Pilot studies of the molecular epidemiology of drug-resistant malaria in Myanmar

缅甸耐药疟疾分子流行病学试点研究

• 批准号: 8356232
• 负责人: CHRISTOPHER V. PLOWE
• 金额: $ 7.28万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-01 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8356232
• 关键词: Aftercare; Antimalarials; Archives; Artemisinins; Asia; Award; Bangladesh; Blood; Blood specimen; Cambodia; Chloroquine resistance; Clinical; Clinical Investigator; Clinical Trials; Collaborations; Combined Modality Therapy; Containment; Country; Cross-Sectional Studies; DNA; Data; Development; Drug resistance; Falciparum Malaria; Foundations; Funding; Future; Gene Structure; Genes; Genetic; Genomics; Genotype; Grant; Health; Individual; Infection; International; Linkage Disequilibrium; Malaria; Maps; Maryland; Measures; Medical Research; Molecular; Molecular Epidemiology; Myanmar; Observational Study; Outcome; Paper; Parasite resistance; Parasites; Pharmaceutical Preparations; Pilot Projects; Plasmodium falciparum; Population; Population Genetics; Preparation; Prevalence; Public Health Schools; Research; Research Training; Resistance; Sampling; Sampling Studies; Scientist; Single Nucleotide Polymorphism; Site; Source; Southeastern Asia; Spottings; Structure; Surveys; Thailand; Treatment Efficacy; United States National Institutes of Health; Universities; Validation; Work; World Health Organization; artemisinine; artesunate; base; candidate marker; drug efficacy; genetic analysis; genome wide association study; molecular marker; population genetic structure; public health relevance; southeast Asian; tool; treatment duration

DESCRIPTION (provided by applicant): The World Health Organization (WHO) is coordinating an aggressive effort to contain artemisinin resistant Plasmodium falciparum malaria in Southeast Asia before it spreads from its recent site of emergence in Western Cambodia. This containment effort is hampered by the lack of surveillance tools to track the extent and direction of the spread of resistance from its focus of origin. Molecular resistance markers such as those used to detect resistance to chloroquine and other antimalarial drugs are not yet available for artemisinin resistance. Without such markers, the only means of mapping artemisinin resistance is to perform clinical trials of artesunate monotherapy, limiting the comprehensiveness and timeliness of resistance data needed to guide containment efforts. A molecular marker of artemisinin resistance would therefore be valuable for surveillance of resistance in Myanmar (formerly known as Burma), the country with the most malaria of any in the region. We propose to work with scientists in Myanmar to conduct a pilot study of P. falciparum population structure and gene flow in preparation for subsequent studies to validate candidate artemisinin resistance markers. We will collect and analyze filter paper blood samples from P. falciparum-infected individuals at several sites across Myanmar. Sources of samples will include archived samples from completed and separately funded antimalarial drug efficacy studies, and an observational cross-sectional survey. DNA extracted from these samples will be subjected to parasite population genetics analyses to measure the extent of population structure and gene flow, information that will be useful in guiding resistance containment efforts. We will also analyze samples for the presence of molecular markers of resistance to artemisinin-based combination therapy (ACT) partner drugs and, as they become available, emerging candidate markers of artemisinin resistance. This pilot study will generate useful data on the extent and prevalence of known resistance markers, and lay the groundwork to help to validate new candidate markers as predictors of clinical resistance. Moreover this project will build a foundation for subsequent research collaboration between the U.S. and Myanmar aimed at validating artemisinin resistance markers with support from future R01 and other grants. To our knowledge this will be the first NIH grant awarded to work directly inside Myanmar, a country of major importance to malaria control and drug resistance containment efforts in Asia. The project will be conducted in collaboration with molecular and clinical investigators at the WHO Collaborating Center for Research and Training on Malaria in the Department of Medical Research, Lower Myanmar. This work is expected to contribute to the development of robust surveillance tools that can be used to track and contain artemisinin resistance in Southeast Asia and elsewhere.

描述（由申请人提供）：世界卫生组织（WHO）正在协调在东南亚遏制抗凝集素疟原虫恶性疟原虫疟疾的积极努力，然后它从最近在柬埔寨西部出现的地点传播。由于缺乏监视工具来跟踪阻力从其起源重点传播的范围和方向，因此阻碍了这种遏制工作。分子抗性标志物（例如用于检测氯喹和其他抗疟药耐药性的标志物，尚未可用于青蒿素耐药性。没有这样的标记，绘制抗毒素耐药性的唯一手段是进行临床临床试验，以限制指导遏制工作所需的耐药性数据的全面性和及时性。因此，一种抗毒素耐药性的分子标志物对于缅甸（以前称为缅甸）的抵抗的监视是有价值的，该国是该地区任何人的疟疾最多的国家。我们建议与缅甸的科学家合作，对恶性疟原虫种群结构和基因流进行试点研究，以准备随后的研究，以验证候选甲r可动蛋白耐药性标记物。我们将收集和分析来自缅甸多个地点的恶性疟原虫感染的个体的滤纸血液样本。样品的来源将包括来自完整和分别资助的抗疟药药物疗效研究的存档样品，以及观察性横断面调查。从这些样品中提取的DNA将进行寄生虫种群遗传学分析，以衡量种群结构和基因流的程度，这将有助于指导耐药性遏制工作。我们还将分析样品是否存在对基于青蒿素的组合疗法（ACT）伴侣药物的抗性分子标记，并且随着它们的可用，它们会出现新兴的Artemisin耐药性候选标志物。这项试验研究将生成有关已知抗性标记的程度和流行率的有用数据，并为有助于验证新候选标记作为临床抗性的预测指标。此外，该项目将为美国和缅甸之间随后的研究合作奠定基础，旨在在未来的R01和其他补助金的支持下验证青蒿素抵抗标记。据我们所知，这将是直接在缅甸内部工作的第一笔NIH赠款，这是一个对亚洲疟疾控制和耐药性遏制工作至关重要的国家。该项目将与WHO医学研究系较低缅甸的疟疾研究与培训合作中心与分子和临床研究人员合作进行。预计这项工作将有助于开发可靠的监视工具，这些工具可用于跟踪和包含东南亚和其他地方的青蒿素耐药性。