In VivoTherapeutic Efficacy of Chloroquine Alone or in Combination with Primaquine against Vivax Malaria in Kolkata, West Bengal, India, and Polymorphism inpvmdr1andpvcrt-oGenes

Abstract

ABSTRACTPlasmodium vivaxmalaria, though benign, has now become a matter of concern due to recent reports of life-threatening severity and development of parasite resistance to different antimalarial drugs. The magnitude of the problem is still undetermined. The present study was undertaken to determine thein vivoefficacy of chloroquine (CQ) and chloroquine plus primaquine inP. vivaxmalaria in Kolkata and polymorphisms in thepvmdr1andpvcrt-ogenes. A total of 250 patients withP. vivaxmonoinfection were recruited and randomized into two groups, A and B; treated with chloroquine and chloroquine plus primaquine, respectively; and followed up for 42 days according to the WHO protocol of 2009. Data were analyzed using per-protocol analyses. We assessed polymorphisms of thepvmdr1 and pvcrt-ogenes by a DNA-sequencing method. Out of the 250 patients recruited, 204 completed a 42-day follow-up period, 101 in group A and 103 in group B. In group A, the non-PCR-corrected efficacy of CQ was 99% (95% confidence interval [CI], 0.944 to 1.00), and in group B, all cases were classified as adequate clinical and parasitological response (ACPR). Day 3 positivity was observed in 11 (5.3%) cases. No specific mutation pattern was recorded in thepvcrt-ogene. Eight nonsynonymous mutations were found in thepvmdr1gene, three of which were new. The Y976F mutation was not detected in any isolate. Chloroquine, either alone or in combination with primaquine, is still effective againstP. vivaxmalaria in the study area. (The study protocol was registered in CTRI [Clinical Trial Registry-India] of the Indian council of Medical Research under registration no. CTRI/2011/09/002031.)