背景:间日疟原虫已成为泰国边境地区的主要物种。间日疟原虫抗疟药耐药性的出现和传播是疟疾防治的重大挑战之一。因此,持续监测耐药性对于监测该地区耐药性的发展是必要的。本研究旨在调查间日疟原虫多药耐药基因1(Pvmdr1)突变的患病率,二氢叶酸还原酶(Pvdhfr),和二氢蝶呤合成酶(Pvdhps)基因赋予对氯喹(CQ)的抗性,乙胺嘧啶(P)和磺胺多辛(S),分别。
方法:在2023年1月至5月之间,从Kanchanaburi省获得了100种间日疟原虫分离株,泰国西部。Pvmdr1,Pvdhfr的核苷酸序列,并对Pvdhps基因进行了扩增和测序。评估了耐药等位基因的单核苷酸多态性(SNP)-单倍型的频率。还分析了连锁不平衡(LD)测试。
结果:在Pvmdr1,T958M,Y976F,F1076L,100%检测到突变,21%,23%的分离株,分别。在Pvdhfr中,四重突变等位基因(I57R58M61T117)在84%的样本中占优势,其次是(L57R58M61T117)11%。对于Pvdhps,检测到双突变等位基因(G383G553)(48%),其次是分离株的三重突变等位基因(G383M512G553)(47%)。Pvdhfr(I57R58M61T117)和Pvdhps(G383G553)等位基因的最普遍组合是六元组突变单倍型(48%)。对于LD分析,在Pvdhfr和Pvdhps基因的基因内和基因间区域之间发现了SNP对的关联。
结论:该研究最近更新了与CQ和SP耐药相关的三种基因突变的高患病率。因此,基因监测对于在该地区加强以进一步评估耐药性的传播非常重要。我们的数据还为早期预警系统提供了耐药性分布的证据,从而威胁到国家一级的间日疟原虫疟疾治疗政策决定。
BACKGROUND: Plasmodium vivax has become the predominant species in the border regions of Thailand. The emergence and spread of antimalarial drug resistance in P. vivax is one of the significant challenges for malaria control. Continuous surveillance of drug resistance is therefore necessary for monitoring the development of drug resistance in the region. This study aims to investigate the prevalence of the mutation in the P. vivax multidrug resistant 1 (Pvmdr1), dihydrofolate reductase (Pvdhfr), and dihydropteroate synthetase (Pvdhps) genes conferred resistance to chloroquine (CQ), pyrimethamine (P) and sulfadoxine (S), respectively.
METHODS: 100 P. vivax isolates were obtained between January to May 2023 from a Kanchanaburi province, western Thailand. Nucleotide sequences of Pvmdr1, Pvdhfr, and Pvdhps genes were amplified and sequenced. The frequency of single nucleotide polymorphisms (SNPs)-haplotypes of drug-resistant alleles was assessed. The linkage disequilibrium (LD) tests were also analyzed.
RESULTS: In Pvmdr1, T958M, Y976F, and F1076L, mutations were detected in 100%, 21%, and 23% of the isolates, respectively. In Pvdhfr, the quadruple mutant allele (I57R58M61T117) prevailed in 84% of the samples, followed by (L57R58M61T117) in 11%. For Pvdhps, the double mutant allele (G383G553) was detected (48%), followed by the triple mutant allele (G383M512G553) (47%) of the isolates. The most prevalent combination of Pvdhfr (I57R58M61T117) and Pvdhps (G383G553) alleles was sextuple mutated haplotypes (48%). For LD analysis, the association in the SNPs pairs was found between the intragenic and intergenic regions of the Pvdhfr and Pvdhps genes.
CONCLUSIONS: The study has recently updated the high prevalence of three gene mutations associated with CQ and SP resistance. Genetic monitoring is therefore important to intensify in the regions to further assess the spread of drug resistant. Our data also provide evidence on the distribution of drug resistance for the early warning system, thereby threatening P. vivax malaria treatment policy decisions at the national level.