No change in slope of log(%parasitemia) after onset of thrombocytopenia that would suggest platelets affecting parasite replication in resolving, non-eCM Pca LV infection. Parasitemia denoted by red circles (left y-axis) with corresponding platelet counts/mL in blue circles (right y-axis) for panels A-B. (A) Parasitemia of Pca-infected mice (n = 10) plotted on a linear scale with latent parasitemia coinciding with thrombocytopenia. (B) Parasitemia in panel A plotted on logarithmic scale and no change in slope occurs at the onset of thrombocytopenia on day 4 PI. This experiment was replicated 3 times. (C) Modeling of log of %(parasitemia) at selected rates of parasite killing by platelets between day 0 and 4 PI assuming sequestration does not affect parasitemia. We model the Pca LV parasitemia in a 20 g mouse, which calculates the initial parasitemia (supplemental Table 1). Platelet killing of Pf-iRBCs is ∼80%,^4,5  and we compare this with a more conservative 40% killing and no killing. At initiation of LV infection, the 20 g mouse has: 1 × 10⁶ iRBCs; 1.6 × 10¹⁰ RBCs; 1.6 × 10⁹ platelets; and a platelet effector to iRBC target ratio >1000, resulting in ∼80% killing of iRBCs by platelets based on in vitro killing of Pf-iRBCs.^4,5  At the onset of thrombocytopenia (day 4PI: ∼0.5% parasitemia; 1.6 × 10¹⁰ RBCs, and 1.6 × 10⁹ platelets), the platelet effector-to-target ratio is 20:1; theoretically, platelet killing is minimal below 160:1.⁵  The period of platelet killing of iRBCs is therefore between day 0 and 4 PI (shaded, labeled “Period of platelet killing”). During ascending parasitemia (day 7PI: ∼6% parasitemia; 1.6 × 10¹⁰ RBCs; and ∼1.6 × 10⁸ platelets), the ratio is 1:600. The parasite replicates each night producing new progeny, and the MOI during period of no killing and determined from panel B is 2.8. If each day during the platelet killing period, 80% or 40% of iRBCs are killed by platelets, then MOI declines to 0.6 (20% of 2.8) and 1.7 (60% of 2.8), respectively. The measured parasitemia (B) fits 0% line rather than 40% or 80% killing. (D) Modeling of log(%parasitemia) assuming similar degrees of iRBC sequestration throughout ascending parasitemia and platelet killing until day 4 PI as described above in panel C. Because the slope of log(%parasitemia) is linear, parasitemia likely reflects overall parasite load. The slope of log(%parasitemia) during period of platelet killing from day 0 to 4PI is 2.8 (B); this estimates effective rate of parasitemia increase with sequestration. Because platelet killing is minimal beyond day 4 PI, this rate of parasitemia increase should increase markedly with an MOI from 2.8 (0% killing) to 14 (80% killing) and 7 (40% killing) after day 4 PI. The measured parasitemia (B) clearly fits 0% platelet killing best. The modeling indicates that the slope of log(%parasitemia) should change markedly if platelet killing occurs.