Feng Jun, Kong Xiangli, Xu Dongmei, Yan He, Zhou Hongning, Tu Hong, Lin Kangming
Chinese Center for Disease Control and Prevention, National Institute of Parasitic Diseases, Shanghai, China.
Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, China.
Front Public Health. 2019 Apr 24;7:95. doi: 10.3389/fpubh.2019.00095. eCollection 2019.
In this study, we aimed to analyse the genetic diversity Kelch 13 (K13) propeller allele of the isolates mainly imported from Southeast Asia and Africa in southern China, including the provinces of Yunnan and Guangxi. At enrolment, we collected blood samples from patients with confirmed cases of malaria infection between January 2012 and December 2017, for analysis. Individual patient information was obtained via a malaria surveillance system. The malaria infections and K13 mutations were diagnosed by using a nested polymerase chain reaction (PCR) method. The K13 mutations were identified in 283 isolates from 18 counties in Yunnan and 22 counties in Guangxi. Of Forty-six isolates (46/283, 16.3%) that harbored K13 mutant alleles were detected: 26.8% in Yunnan (33/123) and 8.1% in Guangxi (13/160). A total of 18 different K13 mutations were detected. Only the F446I mutation was detected in Yunnan isolates, and F446I was more frequent (20/46, 43.5%) than other alleles. Further, the temporal distribution of the F446I mutation ratio from 2012 to 2015 exhibited no significant difference in Yunnan Province (2012, 2/13, 15.4%; 2013, 7/40, 17.5%; 2014, 7/33, 21.2%; 2015, 4/37, 10.8%, = 0.121). A578S allele was the main K13 mutation (5/283, 1.8%) from Africa. The K13 mutants were present in 33.3% of indigenous isolates, 27.4% of isolates from Southeast Asia, and 7.9% of isolates from Africa. The analysis of 10 neutral microsatellite loci of 60 isolates showed that at the TAA109 locus, the expected heterozygosity of F446I ( = 0.112 ± 0.007) was much lower than that of wild type and other mutation types in Myanmar isolates. With respect to geographic distribution, TAA109 also exhibited a significant difference between isolates from Southeast Asia ( = 0.139 ± 0.012) and those from Africa ( = 0.603 ± 0.044). The present findings on the geographic diversity of K13 mutant alleles in may provide a basis for routine molecular surveillance and risk assessment, to monitor artemisinin resistance (ART) in China. Our results will be helpful for enriching the artemisinin resistance database in China during the elimination and post-elimination phases.
在本研究中，我们旨在分析主要从中国南方的东南亚和非洲输入的分离株中，凯尔希13（K13）螺旋桨等位基因的遗传多样性，这些地区包括云南省和广西壮族自治区。在入组时，我们收集了2012年1月至2017年12月期间确诊的疟疾感染患者的血样进行分析。通过疟疾监测系统获取个体患者信息。采用巢式聚合酶链反应（PCR）方法诊断疟疾感染和K13突变。在来自云南18个县和广西22个县的283株分离株中鉴定出K13突变。在检测到的携带K13突变等位基因的46株分离株中（46/283，16.3%）：云南为26.8%（33/123），广西为8.1%（13/160）。共检测到18种不同的K13突变。在云南分离株中仅检测到F446I突变，且F446I比其他等位基因更常见（20/46，43.5%）。此外，2012年至2015年云南省F446I突变率的时间分布无显著差异（2012年，2/13，15.4%；2013年，7/40，17.5%；2014年，7/33，21.2%；2015年，4/37，10.8%，P = 0.121）。A578S等位基因是来自非洲的主要K13突变（5/283，1.8%）。K13突变体存在于33.3%的本地分离株、27.4%的东南亚分离株和7.9%的非洲分离株中。对60株分离株的10个中性微卫星位点的分析表明，在TAA109位点，缅甸分离株中F446I的预期杂合度（P = 0.112±0.007）远低于野生型和其他突变类型。在地理分布方面，东南亚分离株（P = 0.139±0.012）和非洲分离株（P = 0.603±0.044）的TAA109也存在显著差异。本研究关于K13突变等位基因地理多样性的发现可能为中国常规分子监测和风险评估提供依据，以监测青蒿素耐药性（ART）。我们的结果将有助于在消除和消除后阶段丰富中国的青蒿素耐药性数据库。
