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

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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.