Bacterial load slopes represent biomarkers of tuberculosis therapy success, failure, and relapse
Gesham Magombedze, Jotam G. Pasipanodya, Tawanda Gumbo
Abstract
Abstract There is an urgent need to discover biomarkers that are predictive of long-term TB treatment outcomes, since treatment is expense and prolonged to document relapse. We used mathematical modeling and machine learning to characterize a predictive biomarker for TB treatment outcomes. We computed bacterial kill rates, γ f for fast- and γ s for slow/non-replicating bacteria, using patient sputum data to determine treatment duration by computing time-to-extinction of all bacterial subpopulations. We then derived a γ s- slope-based rule using first 8 weeks sputum data, that demonstrated a sensitivity of 92% and a specificity of 89% at predicting relapse-free cure for 2, 3, 4, and 6 months TB regimens. In comparison, current methods (two-month sputum culture conversion and the Extended-EBA) methods performed poorly, with sensitivities less than 34%. These biomarkers will accelerate evaluation of novel TB regimens, aid better clinical trial designs and will allow personalization of therapy duration in routine treatment programs.