RESUMO
OBJECTIVE: To evaluate the impact of smoking on pulmonary tuberculosis (PTB) treatment outcomes and the two-month conversion rates for Mycobacterium tuberculosis sputum cultures among patients with culture-confirmed PTB in an area with a moderate incidence of tuberculosis in Brazil. METHODS: This was a retrospective cohort study of PTB patients diagnosed and treated at the Thoracic Diseases Institute of the Federal University of Rio de Janeiro between 2004 and 2012. RESULTS: Of the 298 patients diagnosed with PTB during the study period, 174 were included in the outcome analysis: 97 (55.7%) were never-smokers, 31 (17.8%) were former smokers, and 46 (26.5%) were current smokers. Smoking was associated with a delay in sputum culture conversion at the end of the second month of TB treatment (relative risk = 3.58 &091;95% CI: 1.3-9.86&093;; p = 0.01), as well as with poor treatment outcomes (relative risk = 6.29 &091;95% CI: 1.57-25.21&093;; p = 0.009). The association between smoking and a positive culture in the second month of treatment was statistically significant among the current smokers (p = 0.027). CONCLUSIONS: In our sample, the probability of a delay in sputum culture conversion was higher in current smokers than in never-smokers, as was the probability of a poor treatment outcome.
Assuntos
Mycobacterium tuberculosis/isolamento & purificação , Fumar/efeitos adversos , Escarro/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Antituberculosos/uso terapêutico , Brasil , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Tuberculose Pulmonar/microbiologiaRESUMO
ABSTRACT Objective: To evaluate the impact of smoking on pulmonary tuberculosis (PTB) treatment outcomes and the two-month conversion rates for Mycobacterium tuberculosis sputum cultures among patients with culture-confirmed PTB in an area with a moderate incidence of tuberculosis in Brazil. Methods: This was a retrospective cohort study of PTB patients diagnosed and treated at the Thoracic Diseases Institute of the Federal University of Rio de Janeiro between 2004 and 2012. Results: Of the 298 patients diagnosed with PTB during the study period, 174 were included in the outcome analysis: 97 (55.7%) were never-smokers, 31 (17.8%) were former smokers, and 46 (26.5%) were current smokers. Smoking was associated with a delay in sputum culture conversion at the end of the second month of TB treatment (relative risk = 3.58 &091;95% CI: 1.3-9.86&093;; p = 0.01), as well as with poor treatment outcomes (relative risk = 6.29 &091;95% CI: 1.57-25.21&093;; p = 0.009). The association between smoking and a positive culture in the second month of treatment was statistically significant among the current smokers (p = 0.027). Conclusions: In our sample, the probability of a delay in sputum culture conversion was higher in current smokers than in never-smokers, as was the probability of a poor treatment outcome.
RESUMO Objetivo: Avaliar o impacto do tabagismo no desfecho do tratamento da tuberculose pulmonar (TBP) e na taxa de conversão da cultura de Mycobacterium tuberculosis no escarro ao final do segundo mês de tratamento em pacientes com TBP confirmada por cultura em um local com incidência de tuberculose moderada no Brasil. Métodos: Estudo de coorte retrospectivo envolvendo pacientes com TBP diagnosticados e tratados no Instituto de Doenças do Tórax da Universidade Federal do Rio de Janeiro entre 2004 e 2012. Resultados: De 298 pacientes com diagnóstico confirmado de TBP no período do estudo, 174 foram incluídos na análise dos desfechos: 97 nunca fumaram (55,7%), 31 eram ex-tabagistas (17,8%), e 46 eram tabagistas atuais (26,5%). O tabagismo foi associado ao atraso na conversão da cultura do final do segundo mês do tratamento (risco relativo = 3,58 &091;IC95%: 1,30-9,86&093;; p = 0,01), assim como ao desfecho de tratamento não favorável (risco relativo = 6,29 &091;IC95%: 1,57-25,21&093;; p = 0,009). A associação entre tabagismo e cultura positiva ao final do segundo mês de tratamento foi estatisticamente significante entre os tabagistas atuais (p = 0.027). Conclusões: Nesta amostra, os pacientes tabagistas atuais apresentaram uma maior probabilidade de atraso na conversão da cultura após dois meses de tratamento e de desfecho de tratamento não favorável do que aqueles que nunca fumaram.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Escarro/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Fumar/efeitos adversos , Fatores de Tempo , Tuberculose Pulmonar/microbiologia , Brasil , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Medição de Risco , Mycobacterium tuberculosis/isolamento & purificação , Antituberculosos/uso terapêuticoRESUMO
BACKGROUND: The combination of rifapentine and moxifloxacin administered daily with other anti-tuberculosis drugs is highly active in mouse models of tuberculosis chemotherapy. The objective of this phase 2 clinical trial was to determine the bactericidal activity, safety, and tolerability of a regimen comprised of rifapentine, moxifloxacin, isoniazid, and pyrazinamide administered daily during the first 8 weeks of pulmonary tuberculosis treatment. METHODS: Adults with sputum smear-positive pulmonary tuberculosis were randomized to receive either rifapentine (approximately 7.5 mg/kg) plus moxifloxacin (investigational arm), or rifampin (approximately 10 mg/kg) plus ethambutol (control) daily for 8 weeks, along with isoniazid and pyrazinamide. The primary endpoint was sputum culture status at completion of 8 weeks of treatment. RESULTS: 121 participants (56% of accrual target) were enrolled. At completion of 8 weeks of treatment, negative cultures using Löwenstein-Jensen (LJ) medium occurred in 47/60 (78%) participants in the investigational arm vs. 43/51 (84%, p = 0.47) in the control arm; negative cultures using liquid medium occurred in 37/47 (79%) in the investigational arm vs. 27/41 (66%, p = 0.23) in the control arm. Time to stable culture conversion was shorter for the investigational arm vs. the control arm using liquid culture medium (p = 0.03), but there was no difference using LJ medium. Median rifapentine area under the concentration-time curve (AUC0-24) was 313 mcg*h/mL, similar to recent studies of rifapentine dosed at 450-600 mg daily. Median moxifloxacin AUC0-24 was 28.0 mcg*h/mL, much lower than in trials where rifapentine was given only intermittently with moxifloxacin. The proportion of participants discontinuing assigned treatment for reasons other than microbiological ineligibility was higher in the investigational arm vs. the control arm (11/62 [18%] vs. 3/59 [5%], p = 0.04) although the proportions of grade 3 or higher adverse events were similar (5/62 [8%] in the investigational arm vs. 6/59 [10%, p = 0.76] in the control arm). CONCLUSION: For intensive phase daily tuberculosis treatment in combination with isoniazid and pyrazinamide, a regimen containing moxifloxacin plus low dose rifapentine was at least as bactericidal as the control regimen containing ethambutol plus standard dose rifampin. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT00728507.
Assuntos
Antituberculosos/uso terapêutico , Fluoroquinolonas/uso terapêutico , Rifampina/análogos & derivados , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Antituberculosos/administração & dosagem , Antituberculosos/efeitos adversos , Antituberculosos/farmacocinética , Estudos de Casos e Controles , Quimioterapia Combinada , Feminino , Fluoroquinolonas/administração & dosagem , Humanos , Isoniazida/administração & dosagem , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Moxifloxacina , Pirazinamida/administração & dosagem , Pirazinamida/uso terapêutico , Rifampina/administração & dosagem , Rifampina/uso terapêuticoRESUMO
BACKGROUND: Being a contact of a pulmonary tuberculosis (TB) case is a risk factor for active and latent TB. The objective of this study is to determine the contact tracing yield using two different programmatic definitions of close contact in the city of Rio de Janeiro, Brazil. METHODS: This is a retrospective quasi-experimental study. Data were obtained by reviewing the medical records from TB index cases and their close contacts admitted to the Outpatient TB Clinic of the Institute of Thoracic Diseases, University of Rio de Janeiro. From January 2001 to December 2004, a close contact was defined as an individual who shared an enclosed space with a TB index case for a total period of ≥ 100 hours, whereas from January 2005 to December 2008 the definition of close contact was changed to an individual who shared an enclosed space with a TB index case ≥ 4 hours a week. The primary outcome of this study was newly diagnosed pulmonary TB cases and the secondary outcome was the prevalence of latent TB infection (LTBI) among close contacts during both periods. RESULTS: From 2001-2004, 810 close contacts from 257 index cases were evaluated and the prevalence of active TB and LTBI were 2% (16/810) and 62% (496/794), respectively. From 2005-2008, 1,310 close contacts from 369 index cases were identified and the prevalence of active TB and LTBI were 2.7% (35/1,310) and 69% (877/1,275), respectively. There was not a statically significant difference in the detection of active TB (p = 0.3) between the 2 time periods, but the detection of LTBI was significant higher (p = 0.003). The number needed to screen (contacts/new cases) decreased from 50 to 37 and the number need to contact trace (index cases/new cases) decreased from 16 to 10 from 2001-2004 to 2005-2008. CONCLUSION: In conclusion, the findings of this study suggest that the less conservative definition of TB close contacts (sharing space ≥ 4 h/week) can be a helpful tool for increasing the rate of diagnosis for newly active pulmonary TB cases and for the detection of LTBI among contacts of active pulmonary TB cases.
Assuntos
Busca de Comunicante/métodos , Busca de Comunicante/estatística & dados numéricos , Tuberculose Latente/epidemiologia , Tuberculose Pulmonar/epidemiologia , Adulto , Brasil/epidemiologia , Feminino , Humanos , Tuberculose Latente/diagnóstico , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Tuberculose Pulmonar/diagnóstico , População Urbana , Adulto JovemRESUMO
We evaluated the accuracy of a point-of-care test designed to measure adherence to isoniazid (INH) preventive therapy in a hospital setting in Rio de Janeiro, Brazil. Patients on treatment with daily INH and patients not receiving INH were included. Sensitivity and specificity of the test were 84%/98% at the first minute, and 95%/98% at the fifth minute, respectively. Among smokers, sensitivity and specificity was reduced (80%/89% at the fifth minute, respectively), but only 17% smoked. This test accurately detected INH metabolites 24h following directly observed INH intake, though sensitivity and specificity may be compromised by tobacco smoke exposure.
Assuntos
Antituberculosos/urina , Isoniazida/urina , Adesão à Medicação , Tuberculose Pulmonar/urina , Adulto , Antituberculosos/administração & dosagem , Brasil , Feminino , Humanos , Isoniazida/administração & dosagem , Masculino , Sensibilidade e Especificidade , Tuberculose Pulmonar/tratamento farmacológicoRESUMO
BACKGROUND: New treatments are needed to shorten the time required to cure tuberculosis and to treat drug-resistant strains. The fluoroquinolone moxifloxacin is a promising new agent that might have additive activity to existing antituberculosis agents. We assessed the activity and safety of moxifloxacin in the initial stage of tuberculosis treatment. METHODS: We undertook a phase II, double-blind, randomised controlled trial of a regimen that included moxifloxacin in adults with sputum smear-positive tuberculosis at one hospital in Rio de Janeiro, Brazil. 170 participants received isoniazid, rifampicin, and pyrazinamide at standard doses and were assigned by permuted block randomisation to receive either moxifloxacin (400 mg) with an ethambutol placebo (n=85) or ethambutol (15-20 mg/kg) plus moxifloxacin placebo (n=85) 5 days per week for 8 weeks. The primary endpoint was the proportion of patients whose sputum culture had converted to negative by week 8. Analysis was by modified intention to treat (ITT); patients whose baseline cultures were negative, contaminated, or contained drug-resistant Mycobacterium tuberculosis were excluded from the analysis. Additionally, all missing 8-week results were deemed treatment failures. This study is registered with ClinicalTrials.gov, number NCT00082173. FINDINGS: 74 patients assigned to the moxifloxacin group and 72 in the ethambutol group were included in the modified ITT population. 125 patients had 8-week data (moxifloxacin n=64, ethambutol n=61); the main reason for absence of data was culture contamination. At 8 weeks, culture conversion to negative had occurred in 59 (80%) of 74 patients in the moxifloxacin group compared with 45 (63%) of 72 in the ethambutol group (difference 17.2%, 95% CI 2.8-31.7; p=0.03). There were 16 adverse events (eight in each group) in 12 patients. Only one event was judged related to study drug (grade 3 cutaneous reaction in the ethambutol group). INTERPRETATION: Moxifloxacin improved culture conversion in the initial phase of tuberculosis treatment. Trials to assess whether moxifloxacin can be used to shorten the duration of tuberculosis treatment are justified.
Assuntos
Antituberculosos/uso terapêutico , Compostos Aza/uso terapêutico , Etambutol/uso terapêutico , Quinolinas/uso terapêutico , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Antituberculosos/efeitos adversos , Compostos Aza/efeitos adversos , Brasil/epidemiologia , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Etambutol/efeitos adversos , Feminino , Fluoroquinolonas , Humanos , Isoniazida/uso terapêutico , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Moxifloxacina , Análise Multivariada , Pirazinamida/uso terapêutico , Quinolinas/efeitos adversos , Rifampina/uso terapêutico , Escarro/microbiologia , Fatores de Tempo , Resultado do Tratamento , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/mortalidadeRESUMO
BACKGROUND: Immune responses to Mycobacterium tuberculosis antigens could serve as surrogate markers of treatment response. METHODS: Using the T-SPOT.TB assay and frozen peripheral blood mononuclear cells, we enumerated ESAT-6- and CFP-10-specific IFN-gamma-producing T cells over time in pulmonary TB patients receiving directly observed treatment. T cell responses (measured as "spot forming cells" or "SFCs") were assessed prior to treatment and at 16 and 24 weeks of treatment. RESULTS: 58 patients were evaluated, of whom 57 were HIV seronegative. Mean (SD) ESAT-6, CFP-10, and summed RD1 specific SFCs declined from 42.7 (72.7), 41.2 (66.4), and 83.8 (105.7) at baseline to 23.3 (39.4, p = 0.01), 23.2 (29.4, p = 0.18), and 46.5 (59.5, p = 0.02) at completion of 24 weeks of treatment, respectively. Only 10% of individuals with a baseline reactive test reverted to negative at treatment week 24. For the group that was culture positive at completion of 8 weeks of treatment compared to the culture negative group, the incidence rate ratio (IRR) of ESAT-6, CFP-10, and summed RD1 specific SFC counts were, respectively, 2.23 (p = 0.048), 1.51 (p = 0.20), and 1.83 (p = 0.047). Patients with cavitary disease had mean ESAT-6 specific SFC counts that were higher than those without cavitary disease (IRR 2.08, p = 0.034). CONCLUSION: IFN-gamma-producing RD1-specific T cells, as measured in the T-SPOT.TB assay, may be directly related to bacterial load in patients undergoing treatment for pulmonary TB. However, high inter-subject variability in quantitative results coupled with failure of reversion to negative of qualitative results in most subjects at treatment completion may limit the utility of this assay as a surrogate marker for treatment efficacy.
Assuntos
Ensaio de Imunoadsorção Enzimática/métodos , Mycobacterium tuberculosis/imunologia , Linfócitos T/imunologia , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Contagem de Células , Método Duplo-Cego , Feminino , Humanos , Interferon gama/metabolismo , Estudos Longitudinais , Masculino , Valor Preditivo dos Testes , Linfócitos T/metabolismo , Resultado do Tratamento , Tuberculose Pulmonar/imunologia , Adulto JovemRESUMO
Several genetic cytokine gene variants have been associated with host susceptibility to infectious diseases, including tuberculosis. Based upon the importance of IFN-gamma in protective immunity against Mycobacterium tuberculosis, and the functional role of the IFN-gamma + 874T/A single nucleotide polymorphism in IFN-gamma production, we genotyped 93 Brazilian tuberculosis patients and 266 asymptomatic health care workers, including 150 individuals with a positive tuberculin skin test, and analyzed the possible association of the +874A low IFN-gamma producer allele with tuberculosis occurrence. Using multivariable logistic regression models, genotype and allele frequencies of the mutant + 874A (low IFN-gamma producer) allele were significantly associated with tuberculosis disease. Heterozygous carriers had a 25% increased chance, while individuals presenting the A/A homozygous genotype had an over two-fold risk of having active tuberculosis (95% CI, 1.16-5.91, P = 0.03). Despite the mixed ethnicity observed in Brazilian populations, the present data agree with observations reported in other populations and thus demonstrate that the functional +874T/A IFN-gamma gene polymorphism is associated with tuberculosis in different populations.
Assuntos
Interferon gama/genética , Polimorfismo de Nucleotídeo Único , Tuberculose/genética , Brasil/epidemiologia , Frequência do Gene , Predisposição Genética para Doença/genética , Genótipo , Humanos , Interferon gama/metabolismo , Modelos Logísticos , Tuberculose/imunologiaRESUMO
INTRODUÇAO: A solução de tuberculina é armazenada em frascos de diferentes tamanhos. Sua adsorção ao frasco pode influenciar o resultado da prova tuberculínica. OBJETIVO: Avaliar o efeito do tamanho do frasco de armazenamento da tuberculina nos resultados obtidos na prova tuberculínica. MÉTODO: Sessenta e três pacientes internados com diagnóstico de tuberculose ativa foram submetidos a duas provas tuberculínicas simultâneas, em ambos os antebraços. A técnica usada foi a de Mantoux e consistiu na aplicação de 0,1 ml de tuberculina armazenada em frascos de 5 ml ou de 1,5 ml, no antebraço direito e no antebraço esquerdo, de forma aleatória. A leitura da induração foi efetuada de forma cega por um único leitor treinado previamente. As leituras com diferenças de até 2 mm foram consideradas resultados concordantes. RESULTADOS: Vinte e um pacientes não tiveram induração e foram excluídos da análise. Entre os 42 pacientes restantes, a média dos diâmetros das indurações obtidas nas provas com tuberculina armazenada nos frascos grandes foi maior do que as obtidas com a armazenada em frascos pequenos. A concordância entre as leituras foi obtida em 40,5 por cento delas (17/42), e a diferença foi negativa (frasco grande menor que frasco pequeno) em 16,7 por cento (7/42) e positiva em 42,9 por cento delas (18/42). CONCLUSAO: O tamanho do frasco de armazenamento da tuberculina pode influenciar o resultado da prova tuberculínica. A adsorção da tuberculina à parede do frasco pode explicar o fenômeno. Os autores alertam para o impacto dessas variações nos estudos epidemiológicos e operacionais.
Assuntos
Humanos , Manejo de Espécimes , Teste Tuberculínico/instrumentação , Tuberculose PulmonarRESUMO
INTRODUÇAO: Fatores genéticos podem desempenhar um importante papel na susceptibilidade à tuberculose (TB) ativa, e polimorfismos de base única (SNPs) em diferentes genes que codificam para citocinas têm sido descritos e associados com doenças. OBJETIVOS: Investigar o quanto polimorfismo na região promotora do gene que codifica para TNF-alfa (-238 e -308) estão associados a ocorrência de TB ativa. MÉTODOS: SNPs dentro do gene de TNF-alfa foram analisados por PCR- RFLP em dois grupos de indivíduos: pacientes com TB (n = 234) e pacientes com pneumopatias não TB (n = 113). RESULTADOS: Neste estudo, o alelo -238A esteve associado significantemente com susceptibilidade à ocorrência de TB e gravidade das formas clínicas (p = 0,00002; OR = 0,15; IC = 0,06-0,36). Por outro lado, o alelo -308A esteve associado significantemente com a proteção a outras formas de doença pulmonar (p = 0,02; OR = 1,95; IC = 1,07-3,58). CONCLUSÕES: Estes resultados preliminares sugerem a importância de estudos genéticos na ocorrência da TB. São necessários outros estudos para melhorar a compreensão sobre a patogênese do M. tb.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Marcadores Genéticos , Polimorfismo Genético , Predisposição Genética para Doença/genética , Fator de Necrose Tumoral alfa , Tuberculose Pulmonar/genética , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Análise de Sequência de DNARESUMO
Introdução: a amplificação de ácido nucleico através da técnica de reaçã em cadeia da polimerase - PCR pode ser útil para o diagnóstico da tuberculose. O objetivo deste trabalho foi padronizar um método molecular para o diagnóstico da TB pulmonar. Material e métodos: iniciadores especificos foram usados para amplificação...