Figure 3.

Time-to-extinction in HFS-TB and morphism-based translation to patients on the standard regimen. Standard regimen kill curve for both bacteria in log-phase growth plus intracellular and in the semi-dormant state. (a) The model explains the depletion of both subpopulations; the orange circles show log-phase/intracellular M. tuberculosis observations, while the grey circles show semi-dormant population observations in the HFS-TB, based on both TTP and log₁₀ cfu/mL. The lines are the model fitting, with the red line representing extracellular log-phase growth and intracellular M. tuberculosis, while the black line is for the persister population. (b) The HFS-TB data were then transformed based on structure-preserving mapping (morphism) to kill curves in patients; shown is the decline of the combined bacteria subpopulations (log-phase plus intracellular plus semi-dormant summation) in patients with TB. Slower depletion of persisters is demonstrated after the transformation, with a wide spread of time-to-extinction. (c) Distribution of time-to-extinction after Latin hypercube sampling. The time-to-extinction is the minimum duration of therapy needed with that regimen. For the standard therapy regimen shown here 6 months therapy would result in time-to-extinction in about 94% of patients, if doses were optimized. 3 M, 3 months; 4 M, 4 months; 6 M, 6 months. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.