title: Sequence analysis of genes associated with resistance to chloroquine and sulphadoxine pyrimethamine in P. falciparum and P. vivax isolates from the Bannu district of Pakistan.
abstract: Plasmodium vivax and Plasmodium falciparum are becoming resistant to drugs including antifolates, sulphonamides and chloroquine. This study was focused at sequence analysis of resistant genes of these parasites against sulphadoxine-pyrimethamine and chloroquine, from Bannu, Pakistan. Known mutations were detected at codons 57, 58 and 117 of pvdhfr gene of P. vivax, while none of the isolates had any pvdhps mutation. Similarly P. falciparum isolates exhibited double 59R+108N mutations in pfdhfr, and single 437G in pfdhps thus demonstrating the existance of triple mutant 59R+108N+437G haplotype in this region. The key chloroquine resistance mutation, 76T in pfcrt was observed in 100% of the P. falciparum isolates, with haplotype SVMNT which is also associated with resistance to amodiaquine. Some novel mutations were also observed in pvdhfr and pfdhfr genes.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. Electronic address: lubnakhatoonqau@gmail.com.
authors.forename: Lubna
authors.initials: L
authors.lastname: Khatoon
authors.forename: Frederick N
authors.initials: FN
authors.lastname: Baliraine
authors.forename: Salman A
authors.initials: SA
authors.lastname: Malik
authors.forename: Guiyun
authors.initials: G
authors.lastname: Yan
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D010154:Pakistan; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D010966:Plasmodium vivax / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D015800:Protozoan Proteins / Q000235:genetics; D011739:Pyrimethamine / Q000494:pharmacology*; D017421:Sequence Analysis; D013413:Sulfadoxine / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D015800:Protozoan Proteins; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine
keywords: Pakistan; Plasmodium falciparum; Plasmodium vivax; Sequence analysis