Additional file 14 of Clinical recovery of Macaca fascicularis infected with Plasmodium knowlesi

Additional file 14: Fig. S5. Characterization of the dynamics of RBC removal and production processes in a representative kra monkey (12C44) during a P. knowlesi infection. To quantify the haemodynamic processes during a P. knowlesi infection, a computational dynamical model was used that was previously developed to faithfully track the blood dynamics in Plasmodium infected monkeys [63–65]. The model was formulated as a set of discrete recursive equations, where the pools of reticulocytes, RBCs, and iRBCs were stratified into age classes. The model directly represents that reticulocytes are released from the bone marrow with a certain age and rate, circulate for a day and then mature into RBCs. Pertinent model results (lines) are superimposed on experimental data (symbols). Shown are the circulating reticulocytes (A), mature RBCs (C), and infected RBCs (F), from which the model allowed the quantification of different causes of RBC removal (D and E). The NHP RBCs normally die after about 100 days due to senescence, or on a daily basis due to “random” effects, such as shear stresses (E). During Plasmodium infections, some of the healthy RBCs are also infected by merozoites and destroyed when the parasites are released (parasitisation, D) or lost to a bystander effect (D). Interestingly, large numbers of RBCs were lost during the infection due to the bystander mechanism (D). The profile of RBCs (C) demonstrates that the kra monkey had severe anaemia and responded appropriately by increasing the erythropoietic output and releasing younger reticulocytes, thereby increasing the reticulocyte maturation time in circulation (B).