Figure 6.

Schematics of P. falciparum parasite dynamics in SCID mice after treatment and potential factors explaining variance and uncertainty. (a) The mechanistic models (orange) presented in this paper assume parasite growth characteristics remain constant throughout treatment and are therefore not capturing late recrudescence. This is in contrast to the exponential model (gray) that compensates for late recrudescence by shifting the curve to low parasite and drug concentrations. Alternative to our mechanistic models, we propose some hypothetical parasite recrudescence curves (blue and green), that include additional phenomena such as altered parasite maturation and parasite dormancy offering possible explanations for late recrudescence. We cannot capture these mechanisms with models without additional data. MIC estimates important for experimental interpretation and translation to humans are shown by yellow square points and are likely to be very different given assumptions about parasite growth behavior after treatment. (b) We hypothesize and extended the sources of variance and uncertainty of the parasite treatment curve described in³⁵ to schematically illustrate parasite phenomena during growth, treatment and recrudescence for antimalarial experiments (murine and possibly human). These extended phenomena include altered parasite maturation, dormancy, and stochastic extinction occurring below the lower limit of quantification hindering estimation.