(A) Estimated parasite numbers during the different life cycle stages reveals that transmission to and from the mosquito is associated with significant decreases in parasite numbers (meros, merozoites; spz, sporozoites; sg salivary gland; EEFs, exoerythrocytic forms). Adapted from Povelones et al [111]. (B) Specific bottlenecks faced by Plasmodium sporozoites: Cartoon of the sporozoites journey from mosquito to mammalian host, highlighting the following bottlenecks: #1 Estimates suggest ~20% of oocyst sporozoites reach the salivary glands; #2 Less than 1% of salivary gland sporozoites are expelled during probing; #3 ~20% of inoculated sporozoites enter the bloodstream; #4 represents several unmeasured bottlenecks, namely the efficiency with which sporozoite arrest in the liver, enter hepatocytes, and develop into liver stages. Artwork by Brandy Lee Bennett.