title: Association between prevalence of chloroquine resistance and unusual mutation in pfmdr-I and pfcrt genes in India.
abstract: This study deals with the underlying causes of failure of chloroquine in the treatment of Plasmodium falciparum infection in some malaria-endemic regions of India. Samples were collected from 141 patients in Purulia from March of 2007 to April of 2008. In vitro drug susceptibility tests, parasitic DNA isolation followed by polymerase chain reaction, and restriction fragment-length polymorphisms of different codons of the pfcrt gene (76) and pfmdr-I genes (86, 1042, and 1246) were assessed. The responses of 141 patients to chloroquine were determined. Prevalence of double pfmdr-I (58.16%) mutation (86Y+1246Y) and some (14.89%) single pfcrt mutations with triple pfmdr-I mutation (76T+86Y+1042D+1246Y) were found. Interestingly, double pfmdr-I mutation (86Y and 1246Y codons) was observed with the early treatment failure cases. These results show, for the first time in India that in vitro chloroquine resistance and in vivo chloroquine treatment failure were caused by double pfmdr-I (P < 0.001) mutation.
authors.affiliation: Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore, West Bengal, India. sdas.vu@gmail.com
authors.forename: Sabyasachi
authors.initials: S
authors.lastname: Das
authors.forename: Subhankari Prasad
authors.initials: SP
authors.lastname: Chakraborty
authors.forename: Amiya Kumar
authors.initials: AK
authors.lastname: Hati
authors.forename: Somenath
authors.initials: S
authors.lastname: Roy
mesh_terms: D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology* / Q000627:therapeutic use; D016054:DNA, Protozoan / Q000032:analysis / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007194:India / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009154:Mutation; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D017211:Treatment Failure
chemical_list: D000962:Antimalarials; D002738:Chloroquine; D016054:DNA, Protozoan; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C513498:Mdr1 protein, Plasmodium falciparum