Malaria parasites adjust liver stage development to synchronise the blood stage of infection with host daily rhythms

Synchronised multiplication of Plasmodium parasites within red blood cells causes periodic malaria fevers. Aligning blood-stage development with the vertebrate host’s feeding-fasting rhythm facilitates within-host survival and between-host transmission. We use the rodent model Plasmodium chabaudi to test when, following development in the liver, the blood stage of infection begins. We find egress from the liver into the blood is aligned with the time of day of rhythmic host feeding, but only in wild type hosts, with egress occurring after a fixed period of pre-erythrocytic development in hosts without a functional canonical clock. However, perturbing the duration over which parasites enter the bloodstream does not affect their multiplication rate in the first few IDCs, suggesting fitness benefits from timing egress anticipates rhythmic challenges or opportunities later in the infection.