Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans

Abstract

Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus), making these mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids). Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance.

Fig 1. Locations of bioassay data for the organophosphates and pyrethroids, 2006 to 2015.

Locations of populations that have been bioassayed (susceptibility and dose response, adult and larval) are shown for both insecticide classes, overlaid on maps of environmental suitability for Ae. aegypti and Ae. albopictus from Kraemer et al. (2015) eLife, 4: e08347.

Fig 2. The frequency of resistance to deltamethrin in Ae. Aegypti, 2006–2015.

Adult bioassays using 0.05% insecticide for 1 hour are denoted as circles and results from nonstandard adult bioassays (including different diagnostic doses and exposure periods) are denoted as triangles. The map is zoomed to the 3 regions with data. (A) Americas. (B) Africa/Arabian Peninsula. (C) Asia.

Fig 3. The level of Ae. aegypti resistance to temephos, 2006–2015.

The ratio of the lethal concentration required to kill half of the sample (LC₅₀ value) obtained by each study to the value obtained for the Rockefeller susceptible strain across studies was calculated. The ratios were then split into 5 classes: values less than 2-fold higher than Rockefeller and each quartile of the remaining distribution. The map is zoomed to the 3 regions with data. (A) Americas. (B) Africa. (C) Asia.

Fig 4. Frequency of insecticide resistance in Aedes albopictus in all years.

The locations of Ae. albopictus populations used in susceptibility (circles) and dose-response (triangles) bioassays for each of the 4 main classes of neurotoxic insecticide. Both adult and larval bioassays are included. Mortality values for 2006–2015 are denoted by larger circles and the years up to 2005 are denoted by smaller circles.

Fig 5. The geographical distribution of the 10 known voltage-gated sodium channel (VGSC) mutations in Aedes aegypti across the 3 continents in which they have been detected.

Association of each mutation with pyrethroid resistance is shown in the key. Font size gives an indication of relative frequency.

Fig 6. The geographical distribution of metabolic resistance detoxification genes based on significant overexpression.

Genes are shown if linked to a resistance phenotype in transcriptomic studies, and a role has been demonstrated by functional validation (in vitro metabolism, ribonucleic acid interference (RNAi), or heterologous expression). All are in Ae. aegypti other than those marked: †Ae. albopictus; *both species.