Project: Optimizing the clinical utility of Whole Genome Sequencing to enhance Drug-Resistant Tuberculosis outcomes

Acronym	Optim-TB (Reference Number: TMA2018CDF-2372)
Duration	01/10/2019 - 30/09/2022
Project Topic	Resistance to anti-tuberculosis drugs has emerged as a key public health challenge of modern times. The last decade has seen an unprecedented increase in resistance to rifampicin and isoniazid (defined as multidrug resistance), and has been supplanted by additional resistance to fluoroquinolones and second line injectable agents: amikacin, kanamycin and capreomycin (defined as extensive resistance). Multidrug resistant TB (MDR-TB) and extensively drug resistant TB (XDR-TB) drive approximately a quarter of the global TB related mortality, are unsustainably costly to treat and pose a major threat to continued transmission of infection. Current treatment options for XDR-TB fail to cure 30-75% of patients with XDR-TB, contributing to an emerging public health crisis. The management of drug-resistant TB is challenged by limitations of our current diagnostics, with limited capacity to detect drug resistance and slow turnaround times. The proposed study is embedded within the CAPRISA 020 Index Study. The study is the first-of-its kind, utilizing the most robust sequencing technology to provide an individualized treatment regimen for patients with drug-resistant TB. The proposed study will focus on improving understanding of the development of resistance in patients undergoing treatment, optimize the extraction of DNA directly from sputum and assess the contribution of the various pathogen factors that impact on drug-resistant TB outcomes. We anticipate translation of the basic science studies linked to the Index trial will improve the utility of sequencing technology to provide a robust real-time diagnostic assay, will provide a comprehensive algorithm for the inclusion and exclusion of drugs based on clinical relevance of resistance mutations, will improve our understanding on the differential pathogenesis and disease outcomes by certain strain types and inform targeted interventions for interrupting transmission. The implications of such a study are profound and will pave the path for new therapeutic and management approaches for drug-resistant TB. In addition to scientific contributions, the proposed project provides training opportunities for junior researchers thereby increasing the critical mass of global health scientists.
Network	EDCTP2
Call	Career Development Fellowships 2018

Project partner

Number	Name	Role	Country
1	Centre for the Aids Programme of Research in South Africa	Coordinator	South Africa