4.6 Article

A combination of metabolic resistance and high frequency of the 1014F kdr mutation is driving pyrethroid resistance in Anopheles coluzzii population from Guinea savanna of Cameroon

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PARASITES & VECTORS
卷 12, 期 -, 页码 -

出版社

BMC
DOI: 10.1186/s13071-019-3523-7

关键词

Anopheles coluzzii; Deltamethrin; Permethrin; DDT; Metabolic resistance; kdr; Cameroon

资金

  1. Wellcome Trust International Training Fellowship in Public Health and Tropical Medicine [WT201918/Z/16/Z]

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BackgroundThe scale-up in the distribution of long-lasting insecticidal nets (LLINs) and indoor residual spraying has significantly reduced malaria burden and mortality. However, insecticide resistance, among other factors, is responsible for a recent rebound in malaria transmission in 2015-2016, threatening the progress so far made. As a contribution towards understanding patterns of resistance and its mechanism in the field we characterized a population of Anopheles gambiae (s.l.) from Gounougou, a Guinea savanna of north/central Cameroon.ResultsIndoor collection conducted in September 2017 identified Anopheles coluzzii and Anopheles arabiensis as the unique Anopheles vector species, with abundances of 83 and 17%, respectively. Analysis of infection with TaqMan assays using heads/thoraces of indoor collected females of An. coluzzii revealed a low Plasmodium falciparum parasite rate of 4.7%. Bioassays conducted with female An. coluzzii revealed extreme resistance, with low mortalities of only 3.751.25%, 3.03 +/- 1.59% and 1.45 +/- 1.45%, respectively, for permethrin, deltamethrin and DDT. In contrast, high susceptibility was obtained with the organophosphates and carbamates, with mortalities in the range of 98-100%. Synergist assays with piperonyl butoxide (PBO) recovered some susceptibility with increased mortality for permethrin to 14.88 +/- 8.74%, and for deltamethrin to 32.50 +/- 10.51% (similar to 27-fold increase compared to mortalities with deltamethrin alone, (2)=29, df=1, P<0.0001). These correlated with the results of cone bioassays which revealed complete loss of efficacy of Olyset (R) Net (0% mortality) and PermaNet (R) 2.0 (0% mortality), and the considerable loss of efficacy of Olyset (R) Plus (mortality of 2 +/- 2%), PermaNet (R) 3.0 side panel (mortality of 2 +/- 2%) and PermaNet3.0 (R) roof (mortality of 16 +/- 5.1%). Time-course bioassays conducted with deltamethrin established a high intensity of resistance, with LT50 of 309.09 (95% CI 253.07-393.71, Fiducial), and a resistance ratio of 93.09 compared with the fully susceptible Ngoussou laboratory colony. TaqMan genotyping revealed a high frequency of the 1014F allele (65.25%) in the An. coluzzii populations. Sequencing of a fragment of the voltage-gated sodium channel identified a single An. arabiensis female harbouring the 1014S kdr mutation.Conclusions This finding of high pyrethroid and DDT resistance in An. coluzzii from north-central Cameroon is a major obstacle to malaria control using pyrethroid bednets and indoor residual spraying with DDT.

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