
Fighting Malaria: Innovations in Vector Control
Sep 27, 2024
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Malaria is transmitted exclusively through the bite of an infected female mosquito, which releases Plasmodium parasites into the host’s bloodstream. Of the c. 3500 mosquito species that exist, only the Anopheles genus are capable of transmitting human malaria. Among these, around 40 species transmit malaria at a level of major concern to public health.
Vector control is a critical component in infection prevention which can be used to focus on a small number of species whilst achieving large gains in reducing malaria transmission. Chemical insecticides are typically used, including organochlorides, carbamates, organophosphates, and pyrethroids. These types of measures are faced with the issues of insecticide resistance, environmental concerns, and effects on non-target organisms. These concerns create a demand for novel and alternative measures for vector control.
Drone technologies
Drones show high potential to aid in the fight against malaria. Potential applications of drone technologies include: identifying larval sites, delivery of genetically-based vector control tools and bioinsecticides via aerial spraying to kill mosquito larvae and delivering drugs and vaccines combined. Drones have been successfully utilised for mosquito control in Kenya, Tanzania, India, Rwanda, and Zanzibar. In Zanzibar, Agras MG-1S drones were used to spray 10 L of a biodegradable chemical agent to cover drinking water basins. In Malawi and near Lake Victoria, DJI Phantom drones are being used to survey and find mosquito breeding grounds.
New biocontrols
Strides are also being made in biocontrol for Mosquitoes. A gene silencing yeast is being utilised to induce larval death of Aedes aegypti. The yeast Saccharomyces cerevisiae was engineered to express short hairpin RNA (shRNA) corresponding to mosquito Rbfox1 genes Targeting Rbfox1 Represses Notch Signalling and Kills Both Larvae and Adult Mosquitoes. This was observed in lab and outdoor semi-field trials conducted on Aedes aegypti. High levels of mortality were observed during simulated field trials where adult females consumed yeast delivered through a sugar bait. Mortality correlated with defects in the mosquito brain. Larvicidal and adulticidal activities were also confirmed in trials conducted on Aedes albopictus, Anopheles gambiae, and Culex quinquefasciatus. Notably, there was no impact on survival of select non-target arthropods. This trial shows potential for yeast RNAi pesticides targeting Rbfox1 development into mosquito larvicides and adulticides for deployment in integrated biorational control programs.
A new bacterium is being deployed to help curb the mosquitos ability to carry diseases. Wolbachia is a bacterium that occurs naturally in around 50% of insect species but less commonly in mosquitoes. Wolbachia makes it more difficult for viruses such as dengue and chikungunya to reproduce inside mosquitoes. The biocontrol method involves artificially introducing Wolbachia to mosquito populations by breeding Wolbachia carrying mosquitoes and releasing them into areas affected by mosquito-borne diseases. This has been demonstrated for arboviruses such as dengue but there is recent evidence it may work for malaria too. A study in 2021 showed that Wolbachia strains are prevalent naturally in wild Anopheles moucheti and Anopheles demeilloni populations, which are vectors of malaria. Furthermore, the Wolbachia possessed genes that can rapidly invade and spread through host populations, which is vital for use in biocontrol. There is less evidence for stable natural Wolbachia infections in Anopheles gambiae, meaning they, and other Anopheles species, are important candidates for artificial infections
Mosquitoes are also being deployed against Mosquitoes. The Mosquitoes are genetically edited to contain a desirable genetic trait and then released to introduce this trait into the extant population via mating. This faces difficulties as Mosquitoes by their nature are mobile and can be distributed across large geographical ranges and it may not be feasible to release enough mosquitoes in a given area to make any impact. Even for an introduced trait neutral to the mosquito, one would have to release a quantity of mosquitoes far in excess of the wild-type into every village population. This can be combatted using ‘gene drives’ (any genetic element that can bias its inheritance among offspring). The strength of this bias is enough that the genetic element can increase in frequency even if it imposes a fitness cost on the host. Gene drives have the potential to introduce traits into a population over a rapid timeframe, even when starting from a low release frequency. To be able to build synthetic versions of gene drives, inspiration has been taken from naturally occurring examples, including sex distorter genes/chromosomes and toxin : antitoxin systems. The most valuable example of a gene drive for vector control has been homing endonuclease genes (HEGs). In both Anopheles gambiae and Anopheles stephensi mosquitoes, CRISPR-based HEGs have shown biased inheritance rates of close to 100%. In order to couple a trait of interest to the gene drive, either the gene drive knocks out an essential gene in the mosquito or the gene drive is tightly linked to a desirable effector gene.
Alongside the four main examples discussed, there are many more innovations being developed in the vector control field. Including: new formulations of Bacillus thuriengiensis and B. sphaericus to increase longevity or tackle increasing resistance, attractive toxic sugar baits, plant based metallic nanoparticles, further developments to the methods around the sterile insect technique and even the use of fish which consume mosquito larvae. In summary there are a large number of innovations taking place within the vector control space to combat the spread of malaria.
Sources:
https://malariajournal.biomedcentral.com/articles/10.1186/s12936-023-04454-0
https://www.mdpi.com/2076-0817/10/10/1251
https://royalsocietypublishing.org/doi/full/10.1098/rstb.2019.0803