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

疟疾是一种由疟原虫引起的蚊媒疾病，是一个重要的公共卫生问题，估计每年造成2.12亿例病例和429 000例死亡。在世卫组织西太平洋区域，包括越南在内的37个国家中有10个存在疟疾流行。在越南，疟疾流行率存在异质性，南部和中部地区发病率最高（占人口的7%，每1000人中有100例）。在过去二十年中成功地将疟疾负担降至消除前水平之后，国家疟疾控制规划（NMCP）最近在2030年前从控制转向消除。虽然确诊病例数在2012年至2016年期间减少了一半以上，至约4200例（恶性疟原虫占56%，间日疟原虫占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已扩散到越南5个省。关于间日疟原虫耐药性的数据很少。耐药寄生虫的即将传播可能会破坏在消除方面取得的进展。耐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）技术来表征来自越南流行省份的约1,000个Pf和Pv样本的遗传图谱。我们将调查不同省份、不同时间样本之间的遗传差异，并检测已知和潜在的新型耐药标记。我们的发现将为NMCP提供关于耐药寄生虫的数据，以协助制定政策，并为疟疾诊断、疫苗和治疗方法的开发提供信息。这项工作将导致对越南疟疾寄生虫基因组的新见解，并建立一个公开的遗传数据资源，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设能力。

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.