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Eliminating Sleeping Sickness with the London School of Hygiene and Tropical Medicine

African trypanosomes are transmitted by the bite of the tsetse fly and cause the debilitating, and often fatal, neglected tropical disease, sleeping sickness or Human African Trypanosomiasis (HAT).  The parasites responsible for 98% of human cases first reside in the patient blood and skin for months to years before invading the central nervous system, where they cause the neurological symptoms of the disease. 

 

HAT is approaching elimination, with the number of cases reported in 2017 dropping to approximately 1,442 from only a dozen African Countries.  However, the reduction in cases also brings about challenges and HAT was included in the WHO roadmap on neglected tropical diseases.  As the burden drops, so does the sensitivity of any diagnostic test.  In this context, new highly sensitive and specific diagnostic tools will be required to accurately monitor the occurrence of new cases and the possible emergence of drug- resistant trypanosomes during the elimination phase.  Most diagnostic tests currently under development are based on optimization of existing methods that may not combine all the requirements to stand up to the harsh constraints imposed by the elimination phase requirements, especially in terms of sensitivity and specificity.

 

Scientists at the Institut Pasteur and the London School of Hygiene and Tropical Medicine are working to adapt the recently developed Specific High-sensitivity Enzymatic Reporter unlocking technology that combines a CRISPR-Cas system and lateral flow test to trypanosomes to provide the sensitivity and specificity required for a diagnostic test in the elimination and post elimination phases of HAT.

Aim and Impact

The development of this system relies on the collateral effect of Cas13a promiscuous RNA cleavage activity upon target recognition. Combining the collateral effect with pre-amplification of RNAs resulted in rapid RNA detection with attomolar (10-18 moles/l) sensitivity and single-base mismatch specificity, in a diagnostic setting. This technology has been used to detect specific strains of Zika and Dengue viruses and distinguish pathogenic bacteria in a mixed sample. Furthermore, the programme's reaction reagents can be lyophilized for cold-chain independence and long-term storage and be readily reconstituted on paper for field applications. A lateral flow test for a simple and rapid readout can be easily implemented after a reaction that does not exceed two hours from the sampling step.

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The partners of this project propose to adapt, optimize and validate a new approach for the detection of trypanosome-specific nucleic acid sequences in human body fluids. This project could provide an ideal field-adapted method for the diagnosis of HAT during the elimination and post-elimination phases.

How can you help?

We are delighted to announce that this project has now secured full funding until its projected end date in 2024.  However, if you are interested in supporting a similar collaboration, please contact our Head of Development, Sarah Bridge about how you can support similar initiatives.

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Email: sarah.bridge@pasteurfoundation.uk

Telephone: +44 7771 838883

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We look forward to hearing from you!

Charity number 1203634

Pasteur Foundation - UK

One Bartholomew Cl, London EC1A 7BL, UK

+44 7771 838883

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