Tuberculosis: where are we?

Mello, Fernanda Carvalho de Queiroz; Silva, Denise Rossato; Dalcolmo, Margareth Pretti

doi:10.1590/s1806-37562017000000450

Cited by 17 publications

(12 citation statements)

References 4 publications

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“…Tuberculosis (TB) is a contagious bacterial disease that is caused by mycobacterium tuberculosis. It ranks among the top 10 worldwide causes of death and is the leading basis of death from a single infectious agent (ranked above HIV/AIDS) [ 1 ]. It usually affects the lungs (pulmonary TB) but can similarly affect other locations (extra pulmonary TB).…”

Section: Introductionmentioning

confidence: 99%

Pulmonary Targeting of Inhalable Moxifloxacin Microspheres for Effective Management of Tuberculosis

et al. 2021

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In the present study, the objective was to attain a localized lung delivery of an anti-tubercular fluoroquinolone, moxifloxacin (MXF), targeting the alveolar macrophages through a non-invasive pulmonary route using inhalable microspheres as a dry powder inhaler approach. MXF-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres (MXF-PLGA-MSs) were fabricated by solvent evaporation technique and optimized by using a central composite statistical design. The morphology and particle size, as well as the flowability of the optimized microspheres, were characterized. In addition, the aerosolization performance of the optimized formula was inspected using an Andersen cascade impactor. Furthermore, in vivo fate following intrapulmonary administration of the optimized formula was evaluated. The optimized MXF-PLGA-MSs were spherical in shape with a particle size of 3.16 µm, drug loading of 21.98% and entrapment efficiency of 78.0%. The optimized formula showed a mass median aerodynamic diameter (MMAD) of 2.85 ± 1.04 µm with a favorable fine particle fraction of 72.77 ± 1.73%, suggesting that the powders were suitable for inhalation. Most importantly, in vivo studies revealed that optimized MXF-PLGA-MSs preferentially accumulated in lung tissue as manifested by a two-fold increase in the area under the curve AUC0–24h, compared to plain drug. In addition, optimized MXF-PLGA-MS sustained drug residence in the lung for up to 24 h following inhalation, compared to plain drug. In conclusion, inhalable microspheres of MXF could be a promising therapeutic approach that might aid in the effective eradiation of tuberculosis along with improving patient adherence to the treatment.

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Section: Introductionmentioning

confidence: 99%

Pulmonary Targeting of Inhalable Moxifloxacin Microspheres for Effective Management of Tuberculosis

et al. 2021

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“…Tuberculosis (TB) is a chronic infectious contagious disease that afflicts humanity since ancient times. Despite being preventable and curable, tuberculosis is the ninth leading cause of death worldwide [1]. In 2016, 10.4 million cases and 1.5 million deaths were documented [2].…”

Section: Introductionmentioning

confidence: 99%

In Silico Study to Identify New Antituberculosis Molecules from Natural Sources by Hierarchical Virtual Screening and Molecular Dynamics Simulations

et al. 2019

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Tuberculosis (TB) is an infection caused by Mycobacterium tuberculosis, responsible for 1.5 million documented deaths in 2016. The increase in reported cases of M. tuberculosis resistance to the main drugs show the need for the development of new and efficient drugs for better TB control. Based on these facts, this work aimed to use combined in silico techniques for the discovery of potential inhibitors to β-ketoacyl-ACP synthase (MtKasA). Initially compounds from natural sources present in the ZINC database were selected, then filters were sequentially applied by virtual screening, initially with pharmacophoric modeling, and later the selected compounds (based on QFIT scores) were submitted to the DOCK 6.5 program. After recategorization of the variables (QFIT score and GRID score), compounds ZINC35465970 and ZINC31170017 were selected. These compounds showed great hydrophobic contributions and for each established system 100 ns of molecular dynamics simulations were performed and the binding free energy was calculated. ZINC35465970 demonstrated a greater capacity for the KasA enzyme inhibition, with a ΔGbind = −30.90 kcal/mol and ZINC31170017 presented a ΔGbind = −27.49 kcal/mol. These data can be used in other studies that aim at the inhibition of the same biological targets through drugs with a dual action.

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“…Tuberculosis (TB) is ranked amongst the top 10 leading causes of death worldwide and is the leading cause of death from a single infectious agent. [1] South Africa (SA) has a high burden of TB, with ~438 000 new cases reported in 2019. [2] The Department of Health in SA has implemented strategies that have been successful in curbing the incidence of TB.…”

Section: Introductionmentioning

confidence: 99%

Occult pulmonary arterial hypertension in patients with previous pulmonary tuberculosis

Kalla

Miri

Seedat

2020

Afr J Thorac Crit Care Med

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Background. Pulmonary tuberculosis (TB) still causes a significant public healthcare burden. Despite successful treatment, TB can lead to permanent lung damage and pulmonary hypertension (PH). PH can also occur in the absence of significant lung damage, leading clinicians to question whether pulmonary TB may cause pulmonary arterial hypertension (PAH), an entity that has not been otherwise described. Objectives. To determine the prevalence of PAH in patients previously treated for TB. Methods. We recruited 20 participants who were previously treated for TB and had no other underlying risk factors for the development of PH. The participants underwent electrocardiography (ECG), chest radiography, lung function tests and echocardiography (ECHO). Data from these non-invasive investigations were evaluated to determine findings that were suggestive of PH. Results. At a median duration of 30 months from diagnosis of TB, no participant had echocardiography findings that were suggestive of PH (pulmonary artery pressure (PAP) ≥40 mmHg). However, there was a negative correlation between the time from diagnosis and right ventricular dysfunction assessed by measuring a tricuspid annular plane systolic excursion (r=-0.5136; p=0.0205). Furthermore, one-third of the participants (n=7) had one or more ECG features supporting PH and 85% of the participants (n=17) demonstrated at least one chest X-ray (CXR) feature of PH. Conclusion. Although our study did not demonstrate ECHO findings supporting PH, ECG and CXR modalities were suggestive. Therefore, future studies consisting of larger cohorts and including the use of other sensitive modalities such as computed tomography are warranted. Moreover, these studies will need to determine whether the entity of PAH secondary to previously treated pulmonary TB exists.

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Tuberculosis: where are we?

Cited by 17 publications

References 4 publications

Pulmonary Targeting of Inhalable Moxifloxacin Microspheres for Effective Management of Tuberculosis

Pulmonary Targeting of Inhalable Moxifloxacin Microspheres for Effective Management of Tuberculosis

In Silico Study to Identify New Antituberculosis Molecules from Natural Sources by Hierarchical Virtual Screening and Molecular Dynamics Simulations

Occult pulmonary arterial hypertension in patients with previous pulmonary tuberculosis

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