Liu Ying, Zhang Tao, Chen Shen-Bo, Cui Yan-Bing, Wang Shu-Qi, Zhang Hong-Wei, Shen Hai-Mo, Chen Jun-Hu
National Institute of Parasitic Diseases, Chinese Center for Diseases Control and Prevention (Chinese Center for Tropical Diseases Research), Shanghai, China.
National Health Commission of the People's Republic of China (NHC) Key Laboratory of Parasite and Vector Biology, Shanghai, China.
Front Microbiol. 2023 Feb 9;14:1071689. doi: 10.3389/fmicb.2023.1071689. eCollection 2023.
In malaria-free countries, imported cases are challenging because interconnections with neighboring countries with higher transmission rates increase the risk of parasite reintroduction. Establishing a genetic database for rapidly identifying malaria importation or reintroduction is crucial in addressing these challenges. This study aimed to examine genomic epidemiology during the pre-elimination stage by retrospectively reporting whole-genome sequence variation of 10 isolates from inland China.
The samples were collected during the last few inland outbreaks from 2011 to 2012 when China implemented a malaria control plan. After next-generation sequencing, we completed a genetic analysis of the population, explored the geographic specificity of the samples, and examined clustering of selection pressures. We also scanned genes for signals of positive selection.
China's inland populations were highly structured compared to the surrounding area, with a single potential ancestor. Additionally, we identified genes under selection and evaluated the selection pressure on drug-resistance genes. In the inland population, positive selection was detected in some critical gene families, including , and . Meanwhile, we identified selection signatures in drug resistance, such as , and , and noticed that the ratio of wild-type and increased after China banned sulfadoxine-pyrimethamine (SP) for decades.
Our data provides an opportunity to investigate the molecular epidemiology of pre-elimination inland malaria populations, which exhibited lower selection pressure on invasion and immune evasion genes than neighbouring areas, but increased drug resistance in low transmission settings. Our results revealed that the inland population was severely fragmented with low relatedness among infections, despite a higher incidence of multiclonal infections, suggesting that superinfection or co-transmission events are rare in low-endemic circumstances. We identified selective signatures of resistance and found that the proportion of susceptible isolates fluctuated in response to the prohibition of specific drugs. This finding is consistent with the alterations in medication strategies during the malaria elimination campaign in inland China. Such findings could provide a genetic basis for future population studies, assessing changes in other pre-elimination countries.
在无疟疾国家，输入性病例颇具挑战，因为与疟疾传播率较高的邻国之间的联系增加了寄生虫重新传入的风险。建立一个用于快速识别疟疾输入或重新传入的基因数据库对于应对这些挑战至关重要。本研究旨在通过回顾性报告来自中国内陆的10株分离株的全基因组序列变异，来研究消除疟疾前阶段的基因组流行病学。
样本采集于2011年至2012年中国实施疟疾控制计划期间的最后几次内陆疫情。在进行下一代测序后，我们完成了群体的遗传分析，探索了样本的地理特异性，并研究了选择压力的聚类情况。我们还扫描基因以寻找正选择信号。
与周边地区相比，中国内陆群体具有高度的结构，有一个单一的潜在祖先。此外，我们鉴定了受选择的基因，并评估了对耐药基因的选择压力。在内陆群体中，在一些关键基因家族中检测到正选择，包括 、 和 。同时，我们在耐药性方面鉴定了选择特征，如 、 和 ，并注意到在中国禁用磺胺多辛 - 乙胺嘧啶（SP）数十年后，野生型 和 的比例增加。
我们的数据为研究消除疟疾前内陆疟疾病原体的分子流行病学提供了机会，其在内陆地区对入侵和免疫逃避基因的选择压力低于周边地区，但在低传播环境中耐药性增加。我们的结果表明，尽管多克隆感染发生率较高，但内陆群体严重分散，感染之间的相关性较低，这表明在低流行情况下超级感染或共同传播事件很少见。我们鉴定了耐药性的选择特征，并发现敏感分离株的比例随着特定药物的禁用而波动。这一发现与中国内陆疟疾消除运动期间用药策略的改变一致。这些发现可为未来的群体研究提供遗传基础，评估其他消除疟疾前国家的变化。
