Case Report: Primaquine Failure for Radical Cure of Plasmodium vivax Malaria in Gambella, Ethiopia.

Failures of primaquine for the treatment of relapsed Plasmodium vivax malaria is a serious challenge to malaria elimination in Ethiopia, where P. vivax accounts for up to 40% of malaria infections. We report here occurrence of a total of 15 episodes of primaquine treatment failure for radical cure in three historical P. vivax malaria patients from Gambella, Ethiopia, during 8-16 months of follow-up in 1985-1987. The total primaquine doses received were 17.5 mg/kg, 25.8 mg/kg, and 35.8 mg/kg, respectively. These total doses are much higher than in previous reports of patients with treatment failure in Ethiopia and East Africa. The possibility of new infection was excluded for these cases as the treatment and follow-up were carried out in Addis Ababa, a malaria-free city. Recrudescences were unlikely, considering the short duration pattern of the recurrences. The cytochrome P450 2D6 (CYP2D6) status for these patients is unknown, but polymorphisms have been described in Ethiopia and may have contributed to primaquine treatment failures. It is suggested that further studies be carried out in Ethiopia to determine the prevalence and distribution of primaquine treatment failures in different ethnic groups, considering the impact of CYP2D6 polymorphisms and the potential value of increasing the primaquine dose to avoid relapse.