Insecticide resistance in Anopheles arabiensis from Ethiopia (2012–2016): a nationwide study for insecticide resistance monitoring

Abstract

BackgroundIndoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) remain the cornerstones of malaria vector control. However, the development of insecticide resistance and its implications for operational failure of preventative strategies are of concern. The aim of this study was to characterize insecticide resistance among Anopheles arabiensis populations in Ethiopia and describe temporal and spatial patterns of resistance between 2012 and 2016.MethodsBetween 2012 and 2016, resistance status of An. arabiensis was assessed annually during the long rainy seasons in study sites from seven of the nine regions in Ethiopia. Insecticide resistance levels were measured with WHO susceptibility tests and CDC bottle bioassays using insecticides from four chemical classes (organochlorines, pyrethroids, organophosphates and carbamates), with minor variations in insecticides tested and assays conducted between years. In selected sites, CDC synergist assays were performed by pre-exposing mosquitoes to piperonyl butoxide (PBO). In 2015 and 2016, mosquitoes from DDT and deltamethrin bioassays were randomly selected, identified to species-level and screened for knockdown resistance (kdr) by PCR.ResultsIntense resistance to DDT and pyrethroids was pervasive across Ethiopia, consistent with historic use of DDT for IRS and concomitant increases in insecticide-treated net coverage over the last 15 years. Longitudinal resistance trends to malathion, bendiocarb, propoxur and pirimiphos-methyl corresponded to shifts in the national insecticide policy. By 2016, resistance to the latter two insecticides had emerged, with the potential to jeopardize future long-term effectiveness of vector control activities in these areas. Between 2015 and 2016, the West African (L1014F) kdr allele was detected in 74.1% (n = 686/926) of specimens, with frequencies ranging from 31 to 100% and 33 to 100% in survivors from DDT and deltamethrin bioassays, respectively. Restoration of mosquito susceptibility, following pre-exposure to PBO, along with a lack of association between kdr allele frequency and An. arabiensis mortality rate, both indicate metabolic and target-site mutation mechanisms are contributing to insecticide resistance.ConclusionsData generated by this study will strengthen the National Malaria Control Programme’s insecticide resistance management strategy to safeguard continued efficacy of IRS and other malaria control methods in Ethiopia.Electronic supplementary materialThe online version of this article (10.1186/s12936-017-2115-2) contains supplementary material, which is available to authorized users.

Genome-wide gene expression profiling reveals that cuticle alterations and P450 detoxification are associated with pyrethroid resistance in Anopheles arabiensis populations from Ethiopia

“…arabiensis against pyrethroids and DDT is widespread. 10 In many Ethiopian An. arabiensis populations an association between the kdr mutation in the VGSC and resistance to pyrethroids and DDT resistance has been observed.…”

“…arabiensis populations an association between the kdr mutation in the VGSC and resistance to pyrethroids and DDT resistance has been observed. 7, 9, 10, 12 However, a number of studies have also pointed to increased detoxification as important in resistant populations, as the resistance phenotype is strong, and because kdr mutations were not fixed at the population level. 10, 12 Metabolic resistance has been observed in other pyrethroid and DDT resistant An.…”

“…7, 9, 10, 12 However, a number of studies have also pointed to increased detoxification as important in resistant populations, as the resistance phenotype is strong, and because kdr mutations were not fixed at the population level. 10, 12 Metabolic resistance has been observed in other pyrethroid and DDT resistant An. arabiensis populations from East-Africa, but the putative involvement of genes encoding detoxification enzymes associated with metabolic resistance was only investigated for populations from Tanzania and Sudan using a whole-genome microarray.…”

“…Because target site mutations are unlikely to fully explain high-level resistance in Ethiopian populations ( 10, 12 and see above), we performed a differential gene expression analysis between each deltamethrin and DDT resistant An. arabiensis population (ASN, CHW or TOL) and both susceptible strains (SEK or MOZ) (Figure 2).…”

Genome‐wide gene expression profiling reveals that cuticle alterations and P450 detoxification are associated with deltamethrin and DDT resistance in Anopheles arabiensis populations from Ethiopia

“…High levels of insecticide resistance have also been reported for An. arabiensis in many countries, including Ethiopia, where we recently surveyed several populations across the country and showed that these An. arabiensis populations exhibited countrywide resistance against DDT and the pyrethroid deltamethrin …”