Malaria Evolution in South Asia

南亚的疟疾演变

• 批准号: 10378538
• 负责人: PRADIPSINH K. RATHOD
• 金额: $ 134.56万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10378538
• 关键词: Africa; Architecture; Artemisinins; Asia; Back; Basic Science; Cells; Cessation of life; Characteristics; Chloroquine; Choking; Clinical Markers; Clinical Research; Collection; Communities; Community Hospitals; Community Surveys; Complex; Country; Culicidae; Disease; Disease model; Dissection; Drug resistance; Drug usage; Evolution; Failure; Family; Far East; Funding; Genomics; Government; Grant; Health; Human; Immunity; India; Indigenous; Infection; Infrastructure; Laboratory Research; Laboratory Study; Latin America; Lead; Link; Malaria; Medical Research; Modernization; Molecular; Morbidity - disease rate; Mutagenesis; Nature; Parasites; Pathogenesis; Pathology; Pathway interactions; Pattern; Persons; Pharmaceutical Preparations; Pharmacoepidemiology; Phenotype; Plasmodium falciparum; Plasmodium vivax; Positioning Attribute; Poverty; Public Health; Research; Resistance; Resources; Rest; Role; Running; Scientist; Severity of illness; Shapes; Site; Southeastern Asia; Training; Travel; United States National Institutes of Health; Urban Community; Variant; Work; base; empowered; experimental study; feeding; human disease; implementation science; interest; international center; malaria transmission; medical schools; molecular marker; molecular phenotype; mortality; novel; parasite genome; programs; response; trait; transmission process; urban area; vector; vector mosquito; vector transmission; welfare

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.

疟疾是一种毁灭性的人类疾病，特别是在最脆弱的亚群中。 这个世界。重要的是要了解疟疾寄生虫将如何应对全球根除 努力。抗药性的出现，这些特征在更广泛的地区的传播，以及 寄生虫进化成可能导致更大病理学的形式尤其令人感兴趣。这个 非洲和东南亚对人类主要的疟疾寄生虫恶性疟原虫进行了研究，但 关于它在南亚的模式，还有很多需要了解。另一种主要的人类疟疾 间日疟原虫继续导致发病率和死亡率。然而，表型解剖 间日疟原虫的特性和间日疟原虫分离株之间变异的正式证明受到以下因素的限制 我们有限的培养它们的能力。在这次续期申请中，我们将研究：(1)在多大程度上 药物使用和抗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征影响耐药性状的传播； 寄生虫对免疫的反应如何触发与宿主细胞的新相互作用并导致严重的 疾病。印度既有恶性疟原虫，也有间日疟原虫，生态条件不同 并可能成为连接东南亚和非洲东部海岸的桥梁。台地 团队合作伙伴将研究疟疾寄生虫在人类宿主、蚊子媒介和受控 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 城市地区新的临床研究地点和偏远偏远地区的社区调查能力 印度的。我们与政府和非政府组织密切合作的能力 并为年轻的印度科学家提供职业机会，极大地便利了当地科学家 我们的工作。疟疾寄生虫耐药性演变及其与疟疾的相互作用的重要发现 蚊子和引发严重疾病的能力将在这一竞争更新中得到进一步追逐。