Cherkaoui, Dounia;
(2022)
Harnessing state-of-the-art diagnostic technologies for point-of-care testing of emerging and neglected tropical diseases.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The emergence of epidemic-prone infectious diseases has been identified as a major global health issue of the twenty-first century. Global strategies have been initiated for the development of drugs, vaccines and diagnostics to fight pandemic threats. Recent breakthroughs in biosensing technologies are strengthening the diagnostic landscape. Stopping pandemics requires collaboration fair and wide access to these state-of-the-art diagnostic technologies. Decentralisation of laboratory testing and adaptation of these technologies to point-of-care testing is one strategy to widen access. Moreover, harnessing state-of-the-art diagnostic tools for rapid, simple and cost-effective decentralised testing can bolster the fight against neglected tropical diseases, which still affect over 1 billion people across the world. In this PhD thesis, I present the development and evaluation of three new in vitro diagnostics targeting topical infectious diseases – Ebola virus disease, COVID-19 and schistosomiasis – adapting a range of state-of-the art biosensing technologies to meet the needs of real-world settings. The first diagnostic developed is a proof-of-concept dual-species antigen test which detects and differentiates the glycoproteins of Zaire and Sudan ebolavirus. Twelve monoclonal antibodies were characterised and functionalised to select species-specific antibody pairs. Finally, two species-specific dipstick components were evaluated in buffer spiked with Ebola recombinant glycoproteins. The second diagnostic presented herein is a rapid multi-gene molecular assay able to simultaneously detect two genes of SARS-CoV-2 using reverse transcription recombinase polymerase amplification. The one-pot assay offered two alternative readouts – dipstick or real-time fluorescence – and a clinical validation using the fluorescence readout was conducted with 91 clinical samples. Last, the first CRISPR-based test for urogenital schistosomiasis was developed and evaluated with parasitic DNA and eggs. An in-house CRISPR-compatible protocol for urine sample extraction was proposed and the assay was lyophilised to facilitate transport and field-testing. To conclude, the diagnostic technology research presented in this thesis is a step towards closing the gap of high-performance tests adapted to infectious diseases and endemic settings. In addition, innovation in access is needed to bring these diagnostic technologies to patients who need them and to achieve universal health coverage.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Harnessing state-of-the-art diagnostic technologies for point-of-care testing of emerging and neglected tropical diseases |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10161665 |
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