Periodic Reporting for period 1 - AVANT (Alternatives to Veterinary ANTimicrobials)
Período documentado: 2020-01-01 hasta 2021-06-30
Antimicrobial resistance (AMR) is a recognized societal problem with serious consequences on public health and economy. Since resistant bacteria can be selected by any use of antibiotics, their use in livestock production poses a threat to human health due to the possible transfer of resistant bacteria to people via direct contact with animals or by consumption of contaminated food of animal origin. AVANT is a multi-actor project bringing together scientists, stakeholders and end-users involved in the fight against AMR in the veterinary sector, including academic and research institutions, animal health enterprises, and veterinary associations. The goal is to develop and test the efficacy and sustainability of a comprehensive set of alternatives to antibiotics for the management of bacterial infections in pigs with particular emphasis on post-weaning diarrhoea (PWD), which is the main reason for antibiotic use in pig production. The AVANT portfolio of alternatives to antibiotics comprise i) gut microbiome modulators such as synbiotics and faecal transplants from healthy donors, ii) innovative medicines targeting the causative pathogen of PWD, enterotoxigenic Escherichia coli (ETEC), iii) immunostimulators that strengthen the host immune response against infection, and iv) feeding strategies for PWD prevention. Based on the results of pre-clinical studies, the three most promising interventions will be selected for a multicentre farm trial in order to test their efficacy on prevention and control of PWD. Data on antibiotic use at the farms involved in the trial will be used to predict the potential effects of each selected alternative to antibiotics on reduction of antibiotic consumption in the EU by mathematical modelling.
During the first 18 months of the project, the various alternatives to antibiotics studied in AVANT were further developed and optimized with regard to formulation, administration route, dosage, etc. before being selected for and tested in the clinical trial. The different products and interventions under study were classified according to the EU regulation and their regulatory strategy was aligned with the planned preclinical studies. Although definitive results on clinical efficacy are not yet available at this early stage of the project, some encouraging preliminary results were generated by the pre-clinical studies:
• A synbiotic product (ProPig) showed a statistically significant effect on prevention of PWD as well as on pig performance (body weight gain, feed intake, and feed conversion rate) when tested on piglets challenged with ETEC under controlled experimental conditions.
• Comparison between different protocols for faecal transplantation showed that filtrate of colon content is more effective than crude colon content for reducing diarrhoea rate, although no significant impact was observed on occurrence of ETEC in the challenged piglets.
• A mix of phage strains with specific lytic activity against ETEC was assembled and a qPCR method was developed and validated for phage quantification.
• Administration of an oral immunostimulant was shown to be as effective as antimicrobial treatment in preventing of PWD in pigs.
• A synbiotic product (ProPig) showed a statistically significant effect on prevention of PWD as well as on pig performance (body weight gain, feed intake, and feed conversion rate) when tested on piglets challenged with ETEC under controlled experimental conditions.
• Comparison between different protocols for faecal transplantation showed that filtrate of colon content is more effective than crude colon content for reducing diarrhoea rate, although no significant impact was observed on occurrence of ETEC in the challenged piglets.
• A mix of phage strains with specific lytic activity against ETEC was assembled and a qPCR method was developed and validated for phage quantification.
• Administration of an oral immunostimulant was shown to be as effective as antimicrobial treatment in preventing of PWD in pigs.
AVANT aims at developing, testing and exploiting of different types of alternatives to antibiotics for treatment and prevention of PWD in pigs. The potential impact of each alternative is evaluated using different indicators, including clinical efficacy, effect on reduction of antibiotic use, and sustainability. The best products and interventions generated by the project will contribute to reduce antibiotic consumption in pig production, providing effective therapeutic and preventive strategies for managing this important disease in pig production while minimizing the risk of AMR transmission from pigs to humans. As such, the project will have a positive impact on both animal health and public health. From a scientific standpoint, AVANT will contribute to understand the effects of each type of alternative on diversity and composition of the pig gut microbiota, providing information on its mechanism(s) of action and on the pathogenesis of PWD. This new knowledge will be disseminated via scientific publications and communications at national and international conferences as well as via social media, press releases and stakeholder engagement. Multiple communication channels will be used to ensure the broadest possible dissemination, including the AVANT website, YouTube channel, Facebook, LinkedIn, ResearchGate, and Twitter.