Project A: Epidemiology of Drug Resistance

疟疾是一种毁灭性的人类疾病，特别是在最脆弱的亚人群中 of the world.了解疟疾寄生虫将如何对全球消灭作出反应很重要 努力耐药性的出现，这些特征向更广泛地区的传播， 寄生虫进化为可能导致更严重病理的形式特别令人感兴趣。的 主要的人类疟疾寄生虫恶性疟原虫在非洲和东南亚进行了研究，但 关于其在南亚的模式，仍有许多东西有待了解。另一种主要的人类疟疾 寄生虫间日疟原虫继续引起发病和死亡。然而，表型解剖 P.限制了间日疟原虫特征和间日疟原虫分离株之间变异的正式证明， 我们培养它们的能力有限。在这次更新申请中，我们将研究：（1） 药物使用和耐药性塑造了印度疟疾寄生虫的演变，（2） 哪些媒介的分布和特性影响耐药性状的传播;（3） 寄生虫对免疫力的反应如何引发与宿主细胞的新型相互作用， 疾病印度同时存在恶性疟原虫和间日疟原虫，但生态条件不同 和相关，并可能作为东南亚和东非东海岸之间的桥梁。梅萨 团队合作伙伴将研究人类宿主、蚊子媒介和控制的疟疾寄生虫。 适应后的实验室研究。在过去的五年里，该团队成功地开发了 在城市地区建立新的临床研究点，并在偏远地区建立社区调查能力 印度。我们与政府和非政府组织密切合作的能力 印度的实体，并为年轻的本地科学家提供专业机会， 我们的工作疟疾寄生虫抗药性演变的关键发现，它们与 蚊子和导致严重疾病的能力将在这次竞争性更新中进一步加强。

Malaria is a devastating human disease, especially amongst the most vulnerable sub-populations of the world. It is important to understand how malaria parasites will respond to global elimination efforts. The emergence of drug resistance, dissemination of these traits to broader localities, and evolution of parasites into forms that may lead to greater pathology are of particular interest. The dominant human malaria parasite, P. falciparum, has been studied in Africa and SE Asia, but much remains to be learned about its patterns in South Asia. The other major human malaria parasite, P. vivax, continues to cause morbidity and mortality. However, phenotypic dissection of P. vivax traits and formal demonstration of variations between P. vivax isolates is restricted by our limited ability to culture them. In this renewal application, we will study: (1) the extent to which drug use and drug resistance shape the evolution of malaria parasites in India, (2) the extent to which vector distribution and characteristics effect transmission of drug resistance traits, and (3) how parasites’ response to immunity triggers novel interactions with host cells and leads to severe disease. India has both P. falciparum and P. vivax, has ecological conditions that are different and relevant, and may act as a bridge between SE Asia and eastern coast of E Africa. The MESA team partners will study malaria parasites in human hosts, mosquito vectors, and controlled laboratory studies after adaptation. Over the last five years, the team has successfully developed new clinical study sites in urban areas and community survey capabilities in remote, isolated parts of India. Our ability to work closely and collaboratively with government and non-governmental entities in India and provide professional opportunities for young, local scientists greatly facilitate our work. Key findings on evolution of drug resistance in malaria parasites, their interactions with mosquitoes, and ability to cause severe disease will be further pursed in this competitive renewal.