Inter-host Transmission of Carbapenemase-Producing Escherichia coli among Humans and Backyard Animals

doi:10.1289/EHP5251

. 2019 Oct;127(10):107009.

doi: 10.1289/EHP5251. Epub 2019 Oct 23.

Inter-host Transmission of Carbapenemase-Producing Escherichia coli among Humans and Backyard Animals

Jiyun Li^{1

2}, Zhenwang Bi³, Shizhen Ma¹, Baoli Chen⁴, Chang Cai^{5

6}, Junjia He¹, Stefan Schwarz^{1

7}, Chengtao Sun¹, Yuqing Zhou¹, Jia Yin^{8

9}, Anette Hulth^{10

11}, Yongqiang Wang¹, Zhangqi Shen¹, Shaolin Wang¹, Congming Wu¹, Lennart E Nilsson¹², Timothy R Walsh^{1

13}, Stefan Börjesson^{12

14}, Jianzhong Shen^{1

15}, Qiang Sun^{8

9}, Yang Wang^{1

15}

Affiliations

¹ Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China.
² College of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan, China.
³ Shandong Academy of Clinical Medicine, Shandong Provincial Hospital, Jinan, Shandong, China.
⁴ Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, Shandong, China.
⁵ China Australia Joint Laboratory for Animal Health Big Data Analytics, College of Animal Science and Technology, Zhejiang Agricultural and Forestry University, Hangzhou, China.
⁶ Research and Innovation Office, Murdoch University, Murdoch, Australia.
⁷ Institute of Microbiology and Epizootics, Centre for Infection Medicine, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
⁸ School of Health Care Management, Shandong University, Jinan, China.
⁹ NHC Key Laboratory of Health Economics and Policy Research (Shandong University), Jinan, China.
¹⁰ Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
¹¹ Public Health Agency of Sweden, Stockholm, Sweden.
¹² Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
¹³ Department of Medical Microbiology and Infectious Disease, Division of Infection and Immunity, Cardiff University, Cardiff, UK.
¹⁴ Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), Uppsala, Sweden.
¹⁵ Beijing Laboratory of Food Quality and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China.

PMID: 31642700
PMCID: PMC6910777
DOI: 10.1289/EHP5251

Inter-host Transmission of Carbapenemase-Producing Escherichia coli among Humans and Backyard Animals

Jiyun Li et al. Environ Health Perspect. 2019 Oct.

. 2019 Oct;127(10):107009.

doi: 10.1289/EHP5251. Epub 2019 Oct 23.

Authors

Affiliations

¹ Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China.
² College of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan, China.
³ Shandong Academy of Clinical Medicine, Shandong Provincial Hospital, Jinan, Shandong, China.
⁴ Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, Shandong, China.
⁵ China Australia Joint Laboratory for Animal Health Big Data Analytics, College of Animal Science and Technology, Zhejiang Agricultural and Forestry University, Hangzhou, China.
⁶ Research and Innovation Office, Murdoch University, Murdoch, Australia.
⁷ Institute of Microbiology and Epizootics, Centre for Infection Medicine, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
⁸ School of Health Care Management, Shandong University, Jinan, China.
⁹ NHC Key Laboratory of Health Economics and Policy Research (Shandong University), Jinan, China.
¹⁰ Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
¹¹ Public Health Agency of Sweden, Stockholm, Sweden.
¹² Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
¹³ Department of Medical Microbiology and Infectious Disease, Division of Infection and Immunity, Cardiff University, Cardiff, UK.
¹⁴ Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), Uppsala, Sweden.
¹⁵ Beijing Laboratory of Food Quality and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China.

PMID: 31642700
PMCID: PMC6910777
DOI: 10.1289/EHP5251

Erratum in

Erratum: "Inter-Host Transmission of Carbapenemase-Producing Escherichia coli among Humans and Backyard Animals".
Li J, Bi Z, Ma S, Chen B, Cai C, He J, Schwarz S, Sun C, Zhou Y, Yin J, Hulth A, Wang Y, Shen Z, Wang S, Wu C, Nilsson LE, Walsh TR, Börjesson S, Shen J, Sun Q, Wang Y. Li J, et al. Environ Health Perspect. 2020 Jan;128(1):19001. doi: 10.1289/EHP6660. Epub 2020 Jan 3. Environ Health Perspect. 2020. PMID: 31898924 Free PMC article. No abstract available.

Abstract

Background: The rapidly increasing dissemination of carbapenem-resistant Enterobacteriaceae (CRE) in both humans and animals poses a global threat to public health. However, the transmission of CRE between humans and animals has not yet been well studied.

Objectives: We investigated the prevalence, risk factors, and drivers of CRE transmission between humans and their backyard animals in rural China.

Methods: We conducted a comprehensive sampling strategy in 12 villages in Shandong, China. Using the household [residents and their backyard animals (farm and companion animals)] as a single surveillance unit, we assessed the prevalence of CRE at the household level and examined the factors associated with CRE carriage through a detailed questionnaire. Genetic relationships among human- and animal-derived CRE were assessed using whole-genome sequencing-based molecular methods.

Results: A total of 88 New Delhi $metallo- β -lactamases$ -type carbapenem-resistant Escherichia coli (NDM-EC), including 17 from humans, 44 from pigs, 12 from chickens, 1 from cattle, and 2 from dogs, were isolated from 65 of the 746 households examined. The remaining 12 NDM-EC were from flies in the immediate backyard environment. The NDM-EC colonization in households was significantly associated with a) the number of species of backyard animals raised/kept in the same household, and b) the use of human and/or animal feces as fertilizer. Discriminant analysis of principal components (DAPC) revealed that a large proportion of the core genomes of the NDM-EC belonged to strains from hosts other than their own, and several human isolates shared closely related core single-nucleotide polymorphisms and $b l a_{NDM}$ genetic contexts with isolates from backyard animals.

Conclusions: To our knowledge, we are the first to report evidence of direct transmission of NDM-EC between humans and animals. Given the rise of NDM-EC in community and hospital infections, combating NDM-EC transmission in backyard farm systems is needed. https://doi.org/10.1289/EHP5251.

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Figures

A schematic representation. The left is a process for sample collection, questionnaire analysis and bioinformatics analysis. The right is setting up a machine learning method for source predictions for carbenem-resistant E. coli. — **Figure 1.**
Schematic diagram of the research workflow. Note: cgSNP, core-genome single-nucleotide polymorphism; CRE, carbapenem-resistant Enterobacteriaceae; DAPC, discriminant analysis of principal components; WGS, whole-genome sequencing.

Map of China, with a scale of 0 to 2000 kilometers in increments of 1000. Further, CREC prevalence in 12 villages with respect to humans (0.0 to 1.3 percent, 1.3 to 2.5 percent, 2.5 to 3.8 percent, 3.8 to 5.0 percent, and 5.0 to 6.3 percent), pigs (0.0 to 5.5 percent, 5.5 to 10.9 percent, 10.9 to 16.4 percent, 16.4 to 21.8 percent, and 21.8 to 27.3 percent), chicken (0.0 to 4.2 percent, 4.2 to 8.3 percent, 8.3 to 12.5 percent, 12.5 to 16.6 percent, and 16.6 to 20.8 percent), dog (0.0 to 1.8 percent, 1.8 to 3.6 percent, 3.6 to 5.5 percent, 5.5 to 7.3 percent, and 7.3 to 9.1 percent), cattle (not collected, 0.0 to 12.7 percent, 12.7 to 19.6 percent, 19.6 to 26.4 percent, and 26.4 to 33.3 percent), and fly (0.0 to 4.4 percent, 4.4 to 8.9 percent, 8.9 to 13.3 percent, 13.3 to 17.8 percent, and 17.8 to 22.2 percent). — **Figure 2.**
Map of the sampling locations and CREC prevalence among humans, pigs, chickens, dogs, cattle and flies in the 12 villages (from village A to L). The white areas represent the un-selected neighboring villages and the letters A-L indicate the 12 selected villages in this study. The color gradation stands for the prevalence of CREC in different villages in different sample types.

Figure 3 comprises a phylogenetic tree to the left and a heatmap to the right. The left phylogenetic tree showed the phylogenetic realtionship of New Delhi metallo-beta-lactamases-type carbapenem-resistant E. coli (NDM-EC) isolates flowed by the isolates codes, distribution of phylogroup, MLST, villages and origin. The right heatmap showed the different antimicrobial resistance gene and virulence-associated genes that these E. coli carrried. — **Figure 3.**
Distribution of *Escherichia coli* phylogroups, multilocus sequence typing (MLST), antimicrobial-resistance, and virulence-associated genes among New Delhi $metallo- β -lactamases$ –type carbapenem-resistant *E. coli* (NDM-EC) isolates from humans and animals across the phylogenetic tree.

Figure 4A is a scatterplot for clusters of E. coli from human, pig, chicken, dog, and cattle. Figure 4B is a graphical representation plotting the prediction accuracy rate across origin for human, pig, chicken, dog, and cattle. Figure 4C comprises five pie diagrams. The distribution is as follows: For humans (n equals 50), 84, 8, 4, 2, and 2 percent. For pig (n equals 50), 78, 8, 6, 4, and 4 percent. For chicken (n equals 50), 54, 20, 12, 8, and 6 percent. For dog (n equals 28), 53, 29, 14, and 4 percent. For cattle (n equals 50), 92, 2, 2, 2, and 2 percent. Figure 4D is a graphical representation plotting membership probability (y-axis) across individuals (x-axis). Figure 4E comprises six horizontal bar graphs each for human, pig, fly, chicken, dog, and cattle. — **Figure 4.**
Source predictions for New Delhi $metallo- β -lactamases$ –type carbapenem-resistant *Escherichia coli* (NDM-EC) isolates using the DAPC model. (A) Scatterplot represents individuals as dots, and groups as inertia ellipses. (B) Testing validation: rows correspond to actual trait, and columns correspond to inferred trait. (C) Successful assignment rates for prediction of testing group. (D) Membership probability of individuals. Others include one cattle and two dogs. Red pentagram stands for *mcr-1*-positive NDM-EC. (E) Probable source of NDM-EC.

Figures 5A and 5B are conceptual diagrams. Figure 5A is a scene about production of Chinese rural villages. Pigs and cattle are kept in their own pens, while dog and chickens are free-ranged in the backyard and farmer are feeding chickens. There are vegetables, animal manure and well in the backyard as well. Humans, animals, vegetables and the water are polluted by NDM-EC bacteria. Figure 5B is possible transmission routes between human, animals (pigs, chicken, dogs, cattle) and environment (water, soil et al). — **Figure 5.**
Diagram showing possible transmission routes for New Delhi $metallo - β -lactamases$ –type carbapenem-resistant *Escherichia coli* (NDM-EC) among humans, animals, and environmental sources in the backyard farm. (A) The production mode in backyard farm in rural China. (B) Possible NDM-EC transmission routes.

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References

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1. Bai ZH, Ma L, Qin W, Chen Q, Oenema O, Zhang FS. 2014. Changes in pig production in China and their effects on nitrogen and phosphorus use and losses. Environ Sci Technol 48(21):12742–12749, PMID: 25292109, 10.1021/es502160v. - DOI - PubMed
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[1] Abao LN, Kono H, Gunarathne A, Promentilla RR, Gaerlan MZ. 2014. Impact of foot-and-mouth disease on pork and chicken prices in Central Luzon, Philippines. Prev Vet Med 113(4):398–406, PMID: 24433637, 10.1016/j.prevetmed.2013.12.005. - DOI - PubMed

[2] Abao LN, Kono H, Gunarathne A, Promentilla RR, Gaerlan MZ. 2014. Impact of foot-and-mouth disease on pork and chicken prices in Central Luzon, Philippines. Prev Vet Med 113(4):398–406, PMID: 24433637, 10.1016/j.prevetmed.2013.12.005. - DOI - PubMed

[3] Bai ZH, Ma L, Qin W, Chen Q, Oenema O, Zhang FS. 2014. Changes in pig production in China and their effects on nitrogen and phosphorus use and losses. Environ Sci Technol 48(21):12742–12749, PMID: 25292109, 10.1021/es502160v. - DOI - PubMed

[4] Bai ZH, Ma L, Qin W, Chen Q, Oenema O, Zhang FS. 2014. Changes in pig production in China and their effects on nitrogen and phosphorus use and losses. Environ Sci Technol 48(21):12742–12749, PMID: 25292109, 10.1021/es502160v. - DOI - PubMed

[5] Beghain J, Bridier-Nahmias A, Le Nagard H, Denamur E, Clermont O. 2018. ClermonTyping: an easy-to-use and accurate in silico method for Escherichia genus strain phylotyping. Microb Genom 4(7):e000192, PMID: 29916797, 10.1099/mgen.1090.000192. - DOI - PMC - PubMed

[6] Beghain J, Bridier-Nahmias A, Le Nagard H, Denamur E, Clermont O. 2018. ClermonTyping: an easy-to-use and accurate in silico method for Escherichia genus strain phylotyping. Microb Genom 4(7):e000192, PMID: 29916797, 10.1099/mgen.1090.000192. - DOI - PMC - PubMed

[7] Bravo-Vasquez N, Di Pillo F, Lazo A, Jiménez-Bluhm P, Schultz-Cherry S, Hamilton-West C. 2016. Presence of influenza viruses in backyard poultry and swine in El Yali wetland, Chile. Prev Vet Med 134:211–215, PMID: 27726887, 10.1016/j.prevetmed.2016.10.004. - DOI - PubMed

[8] Bravo-Vasquez N, Di Pillo F, Lazo A, Jiménez-Bluhm P, Schultz-Cherry S, Hamilton-West C. 2016. Presence of influenza viruses in backyard poultry and swine in El Yali wetland, Chile. Prev Vet Med 134:211–215, PMID: 27726887, 10.1016/j.prevetmed.2016.10.004. - DOI - PubMed

[9] Cars O, Xiao Y, Stålsby Lundborg C, Nilsson LE, Shen J, Sun Q, et al. . 2016. Building bridges to operationalise one health - a Sino-Swedish collaboration to tackle antibiotic resistance. One Health 2:139–143, PMID: 28616488, 10.1016/j.onehlt.2016.09.002. - DOI - PMC - PubMed

[10] Cars O, Xiao Y, Stålsby Lundborg C, Nilsson LE, Shen J, Sun Q, et al. . 2016. Building bridges to operationalise one health - a Sino-Swedish collaboration to tackle antibiotic resistance. One Health 2:139–143, PMID: 28616488, 10.1016/j.onehlt.2016.09.002. - DOI - PMC - PubMed

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Inter-host Transmission of Carbapenemase-Producing Escherichia coli among Humans and Backyard Animals

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Inter-host Transmission of Carbapenemase-Producing Escherichia coli among Humans and Backyard Animals

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