Abstract

BackgroundResistance in malaria vectors to pyrethroids, the most widely used class of insecticides for malaria vector control, threatens the continued efficacy of vector control tools. Target-site resistance is an important genetic resistance mechanism caused by mutations in the voltage-gated sodium channel (Vgsc) gene that encodes the pyrethroid target-site. Understanding the geographic distribution of target-site resistance, and temporal trends across different vector species, can inform strategic deployment of vector control tools.ResultsWe develop a Bayesian statistical spatiotemporal model to interpret species-specific trends in the frequency of the most common resistance mutations, Vgsc-995S and Vgsc-995F, in three major malaria vector species Anopheles gambiae, An. coluzzii, and An. arabiensis over the period 2005–2017. The models are informed by 2418 observations of the frequency of each mutation in field sampled mosquitoes collected from 27 countries spanning western and eastern regions of Africa. For nine selected countries, we develop annual predictive maps which reveal geographically structured patterns of spread of each mutation at regional and continental scales. The results show associations, as well as stark differences, in spread dynamics of the two mutations across the three vector species. The coverage of ITNs was an influential predictor of Vgsc allele frequencies, with modelled relationships between ITN coverage and allele frequencies varying across species and geographic regions. We found that our mapped Vgsc allele frequencies are a significant partial predictor of phenotypic resistance to the pyrethroid deltamethrin in An. gambiae complex populations.ConclusionsOur predictive maps show how spatiotemporal trends in insecticide target-site resistance mechanisms in African An. gambiae vary across individual vector species and geographic regions. Molecular surveillance of resistance mechanisms will help to predict resistance phenotypes and track their spread.

Highlights

  • Resistance in malaria vectors to pyrethroids, the most widely used class of insecticides for malaria vector control, threatens the continued efficacy of vector control tools

  • Hancock et al BMC Biology (2022) 20:46 indoor residual spraying (IRS) and insecticide-treated bed nets (ITNs), are pivotal to malaria prevention, with ITNs in particular being responsible for a large portion of the reductions in malaria cases achieved over the period 2000–2015 [1]

  • Predictive accuracy was assessed by testing the ability of the model ensemble to predict withheld data, which showed a mean absolute prediction error (MAE; the average absolute difference between model predictions and observations) of less than 10% (MAE = 0.083) across all observed voltage-gated sodium channel (Vgsc) allele frequencies (with a root mean square error (RMSE) of 0.137; Additional File 1: Figure S1 and Table S1)

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Summary

Introduction

Resistance in malaria vectors to pyrethroids, the most widely used class of insecticides for malaria vector control, threatens the continued efficacy of vector control tools. The prevalence of insecticide resistance phenotypes in African malaria vector species is highly heterogeneous across geographic space [5], and underpinned by variation in genetic resistance mechanisms [6], which have the potential for rapid long range spread [7]. Where morphologically cryptic vectors are present, susceptibility bioassays are rarely used to measure resistance at the level of individual species and do not provide information about mechanisms of resistance. In due course genomic, surveillance to track the frequency of variants that are associated with phenotypic resistance is more scalable, insensitive to collection and environmental conditions, and can distinguish between different resistance mechanisms across different vector species

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