Clinical Evaluation of a New Highly Sensitive Multiplex qPCR for Detecting tuberculosis and Non-tuberculous Mycobacteria

Tuberculosis (TB) remains a major public health problem in developing countries. Recent reports indicate a constant increase in the prevalence of nontuberculous mycobacteria (NTM) in these traditional TB settings. NTM infection is clinically undistingable from tuberculosis and poses significant challenges in patient management. The sputum smear, the most widely used diagnostic tool for TB is more than 100 years old, misses half of tuberculosis cases, and cannot differentiate between mycobacterial species. The World Health Organization (WHO) recommends Xpert MTB/RIF assay and other molecular tools, however, Xpert MTB/RIF is less sensitive than sputum culture (the current gold standard) and does not address the differential with growing NTM infections. In this application, we propose to leverage the scientific infrastructure and collaboration between the Northwestern Center for Innovation in Global Health Technologies (CIGHT), the SEREFO HIV/TB Laboratory in Mali to evaluate our newly developped Multiplex MTB/NTM assay that can differentiate, at least M. tuberculosis complex (MTBC) from the treatable and the most common NTM, M. avium complex (MAC). Our preliminary data suggest a performance for our assay to be superior to Xpert TB/RIF and comparable to sputum culture. The specific aims of this project are to evaluate the assay in 1) Chronic TB-like cases, 2) TB sputum smear negative cases and 3) Xpert TB/RIF negative cases. We will evaluate the assay sensitivity, specificity, positive and negative predictive values for both MTBC and NTM. The development and validation of such tools will significantly contribute in the fight against both TB and NTM diseases worldwide. Finally, we have assembled an excellent and complementary team to ensure the success of this multidisciplinary and highly innovative project.