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Title: Genetic components of insecticide resistance in Anopheles arabiensis
Author: Howell, Paul I.
ISNI:       0000 0004 7658 8883
Awarding Body: University of Liverpool
Current Institution: Liverpool School of Tropical Medicine
Date of Award: 2018
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Currently 3.3 billion people are at risk of becoming infected with malaria worldwide with over 90% living in sub-Saharan Africa. Recently it was estimated that approximately 131,000 fewer deaths and over 650,000 cases of malaria were averted during the last 15 years. These changes are attributed to the widespread implementation of long-lasting insecticide-treated nets, indoor residual spraying with insecticides, and artemisinin-combined therapeutics across Africa. However, current challenges have resulted in a stalling of progress with insecticide resistance as the most prominent and potentially dangerous. Although there has been recent interest in insecticide resistance in Anopheles arabiensis, much is still unknown. Compared to the other main vectors, its exophilic nature and more catholic diet results in opportunistic feeding thereby circumventing home-based insecticide-treated interventions. Therefore, the goal of this dissertation is to examine insecticide resistance within the under-studied West Africa to better understand the origin and spread of anthropogenic-associated resistance in An. arabiensis by 1) using quantitative trait loci (QTL) analysis, to determine the genetic basis of dieldrin resistance in An. arabiensis from the Sudan, 2) determine the origin and spread of Gaba-296S in the Sahel region and 3) investigate novel bendiocarb resistance in Senegal using a paired QTL/microarray analysis. Using QTL analysis, a single, strong peak was estimated in both the F2 and advanced intercross line families at a similar position on the 2L chromosomal arm. In neither instance did the peak contain with the Gaba-296S mutation, typically implicated in dieldrin resistance, but was found 4Mb upstream towards the telomere near an ATP-binding cassette (ABCB-4) transporter. Second, an approximately 2kb region of gamma-amino butyric acid (GABA) was sequenced in individuals collected from the wild. In resistant individuals, the same base-pair polymorphisms were seen within 10 bases after the Gaba-296S mutation in samples from Senegal, Burkina Faso, and the Sudan. Based on this, it was concluded that a single origin of Gaba-296S had occurred with a subsequent sweep across the Sahel. This is the first broad geographical spread of resistance alleles through reported for this species. Last I investigated bendiocarb resistance in a population from Rufisque, Senegal. While QTL analysis was inconclusive, microarray analysis found the cuticular protein genes CPLCX2 and CPLCG4 overexpressed in the resistant population. Across West Africa, urbanisation and agriculture have had a major impact on the evolution of resistance in An. arabiensis. This dissertation highlights several important attributes that make An. arabiensis a particularly difficult species to control. My hope is that this body of work will stimulate research into the effects of urbanisation and resistance in An. arabiensis, especially in areas where urban and peri-urban agriculture is present.
Supervisor: Donnelly, Martin ; Weetman, David Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral