Transfer of an in vitro model for the evaluation of anticoccidial compounds

The development and wide use of in vitro models (performed outside of a living organism) in biosciences have supported many scientific advances as well as significantly reducing the number of experimental animals used in research. Research in poultry diseases could significantly benefit from in vitro models since implementing and managing the facilities to accommodate chickens is not possible in many institutions and companies. The use of in vitro models could replace experimental chickens in many studies or at least reduce their use. The use of these models could reduce overall time and costs of research, supporting an increased number of research groups conducting research in avian diseases. Poultry is important because it provides the principal source of animal protein for human consumption worldwide. Chicken products are affordable, providing high-quality protein and facing few religious and cultural barriers. Nonetheless, many diseases can affect chickens compromising the economics of meat and egg production. In particular, coccidiosis is a global disease of chickens caused by single-celled parasites. These parasites grow very quickly inside the gut of the chicken causing the disease and rapidly infecting other birds. The control of coccidiosis is usually achieved by administrating in-feed drugs, however, the use of drugs is under pressure globally, influenced by the emergence of resistance, new regulations about their use in farm animals as well as consumer concerns. In consequence, research in novel compounds with anti-parasitic properties is necessary to control coccidiosis and allow the expansion of the poultry industry to keep feeding the global population. At the moment, the anti-parasitic activity of new compounds can only be tested in live animals by expensive experiments that involve large numbers of chickens.

At the light of this increased need for the characterisation of new compounds, at the Royal Veterinary College we have recently developed an in vitro cell culture model that can evaluate the effects of new compounds in the parasite. If a compound does not exhibit any effect, there would not be need for testing it in chickens (total replacement of animals). If a compound shows relevant effects on the parasite, the in vitro model can generate important information for the design of further experiments in chickens, helping to reduce the number of groups needed for testing (reduction in the number of animals). In a first application of the model, we evaluated the anti-parasitic properties of two essential oils. The results allowed reducing the number of chicken in the subsequent in vivo (performed in animals) experiments to 67%. Therefore, this model could have an important impact in the global reduction of the number of animals used for research in anti-parasitic compounds against coccidiosis. Nevertheless, to allow the in vitro model having a global impact, a wider uptake by other research group and companies studying novel compounds is necessary. With this aim, we propose in this project the optimisation and transfer of the model to SALUVET-innova, a R&D company that will implement the model and test compound from ADIBIO and SETNA (animal nutrition companies) in vitro before they perform in vivo experiments - final in vivo tests in field conditions are always necessary for the commercialisation of the product -. In addition, we have planned a communication strategy for a wider uptake of the model by other companies and researchers. We have done the estimation that with the in vitro pre-screening we could reduce experimental animal groups achieving a reduction of 75 out of 125 chickens (60%) per compound tested. This means that if 10 to 20 new compounds are tested per year by our model, a reduction of 750-1,500 chickens out of 4,000 (average number of chickens per year used to test compounds against coccidiosis) could be achieved per annum, meaning a 20-40% overall reduction.

The development of in vitro models can support important advances in biomedical sciences and significantly reduce the use of experimental animals. The transference of these models for a wider uptake is paramount to make results comparable between different research groups and to support a global reduction of animal use in research. At the Royal Veterinary College, we have recently developed and published an in vitro model for the evaluation of anti-parasitic properties of novel compounds intended to be used for control of chicken coccidiosis. Chicken coccidiosis, a costly disease for the poultry industry (>£10 billion annually) caused by protozoa parasites of the genus Eimeria. The control of this disease is mostly achieved by chemoprophylaxis with drugs; nonetheless, there is an overall agreement of the need to improve current methods of control due to the reported resistances, new regulations on their use and public concerns.

Anti-parasitic activity of new compounds is currently evaluated by expensive experiments that involve large numbers of chickens. In a first application of our model, the in vitro pre-screening of two essential oils led to a reduction of 67% of the chickens planned for the in vivo trials. Therefore, this model could have an impact in the replacement/reduction of the number of chickens used for research in new anticoccidials. In order to allow a global impact, we propose in this project the optimisation and transfer of the model to SALUVET-innova, a company focus on knowledge transfer to generate new services and products, which will adopt it and test compounds from ADIBIO and SETNA (animal nutrition companies) as well as and offer its use to other companies and research institutions. We have estimated that if 10 to 20 new compounds are pre-screened per year by the model, a reduction of 750-1,500 chickens out of 4,000 (average number used to test anticoccidials per year) could be achieved per annum, meaning a 20-40% of overall reduction.