Partitioning and quantifying regulatory mechanisms acting on within-host malaria using the effective propagation number

Immune clearance and resource limitation (via red blood cell depletion) shape the peaks and troughs of malaria parasitaemia, which in turn affect disease severity and transmission. Quantitatively partitioning the relative roles of these effects through time is challenging. Using data from rodent malaria we estimate the effective propagation number, which shows that the relative importance of contrasting within-host control mechanisms fluctuates through time and is sensitive to the inoculating parasite dose. Furthermore, the capacity of innate responses to restrict initial parasite growth saturates with parasite dose, and experimentally enhanced innate immunity can affect parasite density indirectly via resource depletion. Our statistical approach offers a tool to improve targeting of drugs or vaccines for human therapy by revealing the dynamics and interactions of within-host regulatory mechanisms.