An insecticide about to be widely deployed inside African homes to combat malaria-carrying mosquitoes is already losing its punch. Two years ago, the World Health Organization (WHO) gave the green light for clothianidin, long used in agriculture to kill crop pests, to be added to the current mainstays of indoor mosquito control, which are losing their effectiveness as the insects develop resistance. Since then, many African countries have been laying plans to spray the walls of homes with the pesticide—it would represent the first new class of chemicals adopted for such use in decades—and looking anxiously for evidence of pre-existing resistance.
Now, scientists at Cameroon’s Centre for Research in Infectious Diseases (CRID) have found it. They recently sampled mosquitoes from rural and urban areas around Yaoundé, the capital, including two key malaria carriers. In one standard susceptibility assay, exposure to clothianidin for 1 hour killed 100% of Anopheles coluzzii. But in some A. gambiae samples as many as 55% of the mosquitoes survived, the group reported in a preprint posted 7 August on the bioRxiv preprint server.
Corine Ngufor, a medical entomologist at the London School of Hygiene & Tropical Medicine, says this appears to be the first report of clear resistance to clothianidin in malaria-carrying insects. “It may spread very quickly and make this new class of insecticide almost useless for malaria vector control within a few years,” she warns.
Colince Kamdem, the CRID research scientist who led the study, says agricultural use of neonicotinoids—the class of chemicals to which clothianidin belongs—likely drove the emergence of the resistant mosquito strains. “WHO would never have recommended this insecticide if such data were available,” he contends.
Tiaan de Jager, director of the University of Pretoria Institute for Sustainable Malaria Control in South Africa, says the study shows it is crucial to test malaria vectors for resistance to an insecticide before deploying it. “It proves how important it is to tailor control methods to a region, such as an area of high agriculture, to ensure the success of the methods and overall program,” he says. “Other novel insecticide chemistries are urgently needed for malaria vector control,” Ngufor adds.
Bed nets coated with long-lasting insecticides and indoor spraying have helped halve malaria mortality and morbidity in the past 2 decades. These programs used insecticides from four classes but relied heavily on pyrethroids because they are cheap and nontoxic to mammals including humans, Kamdem says.
To combat the rise of pyrethroid-resistant mosquitoes, WHO added clothianidin to its “prequalified” list of chemicals acceptable for indoor spraying (and potentially nets). Neonicotinoids have become increasingly controversial as agricultural pesticides because of their impacts on pollinators; Europe has banned their use in agriculture. But farms in Cameroon and elsewhere in Africa rely heavily on them. In agricultural areas, Kamdem says, pesticide residues contaminate standing water that serves as breeding sites for mosquito larvae, favoring the evolution of neonicotinoid resistance.
The Cameroon finding doesn’t surprise German life science company Bayer AG, which manufactures one of the two formulations of clothianidin that malaria programs are considering for indoor spraying. “We supported some work in Côte d’Ivoire to also explore this and it seemed to suggest the same kind of finding, that there was already resistance to the family of insecticides that clothianidin belongs to,” says Sebastian Horstmann, Bayer’s product development manager for the clothianidin formulation. Horstmann says that to thwart, or at least slow, resistance, Bayer is developing new formulations with multiple insecticides for indoor spraying. But Kamdem notes those combinations have yet to be tested on resistant mosquitoes because none had been identified until now.
WHO has not reviewed the study because it has not yet been published in a peer-reviewed journal, says Deusdedit Mubangizi, who coordinates the agency’s “prequalification” assessments of active pharmaceutical products and medicines including insecticides used for mosquito control. But he thinks the chemical could still be an asset in mosquito control. “Resistance to clothianidin is much less prevalent than to other alternative insecticides in current use,” he says. But how long that will last is the great unknown—and concern.