Development of DNA diagnostics of neglected tropical diseases in resource-limited settings

Research output: ThesisDissertation (TU Delft)

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Abstract

The aim of this thesis was to develop a DNA-detection scheme for a point-of-care diagnostic test for Neglected Tropical Diseases (NTDs) for use within resource-limited settings. The scientific innovation is to develop an adaptable DNA-detection scheme, using CRISPR-dCas9 (catalytically inactive Cas9), that can detect the DNA of any pathogen in bodily fluids i.e. in a blood or urine sample. This detection of DNA of the pathogen will be much more reliable than antibody-based tests as it will work independently of the persons immune response. Unlike current antibody-based diagnostic tests, it will be able to distinguish between current and previous infections. Specifically for visceral leishmaniasis (VL), the current rk39 antigen-based rapid diagnostic test lacks specificity and sensitivity in sub-Saharan Africa, where VL remains prevalent. We aim for a DNA-detection scheme that does not require infrastructure, electricity, or skilled laboratory personnel to operate. Furthermore, the DNA-detection scheme will need to be functional at a broad temperature range, yet remain highly sensitive and specific. Such a DNA-detection scheme can be a promising tool for effective diagnoses of NTDs within resource-limited settings, though it needs to be further tested, incorporated into a packaged test format, and validated in the field. Integrating this DNA-detection scheme into a potentially low-cost diagnostic test is a very promising alternative to current diagnostic tests in both high-resource and resource-limited settings.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Delft University of Technology
Supervisors/Advisors
  • Dekker, C., Supervisor
Award date13 Jan 2021
Print ISBNs978-90-8593-463-9
DOIs
Publication statusPublished - 2020

Keywords

  • point-of-care diagnostic test
  • Neglected tropical diseases
  • resource-limited settings
  • visceral leishmaniasis
  • context-driven design
  • CRISPR/cas9

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