**1. Introduction**

The emergence and spread of *Plasmodium falciparum* resistance to most of the existing antimalarial drugs is a key factor that contributes to the global reappearance of malaria [1]. This threat of treatment failure is prompting research oriented to targeting the transmission stages of the pathogen between humans and mosquitoes [2], represented by smaller populations less likely to contain resistant individuals that would benefit from the removal of susceptible parasites [3]. Transmission-blocking vaccines (TBV) aim at stimulating in the human the production of antibodies to actively target and block the parasite development once it is in the mosquito [4]. Among the candidate antigens for TBV strategies are proteins on the surface of the ookinete [5,6], the motile *Plasmodium* stage that forms in the blood bolus and has to traverse the midgut endothelium to progress to the next stage of the parasite, the oocyst.

Among other transmission-blocking strategies that can be envisaged is the interference with parasite–midgut interaction through the inhibitory action of the sulfated glycosaminoglycan (sGAG) heparin and related molecules, which have already shown antimalarial activity against several *Plasmodium* stages in humans. During initial malaria infection in the liver, heparin and heparan sulfate are hepatocyte receptors for sporozoite attachment [7]. In blood stages, heparin antimalarial activity, against which no resistances have been reported so far, unfolds by inhibition of merozoite invasion of the erythrocyte [8]. Chondroitin sulfate proteoglycans in the mosquito midgut and a synthetic polysulfonated polymer that mimics the structure of sGAGs present in the midgut epithelium have been described to bind *Plasmodium* ookinetes during host epithelial cell invasion [9,10], whereas ookinetes and ookinete-secreted proteins possess significant binding to heparin [11,12]. Here, we have explored the potential of heparin against ookinete development.
