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

Many pathogenic organisms, including malaria parasites, produce specialized life stages for within-host multiplication (asexual) versus onward transmission (sexual reproduction). Restrained investment into transmission stage production-by allowing faster multiplication-is predicted to curtail the lifespan of infection via faster host recovery or mortality, a classic tradeoff between the rate and duration of transmission. In contrast, under a reproduction-survival tradeoff, restraining investment into reproduction should extend survival (for parasites, infection duration). To distinguish between these predictions, we develop a within-host mathematical model incorporating immunity to track dynamics across infection age (time since start of blood stage infection) for human malaria infections. When transmission investment is constant across infection age, increased investment reduces infection duration and parasite fitness. Optimal transmission investment occurs at a lower value (around $5\%$) than predicted by models lacking feedback between transmission investment and immunity. When strategies vary with infection age, our model shows that malaria parasites benefit from delaying transmission investment to allow for faster within-host multiplication. We show that adaptive immunity can impose a survival-reproduction tradeoff, an emergent property of the model. Our theoretical framework provides a basis for understanding the timing and duration of infectiousness, with implications for parasite evolution in response to control efforts.