Some mosquitoes are already proof against the newest malaria weapon science

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A solution of clothianidin and another insecticide is sprayed on the walls of a house in Rwanda.

© BAYER

By Munyaradzi MakoniAug. 31, 2020, 12:20 pm

An insecticide that is to be used on a large scale in African homes to combat mosquitoes with malaria is already losing its effectiveness. Two years ago, the World Health Organization (WHO) gave the green light to clothianidin, which has long been used in agriculture to kill plant pests, to add to the current mainstays of indoor mosquito control, which lose their effectiveness when the insects develop resistance. Since then, many African countries have drawn up plans to spray the walls of houses with pesticides – it would be the first new class of chemical to be introduced for such use in decades – and are anxiously looking for evidence of pre-existing resistance.

Now scientists from the Cameroon Center for Infectious Disease Research (CRID) have found it. They recently examined mosquitoes from rural and urban areas around Yaoundé, the capital, including two major malaria carriers. In a standard susceptibility test, exposure to clothianidin for one hour killed 100% of Anopheles coluzzii. In some A. gambiae samples, however, 55% of the mosquitoes survived, the group reported in a preprint published on August 7th on the bioRxiv preprint server.

Corine Ngufor, a medical entomologist at the London School of Hygiene & Tropical Medicine, says this is the first report of clear resistance to clothianidin in malaria-transmitting insects. “It can spread very quickly, rendering this new class of insecticide almost unusable for fighting malaria vectors in a matter of years,” she warns.

Colince Kamdem, the CRID researcher who led the study, says agriculture’s use of neonicotinoids – the class of chemicals that includes clothianidin – likely fueled the emergence of resistant strains of mosquitoes. “WHO would never have recommended this insecticide if such data were available,” he claims.

According to Tiaan de Jager, director of the Institute for Sustainable Malaria Control at the University of Pretoria in South Africa, the study says it is crucial to test malaria vectors for resistance to an insecticide before use. “It shows the importance of aligning control methods with a region such as an area with high agriculture in order to ensure the success of the methods and the overall program,” he says. “There is an urgent need for other novel insecticide chemicals to fight malaria vectors,” added Ngufor.

Bed nets coated with long-lasting insecticides and indoor sprays have helped cut malaria mortality and morbidity in half over the past two decades. These programs used insecticides from four classes, but relied heavily on pyrethroids because they are cheap and non-toxic to mammals, including humans, Kamdem says.

To combat the rise of pyrethroid-resistant mosquitoes, the WHO added clothianidin to its “pre-qualified” list of chemicals suitable for indoor (and possibly netting) spraying. Neonicotinoids are increasingly controversial as agricultural pesticides because of their effects on pollinators. Europe has banned their use in agriculture. But farms in Cameroon and elsewhere in Africa are heavily dependent on them. In agricultural areas, according to Kamdem, pesticide residues contaminate stagnant water, which serves as a breeding ground for mosquito larvae, and encourage the development of neonicotinoid resistance.

The findings in Cameroon come as no surprise to the German life science company Bayer AG, which makes one of the two formulations of clothianidin that are considering malaria programs for indoor spraying. “We supported some work in Côte d’Ivoire to look into this as well, and it seemed the same type of finding to suggest that there was already resistance to the family of insecticides that clothianidin is a part of,” says Sebastian Horstmann, Product Development Manager at Bayer the clothianidin formulation. Horstmann says Bayer is developing new formulations of several insecticides for indoor spraying to thwart or at least slow down resistance. Kamdem notes, however, that these combinations have not yet been tested on resistant mosquitoes as none have been identified.

WHO didn’t review the study because it hasn’t yet been published in a peer-reviewed journal, says Deusdedit Mubangizi, who coordinates the agency’s prequalification assessment for active pharmaceuticals and medicines including mosquito control insecticides. But he believes the chemical could still be an asset to mosquito control. “Resistance to clothianidin is far lower than that of other alternative insecticides currently in use,” he says. But how long that will take is the big unknown – and the worry.

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