1. Epidemiology and Global Health
  2. Microbiology and Infectious Disease
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Transmission dynamics and control of multidrug-resistant Klebsiella pneumoniae in neonates in a developing country

  1. Thomas Crellen  Is a corresponding author
  2. Paul Turner
  3. Sreymom Pol
  4. Stephen Baker
  5. To Nguyen Thi Nguyen
  6. Nicole Stoesser
  7. Nicholas PJ Day
  8. Claudia Turner
  9. Ben S Cooper  Is a corresponding author
  1. Mahidol University, Thailand
  2. University of Oxford, United Kingdom
  3. Oxford University Clinical Research Unit, Viet Nam
Research Article
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Cite this article as: eLife 2019;8:e50468 doi: 10.7554/eLife.50468

Abstract

Multidrug-resistant Klebsiella pneumoniae is an increasing cause of infant mortality in developing countries. We aimed to develop a quantitative understanding of the drivers of this epidemic by estimating the effects of antibiotics on nosocomial transmission risk, comparing competing hypotheses about mechanisms of spread, and quantifying the impact of potential interventions. Using a sequence of dynamic models, we analysed data from a one-year prospective carriage study in a Cambodian neonatal unit with hyperendemic third-generation cephalosporin-resistant K. pneumoniae. All widely-used antibiotics except imipenem were associated with an increased daily acquisition risk, with an odds ratio for the most common combination (ampicillin + gentamicin) of 1.96 (95% CrI 1.18, 3.36). Models incorporating genomic data found that colonisation pressure was associated with a higher transmission risk, indicated sequence type heterogeneity in transmissibility, and showed that within-ward transmission was insufficient to maintain endemicity. Simulations indicated that increasing the nurse-patient ratio could be an effective intervention.

Data availability

Code for reproducing the statisticalmodel fitting and anonymised patient data are available at https://github.com/tc13/transmission-dynamics-klebsiella. The code for the agent based model and parameter values for forward simulations are available at https://github.com/tc13/ward-infection-ABM. Short read sequence data is available from NCBI under accession numbers PRJNA395864 and PR600JEB24970.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Thomas Crellen

    Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    For correspondence
    thomas.crellen@ndm.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2934-1063

  2. Paul Turner

    Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1013-7815

  3. Sreymom Pol

    Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.

  4. Stephen Baker

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1308-5755

  5. To Nguyen Thi Nguyen

    Centre for Tropical Medicine, Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam
    Competing interests
    The authors declare that no competing interests exist.

  6. Nicole Stoesser

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  7. Nicholas PJ Day

    Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.

  8. Claudia Turner

    Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.

  9. Ben S Cooper

    Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    For correspondence
    Ben@tropmedres.ac
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9445-7217

Funding

Wellcome (106698/Z/14/Z)

  • Nicholas PJ Day

Medical Research Council (MR/K006924/1)

  • Ben S Cooper

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Written consent was obtained from mothers before study enrolment. The study was reviewed and approved by the Angkor Hospital for Children Institutional Review Board (1055/13 AHC) and the University of Oxford Tropical Ethics Committee (1047-13).

Reviewing Editor

  1. Miles P Davenport, University of New South Wales, Australia

Publication history

  1. Received: July 25, 2019
  2. Accepted: November 26, 2019
  3. Accepted Manuscript published: December 3, 2019 (version 1)
  4. Version of Record published: January 23, 2020 (version 2)

Copyright

© 2019, Crellen 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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Further reading

    1. Epidemiology and Global Health
    2. Medicine

    A high rate of COVID-19 vaccine hesitancy in a large-scale survey on Arabs

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    Vaccine hesitancy can limit the benefits of available vaccines in halting the spread of COVID-19 pandemic. Previously published studies paid little attention to Arab countries, which has a population of over 440 million. In this study, we present the results of the first large-scale multinational study that measures vaccine hesitancy among Arab-speaking subjects.

    Methods:

    An online survey in Arabic was conducted from 14 January 2021 to 29 January 2021. It consisted of 17 questions capturing demographic data, acceptance of COVID-19 vaccine, attitudes toward the need for COVID-19 vaccination and associated health policies, and reasons for vaccination hesitancy. R software v.4.0.2 was used for data analysis and visualization.

    Results:

    The survey recruited 36,220 eligible participants (61.1% males, 38.9% females, mean age 32.6 ± 10.8 years) from all the 23 Arab countries and territories (83.4%) and 122 other countries (16.6%). Our analysis shows a significant rate of vaccine hesitancy among Arabs in and outside the Arab region (83% and 81%, respectively). The most cited reasons for hesitancy are concerns about side effects and distrust in health care policies, vaccine expedited production, published studies and vaccine producing companies. We also found that female participants, those who are 30–59 years old, those with no chronic diseases, those with lower level of academic education, and those who do not know the type of vaccine authorized in their countries are more hesitant to receive COVID-19 vaccination. On the other hand, participants who regularly receive the influenza vaccine, health care workers, and those from countries with higher rates of COVID-19 infections showed more vaccination willingness. Interactive representation of our results is posted on our project website at https://mainapp.shinyapps.io/CVHAA.

    Conclusions:

    Our results show higher vaccine hesitancy and refusal among Arab subjects, related mainly to distrust and concerns about side effects. Health authorities and Arab scientific community have to transparently address these concerns to improve vaccine acceptance.

    Funding:

    This study received no funding.

    1. Epidemiology and Global Health

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    Background:

    The US Food and Drug Administration authorized COVID-19 convalescent plasma (CCP) therapy for hospitalized COVID-19 patients via the Expanded Access Program (EAP) and the Emergency Use Authorization (EUA), leading to use in about 500,000 patients during the first year of the pandemic for the USA.

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    Conclusions:

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    Funding:

    There was no specific funding for this study. AC was supported in part by RO1 HL059842 and R01 AI1520789; MJJ was supported in part by 5R35HL139854. This project has been funded in whole or in part with Federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority under Contract No. 75A50120C00096.

    1. Epidemiology and Global Health

    High infectiousness immediately before COVID-19 symptom onset highlights the importance of continued contact tracing

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    Background:

    Understanding changes in infectiousness during SARS-COV-2 infections is critical to assess the effectiveness of public health measures such as contact tracing.

    Methods:

    Here, we develop a novel mechanistic approach to infer the infectiousness profile of SARS-COV-2-infected individuals using data from known infector–infectee pairs. We compare estimates of key epidemiological quantities generated using our mechanistic method with analogous estimates generated using previous approaches.

    Results:

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    High infectiousness immediately prior to symptom onset highlights the importance of continued contact tracing until effective vaccines have been distributed widely, even if contacts from a short time window before symptom onset alone are traced.

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    Engineering and Physical Sciences Research Council (EPSRC).