Improved characterisation of MRSA transmission using within-host bacterial sequence diversity
- University of Oxford, United Kingdom
- University of St Andrews, United Kingdom
- Sunpasitthiprasong Hospital, Thailand
- Mahidol University, Thailand
- University of Bath, United Kingdom
- University of Cambridge, United Kingdom
- Cambridge University Hospitals NHS Foundation Trust, United Kingdom
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) transmission in the hospital setting has been a frequent subject of investigation using bacterial genomes, but previous approaches have not yet fully utilised the extra deductive power provided when multiple pathogen samples are acquired from each host. Here, we use a large dataset of MRSA sequences from multiply-sampled patients to reconstruct colonisation of individuals in a high-transmission setting in a hospital in Thailand. We reconstructed transmission trees for MRSA. We also investigated transmission between anatomical sites on the same individual, finding that this either occurs repeatedly or involves a wide transmission bottleneck. We examined the between-subject bottleneck, finding a wide range in the amount of diversity transmitted. Finally, we compared our approach to the simpler method of identifying transmission pairs using single nucleotide polymorphism (SNP) counts. This suggested that the optimum threshold for identifying a pair is 39 SNPs, if sensitivities and specificities are equally weighted.
Data availability
Illumina read data is available in the European Nucleotide Archive as part of study accession number PRJEB4140. Genome assemblies will be made available prior to publication. We are unable to provide patient data for reasons of confidentiality.
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Staphylococcus aureus ST239 diversity in ThailandEuropean Nucleotide Archive, PRJEB4140.
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Evolution of MRSA During Hospital Transmission and Intercontinental SpreadEuropean Nucleotide Archive, PRJEB2489.
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Staphylococcus aureus ST239 diversityEuropean Nucleotide Archive, PRJEB2076.
Article and author information
Author details
Direk Limmathurotsakul
Funding
Wellcome (098051)
- Matthew TG Holden
- Sharon J Peacock
Chief Scientist Office (SIRN10)
- Matthew TG Holden
Wellcome (106698/Z/14/Z)
- Vanaporn Wuthiekanun
Medical Research Council (G1000803)
- Sharon J Peacock
European Research Council (PBDR-339251)
- Matthew D Hall
- Christophe Fraser
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Mark Jit, London School of Hygiene & Tropical Medicine, and Public Health England, United Kingdom
Ethics
Human subjects: Ethical approval was obtained from the Ethical and Scientific Review subcommittee of the Royal Thai Government Ministry of Public Health (85/2550), and the Oxford Tropical Research Ethics Committee (024 07). All patients admitted to the two ICUs were eligible for inclusion and were enrolled after written informed consent, and consent to publish, was obtained.
Version history
- Received: February 26, 2019
- Accepted: October 1, 2019
- Accepted Manuscript published: October 8, 2019 (version 1)
- Accepted Manuscript updated: October 11, 2019 (version 2)
- Version of Record published: January 10, 2020 (version 3)
- Version of Record updated: January 14, 2020 (version 4)
Copyright
© 2019, Hall et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Improved characterisation of MRSA transmission using within-host bacterial sequence diversity
eLife 8:e46402.
https://doi.org/10.7554/eLife.46402
Further reading
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- Epidemiology and Global Health
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Background: Few national-level studies have evaluated the impact of 'hybrid' immunity (vaccination coupled with recovery from infection) from the Omicron variants of SARS-CoV-2.
Methods: From May 2020 to December 2022, we conducted serial assessments (each of ~4000-9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels.
Results: Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than six months earlier, spike levels fell notably and continuously for the nine months post-vaccination. By contrast, among adults infected within six months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than six months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% CI 11-14%) before omicron to 78% (76-80%) by December 2022, equating to 25 million infected adults cumulatively. However, the COVID-19 weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity.
Conclusions: Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected dried blood spots are a practicable biological surveillance platform.
Funding: Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael's Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.
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The chemical composition of foods is complex, variable, and dependent on many factors. This has a major impact on nutrition research as it foundationally affects our ability to adequately assess the actual intake of nutrients and other compounds. In spite of this, accurate data on nutrient intake are key for investigating the associations and causal relationships between intake, health, and disease risk at the service of developing evidence-based dietary guidance that enables improvements in population health. Here, we exemplify the importance of this challenge by investigating the impact of food content variability on nutrition research using three bioactives as model: flavan-3-ols, (–)-epicatechin, and nitrate. Our results show that common approaches aimed at addressing the high compositional variability of even the same foods impede the accurate assessment of nutrient intake generally. This suggests that the results of many nutrition studies using food composition data are potentially unreliable and carry greater limitations than commonly appreciated, consequently resulting in dietary recommendations with significant limitations and unreliable impact on public health. Thus, current challenges related to nutrient intake assessments need to be addressed and mitigated by the development of improved dietary assessment methods involving the use of nutritional biomarkers.
