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?

To develop diagnostics based on host responses that:

• Assess the infection levels, morbidity and/or production impact of helminth infections to guide selection of treatment or control choices.
• Identify stage of infection (acute, chronic, prepatent)
• Identify resistant or resilient hosts

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

• Incomplete knowledge of host immune and immunoregulatory responses to helminth infections, how they vary during the course of infection and how they correlate with the infection intensity and production impacts (see
  section 6A for more details).
• Correlation between host responses and the levels of infection/production impacts may not be linear.
• Immune markers may reflect historic infection. It is difficult to differentiate between current and historic infection.
• Incomplete information available on dynamics of host responses in relation to stage of infection. e.g. juvenile versus adult infection in fluke, hypobiotic larvae).
• Cross-reaction (lack of specificity) between parasite antigens and species, especially when using crude antigen mixtures or native antigen preperations.
• Thresholds for economic impacts need to be understood which is complex based on regional and production system differences.
• Non invasive sampling required eg, milk, saliva

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

• More complete descriptions of immune responses and immunoregulatory responses in hosts to helminth infections in experimentally and naturally infected animals (more details in section 6A).
• Development of quantitative tests to measure level of antibody in relation to parasite load.
• Develop diagnostic techniques for simultaneous (quantitative) detection of (immune responses against) multiple parasites (e.g. Luminex)
• Investigate the use of non-invasive, user-friendly matrices to measure immune responses (e.g. copro-antigen, milk antibodies, saliva antibodies). Including for rapid penside tests such as lateral flow devices and biosensor chips.
• Determine frequency distribution of immune parameters, determine minimum sample size to obtain results that are useful at herd/flock level and minimum number of animals that need to be positive to obtain a positive bulk/pooled sample
• Analysis to identify evidence of cross reactivity of host antibody to a specific parasite antigen and antigens of other helminth species.

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

• Improve knowledge of the specific immune and physiological responses of the host to various nematode and trematode species, including the antibody response to different parasite life cycle stages (section 6A).
• Identify and characterise antigens and other parasite molecules that elicit host responses.
• Improve antibody detection technologies, including isotype specific reagents for each host species’s amplification systems to improve sensitivity; epitope mapping of to improve specificity.
• Develop technologies for penside and/or quantitative detection of (multiple) parasite-specific immune responses, using non-invasive matrices
• Identify end user expectations for parasite diagnostics and incentives/barriers for uptake of diagnostics by end users.
• Select the best parasitological and/or production parameters to identify resilient animals

Existing knowledge including successes and failures

• A range of helminth antigen specific antibody detection assays are available using a range of platforms and for a variety of media (serum, milk, bulk milk).
• Commercial copro-antigen ELISA tests available for Fasciola hepatica