Statistical modelling based on structured surveys of Australian native possum excreta harbouring Mycobacterium ulcerans predicts Buruli ulcer occurrence in humans
- University of Melbourne, Australia
- Millersville University, United States
- CSIRO Health and Biosecurity, Australia
- Victorian Infectious Diseases Reference Laboratory, Australia
- Department of Healt, Australia
- Austin Health, Australia
- 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
Andrew H Buultjens
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
- Bavesh D Kana, University of the Witwatersrand, South Africa
Version history
- Preprint posted: November 17, 2022 (view preprint)
- Received: November 17, 2022
- Accepted: April 13, 2023
- Accepted Manuscript published: April 14, 2023 (version 1)
- 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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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
Further reading
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- Epidemiology and Global Health
Background:
In most of the world, the mammography screening programmes were paused at the start of the pandemic, whilst mammography screening continued in Denmark. We examined the mammography screening participation during the COVID-19 pandemic in Denmark.
Methods:
The study population comprised all women aged 50–69 years old invited to participate in mammography screening from 2016 to 2021 in Denmark based on data from the Danish Quality Database for Mammography Screening in combination with population-based registries. Using a generalised linear model, we estimated prevalence ratios (PRs) and 95% confidence intervals (CIs) of mammography screening participation within 90, 180, and 365 d since invitation during the pandemic in comparison with the previous years adjusting for age, year and month of invitation.
Results:
The study comprised 1,828,791 invitations among 847,766 women. Before the pandemic, 80.2% of invitations resulted in participation in mammography screening within 90 d, 82.7% within 180 d, and 83.1% within 365 d. At the start of the pandemic, the participation in screening within 90 d was reduced to 69.9% for those invited in pre-lockdown and to 76.5% for those invited in first lockdown. Extending the length of follow-up time to 365 d only a minor overall reduction was observed (PR = 0.94; 95% CI: 0.93–0.95 in pre-lockdown and PR = 0.97; 95% CI: 0.96–0.97 in first lockdown). A lower participation was, however, seen among immigrants and among women with a low income.
Conclusions:
The short-term participation in mammography screening was reduced at the start of the pandemic, whilst only a minor reduction in the overall participation was observed with longer follow-up time, indicating that women postponed screening. Some groups of women, nonetheless, had a lower participation, indicating that the social inequity in screening participation was exacerbated during the pandemic.
Funding:
The study was funded by the Danish Cancer Society Scientific Committee (grant number R321-A17417) and the Danish regions.
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- Epidemiology and Global Health
- Genetics and Genomics
Accurate inference of who infected whom in an infectious disease outbreak is critical for the delivery of effective infection prevention and control. The increased resolution of pathogen whole-genome sequencing has significantly improved our ability to infer transmission events. Despite this, transmission inference often remains limited by the lack of genomic variation between the source case and infected contacts. Although within-host genetic diversity is common among a wide variety of pathogens, conventional whole-genome sequencing phylogenetic approaches exclusively use consensus sequences, which consider only the most prevalent nucleotide at each position and therefore fail to capture low frequency variation within samples. We hypothesized that including within-sample variation in a phylogenetic model would help to identify who infected whom in instances in which this was previously impossible. Using whole-genome sequences from SARS-CoV-2 multi-institutional outbreaks as an example, we show how within-sample diversity is partially maintained among repeated serial samples from the same host, it can transmitted between those cases with known epidemiological links, and how this improves phylogenetic inference and our understanding of who infected whom. Our technique is applicable to other infectious diseases and has immediate clinical utility in infection prevention and control.
