Analysis of P falciparum–iRBC deposition in the human spleen. (A,B) Mean (SEM) number of iRBCs/100 RBC in the perifollicular zone (PFZ) or in the red pulp (RP) for ring-iRBCs (R, in PFZ, in RP), schizont-iRBCs (S, in PFZ, in RP), or extra-erythrocytic parasite remnants (EER, in PFZ, in RP) subpopulations (mean from 6 isolated-perfused human spleen experiments, Giemsa-stained sections; WP indicates white pulp). Bar represents 50 μm. Typical aspects of each parasite development stage are shown on the inserts (middle column). (C) Retention index (RI = (“number of iRBCs/100 RBCs” as in panel B)/(circulating parasitemia at the end of the corresponding experiment)) for ring-iRBCs (R) or schizont-iRBCs (S) either in the PFZ or in the RP. An RI of 1 (black dotted line) corresponds to absence of retention. (D,E) Same approach as in panels A,B, but using PAS staining (a indicates central artery). (F) Purple PAS-stained section (bar represents 5 μm) showing the basal membrane of venous sinuses. Working classification of RBC deposition in the spleen red pulp: in the sinus lumen (SL), in the cords in direct contact with the sinus wall basal membrane (cordal abluminal, CoA), or in the cords but without contact with the basal membrane (cordal stricto sensu, Co). (G) RI for ring-iRBCs using the working classification of RBC deposition in the RP defined in panel F. (H,I) Transmission electron microscopy of a human isolated-perfused spleen sample showing a ring-iRBCs (white star) and an uninfected RBC (black star) upstream and downstream of an interendothelial slit (black arrows), respectively. This disposition reflects the cord- (Co) to-sinus lumen (SL) circulation of RBC in the spleen red pulp. The knobless membrane of the ring-iRBC is very close to the sinus wall basal membrane (white arrows). *P < .05, **P ≤ .01, #P < .001, statistically significant difference.