Optimizing spatial sampling strategies for the molecular surveillance of drug resistant malaria

优化耐药疟疾分子监测的空间采样策略

• 批准号: 9911241
• 负责人: Hanna Ehrlich
• 金额: $ 4.55万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-16 至 2023-01-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9911241
• 关键词: Africa South of the Sahara; Anopheles Genus; Anti-malarial drug resistance; Antimalarials; Artemisinins; Arthropods; Behavior; Bite; Blood; Blood Screening; Blood specimen; Burkina Faso; Chemoprevention; Child; Climate; Clinic; Clinical; Clinical Research; Clinical Treatment; Combined Modality Therapy; Communication; Communities; Country; Culicidae; Data; Databases; Developing Countries; Development; Disease; Drug resistance; Epidemiologist; Epidemiology; Feeding behaviors; Fellowship; Female; Future; Gap Junctions; Genotype; Geographic Factor; Geography; Goals; Health; Household; Human; In Vitro; Individual; Intervention; Location; Malaria; Malaria prevention; Mentors; Methods; Modeling; Molecular; Molecular Epidemiology; Monitor; Morbidity - disease rate; Multi-Drug Resistance; Mutation; Parasite resistance; Parasites; Patients; Pharmaceutical Preparations; Pharmacology; Plasmodium; Play; Policies; Population; Prevalence; Prevention; Regimen; Research; Research Personnel; Research Training; Resistance; Rest; Role; Sampling; Seasons; Site; Southeastern Asia; Spatial Distribution; Surveys; Techniques; Therapeutic; Time; Uncertainty; Vector-transmitted infectious disease; base; career; design; disease transmission; efficacy study; epidemiology study; experience; feeding; field study; fitness; global health; human subject; improved; molecular marker; mortality; multidisciplinary; novel; pressure; prospective; resistance mutation; scale up; stem; success; surveillance data; surveillance strategy; tool; transmission process; urban setting; vector; vector control

Project Summary/Abstract Antimalarial drugs are a critical tool in both the treatment and prevention malaria worldwide, yet their success has been hampered by the continual emergence and spread of antimalarial resistance (AMR). In the current climate of multidrug resistance, including resistance to the global front-line drug artemisinin, there is a need to scale up timely and widespread surveillance of AMR. The development of artemisinin resistance in sub- Saharan Africa would have a devastating impact on malaria-related morbidity and mortality. Molecular surveillance, which involves the screening of blood samples to determine the prevalence of molecular markers associated with drug resistance, can be a valuable tool for detecting emergent resistance genotypes before they become widespread. This proposal will first characterize the state of molecular monitoring efforts across sub-Saharan Africa. With the hypothesis that studies remain temporally and geographically clustered, we will use model-based geostatistics to interpolate the prevalence of AMR markers and suggest optimal strategies for future sampling sites. Next, in Burkina Faso, we will assess the utility of an alternative surveillance tool: the use of bloodmeals collected by arthropods, a technique known as xenosurveillance, to monitor molecular markers in humans that have been recently fed upon. We believe xenosurveillance may act as a complementary, rapidly deployable, and acceptable tool for the molecular surveillance of AMR. Finally, because molecular surveillance relies primarily on human-based interventional or cross-sectional trials, the role of the mosquito in transmitting drug resistant parasites remains unexplored. We will leverage our xenosurveillance samples to investigate the impact of vector behavior on the differential transmission of AMR parasites. This project will investigate the prevalence and dynamics of antimalarial resistance at multiple spatial scales. The goal of the proposed research is to help guide policymakers in their efforts to control the spread of AMR in sub-Saharan Africa, where drug pressure stems from both treatment and prevention regimens, and this pharmacological landscape changes regularly alongside the vector control landscape. After the completion of this two-year research and training fellowship, the applicant will have an advanced skillset in geostatistical modeling, molecular epidemiology, scientific communication and extensive field experience. Ultimately, the candidate seeks expertise in spatial analysis and applied epidemiology in order to advance surveillance efforts and improve our understanding of the geographic factors that influence vector-borne disease transmission. A multidisciplinary mentoring team will prepare the applicant for research independence in a career as a global health researcher and vector-borne disease epidemiologist at the nexus of environmental and human health.

项目概要/摘要 抗疟药物是全世界治疗和预防疟疾的重要工具，但它们的成功 抗疟疾耐药性（AMR）的不断出现和蔓延阻碍了这一进程。在当前 多重耐药性的气候，包括对全球一线药物青蒿素的耐药性，有必要 扩大对抗菌素耐药性的及时、广泛的监测。亚群青蒿素耐药性的发展 撒哈拉非洲地区将对疟疾相关的发病率和死亡率产生毁灭性影响。分子 监测，包括筛查血液样本以确定分子标记物的流行率 与耐药性相关，可以成为在之前检测新出现的耐药基因型的宝贵工具。 它们变得普遍。该提案将首先描述分子监测工作的状况 撒哈拉以南非洲。假设研究在时间和地理上保持集群状态，我们将 使用基于模型的地质统计学来插值 AMR 标记的流行率并提出最佳策略 用于未来的采样点。接下来，在布基纳法索，我们将评估另一种监视工具的效用： 使用节肢动物收集的血粉（一种称为异种监视的技术）来监测分子 最近被食用的人类标记。我们相信异种监视可以作为 用于 AMR 分子监测的补充、可快速部署且可接受的工具。最后， 由于分子监测主要依赖于基于人体的干预或横断面试验，因此 蚊子传播耐药寄生虫的机制尚未被探索。我们将利用我们的 异种监视样本研究载体行为对 AMR 差异传播的影响 寄生虫。 该项目将调查多个空间尺度的抗疟疾耐药性的流行率和动态。 拟议研究的目标是帮助指导政策制定者努力控制抗菌素耐药性的传播 撒哈拉以南非洲地区的药物压力源于治疗和预防方案，而这 药理学景观与病媒控制景观一起定期变化。完成后 在这个为期两年的研究和培训奖学金中，申请人将拥有地质统计方面的高级技能 建模、分子流行病学、科学传播和丰富的现场经验。最终， 候选人寻求空间分析和应用流行病学方面的专业知识，以推进监测工作 并提高我们对影响媒介传播疾病传播的地理因素的了解。一个 多学科指导团队将为申请人在全球职业生涯中的研究独立性做好准备 环境与人类健康关系的健康研究员和媒介传播疾病流行病学家。