title: Significant Divergence in Sensitivity to Antimalarial Drugs between Neighboring Plasmodium falciparum Populations along the Eastern Border of Myanmar.
abstract: Malaria parasites in different areas where malaria is endemic display different levels of resistance to antimalarial drugs as the result of varied drug use histories. To provide updated knowledge of drug sensitivities during the malaria elimination phase in Southeast Asia, an epicenter of multidrug resistance, we determined in vitro susceptibilities of culture-adapted Plasmodium falciparum isolates from two eastern border regions (Wa and Kachin) of Myanmar to 10 drugs. Despite their close proximity, the Kachin parasites displayed higher 50% inhibitory concentrations than the Wa parasites to chloroquine, piperaquine, naphthoquine, mefloquine, quinine, pyrimethamine, pyronaridine, lumefantrine, and dihydroartemisinin. Genotyping of genes associated with drug resistance also showed significant differences in the prevalence rates of mutant alleles between the two regions. Particularly, major pfdhfr mutations mediating pyrimethamine resistance and the pfdhps A437G mutation had significantly higher frequencies in the Kachin parasites (P < 0.005). Moreover, when pfdhfr and pfdhps were considered together, the wild-type allele was found only in the Wa samples (22.6%). In addition, the pfmdr1 Y184F mutation reached 38.7% in the Kachin parasites, compared to 9.7% in the Wa parasites, whereas N86Y was only detected in the Wa parasites, at 22.6%. Furthermore, the F446I mutation and all mutations in the propeller domain of the PfK13 gene were significantly more frequent in the Kachin parasites. Collectively, this work demonstrates that even in spatially closely separated regions, parasites can exhibit drastic differences in drug sensitivities and genetic makeups underlying drug resistance, which may reflect regionally different drug histories and genetic drift of these isolated parasite populations.
authors.affiliation: Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, Yunnan Province, China.
authors.forename: Weilin
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, Yunnan Province, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania, USA.|Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, Shenyang, China.
authors.forename: Meilian
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Zenglei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, Kunming Medical University, Kunming, Yunnan Province, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Deng
authors.affiliation: Department of Pathology, Kunming Medical University, Kunming, Yunnan Province, China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, Yunnan Province, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Feng
authors.affiliation: Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, Yunnan Province, China.
authors.forename: Zhaoqing
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania, USA luc2@psu.edu.
authors.forename: Liwang
authors.initials: L
authors.lastname: Cui
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D002681:China; D004352:Drug Resistance, Microbial / Q000187:drug effects; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D008826:Microbial Sensitivity Tests; D009154:Mutation; D002052:Myanmar; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics*
chemical_list: D000962:Antimalarials; D015800:Protozoan Proteins
keywords: Plasmodium falciparum; drug resistance; mutation; population differentiation