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https://www.readbyqxmd.com/read/27903602/whole-genome-sequencing-of-mycobacterium-tuberculosis-provides-insight-into-the-evolution-and-genetic-composition-of-drug-resistant-tuberculosis-in-belarus
#1
Kurt R Wollenberg, Christopher A Desjardins, Aksana Zalutskaya, Vervara Slodovnikova, Andrew J Oler, Mariam Quiñones, Thomas Abeel, Sinead B Chapman, Michael Tartakovsky, Andrei Gabrielian, Sven Hoffner, Aliaksandr Skrahin, Bruce W Birren, Alexander Rosenthal, Alena Skrahina, Ashlee M Earl
The emergence and spread of drug resistant Mycobacterium tuberculosis (DR-TB) is a critical global health issue. Eastern Europe has some of the highest incidences of DR-TB, particularly multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. To better understand the genetic composition and evolution of MDR- and XDR-TB in the region, we sequenced and analyzed the genomes of 138 M. tuberculosis isolates from 97 patients sampled between 2010 and 2013 in Minsk, Belarus. MDR and XDR-TB isolates were significantly more likely to belong to the Beijing lineage than to the Euro-American lineage, and known resistance-conferring loci accounted for the majority of phenotypic resistance to first- and second-line drugs in MDR and XDR-TB...
November 30, 2016: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/27865394/recent-developments-in-genomics-bioinformatics-and-drug-discovery-to-combat-emerging-drug-resistant-tuberculosis
#2
REVIEW
Soumya Swaminathan, Jagadish Chandrabose Sundaramurthi, Alangudi Natarajan Palaniappan, Sujatha Narayanan
Emergence of drug-resistant tuberculosis (DR-TB) is a big challenge in TB control. The delay in diagnosis of DR-TB leads to its increased transmission, and therefore prevalence. Recent developments in genomics have enabled whole genome sequencing (WGS) of Mycobacterium tuberculosis (M. tuberculosis) from 3-day-old liquid culture and directly from uncultured sputa, while new bioinformatics tools facilitate to determine DR mutations rapidly from the resulting sequences. The present drug discovery and development pipeline is filled with candidate drugs which have shown efficacy against DR-TB...
December 2016: Tuberculosis
https://www.readbyqxmd.com/read/27862137/t-cell-responses-and-regulation-and-the-impact-of-in-vitro-il-10-and-tgf-%C3%AE-modulation-during-treatment-of-active-tuberculosis
#3
Siri L Feruglio, Dag Kvale, Anne Ma Dyrhol-Riise
Mycobacterium tuberculosis (Mtb) is particularly challenging for the immune system being an intracellular pathogen, and a variety of T cell subpopulations are activated by the host defense mechanism. In the present study we investigated T cell responses and regulation in active TB patients with drug-sensitive Mtb (n=18) during 24 weeks of efficient anti-TB therapy. T cell activation, differentiation, regulatory T cell (Treg) subsets, Mtb induced T cell proliferation and in vitro IL-10 and TGF-β modulation were analysed by flow cytometry at baseline and after 8 and 24 weeks of therapy, while soluble cytokines in culture supernatants were analysed by a 9-plex Luminex assay...
November 18, 2016: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/27832910/clinical-predictors-of-aminoglycoside-induced-ototoxicity-in-drug-resistant-tuberculosis-patients-on-intensive-therapy
#4
Olusola Ayodele Sogebi, Bolanle Olufunlola Adefuye, Stephen Oluwatosin Adebola, Susan Modupe Oladeji, Taiwo Olugbemiga Adedeji
OBJECTIVE: The study objectives were to determine the incidence of aminoglycoside-induced ototoxicity in institutionalized patients on intensive phase of therapy for drug-resistant Tuberculosis (DR Tb) and also to assess clinical factors which could predict the ototoxicity. METHODS: The study was a prospective analytical study among consecutive DR Tb patients who were admitted for intensive phase of therapy (of 4 months) at the DR-Tb center over a 12-month period...
November 7, 2016: Auris, Nasus, Larynx
https://www.readbyqxmd.com/read/27798208/mechanisms-of-action-and-therapeutic-efficacies-of-the-lipophilic-antimycobacterial-agents-clofazimine-and-bedaquiline
#5
REVIEW
Moloko C Cholo, Maborwa T Mothiba, Bernard Fourie, Ronald Anderson
Drug-resistant (DR)-TB is the major challenge confronting the global TB control programme, necessitating treatment with second-line anti-TB drugs, often with limited therapeutic efficacy. This scenario has resulted in the inclusion of Group 5 antibiotics in various therapeutic regimens, two of which promise to impact significantly on the outcome of the therapy of DR-TB. These are the 're-purposed' riminophenazine, clofazimine, and the recently approved diarylquinoline, bedaquiline. Although they differ structurally, both of these lipophilic agents possess cationic amphiphilic properties that enable them to target and inactivate essential ion transporters in the outer membrane of Mycobacterium tuberculosis...
October 20, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27792837/isoniazid-clearance-is-impaired-among-hiv-tuberculosis-patients-with-high-levels-of-immune-activation
#6
Christopher Vinnard, Shruthi Ravimohan, Neo Tamuhla, Vijay Ivaturi, Jotam Pasipanodya, Shashikant Srivastava, Chawa Modongo, Nicola M Zetola, Drew Weissman, Tawanda Gumbo, Gregory P Bisson
AIMS: Immune activation, which is characteristic of both tuberculosis (TB) and human immunodeficiency virus (HIV) infection, is associated with impaired drug metabolism. We tested the hypothesis that elevated levels of systemic immune activation among adults with HIV/TB initiating ART would be associated with impaired clearance of isoniazid. METHODS: We conducted a prospective observational study of isoniazid pharmacokinetics and systemic immune activation prior to and one month after antiretroviral therapy (ART) initiation...
October 28, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27776588/treatment-outcomes-of-drug-resistant-tuberculosis-patients-in-kenya
#7
D J Mibei, J W Kiarie, A Wairia, M Kamene, M E Okumu
SETTING: Successful treatment of drug-resistant tuberculosis (DR-TB) is crucial in preventing disease transmission and reducing related morbidity and mortality. A standardised DR-TB treatment regimen is used in Kenya. Although patients on treatment are monitored, no evaluation of factors affecting treatment outcomes has yet been performed. OBJECTIVE: To analyse treatment outcomes of DR-TB patients in Kenya and factors associated with successful outcome. DESIGN: Retrospective analysis of secondary data from Kenya's National Tuberculosis, Leprosy and Lung disease programme...
November 2016: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/27769174/severe-adverse-events-during-second-line-tuberculosis-treatment-in-the-context-of-high-hiv-co-infection-in-south-africa-a-retrospective-cohort-study
#8
Kathryn Schnippel, Rebecca H Berhanu, Andrew Black, Cynthia Firnhaber, Norah Maitisa, Denise Evans, Edina Sinanovic
BACKGROUND: According to the World Health Organization, South Africa ranks as one of the highest burden of TB, TB/HIV co-infection, and drug-resistant TB (DR-TB) countries. DR-TB treatment is complicated to administer and relies on the use of multiple toxic drugs, with potential for severe adverse drug reactions. We report the occurrence of adverse events (AEs) during a standardised DR-TB treatment regimen at two outpatient, decentralized, public-sector sites in Johannesburg, South Africa...
October 21, 2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27756712/clinical-management-of-adults-and-children-with-mdr-and-xdr-tb
#9
REVIEW
Keertan Dheda, Kwok Chiu Chang, Lorenzo Guglielmetti, Jennifer Furin, H Simon Schaaf, Dumitru Chesov, Aliasgar Esmail, Christoph Lange
Globally there is a burgeoning epidemic of drug mono-resistant tuberculosis (TB), multi-drug-resistant TB (MDR-TB), and extensively drug-resistant TB (XDR-TB). Almost 20% of all TB strains worldwide are resistant to at least 1 major TB drug including isoniazid. In several parts of the world there is an increasing incidence of MDR-TB, and alarmingly almost a third of MDR-TB cases globally are resistant to either a fluoroquinolone or aminoglycocide. This trend cannot be ignored because DR-TB is associated with greater morbidity compared to drug-sensitive TB, it accounts for almost 25% of global TB mortality, is extremely costly to treat, consuming substantial portions of budgets allocated to national TB programmes in TB endemic countries, and is a major threat to healthcare workers who are already in short supply in resource-poor settings...
October 15, 2016: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/27711122/prevalence-of-drug-resistance-mycobacterium-tuberculosis-among-patients-seen-in-coast-provincial-general-hospital-mombasa-kenya
#10
Ida Pam Ombura, Noel Onyango, Susan Odera, Florence Mutua, Joshua Nyagol
BACKGROUND: Although prevention and control of spread of multi-drug resistant tuberculosis strains is a global challenge, there is paucity of data on the prevalence of DR-TB in patients diagnosed with TB in referral hospitals in Kenya. The present study assessed patients' characteristics and prevalence of drug resistant TB in sputa smear positive TB patients presenting to Coast Provincial General Hospital (CPGH) in Mombasa, Kenya. METHODS: Drug resistance was evaluated in 258 randomly selected sputa smear TB positive cases between the periods of November 2011 to February 2012 at the CPGH-Mombasa...
2016: PloS One
https://www.readbyqxmd.com/read/27686119/changing-prevalence-and-resistance-patterns-in-children-with-drug-resistant-tuberculosis-in-mumbai
#11
Ira Shah, Forum Shah
BACKGROUND: The prevalence of drug-resistant (DR) tuberculosis (TB) in children is increasing. Although, in India, multi-drug-resistant (MDR) TB rates have been relatively stable, the number of children with pre-extensively drug-resistant and extensively drug-resistant (XDR) TB is increasing. AIM: To determine whether the prevalence of DR TB in children in Mumbai is changing and to study the evolving patterns of resistance. METHODS: A retrospective study was undertaken in 1311 paediatric patients referred between April 2007 and March 2013 to the Paediatric TB clinic at B...
August 9, 2016: Paediatrics and International Child Health
https://www.readbyqxmd.com/read/27685837/cd163-levels-pro-and-anti-inflammatory-cytokine-secretion-of-monocytes-in-children-with-pulmonary-tuberculosis
#12
Esin Aktas Cetin, Leyla Pur Ozyigit, Yusuf Metin Gelmez, Erkan Cakir, Ahmet Hakan Gedik, Gunnur Deniz
OBJECTIVES: Childhood tuberculosis (TB) comprises an important part of the world's TB burden. Monocytes set up the early phase of infection because of innate immune responses. Understanding the changes in monocyte subsets during multisystem infectious diseases may be important for the development of novel diagnostic and therapeutic strategies. The aim of this study was to evaluate the monocyte phenotype together with the cytokine secretion profiles of children with pulmonary tuberculosis...
September 29, 2016: Pediatric Pulmonology
https://www.readbyqxmd.com/read/27671062/association-between-embb-codon-306-mutations-phenotypic-resistance-profiles-and-genotypic-characterization-in-clinical-mycobacterium-tuberculosis-isolates-from-hebei-china
#13
Yanan Li, Yuling Wang, Zhi Zhang, Huixia Gao, Haibin Wang, Jinfeng Cao, Shumin Zhang, Yuzhen Liu, Jianhua Lu, Zungui Xu, Erhei Dai
Ethambutol (EMB) is an essential first-line drug for tuberculosis (TB) treatment. Nucleotide substitutions at embB codon 306 (embB306) have been proposed to be a potential marker for EMB resistance and a predictor of broad drug resistance in clinical Mycobacterium tuberculosis isolates. However, discordant findings about the association between embB306 mutations and EMB resistance were reported. Hebei Province is located in the Beijing-Tianjin-Hebei integration region in China; however, little information about the genetic diversity of the embB locus in this area is available...
December 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27642459/patients-with-secondary-amenorrhea-due-to-tuberculosis-endometritis-towards-the-induced-anti-tuberculosis-drug-category-1
#14
Raditya Perdhana, Sutrisno Sutrisno, Yani Jane Sugiri, Siti Candra Windu Baktiyani, Arsana Wiyasa
Tuberculosis (TB) is a disease which can affect various organs, including human's genital organs such as the endometrium. Tuberculosis endometritis can cause clinical symptoms of secondary amenorrhea and infertility. Infertility in genital TB caused by the involvement of the endometrium. The case presentation is 33-year-old woman from dr. Saiful Anwar Public Hospital to consult that she has not menstruated since 5 years ago (28 years old). The diagnosis was done by performing a clinical examination until the diagnosis of secondary amenorrhea due to tuberculosis endometritis is obtained...
2016: Pan African Medical Journal
https://www.readbyqxmd.com/read/27611434/linezolid-associated-optic-neuropathy-in-drug-resistant-tuberculosis-patients-in-mumbai-india
#15
Salil Mehta, Mrinalini Das, Chinmay Laxmeshwar, Sylvie Jonckheere, Sein Sein Thi, Petros Isaakidis
BACKGROUND: Patients on linezolid-containing drug-resistant TB (DR-TB) regimen often develop adverse-events, particularly peripheral and optic neuropathy. Programmatic data and experiences of linezolid-associated optic neuropathy from high DR-TB burden settings are lacking. The study aimed to determine the frequency of and risk-factors associated with linezolid-associated optic neuropathy and document the experiences related to treatment/care of DR-TB patients on linezolid-containing regimens...
2016: PloS One
https://www.readbyqxmd.com/read/27583136/drug-susceptibility-patterns-of-the-mycobacterium-tuberculosis-isolated-from-previously-treated-and-new-cases-of-pulmonary-tuberculosis-at-german-nepal-tuberculosis-project-laboratory-kathmandu-nepal
#16
Gobinda Thapa, Narayan Dutt Pant, Saroj Khatiwada, Binod Lekhak, Bhawana Shrestha
BACKGROUND: Multidrug resistant tuberculosis (MDR-TB) is a serious public health problem in Nepal. It is a major obstacle for the control of the tuberculosis. The main objectives of this study were to determine the prevalence of the multidrug resistant pulmonary tuberculosis and to evaluate the drug susceptibility patterns of Mycobacterium tuberculosis isolated from previously treated and newly diagnosed cases of pulmonary tuberculosis. METHODS: A cross-sectional study was conducted from March 2013 to August 2013 at German-Nepal tuberculosis project (GENETUP) laboratory, Kathmandu, Nepal...
2016: Antimicrobial Resistance and Infection Control
https://www.readbyqxmd.com/read/27574821/diagnostic-pathway-with-multiparametric-magnetic-resonance-imaging-versus-standard-pathway-results-from-a-randomized-prospective-study-in-biopsy-na%C3%A3-ve-patients-with-suspected-prostate-cancer
#17
Francesco Porpiglia, Matteo Manfredi, Fabrizio Mele, Marco Cossu, Enrico Bollito, Andrea Veltri, Stefano Cirillo, Daniele Regge, Riccardo Faletti, Roberto Passera, Cristian Fiori, Stefano De Luca
BACKGROUND: An approach based on multiparametric magnetic resonance imaging (mpMRI) might increase the detection rate (DR) of clinically significant prostate cancer (csPCa). OBJECTIVE: To compare an mpMRI-based pathway with the standard approach for the detection of prostate cancer (PCa) and csPCa. DESIGN, SETTING, AND PARTICIPANTS: Between November 2014 and April 2016, 212 biopsy-naïve patients with suspected PCa (prostate specific antigen level ≤15 ng/ml and negative digital rectal examination results) were included in this randomized clinical trial...
August 27, 2016: European Urology
https://www.readbyqxmd.com/read/27540322/genotypic-detection-of-rpob-and-katg-gene-mutations-associated-with-rifampicin-and-isoniazid-resistance-in-mycobacterium-tuberculosis-isolates-a-local-scenario-kelantan
#18
Nurul-Ain Ismail, Mohd Fazli Ismail, Siti Suraiya Md Noor, Siti Nazrina Camalxaman
BACKGROUND: Drug resistant tuberculosis (DR-TB) remains a public health issue that is of major concern on a global scale. The characterisation of clinical isolates may provide key information regarding the underlying mechanisms of drug resistance, and helps to augment therapeutic options. This study aims to evaluate the frequency of gene mutations associated with Rifampicin (RIF) and Isoniazid (INH) resistance among nine clinical isolates. METHODS: A total of nine drug resistant Mycobacterium tuberculosis clinical isolates were screened for genetic mutations in rpoB and katusing polymerase chain reaction (PCR) amplification and DNA sequencing...
January 2016: Malaysian Journal of Medical Sciences: MJMS
https://www.readbyqxmd.com/read/27532475/immune-activation-by-mycobacterium-tuberculosis-in-hiv-infected-and-uninfected-subjects
#19
Chloé Wyndham-Thomas, Véronique Corbiere, Elodie Selis, Marie-Christine Payen, Jean-Christophe Goffard, Jean-Paul Van Vooren, Françoise Mascart, Violette Dirix
INTRODUCTION: This study investigates the influence of M. tuberculosis infection on immune-activation biomarkers, both in HIV-infected and -uninfected subjects. METHODS: Forty-eight treatment naïve HIV-infected patients and 74 HIV-uninfected subjects were recruited and divided into groups according to their M. tuberculosis-infection status: latent tuberculosis infection (LTBI), active tuberculosis (TB) and no evidence of M. tuberculosis infection. The expression of cellular markers CD38 and HLA-DR on circulating CD8 T-lymphocytes and the plasmatic levels of soluble markers IL-6, sCD14 and D-Dimer were measured and compared between groups...
August 16, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/27509488/diversity-of-human-and-macaque-airway-immune-cells-at-baseline-and-during-tuberculosis-infection
#20
Richard F Silver, Amy J Myers, Jessica Jarvela, JoAnne Flynn, Tara Rutledge, Tracey Bonfield, Philana Ling Lin
Immune cells of the distal airways serve as "first responders" of host immunity to the airborne pathogen Mycobacterium tuberculosis (Mtb). Mtb infection of cynomolgus macaques recapitulates the range of human outcomes from clinically silent latent tuberculosis infection (LTBI) to active tuberculosis of various degrees of severity. To further advance the application of this model to human studies, we compared profiles of bronchoalveolar lavage (BAL) cells of humans and cynomolgus macaques before and after Mtb infection...
December 2016: American Journal of Respiratory Cell and Molecular Biology
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