Grant: Foundation Grant

Cost Effectiveness Analysis; Drug Resistance; Infectious Disease Modeling; Latent Tuberculosis; Randomized Trial; Systematic Reviews And Meta-Analyses; Tuberculosis; Tuberculosis Prevention; Tuberculosis Treatment

<html> <body> <p>Tuberculosis (TB) remains a leading infectious cause of morbidity and death worldwide, and an important problem among the foreign born and indigenous populations in Canada. To achieve the goal of &lsquo;ending TB&rsquo;, announced by Health Canada and the World Health Organization, two major problems must be addressed:<br> 1) Latent TB infection (LTBI) It is estimated that 2 billion persons world-wide have dormant or latent TB, of whom less than 1% are treated now; without treatment approximately 200 million of these will develop active TB in the next 20 years.<br> 2) Drug-resistant TB (DR-TB) is steadily increasing in all countries of the world and the emergence of highly resistant strains raises the spectre of a resurgent and untreatable epidemic. Despite occurrence of more than 1 million cases of INH resistant TB annually, there is astonishingly little research to improve the current inadequate regimens used now<br> </p> <p>My research programme over the next 7 years will investigate pragmatic solutions to two major public health problems, using innovative methods. The first theme is how to increase the detection and treatment of LTBI to prevent TB disease. A multi-centre stepped-wedge cluster randomized trial is planned in Canada and 5 other countries. This will start with a Cascade of Care analysis &ndash; to evaluate barriers to LTBI diagnosis and treatment encountered by close contacts of TB patients. Operational modeling analysis will be used to inform selection, from a "public health tool-kit", of effective interventions identified in a systematic review. These interventions will then be applied in a stepwise and randomized order at participating sites, to measure the impact on contacts identified and treated successfully. Findings will inform the global roll-out of LTBI diagnosis and therapy &ndash; part of the WHO post-2015 end-TB plan<br> </p> <p>The second major theme is to improve treatment of INH resistant-TB. In the first 3 years modeling studies, systematic reviews and individual patient data meta-analyses will examine treatment options for INH resistant TB, including two new drugs &ndash; Bedaquiline and Delamanid, plus Linezolid and fluoro-quinolones. This will inform selection of regimens for a multi-arm, multi-stage randomized trial among patients with INH-Resistant TB in Years 4-7. To enhance feasibility, and reduce costs, both trials will be conducted at study sites that participated in the trial of 4RIF vs 9INH (the 4v9 trial), which has just completed enrolment of 6,871 adults and children<br> </p> <p>I have named a large number of programme experts. Those from McGill will contribute methodological support for conduct and training in multi-disciplinary research. Experts at the other Canadian and international sites, who have collaborated in several past projects, will contribute clinical and epidemiologic expertise. The research environment will be strong at the participating Canadian and international sites&ndash; with excellent clinical services, well trained and experienced research staff, and well trained, interested and motivated investigators<br> </p> <p>Training and mentoring of international and Canadian students in modeling, cost-effectiveness, systematic reviews, field work, data analysis, and trial methods will range from short intensive courses of 1-2 weeks, to multi-year Master&rsquo;s or PhD degree programmes. This research capacity development will take advantage of new McGill programmes, training expertise at other Canadian sites, and the international research network involved in this project.</p> </body> </html>