Mistimed malaria parasites re‐synchronise with host feeding‐fasting rhythms by shortening the duration of intra‐erythrocytic development

Aims
Malaria parasites exhibit daily rhythms in the intraerythrocytic development cycle (IDC) that underpins asexual replication in the blood. The IDC schedule is aligned with the timing of host feeding-fasting rhythms. When the IDC schedule is perturbed to become mismatched to host rhythms, it readily reschedules but it is not known how.

Methods
We intensively follow four groups of infections that have different temporal alignments between host rhythms and the IDC schedule for 10 days, before and after the peak in asexual densities. We compare how the duration, synchrony, and timing of the IDC differs between parasites in control infections and those forced to reschedule by 12 hours, and ask whether the density of parasites affects the rescheduling process.

Results and Conclusions
Our experiments reveal parasites shorten the IDC duration by 2-3 hours to become realigned to host feeding-fasting rhythms with 5-6 days, in a density independent manner. Furthermore, parasites are able to reschedule without significant fitness costs for them or their hosts. Understanding the extent of, and limits on, plasticity in the IDC schedule may reveal targets for novel interventions, such as drugs to disrupt IDC regulation and preventing IDC dormancy conferring tolerance to existing drugs.