Development and validation of novel diagnostic tools for the management and surveillance of snakebite envenoming

The 2024/25 application process is now closed

Visit the MRC DTP/CASE at LSTM pages for further information.

Abstract

Snakebite kills >100,000 people each year and antivenom is the only effective treatment. However, these therapies are largely species-specific due to venom toxin variation among biting snake species. Further, because antivenoms have a poor safety profile, the clinical management of snakebite envenoming often relies on signs of systemic envenoming to be present prior to treatment commencing, resulting in unnecessary delays and contributing to poor patient outcomes. Finally, we currently have poor epidemiological data on which snake species are predominately responsible for causing snakebite in different regions. For all the reasons listed above, there is a compelling need for the development of methodological approaches to facilitate snakebite diagnosis – such tools would be invaluable for epidemiological data collection, rapidly diagnosing evidence of circulating venom in snakebite patients, and/or informing antivenom choice based on biting species. In this project, the successful applicant will use a variety of immunological and molecular approaches to develop and assess the sensitivity and specificity of snakebite diagnostic tools of value for use in snakebite patients in sub-Saharan Africa. Following methodological development, validation experiments will be performed using venom-spiked human samples, followed by assessment using real world samples previously collected from human snakebite patients, including venom quantification during the time course oh hospital stay. The outcomes of this project will be used to support future clinical studies in the region and may also facilitate the development of a first of its kind commercial diagnostic test for snakebite in the African region.

Where does the project lie on the Translational Pathway?

T1 – Basic Research

Expected Outputs

  • Aside from the technical skills training, the expected outputs for this project will be high-impact papers due to the novelty of the project, potentially intellectual property leading to patent applications relating to the future design of a diagnostic device, and new tools that could be readily impactful for measuring snakebite envenoming in future clinical trials and studies.

Training Opportunities

The student will be exposed to a wide variety of research training opportunities, as they will join a well-funded, multi-disciplinary and dynamic team of post docs, students and technicians. Thus, they will have an opportunity to acquire additional laboratory skill sets to those described below:

•            Training in bioinformatic analysis of molecular data

•            Training in molecular technical approaches, including PCR and qPCR

•            Training in in vitro assays of toxin activity

•            Training in immunological approaches, including ELISAs and affinity purification

•            Training in scientific writing and presenting

Skills Required

We expect the student to possess strong organisational and project solving aptitudes. The student would benefit from basic skills in molecular biology and/or protein biochemistry.

Key Publications associated with this project

Casewell et al. 2020. Causes and consequences of snake venom variation.  Trends in Pharmacological Sciences. 41, P570-P581

Theakston and Laing, 2014. Diagnosis of snakebite and the importance of immunological tests in venom research. Toxins 6, 1667-1695

Knudsen et al. 2021. Snakebite envenoming diagnosis and diagnostics. Frontiers in Immunology 12, 661457

 Isbister et al. 2013. Snakebite in Australia: a practical approach to diagnosis and treatment. Medical Journal of Australia 199, 763-768

Lee et al. 2023. Characterising and applying immunoglobulins in snakebite diagnostics: a simple and rapid venom detection assay for four medically important snake species in Southeast Asia. International Journal of Biological Macromolecules 236, 123727