©2005 Copyright Eurekah / Landes Bioscience Do Not Distribute CHAPTER *Corresponding Author: Heather Ferguson—Public Health Entomology Unit, Ifakara Health Research and Development Centre, Tanzania and Laboratory of Entomology, Wageningen University, The Netherlands. Email: heather.ferguson@wur.nl Genetically Modified Mosquitoes for Malaria Control, edited by Christophe Boëte. ©2005 Eurekah.com. Malaria Parasite Virulence in Mosquitoes and Its Implications for the Introduction and Efficacy of GMM Malaria Control Programmes Heather Ferguson,* Sylvain Gandon, Margaret Mackinnon and Andrew Read Abstract I nitial scepticism about the ecological feasibility of the genetically modified mosquito (GM) approach for malaria control 1,2 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. Introduction Initial scepticism about the ecological feasibility of the genetically modified mosquito (GM) approach for malaria control 1,2 has been supported by some recent experimental studies indi- cating that the insertion of transgenes, including those that promote resistance to malaria (Plas- modium sp.), confers a fitness cost to mosquitoes. 3-5 This suggests that the GM approach would have limited epidemiological impact, as the genes carrying refractoriness may not reach suffi- ciently high prevalence in vector populations to reduce disease transmission (see Box 1 for a description of the epidemiological impact of GM). Some argue that the low fitness of GM mosquitoes need not impede the spread of the refractory genes they carry as long as they are linked to an efficient genetic drive mechanism. 6 Certainly genetic drive will increase the rate of gene invasion, but only if a sufficiently high number of inseminations occur in the first place; Boete(Ferguson) 8/2/05, 8:57 AM 1