Genomic Epidemiology of Antimalarial Drug Resistance in Plasmodium falciparum in Southern China

Frontiers in Cellular and Infection Microbiology

Shannon Takala-Harrison¹  Matthew Adams¹  Christopher V. Plowe²  Hui Liu³  Heng-Lin Yang³  Christopher G. Jacob⁴  Shui-Sen Zhou⁵  Lin-Hua Tang⁵  Fang Huang⁵  Zhi-Gui Xia⁵ 

[1] Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, United States;Duke Global Health Institute, Duke University, Durham, NC, United States;Malaria Department, Yunnan Institute of Parasitic Diseases, Puer, China;Malaria Programme, Wellcome Sanger Institute, Cambridge, United Kingdom;National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, Key Laboratory of Parasite and Vector Biology, Ministry of Health, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai, China;

关键词: Plasmodium falciparum;    antimalarial drugs;    artemisinin resistance;    microarrays;    Southern China;   

DOI  :  10.3389/fcimb.2020.610985

来源: Frontiers

【 摘 要 】

Emerging artemisinin resistance in Southeast Asia poses a significant risk to malaria control and eradication goals, including China’s plan to eliminate malaria nationwide by 2020. Plasmodium falciparum was endemic in China, especially in Southern China. Parasites from this region have shown decreased susceptibility to artemisinin and delayed parasite clearance after artemisinin treatment. Understanding the genetic basis of artemisinin resistance and identifying specific genetic loci associated with this phenotype is crucial for surveillance and containment of resistance. In this study, parasites were collected from clinical patients from Yunnan province and Hainan island. The parasites were genotyped using a P. falciparum-specific single nucleotide polymorphism (SNP) microarray. The SNP profiles examined included a total of 27 validated and candidate molecular markers of drug resistance. The structure of the parasite population was evaluated by principal component analysis by using the EIGENSOFT program, and ADMIXTURE was used to calculate maximum likelihood estimates for the substructure analysis. Parasites showed a high prevalence of resistance haplotypes of pfdhfr and pfdhps and moderate prevalence of pfcrt. There was no mutation identified on pfmdr1. Candidate SNPs on chromosomes 10, 13, and 14 that were associated with delayed parasite clearance showed a low prevalence of mutants. Parasites from Southern China were clustered and separated from those from Southeast Asia. Parasites from Yunnan province were substructured from parasites from Hainan island. This study provides evidence for a genomic population with drug resistance in Southern China and also illustrates the utility of SNP microarrays for large-scale parasite molecular epidemiology.

【 授权许可】

CC BY