Keeping time with the host: reconstructing the developmental rhythms of malaria parasites

Abstract Theory predicts that pathogenic organisms benefit from aligning to host circadian rhythms, but observable data provide an incomplete picture of infection rhythms. Models are needed to reconstruct unobservable dynamics and uncover fitness impacts, challenges typified in malaria infections. Malaria parasites often synchronize their development to multiples of 24 hours and reschedule their developmental rhythms following perturbation. Yet it remains uncertain how parasites reschedule—including any cost to parasite multiplication rates— due to the difficulty of detecting parasites in all phases of their development. As parasites mature, the red blood cells they occupy adhere to blood vessel walls (sequestration, an immune evasion tactic) where they cannot be readily sampled. Existing methods cannot determine sequestration timing in vivo nor how that timing varies in perturbed within-host environments. To address these challenges, we fit a mathematical model tracking parasite development and sequestration to high-resolution time series from the rodent malaria parasite Plasmodium chabaudi . We show that parasites hasten late development—but not sequestration—to realign with host rhythms following perturbation. That rescheduling reduces multiplication rates, a result only apparent from model-reconstructed dynamics. Our novel approach recovers the timing of development and sequestration, providing insight into the consequences of circadian rhythms for parasite fitness.