Dynamics of intestinal multidrug-resistant bacteria colonisation contracted by visitors to a high-endemic setting: a prospective, daily, real-time sampling study

Research output: Contribution to journalArticlepeer-review

Authors

  • Anu Kantele
  • Esther Kuenzli
  • David A B Dance
  • Paul N Newton
  • Viengmon Davong
  • Sointu Mero
  • Sari H Pakkanen
  • Andreas Neumayr
  • Christoph Hatz
  • Ann Snaith
  • Teemu Kallonen
  • Jukka Corander

Colleges, School and Institutes

External organisations

  • Swiss Tropical and Public Health Institute (Swiss TPH)
  • University of Oxford
  • Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit
  • University of Basel
  • University of Zurich
  • London School of Hygiene and Tropical Medicine
  • University of Helsinki
  • Cantonal Hospital
  • University of Oslo

Abstract

Background: Antimicrobial resistance is highly prevalent in low-income and middle-income countries. International travel contributes substantially to the global spread of intestinal multidrug-resistant Gram-negative bacteria. Hundreds of millions of annual visitors to low-income and middle-income countries are all exposed to intestinal multidrug-resistant Gram-negative bacteria resulting in 30-70% of them being colonised at their return. The colonisation process in high-exposure environments is poorly documented because data have only been derived from before travel and after travel sampling. We characterised colonisation dynamics by exploring daily stool samples while visiting a low-income and middle-income countries.

Methods: In this prospective, daily, real-time sampling study 20 European visitors to Laos volunteered to provide daily stool samples and completed daily questionnaires for 22 days. Samples were initially assessed at Mahosot Hospital, Vientiane, Laos, for acquisition of extended-spectrum β-lactamase-producing (ESBL) Gram-negative bacteria followed by whole-genome sequencing of isolates at MicrobesNG, University of Birmingham, Birmingham, UK. The primary outcome of the study was to obtain data on the dynamics of intestinal multidrug-resistant bacteria acquisition.

Findings: Between Sept 18 and Sept 20, 2015, 23 volunteers were recruited, of whom 20 (87%) European volunteers were included in the final study population. Although colonisation rates were 70% at the end of the study, daily sampling revealed that all participants had acquired ESBL-producing Gram-negative bacteria at some point during the study period; the colonisation status varied day by day. Whole-genome sequencing analysis ascribed the transient pattern of colonisation to sequential acquisition of new strains, resulting in a loss of detectable colonisation by the initial multidrug-resistant Gram-negative strains. 19 (95%) participants acquired two to seven strains. Of the 83 unique strains identified (53 Escherichia coli, 10 Klebsiella spp, and 20 other ESBL-producing Gram-negative bacteria), some were shared by as many as four (20%) participants.

Interpretation: To our knowledge, this is the first study to characterise in real-time the dynamics of acquiring multidrug-resistant Gram-negative bacterial colonisation during travel. Our data show multiple transient colonisation events indicative of constant microbial competition and suggest that travellers are exposed to a greater burden of multidrug-resistant bacteria than previously thought. The data emphasise the need for preventing travellers' diarrhoea and limiting antibiotic use, addressing the two major factors predisposing colonisation.

Funding: The Finnish Governmental Subsidy for Health Science Research, The Scandinavian Society for Antimicrobial Chemotherapy, the Sigrid Jusélius Foundation, Biotechnology and Biological Sciences Research Council; Wellcome Trust, Medical Research Council; The Royal Society; Joint Programming Initiative on Antimicrobial Resistance, and European Research Council.

Bibliographic note

Funding Information: AK reports investigator-initiated grants from Pfizer and Valneva, outside submitted work. All other authors declare no competing interests. Funding Information: AK was supported by the Finnish Governmental Subsidy for Health Science Research, the Scandinavian Society for Antimicrobial Chemotherapy Foundation, the Sigrid Jusélius Foundation, and the Finnish Cultural Foundation. SJD and AM were funded by Biotechnology and Biological Sciences Research Council (BBR0062611). AS was funded by the Wellcome trust (108876B15Z). AM was also funded by the Medical Research Council (MRS0136601) and The Royal Society (NA150363). TK and JC were supported by Joint Programming Initiative on Antimicrobial Resistance grant Spark from Norwegian Research Council. JC was also supported by European Research Council (742158). We are very grateful to the volunteers and the staff of the Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos, who processed the samples. AM and JC obtained funding for whole-genome sequencing from The Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK. We are also grateful for the support for the work of the Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit by the directors and staff of Mahosot Hospital and the Ministry of Health, Lao.

Details

Original languageEnglish
Pages (from-to)e151-e158
Number of pages8
JournalThe Lancet. Microbe
Volume2
Issue number4
Early online date23 Feb 2021
Publication statusPublished - Apr 2021