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Title: Behavioural and evolutionary responses of Anopheles gambiae S.S. to bednets and pyrethoids
Author: Lynd, Amy
ISNI:       0000 0004 2672 5675
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2008
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Vector control by insecticides is fundamental to the global strategy foOr malaria prevention. Insecticide treated bednets (ITNs) are central to this approach but with only pyrethroids available for ITN use, resistance to this class of insecticides is a major threat. Knock-down resistance to pyrethroids is strongly associated with the presence of a single amino acid substitution (kdr) in the voltage-gated sodium channel in many insects, including African malaria vectors. With the long-term aim of extending the effective lifespan of pyrethroids and ITNs in particular, this study investigated knock-down resistance and behaviour at the bednet interface in Anopheles gambiae s.s. Specifically, the molecular studies aimed to improve the reliability of kdr detection methods, investigate the origins and spread of kdr mutations and determine the strength of the selection pressures acting on them; the behavioural studies investigated non-contact repellency by pyrethroids and arrival patterns ofhost-seeking mosquitoes at a human-baited bednet. Detection of kdr alleles is important in order to monitor the spread of resistance in the field, and a novel kdr detection method (Hot Oligonucleotide Ligation Assay or HOLA) was developed to improve on existing techniques. This method differentiated homozygous and heterozygous individuals for both kdr alleles and was transferred to a resource poor laboratory. HOLA was also used to confirm the first occurrence ofa phenylalanine heterozygous specimen. population genetic based approach was usedserine/ to investigate the relative age ofthe kdr mutations and selection pressures acting upon them. Sequencing ofthe voltage-gated sodium channel gene allowed the identification of 29 novel single nucleotide polymorphisms that were used to screen populations of field collected An. gambiae s.s. from seven locations in Africa. Analysis of the extended haplotypes revealed the signature of the selective sweeps associated with the kdr alleles, and suggested that the serine kdr mutation found in Kenya pre-dated the kdr mutations in West Africa, possibly the result of selection by the historic use of DDT rather than the more recent use of pyrethroids. Data indicated that the spread of the serine mutation in Gabon was recent, possibly due to a selective advantage conferred by co-expression with the phenylalanine kdr mutation and, confirming published data, that it had probably arisen at least twice through novel mutation events. The phenylalanine mutation in West and Central Africa is likely to have been the result of at least two separate mutation events, both ofwhich have been subjected to a strong selective sweep.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available