title: In vivo therapeutic efficacy of chloroquine alone or in combination with primaquine against vivax malaria in Kolkata, West Bengal, India, and polymorphism in pvmdr1 and pvcrt-o genes.
abstract: Plasmodium vivax malaria, 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 the in vivo efficacy of chloroquine (CQ) and chloroquine plus primaquine in P. vivax malaria in Kolkata and polymorphisms in the pvmdr1 and pvcrt-o genes. A total of 250 patients with P. vivax monoinfection 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 the pvmdr1 and pvcrt-o genes 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 the pvcrt-o gene. Eight nonsynonymous mutations were found in the pvmdr1 gene, 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 against P. vivax malaria 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.).
authors.affiliation: Calcutta School of Tropical Medicine, Kolkata, India.
authors.forename: Swagata
authors.initials: S
authors.lastname: Ganguly
authors.forename: Pabitra
authors.initials: P
authors.lastname: Saha
authors.forename: Subhasish K
authors.initials: SK
authors.lastname: Guha
authors.forename: Sonali
authors.initials: S
authors.lastname: Das
authors.forename: Dilip K
authors.initials: DK
authors.lastname: Bera
authors.forename: Asit
authors.initials: A
authors.lastname: Biswas
authors.forename: Pratip K
authors.initials: PK
authors.lastname: Kundu
authors.forename: Bibhuti
authors.initials: B
authors.lastname: Saha
authors.forename: Krishnangshu
authors.initials: K
authors.lastname: Ray
authors.forename: Ardhendu K
authors.initials: AK
authors.lastname: Maji
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007194:India; D016780:Malaria, Vivax / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009154:Mutation; D010966:Plasmodium vivax / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011319:Primaquine / Q000494:pharmacology / Q000627:therapeutic use*; D015800:Protozoan Proteins / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D002738:Chloroquine; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011319:Primaquine; D015800:Protozoan Proteins; C541685:Crt-o protein, Plasmodium vivax; C541684:Mdr1 protein, Plasmodium vivax