Tuberculosis Diagnostics: State of the Art and Future Directions.

Rapid and accurate diagnosis is critical for timely initiation of anti-tuberculosis (TB) treatment, but many people with TB (or TB symptoms) do not have access to adequate initial diagnosis. In many countries, TB diagnosis is still reliant on sputum microscopy, a test with known limitations. However, new diagnostics are starting to change the landscape. Stimulated, in part, by the success and rollout of Xpert MTB/RIF, an automated, molecular test, there is now considerable interest in new technologies. The landscape looks promising with a pipeline of new tools, particularly molecular diagnostics, and well over 50 companies actively engaged in product development, and many tests have been reviewed by WHO for policy endorsement. However, new diagnostics are yet to reach scale, and there needs to be greater convergence between diagnostics development and the development of shorter TB drug regimens. Another concern is the relative absence of non-sputum-based diagnostics in the pipeline for children, and of biomarker tests for triage, cure, and latent TB progression. Increased investments are necessary to support biomarker discovery, validation, and translation into clinical tools. While transformative tools are being developed, high-burden countries will need to improve the efficiency of their health care delivery systems, ensure better uptake of new technologies, and achieve greater linkages across the TB and HIV care continuum. While we wait for next-generation technologies, national TB programs must scale up the best diagnostics currently available, and use implementation science to get the maximum impact.