Modelling the impact of the long-term use of insecticide-treated bed nets on Anopheles mosquito biting time.

Background: Evidence of changing in biting and resting behaviour of the main malaria vectors has been mounting up in recent years as a result of selective pressure by the widespread and long-term use of insecticide-treated bed nets (ITNs), and indoor residual spraying. The impact of resistance behaviour on malaria intervention efficacy has important implications for the epidemiology and malaria control programmes. In this context, a theoretical framework is presented to understand the mechanisms determining the evolution of feeding behaviour under the pressure of use of ITNs.

Methods: An agent-based stochastic model simulates the impact of insecticide-treated bed nets on mosquito fitness by reducing the biting rates, as well as increasing mortality rates. The model also incorporates a heritability function that provides the necessary genetic plasticity upon which natural selection would act to maximize the fitness under the pressure of the control strategy.

Results: The asymptotic equilibrium distribution of mosquito population versus biting time is shown for several daily uses of ITNs, and the expected disruptive selection on this mosquito trait is observed in the simulations. The relative fitness of strains that bite at much earlier time with respect to the wild strains, when a threshold of about 50% of ITNs coverage highlights the hypothesis of a behaviour selection. A sensitivity analysis has shown that the top three parameters that play a dominant role on the mosquito fitness are the proportion of individuals using bed nets and its effectiveness, the impact of bed nets on mosquito oviposition, and the mosquito genetic plasticity related to changing in biting time.

Conclusion: By taking the evolutionary aspect into account, the model was able to show that the long-term use of ITNs, although representing an undisputed success in reducing malaria incidence and mortality in many affected areas, is not free of undesirable side effects. From the evolutionary point of view of the parasite virulence, it should be expected that plasmodium parasites would be under pressure to reduce their virulence. This speculative hypothesis can eventually be demonstrated in the medium to long-term use of ITNs.