Assessing strategies to improve adherence to vivax malaria treatment in the Amazon region using educational materials and a mobile health strategy (AdheVivax project): an exploratory mixed-method study

Adherence to chloroquine–primaquine treatment is essential for preventing Plasmodium vivax recurrence, but the 7-day primaquine regimen may be difficult to complete because of pill burden, adverse effects, early symptom improvement, and forgetfulness. We evaluated a culturally adapted educational and mobile health (mHealth) intervention to support treatment adherence in the Brazilian Amazon. We conducted a sequential exploratory mixed-methods study in Manaus and Ipixuna. In Phase 1, interviews with patients and healthcare providers identified barriers and facilitators to adherence and informed the co-design of a printed educational envelope and SMS/WhatsApp reminders. In Phase 2, 10 primary health units in Manaus were cluster-randomized to intervention or standard care. Adherence was assessed by telephone between days 7 and 12 using the 4-item Morisky Medication Adherence Scale and analyzed using modified Poisson regression with standard errors clustered by health unit. A qualitative sub-study assessed acceptability and appropriateness. Phase 1 identified pill burden, adverse effects, early symptom improvement, limited understanding of dosing instructions, and forgetfulness as key barriers, while treatment supervision and clear guidance supported adherence. In Phase 2, 274 participants were enrolled and 227 were included in the primary outcome analysis, with 117 in the intervention group and 110 in the control group. Overall adherence was 79.3%. Adherence was similar between groups (81.2% vs 77.3%; RR 1.04, 95% CI 0.99–1.11; p = 0.07). Qualitative findings indicated that the intervention was well accepted and appropriate. The educational envelope supported dose organization, while messages reinforced treatment completion and reduced forgetfulness. The intervention did not significantly improve adherence compared with standard care but was feasible, acceptable, and perceived as useful for medication organization and reminder support. These low-cost, culturally adapted tools may complement directly observed therapy where daily supervision is difficult to sustain and may be adapted for low-connectivity settings.