1. Saw Swee Hock School of Public Health, National University of Singapore, Singapore; 2. Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam; 3. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, UK
Hao Chung The1,2,3, Kithalakshmi Vignesvaran1,4, Wei Cong Tan4,5, Rebecca Perez1,3, Natascha May Thevasagayam6, Rick Twee-Hee Ong1, Jonathan Lee Wei Jie5, Niranjan Nagarajan5,7, Melissa Sin Hui Chua4, En Ying Tan4, Si Yu Peng4, Lingyue Zhou4, Shweta Rajkumar Singh1, Wesley Yeung4, Ivan Seah4, Jeanette Teo4, Kyaw Thu Aung8, Paul Anantharajah Tambyah4,5, Kalisvar Marimuthu6,9, Oon Tek Ng6,9, Yin Mo1,3,4,5,10
1 Saw Swee Hock School of Public Health, National University of Singapore, Singapore
2 Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
3 Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford
4 Division of Infectious Diseases, University Medicine Cluster, National University Hospital, Singapore, Singapore
5 Yong Loo Lin School of Medicine, National University of Singapore, Singapore
6 National Centre for Infectious Diseases, Singapore
7 Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore
8 Environmental Health Institute, National Environment Agency, Singapore
9 Tan Tock Seng Hospital, Singapore
10 Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Extended-spectrum beta-lactamase (ESBL) genes, which confer resistance to third-generation cephalosporins in Gram-negative bacteria, are widely disseminated globally through the expansion of successful bacterial clones and mobile plasmids. Chief among the notorious clones is Escherichia coli sequence type 131 (ST131), which inflicts a major burden of community-onset, multidrug resistant extraintestinal infections. Nevertheless, it remains poorly understood in (1) how E. coli ST131 transmits in the community, and (2) what is the relative contribution of clone versus plasmid in mediating ESBL transmission. To answer these questions, we conducted a prospective household cohort study in Singapore, where we enrolled index patients with prior extraintestinal E. coli infections and their household coresidents. Longitudinal stool samples were collected from 135 human participants, six companion animals and environmental swabs from 34 households, from which we isolated >6,500 E. coli isolates. We identified nine carriers who persistently carried E. coli ST131 in high densities for a median carriage duration of 86.35 days (80% credible interval 30.03 – 188.80). Persistent carriers and their coresidents carried genetically similar E. coli ST131 isolates (median single nucleotide polymorphism distance of 2), confirming inter-individual transmission within households. Furthermore, when analysing 393 E. coli genomes from four high ESBL-burden households in depth (2,814 observation participant-days), we found comparable frequencies of clonal and plasmid transmissions (6.1% vs 7.3% of total sequenced bacterial clones/plasmid groups). However, ESBL clonal transmission affected 8 individuals (421 continuous ESBL-positive days), as opposed to 2 individuals (80 days) by ESBL plasmid transmission. Our results highlight asymptomatic persistent carriers as potential reservoirs sustaining ESBL-producing E. coli transmissions, and that ESBL transmissions via clonal propagation had a greater impact compared to that mediated by plasmid horizontal transfer. These findings thus offer potential targets for public health interventions to limit the spread of multidrug resistance.
Dr. Hao Chung The is a senior postdoc fellow in the Molecular Epidemiology Group at the Oxford University Clinical Research Unit (OUCRU) Vietnam, and a visiting senior research fellow at Saw Swee Hock School of Public Health in National University of Singapore (NUS). A trained microbiologist fascinated at how microbes evolve and interact with human, his research combines clinical studies with microbial genomics, metagenomics and molecular biology to address questions in infectious disease epidemiology and evolution, and to translate understandings in bacterial evolution and ecology into better approaches in healthcare.
His works have been published in high impact journals including Nature Communications, PLoS Medicine and npj Biofilms and Microbiomes, with a focus on antimicrobial resistance, genomic epidemiology, bacterial evolution and human disease microbiomes. He has been collaborating with hospitals and researchers in Vietnam and Southeast Asia in antimicrobial resistance and microbiome research, mentoring students and junior researchers, and strengthening research and bioinformatic capacity. Hao has also served as member for WHO Bacterial CORC on Klebsiella pneumoniae, Wellcome Microbiome workshop: Discovering barriers to interventions, and Antimicrobial Chemotherapy Conference.
Presenting author details:
Full name: Chung The Hao
Contact number: +84 96 9937 143 (WhatsApp/Zalo)
Email: haoct@oucru.org
Linkedin: linkedin.com/in/hao-chung-the
Researchgate: researchgate.net/profile/Hao-Chung-2
Google scholar: https://scholar.google.com/citations?user=-_1uYGwAAAAJ&hl=en
ORCID: https://orcid.org/0000-0002-4028-4074
Website: https://www.oucru.org/research/molecular-epidemiology/