Malaria Evolution in South Asia

描述(申请人提供)：全世界约有30亿人面临疟疾的风险，每年约有2.5亿病例，约100万人死亡。虽然部署杀虫剂浸泡的蚊帐、新的药物组合以及可能的新疫苗可能有助于控制疟疾，但我们假设，寄生虫种群规模的缩小将给病原体带来更大的负担，使其以更快的速度发生变化，可能会导致更高的毒力。最初，这种进化可能是为了克服药物并导致耐药性。然而，一旦具备了快速基因变化的能力，这些特征可能会有利于在载体内(有利于疾病传播)和在人类宿主内(可能呈现新的疾病表现)获得新的生态位。这项多中心计划项目申请将研究南亚疟疾寄生虫的进化。疟疾在整个南亚并不是统一的。人们看到从东北部到南部各州物种优势的巨大差异，人们看到严重疟疾的频繁流行，有时原因不明。我们推测南亚存在来自东南亚的恶性疟原虫，表现为对多种药物的加速耐药(ARMD)表型。这可能有助于ARMD恶性疟原虫战胜传统的间日疟原虫。除了抗药性外，ARMD寄生虫所在地点的传播和毒力特性预计也会有所不同。项目主任提出了一个5个项目中心，涉及南亚的流行病学、寄生虫可塑性、发病机制、传播和人类遗传学。印度和美国的医生和学术研究人员之间的科学伙伴关系，以及德里和加尔各答的合作伙伴提供的管理、数据管理和统计支持，将促进这项研究。寄生虫及其与人类和蚊子的相互作用将在阿萨姆邦和特里普拉(靠近缅甸)、兰奇(疟疾高度流行的附近森林地点)、印度中部的瓦达，最后在西部城市孟买和果阿(疟疾城市、地方性低、人类基因多样性高)进行研究。这些结果将使我们了解疟疾在次大陆的传播，以及防止恶性疟疾寄生虫传播的可能障碍和障碍的破坏。

DESCRIPTION (provided by applicant): About 3 billion individuals around the world are at risk for malaria, there are about 250 million cases per year, with about 1 million deaths. While deployment of insecticide impregnated bed nets, new drug combinations, and possibly new vaccines may help control malaria, we hypothesize that shrinking parasite population sizes would place greater burdens on the pathogens to change at faster rates, possibly contributing to higher virulence. Initially, such evolution could be to overcome drugs and cause resistance. However, once the capacity for faster genetic change is in place, the traits may favor acquisition of new niches, within vectors (to favor propagation of the disease) and within human hosts (possibly presenting new disease presentations). This multicenter Program Project application will study the evolution of malaria parasites in South Asia. Malaria is not uniform across South Asia. One sees large variation in species-dominance from NE to Southern states, one sees frequent epidemics of severe malaria, sometimes for unexplained reasons. We hypothesize that South Asia harbors virulent forms of P. falciparum from SE Asia that display the Accelerated Resistance to Multiple Drugs (ARMD) phenotype. This may help ARMD P. falciparum over run traditional P. vivax. In addition to drug resistance, the transmission and virulence properties of sites harboring ARMD parasites, are expected to be different. The Program Director proposes a 5 project Center that touches on epidemiology, parasite plasticity, pathogenesis, transmission, and human genetics in South Asia. Research will be facilitated by scientific partnerships between physicians and academic researchers in India and the US, and by Administration, Data Management, and Statistical support from partners in Delhi and Kolkata. Parasites and their interactions with humans, and mosquitoes, will be studied in Assam and Tripura (near Myanmar), in Ranchi (proximal forested sites with highly endemic malaria), in Wardha in Central India, and finally in the Western cities of Mumbai and Goa (with urban malaria, low endemicity, and high human genetic diversity). The results will teach us about propagation of malaria across subcontinents, and about the possible barriers and breakdown of barriers against the spread of virulent malaria parasites.