Figure 5
Figure 5. Modeling of ring-iRBC clearance during “circulation” and “circulation-recirculation” experiments. The uncovering of 2 ring-iRBC subpopulations. (A-C) Modeling of ring-iRBC parasitemia in the perfusate, shown by a theoretical example: one-compartment without a residual parasitemia (A), 2 compartments without a residual parasitemia (B, the plain line corresponds to the bi-exponential curve, the dotted lines to the mono-exponential curves), and 1 compartment with a residual parasitemia (C, plateau phase). The evaluation of the goodness of fit and the estimated parameters was based on the Akaike Information Criterion (AIC), the variability (VC) of the parameter estimates (the lower the AIC and VC values, the more parsimonious the model), and the random distribution of weighted residuals between measured and predicted concentrations with respect to time. Individual values are shown in Table S1. The AIC was lower for the 2-compartment model and the 1-compartment model with residual parasitemia than for the 1-compartment model without a residual parasitemia. However, for a 2-compartment model, the coefficient of variation of the second half-life parameter was not significant (> 100%). So, the 1-compartment model with residual parasitemia was the best model. (D,E) “Circulation-recirculation” experiments. Part of the iRBC and RBC population prepared for a spleen challenge (“Spleen naive” population) was kept at 37°C in perfusion medium, whereas the other part was perfused through the spleen. (D) Forty minutes after the perfusion onset, iRBCs and RBCs were retrieved from the circulating perfusate (D, “Spleen passaged” population). Both populations were differentially labeled using either PKH-26 or PKH-76 and then pooled and reintroduced into the perfusate 110 to 120 minutes after the initial perfusion step. Clearance kinetics of each iRBC subpopulation established using flow cytometry showing that spleen “naive” ring-iRBCs were cleared, whereas iRBCs previously submitted to approximately 40 spleen passages were not. The most parsimonious model of the kinetics of the “spleen naive” population was again 1 compartment with a residual parasitemia. Mean (individual values) AIC and half-life from 2 independent experiments were similar to that observed during the 6 previous “circulation” experiments (E). The most parsimonious model for the “spleen passaged” population was a residual parasitemia without elimination (Table S1).

Modeling of ring-iRBC clearance during “circulation” and “circulation-recirculation” experiments. The uncovering of 2 ring-iRBC subpopulations. (A-C) Modeling of ring-iRBC parasitemia in the perfusate, shown by a theoretical example: one-compartment without a residual parasitemia (A), 2 compartments without a residual parasitemia (B, the plain line corresponds to the bi-exponential curve, the dotted lines to the mono-exponential curves), and 1 compartment with a residual parasitemia (C, plateau phase). The evaluation of the goodness of fit and the estimated parameters was based on the Akaike Information Criterion (AIC), the variability (VC) of the parameter estimates (the lower the AIC and VC values, the more parsimonious the model), and the random distribution of weighted residuals between measured and predicted concentrations with respect to time. Individual values are shown in Table S1. The AIC was lower for the 2-compartment model and the 1-compartment model with residual parasitemia than for the 1-compartment model without a residual parasitemia. However, for a 2-compartment model, the coefficient of variation of the second half-life parameter was not significant (> 100%). So, the 1-compartment model with residual parasitemia was the best model. (D,E) “Circulation-recirculation” experiments. Part of the iRBC and RBC population prepared for a spleen challenge (“Spleen naive” population) was kept at 37°C in perfusion medium, whereas the other part was perfused through the spleen. (D) Forty minutes after the perfusion onset, iRBCs and RBCs were retrieved from the circulating perfusate (D, “Spleen passaged” population). Both populations were differentially labeled using either PKH-26 or PKH-76 and then pooled and reintroduced into the perfusate 110 to 120 minutes after the initial perfusion step. Clearance kinetics of each iRBC subpopulation established using flow cytometry showing that spleen “naive” ring-iRBCs were cleared, whereas iRBCs previously submitted to approximately 40 spleen passages were not. The most parsimonious model of the kinetics of the “spleen naive” population was again 1 compartment with a residual parasitemia. Mean (individual values) AIC and half-life from 2 independent experiments were similar to that observed during the 6 previous “circulation” experiments (E). The most parsimonious model for the “spleen passaged” population was a residual parasitemia without elimination (Table S1).

Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal