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.

项目总结/摘要 抗疟药物是全球治疗和预防疟疾的重要工具，但它们的成功 由于抗疟药耐药性（AMR）的不断出现和传播，在当前 鉴于多药耐药性的气候，包括对全球一线药物青蒿素的耐药性， 加强对AMR的及时和广泛监测。青蒿素耐药性的发展， 撒哈拉非洲将对与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，以确定分子标志物的流行情况 与耐药性相关，可以作为一个有价值的工具，用于检测新出现的耐药基因型， 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上和地理上保持聚集，我们将 使用基于模型的地统计学来内插AMR标志物的患病率，并提出最佳策略 未来的采样点。接下来，在布基纳法索，我们将评估一种替代监测工具的效用： 利用节肢动物收集的血粉，一种被称为异种监视的技术， 最近被吸食过的人类标记我们认为，对异种生物的监视， 作为AMR分子监测的补充、快速部署和可接受的工具。最后， 由于分子监测主要依赖于以人为基础的干预性或横断面试验， 蚊子在传播抗药性寄生虫方面的作用还没有得到研究。我们将利用我们 异种监测样本，以研究媒介行为对AMR差异传播的影响 寄生虫 该项目将调查多个空间尺度上抗疟药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AMR的传播， 撒哈拉以南非洲，那里的毒品压力来自治疗和预防方案， 药理学景观随着病媒控制景观而定期变化。完成后 这项为期两年的研究和培训奖学金，申请人将有一个先进的技能，在地质统计 建模、分子流行病学、科学交流和丰富的现场经验。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 提高我们对影响病媒传播疾病的地理因素的认识。一 多学科的指导团队将为申请人在全球范围内的职业生涯中的研究独立性做好准备。 在环境和人类健康的关系中，卫生研究人员和病媒传播疾病流行病学家。