Anti-malarial drug effects on parasite dynamics in vivax malaria

Relapses of Plasmodium vivax malaria are prevented by 8-aminoquinolines. If hypnozoites survive, then the subsequent blood stage infections in early relapses (< 2 months) are suppressed by the slowly eliminated anti-malarial drugs used to treat the blood stage infection (chloroquine, artemisinin combination treatments), but they are not usually eliminated. The 8-aminoquinolines have significant blood stage activity which contributes to therapeutic responses. The latent interval from primary infection to early relapse depends on the number of activatable hypnozoites, the dose of anti-malarial, its pharmacokinetic properties, the level of resistance (minimum inhibitory concentration) and immunity. The dose-response relationship for radical curative efficacy of primaquine and tafenoquine is steep over the total dose range from 1.5 to 5 mg base/kg which may explain the poor efficacy of tafenoquine at the currently recommended dose.