Patients with longstanding pPatients with longstanding psoriatic arthritis can achieve DAPSA remission or low disease activity and it correlates to better functional outcomes: results from a Latin-American real-life cohort.

BACKGROUND: Patients with psoriatic arthritis (PsA) experience reduced physical function and impaired quality of life. Better patient-reported functional outcomes are found when lower disease activity is achieved. OBJECTIVES: To evaluate the variation of physical function by HAQ-DI over time in PsA patients treated with standard therapy in a real-life setting: to verify predictors of achieving a minimum clinically important difference (MCID) in function by HAQ-DI (ΔHAQ-DI ≤ - 0.35) and to measure the impact of achieving REM/LDA on long-term function by HAQ-DI. METHODS: This is a longitudinal analysis of a real-life retrospective cohort. Data from PsA patients with at least 4 years of follow-up in the PsA clinic from 2011 to 2019 were extracted from electronic medical records. The variations of physical function by HAQ-DI and disease activity by DAPSA over time were calculated. A multivariate hierarchical regression model was applied to verify predictors of MCID in HAQ-DI. A comparison of HAQ-DI variation between patients with DAPSA REM, LDA, moderate and high disease activity was made using the generalized estimating equation model (GEE), adjusted by Bonferroni test. The Spearman correlation method was applied to verify the correlation of ΔDAPSA and ΔHAQ-DI over time. Statistical analysis was performed in SPSS program version 21.0. RESULTS: Seventy-three patients were included in the analysis. Physical function measured by HAQ-DI was determined by PsA disease activity measured by DAPSA (p < 0.000). A moderate and statistically significant correlation between ΔDAPSA and ΔHAQ-DI was observed (rs = 0.60; p < 0.001). Only patients in DAPSA REM demonstrated a constant decline in HAQ-DI scores during the follow-up. White ethnicity and older age at baseline were predictors for not achieving MCID in HAQ-DI [RR 0.33 (0.16-0.6795% CI p = 0.002) and RR 0.96 (0.93-0.9895% CI p < 0.000), respectively, while higher scores of HAQ-DI at baseline were predictors of achieving MCID [RR 1.71 (1.12-2.6095%CI p = 0.013)]. CONCLUSIONS: In PsA, patients who maintained DAPSA REM/LDA over time had better long-term functional outcomes. Higher HAQ-DI scores at baseline, non-white ethnicity and younger age were predictors for achieving a clinical meaningful improvement of HAQ-DI.

Patients with longstanding psoriatic arthritis can achieve DAPSA remission or low disease activity and it correlates to better functional outcomes: results from a Latin-American real-life cohort

Abstract Background Patients with psoriatic arthritis (PsA) experience reduced physical function and impaired quality of life. Better patient-reported functional outcomes are found when lower disease activity is achieved. Objectives To evaluate the variation of physical function by HAQ-DI over time in PsA patients treated with standard therapy in a real-life setting: to verify predictors of achieving a minimum clinically important difference (MCID) in function by HAQ-DI (ΔHAQ-DI ≤ − 0.35) and to measure the impact of achieving REM/LDA on long-term function by HAQ-DI. Methods This is a longitudinal analysis of a real-life retrospective cohort. Data from PsA patients with at least 4 years of follow-up in the PsA clinic from 2011 to 2019 were extracted from electronic medical records. The variations of physical function by HAQ-DI and disease activity by DAPSA over time were calculated. A multivariate hierarchical regression model was applied to verify predictors of MCID in HAQ-DI. A comparison of HAQ-DI variation between patients with DAPSA REM, LDA, moderate and high disease activity was made using the generalized estimating equation model (GEE), adjusted by Bonferroni test. The Spearman correlation method was applied to verify the correlation of ΔDAPSA and ΔHAQ-DI over time. Statistical analysis was performed in SPSS program version 21.0. Results Seventy-three patients were included in the analysis. Physical function measured by HAQ-DI was determined by PsA disease activity measured by DAPSA (p < 0.000). A moderate and statistically significant correlation between ΔDAPSA and ΔHAQ-DI was observed (rs = 0.60; p < 0.001). Only patients in DAPSA REM demonstrated a constant decline in HAQ-DI scores during the follow-up. White ethnicity and older age at baseline were predictors for not achieving MCID in HAQ-DI [RR 0.33 (0.16-0.6795% CI p = 0.002) and RR 0.96 (0.93-0.9895% CI p < 0.000), respectively, while higher scores of HAQ-DI at baseline were predictors of achieving MCID [RR 1.71 (1.12-2.6095%CI p = 0.013)]. Conclusion In PsA, patients who maintained DAPSA REM/LDA over time had better long-term functional outcomes. Higher HAQ-DI scores at baseline, non-white ethnicity and younger age were predictors for achieving a clinical meaningful improvement of HAQ-DI.

Assessing statins use in a real-world primary care digital strategy: a cross-sectional analysis of a population-wide digital health approach.

Background: The digitization of the primary care system provides an opportunity to evaluate the current use of statins in secondary prevention populations (myocardial infarction or stroke). Methods: We conducted a cross-sectional study (ClinicalTrials.gov, NCT05285085), analysing anonymised data routinely collected by community health workers (CHW) in Brazil between May 2016 and September 2021 to assess the proportion of self-reported statins use and associated factors. Findings: From the 2,133,900 individuals on the database, 35,103 (1.6%), mean age 66.2 years (SD14.6), 49.5% (17,382/35,103) male sex, 50.5% (17,721/35,103) female sex, and 29.6% (10,381/34,975) Caucasians, had a previous myocardial infarction (MI) (n = 11,628; 33.1%) or stroke (n = 25,925; 73.9%). Approximately 50% (17,020/35,103) were from the Northeast region, 78.7% (27,605) from urban zones, and 39.4% (13,845) with social development index (SDI) >0.7. Overall, 6.7% (2346) and 0.6% (212) reported statins and high dose statins use, respectively. Age over 60 years old (OR 1.32 [95% CI 1.19-1.47), living in the Southern region (OR 4.53 [95% CI 3.66-5.60]), having a previous diagnosis of MI (OR 4.53 [95% CI 3.66-5.60]), heart failure (OR 2.29 [95% CI 1.13-1.47]), diabetes (OR 1.50 [95% CI 1.37-1.64]), dyslipidaemia (OR 2.90 [95% CI 2.55-3.29]), chronic kidney disease (OR 1.27 [95% CI 1.08-1.48]) and use of anti-hypertensives (OR 5.47 [95% CI 4.60-6.47]) were associated with statin use. Interpretation: The analysis of a real-world database from a digitized primary care system, allowed us to identify a very low use of statins in secondary prevention Brazilian patients, mostly influenced by socio-demographic factors and co-morbidities. Funding: Novartis Biociências, Brazil.

Asthma control in Brazil: a systematic review.

OBJECTIVES: To explore asthma control in patients undergoing pharmacotherapy on studies in the last 20 years in Brazil. Asthma is a chronic airway inflammation disease with a high prevalence worldwide. Even with a variety of drug treatment improvements, attaining asthma control is challenging, since it should have a personalized approach. In Brazil, studies on the prevalence of asthma control are scarce and usually from a small sample size. DATA SOURCES: A systematic review was performed to assess asthma control in Brazilian population. Terms related to "asthma", "asthma control" and "Brazil" were used in the search strategies in PubMed, BVSalud, Embase and Cochrane Library, including Brazilian Journal of Allergy and Immunology as data sources. A narrative synthesis was performed to report key outcome. STUDY SELECTIONS: In total, 23 studies were included. Most of them were conducted in the Southeastern and Northeast regions, in a short duration. RESULTS: Pediatric and non-pediatric population were assessed, with a higher proportion of female. In pediatric population, those with poorly controlled asthma usually had severe or persistent disease. In elderly, an increased asthma severity was found, although proper treatment might be effective. Most studies (70%) also described exacerbations, hospitalizations (48%), quality of life (39%), and emergency visits (30%). Despite heterogeneity of outcomes and population, studies show an important prevalence of uncontrolled asthma even in patients being treated, with better disease control with treatment improvements. CONCLUSIONS: Studies in Brazil have shown that asthma control remains a challenge and there is still a need for improvement on disease management.

Maintained activity in ankylosing spondylitis patients treated with TNFi and/or NSAID for at least 12 weeks: a cross-sectional study in Brazil.

BACKGROUND: The aim of this study was to evaluate disease activity among patients with axial spondyloarthritis (AS) treated with tumor necrosis factor inhibitors (TNFi) and/or nonsteroidal anti-inflammatory drugs (NSAIDs) for at least 12 weeks in private outpatient settings in Brazil. METHODS: This was a cross-sectional, real-world study conducted in 17 Brazilian private health care institutes. Patients were selected if diagnosed with AS or axial radiographic spondyloarthritis (AxSpA) and treated with NSAIDs or TNFi for at least 12 weeks within the last 26 weeks prior to enrollment. The data were collected from interviewed-based and self-administered questionnaires from patients and physicians. Disease activity was defined as active (≥ 4), low /suboptimal (≥ 2 and < 4) and inactive (< 4) by Bath AS Disease Activity Index (BASDAI) and/or very high (≥ 3.5), high (≥ 2.1 to < 3.5), low (≥ 1.3 to < 2.1), and inactive (< 1.3) by AS Disease Activity Score (ASDAS-CRP). Both patients and physicians' perceptions of disease control were assessed using a numeric rating scale (NRS; 0-inactive to 10-very active disease). RESULTS: The cohort included 378 patients with a mean age of 46 years, and the median time since diagnosis until enrollment was 5.4 years (interquartile range 2.7-10.5). Most patients were treated with TNFi alone (74%), followed by TNFi in combination with NSAID (15%), and NSAID alone (11%). About half AS patients showed active disease and 24% of patients showed low activity/suboptimal disease control despite having been treated for at least 12 weeks. Although TNFi showed better disease control than NSAID, inactive disease was experienced by few patients. The NRS (mean [standard deviation]) score for disease perception was 4.24 (3.3) and 2.85 (2.6) for patients and physicians, respectively. CONCLUSION: This real-world study showed that most AS patients on TNFi and/or NSAID had not achieved an adequate disease control, as almost 75% of them exhibited active disease or low activity/suboptimal disease control. There remains a need for improved disease management among patients with AS.

The Medical Burden of Heart Failure: A Comparative Delineation with Cancer in Brazil

Abstract Background: Due to its poor prognosis and mortality rates, heart failure (HF) has been recognized as a malignant condition, comparable to some cancers in developed countries. Objectives: To compare mortality from HF and prevalent cancers using data from a nationwide database in Brazil. Methods: This was a descriptive, cross-sectional study using secondary data obtained from Brazilian administrative databases of death records and hospitalization claims maintained by the Ministry of Health. Data were analyzed according to main diagnosis, year of occurrence (2005-2015), sex and age group. Descriptive analyses of absolute number of events, hospitalization rate, mortality rate, and in-hospital mortality rate were performed. Results: The selected cancers accounted for higher mortality, lower hospitalization and higher in-hospital mortality rates than HF. In a group analysis, HF showed mortality rates of 100-150 per 100,000 inhabitants over the period, lower than the selected cancers. However, HF had a higher mortality rate than each type of cancer, even when compared to the most prevalent and deadly ones. Regarding hospitalization rates, HF was associated with a higher risk of hospitalization when compared to cancer-related conditions as a group. Conclusions: Our findings indicate that HF has an important impact on mortality, hospitalization and in-hospital mortality, comparable to or even worse than some types of cancer, representing a potential burden to the healthcare system.

Blockade of interleukin seventeen (IL-17A) with secukinumab in hospitalized COVID-19 patients - the BISHOP study.

BACKGROUND: Patients with severe COVID-19 seem to evolve with a compromised antiviral response and hyperinflammation. Neutrophils are critical players in COVID-19. IL-17A plays a major role in protection against extracellular pathogens and neutrophil attraction/activation. We hypothesized that secukinumab, an anti-IL17A monoclonal antibody, could prevent the deleterious hyperinflammation in COVID-19. METHODS: BISHOP was a randomized, open-label, single-centre, phase-II controlled trial. Fifty adult patients hospitalized with PCR-positive Covid-19, were randomized 1:1 to receive 300 mg of secukinumab subcutaneously at day-0 plus standard of care (group A) or standard of care alone (group B). A second dose of 300 mg of secukinumab could be administered on day-7, according to staff judgement. The primary endpoint was ventilator-free days at day-28 (VFD-28). Secondary efficacy and safety outcomes were also explored. RESULTS: An intention-to-treat analysis showed no difference in VFD-28: 23.7 (95%CI 19.6-27.8) in group A vs. 23.8 (19.9-27.6) in group B, p = .62; There was also no difference in hospitalization time, intensive care unit demand and the incidence of circulatory shock, acute kidney injury, fungal or bacterial co-infections. There was no difference in the incidence of severe adverse events. Pulmonary thromboembolism occurred only in males and was less frequent in secukinumab-treated patients (4.2% vs. 26.2% p = .04). There was one death in each group. Upper airway viral clearance was also similar in both groups. CONCLUSION: The efficacy of secukinumab in the treatment of Covid19 was not demonstrated. Secukinumab decreased pulmonary embolism in male patients. There was no difference between groups in adverse events and no unexpected events were observed.

Therapies for hidradenitis suppurativa: a systematic review with a focus on Brazil.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with a significant negative impact on the quality of life of patients. METHODS: We conducted a systematic review to assess current treatment for HS, with a special focus on therapies approved or used in Brazil. We used the PICO framework to improve the research process. The systematic review was reported in line with the PRISMA statement checklist. The search was conducted with clinical questions on two global databases (PubMed (MEDLINE) and Google Scholar) and three databases especially selected to retrieve Brazilian outcomes (BVS, SCIELO and REDALYC). RESULTS: Overall, 4640 articles were screened, 182 articles were analysed and 70 were used in a thematic qualitative analysis. Of these, 12 articles were from Brazil. The evidence-based literature was largely limited to case reports, case series, observational studies and expert opinion. Topical therapy, lifestyle interventions and oral antibiotics appeared as effective measures for mild HS. However, moderate-to-severe HS remains refractory to conventional treatments. CONCLUSION: Some biologic agents, such as adalimumab, infliximab, ustekinumab and secukinumab, have been shown to be effective in the management of moderate-to-severe HS that failed conventional treatment and demonstrated a good tolerability and safety profile.

Maintained activity in ankylosing spondylitis patients treated with TNFi and/or NSAID for at least 12 weeks: a cross-sectional study in Brazil

Abstract Background The aim of this study was to evaluate disease activity among patients with axial spondyloarthritis (AS) treated with tumor necrosis factor inhibitors (TNFi) and/or nonsteroidal anti-inflammatory drugs (NSAIDs) for at least 12 weeks in private outpatient settings in Brazil. Methods This was a cross-sectional, real-world study conducted in 17 Brazilian private health care institutes. Patients were selected if diagnosed with AS or axial radiographic spondyloarthritis (AxSpA) and treated with NSAIDs or TNFi for at least 12 weeks within the last 26 weeks prior to enrollment. The data were collected from interviewed-based and self-administered questionnaires from patients and physicians. Disease activity was defined as active (≥ 4), low /suboptimal (≥ 2 and < 4) and inactive (< 4) by Bath AS Disease Activity Index (BASDAI) and/or very high (≥ 3.5), high (≥ 2.1 to < 3.5), low (≥ 1.3 to < 2.1), and inactive (< 1.3) by AS Disease Activity Score (ASDAS-CRP). Both patients and physicians' perceptions of disease control were assessed using a numeric rating scale (NRS; 0—inactive to 10—very active disease). Results The cohort included 378 patients with a mean age of 46 years, and the median time since diagnosis until enrollment was 5.4 years (interquartile range 2.7-10.5). Most patients were treated with TNFi alone (74%), followed by TNFi in combination with NSAID (15%), and NSAID alone (11%). About half AS patients showed active disease and 24% of patients showed low activity/suboptimal disease control despite having been treated for at least 12 weeks. Although TNFi showed better disease control than NSAID, inactive disease was experienced by few patients. The NRS (mean [standard deviation]) score for disease perception was 4.24 (3.3) and 2.85 (2.6) for patients and physicians, respectively. Conclusion This real-world study showed that most AS patients on TNFi and/or NSAID had not achieved an adequate disease control, as almost 75% of them exhibited active disease or low activity/suboptimal disease control. There remains a need for improved disease management among patients with AS.

Age-related macular degeneration and resource utilization in the Brazilian public healthcare system: a real-world retrospective study.

BACKGROUND: Age-related macular degeneration (AMD) is a disease that causes damage in the macular region of the retina, leading to irreversible blindness. This study aims to understand the profile and care of patients with AMD and its cost at the Brazilian public health system to identify AMD-care needs. METHODS: This is a retrospective observational study of AMD with real-world data from the Brazilian public healthcare system, using DATASUS claim databases. Patients with AMD were selected from 01/Jan/2014 to 31/Jan/2020; had at least one claim of ICD10 code H35.3 (Degeneration of macula and posterior pole), and were submitted to one of two procedures exclusively available for AMD patients - optical coherence tomography (OCT) and medical treatment of retinal disease (antiangiogenic); aged ≥18 years at first ICD10 claim, and presenting at least 1 year of follow-up in the database. We described patients' characteristics, healthcare resource utilization and cost, and the antiangiogenic intravitreal treatment received by AMD patients, including the number of doses and interval time between them. RESULTS: Patients searching for AMD treatment since 2014 were mostly females (59%), white (61%), and a mean age of 72 years. They were mainly located in the Southeast (87%), and few patients were found in the North (1%) and Central-West (1.5%) regions, probably reflecting where the Brazilian guideline to treat AMD (Protocolo Clínico e Diretrizes Terapêuticas - PCDT) was incorporated as routine care for AMD. The average antiangiogenic dose of 2.5 antiangiogenic therapies within a year was below the expected. Most injections had an interval time of 20 to 40 days between doses, although some patients were treated more than 100 days. Another setback is that patients traveled longer distances for OCT and antiangiogenic treatment than overall AMD-healthcare, between 10 and 100 km. CONCLUSIONS: AMD patients seem to be undertreated, as they receive a mean of 2.5 doses of antiangiogenic treatment within a year. Inequalities among regions are evident, as the Southeast and South regions comprise almost all patients receiving the treatment from the public health system, probably reflecting the region with more access to AMD care according to PCDT recommendations.

Relationship of NAT2, CYP2E1 and GSTM1/GSTT1 polymorphisms with mild elevation of liver enzymes in Brazilian individuals under anti-tuberculosis drug therapy.

The relationship of NAT2, CYP2E1 and GSTM1/GSTT1 polymorphisms with mild elevation of liver biomarkers was investigated in individuals under anti-tuberculosis drug therapy. Tuberculosis outpatients (18-70 y) with (n=59) and without (n=40) mild increase of liver enzymes (MILE) at two-month treatment were selected. Blood samples were obtained for DNA extraction and evaluation of serum markers of liver function. NAT2, CYP2E1 and GSTM1/GSTT1 polymorphisms were detected by DNA sequencing, PCR-RFLP, and PCR multiplex. Frequency of NAT2*5/*5 genotype was higher in MILE than in non-MILE group (p=0.04). Patients carrying NAT2*5/*5 genotype had increased susceptibility to MILE (OR: 9.00, 95CI: 1.46-55.48, p=0.018). CYP2E1*5B allele (*1A/*5B plus *5B/*5B genotypes) carriers had a trend for reduced risk for MILE (OR: 0.34, 95CI: 0.11-1.03, p=0.056) that was confirmed by lower levels of liver markers than CYP2E1*1A/*1A carriers after treatment (p<0.05). Moreover, increased post-treatment ALT, AST and total bilirubin were associated with GSTM1*1/GSTT1*1 genotypes (p<0.05). Patients taking CYP2E1 inhibitors had increased susceptibility to MILE (OR: 7.39, 95CI: 1.93-28.29, p=0.003), which was independent of the studied polymorphisms. These results are suggestive that NAT2, CYP2E1 and GSTM1/GSTT1 polymorphisms and concomitant use of CYP2E1 inhibitors contribute to the susceptibility to mild alterations in liver enzymes in patients under anti-tuberculosis drug therapy.

Transcriptional responses of host peripheral blood cells to tuberculosis infection.

Host responses following exposure to Mycobacterium tuberculosis (TB) are complex and can significantly affect clinical outcome. These responses, which are largely mediated by complex immune mechanisms involving peripheral blood cells (PBCs) such as T-lymphocytes, NK cells and monocyte-derived macrophages, have not been fully characterized. We hypothesize that different clinical outcome following TB exposure will be uniquely reflected in host gene expression profiles, and expression profiling of PBCs can be used to discriminate between different TB infectious outcomes. In this study, microarray analysis was performed on PBCs from three TB groups (BCG-vaccinated, latent TB infection, and active TB infection) and a control healthy group. Supervised learning algorithms were used to identify signature genomic responses that differentiate among group samples. Gene Set Enrichment Analysis was used to determine sets of genes that were co-regulated. Multivariate permutation analysis (p < 0.01) gave 645 genes differentially expressed among the four groups, with both distinct and common patterns of gene expression observed for each group. A 127-probeset, representing 77 known genes, capable of accurately classifying samples into their respective groups was identified. In addition, 13 insulin-sensitive genes were found to be differentially regulated in all three TB infected groups, underscoring the functional association between insulin signaling pathway and TB infection.

Variantes genéticas da N-acetiltransferase 2, CYP2E1 e glutationa S-transferase: relação com a segurança terapêutica em pacientes com tuberculose / Genetic variants of N-acetyltransferase 2, CYP2E1 and glutathione S-transferase: relation with therapeutic safety in patients with tuberculosis

Polimorfismos nos genes da n-acetiltransferase 2 (NAT2), CYP2E1 e glutationa S-transferase (GST) têm sido associados a diferenças na resposta ao tratamento da tuberculose. O papel de variantes dos genes NAT2, CYP2E1 e GSTM1/GSTT1, no perfil de segurança do tratamento da tuberculose, foi avaliado em 99 pacientes com tuberculose, sem co-infecção por HIV ou vírus da hepatite, tratados por 6 meses. Amostras de sangue foram colhidas antes e durante o tratamento para avaliação de marcadores de lesão hepatocelular (ASL T e AST), colestase (ALP, GGT e bilirrubinas) e função renal (creatinina). O DNA genômico foi extraído de sangue colhido em EDTA pelo método precipitação salina. Os polimorfismos NAT2 foram analisados por PCR-RFLP e seqüenciamento de DNA. Os polimorfismos da região promotora do CYP2E1 foram detectados por PCR-RFLP e para a análise dos genótipos nulos de (GSTM1*0) foi utilizada a PCR multiplex. Durante o tratamento, 59,6% dos pacientes apresentaram reações adversas aos medicamentos (RAM) e alterações nos marcadores de lesão hepatocelular e colestase, com aumento de 1 a 4 vezes o limite superior de referência. Foi observada forte relação entre RAM e alterações nos marcadores séricos (p< 0,05) e também com o uso de medicação concomitante (p< 0,001)...

APOA1 polymorphisms are associated with variations in serum triglyceride concentrations in hypercholesterolemic individuals.

BACKGROUND: Apolipoprotein A-I gene (APOA1) polymorphisms have been associated with variations in serum low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol. We have investigated whether APOA1 common variants are also associated with variations in basal triglyceride serum concentrations and response to atorvastatin in individuals with hypercholesterolemia. METHODS: APOA1 G-75A and C83T polymorphisms and variations in serum lipids were evaluated in 150 hypercholesterolemic (HC) and 93 normolipidemic (NL) unrelated European-derived Brazilians treated with atorvastatin (10 mg/day for 4 weeks). Genomic DNA was extracted from blood leukocytes using a salting-out method and APOA1 polymorphisms were analyzed by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: G-75A polymorphism was associated with differences in serum concentrations of triglyceride and very low-density lipoprotein (VLDL)-cholesterol (p=0.026) in HC men. After atorvastatin treatment, women carrying the GG/CC haplotype had lower serum triglyceride and VLDL-cholesterol (p=0.020) than non-carriers. In men, the reduction in serum triglyceride in response to atorvastatin was found to be slightly lower in GG/CC haplotype carriers (p=0.051). CONCLUSION: Our data suggest that APOA1 polymorphisms are associated with variations of baseline serum concentrations of triglyceride and VLDL-cholesterol and in response to atorvastatin in a gender-specific manner.

Screening and characterization of mutations in isoniazid-resistant Mycobacterium tuberculosis isolates obtained in Brazil.

We investigated mutations in the genes katG, inhA (regulatory and structural regions), and kasA and the oxyR-ahpC intergenic region of 97 isoniazid (INH)-resistant and 60 INH-susceptible Mycobacterium tuberculosis isolates obtained in two states in Brazil: São Paulo and Paraná. PCR-single-strand conformational polymorphism (PCR-SSCP) was evaluated for screening mutations in regions of prevalence, including codons 315 and 463 of katG, the regulatory region and codons 16 and 94 of inhA, kasA, and the oxyR-ahpC intergenic region. DNA sequencing of PCR amplicons was performed for all isolates with altered PCR-SSCP profiles. Mutations in katG were found in 83 (85.6%) of the 97 INH-resistant isolates, including mutations in codon 315 that occurred in 60 (61.9%) of the INH-resistant isolates and 23 previously unreported katG mutations. Mutations in the inhA promoter region occurred in 25 (25.8%) of the INH-resistant isolates; 6.2% of the isolates had inhA structural gene mutations, and 10.3% had mutations in the oxyR-ahpC intergenic region (one, nucleotide -48, previously unreported). Polymorphisms in the kasA gene occurred in both INH-resistant and INH-susceptible isolates. The most frequent polymorphism encoded a G(269)A substitution. Although KatG(315) substitutions are predominant, novel mutations also appear to be responsible for INH resistance in the two states in Brazil. Since ca. 90.7% of the INH-resistant isolates had mutations identified by SSCP electrophoresis, this method may be a useful genotypic screen for INH resistance.