Interactions of P falciparum–infected RBCs with the microcirculation, and with the spleen during acute and chronic infection in patients with normal or impaired splenic function. (Ai) Simplified frame from Figure 1. For simplicity, all nonsplenic microcirculatory structures—either systemic or pulmonary—have been considered homogenous and are presented as a single microvascular channel at the top of the panel (PFZ MZ: perifollicular or marginal zones; RP: red pulp; interendothelial slits: interendothelial slits). Of note, large vessels correspond to the only compartment that can routinely be explored for the presence of infected RBCs (thin and thick smears, or PCR). Forms observed in the rectangle in the middle of the panel symbolize what is usually observed on patient smears in the corresponding situation. (Aii) Situation in a naïve patient (see text for definition) with a normal spleen function. Interactions are shown separately for the young ring forms (rings, left panel) and the mature forms (right panel). (Aiii) Same situation as above, but integrating the retention of a proportion of rings upstream from interendothelial slits, as recently observed in an ex vivo human spleen model.⁶  (Bi-ii) Comparative modeling of situations during the first acute infection in unsplenectomized (Bi top panel identical to panel Aiii) and splenectomized patients (Bii lower panel). (Ci-ii) Comparison of acute infection in immune unsplenectomized (panel Bi identical to panel Aiii) or splenectomized patients still exposed to P falciparum transmission after splenectomy (Bii). (Di-ii) Putative mechanisms of acute malaria attacks occurring a few weeks after splenectomy in chronic carriers no longer exposed to P falciparum transmission.