Collaborative Research: Genetic-epidemiology framework for malaria mosquito and disease

合作研究：疟疾蚊子和疾病的遗传流行病学框架

• 批准号: 2052363
• 负责人: Abba Gumel
• 金额: $ 30万
• 依托单位: Arizona State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2052363&HistoricalAwards=false
• 关键词: Collaborative; Research; Genetic; epidemiology; framework; Collaborative; Research; Genetic; epidemiology; framework

Malaria is one of the deadliest diseases affecting mankind. The disease, which is caused by the protozoan Plasmodium parasites, is spread between humans via the bite of infected adult female mosquitoes and creates severe public health and socio-economic burdens in regions inhabited by almost half of the world’s population. Each year, malaria infects an average of over 230 million people and causes over 400,000 deaths (mostly in children under the age of five) in endemic areas globally. The widescale use of insecticides-based interventions, notably in the form of long-lasting insecticidal (LLINs) nets and indoor residual spraying (IRS), during the period 2000-2015, has resulted in a dramatic decrease in malaria burden in endemic areas, prompting a concerted global effort to eradicate the disease by 2040. Unfortunately since 2015, the malaria mosquito has developed widespread resistance to all five chemicals used in LLINs and IRS. Insecticide resistance and changes in climatic variables are two of the main impediments to malaria eradication. Since LLINs and IRS are the cornerstone interventions for malaria control, one of the most crucial challenges in the malaria ecology community is to determine whether insecticide resistance affects malaria epidemiology. This project will use mathematical modeling approaches, backed by novel empirical data collected in the laboratory as well as in the field, to provide realistic insight into the impact, control and mitigation of the impediments. The project will provide strategies for realistically achieving malaria eradication using existing insecticides-based control resources. The methodologies and results generated will be made available for broad application, and for studying the transmission dynamics and control of other vector-borne diseases such as chikungunya, dengue, Lyme disease, West Nile virus and Zika virus. The project will support the training of graduate and undergraduate students, as well as the participation of local high school students and teachers.The project will develop a genetic-epidemiology modeling framework for providing realistic insight into the malaria transmission dynamics and control, subject to insecticide pressure. The modeling framework extends the classical Ross-Macdonald compartmental modeling framework for malaria by adding, inter alia, the detailed lifecycle and population genetics of malaria mosquitoes (i.e., genetics of insecticide resistance) and the complex host-vector-parasite interactions. The models will allow for the assessment of the impacts of local changes in climatic variables (notably temperature) on the population abundance of the malaria mosquitoes by genotype. The approach of modeling the host-vector-parasite dynamics, in the context of malaria, will offer significant advances in applied mathematics and numerical analysis, particularly in designing and applying dynamical systems and numerical discretization theories and techniques for studying the transmission dynamics and control of diseases caused by vectors (such as mosquitoes and ticks). Specifically, PIs will (i) design a modeling framework for assessing the role of insecticide resistance on the fitness costs of insecticide resistance at different environmental conditions, (ii) evaluate the role of insecticide resistance on the ability of resistant mosquitoes to transmit malaria and (iii) assess the role of natural environmental factors on the abundance of insecticide resistance genotypes and how it relates to malaria incidence. This project will generate hard-to-get data on the fitness costs of insecticide resistance and impact of resistance on malaria parasite development in mosquitoes, which are so invaluable to the design and parametrization of realistic mathematical models for studying the role of insecticide resistance on the dynamics of malaria mosquitoes and disease. This will provide a realistic framework for the design and testing of resistance management strategies for malaria-endemic areas that only have a small chemical arsenal left to fight the disease. Ultimately, this project will generate conditions, in parameter space, for the effective control or elimination of malaria using existing insecticides-based resources, thereby contributing to the global malaria eradication efforts.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

疟疾是影响人类的最致命的疾病之一。该疾病是由原生动物疟原虫引起的，它通过被感染的成年女性蚊子的咬伤在人类之间传播，并在几乎一半的世界人口感染的地区创造了严重的公共卫生和社会经济伯良。每年，疟疾平均感染了超过2.3亿人，并在全球内部人体地区造成超过40万人死亡（主要是5岁以下儿童）。在2000年至2015年期间，以持久的杀虫（LLIN）网和室内残留喷雾（IRS）的形式泛滥，尤其是以持久的杀虫剂（LLIN）网和室内残留喷雾（IRS）的形式，导致了末端型疟疾的疟疾巨大减少，促使全球疾病的疾病开发，这是由于2040年的不幸。 LLIN和IRS中使用的所有五种化学物质的宽度耐药性。杀虫剂的耐药性和气候变量的变化是消除疟疾的主要障碍。由于LLIN和IRS是控制疟疾的基石干预措施，因此疟疾生态学界最关键的挑战之一是确定杀虫剂耐药性是否影响疟疾流行病学。该项目将采用数学建模方法，并得到实验室和现场收集的新经验数据的支持，以提供对障碍的影响，控制和缓解的现实见解。该项目将提供使用现有基于绝缘的控制资源的现实实现疟疾辐射的策略。所产生的方法和结果将用于广泛应用，并研究其他媒介传播疾病的传播动力和控制，例如基孔肯雅，粉丝，莱姆病，西尼罗河病毒和寨卡病毒。该项目将支持研究生和本科生的培训，以及当地高中生和老师的参与。该项目将开发一个遗传性循环系统建模框架，以提供对受杀虫剂压力的疟疾传播动态和控制的现实见解。该建模框架通过添加疟疾蚊子的详细生命周期和种群遗传学（即杀虫剂耐药性的遗传学）和复杂的宿主 - 载体 - 寄生虫相互作用，扩展了疟疾的古典Ross-Macdonald隔室建模框架。这些模型将允许评估气候变量（尤其是温度）对基因型疟疾蚊子种群丰度的影响。在疟疾的背景下，建模宿主 - 矢量 - 寄生虫动力学的方法将在应用数学和数值分析方面取得重大进展，尤其是在设计和应用动态系统以及数值离散的理论和技术方面，用于研究由媒介（例如蚊子和tick虫）引起的传播动态和控制疾病的控制动力学和控制。具体而言，PIS（i）设计一个建模框架，用于评估绝缘层在不同环境条件下绝缘的适应性成本的作用，（ii）评估绝缘层对抗性蚊子传播疟疾的能力的作用，并评估（iii）评估自然环境因素对杀虫剂抗药性生殖器和疟疾的吸收的作用。该项目将产生有关杀虫剂耐药性和耐药性对疟疾寄生虫发育的影响的难以确定的数据，这对于研究杀虫剂耐药性对疟疾蚊子和疾病动态的作用的设计和参数非常宝贵。这将为疟疾末端区域的抗药性管理策略设计和测试提供一个现实的框架，这些策略仅剩下一个小的化学武器库来抵抗这种疾病。最终，该项目将在参数空间中产生条件，以使用现有基于绝缘的资源来有效控制或进化疟疾，从而有助于全球疟疾消除工作。该奖项反映了NSF的法定任务，并通过使用基金会的知识分子优点和更广泛的影响审查标准来评估被认为是宝贵的支持。