Plasmodium vivax Malaria Relapse Risk Depends on Transmission Intensity: Evidence From a Longitudinal Study in Northwest Thailand

Abstract Background In northwest Thailand, the provision of radical cure to prevent relapses of Plasmodium vivax malaria has decreased P vivax caseloads and decreased transmission. While malaria control measures were increased, we performed a prospective observational rolling cohort study to describe the changing incidence of P vivax malaria and the associated recurrence rates. Methods Healthy nonpregnant glucose-6-phosphate dehydrogenase–normal volunteers who had symptomatic P vivax infection in the previous 12–24 months, but who had not received radical cure, were recruited. Supervised primaquine was given daily for 14 days (0.5 mg base/kg/day). Participants were followed 4 and 8 weeks later, then every 2 months until they developed symptomatic or asymptomatic P vivax malaria. Consultation for febrile illnesses was encouraged between follow-up visits. Participants who developed P vivax malaria were replaced with matched volunteers to maintain a continuous cohort of 200 participants. Results From March 2010 until September 2014, 380 healthy adults and children were enrolled. Ninety-two individuals developed P vivax malaria, 25 within 4 months of enrollment. The annual incidence of P vivax malaria infection decreased from 0.19 in 2010 to 0.09 infections per person-year in 2014. The primaquine failure rate (P vivax malaria within 4 months of treatment) was 75% less than predicted based on earlier assessments that assumed a constant hypnozoite reservoir. Conclusions Declining P vivax transmission reduces the hypnozoite reservoir in the population and the hypnozoite burden in an individual. This increases the apparent efficacy of radical cure in preelimination settings.