In natural Plasmodium falciparum infections, parasitized erythrocytes (PEs)
circulate in the peripheral blood for a period corresponding roughly to th
e first part of the erythrocytic life cycle (ring stage). Later, in blood-s
tage development, parasite-encoded adhesion molecules are inserted into the
erythrocyte membrane, preventing the circulation of the PEs, The principal
molecule mediating PE adhesion is P. falciparum erythrocyte membrane prote
in 1 (PfEMP1), encoded by the polymorphic var gene family. The population o
f parasites is subject to clonal antigenic variation through changes in var
expression, and a single PfEMP1 variant is expressed at the PE surface in
a mutually exclusive manner. In addition to its role in immune evasion, swi
tches in PfEMP1 expression may be associated with fundamental changes in pa
rasite tissue tropism in malaria patients. A switch from CD36 binding to ch
ondroitin sulphate A (CSA) binding may lead to extensive sequestration of P
Es in placenta syncytiotrophoblasts. This is probably a key event in malari
a pathogenesis during pregnancy. The CSA-binding phenotype of mature PEs is
linked to another distinct adhesive phenotype: the recently described CSA-
independent cytoadhesion of ring-stage PEs, Thus, a subpopulation of PEs th
at sequentially displays these two different phenotypes may bind to an indi
vidual endothelial cell or syncytiotrophoblast the asexual blood-stage cycl
e. This that non-circulating (cryptic) parasite throughout suggests that no
n-circulating (cryptic) parasite subpopulations are present in malaria pati
ents.