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Development of new diagnostic tools to identify canine reservoir super-spreaders of Leishmania infantum
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Lison, Aurore (2018) Development of new diagnostic tools to identify canine reservoir super-spreaders of Leishmania infantum. PhD thesis, University of Warwick.
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WRAP_Theses_Lison_2018.pdf - Submitted Version - Requires a PDF viewer. Download (8Mb) | Preview |
Official URL: http://webcat.warwick.ac.uk/record=b3446977~S1
Abstract
Zoonotic visceral leishmaniasis (ZVL) is a vector-borne infection induced by protozoan parasite Leishmania infantum and transmitted from animal reservoir to human. Domestic dogs are the main proven reservoir, and the detection of their transmission potential is a research priority. Longitudinal xenodiagnosis studies of natural infection in dogs showed that a large fraction of transmission events to the sand fly vector is due to a small fraction of the infected canine reservoir population, known as superspreaders. The management of visceral leishmaniasis requires a different approach to current blanket control operations that otherwise require extremely high intervention coverage to successfully include the super-spreaders.
The aims of the study were to discriminate super-spreaders in a mixed reservoir population by developing novel diagnostic tools, and to complete mathematical models based on collected data including transmission potential and tool-implementation in the field. Existing and novel anti-Leishmania antigens were tested in enzyme-linked immunosorbent assays (ELISA) on archived sera collected from a naturally infected cohort population of Brazilian dogs. Their transmission potential was measured by xenodiagnoses during a two years longitudinal study.
Results from serological assays showed that carefully selected threshold-based antigens allowed a more specific test towards reducing transmission; and some of the novel proteins (rK28, K26, rK34) out-performed the currently available test antigens for infection. These antigens were tested for the serodetection of infectiousness and were able to discriminate super-spreaders of Leishmania within the mixed canine population. Based on these results, a prototype of rapid diagnostic test (RDT) was developed based on a brand-new antigen, KL914, and specifically designed for detecting superspreaders. The aim was to setup a field-friendly screening method. The impact of the novel diagnostic tool to detect and remove super-spreaders from the population before the onset of infectiousness was modelled and quantified under different population dynamic scenarios. The mathematical model offered a notice on the diagnostic tool to be applied in the field, and pointed out the limitations and the possible improvement.
This project was funded by the European Union’s Horizon2020 Research and Innovation Program under the Marie Sklodowska-Curie grant agreement.
| Item Type: | Thesis (PhD) | ||||
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| Subjects: | R Medicine > RC Internal medicine S Agriculture > SF Animal culture |
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| Library of Congress Subject Headings (LCSH): | Kala-azar -- Transmission, Kala-azar -- Diagnosis, Dogs -- Diseases, Serology | ||||
| Official Date: | December 2018 | ||||
| Dates: |
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| Institution: | University of Warwick | ||||
| Theses Department: | School of Life Sciences | ||||
| Thesis Type: | PhD | ||||
| Publication Status: | Unpublished | ||||
| Supervisor(s)/Advisor: | Courtenay, Orin | ||||
| Sponsors: | Horizon 2020 (Programme) | ||||
| Format of File: | |||||
| Extent: | 195 leaves : illustrations, charts | ||||
| Language: | eng |
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