Tuberculosis control

Kranzer, Katharina; Khan, Palwasha; Godfrey-Fausset, Peter; Ayles, Helen; Lönnroth, Knut

doi:10.1016/s0140-6736(16)00710-8

Cited by 3 publications

(3 citation statements)

References 4 publications

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“…TB continues to be a serious global health problem, and before the coronavirus pandemic (COVID-19) it was the main cause of death from an infectious agent, being more deadly than HIV [2]. TB worldwide mortality data show that more than one million people die from this single pathogen annually: TB causes an estimated 10 million new cases and around 1.8 million deaths per year [3]. Moreover, it has been reported that approximately one-quarter of the world population shares the TB infection in a latent phase, representing a high-risk population susceptible to future active TB infection [4].…”

Section: Introductionmentioning

confidence: 99%

QSAR Studies, Molecular Docking, Molecular Dynamics, Synthesis, and Biological Evaluation of Novel Quinolinone-Based Thiosemicarbazones against Mycobacterium tuberculosis

et al. 2022

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In this study, a series of novel quinolinone-based thiosemicarbazones were designed in silico and their activities tested in vitro against Mycobacterium tuberculosis (M. tuberculosis). Quantitative structure-activity relationship (QSAR) studies were performed using quinolinone and thiosemicarbazide as pharmacophoric nuclei; the best model showed statistical parameters of R2 = 0.83; F = 47.96; s = 0.31, and was validated by several different methods. The van der Waals volume, electron density, and electronegativity model results suggested a pivotal role in antituberculosis (anti-TB) activity. Subsequently, from this model a new series of quinolinone-thiosemicarbazone 11a–e was designed and docked against two tuberculosis protein targets: enoyl-acyl carrier protein reductase (InhA) and decaprenylphosphoryl-β-D-ribose-2’-oxidase (DprE1). Molecular dynamics simulation over 200 ns showed a binding energy of −71.3 to −12.7 Kcal/mol, suggesting likely inhibition. In vitro antimycobacterial activity of quinolinone-thiosemicarbazone for 11a–e was evaluated against M. bovis, M. tuberculosis H37Rv, and six different strains of drug-resistant M. tuberculosis. All compounds exhibited good to excellent activity against all the families of M. tuberculosis. Several of the here synthesized compounds were more effective than the standard drugs (isoniazid, oxafloxacin), 11d and 11e being the most active products. The results suggest that these compounds may contribute as lead compounds in the research of new potential antimycobacterial agents.

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Section: Introductionmentioning

confidence: 99%

QSAR Studies, Molecular Docking, Molecular Dynamics, Synthesis, and Biological Evaluation of Novel Quinolinone-Based Thiosemicarbazones against Mycobacterium tuberculosis

et al. 2022

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“…Accurate and early diagnosis is important for controlling infection and effective treatment of TB. The current conventional methods for TB diagnosis are primarily smears for acid-fast bacilli (AFB) and Mycobacterium tuberculosis culture (Kranzer et al, 2016 ). However, the AFB smear positivity rate among TB cases was found to be only 20–30%, and the culture requires 4–8 weeks for the growth of M. tuberculosis (Dheda et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Plasma Circular RNAs hsa_circ_0001953 and hsa_circ_0009024 as Diagnostic Biomarkers for Active Tuberculosis

Qing

Peng

et al. 2018

Front. Microbiol.

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Recent studies have demonstrated that circular RNAs (circRNAs) could serve as potential molecular markers for disease diagnosis; however, little is known about their diagnostic value in active tuberculosis (TB). This study first performed a microarray screening of circRNA changes in plasma samples from 3 patients with active pulmonary TB and 3 healthy controls. Then, candidate circRNAs were selected for validation on a quantitative real-time PCR system. Of the 61 differentially expressed circRNAs recorded, 43 and 18 were upregulated and downregulated in the TB group, respectively. Validation assays demonstrated that plasma levels of 6 circRNAs, including hsa_circ_0009024, hsa_circ_0001953, hsa_circ_0008297, hsa_circ_0003528, hsa_circ_0003524 and hsa_circ_0015879 were remarkably increased in TB patients. Plasma levels of hsa_circ_0001953 and hsa_circ_0009024 were correlated with TB severity. Next, hsa_circ_0001953 and hsa_circ_0009024 were assessed in an independent cohort consisting of 120 TB patients and 100 control individuals. An area under the receiver operating characteristic (ROC) curve of 0.915 (95% confidence interval 0.880-0.951; P < 0.001) was obtained for detecting TB, with hsa_circ_0001953 and hsa_circ_0009024 used in combination. Additionally, plasma levels of hsa_circ_0001953 and hsa_circ_0009024 were reduced significantly in patients after treatment (P < 0.001). The present findings indicate that the circRNAs hsa_circ_0001953 and hsa_circ_0009024 may represent novel plasma biomarkers for active TB diagnosis.

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“…However, concerns over resource-requirements and affordability have precluded implementation in low income settings. Moreover, where TB incidence and prevalence are high, and in high HIV prevalence settings, concerns have been raised that household-targeted case-finding approaches may be ineffective as incident TB disease among household contacts comprises only a small fraction of all population TB cases, meaning that household-targeted screening may only contribute marginally to case detection and overall reductions in disease incidence and prevalence [40]. Indeed, the ZAMSTAR trial did not clearly demonstrate the effectiveness of household-based interventions on reducing community TB prevalence and incidence of childhood infection [14].…”

Section: Discussionmentioning

confidence: 99%

Intensified household contact tracing, prevention and treatment support versus enhanced standard of care for contacts of tuberculosis cases in South Africa: study protocol for a household cluster-randomised trial

et al. 2019

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Background Household contact tracing of index TB cases has been advocated as a key part of TB control for many years, but has not been widely implemented in many low-resource setting because of the current dearth of high quality evidence for effectiveness. Innovative strategies for earlier, more effective treatment are particularly important in contexts with hyper-endemic levels of HIV, where levels of TB infection remain extremely high. Methods We present the design of a household cluster-randomised controlled trial of interventions aimed at improving TB-free survival and reducing childhood prevalence of Mycobacterium tuberculosis infection among household contacts of index TB cases diagnosed in two provinces of South Africa. Households of index TB cases will be randomly allocated in a 1:1 ratio to receive either an intensified home screening and linkage for TB and HIV intervention, or enhanced standard of care. The primary outcome will compare between groups the TB-free survival of household contacts over 15 months. All participants, or their next-of-kin, will provide written informed consent to participate. Discussion Evidence from randomised trials is required to identify cost-effective approaches to TB case-finding that can be applied at scale in sub-Saharan Africa. Trial registration ISRCTN16006202 (01/02/2017: retrospectively registered) and NHREC4399 (11/04/2016: prospectively registered). Protocol version: 4.0 (date: 18th January 2018).

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Tuberculosis control

Cited by 3 publications

References 4 publications

QSAR Studies, Molecular Docking, Molecular Dynamics, Synthesis, and Biological Evaluation of Novel Quinolinone-Based Thiosemicarbazones against Mycobacterium tuberculosis

QSAR Studies, Molecular Docking, Molecular Dynamics, Synthesis, and Biological Evaluation of Novel Quinolinone-Based Thiosemicarbazones against Mycobacterium tuberculosis

Plasma Circular RNAs hsa_circ_0001953 and hsa_circ_0009024 as Diagnostic Biomarkers for Active Tuberculosis

Intensified household contact tracing, prevention and treatment support versus enhanced standard of care for contacts of tuberculosis cases in South Africa: study protocol for a household cluster-randomised trial

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