Statistical modelling based on structured surveys of Australian native possum excreta harbouring Mycobacterium ulcerans predicts Buruli ulcer occurrence in humans

  1. Koen Vandelannoote  Is a corresponding author
  2. Andrew H Buultjens
  3. Jessica L Porter
  4. Anita Velink
  5. John R Wallace
  6. Kim R Blasdell
  7. Michael Dunn
  8. Victoria Boyd
  9. Janet AM Fyfe
  10. Ee Laine Tay
  11. Paul DR Johnson
  12. Saras M Windecker
  13. Nick Golding
  14. Timothy P Stinear  Is a corresponding author
  1. University of Melbourne, Australia
  2. Millersville University, United States
  3. CSIRO Health and Biosecurity, Australia
  4. Victorian Infectious Diseases Reference Laboratory, Australia
  5. Department of Healt, Australia
  6. Austin Health, Australia
  7. Curtin University, Australia

Abstract

Background: Buruli ulcer (BU) is a neglected tropical disease caused by infection of subcutaneous tissue with Mycobacterium ulcerans. BU is commonly reported across rural regions of Central and West Africa but has been increasing dramatically in temperate southeast Australia around the major metropolitan city of Melbourne, with most disease transmission occurring in the summer months. Previous research has shown that Australian native possums are reservoirs of M. ulcerans and that they shed the bacteria in their fecal material (excreta). Field surveys show that locales where possums harbor M. ulcerans overlap with human cases of BU, raising the possibility of using possum excreta surveys to predict the risk of disease occurrence in humans.

Methods: We thus established a highly structured 12-month possum excreta surveillance program across an area of 350 km2 in the Mornington Peninsula area 70 km south of Melbourne, Australia. The primary objective of our study was to assess using statistical modelling if M. ulcerans surveillance of possum excreta provided useful information for predicting future human BU case locations.

Results: Over two sampling campaigns in summer and winter, we collected 2282 possum excreta specimens of which 11% were PCR positive for M. ulcerans-specific DNA. Using the spatial scanning statistical tool SaTScan, we observed non-random, co-correlated clustering of both M. ulcerans positive possum excreta and human BU cases. We next trained a statistical model with the Mornington Peninsula excreta survey data to predict the future likelihood of human BU cases occurring in the region. By observing where human BU cases subsequently occurred, we show that the excreta model performance was superior to a null model trained using the previous year's human BU case incidence data (AUC 0.66 vs 0.55). We then used data unseen by the excreta-informed model from a new survey of 661 possum excreta specimens in Geelong, a geographically separate BU endemic area to the southwest of Melbourne, to prospectively predict the location of human BU cases in that region. As for the Mornington Peninsula, the excreta-based BU prediction model outperformed the null model (AUC 0.75 vs 0.50) and pinpointed specific locations in Geelong where interventions could be deployed to interrupt disease spread.

Conclusions: This study highlights the One Health nature of BU by confirming a quantitative relationship between possum excreta shedding of M. ulcerans and humans developing BU. The excreta survey-informed modeling we have described will be a powerful tool for efficient targeting of public health responses to stop BU.

Funding: This research was supported by the National Health and Medical Research Council of Australia and the Victorian Government Department of Health (GNT1152807 and GNT1196396).

Data availability

The computer code and source data used in this study are available here: https://github.com/abuultjens/Possum_scat_survey_predict_human_BU.

Article and author information

Author details

  1. Koen Vandelannoote

    Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia
    For correspondence
    kvandelannoote@pasteur-kh.org
    Competing interests
    The authors declare that no competing interests exist.
  2. Andrew H Buultjens

    Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5984-1328
  3. Jessica L Porter

    Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  4. Anita Velink

    Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. John R Wallace

    Department of Biology, Millersville University, Millersville, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Kim R Blasdell

    CSIRO Health and Biosecurity, Geelong, Australia
    Competing interests
    The authors declare that no competing interests exist.
  7. Michael Dunn

    CSIRO Health and Biosecurity, Geelong, Australia
    Competing interests
    The authors declare that no competing interests exist.
  8. Victoria Boyd

    CSIRO Health and Biosecurity, Geelong, Australia
    Competing interests
    The authors declare that no competing interests exist.
  9. Janet AM Fyfe

    Doherty Institute for Infection and Immunity, Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  10. Ee Laine Tay

    Health Protection branch, Department of Healt, Victoria, Australia
    Competing interests
    The authors declare that no competing interests exist.
  11. Paul DR Johnson

    North Eastern Public Health Unit, Austin Health, Heidelberg, Australia
    Competing interests
    The authors declare that no competing interests exist.
  12. Saras M Windecker

    School of Ecosystem and Forest Sciences, University of Melbourne, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4870-8353
  13. Nick Golding

    Spatial Ecology and Epidemiology Group, Curtin University, Bentley, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8916-5570
  14. Timothy P Stinear

    Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia
    For correspondence
    tstinear@unimelb.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0150-123X

Funding

National Health and Medical Research Council (GNT1152807)

  • Timothy P Stinear

National Health and Medical Research Council (GNT1196396)

  • Timothy P Stinear

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

Ethics

Human subjects: Ethical approval for the use in this study of de-identified human BU case location, aggregated at mesh block level, was obtained from the Victorian Government Department of Health Human Ethics Committee under HREC/54166/DHHS-2019-179235(v3), "Spatial risk map of Buruli ulcer infection in Victoria".

Reviewing Editor

  1. Bavesh D Kana, University of the Witwatersrand, South Africa

Version history

  1. Preprint posted: November 17, 2022 (view preprint)
  2. Received: November 17, 2022
  3. Accepted: April 13, 2023
  4. Accepted Manuscript published: April 14, 2023 (version 1)
  5. Version of Record published: May 2, 2023 (version 2)

Copyright

© 2023, Vandelannoote 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. Koen Vandelannoote
  2. Andrew H Buultjens
  3. Jessica L Porter
  4. Anita Velink
  5. John R Wallace
  6. Kim R Blasdell
  7. Michael Dunn
  8. Victoria Boyd
  9. Janet AM Fyfe
  10. Ee Laine Tay
  11. Paul DR Johnson
  12. Saras M Windecker
  13. Nick Golding
  14. Timothy P Stinear
(2023)
Statistical modelling based on structured surveys of Australian native possum excreta harbouring Mycobacterium ulcerans predicts Buruli ulcer occurrence in humans
eLife 12:e84983.
https://doi.org/10.7554/eLife.84983

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