<i>Plasmodium vivax</i> 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 non-pregnant G6PD 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 (0.5mg base/kg/day). Participants were followed four and eight weeks later, then every two 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. 92 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 per year in 2014. The primaquine failure rate (P. vivax malaria within 4 months of treatment) was 75% less than predicted based on earlier assessments which assumed a constant hypnozoite reservoir. Conclusion 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 pre-elimination settings.