José Ueleres Braga

Effectiveness and safety of clofazimine in multidrug-resistant tuberculosis: a nationwide report from Brazil

Although clofazimine is used to treat multidrug-resistant tuberculosis (MDR-TB), there is scant information on its effectiveness and safety. The aim of this retrospective, observational study was to evaluate these factors as well as the tolerability of clofazimine in populations in Brazil, where it was administered at a daily dose of 100 mg·day−1 (body weight ≥45 kg) as part of a standardised MDR-TB treatment regimen until 2006 (thereafter pyrazinamide was used). All MDR-TB patients included in the Sistema de Informação de Tratamentos Especiais da Tuberculose (SITETB) individual electronic register were analysed. The effectiveness of clofazimine was assessed by comparing the treatment outcomes of patients undergoing clofazimine-containing regimens against those undergoing clofazimine-free regimens and its safety by describing clofazimine-attributed adverse events. A total of 1446 patients were treated with clofazimine-containing regimens and 1096 with pyrazinamide-containing regimens. Although success rates were similar in patients treated with clofazimine versus those treated with pyrazinamide (880 out of 1446, 60.9%, versus 708 out of 1096, 64.6%; p=0.054), clofazimine-treated cases exhibited higher death rates due to tuberculosis than pyrazinamide-treated ones (314 out of 1446, 21.7%, versus 120 out of 1096, 10.9%) but fewer failures (78 out of 1446, 5.4%, versus 95 out of 1096, 8.7%) and less loss to follow-up (144 out of 1446, 10.0%, versus 151 out of 1096, 13.8%). No relevant differences were detected when comparing adverse events in patients treated with clofazimine-containing regimens to those treated with clofazimine-free regimens. However, the incidence of side-effects was less than previously reported (gastro-intestinal complaints: 10.5%; hyper-pigmentation: 50.2%; neurological disturbances: 9–13%). The first nationwide report on the efficacy and safety of clofazimine when used within a standard MDR-TB regimen http://ow.ly/jRAb309DNC8

Fatores associados à Hipertensão Arterial Sistêmica autorreferida segundo VIGITEL nas 26 capitais brasileiras e no Distrito Federal em 2008

The menopause is the stage of a womans life when the transition from the reproductive to the non-reproductive condition occurs. The objective was to conduct a nutritional assessment of 30 postmenopausal women aged between 40 and 65, by compiling data from the first consultation of nutritional records related to food intake, as well as anthropometric and biochemical data. It was observed that the average result found for body mass index was considered high, being characterized as overweight (30.7 ± 5.9kg/m2) and waist circumference revealed a very high risk for developing cardiovascular disease (98.2 ± 15.9cm). Saturated fats were above the recommended level (8.14 ± 3.63%), whereas monounsaturated and polyunsaturated fats were lower resulting in 6.47 ± 3.40% and 5.37 ± 2.60% respectively. The average calcium intake was 549.63 ± 315.87mg, while vitamin D intake was 549.63 ± 315.87mcg, both of which were considered inadequate. Triglycerides were classified as optimal (134,3 ± 85,4mg/dL), total cholesterol was borderline (223.9 ± 141.3md/dL), HDL-C adequate (54.3 ± 18.5mg/dL) and LDL-C desirable (128.4 ± 45.1mg/dL). The results demonstrate that nutritional care is important and can prevent specific comorbidities in this age group, contributing to the quality of life of menopausal women.O objetivo deste artigo e estudar a associacao entre estilo de vida e estado nutricional e prevalencia de Hipertensao Arterial Sistemica (HAS) autorreferida, ponderada pelo sistema de Vigilância de Fatores de Risco e Protecao para Doencas Cronicas por Inquerito Telefonico (VIGITEL) e padronizada por idade e sexo, em individuos adultos das 26 capitais brasileiras e Distrito Federal em 2008. Calculou-se para cada capital a prevalencia de HAS padronizada pelo metodo direto. Realizou-se regressao linear multipla dos fatores de interesse em relacao a prevalencia de HAS ponderada e padronizada por sexo e idade. Apos a padronizacao, a prevalencia de HAS tendeu a aumentar nas capitais com populacao mais jovem e a diminuir naquelas com mais idosos. Nos modelos de regressao, mantiveram-se associados a prevalencia de HAS, ponderada e padronizada, o excesso de peso e o consumo de frutas e hortalicas. Porem, a atividade fisica associou-se negativamente apenas a prevalencia de HAS ponderada. Observou-se, com a prevalencia ponderada e padronizada de HAS, associacao positiva com excesso de peso e consumo regular de frutas e hortalicas e apenas com a prevalencia ponderada observou-se associacao inversa dessa morbidade com a pratica de atividade fisica.

Resistance profile of drugs composing the “shorter” regimen for multidrug-resistant tuberculosis in Brazil, 2000–2015

The difficulties in managing multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant (XDR) TB are well known. The regimens are very expensive, often toxic, and require up to 24 months to achieve an acceptable probability of success [1–3]. The first nationwide report on the drug resistance profile of the drugs composing the WHO “shorter” regimen in Brazil http://ow.ly/XfJa3096FsT

Social inequalities in neonatal mortality and living condition

OBJECTIVE To evaluate the association between the spatial distribution of neonatal mortality and living conditions, and to analyze trends in the social inequalities, related to this mortality, in Salvador, Bahia, Brazil, 2000 - 2006. METHODS The citys Information Zones, the unit of analysis used in this study, were grouped into strata reflecting high, intermediate, low and very low living conditions, based on a living conditions index (LCI). Neonatal mortality rates were calculated for each stratum. Spearmans correlation, linear regression and relative risks were used in the data analysis. RESULTS Neonatal mortality in Salvador was found to be associated with living conditions, with risks of 53, 56 and 59% greater, respectively, in the intermediate, low and very low strata, when compared to the high living conditions stratum. Only the intermediate living conditions stratum shows a significant decline in neonatal mortality (β = -0.93; p = 0.039). In the stratum of high living conditions, it was observed a stagnation of this mortality. CONCLUSIONS Poorer living conditions were associated to higher risks of neonatal mortality. The slight decline in social inequalities, found in neonatal mortality, was due to a decline in the intermediate living conditions stratum. Although dependent on the access to quality healthcare services and life support technologies, a more consistent reduction in the neonatal mortality and its associated inequalities will only be achieved when broader-reaching public policies are implemented, improving the living conditions, and mainly focusing on priority groups.

Prevalence and factors associated with latent tuberculosis infection in an indigenous population in the Brazilian Amazon.

INTRODUCTION Recent studies have shown a high incidence and prevalence of latent tuberculosis infection (LTBI) in indigenous populations around the World. We aimed to estimate the prevalence and annual risk of infection (ARI) as well as to identify factors associated with LTBI in an indigenous population from the Brazilian Amazon. METHODS We conducted a cross-sectional study in 2011. We performed tuberculin skin tests (TSTs), smears and cultures of sputum samples, and chest radiographs for individuals who reported cough for two or more weeks. Associations between LTBI (TST ≥5mm) and socio-demographic, clinical, and epidemiological characteristics were investigated using Poisson regression with robust variance. Prevalence ratio (PR) was used as the measure of association. RESULTS We examined 263 individuals. The prevalence of LTBI was 40.3%, and the ARI was 2.4%. Age ≥15 years [PR=5.5; 95% confidence interval (CI): 3.5-8.6], contact with tuberculosis (TB) patients (PR=3.8; 95% CI: 1.2-11.9), previous TB history (PR=1.4; 95% CI: 1.2-1.7), and presence of Bacillus Calmette-Guérin (BCG) scar (PR=1.9, 95% CI: 1.2-2.9) were associated with LTBI. CONCLUSIONS Although some adults may have been infected years prior, the high prevalence of infection and its strong association with age ≥15 years, history of TB, and recent contact with TB patients suggest that the TB transmission risk is high in the study area.

Does my patient have chronic Chagas disease? Development and temporal validation of a diagnostic risk score

INTRODUCTION With the globalization of Chagas disease, unexperienced health care providers may have difficulties in identifying which patients should be examined for this condition. This study aimed to develop and validate a diagnostic clinical prediction model for chronic Chagas disease. METHODS This diagnostic cohort study included consecutive volunteers suspected to have chronic Chagas disease. The clinical information was blindly compared to serological tests results, and a logistic regression model was fit and validated. RESULTS The development cohort included 602 patients, and the validation cohort included 138 patients. The Chagas disease prevalence was 19.9%. Sex, age, referral from blood bank, history of living in a rural area, recognizing the kissing bug, systemic hypertension, number of siblings with Chagas disease, number of relatives with a history of stroke, ECG with low voltage, anterosuperior divisional block, pathologic Q wave, right bundle branch block, and any kind of extrasystole were included in the final model. Calibration and discrimination in the development and validation cohorts (ROC AUC 0.904 and 0.912, respectively) were good. Sensitivity and specificity analyses showed that specificity reaches at least 95% above the predicted 43% risk, while sensitivity is at least 95% below the predicted 7% risk. Net benefit decision curves favor the model across all thresholds. CONCLUSIONS A nomogram and an online calculator (available at http://shiny.ipec.fiocruz.br:3838/pedrobrasil/chronic_chagas_disease_prediction/) were developed to aid in individual risk estimation.

Predictors of mortality in multidrug-resistant tuberculosis patients from Brazilian reference centers, 2005 to 2012

OBJECTIVES To determine the main predictors of death in multidrug-resistant (MDRTB) patients from Brazil. DESIGN Retrospective cohort study, a survival analysis of patients treated between 2005 and 2012. RESULTS Of 3802 individuals included in study, 64.7% were men, mean age was 39 (1-93) years, and 70.3% had bilateral pulmonary disease. Prevalence of human immunodeficiency virus (HIV) was 8.3%. There were 479 (12.6%) deaths. Median survival time was 1452 days (4 years). Factors associated with increased risk of death were age greater than or equal to 60 years (hazard rate [HR] = 1.6, confidence interval [CI] = 1.15-2.2), HIV co-infection (HR = 1.46; CI = 1.05-1.96), XDR resistance pattern (HR = 1.74, CI = 1.05-2.9), beginning of treatment after failure (HR = 1.72, CI = 1.27-2.32), drug abuse (HR = 1.64, CI = 1.22-2.2), resistance to ethambutol (HR = 1.30, CI = 1.06-1.6) or streptomycin (HR = 1.24, CI = 1.01-1.51). Mainly protective factors were presence of only pulmonary disease (HR = 0.57, CI = 0.35-0.92), moxifloxacin use (HR = 0.44, CI = 0.25-0.80), and levofloxacin use (HR = 0.75; CI = 0.60-0.94). CONCLUSION A more comprehensive approach is needed to manage MDRTB, addressing early diagnostic, improving adhesion, and comorbidities, mainly HIV infection and drug abuse. The latest generation quinolones have an important effect in improving survival in MDRTB.

Equivalência das reações cutâneas do PPD-Rt23 do Statens Seruminstitut e do PPD do Laboratório Pimenta Abreu

A tuberculina PPD Rt23 preparada pelo Statens Seruminstitut de Copenhague, foi desenvolvida e testada em uma ação conjunta desse instituto e da Organização Mundial de Saúde para que um produto padronizado e de alta qualidade fosse usado em todo o mundo (1) . Entretanto, nos últimos anos, tem surgido na literatura questionamentos quanto à potência do PPD Rt23, como sugerido no trabalho de pesquisadores coreanos (2) . Segundo argumentos apresentados por Haslov (3) o problema pode ocorrer quando se usam preparações locais a partir da diluição de concentrados do Rt23 como aconteceu no exemplo do México (4) . Nesse caso, o controle de qualidade dessas preparações passou a ser considerado uma questão estratégica