Towards genetic manipulation of wild mosquito populations to combat malaria: advances and challenges

Abstract

SUMMARYMalaria kills millions of people every year, yet there has been little progress in controlling this disease. For transmission to occur, the malaria parasite has to complete a complex developmental cycle in the mosquito. The mosquito is therefore a potential weak link in malaria transmission, and generating mosquito populations that are refractory to the parasite is a potential means of controlling the disease. There has been considerable progress over the last decade towards developing the tools for creating a refractory mosquito. Accomplishments include germline transformation of several important mosquito vectors, the completed genomes of the mosquito Anopheles gambiae and the malaria parasite Plasmodium falciparum, and the identification of promoters and effector genes that confer resistance in the mosquito. These tools have provided researchers with the ability to engineer a refractory mosquito vector, but there are fundamental gaps in our knowledge of how to transfer this technology safely and effectively into field populations. This review considers strategies for interfering with Plasmodium development in the mosquito, together with issues related to the transfer of laboratory-acquired knowledge to the field, such as minimization of transgene fitness load to the mosquito, driving genes through populations, avoiding the selection of resistant strains, and how to produce and release populations of males only.

Experimental analysis of the blood-sucking mechanism of female mosquitoes

“…They have been studied mainly in connection with the transmission of tropical diseases, such as malaria and yellow fever (Dekker et al, 2005;Riehle et al, 2003). To suck blood from a host through a long and slender proboscis, female mosquitoes utilize pumping organs located in their head.…”

Nature beats nurture: a case study of the physiological fitness of free-living and laboratory-reared maleAnopheles gambiae s.l.

“…gambiae s.s. Giles and its sibling species An. arabiensis Patton, because little is known about the biology of this sex , and because these species are the most important vectors of malaria in Africa (Gillies and DeMeillon, 1968;White, 1974) and thus a leading target for control measures based on the release of genetically modified (Ito et al, 2002;Riehle et al, 2003) and/or sterile males (Helinski et al, 2006a). Consequently there is an urgent need to understand the life history and performance of free-living male An.…”

Perspectives in the control of infectious diseases by transgenic mosquitoes in the post-genomic era: a review

“…Recent research on the fitness of transgenic mosquitoes, including measurements of longevity and fertility and use of population cages, has been performed. Most of these studies (Riehle et al 2003, Marrelli et al 2006a, showed a reduced fitness load of transgenic mosquitoes, when compared to the wild population. Only one transgene, the peptide SM1 expressed in An.…”

“…This latter aspect is of practical importance because in such cases the transgene(s) can be driven through a population only once (Riehle et al 2003).…”