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Prevalence of molecular markers associated with drug resistance of Plasmodium vivax isolates in Western Yunnan Province, China.

ABSTRACT: BACKGROUND:Plasmodium vivax is the most widely distributed malaria parasite, and its drug resistance poses unique challenges to malaria elimination. The Greater Mekong Subregion (GMS) is known as the global epicenter of multidrug resistance. Surveillance of molecular markers associated with drug resistance in this area will help to inform drug policy. METHODS:Dry blood spots from 58 patients out of 109 with P. vivax infection between 2017, December and 2019, March were obtained from Yingjiang County, Yunnan Province, along the China-Myanmar border. Pvdhfr, Pvdhps, Pvmdr1 and Pvcrt-o were amplified and sequenced to assess gene mutations. The polymorphism and prevalence of these molecular markers were analyzed. RESULTS:Mutations in Pvdhfr at codons 57, 58, 61, 99 and 117 were detected in 27.59, 48.28, 27.59, 32.76 and 48.28% of the isolates, respectively. Single mutant haplotype (I13F57S58T61S99S117I173) was the most frequent (29.31%, 17/58), followed by double mutant haplotype (20.69%, 12/58). Of three types of tandem repeat variations of Pvdhfr, deletion type was the most common. Pvdhps showed a lower prevalence among mutation genotypes. Single mutant was dominant and accounted for 34.48% (20/58). Prevalence of Pvmdr1 mutations at codons 958 and 1076 were 100.00% and 84.48%, respectively. The proportion of double and single mutant types was 84.48% (49/58) and 15.52% (9/58), respectively. Eleven samples (18.97%, 11/58) showed K10 "AAG" insertion in chloroquine resistance transporter gene Pvcrt-o. CONCLUSIONS:There was moderate diversity of molecular patterns of resistance markers of Pvdhfr, Pvdhps, Pvmdr1 and Pvcrt-o in imported P. vivax cases to Yingjiang county in Western Yunnan, along the China-Myanmar border. Prevalence and molecular pattern of candidate drug resistance markers Pvdhfr, Pvdhps, Pvmdr1 and Pvcrt-o were demonstrated in this current study, which would help to update drug policy.

SUBMITTER: Wang X

PROVIDER: S-EPMC7183581 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Prevalence of molecular markers associated with drug resistance of Plasmodium vivax isolates in Western Yunnan Province, China.

Wang Xiaoxiao X Ruan Wei W Zhou Shuisen S Feng Xinyu X Yan He H Huang Fang F

BMC infectious diseases 20200425 1

<h4>Background</h4>Plasmodium vivax is the most widely distributed malaria parasite, and its drug resistance poses unique challenges to malaria elimination. The Greater Mekong Subregion (GMS) is known as the global epicenter of multidrug resistance. Surveillance of molecular markers associated with drug resistance in this area will help to inform drug policy.<h4>Methods</h4>Dry blood spots from 58 patients out of 109 with P. vivax infection between 2017, December and 2019, March were obtained fr ...[more]

PMID: 32334523

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Project description:Yunnan Province, China is thought to be the original source of biovar Orientalis of Yersinia pestis, the causative agent of the third plague pandemic that has spread globally since the end of the 19th century. Although encompassing a large area of natural plague foci, Y. pestis strains have rarely been found in live rodents during surveillance in Yunnan, and most isolates are from rodent corpses and their fleas. In 2017, 10 Y. pestis strains were isolated from seven live rodents and three fleas in Heqing County (HQ) of Yunnan. These strains were supposed to have low virulence to local rodents Eothenomys miletus and Apodemus chevrieri because the rodents were healthy and no dead animals were found in surrounding areas, as had occurred in previous epizootic disease. We performed microscopic and biochemical examinations of the isolates,and compared their whole-genome sequences and transcriptome with those of 10 high virulence Y. pestis strains that were isolated from the adjacent city (Lijiang). We analyzed the phenotypic, genomic, and transcriptomic characteristics of live rodent isolates. The isolates formed a previously undefined monophyletic branch of Y. pestis that was named 1.IN5. Six SNPs, two indels, and one copy number variation were detected between live rodent isolates and the high virulence neighbors. No obvious functional consequence of these variations was found according to the known annotation information. Among the genes that were differentially expressed between the live rodent isolates and their high virulence neighbors, we detected five iron transfer-related genes that were significantly up-regulated in live rodent isolates compared with high virulence isolates (|log2 (FC) | >1, p.adjust <0.05), indicating these genes may be related to the low-virulence phenotype. The novel genotype of Y. pestis reported here provides further insights into the evolution and spread of plague as well as clues that may help to decipher the virulence mechanism of this notorious pathogen.

Dataset Information

Prevalence of molecular markers associated with drug resistance of Plasmodium vivax isolates in Western Yunnan Province, China.

Publications

Prevalence of molecular markers associated with drug resistance of Plasmodium vivax isolates in Western Yunnan Province, China.

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