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Depressed Gamma Interferon Responses and Treatment Outcomes in Tuberculosis Patients: a Prospective Cohort Study.

ABSTRACT: Immunosuppression induced by Mycobacterium tuberculosis is important in the pathogenesis of active tuberculosis (TB). However, the impact of depressed TB-specific and non-TB-specific gamma interferon (IFN-?) response on the treatment outcomes of TB patients remains uncertain. In this prospective cohort study, culture- or pathology-proven active TB patients were enrolled and QuantiFERON-TB Gold In-Tube (QFT-GIT) assays were performed before the initiation of anti-TB treatment. TB-specific IFN-? responses (TB antigen tube subtracted from the nil tube) and non-TB-specific IFN-? responses (mitogen tube subtracted from the nil tube) were measured and associated with treatment outcomes, including 2-month culture conversion and on-treatment mortality. A total of 212 active TB patients were included in the analysis. We observed a close correlation between decreased lymphocyte count and lower non-TB-specific IFN-? responses but not TB-specific IFN-? responses. Patients with lower non-TB-specific IFN-? responses had lower 2-month culture conversion rate (71.1% versus 84.7%, respectively; P = 0.033) and higher on-treatment mortality (22.6% versus 5.7%, respectively; P = 0.001) than those with higher non-TB-specific IFN-? responses. In multivariate analysis, depressed non-TB-specific IFN-? response was an independent factor associated with 2-month sputum culture nonconversion (odds ratio [OR], 2.49; 95% CI [95% confidence interval], 1.05 to 5.90) and on-treatment mortality (hazard ratio [HR], 2.76; 95% CI, 1.15 to 6.62). In contrast, depressed TB-specific IFN-? responses were significantly associated with higher on-treatment mortality in univariate analysis but not in multivariate analysis. Our findings suggest that depressed non-TB-specific responses, but not TB-specific IFN-? responses, as measured by QFT-GIT before the initiation of anti-TB treatment, were significantly associated with worse treatment outcomes in TB patients.

SUBMITTER: Feng JY

PROVIDER: S-EPMC6156303 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Depressed Gamma Interferon Responses and Treatment Outcomes in Tuberculosis Patients: a Prospective Cohort Study.

Feng Jia-Yih JY Pan Sheng-Wei SW Huang Shiang-Fen SF Chen Ying-Ying YY Lin Yung-Yang YY Su Wei-Juin WJ

Journal of clinical microbiology 20180925 10

Immunosuppression induced by <i>Mycobacterium tuberculosis</i> is important in the pathogenesis of active tuberculosis (TB). However, the impact of depressed TB-specific and non-TB-specific gamma interferon (IFN-γ) response on the treatment outcomes of TB patients remains uncertain. In this prospective cohort study, culture- or pathology-proven active TB patients were enrolled and QuantiFERON-TB Gold In-Tube (QFT-GIT) assays were performed before the initiation of anti-TB treatment. TB-specific ...[more]

PMID: 30068533

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Project description:BACKGROUND:An estimated 10% of tuberculosis (TB) deaths are attributable to problematic alcohol use globally, however the causal pathways through which problem alcohol use has an impact on TB treatment outcome is not clear. This study aims to improve understanding of these mechanisms. Specifically, we aim to 1) assess whether poor TB treatment outcomes, measured as delayed time-to-culture conversion, are associated with problem alcohol use after controlling for non-adherence to TB pharmacotherapy; and 2) to determine whether pharmacokinetic (PK) changes in those with problem alcohol use are associated with delayed culture conversion, higher treatment failure/relapse rates or with increased toxicity. METHODS:Our longitudinal, repeated measures, prospective cohort study aims to examine the associations between problem alcohol use and TB treatment outcomes and to evaluate the effect of alcohol on the PK and pharmacodynamics (PD) of TB drugs. We will recruit 438 microbiologically confirmed, pulmonary TB patients with evidence of rifampicin susceptibility in Worcester, South Africa with 200 HIV uninfected patients co-enrolled in the PK aim. Participants are followed for the six months of TB treatment and an additional 12 months thereafter, with sputum collected weekly for the first 12 weeks of treatment, alcohol consumption measures repeated monthly in concert with an alcohol biomarker (phosphatidylethanol) measurement at baseline, and in person directly observed therapy (DOT) using real-time mobile phone-based adherence monitoring. The primary outcome is based on time to culture conversion with the second objective to compare PK of first line TB therapy in those with and without problem alcohol use. DISCUSSION:Globally, an urgent need exists to identify modifiable drivers of poor TB treatment outcomes. There is a critical need for more effective TB treatment strategies for patients with a history of problem alcohol use. However, it is not known whether poor treatment outcomes in alcohol using patients are solely attributable to noncompliance. This study will attempt to answer this question and provide guidance for future TB intervention trials. TRIAL REGISTRATION:Clinicaltrials.gov Registration Number: NCT02840877 . Registered on 19 July 2016.

Project description:BackgroundTuberculosis (TB) still represents a major public health problem in Latin America, with low success and high default rates. Poor adherence represents a major threat for TB control and promotes emergence of drug-resistant TB. Expanding social protection programs could have a substantial effect on the global burden of TB; however, there is little evidence to evaluate the outcomes of socioeconomic support interventions. This study evaluated the effect of a conditional cash transfer (CCT) policy on treatment success and default rates in a prospective cohort of socioeconomically disadvantaged patients.Methods and findingsData were collected on adult patients with first diagnosis of pulmonary TB starting treatment in public healthcare facilities (HCFs) from 16 health departments with high TB burden in Buenos Aires who were followed until treatment completion or abandonment. The main exposure of interest was the registration to receive the CCT. Other covariates, such as sociodemographic and clinical variables and HCFs' characteristics usually associated with treatment adherence and outcomes, were also considered in the analysis. We used hierarchical models, propensity score (PS) matching, and inverse probability weighting (IPW) to estimate treatment effects, adjusting for individual and health system confounders. Of 941 patients with known CCT status, 377 registered for the program showed significantly higher success rates (82% versus 69%) and lower default rates (11% versus 20%). After controlling for individual and system characteristics and modality of treatment, odds ratio (OR) for success was 2.9 (95% CI 2, 4.3, P < 0.001) and default was 0.36 (95% CI 0.23, 0.57, P < 0.001). As this is an observational study evaluating an intervention not randomly assigned, there might be some unmeasured residual confounding. Although it is possible that a small number of patients was not registered into the program because they were deemed not eligible, the majority of patients fulfilled the requirements and were not registered because of different reasons. Since the information on the CCT was collected at the end of the study, we do not know the exact timing for when each patient was registered for the program.ConclusionsThe CCT appears to be a valuable health policy intervention to improve TB treatment outcomes. Incorporating these interventions as established policies may have a considerable effect on the control of TB in similar high-burden areas.

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Depressed Gamma Interferon Responses and Treatment Outcomes in Tuberculosis Patients: a Prospective Cohort Study.

Publications

Depressed Gamma Interferon Responses and Treatment Outcomes in Tuberculosis Patients: a Prospective Cohort Study.

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