Abstract
The COVID-19 pandemic highlighted the inequities across the globe in accessing vital therapeutics, vaccines and diagnostics to adequately respond to the threat of SARS-CoV-2. Diagnostics are the front-line of defence in infectious disease outbreaks and are required for importance surveillance of infectious diseases to inform public health decisions. The aim of this thesis was to investigate alternative diagnostic methodologies and tools that can be applied to viral surveillance in the absence of gold-standard diagnostics. In this thesis I present four results chapters that investigate the alternative diagnostics that can be used in the context of seroprevalence, mutation screening and multi-pathogen surveillance.The first chapter presents a diagnostic evaluation of eight different brands of Antibody lateral flow tests (AbLFTs), with serum samples collected from individuals who had recently received a dose of one of the available COVID-19 vaccines. The main finding of this study was that sensitivity was highly variable across the different brands of AbLFT when compared to results from CMIA but increased from dose 1 to dose 2 but some brands achieved very high sensitivities across both doses.
Following on from this in response to the emerging SARS-CoV-2 variants of concern (VOC) I designed a high-resolution melt (HRM) assay for the detection and differentiation of lineage defining VOC mutations to provide a lower-cost screening method in regions where sequencing infrastructure is overwhelmed or limited. I evaluated these assays in a cohort of SARS-CoV-2 positive (by RT-qPCR) individuals collected in Liverpool, UK. The main findings from this were that the HRM assays were able to detect and differentiate the VOC mutations with high sensitivity when compared to Oxford Nanopore Sequencing on the MinION.
In Chapter 4 I updated the assay from the previous chapter and evaluated its performance in SARS-CoV-2 positive samples collected in Western Kenya and Burkina Faso throughout 2021-2022. These assays showed high sensitivity when compared to Oxford Nanopore Sequencing and I was able to screen a large sample set of 506 samples to demonstrate the use of the HRM assay to show the epidemiology of the VOCs in Western Kenya that agreed with findings from epidemiological papers published at the time that used sequencing.
I have shown that alternative methods can be applied to generate comparable results to the gold standard reference tests. To ensure pandemic preparedness in anticipation for the next outbreak or pandemic it is crucial to continue capacity building and development of pathogen surveillance networks across the globe. By exploring alternative methods of conducting viral surveillance, we expand the available tools at our disposal to improve accessibility of conducting viral surveillance
both during a pandemic and in peacetime.
| Date of Award | 19 Jun 2026 |
|---|---|
| Original language | English |
| Awarding Institution |
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| Supervisor | Emily Adams (Supervisor) & Thomas Edwards (Supervisor) |
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