Using whole genome sequencing to reveal malaria parasite genetic diversity and drug resistance in Vietnam

利用全基因组测序揭示越南疟原虫遗传多样性和耐药性

• 批准号: MR/R026297/1
• 负责人: Taane Clark
• 金额: $ 57.37万
• 依托单位: London School of Hygiene & Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FR026297%2F1
• 关键词: Using; whole; genome; sequencing; reveal

Malaria, a mosquito-borne disease caused by Plasmodium parasites, is an important public health problem causing an estimated 212 million cases and 429,000 deaths annually. In the WHO Western Pacific Region, 10 out of 37 countries, including Viet Nam, are endemic for malaria. In Viet Nam, there is heterogeneity in malaria prevalence, with the Southern and Central regions with the highest morbidity (7% of population with >1 case per 1000 people). After successfully reducing the malaria burden to pre-elimination levels over the past two decades, the National Malaria Control Programme (NMCP) has recently switched from control to elimination by 2030. Whilst the number of confirmed cases has more than halved between 2012 and 2016 to ~4,200 (P. falciparum 56%, P. vivax 42%), there is now evidence that P. falciparum malaria parasites resistant to frontline treatments have spread to five Vietnamese provinces. Very little data is available for P. vivax drug resistance. The imminent spread of drug-resistant parasites can undermine progress made towards elimination. Drug resistance is caused by mutations in the parasite genomes. Therefore to provide biological insights, we propose to characterise the genetic profiles of ~1,000 Pf and Pv samples sourced from endemic provinces in Viet Nam using cutting edge whole genome sequencing (WGS) technologies. We will investigate genetic differences between samples, within province, across time, and detect known and potentially novel drug resistance markers. Our findings will provide data to the NMCP on drug resistant parasites to assist policy development, and inform the development of diagnostics, vaccines and treatments for malaria. The work will lead to new insights into the genomes of Vietnamese malaria parasites, as well as establish a publically available genetic data resource to facilitate future malaria research. Further, the application of WGS technologies in Viet Nam will build capacity for future genomic investigations.

疟疾是一种由疟原虫寄生虫引起的蚊媒疾病，是一个重要的公共卫生问题，每年估计造成2.12亿例病例和42.9万人死亡。在世卫组织西太平洋区域，37个国家中有10个国家，包括越南，是疟疾流行区。在越南，疟疾流行率参差不齐，南部和中部地区的发病率最高（占人口的7%，每1 000人中有1例以上）。在过去20年成功地将疟疾负担降低到消灭前的水平之后，国家疟疾控制计划（NMCP）最近从控制转向到2030年消灭。虽然确诊病例数量在2012年至2016年期间减少了一半以上，达到约4，200例（恶性疟原虫56%，间日疟原虫42%），但现在有证据表明，对一线治疗具有抗药性的恶性疟原虫疟疾寄生虫已蔓延到越南的五个省份。关于间日疟原虫耐药性的数据很少。抗药性寄生虫即将蔓延，这可能会破坏消灭工作取得的进展。抗药性是由寄生虫基因组的突变引起的。因此，为了提供生物学见解，我们建议使用尖端的全基因组测序（WGS）技术对来自越南流行省份的约1，000个Pf和Pv样本的遗传图谱进行分析。我们将调查样本之间的遗传差异，省内，跨时间，并检测已知的和潜在的新的耐药标志物。我们的研究结果将为NMCP提供关于抗药性寄生虫的数据，以协助政策制定，并为疟疾诊断，疫苗和治疗的发展提供信息。这项工作将导致对越南疟疾寄生虫基因组的新见解，并建立一个可用的遗传数据资源，以促进未来的疟疾研究。此外，WGS技术在越南的应用将为未来的基因组研究建立能力。

项目成果

Rapid profiling of Plasmodium parasites from genome sequences to assist malaria control.

• DOI: 10.1186/s13073-023-01247-7
• 发表时间: 2023-11-10
• 期刊: Genome medicine
• 影响因子: 12.3
• 作者: Phelan JE;Turkiewicz A;Manko E;Thorpe J;Vanheer LN;van de Vegte-Bolmer M;Ngoc NTH;Binh NTH;Thieu NQ;Gitaka J;Nolder D;Beshir KB;Dombrowski JG;Di Santi SM;Bousema T;Sutherland CJ;Campino S;Clark TG
• 通讯作者: Clark TG