External validation of a mobile clinical decision support system for diarrhea etiology prediction in children: a multicenter study in Bangladesh and Mali

  1. Stephanie Chow Garbern  Is a corresponding author
  2. Eric J Nelson
  3. Sabiha Nasrin
  4. Adama Mamby Keita
  5. Ben J Brintz
  6. Monique Gainey
  7. Henry Badji
  8. Dilruba Nasrin
  9. Joel Howard
  10. Mami Taniuchi
  11. James A Platts-Mills
  12. Karen L Kotloff
  13. Rashidul Haque
  14. Adam C Levine
  15. Samba O Sow
  16. Nur Haque Alam
  17. Daniel T Leung  Is a corresponding author
  1. Brown University, United States
  2. University of Florida, United States
  3. International Centre for Diarrhoeal Disease Research, Bangladesh
  4. Centre for Vaccine Development, Mali
  5. University of Utah, United States
  6. Rhode Island Hospital, United States
  7. Center for Vaccine Development, Mali
  8. University of Maryland School of Medicine, United States
  9. University of Kentucky, United States
  10. University of Virginia, United States
  11. University of Maryland, United States

Abstract

Background: Diarrheal illness is a leading cause of antibiotic use for children in low- and middle-income countries. Determination of diarrhea etiology at the point-of-care without reliance on laboratory testing has the potential to reduce inappropriate antibiotic use.

Methods: This prospective observational study aimed to develop and externally validate the accuracy of a mobile software application ('App') for the prediction of viral-only etiology of acute diarrhea in children 0-59 months in Bangladesh and Mali. The App used a previously derived and internally validated model consisting of patient-specific ('present patient') clinical variables (age, blood in stool, vomiting, breastfeeding status, and mid-upper arm circumference) as well as location-specific viral diarrhea seasonality curves. The performance of additional models using the 'present patient' data combined with other external data sources including location-specific climate, data, recent patient data, and historical population-based prevalence were also evaluated in secondary analysis. Diarrhea etiology was determined with TaqMan Array Card using episode-specific attributable fraction (AFe) >0.5.

Results: Of 302 children with acute diarrhea enrolled, 199 had etiologies above the AFe threshold. Viral-only pathogens were detected in 22% of patients in Mali and 63% in Bangladesh. Rotavirus was the most common pathogen detected (16% Mali; 60% Bangladesh). The present patient + viral seasonality model had an AUC of 0.754 (0.665-0.843) for the sites combined, with calibration-in-the-large α=-0.393 (-0.455 - -0.331) and calibration slope β=1.287 (1.207 - 1.367). By site, the present patient + recent patient model performed best in Mali with an AUC of 0.783 (0.705 - 0.86); the present patient + viral seasonality model performed best in Bangladesh with AUC 0.710 (0.595 - 0.825).

Conclusion: The App accurately identified children with high likelihood of viral-only diarrhea etiology. Further studies to evaluate the App's potential use in diagnostic and antimicrobial stewardship are underway.

Funding: Funding for this study was provided through grants from the Bill and Melinda Gates Foundation (OPP1198876) and the National Institute of Allergy and Infectious Diseases (R01AI135114). Several investigators were also partially supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK116163). This investigation was also supported by the University of Utah Population Health Research (PHR) Foundation, with funding in part from the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR002538. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in the study design, data collection, data analysis, interpretation of data, or in the writing or decision to submit the manuscript for publication.

Data availability

The de-identified dataset is included as Supplementary File 5 and has been deposited on Dryad. The modeling code and additional files needed to run the code are deposited on GitHub at https://github.com/LeungLab/DiaPR_Phase1

The following data sets were generated

Article and author information

Author details

  1. Stephanie Chow Garbern

    Department of Emergency Medicine, Brown University, Providence, United States
    For correspondence
    sgarbern@brown.edu
    Competing interests
    Stephanie Chow Garbern, received consultancy fees from the University of Utah, in relation to project Development of clinical decision tools for management of diarrhea of children in high and low resource settings" (R01AI135114.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0919-2841
  2. Eric J Nelson

    Department of Pediatrics, University of Florida, Gainesville, United States
    Competing interests
    Eric J Nelson, is associated with a patent on data collection components in the 'Outbreak Responder' (Patent Publication Number 2020/0082921), of which the original 'Rehydration Calculator' was a component. These components are not included in the software referenced and published herein. Has no financial interest in the 'Rehydration Calculator' herein or the original 'Outbreak Responder' software..
  3. Sabiha Nasrin

    International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
    Competing interests
    No competing interests declared.
  4. Adama Mamby Keita

    Centre for Vaccine Development, Bamako, Mali
    Competing interests
    No competing interests declared.
  5. Ben J Brintz

    Department of Internal Medicine, University of Utah, Salt Lake City, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4695-0290
  6. Monique Gainey

    Department of Emergency Medicine, Rhode Island Hospital, Providence, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2860-9104
  7. Henry Badji

    Center for Vaccine Development, Bamako, Mali
    Competing interests
    No competing interests declared.
  8. Dilruba Nasrin

    Center for Vaccine Development and Global Healt, University of Maryland School of Medicine, Baltimore, United States
    Competing interests
    Dilruba Nasrin, received travel funding for training and monitoring data collection in Mali. The author has no other competing interests to declare..
  9. Joel Howard

    Department of Pediatrics, University of Kentucky, Lexington, United States
    Competing interests
    No competing interests declared.
  10. Mami Taniuchi

    Department of Medicine, University of Virginia, Charlottesville, United States
    Competing interests
    No competing interests declared.
  11. James A Platts-Mills

    Department of Medicine, University of Virginia, Charlottesville, United States
    Competing interests
    No competing interests declared.
  12. Karen L Kotloff

    Department of Pediatrics, University of Maryland, Baltimore, United States
    Competing interests
    No competing interests declared.
  13. Rashidul Haque

    International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
    Competing interests
    No competing interests declared.
  14. Adam C Levine

    Department of Emergency Medicine, Brown University, Providence, United States
    Competing interests
    Adam C Levine, received consultancy fees from the University of Utah, in relation to project Development of clinical decision tools for management of diarrhea of children in high and low resource settings" (R01AI135114.
  15. Samba O Sow

    Center for Vaccine Development, Bamako, Mali
    Competing interests
    No competing interests declared.
  16. Nur Haque Alam

    International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
    Competing interests
    No competing interests declared.
  17. Daniel T Leung

    Internal Medicine (Infectious Diseases), University of Utah, Salt Lake City, United States
    For correspondence
    daniel.leung@utah.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8401-0801

Funding

Bill and Melinda Gates Foundation (OPP1198876)

  • Daniel T Leung

National Institute of Allergy and Infectious Diseases (R01AI135114)

  • Daniel T Leung

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK116163)

  • Monique Gainey

National Center for Advancing Translational Sciences (UL1TR002538)

  • Ben J Brintz

National Institutes of Health (R21TW010182)

  • Eric J Nelson

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

Ethics

Human subjects: Informed consent was obtained from all study participants as described in Materials and Methods. Ethical approval was obtained from the icddr,b Ethical Review Committee (PR-19095), the University of Sciences, Techniques, and Technologies of Bamako Ethics Committee (2019-153), and the University of Utah Institutional Review Board (IRB_00121790).

Reviewing Editor

  1. Joshua T Schiffer, Fred Hutchinson Cancer Research Center, United States

Publication history

  1. Received: July 18, 2021
  2. Preprint posted: August 1, 2021 (view preprint)
  3. Accepted: February 5, 2022
  4. Accepted Manuscript published: February 9, 2022 (version 1)
  5. Version of Record published: March 8, 2022 (version 2)

Copyright

© 2022, Garbern 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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  1. Stephanie Chow Garbern
  2. Eric J Nelson
  3. Sabiha Nasrin
  4. Adama Mamby Keita
  5. Ben J Brintz
  6. Monique Gainey
  7. Henry Badji
  8. Dilruba Nasrin
  9. Joel Howard
  10. Mami Taniuchi
  11. James A Platts-Mills
  12. Karen L Kotloff
  13. Rashidul Haque
  14. Adam C Levine
  15. Samba O Sow
  16. Nur Haque Alam
  17. Daniel T Leung
(2022)
External validation of a mobile clinical decision support system for diarrhea etiology prediction in children: a multicenter study in Bangladesh and Mali
eLife 11:e72294.
https://doi.org/10.7554/eLife.72294

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