New weapons to fight malaria transmission: A historical view

Abstract

The stagnation of our fight against malaria in recent years, mainly due to the development of mosquito insecticide resistance, argues for the urgent development of new weapons. The dramatic evolution of molecular tools in the last few decades led to a better understanding of parasite-mosquito interactions and coalesced in the development of novel tools namely, mosquito transgenesis and paratransgenesis.Here we provide a historical view of the development of these new tools and point to some remaining challenges for their implementation in the field.

Demonstration of RNAi Yeast Insecticide Activity in Semi-Field Larvicide and Attractive Targeted Sugar Bait Trials Conducted on Aedes and Culex Mosquitoes

“…This might, in turn, open the potential for the registry of second-generation ATSBs that include RNAi yeast as an active ingredient. RNAi yeast ATSBs could enhance existing ATSB technology as a mosquito-specific next-generation ATSB, the use of which could help combat insecticide resistance, a growing problem which must be addressed by the development of new interventions [24][25][26]. The specificity of the Sh.463 shRNA insecticide for mosquitoes, as illustrated by the observed lack of impact of this insecticide on other insects [4], makes it an eco-friendly alternative to broad-based insecticides.…”

One Health Perspective of Malaria Transmission

“…The generation of transgenic mosquitoes poses a significant challenge, involving issues related to regulations, ethics and social aspects linked with the introduction of genetically modified organisms into the natural environment [133]. The transition of this approach from controlled laboratory settings to field trials in disease-endemic countries (DECs) is a gradual process aimed at maximising potential epidemiological benefits while minimising potential complications during implementation [134].…”

“…The transition of this approach from controlled laboratory settings to field trials in disease-endemic countries (DECs) is a gradual process aimed at maximising potential epidemiological benefits while minimising potential complications during implementation [134]. Among the multitude of factors to be taken into account is the irreversible nature of releasing organisms, as once released, it becomes exceedingly challenging to retrieve them in case issues emerge [133]. Unlike traditional methods of vector control, the utilisation of transgenic mosquitoes will encounter varying expectations from different stakeholders.…”

The transcriptional response in mosquitoes distinguishes between fungi and bacteria but not Gram types

“…These interactions have great relevance to disease transmission dynamics, as the tripartite interplay between mosquito host, environmental/gut microbes, and human pathogens affects the competence of the mosquito vector [ 2 – 4 ]. Bacteria and fungi may also be of use in vector control strategies, such as paratransgenesis [ 5 ] and biological pest management [ 6 ]. Finally, as insects’ interactions with a wide range of microbes are mediated by a small number of immune-related pathways, lessons learned about mosquitoes’ immune response to bacteria or fungi can give useful insights into their response to Plasmodium parasites and viruses.…”