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JPIAMR-JPI Antimikrobiell resistens

Piloting on-site interventions for reducing antimicrobial use in livestock farming in emerging economies

Awarded: NOK 4.6 mill.

Countries with emerging economies experience an intensification in livestock production. As a consequence, the consumption of antibiotics increases, and with that, the problem of antibiotic resistance that can spread from production animals to humans and the environment. A significant part of the antibiotic use in the world today goes to pig and poultry production in Asia. A country with such a growing economy is Thailand. This project will use pig production in Thailand as a case and test measures that can help reduce the use of antibiotics in livestock production. The role of the Norwegian Veterinary Institute is to contribute with data, like mapping the presence of resistant bacteria in samples from pigs, pig farmers and from a control group of people who have not been in contact with pigs. In addition, in-depth analyses of the resistant bacteria will be performed, using whole sequence sequencing. Sampling of pig farms and humans in Thailand started in late September 2018 and was finished in December the same year. The initial laboratory work was carried out at the University of Khon Kaen. Follow-up investigations were performed at the Norwegian Veterinary Institute, in collaboration with partner Uppsala University. A total of 164 farm were included in the project. Two categories of pig farm were sampled; small scale family owned farms (1-50 sows) and larger more intensified company owned pigs farms (100-500 sows). From each sample randomly Escherichia coli and Klebsiella spp were picked and included for further investigations. All samples were also screened selectively for E. coli and Klebsiella pneumonia resistant to critically important antibiotics. As of September 2020, a total of 546 E. coli and Klebsiella isolates that are resistant to cephalosporins, carbapenems and colistin have been genome sequenced. In addition, 241 Klebsiella isolates are genome sequenced in order to study population structure, virulence and resistance. Results from Klebsiella genom analyses showed low occurrence of antimicrobial resistance. However, findings of convergent multiresistant and hypervirulent strains were demonstrated. Such isolates were found in samples from both animals and humans. Furthermore, highly similar strains were detected from pigs and humans, indicating zoonotic transmission between the reservoars to some extent. One K. pneumonia strain was studied in detail and this strain contained a novel variant of an mcr gene encoding resistance to colistin; mcr-3.40. This gene was located on a conjugative plasmid and this plasmid also harboured another mcr gene (mcr-2.3), in addition to a gene encoding resistance to 3rd generation cephalosporins. The mcr-2.3 was flanked by novel insertion sequence; ISKpn71. Furthermore, sequencing of a selection of highly multidrug resistant E. coli has been performed with a technology that produces longer sequences than traditional genome sequencing. This enabled in-depth investigations of plasmids harbouring genes encoding resistance to colistin. In Thailand, it is expected that larger production units will replace the family owned small-scale production pig farms in years to come. Our data show a higher frequency of multi-resistance in E. coli from pigs than from humans. Furthermore, more multi-resistant E. coli in larger and more intensified pig production units compared to family-owned small-scale farms was found. In addition, farm with drug resistant-E. coli, were located closer to drugstores and a had higher proportion of disease than farms without drug resistant-E. coli. As a part of the project, interviews were performed to map routines for use of antimicrobial agents in the two categories of swinefarms. Small-scale family owned farms got advice from pharmacies on how to use antibiotics, whereas the larger company owed production units used their own veterinary consultant. Antibiotics were primarily used for treatment of disease on the small family owned farms. On the larger company-owned farms antibiotics were to a wide extent used as disease prevention measure. Is expected that pig farming will change from small-scale to medium-scale. In order to control the future use an antibiotics the results from the project suggest to strengthening access to professional animal health services for all farmers, review of the competence and role of veterinary pharmacies in selling antibiotics and adjustment of farming company animal health protocols towards more medically rational use of antibiotics. In addition, measures to improve biosecurity and preventive measures to ensure good animal health should be prioritized in order to be able to reduce antibiotic use in pig production.

Prosjektet har fremskaffet viktig kunnskap om antibiotikaresistens og forbruk av antibiotika til svin i studieområdet i Nord-Thailand. Data generert i prosjektet kan bidra til å danne grunnlag for anbefalinger som kan redusere antibiotikabruken i svineproduksjonen i land med «voksende økonomier». Dette kan igjen bidra til å redusere utviklingen av antibiotikaresistente bakterier. For deltagerne har prosjektet muliggjort multi-disiplinært samarbeide i et internasjonalt consortium og Veterinærinstituttets ansatte har fått erfaring med prøvetaking, mikrobiologi, antibiotikaresistens og svineproduksjon i Asia. En post doc har vært tilknyttet prosjektet og dette har bidratt til forskerutdanning og rekruttering til vitenskapelig stilling.

Increasing intensification and expansion of the livestock sector in emerging economies is a large user of antimicrobials, driving the global emergence of antimicrobial resistant bacteria in livestock, humans and the environment. The objective here is to test interventions aimed to reduce antimicrobial use (AMU) in livestock in emerging economies using pig production in Thailand as a study case. Regulations may not be sufficient to reduce AMU in the livestock sector and can therefore have limited impact on the resulting development of AMR in the biota. Thus, there is a need to find interventions that do not depend solely on regulation. The novelty is that we will test interventions by computer simulations based on primary data generated through a One Health approach. Based on known distributions of pig production we will record knowledge, attitudes and practices related to AMU and animal management among pig farmers. Then we will collect samples from pigs, pig farmers and control human subjects who are not in contact with pigs and perform phenotypic and molecular analysis of the AMR profiles. Using these data-sets, we will do spatial analyses and model the impacts of altering variables for practices related to AMU, animal management and farm structure, with emphasis on farmers’ incentives, to explore whether these would be expected to lead to a reduction in AMU. Ultimately, we will assess if such a reduction can be related to the burden of AMR in pigs, pig farmers and non-exposed humans. Finally, we will assess the economic and social feasibility of the tested interventions.

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JPIAMR-JPI Antimikrobiell resistens