Immunity can impose a reproduction-survival tradeoff on human malaria parasites

Many pathogenic organisms produce specialized life stages for within-host multiplication versus on-ward transmission, including malaria parasites. Traits that enable faster multiplication—including limited investment into transmission stage production—should put host health at greater risk (all else equal). Yet it is not clear why parasites do not evolve ever faster multiplication rates, since malaria parasites do not appear to adhere to tradeoffs between the rate and duration of transmission that are classically predicted to constrain parasite evolution. To address this puzzle, we introduce an age-of-infection structured within-host mathematical model incorporating dynamic immune clearance to investigate potential tradeoffs and understand how parasites optimize their transmission investment. When investment is constant across all ages of infection, increased transmission investment reduces infection duration and parasite fitness, with optimal investment occurring at a relatively low value (around 5%), far lower than the optimum recovered from models that lack dynamic feedbacks between parasite investment and immune clearance. For age-varying strategies, our model shows that malaria parasites can enhance their fitness by delaying transmission investment to allow for faster within-host multiplication initially. Our results indicate that adaptive immunity can impose a survival-reproduction tradeoff that explains why malaria parasites cannot evolve ever faster within-host multiplication. Our theoretical framework provides a basis for understanding how transmission investment strategies alter the timing of infectiousness over the lifespan of malaria infections, with implications for parasite evolution in response to control efforts.