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João Baptista de Oliveira E Souza Filho, Mauro Sanchez, José Manoel de Seixas, Carmen Maidantchik, Rafael Galliez, Adriana da Silva Rezende Moreira, Paulo Albuquerque da Costa, Martha Maria Oliveira, Anthony David Harries, Afrânio Lineu Kritski
Tuberculosis (TB) remains a significant public health challenge, motivated by the diversity of healthcare epidemiological settings, as other factors. Cost-effective screening has substantial importance for TB control, demanding new diagnostic tools. This paper proposes a decision support tool (DST) for screening pulmonary TB (PTB) patients at a secondary clinic. The DST is composed of an adaptive resonance model (iART) for risk group identification (low, medium and high) and a multilayer perceptron (MLP) neural network for classifying patients as active or inactive PTB...
July 2018: Tuberculosis
Vesla Kullaya, Andre van der Ven, Stellah Mpagama, Blandina T Mmbaga, Philip de Groot, Gibson Kibiki, Quirijn de Mast
The immune effects of platelets and platelet-leukocyte aggregation are increasingly recognized. We studied the occurrence of platelet-monocyte aggregation (PMA) in patients with pulmonary tuberculosis (TB), the processes underlying PMA and consequences for cytokine responses. In a cross-sectional study involving 65 Tanzanian TB patients in different phases of treatment and 29 healthy controls, TB patients had a significantly higher PMA. This increased PMA in TB patients was associated with increased monocyte CCR5, CD16 expression and PF4, but not with increased membrane-expressed or soluble P-selectin expression...
July 2018: Tuberculosis
Nan Aye Thida Oo, Lai Lai San, Jeewan Thapa, Khin Saw Aye, Wah Wah Aung, Chie Nakajima, Yasuhiko Suzuki
Numerous studies report that mutations of rpsL (encoding the S12 protein), rrs (encoding 16S rRNA) and gidB (encoding rRNA methyltransferase) are responsible for conferring resistance to streptomycin (STR), which is usually used in both multidrug-resistant tuberculosis (MDR-TB) treatments and re-treatments in Myanmar. The aim of this study was to explore the variation and frequency of mutations in rpsL, rrs and gidB in 141 STR-resistant MDR-TB isolates from Myanmar. Most isolates belonged to the Beijing genotype (105, 74...
July 2018: Tuberculosis
R Sarkar, C Mdladla, L Macingwana, R-D Pietersen, A H Ngwane, D L Tabb, P D van Helden, I Wiid, B Baker
The emerging resistance of tuberculosis (TB) to current first line drugs (isoniazid, rifampicin, pyrazinamide, ethambutol) warrants alternative treatment approaches with broad-spectrum efficacy. Previously, we have shown that sulfamethoxazole (SMX) has synergestic activity with rifampicin against Mycobacterium tuberculosis. The primary target of SMX is folP1 in mycobacteria; however, SMX may affect other secondary targets in M. tuberculosis. This study investigated the potential additional targets of SMX in a clinical isolate of M...
July 2018: Tuberculosis
Yingjia Li, Haijing Tang, Hui Qi, Chen Shen, Lin Sun, Jieqiong Li, Fang Xu, Weiwei Jiao, Xu Yang, Adong Shen
Previous studies have revealed the important contribution of the immune response and oxidative stress to the development of anti-tuberculosis drug-induced hepatotoxicity (ATDH). To investigate whether single-nucleotide polymorphisms (SNPs) of the cytokine gene interleukin-6 (IL6) and oxidative stress genes xanthine dehydrogenase/oxidase (XO) and inducible nitric oxide synthase (NOS2) were associated with susceptibility to ATDH, we performed a case-control study including 41 ATDH cases and 116 ATDH-free controls in Chinese Han children...
July 2018: Tuberculosis
Charlotte Genestet, Fanny Bernard-Barret, Elisabeth Hodille, Christophe Ginevra, Florence Ader, Sylvain Goutelle, Gérard Lina, Oana Dumitrescu
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) complex remains a deadly infectious disease worldwide. Mtb is an intracellular pathogen, and autophagy is an essential component of the immune response leading to TB clearance. Anti-TB treatment is based on classical isoniazid (INH) and rifampicin (RIF), but also new drugs, such as linezolid (LNZ) and bedaquiline (BDQ). However, little is known about these antibiotics' impact on Mtb intra-macrophagic behavior independent of their impact on host cells...
July 2018: Tuberculosis
Fengge Li, Lili Feng, Chunyan Jin, Xiaoyu Wu, Lingbo Fan, Sidong Xiong, Yuanshu Dong
Tuberculosis is a severe infectious disease caused by Mycobacterium tuberculosis (Mtb). LpqT is a lipoprotein of Mtb identified as a candidate virulence factor by a high-throughput screen searching for genes important for mycobacteria intracellular survival. To investigate its function, we constructed M. smegmatis strains deficient of LpqT or overexpressing LpqT. Wildtype or LpqT modified M. smegmatis strains were used to infect macrophages and mice, and intracellular survival of mycobacteria was measured. We found that LpqT can improve M...
July 2018: Tuberculosis
Kanchan Ajbani, Mubin Kazi, Swapna Naik, Rajeev Soman, Anjali Shetty, Camilla Rodrigues
Tubercular meningitis (TBM) is a serious form of tuberculosis (TB). The diagnosis of TBM & susceptibility/resistance is difficult as TB MGIT culture lacks sensitivity & timeliness. Timely and accurate diagnosis of the TBM is the need of the hour for initiation of appropriate therapy. We have exploited pyrosequencing to detect TB and associated Multi/extensively drug resistant (MDR/ XDR-TB) directly from Cerebrospinal Fluid (CSF) specimens.
July 2018: Tuberculosis
Yanfeng Zhao, Xiqin Yang, Xuhui Zhang, Qin Yu, Ping Zhao, Jianxia Wang, Cuimi Duan, Jiangxue Li, Heather Johnson, Xiaoyan Feng, Heqiu Zhang
OBJECTIVE: We aimed to determine whether IP-10 and RANTES plasma levels can be used in diagnosis and monitoring of pulmonary tuberculosis (PTB). METHODS: Plasma levels of cytokines/chemokines were measured using a Bio-Plex® multiplex cytokine assay system in a cohort containing 457 clinically suspected PTB patients including a training set (n = 41)and two independent test sets A (n = 242) and B (n = 174). RESULTS: Plasma levels of IP-10 and RANTES were significantly higher in PTB patients than healthy controls' in both training and independent test sets (P < 0...
July 2018: Tuberculosis
Nathally Claudiane de Souza Santos, Regiane Bertin de Lima Scodro, Aryadne Larissa de Almeida, Vanessa Pietrowski Baldin, Sandra Sayuri Nakamura de Vasconcelos, Vera Lucia Dias Siqueira, Katiany Rizzieri Caleffi-Ferracioli, Paula Aline Zanetti Campanerut-Sá, Rosilene Fressatti Cardoso
SETTING: The increase of multidrug and extensively drug resistant Mycobacterium tuberculosis strains turns the search for new tuberculosis (TB) treatment options of paramount importance. OBJECTIVE: In this sense, the present study evaluates the in vitro activity of isoniazid (INH)/rifampicin (RIF)/levofloxacin (LVX) and INH/RIF/linezolid (LNZ) combinations in resistant M. tuberculosis. DESIGN: The activities of the combinations were evaluated with M...
July 2018: Tuberculosis
Laíse Adriane Hegeto, Katiany R Caleffi-Ferracioli, Sandra S Nakamura-Vasconcelos, Aryadne Larissa de Almeida, Vanessa Pietrowski Baldin, Celso Vataru Nakamura, Vera Lúcia D Siqueira, Regiane B L Scodro, Rosilene Fressatti Cardoso
Tuberculosis (TB) is an important public health problem worldwide and the emergence of multidrug-resistant (MDR) TB and extensively drug-resistant (XDR) TB worsened the global context. The resistance in Mycobacterium tuberculosis, the causative agent of TB, can partially derive from efflux pumps (EPs) activity in plasma membrane. Due to the recent discovery of piperine (PIP), an organic alkaloid compound, increasing the bioavailability of various drugs, the current assay evaluated the combined activity of PIP and anti-TB drugs in susceptible and resistant M...
July 2018: Tuberculosis
Elena Martinez, Daneeta Hennessy, Peter Jelfs, Taryn Crighton, Sharon C-A Chen, Vitali Sintchenko
Genome-wide analysis of 517 Mycobacterium tuberculosis isolates from New South Wales, Australia, have identified previously reported and 8 new mutations in Rv0678 and atpE genes linked to in vitro resistance to bedaquiline, a new class of antimycobacterial drugs. These mutations were present in 2.9% of prospectively sequenced genomes but in 10.6% of strains that were phenotypically multidrug-resistant. However only 14% of isolates with these mutations demonstrated elevated minimum inhibitory concentrations to bedaquiline...
July 2018: Tuberculosis
Edson T Mambuque, Estefanía Abascal, Rouxjeane Venter, Helder Bulo, Emilio Bouza, Grant Theron, Alberto L García-Basteiro, Darío García-de-Viedma
Genotyping of Mycobacterium tuberculosis (MTB) isolates has markedly improved our knowledge of its transmission dynamics. MIRU-VNTR is considered the reference molecular tool for MTB fingerprinting. However, the dependence of this technique on cultured isolates means that we lack molecular epidemiology data from many settings where culture facilities have not been implemented. Efforts have been made to adapt the MIRU-VNTR procedure to direct analysis of clinical specimens, although implementation of these efforts has not proven successful...
July 2018: Tuberculosis
Yongge Liu, Makoto Matsumoto, Hidekaza Ishida, Kinue Ohguro, Masuhiro Yoshitake, Rajesh Gupta, Lawrence Geiter, Jeffrey Hafkin
Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is the leading cause of death from an infectious disease globally. The widespread and ever-increasing resistance to TB drugs is reducing the effectiveness of treatment and jeopardizing TB control. New effective drugs with acceptable safety profiles are needed to turn the tide. Since the early 1990s, Otsuka Pharmaceutical Co., Ltd. has had a TB drug development program that resulted in the selection and development of delamanid (OPC-67683, Deltyba® ), a first-in-class bicyclic nitroimidazole...
July 2018: Tuberculosis
Lélia Pacheco Corrêa Barros, Karina Pena Del Rio, Tatiane Dos Santos Conceição Carvalho, Maria do Carmo Freire Ribeiro Pinto, Kelly Cristina Gallan de Moura, Priscila Cristina Bartolomeu Halicki, Daniela Fernandes Ramos, Pedro Eduardo Almeida da Silva
Tuberculosis (TB) is the cause of more than one million deaths worldwide, and despite being a curable disease, some factors can make therapy difficult, emphasizing the need for the development of new drugs that may potentiate the action of the classic anti-TB antimicrobials. Naphthoimidazoles show a broad spectrum of biological activities, including antimycobacterial activity. The aim of this study was to evaluate the anti-Mycobacterium tuberculosis activity of nine naphthoimidazoles, alone and combined with isoniazid (INH) and rifampicin (RIF)...
July 2018: Tuberculosis
Qi Zheng, Jim Werngren
In 2003 Werngren and Hoffner reported the earliest quantitative mutability study comparing Beijing and non-Beijing strains of Mycobacterium tuberculosis. Their null findings appeared to be at odds with the then-popular hypothesis favoring characterization of the Beijing genotype by mutability. Three recent attempts to reexamine the experimental data have resulted in three successively smaller p-values in the literature, each supposedly buttressing a non-null conclusion. In addition to identifying errors responsible for the three misleading p-values, we focus on salutary lessons that will facilitate future research on microbial mutability...
July 2018: Tuberculosis
Nicole L Messina, Susie Germano, Rhian Bonnici, Lai-Yang Lee, Andrew J Daley, Andrea Bustamante, Peter Jelfs, Nigel Curtis
A recent shortage in supply of Bacille Calmette-Guérin (BCG), the live attenuated vaccine given to protect against tuberculosis (TB) caused major disruption to global vaccination programs. In this study, we assessed whether quantification of viable bacteria, could be used to inform the use of the BCG vaccine beyond its manufacturer-assigned expiration date. The viability of a single batch of BCG-Denmark was tested in three independent laboratories. There was high inter-vial and inter-laboratory variability in viability counts, however all three laboratories detected a decrease in BCG viability over time...
July 2018: Tuberculosis
Anita G Amin, Prithwiraj De, John S Spencer, Patrick J Brennan, Joshua Daum, Barbara G Andre, Maju Joe, Yu Bai, Lars Laurentius, Marc D Porter, William J Honnen, Alok Choudhary, Todd L Lowary, Abraham Pinter, Delphi Chatterjee
TB diagnosis and treatment monitoring in resource limited regions rely heavily on serial sputum smear microscopy and bacterial culture. These microbiological methods are time-consuming, expensive and lack adequate sensitivity. The WHO states that improved TB diagnosis and treatment is imperative to achieve an end to the TB epidemic by 2030. Commercially available lipoarabinomannan (LAM) detection tools perform at low sensitivity that are highly dependent on the underlying immunological status of the patient; those with advanced HIV infection perform well...
July 2018: Tuberculosis
Evelyn Guirado, Murugesan Vs Rajaram, Ajay Chawla, Joanna Daigle, Krista Md La Perle, Eusondia Arnett, Joanne Turner, Larry S Schlesinger
Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear transcription factor belonging to the superfamily of ligand-activated nuclear receptors. It is activated by diverse endogenous lipid metabolites as well as by exogenous ligands such as the thiazolidinediones. It regulates cellular metabolism, proliferation, differentiation, and inflammation, the latter in part through trans-repression of pro-inflammatory cytokines. PPARγ is highly expressed in alternatively activated alveolar macrophages (AMs), a primary host cell for airborne Mycobacterium tuberculosis (M...
July 2018: Tuberculosis
Harish Shukla, Shaheb Raj Khan, Rohit Shukla, Manju Yasoda Krishnan, Md Sohail Akhtar, Timir Tripathi
Ascorbate has been demonstrated to interfere with the growth of Mycobacterium tuberculosis. It scavenges oxygen in the culture medium to induce dormancy of M. tuberculosis. It kills the mycobacteria by generating reactive oxygen intermediates via iron mediated Fenton reactions. In this study, we observed that ascorbate can inhibit M. tuberculosis isocitrate lyase (MtbICL) with an IC50 of 2.15 mΜ. MtbICL is an essential enzyme for the survival of M. tuberculosis under dormancy. We studied the effect of ascorbate on the growth of M...
July 2018: Tuberculosis
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