ABSTRACT
Initial scepticism about the ecological feasibility of the genetically modified mosquito (GM) approach for malaria control1,2 has been supported by some recent experimental studies indicating that the insertion of transgenes, including those that induce refractoriness to malaria, confers a fitness cost to mosquitoes.3-5 However, consideration of the possible fitness advantages of not becoming infected is also required to evaluate the net fitness of transgenic mosquitoes when introduced into natural populations. Therefore knowledge of whether ma laria parasites are virulent to their vectors, and if so, to what magnitude, has direct relevance for forecasting the success of the GM approach. Here we summarize all known detrimental effects of malaria parasites on their mosquito vectors, and discuss their implications to the introduc tion of malaria-refractory genes in nature. Furthermore we review the mode of action by which transgenes generate refractoriness, and speculate on the evolutionary responses of Plasmodium to this killing mechanism. Finally, the virulence implications of current candidate GM phenotypes, both to mosquitoes and humans, are discussed.
