Development and validation of a patient-informed educational booklet for G6PD-deficient patients receiving weekly primaquine for vivax malaria in Brazil: an exploratory sequential mixed-methods study

Abstract Background Plasmodium vivax accounts for approximately 80% of malaria cases in the Brazilian Amazon and remains a major challenge to malaria elimination. The introduction of quantitative glucose-6-phosphate dehydrogenase (G6PD) testing and weekly primaquine (0.75 mg/kg for 8 weeks) has improved treatment safety for G6PD-deficient patients. However, little is known about patients' understanding of G6PD deficiency, adherence to weekly treatment, or recognition of the warning signs of hemolysis. This study explored patients' experiences with weekly primaquine therapy and developed and validated a culturally adapted educational booklet. Methods An exploratory sequential mixed-methods study was conducted in Manaus (Amazonas) and Porto Velho (Rondônia), Brazil, between May 2023 and December 2024. Twenty-three G6PD-deficient patients receiving weekly primaquine participated in semi-structured interviews analyzed using thematic analysis. The findings guided the development of an educational booklet, which was subsequently validated by 10 experts using the Suitability Assessment of Materials (SAM) and by 10 G6PD-deficient patients. Content validity was assessed using the Item-level Content Validity Index (I-CVI), Scale-level Content Validity Index based on the average method (S-CVI/Ave), and modified kappa. Results Two themes emerged: (1) Challenges in communication and understanding of the G6PD deficiency diagnosis, resulting in limited knowledge, confusion, fear, and misunderstanding of the purpose of G6PD testing; and (2) factors influencing adherence to weekly primaquine therapy, including good acceptance of the regimen but frequent misinterpretation of hemolysis signs, particularly dark urine, as an expected treatment effect. The educational booklet demonstrated excellent content validity (S-CVI/Ave = 0.97 among experts and 0.91 among the target audience). Although one cultural adequacy item showed lower agreement, qualitative feedback confirmed the booklet's relevance and acceptability. Conclusions Communication gaps at the time of G6PD deficiency diagnosis may hinder patients’ understanding of weekly primaquine treatment and delay recognition of haemolysis warning signs, despite generally favourable perceptions of the regimen. The patient-informed educational booklet demonstrated high content validity and acceptability and may support clearer counselling and safer delivery of radical cure. Integrating culturally appropriate patient education into the implementation of quantitative G6PD testing may strengthen the safe use of 8-aminoquinolines and support Plasmodium vivax malaria elimination efforts.