Prosjektnummer
902028
GillMed – Ikke-steroide antiinflammatoriske legemidler (NSAIDs) for behandling av kompleks gjellesykdom (CGD) / GillMed – Nonsteroidal anti-inflammatory drugs (NSAIDs) for treatment of complex gill disease (CGD)
Background
Complex gill disease (CGD) is a multifactorial disease with no clear single aetiology and is one of the three major health issues in the Norwegian salmon and trout industries. Currently, industry utilises freshwater or hydrogen peroxide baths to control the effects of CGD where amoebae (AGD) are involved, but these treatments involve handling which may cause injury, fish stress, are labour intensive and expensive, and sometimes ineffective. Relatively few veterinary medicinal products (VMPs) have been developed specifically for use in farmed fish, but a wider range is available under the veterinary cascade including for example anti-inflammatories, which may support recovery of fish with CGD.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of therapeutics that are designed to reduce pain, fever and inflammation. Inflammation is one of the key responses and pathologies associated with CGD (Herrero et al. 2018) and has been described for specific gill insults such as jellyfish (Aurelia sp.) (Baxter et al. 2011, Rodger et al. 2011), tenacibaculosis (Smage et al. 2017, Nowlan et al. 2020, Slinger et al. 2020) and AGD (Morrison et al. 2012). Targetted, short acting NSAIDs therapeutics at the time when CGD is diagnosed may reduce the inflammatory response thereby reducing pain and time to recover. This project is part of a wider initiative to provide information to fish vets prescribing under the cascade system and investigates the safety and efficacy of NSAIDs as a treatment for CGD.
Complex gill disease (CGD) is a multifactorial disease with no clear single aetiology and is one of the three major health issues in the Norwegian salmon and trout industries. Currently, industry utilises freshwater or hydrogen peroxide baths to control the effects of CGD where amoebae (AGD) are involved, but these treatments involve handling which may cause injury, fish stress, are labour intensive and expensive, and sometimes ineffective. Relatively few veterinary medicinal products (VMPs) have been developed specifically for use in farmed fish, but a wider range is available under the veterinary cascade including for example anti-inflammatories, which may support recovery of fish with CGD.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of therapeutics that are designed to reduce pain, fever and inflammation. Inflammation is one of the key responses and pathologies associated with CGD (Herrero et al. 2018) and has been described for specific gill insults such as jellyfish (Aurelia sp.) (Baxter et al. 2011, Rodger et al. 2011), tenacibaculosis (Smage et al. 2017, Nowlan et al. 2020, Slinger et al. 2020) and AGD (Morrison et al. 2012). Targetted, short acting NSAIDs therapeutics at the time when CGD is diagnosed may reduce the inflammatory response thereby reducing pain and time to recover. This project is part of a wider initiative to provide information to fish vets prescribing under the cascade system and investigates the safety and efficacy of NSAIDs as a treatment for CGD.
Objectives
Main objective
To assess the safety and efficacy of specific non-steroidal anti-inflammatories drugs (NSAIDs) to reduce pathology and provide symptomatic relief of Atlantic salmon experiencing gill injury.
Sub-objectives
1. To write a literature review on the NSAID options in farmed animals (focusing on poultry, porcine, sheep, cattle and finfish), and determine three top candidates for the palatability trial.
2. To evaluate the safety and palatability of 3 optional NSAID products in a short 3-week study at 3 doses in Atlantic salmon.
3. In parallel to this, to look at host-response data to determine if COX-1 and COX-2 pathways are associated with AGD, jellyfish, co-infection or algal exposure – this will be performed with a mix of archived laboratory samples and field samples.
4. To determine the efficacy of 1 x NSAID for the treatment of gill disease by using the following gill models:
o AGD challenge (Neoparamoeba perurans)
o Jellyfish challenge (Aurelia aurita)
o Jellyfish challenge with secondary Tenacibaculum maritimum co-infection
5. To determine and recommend the next steps for product application and registration for industry use.
6. To design a method for the evaluation of NSAID products in vivo for gill diseases.
7. To determine commercial feasibility and map to commercialisation of this product for industry use.
Main objective
To assess the safety and efficacy of specific non-steroidal anti-inflammatories drugs (NSAIDs) to reduce pathology and provide symptomatic relief of Atlantic salmon experiencing gill injury.
Sub-objectives
1. To write a literature review on the NSAID options in farmed animals (focusing on poultry, porcine, sheep, cattle and finfish), and determine three top candidates for the palatability trial.
2. To evaluate the safety and palatability of 3 optional NSAID products in a short 3-week study at 3 doses in Atlantic salmon.
3. In parallel to this, to look at host-response data to determine if COX-1 and COX-2 pathways are associated with AGD, jellyfish, co-infection or algal exposure – this will be performed with a mix of archived laboratory samples and field samples.
4. To determine the efficacy of 1 x NSAID for the treatment of gill disease by using the following gill models:
o AGD challenge (Neoparamoeba perurans)
o Jellyfish challenge (Aurelia aurita)
o Jellyfish challenge with secondary Tenacibaculum maritimum co-infection
5. To determine and recommend the next steps for product application and registration for industry use.
6. To design a method for the evaluation of NSAID products in vivo for gill diseases.
7. To determine commercial feasibility and map to commercialisation of this product for industry use.
Expected project impact
Short term
• Improve industry understanding of the inflammatory pathways associated with various gill pathologies described in CGD.
• If specific NSAIDs are effective and the authorities permit application of special exemptions, then veterinarian prescription and application on salmon farms could be undertaken by project end.
Long term
• New treatment options for salmon farms and vets that provide symptomatic relief of CGD in fish populations could significantly improve survival rates, time to recovery from gill injury, welfare and performance.
Short term
• Improve industry understanding of the inflammatory pathways associated with various gill pathologies described in CGD.
• If specific NSAIDs are effective and the authorities permit application of special exemptions, then veterinarian prescription and application on salmon farms could be undertaken by project end.
Long term
• New treatment options for salmon farms and vets that provide symptomatic relief of CGD in fish populations could significantly improve survival rates, time to recovery from gill injury, welfare and performance.
Project design and implementation
The project consists of the following work packages (WPs):
WP1: Literature review on COX 1 and COX 2 inflammatory pathways in finfish; and the mode of action of selected NSAIDs that could be used in aquaculture
Lead: Chloe English (Nautilus Collaboration)
Partners: PatoGen, CSIRO, Moredun Scientific, and Mowi
Conduct a literature review on non-steroidal anti-inflammatories and their use in symptomatic relief for farmed animals (focusing on poultry, porcine and cattle – both dairy and meat, finfish), inclusion methods in diet, formulations including in-feed and injectable, palatability enhancements, target inflammatory pathways and doses/durations applicable in intensive animal production.
WP2: Evaluate the safety and palatability of 3 optional NSAID products in Atlantic salmon
Lead: James Wynne (CSIRO)
Partner: Nautilus Collaboration
WP3: Desktop examination of COX 1 and COX 2 pathways associated with the disease processes in CGD in existing datasets of different gill diseases and archived samples of CGD
Lead: James Wynne (CSIRO)
Partners: Nautilus Collaboration, PatoGen, and Mowi
Task 3.1: Analyse existing gill disease data sets for markers associated with the COX 1 and COX 2 pathways using samples that have come from tank-based trials.
Task 3.2: Using the sub-goal 2 markers (local targets), analyse archived samples that have been diagnosed with CGD, with a range of pathogens – include a wide range of pathogens to determine if there are local targets that could be affected by NSAIDs to determine the likelihood of efficacy in-field.
WP4: Determine the efficacy of one NSAID product in Atlantic salmon using three gill disease models including AGD, jellyfish, and jellyfish co-infection model with Tenacibaculum
4.1: AGD challenge
Lead: James Wynne (CSIRO)
Partner: Nautilus Collaboration
4.2: Jellyfish challenge
Lead: William Roy (Moredun Scientific)
Partner: PatoGen
4.3 Jellyfish and Tenacibaculum co-infection challenge
Lead: William Roy (Moredun Scientific)
Partners: PatoGen and CSIRO
WP5: Assess initial commercial feasibility of NSAIDs and recommendations for next steps
Lead: Christine Huynh, Nautilus Collaboration
Partners: PatoGen, CSIRO, Moredun Scientific, and Mowi
In the final report for the project, a short analysis will be written on the feasibility of using NSAIDs for CGD based on Norwegian legislation. This will combine the knowledge garnered in each of the work packages and develop some recommendations for the next steps.
The project consists of the following work packages (WPs):
WP1: Literature review on COX 1 and COX 2 inflammatory pathways in finfish; and the mode of action of selected NSAIDs that could be used in aquaculture
Lead: Chloe English (Nautilus Collaboration)
Partners: PatoGen, CSIRO, Moredun Scientific, and Mowi
Conduct a literature review on non-steroidal anti-inflammatories and their use in symptomatic relief for farmed animals (focusing on poultry, porcine and cattle – both dairy and meat, finfish), inclusion methods in diet, formulations including in-feed and injectable, palatability enhancements, target inflammatory pathways and doses/durations applicable in intensive animal production.
WP2: Evaluate the safety and palatability of 3 optional NSAID products in Atlantic salmon
Lead: James Wynne (CSIRO)
Partner: Nautilus Collaboration
WP3: Desktop examination of COX 1 and COX 2 pathways associated with the disease processes in CGD in existing datasets of different gill diseases and archived samples of CGD
Lead: James Wynne (CSIRO)
Partners: Nautilus Collaboration, PatoGen, and Mowi
Task 3.1: Analyse existing gill disease data sets for markers associated with the COX 1 and COX 2 pathways using samples that have come from tank-based trials.
Task 3.2: Using the sub-goal 2 markers (local targets), analyse archived samples that have been diagnosed with CGD, with a range of pathogens – include a wide range of pathogens to determine if there are local targets that could be affected by NSAIDs to determine the likelihood of efficacy in-field.
WP4: Determine the efficacy of one NSAID product in Atlantic salmon using three gill disease models including AGD, jellyfish, and jellyfish co-infection model with Tenacibaculum
4.1: AGD challenge
Lead: James Wynne (CSIRO)
Partner: Nautilus Collaboration
4.2: Jellyfish challenge
Lead: William Roy (Moredun Scientific)
Partner: PatoGen
4.3 Jellyfish and Tenacibaculum co-infection challenge
Lead: William Roy (Moredun Scientific)
Partners: PatoGen and CSIRO
WP5: Assess initial commercial feasibility of NSAIDs and recommendations for next steps
Lead: Christine Huynh, Nautilus Collaboration
Partners: PatoGen, CSIRO, Moredun Scientific, and Mowi
In the final report for the project, a short analysis will be written on the feasibility of using NSAIDs for CGD based on Norwegian legislation. This will combine the knowledge garnered in each of the work packages and develop some recommendations for the next steps.
Dissemination of project results
The following industry extension and communication activities will be taken for the project:
• Two peer reviewed publications that are open access with pre-prints
• Two popular science articles published in an online magazine
• 1–2 conference presentations
• Industry workshop or webinar for further extension (online)
The following industry extension and communication activities will be taken for the project:
• Two peer reviewed publications that are open access with pre-prints
• Two popular science articles published in an online magazine
• 1–2 conference presentations
• Industry workshop or webinar for further extension (online)