title: Comparative assessment on the prevalence of mutations in the Plasmodium falciparum drug-resistant genes in two different ecotypes of Odisha state, India.
abstract: Considering malaria as a local and focal disease, epidemiological understanding of different ecotypes of malaria can help in devising novel control measures. One of the major hurdles in malaria control lies on the evolution and dispersal of the drug-resistant malaria parasite, Plasmodium falciparum. We herewith present data on genetic variation at the Single Nucleotide Polymorphism (SNP) level in four different genes of P. falciparum (Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps) that confer resistance to different antimalarials in two different eco-epidemiological settings, i.e. Hilly-Forest (HF) and Riverine-Plain (RP), in a high malaria endemic district of Odisha state, India. Greater frequency of antimalarial resistance conferring SNPs and haplotypes was observed in all four genes in P. falciparum, and Pfdhps was the most variable gene among the four. No significant genetic differentiation could be observed in isolates from HF and RP ecotypes. Twelve novel, hitherto unreported nucleotide mutations could be observed in the Pfmdr1 and Pfdhps genes. While the Pfdhps gene presented highest haplotype diversity, the Pfcrt gene displayed the highest nucleotide diversity. When the data on all the four genes were complied, the isolates from HF ecotype were found to harbour higher average nucleotide diversity than those coming from RP ecotype. High and positive Tajima's D values were obtained for the Pfcrt and Pfdhfr genes in isolates from both the HF and RP ecotypes, with statistically significant deviation from neutrality in the RP ecotype. Different patterns of Linkage Disequilibrium (LD) among SNPs located in different drug-resistant genes were found in the isolates collected from HF and RP ecotypes. Whereas in the HF ecotype, SNPs in the Pfmdr1 and Pfdhfr were significantly associated, in the RP ecotype, SNPs located in Pfcrt were associated with Pfmdr1, Pfdhfr and Pfdhps. These findings provide a baseline understanding on how different micro eco-epidemiological settings influence evolution and spread of different drug resistance alleles. Our findings further suggest that drug resistance to chloroquine and sulfadoxine-pyrimethamine is approaching fixation level, which requires urgent attention of malaria control programme in India.
authors.affiliation: National Institute of Malaria Research, Indian Council of Medical Research, Sector-8, Dwarka, New Delhi 110077, India.
authors.forename: Narayani Prasad
authors.initials: NP
authors.lastname: Kar
authors.affiliation: National Institute of Malaria Research, Indian Council of Medical Research, Sector-8, Dwarka, New Delhi 110077, India.
authors.forename: Kshipra
authors.initials: K
authors.lastname: Chauhan
authors.affiliation: National Institute of Malaria Research, Indian Council of Medical Research, Sector-8, Dwarka, New Delhi 110077, India.
authors.forename: Nutan
authors.initials: N
authors.lastname: Nanda
authors.affiliation: National Institute of Malaria Research, DHS Building, Campal, Panaji, Field Unit, Goa 403001, India.
authors.forename: Ashwani
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Biology, New York University, 12 Waverly Place, New York, NY 10009, USA.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Carlton
authors.affiliation: National Institute of Malaria Research, Indian Council of Medical Research, Sector-8, Dwarka, New Delhi 110077, India. Electronic address: aparup@mrcindia.org.
authors.forename: Aparup
authors.initials: A
authors.lastname: Das
mesh_terms: D000483:Alleles; D000962:Antimalarials / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D004094:Dihydropteroate Synthase / Q000235:genetics*; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics*; D060146:Ecotype; D015870:Gene Expression; D006239:Haplotypes; D006801:Humans; D007194:India / Q000453:epidemiology; D015810:Linkage Disequilibrium; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology* / Q000469:parasitology; D026901:Membrane Transport Proteins / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009154:Mutation; D010963:Plasmodium falciparum / Q000235:genetics* / Q000254:growth & development; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics*; D011739:Pyrimethamine / Q000494:pharmacology; D013413:Sulfadoxine / Q000494:pharmacology; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
chemical_list: D000962:Antimalarials; D002738:Chloroquine; D004094:Dihydropteroate Synthase; D004338:Drug Combinations; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; D011739:Pyrimethamine; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum; C001205:fanasil, pyrimethamine drug combination
keywords: Drug resistant genes; Ecotypes; Malaria; Odisha; Plasmodium falciparum