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Daily News Blog

01
Jul

Disease Carrying Mosquitoes Developing Resistance to Widely Used Mosquito Control Pesticides

(Beyond Pesticides, July 1, 2021) Yellow fever mosquitoes (Aedes aegypti) are evolving resistance to the pyrethroid insecticide permethrin, according to a study published by Colorado State University, highlighting the need to adopt ecologically-based mosquito management. Widespread, intensive use of the pesticide in mosquito control has allowed genetic mutations to persist among these mosquito populations, causing subsequent resistance to permethrin. Pyrethroids are one of the few remaining classes of insecticides available to control yellow fever mosquitos, and resistance threatens the ability to prevent disease outbreaks with chemical-intensive methods. Yellow fever mosquitoes are a vector for numerous untreatable diseases in humans, including dengue, chikungunya fever, and Zika viruses. Hence, this study highlights the significance of addressing pest resistance to pesticide control, particularly to mitigate disease exposure and effects. The researchers note, “This knowledge can help scientists understand how mosquitoes have evolved resistance and when a population can no longer be controlled with permethrin. This understanding will be necessary to develop tools to support future insecticide management strategies.”

Researchers sequenced the genome of resistant and knockdown (either recovered or dead) mosquitoes after permethrin exposure using a bottle bioassay. The aim was to identify genomic variants/biomarkers associated with specific resistance mechanisms. Two common pyrethroid resistance mechanisms occur among yellow fever mosquitoes: knockdown resistance involving “amino acid substitutions at the pyrethroid target site—the voltage-gated sodium channel (VGSC); [and] enhanced metabolism by detoxification enzymes.” Whether a mosquito displays a resistance or knockdown response to insecticide exposure depends on pyrethroid concentration and genetic background.

The results identify a significant association between pyrethroid resistance and thousands of different single-nucleotide polymorphisms (SNPs) mutations in VGSC. SNPs are variations in genetic sequences (a point mutation) responsible for producing different alleles or gene variants. SNPs in the VGCC and GABA receptor genes have associations with mosquito recovery after knockdown exposure. Furthermore, the study finds a moderate association between resistance and recovery among mosquitoes with mutations in detoxification and cuticle protein genes.

Insecticide resistance has been an issue since the introduction of DDT (dichlorodiphenyltrichloroethane) in the 1940s. In 1972, the U.S. banned the compound as it is highly persistent and harmful to the environment and natural resources. Furthermore, the chemical compound is known to accumulate in fatty human and animal tissue. Exposure to DDT and its breakdown products has links to reproductive dysfunction, endocrine disruption, neurotoxicity, cancer, diabetes, and obesity. Although DDT is no longer manufactured or used in much of the world, its use continues in 19 countries (including China—the primary manufacturer), mainly for mosquito control. In West Africa, DDT resistance was widespread in 53 percent of the territory during 2005 and expanded to 97 percent of the area by 2017. In 2018, Beyond Pesticides reported that “Rampant overuse [of DDT], both to control disease vectors and in agriculture, resulted in the development of significant resistance to the compound. Today, DDT resistance is widespread in Anopheles mosquitoes.” In 2017, Pesticide Action Network North America (PANNA) noted, “Of the 73 countries that provided monitoring data to WHO [the United Nations World Health Organization] from 2010 onward, 60 countries reported insect resistance to at least one insecticide and 50 reported resistance to 2 or more insecticides. This highlights the problem of relying on insecticide-based strategies for vector control. […] Ultimately, disease vectors and parasites develop resistance to the insecticide, and it becomes almost ineffective in the long run.”

With a DDT ban in most countries, the compound is not the only chemical pesticide promoting resistance as several current-use insecticides pose the same threat. Mosquitoes have become increasingly resistant to synthetic pyrethroids, in addition to other classes of insecticides, such as carbamates and organophosphates. For example, in 2005, mean mortality to deltamethrin was below the WHO (World Health Organization) threshold for confirmed resistance across 15 percent of West Africa; by 2017, that figure rose to 98 percent. East Africa has seen a real, though somewhat less dramatic, increase in resistance to pyrethroids, with an analogous rise in the spread during the same period from 9% to 45% of the region. Therefore, the development of mosquito resistance to these insecticides means that existing mosquito control programs are becoming far less effective.

Development of resistance is an entirely normal, adaptive phenomenon: organisms evolve, “exploiting” beneficial genetic mutations that give them a survival advantage. However, resistance is growing in all sectors of pest control, including critically needed agriculture and medicine. For nearly a century, the human response to resistance is the development of a compound that kills the resistant organism (whether pest or weed or bacterium or fungus), which works for a while. However, the dependence on chemical solutions is increasingly failing. Whether it is antibiotics for bacterial infections, herbicides for weeds/pests, or insecticides to mitigate vector-borne diseases, organisms are becoming resistant to usually toxic compounds. Once an organism inevitably becomes resistant to a particular chemical control, people — the chemical industry, researchers, applicators, farmers, public health workers, clinicians, et al. — will have typically moved on to the subsequent chemical “solution.” PANNA notes, “The World Health Organization underscored the problem in their 2012 guidance on policymaking for Integrated Vector Management (IVM): ‘Resistance to insecticides is an increasing problem in vector control because of the reliance on chemical control and expanding operations…Furthermore, the chemical insecticides used can have adverse effects on health and the environment.’”

Beyond Pesticides has written extensively on the issue of resistance, particularly the relationship to the use of agricultural and other land-management pesticides, with the central message: resistance is a symptom of the ineffectiveness of chemical-intensive agriculture and leads to increased use of more and more toxic pesticides. In addition, resistance in one of the “sectors” mentioned above can “crossover” to become problematic in another. Agricultural and veterinary uses of antibiotics significantly contribute to the resistance of certain bacteria or fungi to antibiotics that have historically knocked down such infections in humans. Examples include familiar drug names: penicillin, vancomycin, azithromycin, and fluconazole — all of which have become less and less effective as pathogens have developed resistance to them. Furthermore, health officials warn that continuous use of agroindustry-dominant glyphosate will perpetuate antibiotic resistance. Bayer/Monsanto patents glyphosate as an antibiotic since exposure hinders enzymatic pathways in many bacteria and parasites, serving as an antimicrobial. However, glyphosate kills bacterial species beneficial to humans and incorporated in probiotics yet allows harmful bacteria to persist, leading to resistance. This increase in resistance is evident among crops genetically engineered (GE) to be herbicide-tolerant, including glyphosate-tolerant GE seeds. Although one purpose of GE crops is to reduce pesticide use, an increase in resistance can result in additional pesticide use to compensate. 

Overall, the results demonstrate genetic changes result in the development of two types of pyrethroid resistance: VGSC and detoxification metabolism. Researchers suggest mosquitos that recovery from the initial insecticide knockdown contribute to resistance in the field. Sublethal exposure may be responsible for the mosquito’s ability to recover. Rather than dying from dehydration and predation, recovery mechanisms allow mosquitoes to develop resistance over time. This study enables researchers to fully understand the genetic differences among mosquitos who exhibit resistance and those who recover or die. Knowing the role genes play in pesticide metabolism can help researchers fully understand how resistance evolves under field-realistic conditions.

Growing pesticide resistance often leads to an increase in chemical inputs to control pests. Exposure to permethrin already has implications for human health, including cancer, endocrine (hormone) disruption, reproductive dysfunction, neurotoxicity, and kidney/liver damage. Mosquito resistance can augment the use of chemical control methods, including the addition of toxic synergists like piperonyl butoxide (PBO), known to cause and exacerbate adverse health effects from exposure. Therefore, researchers need to understand the mechanisms prompting pesticide resistance among mosquito populations to safeguard human health from disease lacking effective treatment and vaccines.

Beyond Pesticides advocates for alternatives to chemical approaches. The most successful mosquito control programs combine various strategies with community education and require government commitment and political will. For example, Vietnam reduced malaria deaths by 97% and malaria cases by 59% when it switched in 1991 from malaria eradication attempts using DDT to a DDT-free malaria control program. Additionally, a program in central Kenya involves using livestock as bait, introducing biological controls, and distributing mosquito nets in affected areas. Beyond Pesticides maintains that management strategies to combat insect-borne diseases cannot be successful if they are chemical-intensive. These strategies ignore the underlying conditions that exacerbate the spread of the disease. 

Jay Feldman, executive director of Beyond Pesticides, has noted, “We should be advocating for a just world where we no longer treat poverty and development with poisonous band-aids but join together to address the root causes of insect-borne disease because the chemical-dependent alternatives are ultimately deadly for everyone.” He also said, “We should focus on the deplorable living conditions and inequitable distribution of wealth and resources worldwide that give rise to squalor, inhumane living conditions, and the poor state of development that, together, breed insect-borne diseases like malaria.”

Even if yellow fever, dengue, and chikungunya, are not a local concern, there remains general concern surrounding the diseases mosquitoes can transmit, including West Nile virus and Zika. Beyond Pesticides provides valuable information on mosquito management and insect-borne diseases on the Mosquito Management and Insect-Borne Diseases section devoted to these issues. Furthermore, keep up on pesticide-related science and news, including mosquitos and pesticide resistance on Beyond Pesticides’ Daily News blog.

All unattributed positions and opinions in this piece are those of Beyond Pesticides.

Source: Science DailyPLOS Genetics

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