Does AMR in livestock contribute to AMR in people in NE India? An interdisciplinary study.

Lead Research Organisation: University of Cambridge
Department Name: Veterinary Medicine

Abstract

Considerable amounts of antibiotics are used in the rearing of livestock and the use of these antibiotics leads to the selection of bacteria that are resistant. There is some evidence that these bacteria may contribute to resistance levels in bacteria that cause human disease. This research aims to investigate if antibiotic resistant strains of bacteria found in farms are also found in cases of human disease in a region of North East India. This project will also record the use of antibiotics on farms, and to investigate the human behavioural and animal health factors that influence antibiotic use. The study combines microbiological and social science research methods. Agriculture in this area consists mainly of smaller livestock enterprises typical of many rural settings in India. The aim is to provide a comprehensive description of the distribution of resistant bacteria in humans, livestock (including aquaculture) and the environment together with a thorough study of the context which leads to the selection of these bacteria in order to understand which antibiotics (and the quantities) are used and why. The project also aims to increase the research capacity in India to continue this work through increased experience and training in the application of DNA sequencing and social science methods for research into antibiotic resistance.

The specific research work that will be performed is:

1. Sampling on farms in order to bacteria from animals, people, the environment and retail meat products, together with bacteria from cases of human disease from local hospitals.

2. Collection of data from farms to record antibiotic use, how and why decisions are made to use antibiotics, which individuals are influencing these decisions, and what factors affect the decision-making process (to include how presumptive diagnoses are made, societal hierarchy, prior knowledge, education, attitudes, and economic factors) using established social science research methods .

3. DNA sequencing of the bacteria in order to characterise the mechanisms responsible for antibiotic resistance, and to compare the relatedness of agricultural and hospital bacteria. This enables us to determine if there is transmission of antibiotic resistance from farm animals to people.

4. To develop antibiotic stewardship advice, materials and programmes that are tailored to a rural Indian context in order to maximise animal health and ensure rational use of antibiotics.

Good quality scientific evidence is needed to ensure that any restrictions on antibiotic use on farms are rational, and targeted appropriately. Regardless of any contribution to human antibiotic resistance better antibiotic stewardship in agriculture will reduced levels of resistance in livestock and lead to improved animal health.

Planned Impact

The impact from this research will result from the answer to the question "Is antibiotic resistance transmitted to man from livestock?". If it is we will also identify the bacterial species and types of resistance that are involved. This evidence is essential if there are to be informed decisions concerning efforts to control the use of antibiotics on farms. Our research is likely to identify specific routes of transmission (i.e. via farm workers, environmental reservoirs, retail food products etc) which would enable the development of risk assessment models and the design of interventions where the risks are highest. The research will identify how much antibiotic is being used on farms and the reasons why it is being used which in turn will enable the identification of ineffective or inappropriate antibiotic use. This information will help in the design of targeted antibiotic stewardship programmes that address the barriers to rational antibiotic use that are specific to the rural agricultural settings in India.

Social and economic benefits will accrue. A reduction in antibiotic resistance in human disease will lead to more effective and timely treatment of infectious disease with patients returning to work more rapidly and leading to lower healthcare costs. Improved animal health will lead to greater agricultural productivity and reductions in the economic losses associated with infectious disease. As farm incomes make a major contribution to rural family incomes with limited economic resources, better economic performance will lead to a reduction in poverty.

Publications

10 25 50

 
Description Researchers working on this award have published 5 papers.

In one paper we show that a type of bacteria (coagulase-negative staphylococci) collected from fish being sold for food in a market are resistant to a high-end antibiotic (teicoplanin). This clearly demonstrates how this important type of resistance can be acquired by people in India and further monitoring is important.

In another paper we look at the prevalence of a particular strain of MRSA (ST88-IV-t2526) in local retail fish markets in NE India. We show that this type of MRSA which is has been responsible for human disease is present in fish and represents a potential public health risk.

In a third paper we show that fish-borne bacteria, a methicillin resistant Staphylococcus haemolyticus carrying atypical staphylococcal cassette chromosome mec (SCCmec) elements, is present in a fish market sample. This bacteria represents a novel combination of species and type of bacteria that is of potential significance to human health.

We published a paper that describes an assessment of antimicrobial resistance in a particularly important set of Gram negative bacteria (Escherichia coli and Klebsiella pneumoniae) which are multi drug resistant with extended spectrum betalactam (penicillin) resistance in samples from from food fishes, Assam, India. These bacteria are significant human pathogens and this work demonstrates how people may get infected via the food chain.

One key finding that has been discovered involves work that was performed during the Covid-19 pandemic when we were unable to collect samples or data in India. This unplanned work involves the discovery that a type of MRSA evolved on hedgehogs around 200 years ago. We were investigating the surprising discovery - from hedgehog surveys from Denmark and Sweden - that up to 60% of hedgehogs carry a type of MRSA called mecC-MRSA. We were able to show that methicillin resistance evolved in Staphylococcus aureus as an adaptation to having to exist side-by-side on the skin of hedgehogs with the fungus Trichophyton erinacei, which produces its own antibiotics similar to penicillin. The resulting methicillin-resistant Staphylococcus aureus was shown to have evolved long before people started using antibiotics in medical and agricultural settings.
Exploitation Route The current outcomes of this research indicate that the food chain is clearly the potential source for many important human pathogens and antimicrobial resistance. This information can be used to inform strategies designed to reduce burdens of disease and spread of antibiotic resistance in Indian fish retail markets.
Sectors Agriculture, Food and Drink

 
Description UKRI ODA Funding for Impact: Delivery of Antibiotic Stewardship Workshops in LMI Countries
Amount £49,994 (GBP)
Organisation University of Cambridge 
Sector Academic/University
Country United Kingdom
Start 01/2023 
End 04/2023
 
Title Bioinformatics capacity building 
Description Training has been provided to over 20 Indian researchers on the bioinformatic analysis of genome sequencing data generated by the project. The training also include giving access to MRC-CLIMB computing facilities. 
Type Of Material Improvements to research infrastructure 
Year Produced 2019 
Provided To Others? Yes  
Impact This has enabled Indian collaborators and other Indian researchers the ability to undertake research on bacterial genome sequences generated by this project and from other projects they have undertaken. 
 
Title Social science research methodology training 
Description In addition to training Indian social science colleagues in this methodology we also provided veterinarians and microbiologists with a general introduction to the methodologies that can be used in cross disciplinary studies. Training in social science techniques was delivered to Indian researchers through an initial workshop to introduce key concepts and techniques including participatory, ethnographic and behavioural (economics) research. The didactic teaching was followed by practical training by pairing UK social scientists with Indian researchers through an initial cycle of Rapid Ethnographic Assessment (REA) on farms in the region. During a second REA on a subsequent farm, the Indian researcher worked autonomously under supervision from the UK social scientist. This approach enables Indian researchers who are unfamiliar with the REA and Participatory Rural Appraisal (PRA) processes to become confident with the techniques and to work independently through subsequent cycle(s) across additional farms. Thus the process has built Indian capacity for this research. 
Type Of Material Improvements to research infrastructure 
Year Produced 2019 
Provided To Others? No  
Impact None as yet 
 
Title Bacterial genomic sequencing 
Description Short read sequencing data from DNA prepared from bacteria isolated during the sampling of livestock, environment and foodstuffs in Guwahati 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? No  
Impact None to date 
URL https://microbesng.com/portal/projects/2AC7D8CA-7272-4485-BEDE-9021D329A602/
 
Description Neostar 
Organisation Gauhati Medical College and Hospital
Country India 
Sector Academic/University 
PI Contribution India-UK partnership that made a joint application for funding from Indian DBT and UKRI
Collaborator Contribution Indian partner collaborated on design of the research and undertake the sampling of livestock, people, food stuffs and the environment in Assam. Indian partners also collect social science data from the communities we sample from.
Impact This is a cross disciplinary collaboration involving microbiologists and social scientists.
Start Year 2018
 
Description Neostar 
Organisation Indian Council of Agricultural Research
Department The Central Institute of Fisheries Technology
Country India 
Sector Academic/University 
PI Contribution India-UK partnership that made a joint application for funding from Indian DBT and UKRI
Collaborator Contribution Indian partner collaborated on design of the research and undertake the sampling of livestock, people, food stuffs and the environment in Assam. Indian partners also collect social science data from the communities we sample from.
Impact This is a cross disciplinary collaboration involving microbiologists and social scientists.
Start Year 2018
 
Description Neostar 
Organisation Indian Council of Agricultural Research
Country India 
Sector Charity/Non Profit 
PI Contribution India-UK partnership that made a joint application for funding from Indian DBT and UKRI
Collaborator Contribution Indian partner collaborated on design of the research and undertake the sampling of livestock, people, food stuffs and the environment in Assam. Indian partners also collect social science data from the communities we sample from.
Impact This is a cross disciplinary collaboration involving microbiologists and social scientists.
Start Year 2018
 
Description Neostar 
Organisation Indian Institute of Technology Delhi
Country India 
Sector Academic/University 
PI Contribution India-UK partnership that made a joint application for funding from Indian DBT and UKRI
Collaborator Contribution Indian partner collaborated on design of the research and undertake the sampling of livestock, people, food stuffs and the environment in Assam. Indian partners also collect social science data from the communities we sample from.
Impact This is a cross disciplinary collaboration involving microbiologists and social scientists.
Start Year 2018
 
Description Neostar 
Organisation National Institute of Veterinary Epidemiology and Disease Informatics
Country India 
Sector Public 
PI Contribution India-UK partnership that made a joint application for funding from Indian DBT and UKRI
Collaborator Contribution Indian partner collaborated on design of the research and undertake the sampling of livestock, people, food stuffs and the environment in Assam. Indian partners also collect social science data from the communities we sample from.
Impact This is a cross disciplinary collaboration involving microbiologists and social scientists.
Start Year 2018
 
Description BBC Radio 4, (Jan 6th, 2022): 6pm News. Interview about the evolution of mecC MRSA in hedgehogs. 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact National BBC Radio 4 news - interview providing context and further information about our research
Year(s) Of Engagement Activity 2022
URL https://www.bbc.co.uk/sounds/play/m001329j
 
Description BBC Radio 5/BBC Cambridgeshire (Jan 9th, 2022): Naked Scientists. Interview about the evolution of mecC MRSA in hedgehogs. 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact National radio (BBC R5) interview discussing research findings. Explaining the findings to a general audience in non-technical language (https://www.bbc.co.uk/sounds/play/m0013996)
Year(s) Of Engagement Activity 2022
URL https://www.thenakedscientists.com/articles/interviews/gadget-and-gaming-trends-2022
 
Description BBC Radio 5/BBC Cambridgeshire (July 18th, 2021): Naked Scientists. Colistin resistance in dometic pets. 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact National BBC Radio 5 interview commenting on colistin resistance
Year(s) Of Engagement Activity 2021
URL https://www.thenakedscientists.com/podcasts/short/antibiotic-resistant-bacteria-dogs
 
Description Interview for Candadian TV and Radio 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Interview broadcast in Canada and published on news website entitled "MRSA occurred 200 years ago in nature long before antibiotics: study"
Year(s) Of Engagement Activity 2022
URL https://www.ctvnews.ca/health/mrsa-occurred-200-years-ago-in-nature-long-before-antibiotics-study-1....
 
Description Interview for New York times 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Interview to journalist resulted in this story: Hedgehogs Are a Source of Drug-Resistant Bacteria, Study Finds
Year(s) Of Engagement Activity 2022
URL https://www.nytimes.com/2022/01/05/science/hedgehog-mrsa-drug-resistant-bacteria.html
 
Description Interview for article published in general interest science magazine (New Scientist) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Generated an article published in the magazine and on-line entitled "A type of mrsa evolved in hedgehogs long before the first antibiotics were used in medicine"
Year(s) Of Engagement Activity 2022
URL https://institutions.newscientist.com/article/2303390-a-type-of-mrsa-evolved-in-hedgehogs-long-befor...
 
Description Interview for article published in national newspaper (Daily Mail) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Generated an article published in the newspaper and on-line entitled "Superbug MRSA arose in hedgehogs before discovery of antibiotics, study suggests"
Year(s) Of Engagement Activity 2022
URL https://www.dailymail.co.uk/wires/pa/article-10371931/Superbug-MRSA-arose-hedgehogs-discovery-antibi...
 
Description Interview for article published in national newspaper (The Guardian) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Generated an article published in the newspaper and on-line entitled "Hedgehogs had MRSA superbug long before antibiotics use, research finds"
Year(s) Of Engagement Activity 2022
URL https://www.theguardian.com/science/2022/jan/06/hedgehogs-had-mrsa-superbug-long-before-antibiotics-...
 
Description Interview for article published in national newspaper (The Independent) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Generated an article published in the newspaper and on-line entitled "MRSA superbug first arose in hedgehogs before discovery of antibiotics, study suggests"
Year(s) Of Engagement Activity 2022
URL https://www.independent.co.uk/news/science/mrsa-hedgehogs-antibiotics-study-b1987185.html
 
Description Interview for article published in national newspaper (The Telegraph) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Generated an article published in the newspaper and on-line entitled "Are humans really to blame for MRSA superbug? It turns out the answer is a prickly subject"
Year(s) Of Engagement Activity 2022
URL https://www.telegraph.co.uk/news/2022/01/05/mrsa-superbug-emerged-hedgehogs-200-years-ago-study-find...
 
Description Interview for article published in national newspaper (The Times) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Resulted in article published in newspaper and on-line "Superbug MRSA may have evolved in hedgehogs about 200 years ago"
Year(s) Of Engagement Activity 2022
URL https://www.thetimes.co.uk/article/superbug-mrsa-may-have-evolved-in-hedgehogs-about-200-years-ago-s...
 
Description Interview for international news (US PBS radio) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Interview in response to publication of our research providing lay summary and describing significance broadcast on US national radio and published on their website
Year(s) Of Engagement Activity 2022
URL https://www.pbs.org/newshour/science/what-hedgehogs-can-teach-us-about-antibiotic-resistance
 
Description Interview with BBC journalist for BBC website 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Interview with Victoria Gill resulted in BBC News website article titled "Antibiotic-resistant superbug evolved on hedgehogs"
Year(s) Of Engagement Activity 2022
URL https://www.bbc.co.uk/news/science-environment-59883336
 
Description Stakeholder workshop with semi-rural farming community in Silagrant, Guwahati 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Study participants or study members
Results and Impact Approximately 40 members of the community and the community council met with researchers to discuss the issues surrounding antibiotic use and animal health.
Year(s) Of Engagement Activity 2019