Management of post-weaning diarrhoea and the implications for AMR in response to the upcoming ban on zinc supplementation in pigs.

Lead Research Organisation: University of Edinburgh
Department Name: Roslin Institute

Abstract

Piglet weaning through separation from the sow is a critical and stressful period in the life of a pig. At this stage piglets are particularly vulnerable to gut problems and have a tendency to develop a condition called post-weaning diarrhoea. This disease is primarily caused by bacteria and viruses which challenge the piglet's immature gut, and is a welfare and economic concern to farmers, because piglets suffer weight loss, discomfort and sometimes death. Zinc oxide is currently added to pig feed as a dietary supplement to reduce post-weaning diarrhoea and boost growth. However, whilst Zinc oxide improves piglet gut health, there are environmental concerns due to the potential contamination of land with zinc through pig manure and waste. High zinc levels are also thought to promote the ability of bacteria to evade antibiotics, resulting in antimicrobial resistance. For these reasons, from June 2022 the supplementation of pig feed with high levels of Zinc oxide will be banned in the UK and Europe. Within the pig farming sector there are serious concerns that this ban will have a damaging impact on the health and welfare of piglets during weaning. Farmers and veterinarians anticipate post-weaning diarrhoea will become harder to manage and will require more medical treatment. As a consequence, antibiotic use to treat piglet gut infections may increase, exacerbating already high usage within the pig industry. This has implications for limiting levels of antimicrobial resistance in livestock and the food-chain.

Working directly with farmers during the transitional period to "zero zinc", in this study we aim to investigate the impact of the ban on piglet health and growth. Our goal is to identify practical measures that will make an on-farm difference to reducing disease, whilst improving animal welfare and productivity. We will examine a range of farm management, husbandry and biological measures, to see which factors influence post-weaning diarrhoea in piglets. We will do this by collecting pig faecal samples from farms both before and after the introduction of the June 2022 ban, and identifying any changes in the type and numbers of microbes found in piglet faeces. We will look at the composition of the "friendly" gut bacteria, as well as disease-causing bugs, and examine levels of resistance to antibiotics. At the same time we will analyse data from participating farms to measure piglet health status, and track any management changes farmers may have introduced to lessen the impact of the Zinc oxide ban. This, together with a questionnaire-based survey of pig farmers across the UK, will provide a picture of both the perceptions and reality of the Zinc oxide ban on piglet weaning. Crucially, by working directly with farmers, we hope to find acceptable solutions that may reduce disease in piglets, whilst providing information to help offset the uncertainty accompanying the journey to "zero zinc".

Technical Summary

Piglet weaning is a critical life-stage, associated with high vulnerability to diarrhoeal disease and poor weight gain. Post-weaning diarrhoea (PWD) is a condition that causes considerable economic loss to the pig industry due to the impact on this most pivotal phase of a pig's production cycle. Zinc oxide (ZnO) is currently used as a feed additive at pharmacological levels of 2500 ppm to mitigate the challenges during weaning, reducing diarrhoeal incidence while improving production measures such as weight gain. However, there is an environmental impact of high ZnO usage, which is also associated with an increase in antimicrobial resistance within the pig gut microbiota.
From mid-2022, ZnO supplementation of weaner/post-weaning piglet diets will not be permitted above a maximum level of 150 ppm. It is anticipated that this will result in an increase in PWD, impacting pig productivity, animal health and welfare. This project will have two main objectives, the first the establishment of a bio-bank of pre- and post-ban faecal samples for microbial analysis to elucidate the impact of the ZnO ban on pathogen occurrence, antimicrobial resistance indicator genes and microflora composition in weaning and later aged pigs. The second, an epidemiological analysis of data from participating farms to identify potential risk factors affecting diarrhoeal disease, together with on-farm motivations and barriers towards management of health throughout the weaning period.
The immediate months prior to implementation of the June 2022 ban, together with the period of withdrawal, present a unique opportunity to objectively compare the pre- and post-ban experience of PWD within the UK pig sector. Directly working with stakeholders, this project aims to identify practical measures for on-farm implementation to reduce disease occurrence and improve productivity, whilst providing information to help offset the uncertainty accompanying the transition to "zero zinc".

Publications

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Description The aim of this longitudinal study was to compare key markers for the two main pathogens associated with post-weaning diarrhoea, namely enterotoxigenic Escherichia coli and rotavirus, to examine any change in frequency and pathogen strain before and after removal of therapeutic zinc oxide (ZnO) supplementation at 2500 ppm from weaner diet. The study also aimed to identify any changes in carriage of antimicrobial resistance genes in herds before and after ZnO withdrawal, because metals such as zinc are associated with the carriage of multiple drug resistance in bacterial populations. We further aimed to compare the gut microflora composition pre- and post-withdrawal of ZnO, in order to identify components that may be associated with disease or with better resilience to diarrhoea. Finally, we aimed to identify management, husbandry and biological factors which may mitigate the impact of ZnO removal from feed on the incidence of post-weaning diarrhoea and poor weight gain, through epidemiological analysis of data from participating farms and from a wider survey of the UK pig industry.

Prior to the start of the current project, in January 2022, the planned implementation of the UK regulatory removal of ZnO supplementation from weaner diet was delayed by two years, from the original date aligned with the European Union withdrawal timetable of June 2022, until a later date in the UK of June 2024. This UK regulatory change to implementation has meant that this priming Phase 1 study has only been able to collect pre-withdrawal samples and a small number of early post-withdrawal samples from recruited herds, because many herds decided to delay the withdrawal of ZnO from their weaner diets until 2024, due to concerns about the impact on piglet health and welfare. Therefore, the original project objectives have been rolled over onto a new, onward Phase 2 project, for which the consortium team have been successful in obtaining further BBSRC funding through a responsive mode grant application. This Phase 2 funding is a three-year consortium award of value £1.1 million across four academic institutions, and with additional financial and in-kind contributions from an industry partner. This new Phase 2 award commenced in March 2024 and will run until February 2027.

To date, twenty-four commercial herds have been recruited to the planned longitudinal survey established during this Phase 1 award, that will progress beyond the end of the award into Phase 2. Field samples and data have been collected from these herds over the past 12 months, with all pre-withdrawal samples collected, and early post-withdrawal samples from one third of herds that withdrew ZnO during 2023. The remaining two-thirds of herds will remove ZnO over the next four months, before the end of June 2024.

Data from the pre-withdrawal samples analysed so far have identified the predominant enterotoxigenic E. coli virulence factors currently circulating in the sampled herds in England, Scotland and Northern Ireland, with the F4 antigen greatest at both sample and herd level in England and Scotland, and F18 dominating in Northern Ireland. All herds yielded weaner samples that were positive for rotavirus A, B and C subtypes, and rotavirus H was not detected. Finally, the presence of integron mobile genetic elements, used as a proxy marker for multiple drug resistance carriage, was widespread in all herds.

A low temperature biobank of the collected faecal samples has been established as a resource for the ongoing project and for future research into pathogens associated with post-weaning diarrhoea, microbiome resilience and transmission of antimicrobial resistance within commercial herds in the UK. Currently we have banked over 1200 samples from a range of life stages and timepoints during the transition to full ZnO removal across the recruited herds. A laboratory information management system has been established to enable optimal curation of the herd samples and data, and to ensure data security.

A producer attitude social survey interview study has been developed, to obtain detailed in-person feedback from producers on the impact of ZnO removal. This is based on a telephone interview questionnaire format, which has been designed, piloted and ethically approved. To date eight interviews with producers from a subset of the recruited study herds have been conducted pre-withdrawal. These interviews have provided detailed insight into the challenges, barriers and attitudes of producers for managing post-weaning diarrhoea in their herds and their concerns regarding the UK wide regulatory removal of ZnO supplementation from weaner diets.

Finally, to gain a wider understanding of the impact of ZnO withdrawal across the whole industry, beyond the herds recruited to the longitudinal study, a UK-wide pig livestock sector online survey has been developed. This survey has been designed, piloted, ethically approved and launched through newsletters and social media sites across a number of national organisations and veterinary practices, targeting pig producers. This online survey is currently ongoing, with an aim to collect responses from over 60 producers in total, and will report outcomes in the next few months.
Exploitation Route The aim of the project was to identify practical measures that will make on-farm difference to reduce post-weaning diarrhoea and improve animal health, welfare and productivity, whilst providing information to help offset the uncertainty within the pig industry accompanying the regulatory withdrawal of pharmacological zinc oxide (ZnO) supplementation from weaner piglet diets, which will come into effect in the UK by June 2024. The consortium team have recently been successful in obtaining further funding in the form of a three-year award to progress and develop this priming Phase 1 project further, into a more comprehensive Phase 2 research programme. This new Phase 2 award commenced March 2024.

During Phase 2, we will continue the ongoing longitudinal commercial herd survey, and report on observed changes in the incidence of, and pathogen strains associated with, post-weaning diarrhoea during the transition to full withdrawal of ZnO in our study herds, between 2022 at the start of the study (this award, Phase 1) through to the end of 2025, 18 months after regulatory removal is enforced in the UK (mid-Phase 2).
These data will inform on the key strains and antigens causing disease in the study herds, of relevance to vaccination preventative strategies, important to both livestock and pharmaceutical sectors.
Further, by monitoring antimicrobial usage and identifying key antimicrobial resistance genes within the study herds pre- and post- ZnO withdrawal, we will examine whether this UK regulatory policy change has a demonstrable impact on reducing the antimicrobial resistance reservoir in study herds, of significance both to the livestock industry and public health.
Finally, by comparing the faecal microbiome in herds pre- and post-withdrawal and between herds with high and lower levels of the key pathogens of concern, we aim to identify microbiome consortia that may be beneficial by promoting better outcomes during piglet weaning. These data may inform the future development of novel feed supplements to mimic the current action of ZnO during weaning, of relevance to this livestock sector and to the nutritional and pharmaceutical industry.
Sectors Agriculture

Food and Drink

Environment

Healthcare

Government

Democracy and Justice

Pharmaceuticals and Medical Biotechnology

Other

 
Description Intended and unintended consequences of the ZnO ban from pig diets on antimicrobial resistance, post-weaning diarrhoea and the microbiome.
Amount £1,110,610 (GBP)
Funding ID BB/Y004086/1 (and linked consortium codes BB/Y003918/1; BB/Y004108/1; BB/Y003861/1) 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 03/2024 
End 02/2027
 
Description National Farmers Union Scotland - Sector Working Group 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Industry/Business
Results and Impact Short, two slide presentation to a meeting of a sector working group, outlining the project aims and activities, with discussion.
Year(s) Of Engagement Activity 2023
 
Description National Farmers Union Scotland - Sector Working Group visit to research organisation for a meeting and presentations 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Industry/Business
Results and Impact A morning and lunch visit to our research organisation by members of a livestock sector working group of the NFU Scotland, for presentations about research activities being conducted by our institution relevant to the working group's livestock sector and for discussion about potential impact, opportunities and the sector's primary disease concerns and priorities. The attending members were livestock producers and associated industries.
Year(s) Of Engagement Activity 2023
 
Description Participation in funder workshop meeting at the National Farmers Union, Stoneleigh 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact The funding body that provided the award organised a workshop meeting to allow presentation of research results from the funded project to the wider livestock industry, stakeholder representatives from relevant organisations, veterinary professionals and other researchers in the field. I gave an oral presentation of this particular research project to the audience.
Year(s) Of Engagement Activity 2023
 
Description Pig Veterinary Society Autumn Meeting 2022 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The project was described to a professional veterinary audience during a presentation outlining the results of a Rapid Evidence Assessment investigating options for managing post-weaning diarrhoea in weaning piglets without the use of in-feed, pharmacological supplementation with Zinc oxide.
Year(s) Of Engagement Activity 2022
 
Description Poster Presentation on zinc oxide use in pigs at the Edinburgh AMR Forum Showcase 2022 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact Presented a poster of the project at the meeting entitled "Ban on zinc supplementation in pig feed: management of post-weaning diarrhoea and the implications for AMR" at the University of Edinburgh on 21/11/22. The poster led to discussion of the project with a Sixth form pupil from a local school who was attending the meeting, as well as other colleagues.
Year(s) Of Engagement Activity 2022