Future Prospects for Using Clinical Phenotypes in Tuberculosis Precision Medicine—An Approach for Clinical Management

Developing shorter treatment regimens for tuberculosis requires careful characterization of the clinical phenotype, which is defined by patient characteristics, radiological extent of disease, mycobacterial burden, drug susceptibility, and host response. Advances in 'omics and model-informed precision dosing, as well as integrated algorithms using artificial intelligence, need to be adapted and validated in clinical trials to improve classification of patients for stratified treatment. When treatment is initiated based on the clinical phenotype, monitoring of treatment response can be improved by quantification of bacterial load, transcriptomic and epigenetic biosignatures for sputum-free monitoring, and assessing disease burden by radiological and symptom scoring tools. Many of these tools are suitable for high-endemic settings. Such integrated monitoring allows prompt drug adjustments for rapid reduction in bacterial load, which prevents development of drug resistance and achieves relapse-free cure even with shorter treatment.