Mechanisms driving the escalation of insecticide resistance in Anopheles funestus and its impact on malaria parasite transmission and vector control in Uganda

Abstract

This thesis investigates the mechanisms driving pyrethroid resistance escalation in Anopheles funestus, a major malaria vector, focusing on genetic markers, structural variants, and overexpressed genes linked to insecticide survival. It examines temporal resistance patterns, population dynamics, and transcriptomic profiles of resistant mosquitoes, alongside results from the first experimental hut trial in Uganda. These findings shed light on the persistence of malaria vectors despite sustained vector control efforts.
In Chapter 1, the study begins by outlining the rationale, objectives, and conceptual framework, providing a foundation for understanding insecticide resistance in malaria vectors.
In Chapter 2, the thesis explores malaria as a disease, focusing on An. funestus biology, ecology, and behaviour, while reviewing malaria control strategies, particularly insecticide-based vector control methods. A comprehensive discussion of insecticide resistance, detection, and management follows, concluding with perspectives on the future of vector control in Africa and critical steps for success.
In Chapter 3, findings from a published objective analysing the temporal dynamics of insecticide resistance and bionomics over three years of sampling are presented, highlighting resistance trends and population changes.
In Chapter 4, using RNAseq and several bioinformatic pipelines, the molecular mechanisms driving baseline and escalated pyrethroid resistance are uncovered, identifying key genetic and transcriptomic factors as well mutations and genomic signals associated with resistance escalation.
In Chapter 5, results from the first experimental hut trial in Uganda are reported, evaluating the impact of escalated resistance on the efficacy of next-generation and pyrethroid-only bednets, with resistance markers used to assess how resistance affects bednet performance.
In Chapter 6, the thesis concludes by synthesizing the findings, discussing their implications for malaria vector control, identifying gaps for future research, and proposing directions to enhance resistance management and vector control strategies.

Date of Award	22 Sept 2025
Original language	English
Awarding Institution	Liverpool School of Tropical Medicine
Supervisor	Charles Wondji (Supervisor), Jack Hearn (Supervisor), Jonathan Kayondo (Supervisor) & Magellan Tchouakui (Supervisor)