S Dian, V Yunivita, A R Ganiem, T Pramaesya, L Chaidir, K Wahyudi, T H Achmad, A Colbers, L Te Brake, R van Crevel, R Ruslami, R Aarnoutse
High doses of rifampin may help patients with tuberculous meningitis (TBM) to survive. Pharmacokinetic pharmacodynamic evaluations suggested that rifampin doses higher than 13 mg/kg given intravenously or 20 mg/kg given orally (as previously studied) are warranted to maximize treatment response. In a double-blind, randomized, placebo-controlled phase II trial, we assigned 60 adult TBM patients in Bandung, Indonesia, to standard 450 mg, 900 mg, or 1,350 mg (10, 20, and 30 mg/kg) oral rifampin combined with other TB drugs for 30 days...
December 2018: Antimicrobial Agents and Chemotherapy
Radhey S Gupta, Brian Lo, Jeen Son
The genus Mycobacterium contains 188 species including several major human pathogens as well as numerous other environmental species. We report here comprehensive phylogenomics and comparative genomic analyses on 150 genomes of Mycobacterium species to understand their interrelationships. Phylogenetic trees were constructed for the 150 species based on 1941 core proteins for the genus Mycobacterium , 136 core proteins for the phylum Actinobacteria and 8 other conserved proteins. Additionally, the overall genome similarity amongst the Mycobacterium species was determined based on average amino acid identity of the conserved protein families...
2018: Frontiers in Microbiology
Paul K Drain, Kristina L Bajema, David Dowdy, Keertan Dheda, Kogieleum Naidoo, Samuel G Schumacher, Shuyi Ma, Erin Meermeier, David M Lewinsohn, David R Sherman
Tuberculosis (TB) is the leading infectious cause of mortality worldwide, due in part to a limited understanding of its clinical pathogenic spectrum of infection and disease. Historically, scientific research, diagnostic testing, and drug treatment have focused on addressing one of two disease states: latent TB infection or active TB disease. Recent research has clearly demonstrated that human TB infection, from latent infection to active disease, exists within a continuous spectrum of metabolic bacterial activity and antagonistic immunological responses...
October 2018: Clinical Microbiology Reviews
Lucky G Ngwira, Elizabeth L Corbett, McEwen Khundi, Grace L Barnes, Austin Nkhoma, Michael Murowa, Silvia Cohn, Lawrence H Moulton, Richard E Chaisson, David W Dowdy
Background: Tuberculosis (TB) remains the leading cause of death among HIV-positive individuals globally. Screening for TB at the point of HIV diagnosis with a high-sensitivity assay presents an opportunity to reduce mortality. Methods: We performed a cluster randomized trial of TB screening among adults newly diagnosed with HIV in 12 primary health clinics in rural Thyolo, Malawi ( NCT01450085). Clinics were allocated in a 1:1 ratio to perform either point-of-care Xpert MTB/RIF (Xpert) or point-of-care light-emitting diode fluorescence microscopy (LED FM) for individuals screening positive for TB symptoms...
July 27, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Ankur Gupta-Wright, Elizabeth L Corbett, Joep J van Oosterhout, Douglas Wilson, Daniel Grint, Melanie Alufandika-Moyo, Jurgens A Peters, Lingstone Chiume, Clare Flach, Stephen D Lawn, Katherine Fielding
BACKGROUND: Current diagnostics for HIV-associated tuberculosis are suboptimal, with missed diagnoses contributing to high hospital mortality and approximately 374 000 annual HIV-positive deaths globally. Urine-based assays have a good diagnostic yield; therefore, we aimed to assess whether urine-based screening in HIV-positive inpatients for tuberculosis improved outcomes. METHODS: We did a pragmatic, multicentre, double-blind, randomised controlled trial in two hospitals in Malawi and South Africa...
July 28, 2018: Lancet
Dick Menzies, Menonli Adjobimey, Rovina Ruslami, Anete Trajman, Oumou Sow, Heejin Kim, Joseph Obeng Baah, Guy B Marks, Richard Long, Vernon Hoeppner, Kevin Elwood, Hamdan Al-Jahdali, Martin Gninafon, Lika Apriani, Raspati C Koesoemadinata, Afranio Kritski, Valeria Rolla, Boubacar Bah, Alioune Camara, Isaac Boakye, Victoria J Cook, Hazel Goldberg, Chantal Valiquette, Karen Hornby, Marie-Josée Dion, Pei-Zhi Li, Philip C Hill, Kevin Schwartzman, Andrea Benedetti
BACKGROUND: A 9-month regimen of isoniazid can prevent active tuberculosis in persons with latent tuberculosis infection. However, the regimen has been associated with poor adherence rates and with toxic effects. METHODS: In an open-label trial conducted in nine countries, we randomly assigned adults with latent tuberculosis infection to receive treatment with a 4-month regimen of rifampin or a 9-month regimen of isoniazid for the prevention of confirmed active tuberculosis within 28 months after randomization...
August 2, 2018: New England Journal of Medicine
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