Roadmap for development of diagnostic tests for helminths

What are we trying to achieve and why? What is the problem we are trying to solve?

Most helminth infections elicit T helper cell type 2 immune responses. These cellular responses are important, both in orchestrating the B cell response and in eliciting potentially protective immune responses. The research question is, could cell-mediated immune responses be used as a more accurate alternative to antibody responses for detection of
helminth parasite infection? For example, using the interferon γ response of T cells in response to parasite specific antigen and B cell ELISPOT assays for specific/quantitative tests.

What are the scientific and technological challenges (knowledge gaps needing to be addressed)?

• Incomplete knowledge of cellular immune responses during helminth infection
• Incomplete understanding of immunoregulatory responses induced by parasite infection and how they may affect detection of parasite specific responses.
• Lack of technologies that could be used to detect specific cellular responses for diagnostic purposes in target livestock species.
• Animal to animal variation in cellular responses.
• Incomplete knowledge of temporal development of cellular immune responses over the course of an infection, particularly in naturally exposed animals between different parasite stages including immature and and inhibited stages.
• Lack of tools/reagents to probe cellular immune responses in target livestock species.eg recombinant cytokines, cytokine specific antibodies

What approaches could/should be taken to address the research question?

• Analysis of parasite specific cellular immune responses following both experimental and natural infection
• Description of the of immunoregulatory responses induced by parasite infection and how these affect detection of parasite specific responses.
• Development of rapid, user friendly technologies that could be used to detect specific cellular responses for diagnostic purposes.
• Investigation of immune responses in populations of animals naturally exposed to infecton to quantify animal to animal variation in cellular responses.
• Development of a panel of stage specific antigens that can be used to differentiate between early and chronic infections and developing and inhibited larvae.

What else needs to be done before we can solve this need?

• Development of defined, repeatable challenge models/systems under experimental and natural challenge to define cellular immune responses, immunoregulatory responses and stage specific responses in vivo/ex vivo.
• Development of tools to probe cellular immune responses in target livestock species.
• Panels of defined stage specific antigens.
• Population level studies (GWAS) to identify and quantify animal to animal variation in response to helminth parasites.

Existing knowledge including successes and failures

• A range of experimental challenge models have been developed for the major helminth species. However field level exposure systems are much less well developed. Field challenge experiments depend on conditions in a particular year (e.g for natural fluke challenge experiments) or level of contamination of pasture.
• There are few examples of stage specific antigens to which cellular immune responses have been well characterised.
• There are few examples of GWAS for parasites in ruminants.
• There are few examples of cellular markers that are used for diagnosis.
• The bovine tuberculosis interferon γ is one of the few examples on the market.
• Technology lacks behind that of antibody detection tests.