RESUMO
BACKGROUND: The implementation of rapid drug susceptibility testing (DST) is a current global priority for TB control. However, data are scarce on patient-relevant outcomes for presumptive diagnosis of drug-resistant tuberculosis (pDR-TB) evaluated under field conditions in high burden countries. METHODS: Observational study of pDR-TB patients referred by primary and secondary health units. TB reference centers addressing DR-TB in five cities in Brazil. Patients age 18 years and older were eligible if pDR-TB, culture positive results for Mycobacterium tuberculosis and, if no prior DST results from another laboratory were used by a physician to start anti-TB treatment. The outcome measures were median time from triage to initiating appropriate anti-TB treatment, empirical treatment and, the treatment outcomes. RESULTS: Between February,16th, 2011 and February, 15th, 2012, among 175 pDR TB cases, 110 (63.0%) confirmed TB cases with DST results were enrolled. Among study participants, 72 (65.5%) were male and 62 (56.4%) aged 26 to 45 years. At triage, empirical treatment was given to 106 (96.0%) subjects. Among those, 85 were treated with first line drugs and 21 with second line. Median time for DST results was 69.5 [interquartile - IQR: 35.7-111.0] days and, for initiating appropriate anti-TB treatment, the median time was 1.0 (IQR: 0-41.2) days. Among 95 patients that were followed-up during the first 6 month period, 24 (25.3%; IC: 17.5%-34.9%) changed or initiated the treatment after DST results: 16/29 MDRTB, 5/21 DR-TB and 3/45 DS-TB cases. Comparing the treatment outcome to DS-TB cases, MDRTB had higher proportions changing or initiating treatment after DST results (p = 0.01) and favorable outcomes (p = 0.07). CONCLUSIONS: This study shows a high rate of empirical treatment and long delay for DST results. Strategies to speed up the detection and early treatment of drug resistant TB should be prioritized.
Assuntos
Antituberculosos/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/tratamento farmacológico , Adulto , Idoso , Brasil , Farmacorresistência Bacteriana , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/patogenicidade , Resultado do Tratamento , Tuberculose/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologiaRESUMO
Previous studies have demonstrated that cells from both multi-drug-resistant tuberculosis (MDR-TB) and non-tuberculous mycobacteria (NTM) patients respond poorly to mycobacterial antigens in vitro. In the present study, we compared the in vitro response of cells isolated from sensitive TB (NR-TB)-, MDR-TB- and NTM-infected patients. Analysis of T cell phenotype ex vivo revealed that both MDR-TB and NTM patients present an increased percentage of CD4(+) CD25(+-) forkhead box protein 3 (FoxP3)(+) and CD4(+) CD25(+) CD127(-) regulatory T (T(reg) ) cells when compared to NR-TB. Increased numbers of T(reg) cells and interleukin (IL)-10 serum levels were detected in MDR-TB, whereas elevated serum transforming growth factor (TGF)-ß was found in the NTM group. Cells of MDR-TB patients stimulated with early secretory antigenic target (ESAT)-6, but not purified protein derivative (PPD), showed a lower frequency of CD4(+) /interferon (IFN)-γ(+) T cells and enhanced CD4(+) CD25(+) FoxP3(+) , CD4(+) CD25(+) CD127(-) and CD4(+) CD25(+) IL-10(+) T cell population. In addition, increased IL-10 secretion was observed in cultured MDR-TB cells following ESAT-6 stimulation, but not in NR-TB or NTM patients. In vitro blockade of IL-10 or IL-10Rα decreased the CD4(+) CD25(+) FoxP3(+) frequencies induced by ESAT-6 in MDR-TB, suggesting a role of IL-10 on impaired IFN-γ responses seen in MDR-TB. Depletion of CD4(+) CD25(+) T lymphocytes restored the capacity of MDR-TB T cells to respond to ESAT-6 in vitro, which suggests a potential role for T(reg) /T regulatory 1 cells in the pathogenesis of MDR-TB. Together, our results indicate that although the similarities in chronicity, NTM- and MDR-TB-impaired antigenic responses involve different mechanisms.
Assuntos
Tolerância Imunológica , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Tuberculose Resistente a Múltiplos Medicamentos/imunologia , Tuberculose Pulmonar/imunologia , Adulto , Idoso , Antígenos de Bactérias/imunologia , Antígenos CD/metabolismo , Proteínas de Bactérias/imunologia , Células Cultivadas , Citocinas/imunologia , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Imunofenotipagem , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Rifampina/uso terapêutico , Subpopulações de Linfócitos T/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Adulto JovemRESUMO
Foi realizada uma investigacao domiciliar junto aos familiares de 154 criancas menores de 5 anos que morreram por pneumonia em Porto Alegre, entre abril de 1987 e marco de 1988; incluiu 91,67% dos obitos que ocorreram no periodo. Detectaram-se diferencas entre as informacoes constantes na Declaracao de Obito e as obtidas atraves das entrevistas. O numero de mortes domiciliares foi de 69 (44,80%) casos e 19 (12,34%) criancas morreram antes de 24 horas deinternacao. Ocorreram 66 (42,86%) obitos em hospital. Discutem-se as causas e suas possiveis associacoes entre elas para a ocorrencia da morte ser hospitalar ounao, fazendo uma extrapolacao a outros estados do pais .