Roadmap for development of therapeutics for helminths

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

• Can we achieve standardized guidelines for clinical and genetic tests to detect drug resistance? We needofficial guidelines across a variety of animal and important parasite species.
• Can we have a test for field use to detect early stages of drug resistance?
• Could it be possible to validate more genetic markers as predictive of drug resistance under field conditions?

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

• Lack of standardization of the faecal egg count reduction test(FECRT) to detect anthelmintic resistance, especially in cattle (is the presence of drug resistance indicated by a FECR of less than 90 or 95%? Is it essential to have a control group?; Is it performed with individual or composite faecal samples?; etc.).
• Lack of accessible tests for early detection of anthelmintic resistance available to use in the field.
• Poor understanding of suitable genetic markers of resistance for the available anthelmintics, including the most commonly used such as the macrocyclic lactones.

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

• Implement practical on-farm tests with high sensitivity for detection of anthelmintic resistance in livestock animals.
• Implement coherent and clear guidelines for different methods to detect resistance to anthelmintic compounds.
• Implement genomic approaches to characterize resistance, in order to identify genetic markers for the diagnostic of anthelmintic resistance.

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

• Improve knowledge about the genomes of livestock helminth species.
• Review current guidelines about clinical tests for drug resistance (as FECRT): what are the best methods for calculating confidence intervals? ; what is the sample size of animals and the number of eggs pre-treatment that would allow a reliable assessment of drug efficacy (provide high statistical power)?
• Specialized equipment for performing genetic tests (for example, pyrosequencers or MiSeq DNA sequencers) should be more widely available in veterinary laboratories.

Existing knowledge including successes and failures

• The traditional method for detecting drug resistance on farms, the faecal egg count reduction test, presents variable results, depending on study design, parasite/hosts interactions, egg counts, etc. Additionally, the resistance status of the parasites is not known until after an anthelmintic treatment.
• Although the FECRT is the only test available at the farm level, it has poor sensitivity and cannot reliably detect resistance in the early emerging stages, whereas genetic tests (pyrosequencing, Illumina sequenicng) can detect resistance parasites on a farm before a decrease in drug efficacy is detected.
• Genetic tests, if readily available, would be useful to veterinarians and producers because of the ability to detect resistance before treatment.
• Genetic tests allow an estimation of the percentage of resistant parasites in the parasite population in a herd/flock (for example
  through the analysis of SNPs 167, 198 and 200 for the detection of benzimidazole resistance).