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Evolutionary biology, evolution-proof insecticides and malaria control

December 11, 2009 - 13:49 -- Yannis Michalakis

Yannis Michalakis & François Renaud GEMI, CNRS-IRD UMR 2724, Montpellier, France,


Evolutionary thinking started pervading vector control strategies and planning since it was used to explain and manage insecticide resistance. More recently it has been used in the planning of GMMs (Genetically Modified Mosquitoes).


A new promising avenue was recently opened by Andrew Read and his colleagues.

They remarked that a vector control strategy would not elicit the evolution of resistance if it disrupts malaria transmission without, or hardly, affecting vector fitness. A way to implement such a strategy could take advantage of the relatively long, 10 – 14 days or longer, extrinsic incubation period, the time necessary for Plasmodium to produce its transmissible stages within its mosquito vectors. Because of this relatively long incubation period malaria is transmitted by the relatively old mosquitoes, which have already reproduced. Any “agent” killing mosquitoes late in their life but before they transmit malaria could be evolution-proof since it would essentially act as a mosquito senescence gene.


Entomopathogenic fungi, such as Beauveria or Metarhizium, seem to have the desired properties: they kill mosquitoes relatively late in their life but before malaria transmission. Moreover, they cause higher mortality in Plasmodium infected mosquitoes, which should not only retard any potential resistance to the fungi, but also enhance any mosquito resistance to Plasmodium. They can be produced industrially, as they have been used on a large scale for locust control. The anti-acridian experience has shown that, if necessary, it is possible to select and use taxon-specific fungal isolates. Finally, recent empirical and theoretical studies have shown that these pathogens can act synergistically with conventional insecticides to lower malaria transmission and decrease insecticide resistance. This is particularly promising as it is highly plausible that the combination of control approaches is more prone to yield sustainable vector control; it is also probably more pragmatic.


While this approach looks indeed very promising in not eliciting an evolutionary response from the vector, it is necessary to think and work on the potential effects it could have on Plasmodium. Indeed, even though such insecticides would be evolution-proof with respect to insecticide resistance, it is highly likely they will trigger Plasmodium evolution.


The relatively long extrinsic incubation period of Plasmodium, actually a shared characteristic with other mosquito-borne parasites such as the dengue virus, seems a priori puzzling – all else being equal selection would tend to decrease it. It is thus believed that at present shorter Plasmodium developmental times must incur a disadvantage, e.g. in infectivity. A large-scale application of the evolution-proof insecticides would dramatically change the adaptive landscape of Plasmodium, as long development would become the equivalent of a lethal gene – all long-developing Plasmodia would die if coverage is high. It is thus expected that because of this potentially massive selection Plasmodium will evolve shorter development times. How fast this will happen depends on whether there is already variation for this trait in Plasmodium populations or whether it is necessary to wait till mutation generates the right kind.


In any case, predicting the potential effects of such evolution is impossible at present because we do not know how developmental time in the mosquito is linked to infectiousness and virulence within the mosquito, nor do we know how it is linked to virulence in the vertebrate hosts. It may turn out to be the case that fast developing Plasmodium are less infective without being more virulent on humans. In this case the evolution of fast developing Plasmodium may be even more advantageous than the initial effects of evolution-proof insecticides on malaria transmission. But until the appropriate experiments are conducted we cannot know what the answer is.


Evolutionary biology has already proved extremely useful in devising control strategies, e.g. through the consideration of driving mechanisms for GMMs. It continues to do so with the proposition of evolution-proof insecticides. We feel that a major contribution it may make to the fight against diseases is through the evaluation of potential evolutionary responses of parasites to control policies. Indeed, the evolution of more virulent parasites following human intervention could be even more dreadful than the evolution of insecticide resistance.


Submitted by Christophe Boete on

Just to add a short information, I would recommend to anyone (even if this not only dealing with malaria... ) and especially for the ones remaining skeptical about the crucial importance of evolution in infectious diseases and the need to take it into account for public health issues, to have a look at the following paper presenting empirical evidences of parasite evolution after vaccination: Gandon, S. & Day, T. (2008). Evidences of parasite evolution after vaccination. Vaccine 26: C4-C7.

About the potential evolutionary responses of malaria parasites to control intervention, this is clearly largely understudied despite the real need to predict it. Concerning the release of GM Plasmodium- refractory mosquitoes, Ferguson et al. 2007 have discussed the potential consequences in term of virulence both to mosquitoes and humans.

Christophe Boëte

Research ///