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

Lead Research Organisation: Cardiff University
Department Name: School of Medicine

Abstract

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.

Planned Impact

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.

Publications

10 25 50
publication icon
Andrey DO (2020) An Emerging Clone, Klebsiellapneumoniae Carbapenemase 2-Producing K. pneumoniae Sequence Type 16, Associated With High Mortality Rates in a CC258-Endemic Setting. in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

publication icon
Collignon P (2019) Antibiotic resistance, stewardship, and consumption - Authors' reply. in The Lancet. Planetary health

publication icon
Davies M (2018) A colistin crisis in India. in The Lancet. Infectious diseases

publication icon
Farzana R (2019) Emergence of mcr-1 mediated colistin resistant Escherichia coli from a hospitalized patient in Bangladesh in The Journal of Infection in Developing Countries

 
Description 1. We have found that both in China and Thailand there is no cross over of Campylobacter clones between humans and poultry - a very surprising result.

2. In Thailand we found that flies collected within a 10km fly of Phitsanulok carried the same (identical) hyper-virulent strain of Klebsiella pneumoniae - a very curious result.
Exploitation Route Once this study is completed we hope to able to guide policy changes in animal husbandry and public health.
Sectors Agriculture, Food and Drink,Environment,Healthcare

 
Description 1. To implement policy changes regarding the cross-contamination of chickens and humans with Campylobacter 2. Our data has helped the policy for the withdrawal of colistin as a growth promoter in China and as a consequence colistin resistance in China among the animal sector is dropping rapidly. We have shown that the withdraw of colistin has dramatically reduced mar and colistin resistance. 3. We have been in discussions with Thai authorities about food biosafety and sustainability whilst trying to curb the growing threat of AMR
First Year Of Impact 2020
Sector Agriculture, Food and Drink,Communities and Social Services/Policy,Education,Environment,Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic

 
Description Determining the clinical and environmental impact, burden and cost of Extensively Drug Resistant Enterobacteriaceae in China (DETER-XDRE-CHINA-HUB)
Amount £2,800,000 (GBP)
Funding ID MR/S013768/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 02/2019 
End 01/2022
 
Description Chinese collaborators 
Organisation Chinese Academy of Sciences
Department Research Center for Eco-environmental Sciences
Country China 
Sector Academic/University 
PI Contribution The UK budget will also support IoM ( 101K) for their DXC-HUB research activities in WP5, WP8 and WP12. This engagement was meant to be enhanced by quarterly meetings but due COVID and travel restrictions these were unable to take place and therefore that level of engagement and oversight for WP5, WP8 and WP12 was not optimal.
Collaborator Contribution Please see above for limitations by COVID-19 and travelling. Yang Wang (Chinese PI) oversaw the work by the IoM to ensure the data required was delivered.
Impact This collaboration is multi-disciplinary.
Start Year 2018
 
Description Collaboration with Dr. Pannika Nuimsup 
Organisation Naresuan University
Country Thailand 
Sector Academic/University 
PI Contribution Estimate £140 through added Newton fund awards and Thai Research Council. This includes exchange students and post-docs post COVID.
Collaborator Contribution See above - it was a collaborative involvement.
Impact Please see papers and awards.
 
Description Partnership 
Organisation China Agricultural University (CAU)
Country China 
Sector Academic/University 
PI Contribution I have taken on co-PhD supervision and also housed PDRAs in the UK as part of this collaboration.
Collaborator Contribution Yang Wang and I have been collaborating on AMR research since 2014 and we have jointly published over 43 papers contributing to REF etc.
Impact Very multi-disciplinary
Start Year 2013
 
Description Sequencing partnership in Hanoi, Vietnam 
Organisation National Institute Of Hygiene And Epidemiology
Country Viet Nam 
Sector Hospitals 
PI Contribution We have bought and help install a Mi-Seq in NIHE. Due to COVID-19 we are unable to travel there to do any training.
Collaborator Contribution 2016-2017 The Walsh team's investigator tasked with AMR genomics (Vietnam) project takes maternity leave. 2017 Hanoi Meeting: Walsh meets with multiple MoH departments representing OUCRU & NIHE. Advises that cooperation between the institutes on Fleming Fund resources will be required; that not doing so will impede AMR genomics project. OUCRU & NIHE apply separately for Fleming Fund, in competition. OUCRU's prior agreement and future ability to support NIHE-based sequencing operations suffers significant setback, impacting operations to present(2020). NIHE simultaneously acclimatizes to unexpected (&/or previously undisclosed) funding shortages in 2017, adding to the already challenging project environment. 2018-2019 Walsh works toward and succeeds in negotiating a quote for Illumina to provide a MiSeq far below standard cost. The laboratory conditions required for running the MiSeq are shared with NIHE. NIHE is unable to meet the requirements, necessitating a delay for laboratory refurbishment. 2019 15JAN-31JAN NIHE completes refurbishing laboratory space with suitable climate control, isolation, and vibration dampening for MiSeq operation. Walsh group begins renegotiating now-lapsed agreement with Illumina. 11APR Illumina provides quote for MiSeq to Walsh Group 13MAY-06JUN MiSeq purchase order sent to Illumina 13MAY-06JUN Significant delay waiting for Illumina to process purchase order. Multiple requests for updates from Walsh group. 06JUN Illumina reviews purchase order and informs Walsh group that quote would be unable to be fulfilled directly. Illumina advises obtaining a new quote from the sole authorized reseller in Vietnam: BioMedic JST. 06JUN-27JUN Cardiff University's supplier setup and procurement teams corresponded extensively with BioMedic to set them up as a University-approved supplier. This normally takes 2-3 weeks. The supplier setup team agreed to action it immediately due to the exceptional and time sensitive nature of the order, but the process was significantly hampered by BioMedic's non-acceptance of the terms and payment methods used with Illumina. We obtained a new BioMedic-specific quote (procurement would not accept the quote obtained from Illumina for payment to BioMedic, understandably). During this period Procurement + BioMedic also came to terms on a payment method stipulating a bank guarantee which BioMedic mostly provided (they provided a bank document guaranteeing the same stipulations upon non-delivery), which was then meant to allow us to pay up front. 27JUN The Walsh group received word that Biomedic Scientific Material JSC was approved and resubmitted all amended requisition documents on the same day. 05JUL "We're informed by Cardiff University's Overseas Payments team that the guarantee BioMedic provided is from a bank which Cardiff University's bank does not trust for guaranteeing purposes. Three actions taken: [1] request that BioMedic produces a guarantee from a trusted bank operating in Vietnam (the suggestion being AUSTRALIA & NEW ZEALAND BANKING GROUP LTD (ANZ)), or [2] request that, alternatively, BioMedic agree to the suggested terms of 80% payment on delivery and 20% payment on installation [3] request for Cardiff University's bank to provide a larger list of SWIFT-compliant banks for BioMedic's guaranteeing purposes. On 06JUL BioMedic informed us that they would be on a company holiday from 07JUL-11JUL, promising to immediately pick up correspondence on their return." 05JUL-16AUG Cardiff University Procurement, the Walsh team, and BioMedic JST negotiate terms until acceptable to all parties. 16AUG Signed contract sent to BioMedic JST. 20AUG Walsh group's central contact at BioMedic JST leaves the company. Progress halts for two weeks. 03SEP Replacement staff member at BioMedic JST resumes communications with Walsh team. 06SEP First MiSeq is delivered to NIHE. Installation pending. 29OCT MiSeq engineer sends the Walsh team his site report. The standard laboratory conditions all pass per Illumina standards. However, Hanoi power grid fluctuations are found to be too unstable to safely operate the MiSeq. To resolve, engineer suggests installing a high capacity, defined output UPS prior to MiSeq installation. 29OCT-13NOV Walsh group arranges installation of UPS in NIHE. 13DEC MiSeq engineer reports that MiSeq has been installed. Roughly 2/3 of validation metrics fail. Illumina Singapore (MiSeq) manufacturer is found to have sent faulty instrument. 2020 06JAN Replacement MiSeq installed at NIHE. 10JAN Replacement MiSeq passes all validation metrics. 10JAN-present Delays associated with NIHE priority responsibilities (COVID-19 outbreak surveillance and control).
Impact List of outcomes are in the outcome section and linked to this project.
Start Year 2017
 
Description 11th September 2019. Geneva ICPIC. "Should you screen for carbapenem resistance in ICU" 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited workshop at ICPIC 2019.
Year(s) Of Engagement Activity 2019
 
Description 12th December 2019. Adana, Turkey. "Dissemination of AMR and Refugees" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Workshop to discuss the transmission of AMR among in refugees in Turkey
Year(s) Of Engagement Activity 2019
 
Description 12th October 2019. AMR European workshop. "Global Analysis of Gram-negative resistance". 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Workshop of detecting AMR in clinical specimens
Year(s) Of Engagement Activity 2019
 
Description 12th September 2019. Geneva ICPIC. "An update on global colistin resistance". 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited interactive workshop to speak on the issues surrounding colisin resistance.
Year(s) Of Engagement Activity 2019
 
Description 14th January. Bracknell, UK BBSRC Annual meeting. "CUT-SEC update". 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact BBSRC workshop in Bracknell to discuss each funded project and how this interlinks with other funded programs to provide cross-fertilisation of science.
Year(s) Of Engagement Activity 2019
 
Description 20th November 2019. Guangdong. DETER-XDR-China Synopsis 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Workshop on future UK-Sino engagement.
Year(s) Of Engagement Activity 2019
 
Description 22nd November 2019. Chang-Mai. CUT-SEC update and outputs planning session. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact CUT-SEC workshop in ChangMai to discuss data and future plans.
Year(s) Of Engagement Activity 2019
 
Description 22nd October 2019. UK Antibiotics Research. "One Health Approach to understanding AMR" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Formal presentation with cabinet ministers and CMO etc.
Year(s) Of Engagement Activity 2019
 
Description 24th Match 2019. Beijing. "One-health approach to AMR: where are the gaps?" 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Invited lecturer on the issues of Global AMR and particularly related to China.
Year(s) Of Engagement Activity 2019
 
Description 26th January 2020. Islamabad. "Burden of AMR in neonatal sepsis in Pakistan" 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact Formal presentation in Islamabad to discuss project feedback on BARNARDS neonatal program and the global burden of AMR.
Year(s) Of Engagement Activity 2019
 
Description 2nd December 2019. Kigali. "Burden of AMR in neonatal sepsis in Africa" 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact Project meeting in Rwanda to discuss results of study and generally the global burden of AMR.
Year(s) Of Engagement Activity 2019
 
Description 5th September 2019. EC IMI ND4BB Annual Meeting, Warsaw. "The global microbiological perspective on drug design: a reality check". 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Invited talk to EC ND4BB IMI.
Year(s) Of Engagement Activity 2019
 
Description 6th Feb 2020. Lublin, Poland. Polish Society of infectious Diseases. "One Health Approach to AMR: Dream or Scream?" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Key symposium lecture discussing the plights of global AMR.
Year(s) Of Engagement Activity 2019
 
Description 7th June 2019. Dhaka. "Present and Future issues of AMR in Bangladesh" 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Invitation by BCDC to talk on the issues of AMR in Bangladesh.
Year(s) Of Engagement Activity 2019
 
Description 9th September 2019. WHO/CDC Think Tank meeting. "Application of WGS in LMICs". 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Selected meeting by WHO/CDC in Geneva for understanding future of infections.
Year(s) Of Engagement Activity 2019
 
Description AMR European workshop, Rome. "Global Dissemination of Gram-negative resistance". 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact International lecturer
Year(s) Of Engagement Activity 2019
 
Description July 13th-15th 2019 Beijing. DXC-HUB meeting. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact Group Sino-UK meeting
Year(s) Of Engagement Activity 2019
 
Description July 18th 2019. London. A global perspective on AMR in Gram-negative bacteria 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact International meeting in Kensington, London by ISID.
Year(s) Of Engagement Activity 2019
 
Description WHO advisory meeting on future landscape for tripartite AMR 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Formal WHO meeting in Geneva to discuss the WHO current AMR initiatives.
Year(s) Of Engagement Activity 2021