title: High prevalence of pfdhfr-pfdhps triple mutations associated with anti-malarial drugs resistance in Plasmodium falciparum isolates seven years after the adoption of sulfadoxine-pyrimethamine in combination with artesunate as first-line treatment in Iran.
abstract: The spread of anti-malarial drug resistance will challenge any malaria control and elimination strategies, and routine monitoring of resistance-associated molecular markers of commonly used anti-malarial drugs is very important. Therefore, in the present investigation, the extent of mutations/haplotypes in dhfr and dhps genes of Plasmodium falciparum isolates (n=72) was analyzed seven years after the introduction of sulfadoxine-pyrimethamine (SP) plus artesunate (AS) as first-line anti-malarial treatment in Iran using PCR-RFLP methods. The results showed that the majority of the patients (97.2%) carried both 59R and 108N mutations in pure form with wild-type genotype at positions N51 and I164. Additionally, a significant increase (P<0.05) was observed in the frequency of R59N108/G437 haplotype (79.2%) during 2012-2014. This raise was because of the significant increase (P<0.05) in the frequency of 437G mutation (81.9%), which more likely was due to more availability of SP as anti-malarial drug for treatment of falciparum patients in these malaria-endemic areas of Iran. However, no quintuple mutations associated with treatment failure were detected. In conclusion, the present results along with in vivo assays suggest that seven years after the adoption of SP-AS as the first-line treatment in Iran, this drug remains efficacious for treatment of uncomplicated falciparum malaria, as a partner drug with AS in these malaria-endemic areas.
authors: Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, Tehran, Iran.
authors: Maryam
authors: M
authors: Rouhani
authors: Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, Tehran, Iran. Electronic address: zakeris@yahoo.com.
authors: Sedigheh
authors: S
authors: Zakeri
authors: Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, Tehran, Iran.
authors: Sakineh
authors: S
authors: Pirahmadi
authors: National Program Manager for Malaria Control, Ministry of Health and Medical Education, Tehran, Iran.
authors: Ahmad
authors: A
authors: Raeisi
authors: Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, Tehran, Iran.
authors: Navid Dinparast
authors: ND
authors: Djadid
mesh_terms: D000293:Adolescent; D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003062:Codon; D004351:Drug Resistance; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007492:Iran / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology*; D008875:Middle Aged; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use; D013413:Sulfadoxine / Q000494:pharmacology / Q000627:therapeutic use; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D003062:Codon; C578917:sulfadoxine-pyrimethamine-artesunate; D013413:Sulfadoxine; D000426:Alcohol Dehydrogenase; D013762:Tetrahydrofolate Dehydrogenase; D011739:Pyrimethamine
keywords: Drug resistance; Molecular analysis; Plasmodium falciparum; Sulfadoxine–pyrimethamine; pfdhfr; pfdhps