Plasmodium falciparum transmission can be modulated by both blood meal- and mosquito-derived nitric oxide

Previous work has revealed that NO exerts a concentration-dependent modulation of Plasmodium falciparum exflagellation, the production of male gametocytes within the mosquito midgut. Here, we demonstrate that the addition of the NO donor, S-nitroso-N-acetyl-D,L-penicillamine (SNAP; 150 μM) to the blood feed of Anopheles stephensi inhibits infectivity of P. falciparum at both oocyst and sporozoite stages of development compared to controls. In addition, treatment of the mosquito glucose with 2% L-arginine (L-arg, a substrate for NO synthesis) negatively modulates infectivity in an additive manner with the addition of SNAP to the blood feed. Infectivity is enhanced, however, by the addition of 0.625 g/L aminoguanidine hemisulphate (AG; an NO inhibitor) to either the blood feed or the mosquito glucose, and again there is an additive enhancement when both the blood and the glucose are treated. The results correlate with previous observations in rodent malaria.