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Over the past three decades, a lot of research has been conducted on remote sensing-based techniques for estimating aboveground biomass (AGB) in forest ecosystems. Due to the complexity of satellite images, the conventional image classification methods have been unable to meet the actual application needs. In our proposed work, the estimation of aboveground biomass has been performed on the basis of a Region of Interest (RoI). Initially, this method is employed to measure the green portions of the areas at the local level. The biomass of the subtropical woods in the areas of India, Indonesia, and Thailand is estimated in this work, using data from Deep Globe LIDAR images. Initially, the satellite images are pre-processed. The ROI method is used to select the green portion of the area. The green portion in the satellite images is segmented using the K-means algorithm and binary classification. An empirical formula is used to calculate the carbon weight. The results obtained show 92% accuracy.

Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis (Mtb). The present work reports the design and synthesis of a hybrid of the precursors of rifampicin and clofazimine, which led to the discovery of a novel Rifaphenazine (RPZ) molecule with potent anti-TB activity. In addition, the efficacy of RPZ was evaluated in-vitro using the reference strain Mtb H37Rv. Herein, 2,3 diamino phenazine, a precursor of an anti-TB drug clofazimine, was tethered to the rifampicin core. This 2,3 diamino phenazine did not have an inherent anti-TB activity even at a concentration of up to 2 µg/mL, while rifampicin did not exhibit any activity against Mtb at a concentration of 0.1 µg/mL. However, the synthesized novel Rifaphenzine (RPZ) inhibited 78% of the Mtb colonies at a drug concentration of 0.1 µg/mL, while 93% of the bacterial colonies were killed at 0.5 µg/mL of the drug. Furthermore, the Minimum Inhibitory Concentration (MIC) value for RPZ was 1 µg/mL. Time-kill studies revealed that all bacterial colonies were killed within a period of 24 h. The synthesized novel molecule was characterized using high-resolution mass spectroscopy and NMR spectroscopy. Cytotoxicity studies (IC 50 ) were performed on human monocytic cell line THP-1, and the determined IC50 value was 96 µg/mL, which is non-cytotoxic.

Background & objectives: The National Tuberculosis (TB) Control Programme has transitioned from thrice-weekly to daily drug treatment regimens in India. This preliminary study was conceived to compare the pharmacokinetics of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) in TB patients being treated with daily and thrice weekly anti-TB treatment (ATT). Methods: This prospective observational study was undertaken in 49 newly diagnosed adult TB patients receiving either daily ATT (n=22) or thrice-weekly ATT (n=27). Plasma RMP, INH and PZA were estimated by high-performance liquid chromatography. Results: The peak concentration (Cmax) of RMP was significantly higher (RMP: 8.5 µg/ml vs. 5.5 µg/ml; P=0.003) and Cmax of INH was significantly lower (INH: 4.8 µg/ml vs. 10.9 µg/ml; P<0.001) in case of daily dosing compared to thrice-weekly ATT. Cmax of drugs and doses was significantly correlated. A higher proportion of patients had subtherapeutic RMP Cmax (8.0 µg/ml) during thrice-weekly compared to daily ATT (78% vs. 36%; P=0.004). Multiple linear regression analysis showed that Cmax of RMP was significantly influenced by the dosing rhythm, pulmonary TB and Cmax of INH and PZA by the mg/kg doses. Interpretation & conclusions: RMP concentrations were higher and INH concentrations were lower during daily ATT, suggesting that INH doses may need to be increased in case of a daily regimen. Larger studies are, however, required using higher INH doses when monitoring for adverse drug reactions and treatment outcomes.

Tuberculosis (TB) remains a major public health problem, representing the second leading cause of death from infectious diseases globally, despite being nearly 100 % curable. Multidrug-resistant (MDR)-TB, a form of TB resistant to isoniazid and rifampicin (rifampin), two of the key first-line TB drugs, is becoming increasingly common. MDR-TB is treated with a combination of drugs that are less effective but more toxic than isoniazid and rifampicin. These drugs include fluoroquinolones, aminoglycosides, ethionamide, cycloserine, aminosalicyclic acid, linezolid and clofazimine among others. Minor adverse effects are quite common and they can be easily managed with symptomatic treatment. However, some adverse effects can be life-threatening, e.g. nephrotoxicity due to aminoglycosides, cardiotoxicity due to fluoroquinolones, gastrointestinal toxicity due to ethionamide or para-aminosalicylic acid, central nervous system toxicity due to cycloserine, etc. Baseline evaluation may help to identify patients who are at increased risk for adverse effects. Regular clinical and laboratory evaluation during treatment is very important to prevent adverse effects from becoming serious. Timely and intensive monitoring for, and management of adverse effects caused by, second-line drugs are essential components of drug-resistant TB control programmes; poor management of adverse effects increases the risk of non-adherence or irregular adherence to treatment, and may result in death or permanent morbidity. Treating physicians should have a thorough knowledge of the adverse effects associated with the use of second-line anti-TB drugs, and routinely monitor the occurrence of adverse drug reactions. In this review, we have compiled safety and tolerability information regarding second-line anti-TB drugs in both adults and children.

Nevirapine, a component of antiretroviral therapy (ART) in resource-limited settings, known for auto-induction of metabolism, is initiated at half therapeutic dose until day 14 ('lead-in period'), and subsequently escalated to full dose. However, studies have shown that this dosing strategy based on adult studies may not be appropriate in children, given that younger children have higher drug clearance rates. In this prospective cohort study, we studied trough plasma nevirapine levels by high performance liquid chromatography (HPLC) at days 7, 14 (lead-in period) and 28 (full dose period) after ART initiation amongst HIV-1 infected children initiating nevirapine-based ART in southern India. Among the 20 children (50% male, median age 9 years) included in the study, sub-therapeutic trough plasma nevirapine concentration (<4μg/ml) was seen in 65% (13/20) of children during the lead-in period within two weeks of ART initiation and among 10% of children at 4 weeks during full-dose nevirapine. Adherence was documented as ≥95% in all children by both caregiver self-report and pill count. Median nevirapine concentrations achieved at week 1 was 4.8 μg/ml, significantly lower than 8 μg/ml, the concentration achieved at week 4 (p = 0.034). Virological failure at one year of ART was observed in six children, and was not associated with median nevirapine concentration achieved during week 1, 2 or 4. We conclude that the dose escalation strategy currently practiced among young children living with HIV-1 resulted in significant subtherapeutic nevirapine concentration (≤4μg/ml) during the lead-in period. We call for a closer look at pediatric-focused dosing strategies for nevirapine initiation in young children. Further studies to establish age-appropriate threshold nevirapine concentration are warranted in young children to corroborate the role of therapeutic drug monitoring in predicting virological outcome.

Tuberculosis is one of the major public health problems worldwide. Modern antituberculous treatment can cure most patients; cure rates > 95% are achieved with standard short-course chemotherapy regimens containing isoniazid, rifampicin, pyrazinamide, and ethambutol among patients with drug-susceptible strains of tuberculosis; however, a small proportion do not respond to treatment or develop serious adverse events. Pharmacogenomic studies of drugs used in the treatment of tuberculosis could help us understand intersubject variations in treatment response. In this review, we compiled pharmacogenomic data on antituberculous drugs that were available from different settings that would give a better insight into the role of pharmacogenomics in the treatment of tuberculosis, thereby enhancing the efficacy and limiting the toxicity of existing antituberculosis medications. The PubMed database was searched from 1960 to the present using the keywords \"tuberculosis\", \"antituberculosis treatment\", \"isoniazid\", \"rifampicin\", \"pyrazinamide\", \"ethambutol\", \"pharmacogenomics\", and \"polymorphism\". Abstracts from meetings and review articles were included. Studies conducted in different settings suggest that pharmacogenomics plays a significant role in isoniazid metabolism, and impacts both treatment efficacy and frequency of adverse reactions. Single nucleotide polymorphisms influencing plasma rifampicin concentrations are also reported. No data are available regarding other first-line drugs, ie, ethambutol and pyrazinamide. There is a need to incorporate pharmacogenomics into clinical trials of tuberculosis in order to understand the factors impacting therapeutic success and occurrence of adverse drug effects.

We measured hair and plasma concentrations of isoniazid among sixteen children with tuberculosis who underwent personal or video-assisted directly observed therapy and thus had 100% adherence. This study therefore defined typical isoniazid exposure parameters after two months of treatment among fully-adherent patients in both hair and plasma (plasma area under the concentration-time curve, AUC, estimated using pharmacokinetic data collected 0, 2, 4, and 6 hours after drug administration). We found that INH levels in hair among highly-adherent individuals did not correlate well with plasma AUC or trough concentrations, suggesting that each measure may provide incremental and complementary information regarding drug exposure in the context of TB treatment.

Background. The role of drug concentrations in clinical outcomes in children with tuberculosis is unclear. Target concentrations for dose optimization are unknown. Methods. Plasma drug concentrations measured in Indian children with tuberculosis were modeled using compartmental pharmacokinetic analyses. The children were followed until end of therapy to ascertain therapy failure or death. An ensemble of artificial intelligence algorithms, including random forests, was used to identify predictors of clinical outcome from among 30 clinical, laboratory, and pharmacokinetic variables. Results. Among the 143 children with known outcomes, there was high between-child variability of isoniazid, rifampin, and pyrazinamide concentrations: 110 (77%) completed therapy, 24 (17%) failed therapy, and 9 (6%) died. The main predictors of therapy failure or death were a pyrazinamide peak concentration <38.10 mg/L and rifampin peak concentration <3.01 mg/L. The relative risk of these poor outcomes below these peak concentration thresholds was 3.64 (95% confidence interval [CI], 2.28–5.83). Isoniazid had concentration-dependent antagonism with rifampin and pyrazinamide, with an adjusted odds ratio for therapy failure of 3.00 (95% CI, 2.08–4.33) in antagonism concentration range. In regard to death alone as an outcome, the same drug concentrations, plus z scores (indicators of malnutrition), and age <3 years, were highly ranked predictors. In children <3 years old, isoniazid 0- to 24-hour area under the concentration-time curve <11.95 mg/L × hour and/or rifampin peak <3.10 mg/L were the best predictors of therapy failure, with relative risk of 3.43 (95% CI, .99–11.82). Conclusions. We have identified new antibiotic target concentrations, which are potential biomarkers associated with treatment failure and death in children with tuberculosis.

Introduction Contrasting findings have been published regarding the effect of human immunodeficiency virus (HIV) on tuberculosis (TB) drug pharmacokinetics (PK). Objectives The aim of this systematic review was to investigate the effect of HIV infection on the PK of the first-line TB drugs (FLDs) rifampicin, isoniazid, pyrazinamide and ethambutol by assessing all published literature. Methods Searches were performed in MEDLINE (through PubMed) and EMBASE to find original studies evaluating the effect of HIV infection on the PK of FLDs. The included studies were assessed for bias and clinical relevance. PK data were extracted to provide insight into the difference of FLD PK between HIV-positive and HIV-negative TB patients. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and its protocol was registered at PROSPERO (registration number CRD42017067250). Results Overall, 27 studies were eligible for inclusion. The available studies provide a heterogeneous dataset from which consistent results could not be obtained. In both HIV-positive and HIV-negative TB groups, rifampicin (13 of 15) and ethambutol (4 of 8) peak concentration ( C max ) often did not achieve the minimum reference values. More than half of the studies (11 of 20) that included both HIV-positive and HIV-negative TB groups showed statistically significantly altered FLD area under the concentration–time curve and/or C max for at least one FLD. Conclusions HIV infection may be one of several factors that reduce FLD exposure. We could not make general recommendations with respect to the role of dosing. There is a need for consistent and homogeneous studies to be conducted.

Abstract Background The relationships between first-line drug concentrations and clinically important outcomes among patients with tuberculosis (TB) remain poorly understood. Methods We enrolled a prospective cohort of patients with new pulmonary TB receiving thrice-weekly treatment in India. The maximum plasma concentration of each drug was determined at months 1 and 5 using blood samples drawn 2 hours postdose. Subtherapeutic cutoffs were: rifampicin <8 µg/mL, isoniazid <3 µg/mL, and pyrazinamide <20 µg/mL. Factors associated with lower log-transformed drug concentrations, unfavorable outcomes (composite of treatment failure, all-cause mortality, and recurrence), and individual outcomes were examined using Poisson regression models. Results Among 404 participants, rifampicin, isoniazid, and pyrazinamide concentrations were subtherapeutic in 85%, 29%, and 13%, respectively, at month 1 (with similar results for rifampicin and isoniazid at month 5). Rifampicin concentrations were lower with human immunodeficiency virus coinfection (median, 1.6 vs 4.6 µg/mL; P = .015). Unfavorable outcome was observed in 19%; a 1-μg/mL decrease in rifampicin concentration was independently associated with unfavorable outcome (adjusted incidence rate ratio [aIRR], 1.21 [95% confidence interval {CI}, 1.01–1.47]) and treatment failure (aIRR, 1.16 [95% CI, 1.05–1.28]). A 1-μg/mL decrease in pyrazinamide concentration was associated with recurrence (aIRR, 1.05 [95% CI, 1.01–1.11]). Conclusions Rifampicin concentrations were subtherapeutic in most Indian patients taking a thrice-weekly TB regimen, and low rifampicin and pyrazinamide concentrations were associated with poor outcomes. Higher or more frequent dosing is needed to improve TB treatment outcomes in India. In a prospective cohort of patients with newly diagnosed pulmonary tuberculosis receiving standard thrice-weekly antituberculosis treatment in India, lower rifampicin concentration was associated with Human Immunodeficiency Virus coinfection and independently associated with unfavorable treatment outcomes.