RESUMO
CONTEXT: Fixed-dose combinations (FDCs) of drugs for treatment of tuberculosis have been advocated to prevent the emergence of drug resistance. OBJECTIVE: To assess the efficacy and safety of a 4-drug FDC for the treatment of tuberculosis. DESIGN, SETTING, AND PATIENTS: The Study C trial, a parallel-group, open-label, noninferiority, randomized controlled trial conducted in 11 sites in Africa, Asia, and Latin America between 2003 and 2008. Patients were 1585 adults with newly diagnosed smear-positive pulmonary tuberculosis. INTERVENTIONS: Patients were randomized to receive daily treatment with 4 drugs (rifampicin, isoniazid, pyrazinamide, ethambutol) given as an FDC (n = 798 patients) or separately (n = 787) in the 8-week intensive phase of treatment. MAIN OUTCOME MEASURE: Favorable treatment outcome, defined as negative culture result at 18 months post randomization and not having already been classified as unfavorable. Noninferiority was dependent on consistent results from a per-protocol and modified intention-to-treat analysis, using 2 different models for the latter, classifying all changes of treatment or refusal to continue treatment (eg, bacteriological failure/relapse, adverse event, default, drug resistance) as unfavorable (model 1) and classifying changes of treatment for reasons other than therapeutic outcomes according to their 18-month bacteriological outcome if available (post hoc model 2). The prespecified noninferiority margin was 4%. RESULTS: In the per-protocol analysis, 555 of 591 patients (93.9%) had a favorable outcome in the FDC group vs 548 of 579 (94.6%) in the separate-drugs group (risk difference, -0.7% [90% confidence interval {CI}, -3.0% to 1.5%]). In the model 1 analysis, 570 of 684 patients (83.3%) had a favorable outcome in the FDC group vs 563 of 664 (84.8%) in the separate-drugs group (risk difference, -1.5% [90% CI, -4.7% to 1.8%]). In the post hoc model 2 analysis, 591 of 658 patients (89.8%) in the FDC group and 589 of 647 (91.0%) in the separate-drugs group had a favorable outcome (risk difference, -1.2% [90% CI, -3.9% to 1.5%]). Adverse events related to trial drugs were similarly distributed among treatment groups. CONCLUSIONS: Compared with a regimen of separately administered drugs, a 4-drug FDC regimen for treatment of tuberculosis satisfied prespecified noninferiority criteria in 2 of 3 analyses. Although the results do not demonstrate full noninferiority of the FDCs compared with single drugs given separately using the strict definition applied in this trial, use of FDCs is preferred because of potential advantages associated with the administration of FDCs compared with separate-drug formulations. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00216333.
Assuntos
Antituberculosos/administração & dosagem , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Antituberculosos/efeitos adversos , Quimioterapia Combinada , Etambutol/administração & dosagem , Etambutol/efeitos adversos , Feminino , Humanos , Isoniazida/administração & dosagem , Isoniazida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pirazinamida/administração & dosagem , Pirazinamida/efeitos adversos , Rifampina/administração & dosagem , Rifampina/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
Using geographic information system and molecular tools, we characterized a possible outbreak of tuberculosis caused by Mycobacterium tuberculosis Beijing strain in 17 patients in Cotonou, Benin, during July 2005-October 2006. Most patients lived or worked in the same area and frequented the same local drinking bar. The isolates were streptomycin resistant.
Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/genética , Estreptomicina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/epidemiologia , Benin/epidemiologia , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Surtos de Doenças , Feminino , Predisposição Genética para Doença , Soropositividade para HIV/complicações , Soropositividade para HIV/epidemiologia , Humanos , Masculino , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/genética , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/genéticaRESUMO
We report 3 patients with laboratory-confirmed Buruli ulcer in Kafufu/Luremo, Angola, and Kasongo-Lunda, Democratic Republic of Congo. These villages are near the Kwango/Cuango River, which flows through both countries. Further investigation of artisanal alluvial mining as a risk factor for Buruli ulcer is recommended.
Assuntos
Úlcera de Buruli/diagnóstico , Úlcera de Buruli/epidemiologia , Reservatórios de Doenças/microbiologia , Mycobacterium ulcerans , Adolescente , Adulto , Angola/epidemiologia , Antibióticos Antituberculose/uso terapêutico , Biópsia , Úlcera de Buruli/tratamento farmacológico , Úlcera de Buruli/patologia , República Democrática do Congo/epidemiologia , Diamante , Feminino , Humanos , Masculino , Mineração , Rifampina/uso terapêutico , Fatores de Risco , Rios , Pele/microbiologia , Pele/patologia , Estreptomicina/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: To report the experience of Benin, where Buruli ulcer (BU) is endemic, in the implementation of diagnostic laboratory services. METHODS AND RESULTS: There has been a gradual introduction of biologic diagnostic activities for BU comprising (1) training of a laboratory technician in a highly experienced reference laboratory; (2) acquiring indispensable laboratory start-up materials; (3) progressive development of diagnostic laboratory activities; (4) regular external quality assessment with an experienced reference laboratory and (5) decentralization of activities to various clinical diagnostic and treatment centres for BU in Benin. CONCLUSION: Setting up a reference laboratory for BU is a continuous process, which necessitates motivated personnel and the cooperation of an experienced external reference laboratory.