The Therapeutic potential of interferon-gamma in tuberculosis

Tuberculosis is one of the critical health problems worldwide. The search for ways to improve the results of tuberculosis treatment and overcome drug resistance lies in understanding the pathogenesis of the development of the infectious process. The interferon system, particularly the role of interferon-gamma, has been identified as the main link in the immune response in tuberculosis. The clinical efficacy of interferon-gamma has been studied and evaluated in clinical trials since the end of the last century. There was obtained evidence of the clinical efficacy of interferon-gamma as part of complex therapy. Recent experimental data make it possible to consider interferon-gamma as a promising therapeutic option for the treatment of multidrug-resistant tuberculosis as part of complex therapy worthy of further studies.

Therapeutic effect of cycloserine combined with anti-tuberculosis drugs in the treatment of multidrug-resistant tuberculosis

Purpose: The present study analyzes the comprehensive therapeutic effect of cycloserine, in combination with anti-tuberculosis drugs using chest X-ray and chest CT (computed tomography) scan techniques. Methods: A total of 90 patients, diagnosed with multidrug resistant tuberculosis (MDR TB) were subjected to chest x-ray and CT scan before and after treatment in the two groups. Different views such as sagittal, coronal, lung window and multiplanar imaging of mediastinal window were taken. Some parameters such as case detection rate (CDR) in chest X-ray and CT scan and comprehensive curative effect were observed in two groups. Further, the changes in chest CT signs in addition to absorption of focus, cavity closure and changes in CT extra pulmonary signs were also observed. Results: The clinical profile of the patients and the course of disease were statistically insignificant (p > 0.05). Total effectiveness rate and case detection rate (CDR) values exhibited a significant difference between the groups (p < 0.05). Lung consolidation, nodules and cavities significantly improved in both groups before and after the treatment (p < 0.05). Both groups showed significant improvements in extrapulmonary signs in CT scan (p < 0.05) after the treatment. Conclusion: Based on the study outcomes, the CT scan method has good potentials for diagnosing and treating MDR TB at the early stages. Further, it can clarify the signs and outcomes of the disease at early stages, thus providing the medical fraternity a great opportunity to cure the disease.

Strategies employed to evade the host immune response and the mechanism of drug resistance in Mycobacterium tuberculosis: In search of finding new targets

: The partial effectiveness of the host immune response to M. tuberculosis drives bacteria into a latent state, but it is difficult to eliminate the bacteria completely. Usually, this latent condition of M. tuberculosis is reversible, and reactivation of tuberculosis is the leading cause of the majority of transmission. A number of studies performed on animal models and in humans have not yet provided a detailed understanding of the mechanisms or correlates of immunity of M. tuberculosis infection or why there is a significant immunity failure to remove the pathogen. Moreover, the mechanism of resistance involved in drug-resistant M. tuberculosis leading to the emergence of strains of bacteria that show significant resistance to the majority of anti-tuberculosis drugs. We have also provided the recent findings and trends regarding the development of new drug molecules to treat drug and multidrug-resistant tuberculosis and the advancements in immunotherapy in the treatment of drug-resistant tuberculosis. This article provides an in-depth and critical analysis of various strategies employed by the drug-resistant M. tuberculosis to escape the host immune response, as a result of which this bacterium persists in the host for a longer period of time and leads to the development of tuberculosis infection. Furthermore, we also discussed the new targets for the effective treatment of drug resistant tuberculosis.

Validity of automated audiometry for hearing examination in patients with multidrug-resistant tuberculosis

Background: The objective of this study was to test the validity of automated audiometry as a method of hearing examination in patients with multidrug-resistant tuberculosis. Methods: This was a cross-sectional comparative study with a retrospective approach, using patient medical records. Patients with multidrug-resistant tuberculosis (MDR-TB) were recruited based-on medical records that met the inclusion and exclusion criteria at the Pulmonology outpatient unit, then referred to the Otorhinolaryngology outpatient unit of the Dr. Soetomo Academic Medical Center. The subjects’ hearing function was measured with two different devices (automated audiometer and conventional audiometer) before being given anti-tuberculosis drug therapy (aminoglycoside injection) as ototoxicity monitoring from July to December 2019 period. Sensitivity and specificity analysis was used to assess the validity of the test. Results: A total of 36 patients (72 ears) were included. The comparison test results using the Mann-Whitney test showed that there were significant differences between automated audiometry and conventional audiometry in both ears. Analysis values were: sensitivity 80-97%, specificity 37-96%, positive predictive value 74-98%, and negative predictive value 59-96%. Conclusions: Automated audiometry is valid for use as a method of hearing examination and monitoring in patients with multidrug-resistant tuberculosis.

Modeling treatment effect modification in multidrug-resistant tuberculosis in an individual patientdata meta-analysis

Effect modification occurs while the effect of the treatment is not homogeneous across the different strata of patient characteristics. When the effect of treatment may vary from individual to individual, precision medicine can be improved by identifying patient covariates to estimate the size and direction of the effect at the individual level. However, this task is statistically challenging and typically requires large amounts of data. Investigators may be interested in using the individual patient data from multiple studies to estimate these treatment effect models. Our data arise from a systematic review of observational studies contrasting different treatments for multidrug-resistant tuberculosis, where multiple antimicrobial agents are taken concurrently to cure the infection. We propose a marginal structural model for effect modification by different patient characteristics and co-medications in a meta-analysis of observational individual patient data. We develop, evaluate, and apply a targeted maximum likelihood estimator for the doubly robust estimation of the parameters of the proposed marginal structural model in this context. In particular, we allow for differential availability of treatments across studies, measured confounding within and across studies, and random effects by study.

Effect modification of greenness on PM2.5 associated all-cause mortality in a multidrug-resistant tuberculosis cohort

RationaleEvidence for the association between fine particulate matter (PM2.5) and mortality among patients with tuberculosis (TB) is limited. Whether greenness protects air pollution-related mortality among patients with multidrug-resistant tuberculosis (MDR-TB) is completely unknown.Methods2305 patients reported in Zhejiang and Ningxia were followed up from MDR-TB diagnosis until death, loss to follow-up or end of the study (31 December 2019), with an average follow-up of 1724 days per patient. 16-day averages of contemporaneous Normalised Difference Vegetation Index (NDVI) in the 500 m buffer of patient’s residence, annual average PM2.5 and estimated oxidant capacity Ox were assigned to patients regarding their geocoded home addresses. Cox proportional hazards regression models were used to estimate HRs per 10 μg/m3 exposure to PM2.5 and all-cause mortality among the cohort and individuals across the three tertiles, adjusting for potential covariates.ResultsHRs of 1.702 (95% CI 1.680 to 1.725) and 1.169 (1.162 to 1.175) were observed for PM2.5 associated with mortality for the full cohort and individuals with the greatest tertile of NDVI. Exposures to PM2.5 were stronger in association with mortality for younger patients (HR 2.434 (2.432 to 2.435)), female (2.209 (1.874 to 2.845)), patients in rural (1.780 (1.731 to 1.829)) and from Ningxia (1.221 (1.078 to 1.385)). Cumulative exposures increased the HRs of PM2.5-related mortality, while greater greenness flattened the risk with HRs reduced in 0.188–0.194 on average.ConclusionsIndividuals with MDR-TB could benefit from greenness by having attenuated associations between PM2.5 and mortality. Improving greener space and air quality may contribute to lower the risk of mortality from TB/MDR-TB and other diseases.