Malaria is transmitted via gametocyte-infected erythrocytes (GIEs) that are taken up when a mosquito bites. Immature, rigid GIEs are sequestered in the bone marrow; upon release into the peripheral blood they show increased deformability, which allows them to pass through the spleen.
A new approach to blocking malaria transmission harnesses this change in deformability, which is regulated by parasite cyclic AMP-dependent kinase signalling. By increasing cAMP levels pharmacologically, researchers were able to turn mature, deformable GIEs into stiff, non-transmissable gametocytes. Conversely, inhibiting the cAMP-dependent kinase rendered immature gametocytes more deformable.
“Our molecular observations have the potential to be translated into therapies for blocking malaria transmission by demonstrating that raising cAMP levels with sildenafil (Viagra) renders mature gametocytes rigid,” the authors write in PLoS Pathogens
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(online, 7 May 2015).