In Vitro Sensitivities of Plasmodium falciparum Isolates from the China-Myanmar Border to Piperaquine and Association with Polymorphisms in Candidate Genes
机构:[1]Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, Yunnan, China[2]Department of Cell Biology and Genetics, Kunming Medical University, Kunming, Yunnan, China[3]Department of Pathology, Kunming Medical University, Kunming, Yunnan, China[4]The First Affiliated Hospital, Kunming Medical University, Kunming, Yunnan, China昆明医科大学附属第一医院[5]Department of Entomology, Pennsylvania State University, University Park, Pennsylvania, USA
The recent reports of resistance in Plasmodium falciparum to artemisinin derivatives and their partner drugs demand intensive studies toward understanding the molecular mechanisms of resistance. In this study, we examined the in vitro susceptibility of 63 P. falciparum field isolates collected from the China-Myanmar border area to chloroquine (CQ) and piperaquine (PPQ). Parasite isolates remained highly resistant to CQ, with the geometric mean 50% inhibitory concentration (IC50) of 252.7 nM and a range of 51.9 to 1,052.0 nM. In comparison, these parasites had a geometric mean IC50 of 28.4 nM for PPQ, with a fairly wide range of 5.3 to 132.0 nM, suggesting that certain parasite isolates displayed relatively high levels of resistance to PPQ. Interestingly, within the 4 years of study, the parasites exhibited a continuous decline in susceptibilities to both CQ and PPQ, and there was a significant correlation between responses to CQ and PPQ (Pearson correlation coefficient = 0.79, P < 0.0001). Consistent with the CQ-resistant phenotype, all parasites carried the pfcrt K76T mutation, and most parasites had the CVIET type that is prevalent in Southeast Asia. In contrast, pfmdr1 mutations were relatively rare, and no gene amplification was detected. Only the pfmdr1 N1042D mutation was associated with resistance to CQ. For the pfmrp1 gene, four substitutions reached relatively high prevalence of >22%, and the I876V mutation was associated with reduced sensitivity to CQ. However, we could not establish a link between PPQ responses and the polymorphisms in the three genes associated with quinoline drug resistance.
基金:
National Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1R01AI075429]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81161120421, 31260508, U1202226]; National Institute of Allergy and Infectious Diseases, NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [U19AI089672]
第一作者机构:[1]Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, Yunnan, China
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推荐引用方式(GB/T 7714):
Hao Mingming,Jia Dandan,Li Qing,et al.In Vitro Sensitivities of Plasmodium falciparum Isolates from the China-Myanmar Border to Piperaquine and Association with Polymorphisms in Candidate Genes[J].ANTIMICROBIAL AGENTS AND CHEMOTHERAPY.2013,57(4):1723-1729.doi:10.1128/AAC.02306-12.
APA:
Hao, Mingming,Jia, Dandan,Li, Qing,He, Yongshu,Yuan, Lili...&Cui, Liwang.(2013).In Vitro Sensitivities of Plasmodium falciparum Isolates from the China-Myanmar Border to Piperaquine and Association with Polymorphisms in Candidate Genes.ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,57,(4)
MLA:
Hao, Mingming,et al."In Vitro Sensitivities of Plasmodium falciparum Isolates from the China-Myanmar Border to Piperaquine and Association with Polymorphisms in Candidate Genes".ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 57..4(2013):1723-1729