Elucidating the mechanisms of insecticide resistance in malaria vector populations from four endemic countries in Sub-Saharan Africa
Characterising phenotypic resistance to pyrethroids in eleven study sites across four countries.
The development of novel vector control interventions is dependent on an understanding of the mechanisms by which resistance arises. Local, high quality entomological data are essential to inform selection of optimal mixes of interventions to maximise impact. This thesis characterises phenotypic resistance to pyrethroids in eleven study sites across four countries in West, Central and East Africa and uses Next Generation Sequencing to elucidate mechanisms of resistance. We investigate microbial mediated insecticide resistance in deltamethrin resistant An. coluzzii from Cote d鈥橧voire, target site mutations in pyrethroid resistant An. gambiae s.l. from the Democratic Republic of the Congo (DRC), gene expression profiles of permethrin resistant An. arabiensis of varying ages from Tanzania and gene and microbial expression profiles of permethrin resistant An. coluzzii displaying reduced PBO synergy from Guinea.
The use of NGS in this thesis identified novel SNPs, bacterial species, and a wide range of detoxification, cuticular, salivary and ABC transporter genes associated with phenotypic pyrethroid resistance. Their identification would not have been possible using standard PCR screening assays, which only detect known mutations. Where resources are available, NGS methods should be used more widely in entomological surveillance to better inform malaria vector control tools.
Speaker
Bethanie Pelloquin, LSHTM
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