China/UK/Thailand Program on Poultry Biosafety for Salmonella, E. coli and Campylobacter (CUT-SEC)

The world's population is increasing, particularly in low-middle income countries and by 2050 as a global community we will have to feed an additional 2 billion people. This population explosion will place greater emphasis on meat production, particularly poultry. It is estimated by the world bank that by 2030, China, India and SE Asia will supply 80% of the world meat trade which will include national consumption and international export. The question is - how will this be met? Poultry farming will need to intensify to meet these global needs with the inevitable increase in antibiotic consumption used in animal feeds despite reservations from world authorities (WHO, FAO etc.). The AMR prevalence in chicken is considerably higher than other animal sectors due to the use of uncontrolled animal feeds and the potential for cross-contamination, either during growth or at slaughter. We use antibiotics to fatten and increase poultry growth yield yet this too in causing serious antibiotic resistance in human pathogens.

Antimicrobial resistance (AMR) is now deemed to be the biggest global threat facing humanity in the 21C. AMR has taken center stage as a global health issue yet most non-specialists are unaware the impact AMR will have on global populations and the potential it has of taking the treatment of infections back to the "dark ages". Hitherto, most studies around the world studying the impact of AMR have been small, one dimensional and often biased - too focused on AMR bacteria as oppose to studying the whole bacterial population. To understand the impact of AMR in the poultry sector we have established a network in Nth Thailand and mid-Eastern China (Shandong) and will undertake a comprehensive sampling strategy to examine key human food pathogens (Campylobacter, Salmonella and E. coli) in farms, the environment (water, flies, wild-birds) and community (human normal flora) and infections (urinary tract infections and gastroenteritis).

Our Study (called CUT-SEC) has a comprehensive sampling platform: work package (WP) 1, chicken and duck sampling from hatcheries to slaughter; WP2, flies and wild birds; WP3, water samples and seepage; WP4, domestic animals on or near farms; WP5 Normal human rectal flora; WP6 community infections. We will analyze at least 70 samples every 3 months to examine seasonal variation and sample from Nth Thailand and Shandong. Bacteria will be analyzed by basic microbiology techniques and selected to be whole genome sequenced where we can interrogate the bacteria's whole DNA and compare it to other bacteria to see if they have spread from one sector (e.g. flies) to another (e.g. humans). This study will also sequence all the bacteria in the human gut to understand the dynamics of AMR bacterial populations. We will also undertake controlled experiments in chicken farms to monitor the spread on SEC and use mathematical models to understand how AMR pathogens spread in animals and their impact on human infections. The impact of this CUT-SEC will have immense consequences for the animal, human and economic sectors in Thailand and China. Our network is well established, has a proven track record of working together in Thailand and China and expertise to undertake this exciting and challenging proposal.

Our recently work in China has been instrumental in forcing the withdrawal of colistin from the animal sector (Walsh TR and Wu Y. China bans colistin as feed addictive (growth promoter) in animals. Lancet Infect Dis. 2016. Oct;16(10):1102-3.). We have also provided evidence that has been considered in the Thai government who very recently announced the withdrawal of colistin from the Thai agricultural sector. As part of our "pathways to impact" we have established links with Thai and Chinese Ministries (Health, Animal and Environment) which is in keeping with the Fleming Fund (FF) ethos of working through local governments on National Action Plans (NAPs). As an example of our government involvement, please see the attached letter of support from Dr. Gong at the Chinese Ministry of Veterinary Medicine.

1. Change of Ministerial policies in China and Thailand. Our previous studies have already highlighted the need to review the use of antibiotics in these countries - particularly in Thailand where colistin is still used as a growth promoter (we are unsure as to when the ban will become law). The evidence provided from CUT-SEC will enable the Chinese and Thai governments to make informed decisions as to aid their respective populations in preventing an antibiotic resistance and impact on the treatment of infections. Moreover, within CUT-SEC we have a serious of intervention studies (WP10 A-C) where we hope to produce concrete evidence (supported by mathematical modelling - WP11) to support the implementation of these interventions to improve chicken/duck biosafety.
2. Chinese and Thai Ministries of Agriculture (MoA). As part of CUT-SEC we will sample the poultry (chickens and ducks) sector and provide key evidence to the MoA in China and Thailand which is currently lacking i.e. what are the dominant SEC clones? what are the drivers for their dissemination? what is the impact of AMR on the SEC and how does this impact on human colonisation and infections? Our data can be used by the each government to examine the stability of SEC/AMR in their animal sectors (farm animals and retail meat), and examine the impact of this on the normal human fecal flora and possibly causes of MDR endogenous infections.
3. Chinese and Thai Ministries of Health (MoH). In China, through collaborating with Prof Wu, we are already well connected to the Chinese Ministry of Health and we hope to mirror such working relationships in Thailand. Our unique data of SEC on community infections (UTIs and gastroenteritis) will be very useful to examine their clinical impact and whether SEC are associated with worse outcomes (prolonged hospital stay, severity of infections, morbidity).
4. Chinese and Thai Ministries of Environment. Through CUT-SEC we will examine aspects of the environment and collect unique data that will inform the extent on SEC/AMR environmental contamination. Accordingly, we will also reach out to Chinese and Thai ministries dealing with pollution and environmental waste and engage with them on key issues of environmental SEC/AMR niches and their impact on animal and human health.
5. Chinese and Thai Farming Communities. Through our farm animal sampling (WP1) and environmental sampling (WP3-4) we will be able to affirm the importance of, for example, flies in spreading SEC throughout the farming community and can explore simple intervention measures to prevent further "flock/herd contamination"
6. High-impact Journals, World Press and International AMR Bodies. Our data will be published in high-impact peer review journals and according attract media attention (both UK and global - see "pathways to impact') and will be able to apply pressure on the WHO, FAO, and WHA to examine policies and international remits on AMR as we have done previously.