Using Next-Generation Genomics to Study Antimalarial Drug Resistance in India

这项工作的长期目标是使用新技术找到更好的诊断和治疗方法 印度的抗疟疾抗药性寄生虫患者。耐药性是对人类健康的巨大威胁 对病人的治疗，以及在恶性疟原虫中，对所有一线抗疟疾药物都产生了抗药性 毒品。事实上，在许多国家，已经有几种药物不得不停用。药物监测 耐药性是一个重大挑战，因为一旦治疗失败足够多，就会引起人们对 阻力，阻力的蔓延可能会很好地推进。在这个项目中，我们建议使用新的 包括下一代基因组学在内的技术，以研究印度的抗疟疾耐药性。具体来说， 我们将：(1)使用新一代测序技术来检测故障早期迹象的证据 作用于恶性疟原虫和间日疟原虫中的氯喹；(2)开发一种非遗传诊断试验来识别药物 (3)构建了疟原虫遗传多样性图谱。 印度间日疟原虫以确定连锁不平衡并为单倍型图谱提供初步数据 可用于耐药关联研究。该项目是复合体研究中心的一部分 印度的疟疾(CSCMi)。这项工作将是印度临床医生和 流行病学家以及美国的遗传学家和进化生物学家将开发下一代 减轻恶性疟原虫和间日疟原虫健康负担所需的耐药性管理工具 印度次大陆的负担。

The long-term objectives of this work are to use novel technologies to find better ways to diagnose and treat patients with antimalarial drug resistant parasites in India. Drug resistance is a tremendous threat to the treatment of patients, and in P. falciparum, resistance has arisen against all classes of first line anti-malaria drugs. Indeed, several have had to be withdrawn from use in many in countries. Surveillance for drug resistance is a significant challenge, because once enough treatment failures have aroused suspicions of resistance, the spread of resistance is likely to be well advanced. In this project, we propose to use new technologies, including next generation genomics, to study anti-malarial drug resistance in India. Specifically, we will: (1) use new generation sequencing technologies to detect evidence of the eariy signs of failure of ACT in P. falciparum and chloroquine in P. vivax; (2) Develop a non-genetic diagnostic test to identify drug resistance forms of Plasmodium parasites in natural infections; (3) Construct a genetic diversity map of P. vivax in India to determine linkage disequilibrium and provide preliminary data for a haplotype map that can be used for association studies of drug resistance. This project is part of a Center for the Study of Complex Malaria in India (CSCMi). The work, which will be a collaboration between Indian clinicians and epidemiologists, and US-based geneticists and evolutionary biologists, will develop next generation resistance management tools necessary for reducing the burden of both P. falciparum and P. vivax health burdens on the Indian subcontinent.