Rapid diagnosis of Mycobacterium tuberculosis resistance, beyond rifampicin

The availability of diagnostic tools for detecting resistance to tuberculosis (TB) drugs remains a challenge in low-income countries where they are needed most. Rapid molecular tests are available at the decentralized level to diagnose resistance to rifampicin, the key first-line anti-TB drug. However, available assays to diagnose resistance to other drugs are technically demanding and only available in reference laboratories. As a result, rifampicin-resistant (RR) patients with resistance to additional TB drugs are often treated with ineffective and potentially toxic drugs. In this proposal, we intend to evaluate the performance of new tools for diagnosing this resistance that can be implemented at different levels of the diagnostic pyramid. In addition, we will determine for the first time, using comprehensive data from the sub-Saharan African (SSA) region, the phylogeography of the Mycobacterium tuberculosis complex (MTBC) lineages, the specific MTBC gene mutations circulating in the region, as well as their diagnostic implications. We will also be able to better understand the transmission dynamics of (RR)TB in SSA. We anticipate that this large and unique study will generate key evidence that will be used by the World Health Organization (WHO) to issue new policies on the diagnosis and management of RR-TB. The impact of this study, and thus its results, will likely contribute to improved RR-TB control in SSA and beyond.