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: 10322453
• 负责人: Hanna Ehrlich
• 金额: $ 1.09万
• 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 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10322453
• 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; Developing Countries; Development; Disease; Drug resistance; Epidemiologist; Epidemiology; Feeding behaviors; Fellowship; Female; Future; 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; public database; 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.

项目摘要/摘要 抗疟药是全球治疗和预防疟疾的关键工具，但它们的成功 抗性抗性（AMR）的持续出现和传播所阻碍。在电流中 多药耐药性的气候，包括对全球前线药物青蒿素的抗性，需要 及时扩展AMR的广泛监视。亚半氨甲蛋白耐药性的发展 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 监视，涉及筛查血液样本以确定分子标记的患病率 与耐药性相关，可以是检测出现抗性基因型之前的有价值的工具 他们变得广泛。该建议将首先表征跨分子监测工作的状态 撒哈拉以南非洲。通过假设研究在时间和地理上仍然存在，我们将 使用基于模型的地统计学来插入AMR标记的流行率并提出最佳策略 用于将来的抽样网站。接下来，在布基纳法索，我们将评估替代监视工具的实用性： 使用节肢动物收集的血液（一种被称为Xenosurbhoodance的技术）来监测分子 最近被喂养的人类的标记。我们认为Xenosurbhoolance可能会充当 互补，可快速可部署和可接受的工具，用于AMR的分子监测。最后， 由于分子监测主要依赖于人类的介入或横断面试验，所以该角色 蚊子传播抗药性寄生虫的蚊子仍未开发。我们将利用我们的 异种监视样品，以研究向量行为对AMR差异传播的影响 寄生虫。 该项目将研究在多个空间尺度下抗疟疾的患病率和动力学。 拟议的研究的目的是帮助指导决策者控制AMR的传播 撒哈拉以南非洲，药物压力源于治疗和预防方案，这 药理学景观在矢量控制景观旁定期变化。完成后 这项为期两年的研究和培训奖学金，申请人将具有地理上的高级技能 建模，分子流行病学，科学交流和广泛的现场经验。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，以促进监视工作 并提高我们对影响媒介传播的地理因素的理解。一个 多学科指导团队将为申请人做好准备，以使申请人成为全球职业的研究独立性 卫生研究人员和媒介传播疾病的流行病学家，环境与人类健康联系。

项目成果

Molecular surveillance of antimalarial partner drug resistance in sub-Saharan Africa: a spatial-temporal evidence mapping study.

• DOI: 10.1016/s2666-5247(20)30094-x
• 发表时间: 2020-09
• 期刊: The Lancet. Microbe
• 作者: Ehrlich HY;Jones J;Parikh S
• 通讯作者: Parikh S

Tracking antimalarial drug resistance using mosquito blood meals: a cross-sectional study.

• DOI: 10.1016/s2666-5247(23)00063-0
• 发表时间: 2023-06
• 期刊: LANCET MICROBE
• 影响因子: 38.2
• 作者: Ehrlich, Hanna Y.;Some, Fabrice;Bazie, Thomas;Ebou, Catherine Neya;Dembele, Estelle Lotio;Balma, Richard;Goodwin, Justin;Wade, Martina;Bei, Amy K.;Ouedraogo, Jean-Bosco;Foy, Brian;Dabire, Roch K.;Parikh, Sunil
• 通讯作者: Parikh, Sunil