£1million study to aid fight against malaria

The Medical Research Council is funding a £1 million study in Liverpool, UK, to investigate mutations in malaria-spreading mosquitoes that may be making them resistant to insecticides.

Malaria infects 200 million people every year and is a huge health and economic burden on many countries, particularly in sub-Saharan Africa. Indoor spraying of insecticides and use of chemically-treated bed-nets currently help kill off millions of mosquitoes but that shield of protection could soon fall.

“Mosquitoes started evolving a degree of resistance through mutations a number of years ago but now new mutations have been discovered that almost always occur together with the first mutations,” explained Dr Andrias O’Reilly, senior lecturer in neurobiology in LJMU’s School of Biological and Environmental Sciences.

“We suspect these second mutations are turbo-boosting resistance and the bad news is they are popping up in different parts of Africa.”

22 new mutations

Pyrethroid insecticides target a molecule in the insect’s nervous system called a sodium channel. A recent study sequenced the channel gene in 1,142 mosquitoes tested in 13 African countries and twenty new mutations were discovered.

The Liverpool scientists are tasked with finding out the extent to which the new mutations boost resistance, and, crucially, to identifying which mutations are the most resistant.

Dr O’Reilly is collaborating with Dr Tony Nolan, Professor Martin Donnelly and Dr Linda Grigoraki at the Liverpool School of Tropical Medicine.

The LSTM team will use gene-editing technology to introduce each mutation into mosquitoes and then test commonly used pyrethroid insecticides to see which mutant insects survive.

Ranking of resistance

At LJMU, the team will be using a technique called electrophysiology to detect the tiny electrical current that flows when positively-charged sodium ions move through the channel molecule.

“This will tell us how the insecticides affect function of the mosquito channel (when it opens or is non-conductive) and if mutations of the channel prevent the insecticides from interfering with its function,” explained Andrias. “Simultaneously, we will make a 3-D atomic model of the sodium channel to see how mutations might affect the structure of the protein and its interactions with the insecticide molecules.”

Overall, the project aims to identify which mutations are actually associated with resistance and over three years seeks to draw up a hit-list of mutations, ranked according to their magnitude on insecticide resistance.

Knowing which mutations to track is important for monitoring the spread of resistance in the field.

Most effective spray?

Furthermore, the use of a range of different pyrethroids in the studies will help identify which type of pyrethroid is most effective against each mutation.

“This, we hope will be particularly useful to the teams of insecticide sprayers, so they can select the most effective chemicals for spraying or use in bednets for each particular geographical area,” added Andrias.