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Vasyl Kovalishyn, Julie Grouleff, Ivan Semenyuta, Vitaliy O Sinenko, Sergiy R Slivchuk, Diana Hodyna, Volodymyr Brovarets, Volodymyr Blagodatny, Gennady Poda, Igor V Tetko, Larysa Metelytsia
The problem of designing new anti-tubercular drugs against multiple-drug-resistant tuberculosis (MDR-TB) was addressed using advanced machine learning methods. Since there are only few published measurements against MDR-TB, we collected a large literature dataset and developed models against the non-resistant H37Rv strain. The predictive accuracy of these models had a coefficient of determination q2 = 0.7-0.8 (regression models), and balanced accuracies of about 80% (classification models) with cross-validation and independent test sets...
March 14, 2018: Chemical Biology & Drug Design
Liping Yan, Xiaohong Kan, Limei Zhu, Kaijin Xu, Jianjun Yin, Li Jie, Yong Li, Ji Yue, Wenyu Cui, Juan Du, Lihua Wang, Shouyong Tan, Xiangao Jiang, Zhong Zeng, Shenghui Xu, Lin Wang, Yu Chen, Weiguo He, Xusheng Gao, Dapeng Bai, Chengjie Zhao, Xiaofeng Yan, Yuyin Zhu, Yumei Fan, Lanpin Xie, Aihua Deng, Qing Zhang, Heping Xiao
PURPOSE: We designed a prospective, multicenter, randomized, controlled study to assess a 5-month regimen compared with the standard regimen on previously treated patients with pulmonary tuberculosis (TB). METHODS: We enrolled 917 sputum smear-positive patients undergoing additional treatment in 27 major tuberculosis hospitals in China. Patients were randomly assigned to a test group (n = 626)treated with a 5-month regimen of moxifloxacin, pasiniazid, rifabutin, ethambutol, and pyrazinamide or a reference group (n = 291) treated with an 8-month regimen of isoniazid, rifampicin, and streptomycin...
March 5, 2018: Clinical Therapeutics
Mathieu Bastard, Elisabeth Sanchez-Padilla, Philipp du Cros, Atadjan Karimovich Khamraev, Nargiza Parpieva, Mirzagaleg Tillyashaykov, Armen Hayrapetyan, Kamene Kimenye, Shazina Khurkhumal, Themba Dlamini, Santiago Fadul Perez, Alex Telnov, Cathy Hewison, Francis Varaine, Maryline Bonnet
BACKGROUND: The emergence of resistance to anti-tuberculosis (DR-TB) drugs and the HIV epidemic represent a serious threat for reducing the global burden of TB. Although data on HIV-negative DR-TB treatment outcomes are well published, few data on DR-TB outcomes among HIV co-infected people is available despite the great public health importance. METHODS: We retrospectively reported and compared the DR-TB treatment outcomes of HIV-positive and HIV-negative patients treated with an individualized regimen based on WHO guidelines in seven countries: Abkhazia, Armenia, Colombia, Kenya, Kyrgyzstan, Swaziland and Uzbekistan...
2018: PloS One
Nontuthuko E Maningi, Luke T Daum, John D Rodriguez, Halima M Said, Remco P H Peters, John Osei Sekyere, Gerald W Fischer, James P Chambers, P Bernard Fourie
Modern advances in genomics provide an opportunity to re-interpret historical bacterial culture collections. In this study, genotypic antibiotic resistance profiles of Mycobacterium tuberculosis isolates from an historical 20-year-old multidrug-resistant tuberculosis (MDR-TB) culture collection in South Africa are described. DNA samples extracted from the phenotypically MDR-TB isolates (n=240) were assayed by Hain line probe assay (LPA) for the confirmation of MDR-TB and by Illumina Miseq whole genome sequencing (WGS) for the characterization of mutations in eight genes ( rpo B, kat G, inh A, rps L, pnc A, emb B, gyr A and rrs ) that are known to code for resistance to commonly used anti-TB agents...
March 7, 2018: Journal of Clinical Microbiology
Qiao Liu, Peng Lu, Leonardo Martinez, Haitao Yang, Wei Lu, Xiaoyan Ding, Limei Zhu
BACKGROUND: Few prospective cohort studies, none in China, have investigated the relationship between treatment outcomes of multidrug-resistant tuberculosis (MDR-TB) patients and sputum culture conversion. Factors affecting the time of the culture conversion throughout the whole course of the treatment have rarely been investigated. METHODS: This study was performed in four cities in Jiangsu province, China. MDR-TB patients were consecutively enrolled between December 2011 and March 2014...
March 6, 2018: BMC Infectious Diseases
Gunar Günther, Frank van Leth, Sofia Alexandru, Neus Altet, Korkut Avsar, Didi Bang, Raisa Barbuta, Graham Bothamley, Ana Ciobanu, Valeriu Crudu, Manfred Danilovits, Martin Dedicoat, Raquel Duarte, Gina Gualano, Heinke Kunst, Wiel de Lange, Vaira Leimane, Anne-Marie McLaughlin, Cecile Magis-Escurra, Inge Muylle, Veronika Polcová, Cristina Popa, Rudolf Rumetshofer, Alena Skrahina, Varvara Solodovnikova, Victor Spinu, Simon Tiberi, Piret Viiklepp, Christoph Lange
BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a major burden to public health in Europe. Reported treatment success rates are around 50% or less and cure rates are even lower. METHODS: We performed a prospective cohort study, analyzing management and treatment outcomes stratified by incidence of patients with MDR-TB in Europe. Treatment outcomes were compared by WHO and alternative simplified definitions. RESULTS: 380 patients with MDR-TB were recruited and followed-up between 2010 and 2014 in 16 European countries...
March 6, 2018: American Journal of Respiratory and Critical Care Medicine
T Baird, E Donnan, C Coulter, G Simpson, A Konstantinos, G Eather
SETTINGp: Multidrug-resistant tuberculosis (MDR-TB) is a growing concern worldwide. In Australia, although the incidence of MDR-TB remains low, Queensland is at an increased risk due to its proximity to Papua New Guinea (PNG). OBJECTIVE: To examine the epidemiology, clinical features and outcomes of MDR-TB in Queensland, with a comparison between cross-border PNG and non-cross-border patients. DESIGN: Retrospective case series of all MDR-TB patients in Queensland between 1 January 2000 and 31 December 2014...
February 1, 2018: International Journal of Tuberculosis and Lung Disease
E Pavlenko, A Barbova, A Hovhannesyan, Z Tsenilova, A Slavuckij, B Shcherbak-Verlan, A Zhurilo, E Vitek, G Skenders, I Sela, A M Cabibbe, D M Cirillo, P de Colombani, M Dara, A Dean, M Zignol, A Dadu
SETTING: The true prevalence of multidrug-resistant tuberculosis (MDR-TB) in Ukraine is not known. Available data are a decade old and limited to only one province. OBJECTIVE: To determine the prevalence of MDR-TB among new and previously treated TB cases in Ukraine and explore the risk factors associated with drug resistance. METHODS: A total of 1550 sputum smear-positive pulmonary TB patients were recruited from 40 clusters throughout Ukraine...
February 1, 2018: International Journal of Tuberculosis and Lung Disease
Gladys Kigozi, Michelle Engelbrecht, Christo Heunis, André Janse van Rensburg
BACKGROUND: In 2012, the World Health Organization launched guidelines for systematically investigating contacts of persons with infectious tuberculosis (TB) in low- and middle-income countries. As such, it is necessary to understand factors that would influence successful scale-up. This study targeted household contacts of newly-diagnosed infectious TB patients in the Mangaung Metropolitan district to explore factors associated with non-attendance of clinical evaluation. METHOD: In September-October 2016, a pilot study of household contacts was conducted...
March 5, 2018: BMC Infectious Diseases
Sadia Naz, Umar Farooq, Sajid Ali, Rizwana Sarwar, Sara Khan, Ruben Abagyan
Multidrug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) has emerged as global health threat, causing millions of deaths worldwide. Identification of new drug candidates for tuberculosis (TB) by targeting novel and less explored protein targets will be invaluable for antituberculosis drug discovery. We performed structure based virtual screening of eMolecules database against a homology model of relatively unexplored protein target: the α-subunit of Tryptophan synthase (α-TRPS) from Mycobacterium tuberculosis essential for bacterial survival...
March 3, 2018: Journal of Biomolecular Structure & Dynamics
Xiaoguang Wu, Yu Pang, Yanhua Song, Wenzhu Dong, Tingting Zhang, Shuan Wen, Hairong Huang, Mengqiu Gao
In this study, we identified a multidrug-resistant tuberculosis (MDR-TB) outbreak in a high school in northern China. The aim of this work was to describe TB transmission, drug resistance and treatment outcomes for this patient cluster. In January 2017, pulmonary TB was identified in a 17-year-old boy in northern China. Subsequently, a total of 11 TB cases were identified during 6-month follow-up of attendees of the same school. Of five students with latent TB infection (LTBI) receiving isoniazid preventive therapy (IPT), two pulmonary TB cases (40...
February 28, 2018: Epidemiology and Infection
Amal Oudghiri, Hind Karimi, Fouad Chetioui, Fathiah Zakham, Jamal Eddine Bourkadi, My Driss Elmessaoudi, Amin Laglaoui, Imane Chaoui, Mohammed El Mzibri
BACKGROUND: The emergence of extensively drug-resistant tuberculosis (XDR-TB) has raised public health concern for global TB control. Although multi drug-resistant tuberculosis (MDR- TB) prevalence and associated genetic mutations in Morocco are well documented, scarce information on XDR TB is available. Hence, the evaluation of pre-XDR and XDR prevalence, as well as the mutation status of gyrA, gyrB, rrs, tlyA genes and eis promoter region, associated with resistance to second line drugs, is of great value for better management of M/XDR TB in Morocco...
February 27, 2018: BMC Infectious Diseases
Muthupandian Saravanan, Selam Niguse, Mahmud Abdulkader, Ephrem Tsegay, Haftamu Hailekiros, Atsbeha Gebrekidan, Tadele Araya, Arivalagan Pugazhendhi
Tuberculosis (TB) remains a major global health problem and ranks as the second leading cause of death among deaths caused by infectious diseases worldwide. Although the availability of short-course regimens as first-line anti-tuberculosis drugs, the emergence of drug-resistant Mycobacterium tuberculosis strains pose a major challenge to the prevention and control efforts of national tuberculosis programs (NTPs). M. tuberculosis changes its cellular environment with the mechanisms that have been evolved since prehistoric times...
February 24, 2018: Microbial Pathogenesis
Y-M Fan, S-P Ding, Z-J Bao, L-M Wu, L-B Zhen, Q Xia, M Zhu
OBJECTIVE: To examine the clinical outcomes and associated prognostic factors among patients with multidrug-resistant tuberculosis (MDR-TB) in China. METHODS: This retrospective study involved 243 patients with MDR-TB. All patients received standard regimens containing para-amino salicylic acid (PAS) and/or cycloserine (CS). The demographic, social and clinical characteristics of patients were recorded and the patients were followed up for 24 months. RESULTS: Treatment success was closely associated with young age, non-farming occupations, shorter history or smoking, normal urine results, initial MDR-TB treatment regimen, increased haemoglobin, direct bilirubin, uric acid and thyroid stimulating hormone (TSH) levels, and lower white blood cell, neutrophil and blood platelet counts (all P < 0...
March 1, 2018: International Journal of Tuberculosis and Lung Disease
J R Francis, P Manchikanti, C C Blyth, J Denholm, C Lowbridge, C Coulter, E Donnan, R Stapledon, V L Krause, J Waring
OBJECTIVE: To describe the epidemiology and outcomes of multidrug-resistant tuberculosis (MDR-TB) diagnosed in Australia between 1998 and 2012. DESIGN: A retrospective review was undertaken involving all patients with laboratory-confirmed MDR-TB notified in Australia between 1998 and 2012 inclusive. Demographic, clinical and laboratory features are described. Clinical outcomes were defined according to World Health Organization definitions of treatment success (cure and treatment completion), treatment failure, death, loss to follow-up (including transfer out), or not evaluated at treatment completion...
March 1, 2018: International Journal of Tuberculosis and Lung Disease
A Van Deun, T Decroo, A Piubello, B C de Jong, L Lynen, H L Rieder
Current World Health Organization guidelines for the formulation of treatment regimens for multidrug-resistant tuberculosis (MDR-TB) pay too little attention to the microbiological activity of anti-tuberculosis drugs. Here, we draw lessons from the pioneering work done on shorter MDR-TB treatment regimens and the current knowledge of the bactericidal and sterilizing properties of the drugs to inform the composition of treatment regimens for MDR-TB. We propose to reserve the term 'core drug' for the one drug in a regimen that contributes most to relapse-free cure...
March 1, 2018: International Journal of Tuberculosis and Lung Disease
Laura B Nellums, Kieran Rustage, Sally Hargreaves, Jon S Friedland
BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a growing concern in meeting global targets for TB control. In high-income low-TB-incidence countries, a disproportionate number of MDR-TB cases occur in migrant (foreign-born) populations, with concerns about low adherence rates in these patients compared to the host non-migrant population. Tackling MDR-TB in this context may, therefore, require unique approaches. We conducted a systematic review and meta-analysis to identify and synthesise data on MDR-TB treatment adherence in migrant patients to inform evidence-based strategies to improve care pathways and health outcomes in this group...
February 22, 2018: BMC Medicine
Agibothu Kupparam Hemanth Kumar, Alok Kumar, Thiruvengadam Kannan, Rakesh Bhatia, Dipti Agarwal, Santosh Kumar, Rajeshwar Dayal, Sheo Pratap Singh, Geetha Ramachandran
We studied the pharmacokinetics of levofloxacin (LFX), pyrazinamide (PZA), ethionamide (ETH) and cycloserine (CS) in children with multidrug-resistant tuberculosis (MDR TB) being treated according to the Revised National TB Control Programme (RNTCP) guidelines in India. This observational, pharmacokinetic study was conducted in 25 children with MDR TB at the Sarojini Naidu Medical College, Agra, India who were being treated with a 24-month daily regimen. Serial blood samples were collected after directly observed administration of drugs...
February 20, 2018: Antimicrobial Agents and Chemotherapy
Poonam Ramesh Naik, Patrick K Moonan, Abhay Subhashrao Nirgude, Hemant Deepak Shewade, Srinath Satyanarayana, Pracheth Raghuveer, Malik Parmar, Chinnappareddy Ravichandra, Anil Singarajipura
Of patients with multidrug-resistant tuberculosis (MDR TB), <50% complete treatment. Most treatment failures for patients with MDR TB are due to death during TB treatment. We sought to determine the proportion of deaths during MDR TB treatment attributable to TB itself. We used a structured verbal autopsy tool to interview family members of patients who died during MDR TB treatment in India during January-December 2016. A committee triangulated information from verbal autopsy, death certificate, or other medical records available with the family members to ascertain the underlying cause of death...
March 2018: Emerging Infectious Diseases
Aziza Ghanie Icksan, Martin Raja Sonang Napitupulu, Mohamad Arifin Nawas, Fariz Nurwidya
Background: Imaging has a big role in tuberculosis (TB) diagnosis and chest X-ray is preferable because it is available in primary health care and can point out the location, area, and morphology of lesions, such as cavity, consolidation, pleural effusions, and fibrosis. We aimed to compare the chest X-ray findings in multi-drug resistant TB (MDR-TB) and in drug-sensitive TB (DS-TB) cases. Methods: This is a retrospective cross-sectional study which compares chest X-ray findings of two groups of patients, involving 183 DS-TB patients and 183 MDR-TB patients...
January 2018: Journal of Natural Science, Biology, and Medicine
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