title: Disrupting rhythms in Plasmodium chabaudi: costs accrue quickly and independently of how infections are initiated.
abstract: BACKGROUND
  In the blood, the synchronous malaria parasite, Plasmodium chabaudi, exhibits a cell-cycle rhythm of approximately 24 hours in which transitions between developmental stages occur at particular times of day in the rodent host. Previous experiments reveal that when the timing of the parasite's cell-cycle rhythm is perturbed relative to the circadian rhythm of the host, parasites suffer a (~50%) reduction in asexual stages and gametocytes. Why it matters for parasites to have developmental schedules in synchronization with the host's rhythm is unknown. The experiment presented here investigates this issue by: (a) validating that the performance of P. chabaudi is negatively affected by mismatch to the host circadian rhythm; (b) testing whether the effect of mismatch depends on the route of infection or the developmental stage of inoculated parasites; and, (c) examining whether the costs of mismatch are due to challenges encountered upon initial infection and/or due to ongoing circadian host processes operating during infection.
  
  
  METHODS
  The experiment simultaneously perturbed the time of day infections were initiated, the stage of parasite inoculated, and the route of infection. The performance of parasites during the growth phase of infections was compared across the cross-factored treatment groups (i e, all combinations of treatments were represented).
  
  
  RESULTS
  The data show that mismatch to host rhythms is costly for parasites, reveal that this phenomenon does not depend on the developmental stage of parasites nor the route of infection, and suggest that processes operating at the initial stages of infection are responsible for the costs of mismatch. Furthermore, mismatched parasites are less virulent, in that they cause less anaemia to their hosts.
  
  
  CONCLUSIONS
  It is beneficial for parasites to be in synchronization with their host's rhythm, regardless of the route of infection or the parasite stage inoculated. Given that arrested cell-cycle development (quiescence) is implicated in tolerance to drugs, understanding how parasite schedules are established and maintained in the blood is important.
authors.affiliation: Institutes of Evolution, Immunology and Infection Research, University of Edinburgh, Edinburgh, UK. Aidan.Odonnell@ed.ac.uk.
authors.forename: Aidan J
authors.initials: AJ
authors.lastname: O'Donnell
authors.forename: Nicole
authors.initials: N
authors.lastname: Mideo
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Reece
mesh_terms: D000818:Animals; D002940:Circadian Rhythm; D008288:Malaria / Q000469:parasitology*; D008297:Male; D051379:Mice; D016788:Plasmodium chabaudi / Q000254:growth & development*; D012377:Rodentia / Q000469:parasitology* / Q000502:physiology*