Moss, SJ; (2024) Genomic epidemiology of Plasmodium falciparum and its Anopheline vectors in the context of malaria control on the Bijagós Archipelago of Guinea-Bissau. PhD thesis, London School of Hygiene & Tropical Medicine. DOI: https://doi.org/10.17037/PUBS.04674964
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Abstract
This thesis uses genomic techniques to investigate the genetic diversity and antimalarial resistance status of the Plasmodium falciparum parasite, and the genetic diversity and insecticide resistance status of key Anopheles gambiae sensu lato vectors, on the Bijagós Archipelago of Guinea-Bissau. This investigation was conducted in the context of malaria control interventions on this remote Archipelago, where the genomic epidemiology of malaria has not previously been studied. Selective whole-genome amplification was used to investigate population dynamics and drug resistance mutations in whole genome sequence (WGS) data from Bijagós P. falciparum isolates. This analysis identified fixation of the pfdhfr mutations N51I and S108N, associated with resistance to sulphadoxine-pyrimethamine, and the continued presence of pfcrt K76T, associated with chloroquine resistance. P. falciparum from the Archipelago clustered with samples from mainland West Africa without forming a separate phylogenetic group. This thesis continues by analysing the insecticide resistance status of the major vector Anopheles gambiae. High throughput multiplex amplicon sequencing is used to identify molecular markers of insecticide resistance, revealing four single-nucleotide polymorphisms (SNPs) previously associated with pyrethroid resistance, and an additional eight previously unreported SNPs. This genomic analysis is built upon with phenotypic bioassays in the Bijagós to investigate susceptibility to deltamethrin, and deltamethrin resistance is identified on Bubaque island. WGS data from deltamethrin resistant and susceptible An. gambiae sensu stricto is then analysed to identify insecticide resistance associated SNPs and signatures of selection. Genome wide selection scans are conducted, identifying two selective sweeps in the population, which overlap with metabolic genes previously associated with insecticide resistance, including cyp9k1 and the cyp6aa/cyp6p gene cluster. The population dynamics and insecticide resistance status of the malaria vector Anopheles melas, which is abundant on the islands, are then analysed. This analysis identifies two separate phylogenetic clusters of An. melas and investigates genetic differentiation, signatures of selection, and structural variation within the genome. This thesis generates and analyses the first WGS data for P. falciparum, An. gambiae s.l., and An. melas from the Bijagós Archipelago, and includes the first phenotypic testing for deltamethrin resistance on the islands; contributing data and analyses of significance to malaria control policy in the region.
Item Type | Thesis |
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Thesis Type | Doctoral |
Thesis Name | PhD |
Contributors | Last, A; Campino, S; Krishna, S and Clark, TG |
Faculty and Department | Faculty of Infectious and Tropical Diseases > Dept of Clinical Research |
Funder Name | Medical Research Council London Intercollegiate Doctoral Training Partnership |
Copyright Holders | Sophie Judith Moss |
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Filename: 2023_ITD_PhD_Moss_S_Approved_2.0.pdf
Licence: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
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