Enhancing Primaquine Adherence for Plasmodium vivax Malaria: A Cluster-Randomized Controlled Trial in Myanmar

The rising prevalence of Plasmodium vivax (P. vivax) malaria challenges elimination efforts, particularly in the Greater Mekong Subregion, although adherence to the required 14-day primaquine (PQ) regimen remains a major obstacle. This study evaluated the effectiveness of a family-administered, directly observed treatment intervention in improving adherence to PQ among patients with confirmed P. vivax from October 2022 to March 2023. A cluster-randomized controlled trial was conducted in five intervention villages and five control villages in Kachin State, Myanmar. A total of 427 patients in the intervention group (supervised dosing) and 425 patients in the control group (unsupervised dosing), all diagnosed with P. vivax, underwent a 14-day PQ regimen, with the intervention group being supervised by trained family members. Pill counts on day 14 were assessed and compared between the two groups using Poisson generalized linear mixed models. Parasite reappearance identified by polymerase chain reaction was compared between the two groups using survival analysis. Cumulative malaria incidence at baseline, as well as at months 6 and 12, was compared between the two groups. Treatment adherence was significantly higher in the intervention group (98.8%) compared with the control group (77.6%). Parasite reappearance rates were similar between the groups (P = 0.20) on days 14, 28, and 42. However, the cumulative incidence of malaria over 1 year was significantly lower in the intervention group (P <0.001) compared with the control group. In malaria-endemic areas with limited resources, a family-administered, directly observed treatment intervention offers an efficient approach to enhance PQ adherence and achieve the radical cure of P. vivax malaria.