origin of infection (O) had the lowest (α < 0.2). Completion times were similar between NOVA and DENOVA but varied by specialty. Conclusion: The reproducibility of these scores is limited, especially near critical thresholds, highlighting the need to complement scoring tools with clinical judgment in EfB.

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Abstract Background Oropouche Virus (OROV) is an arbovirus endemic to parts of Central and South America, historically confined to the Amazon region. In 2023‒2024, a significant expansion of OROV circulation was reported in Brazil, including autochthonous transmission in Salvador, Bahia. Despite its growing relevance, clinical descriptions are limited and mainly associated with the new lineage. Method We conducted a passive surveillance study based on medical records of patients confirmed by RT-qPCR for OROV infection who were treated at an Emergency Care Unit in Salvador, Bahia, between April and July 2024. Sociodemographic, clinical, and laboratory data were collected. Results We collected information from 11 RT-PCR-confirmed patients with a mean age of 38-years, and a female predominance (55 %). The most prevalent symptoms were fever (100 %) and headache (100 %), myalgia (90 %), nausea (73 %), and arthralgia (55 %). No cases of severe or fatal outcomes were observed. Conclusions This study contributes to the clinical characterization of Oropouche fever in an emerging urban transmission setting outside the traditional endemic areas. The findings support the need for including OROV in the differential diagnosis of acute febrile illnesses, strengthening molecular surveillance, and expanding awareness among clinicians in non-Amazonian regions.

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Abstract This study evaluated self-reported immunization coverage against respiratory viruses among dental surgeons and analyzed whether adherence was associated with vaccine-N promotion behaviors in clinical practice. A cross-sectional online survey was conducted between January and April 2025 among dentists registered with the São Paulo Regional Council of Dentistry (CROSP). Of approximately 98,000 dentists, 604 (≈0.6 %) returned responses. Information on sociodemographic characteristics, vaccination status for COVID-19, influenza, and hepatitis B, and professional behaviors related to vaccine promotion was collected through a self-administered questionnaire, without verification of immunization cards. Among 604 participants, adherence was high for COVID-19 primary vaccination (95.2 %), at least one booster dose (90.9 %), and hepatitis B (81.0 %), whereas annual influenza vaccination fell below the ≥ 90 % threshold used to define high coverage (61.1 %). Professional behaviors were less frequent: 17.7 % routinely asked patients about vaccination, 36.2 % actively recommended vaccines, and 17.3 % verified staff vaccination. Questioning patients was positively associated with recommending vaccines (ρ = 0.248; p < 0.001) and remained independently associated with it in multivariable analysis (adjusted OR = 4.02; 95 % CI 2.53‒6.40; p < 0.001). Coverage was heterogeneous and few professionals translated adherence into vaccine-promotion practices. Integrating vaccine assessment into dental anamnesis and strengthening policies for staff vaccination are opportunities to align dental practice with public health goals.