Slowing the development of insecticide resistance in malaria mosquitoes: Application of a spatially complex simulation model

Background: The fight against malaria is threatened by lack of sustainability of current tools as mosquitoes become resistant to insecticides and malaria parasites become resistant to malaria drugs.  Numerous resistance management strategies to slow evolution of resistance of mosquitoes have been examined. We transformed a strategy successfully applied to row-crop agroecosystems to the mosquito resistance milieu, modeling malaria mosquitoes and their ecology to examine evolution of resistance. 

Methods: We defined malaria mosquito resistance management (MMRM) as an agroecosystem, and modeled malaria mosquitos in two habitats which we called urban and pasture. The urban habitat included people and diverse environments; pesticides, including insecticides, insecticide-treated-bed nets, indoor residual spraying, or any other insecticide/pesticide combination used to kill or subdue malaria mosquitoes near people. The pasture environment was used as a “refuge”, where a refuge is any untreated environment possibly with dead-end hosts to malaria vectors, e.g., cattle, which contribute to a susceptible malaria mosquito gene pool.   We applied resistance management simulation software to MMRM to conduct spatial and temporal assessment of factors impacting malaria mosquito resistance. The model uses life history tables to move discrete populations of anopheline mosquitos through age classes, from eggs to adults, designating stochastic transition probabilities among age classes as well as probability of mosquito dispersal.  We modeled three species of mosquitoes for which malaria transmission data are available and used mosquito feeding preference for cattle to that for humans described in the literature.  We compared resistance evolution with and without the use of a refuge.

Results: .In all cases, resistance evolved more slowly when a refuge was used, especially for zoophilic mosquitoes. Resistance allele frequencies of at least fifty percent evolved more slowly using longer intervals between treatments (e.g., sprays, bed-nets) in all anopheline species analyzed. Resistance also evolved in untreated populations. The most anthropophilic mosquito had the shortest time to evolve resistance regardless of treatment interval or environment.

Conclusions: The utilization of refuges, common practice in certain agricultural systems, may also provide a means of slowing the spread of insecticide resistance in malaria vector mosquitoes. The rural environment (e.g., pasture) was never sprayed, but resistance usually evolved, reflecting dispersal between environments, therefore, effective management of malaria mosquito resistance requires an entire landscape assessment.