Relapses Contribute Significantly to the Risk of Plasmodium vivax Infection and Disease in Papua New Guinean Children 1-5 Years of Age

Background. Plasmodium vivax forms long-lasting hypnozoites in the liver. How much they contribute to the burden of P. vivax malaria in children living in highly endemic areas is unknown. Methods. In this study, 433 Papua New Guinean children aged 1-5 years were Randomized to receive artesunate (7 days) plus primaquine (14 days), artesunate alone or no treatment and followed up actively for recurrent Plasmodium infections and disease for 40 weeks. Results. Treatment with artesunate-primaquine reduced the risk of P. vivax episodes by 28% (P=.042) and 33% (P=.015) compared with the artesunate and control arms, respectively. A significant reduction was observed only in the first 3 months of follow-up (artesunate-primaquine vs control, -58% [P=.004]; artesunate-primaquine vs artesunate, -49% [P=.031]) with little difference thereafter. Primaquine treatment also reduced the risk of quantitative real-time polymerase chain reaction-and light microscopy-positive P. vivax reinfections by 44% (P<.001) and 67% (P<.001), respectively. Whereas primaquine treatment did not change the risk of reinfection with Plasmodium falciparum, fewer P. falciparum clinical episodes were observed in the artesunate-primaquine arm. Conclusions. Hypnozoites are an important source of P. vivax infection and contribute substantially to the high burden of P. vivax disease observed in young Papua New Guinean children. Even in highly endemic areas with a high risk of reinfection, antihypnozoite treatment should be given to all cases with parasitologically confirmed P. vivax infections.