Fig. 3

Whole blood chloroquine levels following the treatment of adults with acute vivax malaria (dose 25 mg base/kg) on the Thailand—Myanmar border. The three grey lines show the 95th, 50th and 5th percentiles for the observed data. The corresponding 95% confidence intervals from 1000 simulations based on the population pharmacokinetic model are shown as shaded areas. The black dots are the true observations; from Hoglund et al. [60]. The upper horizontal blue arrowed line shows the corresponding 50th percentile whole blood chloroquine concentrations at the approximate time of tropical P. vivax relapse liberation of merozoites into the circulation, and the lower blue arrowed line shows the corresponding approximate whole blood chloroquine concentration at relapse patency. The first relapse of P. vivax malaria emerges around 14 days after starting treatment (first vertical light-blue dashed line) at which time the whole blood chloroquine levels have fallen to around 150 ng/mL. If artesunate (5–7 days) had been the treatment there would have been no suppression of blood-stage multiplication of the relapse, as the drug would have been fully eliminated a week earlier. Relapses following artesunate would have become apparent around 3 weeks after starting treatment (green line). With the slowly eliminated chloroquine relapses are delayed by suppression of multiplication. The exact sub-microscopic profile is unknown but should be within the yellow lines (limits). Based on concentration-effect modelling by Watson et al. [58] the most likely parasitaemia-time profile is shown by the red line. The smaller graph on the right shows a chloroquine in-vitro susceptibility assessment by Russell et al. [65]