RESUMO
BACKGROUND: Depending on the presence of mutations that determine isoniazid (INH) susceptibility (katG and inhA), Mycobacterium tuberculosis may be susceptible to high doses of INH or ethionamide (ETH). OBJECTIVE: To describe the INH resistance profile and association of katG mutation with previous INH treatment and level of drug resistance based on rapid molecular drug susceptibility testing (DST) in southern Brazil and central Mozambique. DESIGN: Descriptive study of 311 isolates from Ribeirão Preto, São Paulo, Brazil (2011-2014) and 155 isolates from Beira, Mozambique (2014-2015). Drug resistance patterns and specific gene mutations were determined using GenoType(®) MTBDRplus. RESULTS: katG gene mutations were detected in 12/22 (54.5%) Brazilian and 32/38 (84.2%) Mozambican isolates. inhA mutations were observed in 9/22 (40.9%) isolates in Brazil and in 4/38 (10.5%) in Mozambique. Both katG and inhA mutations were detected in respectively 1/22 (5%) and 2/38 (5.2%). The difference in the frequency of katG mutations in Brazil and Mozambique was statistically significant (P = 0.04). katG mutations were present in 68.8% (33/48) of patients previously treated with INH and 31.2% (15/48) of patients without previous INH. This difference was not statistically significant (P = 0.223). CONCLUSION: INH mutations varied geographically; molecular DST can be used to guide and accelerate decision making in the use of ETH or high doses of INH.
Assuntos
Antituberculosos/uso terapêutico , Proteínas de Bactérias/genética , Catalase/genética , Análise Mutacional de DNA , Farmacorresistência Bacteriana Múltipla/genética , Etionamida/uso terapêutico , Isoniazida/uso terapêutico , Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Oxirredutases/genética , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Brasil/epidemiologia , Tomada de Decisão Clínica , Humanos , Testes de Sensibilidade Microbiana , Moçambique/epidemiologia , Mycobacterium tuberculosis/genética , Seleção de Pacientes , Valor Preditivo dos Testes , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologiaRESUMO
Resistance to Mycobacterium tuberculosis is a reality worldwide, and its diagnosis continues to be difficult and time consuming. To face this challenge, the World Health Organization has recommended the use of rapid molecular tests. We evaluated the routine use (once a week) of a line probe assay (Genotype MTBDRplus) for early diagnosis of resistance and for assessment of the main related risk factors over 2 years. A total of 170 samples were tested: 15 (8.8%) were resistant, and multidrug resistance was detected in 10 (5.9%). The sensitivity profile took 3 weeks (2 weeks for culture and 1 week for rapid testing). Previous treatment for tuberculosis and the persistence of positive acid-fast smears after 4 months of supervised treatment were the major risk factors observed. The use of molecular tests enabled early diagnosis of drug-resistant bacilli and led to appropriate treatment of the disease. This information has the potential to interrupt the transmission chain of resistant M. tuberculosis.
Assuntos
DNA Bacteriano/genética , Técnicas de Genotipagem/métodos , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Adulto , Antituberculosos/farmacologia , Técnicas Bacteriológicas/métodos , Brasil , Diagnóstico Precoce , Feminino , Humanos , Isoniazida/farmacologia , Masculino , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Rifampina/farmacologia , Fatores de Risco , Sensibilidade e Especificidade , Tuberculose Resistente a Múltiplos Medicamentos/microbiologiaRESUMO
The generation and maintenance of memory antibody response by different primary immunization schedules with the Cuban-produced outer membrane protein based vaccine was investigated in a murine model. We analyzed the duration of the antibody response (IgG-ELISA and bactericidal titer) and the effect of a booster dose on the antibody response. The IgG avidity index was determined in an attempt to find a marker for memory development. This study also included an analysis of IgG subclasses induced by primary and booster immunization. The specificity of bactericidal antibodies was investigated using local strains of the same serotype/serosubtype (4,7:P1.19,15) as the vaccine strain and mutant strains lacking major outer membrane proteins. A significant recall response was induced by a booster dose given 7 months after a primary series of 2, 3 or 4 doses of vaccine. The primary antibody response showed a positive dose-effect. In contrast, a negative dose-effect was found on the booster bactericidal antibody response. There was a significant increase in IgG1 levels after the fourth and booster doses. Three doses of vaccine were required to induce a significant increase in IgG avidity. Two injections of vaccine induced a significant antibody response to PorA protein, while 4 injections induced a larger range of specificities.