title: ROLES OF BITING PREFERENCE AND INSECTICIDE RESISTANCE IN DETERMINING MALARIA TRANSMISSION HETEROGENEITY IN THE GAMBIA
Creators: name: Opondo, KO
Publisher: name: University of Liverpool Repository
Year: 2016

description: Malaria continues to cause immense public health pressure to poor and developing countries in the tropical world hindering economic development. Malaria control using long-lasting insecticide-treated bed nets (LLINS) and indoor residual spraying (IRS) have contributed significantly to the reduction of malaria transmission. However, this reduction in transmission is not uniform. Particular foci ‘hotspots’ that do not respond as anticipated to control tools have become common in low-moderate transmission settings like The Gambia. While several factors contribute to heterogeneity in malaria transmission, the roles that malaria vectors with differing behaviour, ecology and susceptibility to insecticides play in these hotspots is poorly understood. This thesis aimed to investigate whether vector-related factors might contribute to malaria transmission heterogeneity in The Gambia. First, I demonstrated how the three major malaria vectors; Anopheles gambiae s.s., Anopheles arabiensis and An. coluzzii varied in relative abundance between villages of varying transmission intensities. Susceptibility to deltamethrin and DDT varied significantly among species and locales with An. gambiae s.s. from the east of the country by far the most resistant. There was a correlation between An. gambiae s.s. phenotypic resistance to DDT and malaria transmission in 2013, driven by the east of the country which experiences higher malaria transmission. The major driver of insecticide resistance to DDT and deltamethrin was the target site mutation, Vgsc-1014F although another target site mutation Vgsc-1575Y and a metabolic gene variant Gste2-119T were also implicated, albeit to a far lesser extent. The frequency of Vgsc-1014F in An. gambiae s.s. remained low in a second sampling year in western populations but approached fixation in in the east. Generally, whether resistant or susceptible, malaria vectors in the study villages primarily fed on humans, except An. funestus, sampled for the first time in the centre of the country, which fed more on cows. As a preliminary study, I investigated whether resistant populations naturally exposed to insecticides in the wild would still be resistant when older, since laboratory studies typically suggest a decline with age. Results suggested that selection by insecticides may result in resistance remaining in older mosquito cohorts, and marker-based prediction of resistance remained effective. Finally, I used microsatellites to study population genetic structure of An. gambiae s.s. to investigate the origin and likelihood of spread of the strong insecticide resistance phenotypes in the east of The Gambia. Results suggested that although distance was the primary isolating factor among population samples, different ecologies representing coastal marine and drier inland ecosystems may also play a part in partitioning populations from the east and west of the country, likely maintained by large scale rice farming in the central area, dominated by An. coluzzii. Strong differentiation of eastern populations from Senegalese samples did not support a hypothesis of gradual spread of resistance, and Vgsc-L1014F differentiation far exceeded the neutral signal implicating local selection. Resistance to pyrethroids and DDT observed in The Gambia either represented one or more de novo mutations or rare migrants from Senegal subjected to varying local selection pressures. The results presented in this thesis highlight how local variation in characteristics of vector populations is important in driving malaria heterogeneity. To tailor control interventions to tackle high malaria transmission zones, it will be useful for National Malaria Control Programmes to investigate the type of malaria vectors present, their behaviours and insecticide resistance profiles.