Failure of Supervised Chloroquine and Primaquine Regimen for the Treatment of Plasmodium vivax in the Peruvian Amazon

The widespread use of primaquine (PQ) and chloroquine (CQ), together, may be responsible for the relatively few, isolated cases of chloroquine-resistant P. vivax (CQRPV) that have been reported from South America. We report here a case of P. vivax from the Amazon Basin of Peru that recurred against normally therapeutic blood levels of CQ. Four out of 540 patients treated with combination CQ and PQ had a symptomatic recurrence of P. vivax parasitemia within 35 days of treatment initiation, possibly indicating CQ failure. Whole blood total CQ level for one of these four subjects was 95？ng/ml on the day of recurrence. Based on published criteria that delineate CQRPV as a P. vivax parasitemia, either recrudescence or relapse, that appears against CQ blood levels >100？ng/mL, we document the occurrence of a P. vivax strain in Peru that had unusually high tolerance to the synergistic combination therapy of CQ + PQ that normally works quite well. 1. Introduction P. vivax is the most prevalent cause of human malaria in the Americas, accounting for more than 70% of total cases reported [1]. Chloroquine (CQ) at a dose of 25？mg/kg over three days remains the first line therapy for vivax malaria. To prevent relapse, CQ is normally given in combination with primaquine (PQ). PQ is given to all nonpregnant patients greater than 6 months of age with normal activity of glucose-6-phosphate dehydrogenase (G-6-PD). The Peruvian National Malaria Control Program changed from the standard 14-day course of PQ at 0.25？mg/kg/day to a 7-day regimen of 0.5？mg/kg/day in 1998. Both regimens achieve a total adult PQ dose of 210？mg which is assumed to be widely effective against the hypnozoite stage of P. vivax strains acquired outside of Southeast Asia and the Indo-Pacific Islands. Widespread chloroquine resistance (CQR) has been reported in some areas of the world, although, up until now, only two confirmed cases have been reported in Peru [2, 3]. Recurrence of P. vivax following treatment can be classified as recrudescence, which is the recurrence of parasitemia originating from subpatent trophozoites that survived in the blood following treatment, relapse which is the recurrence of parasitemia originating from latent hypnozoites in the liver, or reinfection with a new strain [2]. Recrudescence occurs when the blood stage antimalarial drug such as chloroquine fails, either due to inadequate dosing or resistance of the blood stage parasites to the drug. Relapse can occur in the absence of a specific treatment against the hypnozoite stage or when the liver stage antimalarial drug such