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BACKGROUND: One of the three main targets of the World Health Organization (WHO) End TB Strategy (2015-2035) is that no tuberculosis (TB) patients or their households face catastrophic costs (defined as exceeding 20% of the annual household income) because of the disease. Our study seeks to determine, as a baseline, the magnitude and main drivers of the costs associated with TB disease for patients and their households and to monitor the proportion of households experiencing catastrophic costs in Brazil. METHODS: A national cross-sectional cluster-based survey was conducted in Brazil in 2019-2021 following WHO methodology. TB patients of all ages and types of TB were eligible for the survey. Adult TB patients and guardians of minors (<18 years old) were interviewed once about costs, time loss, coping measures, income, household expenses, and asset ownership. Total costs, including indirect costs measured as reported household income change, were expressed as a percentage of annual household income. We used descriptive statistics to analyze the cost drivers and multivariate logistic regression to determine factors associated with catastrophic costs. RESULTS: We interviewed 603 patients, including 538 (89%) with drug-sensitive (DS) and 65 (11%) with drug-resistant (DR) TB. Of 603 affected households, 48.1% (95%CI: 43-53.2) experienced costs above 20% of their annual household income during their TB episode. The proportion was 44.4% and 78.5% among patients with DS- and DR-TB, respectively. On average, patients incurred costs of US$1573 (95%CI: 1361.8-1785.0) per TB episode, including pre-diagnosis and post-diagnosis expenses. Key cost drivers were post-diagnosis nutritional supplements (US$317.6, 95%CI: 232.7-402.6) followed by medical costs (US$85.5, 95%CI: 54.3-116.5) and costs of travel for clinic visits during treatment (US$79.2, 95%CI: 61.9-96.5). In multivariate analysis, predictors of catastrophic costs included positive HIV status (aOR = 3.0, 95%CI:1.1-8.6) and self-employment (aOR = 2.7, 95%CI:1.1-6.5); high education was a protective factor (aOR = 0.1, 95%CI:0.0-0.9). CONCLUSIONS: Although the services offered to patients with TB are free of charge in the Brazilian public health sector, the availability of free diagnosis and treatment services does not alleviate patients' financial burden related to accessing TB care. The study allowed us to identify the costs incurred by patients and suggest actions to mitigate their suffering. In addition, this study established a baseline for monitoring catastrophic costs and fostering a national policy to reduce the costs to patients for TB care in Brazil.
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Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Adulto , Humanos , Adolescente , Brasil/epidemiología , Estrés Financiero , Estudios Transversales , Tuberculosis/epidemiología , Costos y Análisis de Costo , RentaRESUMEN
BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a serious global public health concern associated with social vulnerability. In Brazil, the Unified Health System (SUS, Portuguese) provides free diagnosis and treatment for MDR-TB; however, other expenses may still be incurred for patients and their families which, according to the World Health Organization (WHO), can be catastrophic when these costs surpass 20.0% of the annual household income. This study aimed to assess the extent of catastrophic costs related to the diagnostic and therapeutic aspects of MDR-TB among patients receiving care at an outpatient clinic in Rio de Janeiro. METHODS: This prospective study used convenience sampling from July 2019 to June 2021. Data regarding direct and indirect costs were collected using a standardized questionnaire endorsed by the WHO. To analyze any impoverishment occurred from MDR-TB, a threshold established by the Brazilian Institute of Geography and Statistics for 2019 and 2020 of US$ 79,562 and US$ 94,5273, respectively, was applied. Descriptive statistics were used for data analysis, including mean; standard deviation; variation coefficient; median; and maximum, minimum, and interquartile ranges. RESULTS: A total of 65 patients were interviewed. Among the participants, 73.8% experienced catastrophic costs, with indirect costs exerting the most significant impact (median: US$ 3,825.9), in contrast to direct costs (median: US$ 542.7). When comparing the periods before and after diagnosis, the prevalence of poverty increased from 12.0% to 28.0%. CONCLUSIONS: Despite the support from the SUS in Brazil, diagnostic and therapeutic cascades incur additional costs, exacerbating social vulnerability among patients with MDR-TB.
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Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Brasil/epidemiología , Estudios Prospectivos , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Pobreza , Instituciones de Atención AmbulatoriaRESUMEN
ABSTRACT Background: Multidrug-resistant tuberculosis (MDR-TB) is a serious global public health concern associated with social vulnerability. In Brazil, the Unified Health System (SUS, Portuguese) provides free diagnosis and treatment for MDR-TB; however, other expenses may still be incurred for patients and their families which, according to the World Health Organization (WHO), can be catastrophic when these costs surpass 20.0% of the annual household income. This study aimed to assess the extent of catastrophic costs related to the diagnostic and therapeutic aspects of MDR-TB among patients receiving care at an outpatient clinic in Rio de Janeiro. Methods: This prospective study used convenience sampling from July 2019 to June 2021. Data regarding direct and indirect costs were collected using a standardized questionnaire endorsed by the WHO. To analyze any impoverishment occurred from MDR-TB, a threshold established by the Brazilian Institute of Geography and Statistics for 2019 and 2020 of US$ 79,562 and US$ 94,5273, respectively, was applied. Descriptive statistics were used for data analysis, including mean; standard deviation; variation coefficient; median; and maximum, minimum, and interquartile ranges. Results: A total of 65 patients were interviewed. Among the participants, 73.8% experienced catastrophic costs, with indirect costs exerting the most significant impact (median: US$ 3,825.9), in contrast to direct costs (median: US$ 542.7). When comparing the periods before and after diagnosis, the prevalence of poverty increased from 12.0% to 28.0%. Conclusions: Despite the support from the SUS in Brazil, diagnostic and therapeutic cascades incur additional costs, exacerbating social vulnerability among patients with MDR-TB.
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OBJECTIVE: To analyze the association of dysglycemia with clinical, laboratory, and radiographic characteristics of patients with pulmonary tuberculosis (PTB), as well as with their tuberculosis treatment outcomes. METHODS: This was a longitudinal study involving 140 patients diagnosed with PTB (positive cultures for Mycobacterium tuberculosis or positive Xpert MTB/RIF results from sputum samples). Patients were evaluated at diagnosis (M0), after completing the second month of treatment (M2), and at the end of treatment (MEND). At M0, the patients were classified into three groups: normoglycemia+PTB (NGTB); pre-diabetes mellitus+PTB (PDMTB), and diabetes mellitus+PTB (DMTB), in accordance with glycated hemoglobin levels (< 5.7%, 5.7%-6.4%, and ≥ 6.5%, respectively). Treatment outcomes were classified as favorable (cure or treatment completion) and unfavorable (death, loss to follow-up, or treatment failure). RESULTS: In our sample, 76 patients (61.4%) had dysglycemia, 20 of whom (14.3%) had DM at M0. The patients with dysglycemia, in comparison with those in the NGTB group, more frequently presented with positive sputum smear microscopy (94.2% vs. 75.9%; p = 0.003); cavities (80.2% vs. 63.0%; p = 0.03); bilateral lesions (67.4% vs. 46.0%; p = 0.02); and higher median of affected thirds of the lungs (3.0 vs. 2.0; p = 0.03) on chest radiography. No significant differences regarding outcomes were found among the groups, but tuberculosis lethality was higher in the DMTB group than in the PDMTB and NGTB groups (20% vs. 2.2%). CONCLUSIONS: PTB patients with dysglycemia had laboratory and radiographic manifestations indicative of more advanced disease, and the risk of death was higher in the DMTB group. These findings reinforce the recommendation for early screening for DM in patients with newly diagnosed tuberculosis in order to reduce the risk of death during treatment.
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Tuberculosis Pulmonar , Tuberculosis , Humanos , Estudios Longitudinales , Tuberculosis Pulmonar/diagnóstico por imagen , Tuberculosis Pulmonar/tratamiento farmacológico , Laboratorios Clínicos , Resultado del TratamientoRESUMEN
ABSTRACT Objective: To analyze the association of dysglycemia with clinical, laboratory, and radiographic characteristics of patients with pulmonary tuberculosis (PTB), as well as with their tuberculosis treatment outcomes. Methods: This was a longitudinal study involving 140 patients diagnosed with PTB (positive cultures for Mycobacterium tuberculosis or positive Xpert MTB/RIF results from sputum samples). Patients were evaluated at diagnosis (M0), after completing the second month of treatment (M2), and at the end of treatment (MEND). At M0, the patients were classified into three groups: normoglycemia+PTB (NGTB); pre-diabetes mellitus+PTB (PDMTB), and diabetes mellitus+PTB (DMTB), in accordance with glycated hemoglobin levels (< 5.7%, 5.7%-6.4%, and ≥ 6.5%, respectively). Treatment outcomes were classified as favorable (cure or treatment completion) and unfavorable (death, loss to follow-up, or treatment failure). Results: In our sample, 76 patients (61.4%) had dysglycemia, 20 of whom (14.3%) had DM at M0. The patients with dysglycemia, in comparison with those in the NGTB group, more frequently presented with positive sputum smear microscopy (94.2% vs. 75.9%; p = 0.003); cavities (80.2% vs. 63.0%; p = 0.03); bilateral lesions (67.4% vs. 46.0%; p = 0.02); and higher median of affected thirds of the lungs (3.0 vs. 2.0; p = 0.03) on chest radiography. No significant differences regarding outcomes were found among the groups, but tuberculosis lethality was higher in the DMTB group than in the PDMTB and NGTB groups (20% vs. 2.2%). Conclusions: PTB patients with dysglycemia had laboratory and radiographic manifestations indicative of more advanced disease, and the risk of death was higher in the DMTB group. These findings reinforce the recommendation for early screening for DM in patients with newly diagnosed tuberculosis in order to reduce the risk of death during treatment.
RESUMO Objetivo: Analisar a associação de disglicemia e características clínicas, laboratoriais e radiográficas em pacientes com tuberculose pulmonar (TBP), bem como a associação de disglicemia e desfechos do tratamento da tuberculose. Métodos: Estudo longitudinal com 140 pacientes com diagnóstico de TBP (culturas de escarro positivas para Mycobacterium tuberculosis ou resultados positivos do teste Xpert MTB/RIF em amostras de escarro). Os pacientes foram avaliados no momento do diagnóstico (M0), após dois meses de tratamento (M2) e no fim do tratamento (MFIM). Em M0, os pacientes foram divididos em três grupos: normoglicemia+TBP (NGTB); pré-diabetes mellitus+TBP (PDMTB) e diabetes mellitus+TBP (DMTB), de acordo com os níveis de hemoglobina glicada (< 5,7%, 5,7%-6,4% e ≥ 6,5%, respectivamente). Os desfechos do tratamento foram classificados em favoráveis (cura ou conclusão do tratamento) e desfavoráveis (óbito, perda de seguimento ou falência do tratamento). Resultados: Em nossa amostra, 76 pacientes (61,4%) apresentavam disglicemia, 20 (14,3%) dos quais apresentavam DM em M0. Os pacientes com disglicemia, em comparação com os do grupo NGTB, apresentaram mais frequentemente baciloscopia de escarro positiva (94,2% vs. 75,9%; p = 0,003); cavidades (80,2% vs. 63,0%; p = 0,03); lesões bilaterais (67,4% vs. 46,0%; p = 0,02) e maior mediana de terços pulmonares acometidos (3,0 vs. 2,0; p = 0,03) na radiografia de tórax. Não foram observadas diferenças significativas entre os grupos quanto aos desfechos, mas a letalidade da tuberculose foi maior no grupo DMTB do que nos grupos PDMTB e NGTB (20% vs. 2,2%). Conclusões: Pacientes com TBP e disglicemia apresentaram manifestações laboratoriais e radiográficas indicativas de doença mais avançada, e o risco de óbito foi maior no grupo DMTB. Esses achados reforçam a recomendação de detecção precoce de DM em pacientes com tuberculose recém-diagnosticada, a fim de reduzir o risco de óbito durante o tratamento.
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The aim of this study was to evaluate the concordance between two versions of the scoring system (2011 and 2019), recommended by the Brazilian Ministry of Health, for the diagnosis of pulmonary tuberculosis (PTB) in children and adolescents. A retrospective descriptive study was performed to assess the medical records of children and adolescents with PTB, in TB units from Brazilian cities located in Rio de Janeiro, Minas Gerais, and Parana States, from January 1 st , 2004, to December 1 st , 2018. Patients aged 0 to 18 years old with a diagnosis of PTB were included. The comparison between the two scoring systems showed a moderate concordance according to the κ coefficient value = 0.625. Fourteen patients showed a reduction in the TB score, going from 30 points in the 2011, to 25 points or less in the 2019 one. Seventy one percent of these 14 patients had radiological changes suggestive of PTB and 86% had tuberculin skin tests greater than 10 mm. The study concluded that a moderate agreement was observed between the 2011 and 2019 scoring systems, with an increase in the number of patients scoring 25 points or less in 2019, which can eventually hinder the diagnosis of PTB.
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Tuberculosis Pulmonar , Adolescente , Brasil/epidemiología , Niño , Preescolar , Ciudades , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos , Prueba de Tuberculina , Tuberculosis Pulmonar/diagnósticoRESUMEN
The epidemiological relevance of tuberculosis is directly related to the socioeconomic profile of a given country. Vulnerability to tuberculosis is influenced by biological factors (e.g., malnutrition, HIV infection, and age) and social factors (e.g., unhealthy housing, high population density, inappropriate working conditions, and lack of access to health services). In many cases, multiple vulnerabilities occur in conjunction. We propose here a reflection on tuberculosis from the point of view of the social determinants of health, as well as the costs associated with its diagnosis and treatment in Brazil, based not only on data in the international literature but also on evidence related to the national context. Given the magnitude of tuberculosis as a socially mediated disease, there is an evident need for greater involvement of health professionals and of the scientific community to implement relevant operational and research measures to understand the social conditions influencing the health-illness continuum for tuberculosis patients. Although the recent economic crisis in Brazil has contributed to increased mortality from all causes, including tuberculosis, health and social protection expenditures have mitigated detrimental health effects. The evidence presented here underscores the importance of public social protection policies for minimizing the effects of tuberculosis indicators, with the aim of eliminating tuberculosis in Brazil.
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Enfermedad Catastrófica/economía , Atención a la Salud/economía , Determinantes Sociales de la Salud , Tuberculosis/economía , Antituberculosos/uso terapéutico , Brasil/epidemiología , Costo de Enfermedad , Costos y Análisis de Costo , Costos de la Atención en Salud , Humanos , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiologíaRESUMEN
AIM: To evaluate the clinical characteristics, diagnostic approach, and treatment outcomes of tuberculosis (TB) in children living in a high-burden metropolitan area. METHODS: This was a retrospective study, based on a medical chart review, involving children under 15 years old treated for TB between 2007 and 2016, in four primary health units (PHU) and three reference centers (RC) in five cities of Rio de Janeiro metropolitan area. Factors associated with TB treatment setting, microbiological diagnosis, and treatment outcomes were evaluated. RESULTS: A total of 544 children were enrolled; 71% were treated in PHU, 36% were under 5 years old, and 72% had pulmonary TB (PTB). The HIV prevalence was 10% (31/322). Fifty-three percent had at least one microbiological test for TB, 68% of them (196/287) had TB confirmed. Among 222 children with previous TB contact, information on LTBI was available for 78 (35%), and only 17% (13/78) were treated. Extrapulmonary TB (56% vs 32%), microbiologically confirmed TB (77% vs 60%), and HIV positivity (18.5% vs 4.0%) were significantly more frequent in RC. Treatment in RC (odds ratio (OR) 3.08, 95% confidence interval (CI) 1.74-5.44) and PTB (OR 2.47, 95% CI 1.34-4.56) were independently associated with a microbiological diagnosis of TB. The treatment success rate was 85%. In the logistic regression analysis, HIV-infected children had a 2.5-fold higher risk of an unfavorable outcome (OR 2.53, 95% CI 1.0-6.38; p = 0.05). CONCLUSIONS: Opportunities for TB prevention and early TB treatment are missed due to suboptimal close contact screening. Microbiological diagnosis of TB and drug susceptibility testing in children should be made available through more sensitive and accessible tests.
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Tuberculosis Pulmonar/epidemiología , Adolescente , Antituberculosos/uso terapéutico , Brasil/epidemiología , Niño , Preescolar , Ciudades/estadística & datos numéricos , Femenino , Infecciones por VIH/epidemiología , Humanos , Lactante , Masculino , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Mycobacterium tuberculosis/fisiología , Prevalencia , Estudios Retrospectivos , Resultado del Tratamiento , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiologíaRESUMEN
Tuberculosis (TB) remains a significant public health challenge, motivated by the diversity of healthcare epidemiological settings, as other factors. Cost-effective screening has substantial importance for TB control, demanding new diagnostic tools. This paper proposes a decision support tool (DST) for screening pulmonary TB (PTB) patients at a secondary clinic. The DST is composed of an adaptive resonance model (iART) for risk group identification (low, medium and high) and a multilayer perceptron (MLP) neural network for classifying patients as active or inactive PTB. Our tool attains an overall sensitivity (SE) and specificity (SP) of 92% (95% CI; 79-97) and 58% (95% CI; 47-68), respectively. SE values for smear-positive and smear-negative patients are 96% (95% CI; 80-99) and 82% (95% CI; 52-95), as well as higher than 83% (95% CI; 43-97) in low and high-risk cases. Even in scenarios with prevalence up to 20%, negative predictive values superior to 95% are obtained. The proposed DST provides a quick and low-cost pretest for presumptive PTB patients, which is useful to guide confirmatory testing and patient management, especially in settings with limited resources in low and middle-incoming countries.
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Técnicas Bacteriológicas , Sistemas de Apoyo a Decisiones Clínicas , Técnicas de Apoyo para la Decisión , Pulmón/microbiología , Tamizaje Masivo/métodos , Mycobacterium tuberculosis/aislamiento & purificación , Redes Neurales de la Computación , Tuberculosis Pulmonar/diagnóstico , Adulto , Brasil/epidemiología , Bases de Datos Factuales , Diagnóstico por Computador , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Esputo/microbiología , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/microbiología , Adulto JovenRESUMEN
BACKGROUND: The use of liquid medium (MGIT960) for tuberculosis (TB) diagnosis was recommended by WHO in 2007. However, there has been no evaluation of its effectiveness on clinically important outcomes. METHODS AND FINDINGS: A pragmatic trial was carried out in a tertiary hospital and a secondary health care unit in Rio de Janeiro City, Brazil. Participants were 16 years or older, suspected of having TB. They were excluded if only cerebral spinal fluid or blood specimens were available for analysis. MGIT960 technique was compared with the Lowenstein-Jensen (LJ) method for laboratory diagnosis of active TB. Primary outcome was the proportion of patients who had their initial medical management changed within 2 months after randomisation. Secondary outcomes were: mean time for changing the procedure, patient satisfaction with the overall treatment and adverse events. Data were analysed by intention-to-treat. Between April 2008 and September 2011, 693 patients were enrolled (348 to MGIT, 345 to LJ). Smear and culture results were positive for 10% and 15.7% of participants, respectively. Patients in the MGIT arm had their initial medical management changed more frequently than those in the LJ group (10.1% MGIT vs 3.8% LJ, RR 2.67 95% CI 1.44-.96, p = 0.002, NNT 16, 95% CI 10-39). Mean time for changing the initial procedure was greater in LJ group at both sites: 20.0 and 29.6 days in MGIT group and 52.2 and 64.3 in LJ group (MD 33.5, 95% CI 30.6-36.4, p = 0.0001). No other important differences were observed. CONCLUSIONS: This study suggests that opting for the MGIT960 system for TB diagnosis provides a promising case management model for improving the quality of care and control of TB. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN79888843.
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Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis/diagnóstico , Adolescente , Adulto , Antituberculosos/uso terapéutico , Técnicas Bacteriológicas , Brasil , Femenino , Humanos , Masculino , Persona de Mediana Edad , Juego de Reactivos para Diagnóstico , Atención Secundaria de Salud , Atención Terciaria de Salud , Tuberculosis/tratamiento farmacológico , Tuberculosis/microbiología , Adulto JovenRESUMEN
In view of the fact that the World Health Organization has recommended the use of the mycobacteria growth indicator tube (MGIT) 960 system for the diagnosis of tuberculosis and that there is as yet no evidence regarding the clinical impact of its use in health care systems, we conducted a pragmatic clinical trial to evaluate the clinical performance and cost-effectiveness of the use of MGIT 960 at two health care facilities in the city of Rio de Janeiro, Brazil, where the incidence of tuberculosis is high. Here, we summarize the methodology and preliminary results of the trial. (ISRCTN.org Identifier: ISRCTN79888843 [http://isrctn.org/]) In view of the fact that the World Health Organization has recommended the use of the mycobacteria growth indicator tube (MGIT) 960 system for the diagnosis of tuberculosis and that there is as yet no evidence regarding the clinical impact of its use in health care systems, we conducted a pragmatic clinical trial to evaluate the clinical performance and cost-effectiveness of the use of MGIT 960 at two health care facilities in the city of Rio de Janeiro, Brazil, where the incidence of tuberculosis is high. Here, we summarize the methodology and preliminary results of the trial. (ISRCTN.org Identifier: ISRCTN79888843 [http://isrctn.org/]).
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Pruebas Diagnósticas de Rutina/métodos , Instituciones de Salud , Técnicas Microbiológicas/métodos , Mycobacterium tuberculosis/crecimiento & desarrollo , Sector Público , Tuberculosis/diagnóstico , Brasil , Medios de Cultivo , Humanos , Salud PúblicaRESUMEN
In view of the fact that the World Health Organization has recommended the use of the mycobacteria growth indicator tube (MGIT) 960 system for the diagnosis of tuberculosis and that there is as yet no evidence regarding the clinical impact of its use in health care systems, we conducted a pragmatic clinical trial to evaluate the clinical performance and cost-effectiveness of the use of MGIT 960 at two health care facilities in the city of Rio de Janeiro, Brazil, where the incidence of tuberculosis is high. Here, we summarize the methodology and preliminary results of the trial. (ISRCTN.org Identifier: ISRCTN79888843 [http://isrctn.org/]).
Em razão da recomendação da Organização Mundial da Saúde sobre o uso do sistema mycobacteria growth indicator tube (MGIT) 960 para o diagnóstico de tuberculose e da falta de evidências sobre o impacto clínico de sua incorporação em sistemas de saúde, um ensaio clínico pragmático está sendo conduzido para avaliar o desempenho clínico e a relação custo-efetividade do MGIT 960 em duas unidades do Sistema Único de Saúde na cidade do Rio de Janeiro, que tem uma elevada incidência de tuberculose. Apresentamos aqui, de forma sintética, o método e resultados preliminares do ensaio. (ISRCTN.org Identifier: ISRCTN79888843 [http://isrctn.org/]).
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Humanos , Pruebas Diagnósticas de Rutina/métodos , Instituciones de Salud , Técnicas Microbiológicas/métodos , Mycobacterium tuberculosis/crecimiento & desarrollo , Sector Público , Tuberculosis/diagnóstico , Brasil , Medios de Cultivo , Salud PúblicaRESUMEN
Isoniazid (INH), one of the most important drugs used in antituberculosis (anti-TB) treatment, is also the major drug involved in hepatotoxicity. Differences in INH-induced toxicity have been attributed to genetic variability at several loci, such as NAT2, CYP2E1, GSTM1 and GSTT1, that code for drug-metabolising enzymes. Our goal was to examine the polymorphisms in these enzymes as susceptibility factors to anti-TB drug-induced hepatitis in Brazilian individuals. In a case-control design, 167 unrelated active tuberculosis patients from the University Hospital of the Federal University of Rio de Janeiro, Brazil, were enrolled in this study. Patients with a history of anti-TB drug-induced acute hepatitis (cases with an increase to 3 times the upper limit of normal serum transaminases and symptoms of hepatitis) and patients with no evidence of anti-TB hepatic side effects (controls) were genotyped for NAT2, CYP2E1, GSTM1 and GSTT1 polymorphisms. Slow acetylators had a higher incidence of hepatitis than intermediate/rapid acetylators [22% (18/82) vs. 9.8% (6/61), odds ratio (OR), 2.86, 95% confidence interval (CI), 1.06-7.68, p = 0.04). Logistic regression showed that slow acetylation status was the only independent risk factor (OR 3.59, 95% CI, 2.53-4.64, p = 0.02) for the occurrence of anti-TB drug-induced hepatitis during anti-TB treatment with INH-containing schemes in Brazilian individuals.
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Antituberculosos/efectos adversos , Arilamina N-Acetiltransferasa/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Citocromo P-450 CYP2E1/genética , Glutatión Transferasa/genética , Isoniazida/efectos adversos , Polimorfismo Genético , Acetilación , Adulto , Brasil/etnología , Estudios de Casos y Controles , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Factores de Riesgo , Tuberculosis Pulmonar/tratamiento farmacológicoRESUMEN
Isoniazid (INH), one of the most important drugs used in antituberculosis (anti-TB) treatment, is also the major drug involved in hepatotoxicity. Differences in INH-induced toxicity have been attributed to genetic variability at several loci, such as NAT2, CYP2E1, GSTM1 and GSTT1, that code for drug-metabolising enzymes. Our goal was to examine the polymorphisms in these enzymes as susceptibility factors to anti-TB drug-induced hepatitis in Brazilian individuals. In a case-control design, 167 unrelated active tuberculosis patients from the University Hospital of the Federal University of Rio de Janeiro, Brazil, were enrolled in this study. Patients with a history of anti-TB drug-induced acute hepatitis (cases with an increase to 3 times the upper limit of normal serum transaminases and symptoms of hepatitis) and patients with no evidence of anti-TB hepatic side effects (controls) were genotyped for NAT2, CYP2E1, GSTM1 and GSTT1 polymorphisms. Slow acetylators had a higher incidence of hepatitis than intermediate/rapid acetylators [22 percent (18/82) vs. 9.8 percent (6/61), odds ratio (OR), 2.86, 95 percent confidence interval (CI), 1.06-7.68, p = 0.04). Logistic regression showed that slow acetylation status was the only independent risk factor (OR 3.59, 95 percent CI, 2.53-4.64, p = 0.02) for the occurrence of anti-TB drug-induced hepatitis during anti-TB treatment with INH-containing schemes in Brazilian individuals.