Plasmodium falciparum adhesion in the placenta

Plasmodium falciparum parasites sequester in the human placenta, and placental malaria is associated with disease and death of both mother and child. Placental isolates of P. falciparum uniformly bind to chondroitin sulfate A on the syncytiotrophoblast. Forms of the variant surface antigen PfEMP1 that bind chondroitin sulfate A in vitro (PfEMP1(varCSA)) are highly conserved in many field isolates. Two related forms of PfEMP1(varCSA) are commonly expressed by placental isolates, but these are also transcribed by most non-placental isolates. PfEMP1(varCSA) gene transcription is not upregulated when parasites are selected to bind chondroitin sulfate A, but other PfEMP1 forms may be upregulated. Young ring-stage parasites derived from chondroitin sulfate A-binding isolates may also bind to the endothelium through a process that does not involve PfEMP1 or chondroitin sulfate A. Adhesins and other surface proteins of placental parasites are targets of naturally occurring antibodies associated with protection and therefore could be used to develop vaccines that prevent malaria in pregnancy.