Artemisinin-naphthoquine plus lower-dose primaquine to treat and prevent recurrence of Plasmodium vivax malaria: an open-label randomized and non-inferiority trial

Abstract

Abstract Background: Plasmodium vivax malaria with the widest geographic distribution is also capable of causing severe disease and death. Primaquine is the main licensed antimalarial drug that can kill hypnozoites. The dose-dependent acute haemolysis in individuals with glucose-6-phospate dehydrogenase (G6PD) deficiency is the main safety concern in use of primaquine. The recommended treatment regimen for P. vivax malaria is chloroquine plus primaquine over 14 days (CQPQ14) in Myanmar. The study aimed to evaluate the therapeutic efficacy, safety and adherence of the regimen of artemisinin-naphthoquine plus primaquine over 3 days (ANPQ3) in patients of P. vivax infections compared to those of CQPQ14. Methods: A patient in group ANPQ3 was given fixed-dose artemisinin-naphthoquine (a total 24.5mg per kilogram) plus a lower total primaquine dose (0.9 mg per kilogram)over 3 days (group ANPQ3). The patient in group CQPQ14 were given a total chloroquine dose of 30 mg per kilogram of body weight over 3 days plus a total primaquine dose of 4.2 mg per kilogram over 14 days. All patients were followed up for 365 days. Results: A total of 288 patients were completed follow up, 172 in group ANPQ3 and 116 in group CQPQ14. No recurrences were observed till day 57. By day 182, a total 31 recurrences were recorded: 12 (7.0%) in Group ANPQ3 and 4 (3.4%) patients in Group CQPQ14. The difference of recurrence-free patients was 3.5 (-8.6 – 1.5) percentage points between group ANPQ3 and group CQPQ14 (P=0.2946). By day 365, the percentage of recurrence-free patient was not significant between the two groups (P=0.2257). Mean fever and parasite clearance time of group ANPQ3 were shorter than those of group CQPQ14 (P≤0.001). No any severe adverse effect was observed in group ANPQ3, but 5 (3.9%) patients with acute haemolysis in group CQPQ14 (P=0.013).Medication percentage of group ANPQ3 was significantly higher than that of group CQPQ14 (P<0.0001). Conclusions: The radial cue efficacy is no non-inferiority between the ANPQ3 and the CQPQ14. The ANPQ3 clears fever and parasites faster than the CQPQ14. The ANPQ3 is a safer and better adherence treatment regimen for P. vivax malaria along China-Myanmar border.