04262nas a2200373 4500000000100000008004100001260003700042653004000079653005700119653002100176653002500197653001700222653002700239653002900266100002000295700001700315700001400332700001300346700001500359700001600374700001100390700001100401700001200412700001100424700001500435700001700450700001400467700001500481245016700496856026000663490000700923520294400930022001403874 2023 d beLife Sciences Publications, Ltd10aGeneral Immunology and Microbiology10aGeneral Biochemistry, Genetics and Molecular Biology10aGeneral Medicine10aGeneral Neuroscience10aBuruli ulcer10aMycobacterium ulcerans10aAustralian native possum1 aVandelannoote K1 aBuultjens AH1 aPorter JL1 aVelink A1 aWallace JR1 aBlasdell KR1 aDunn M1 aBoyd V1 aFyfe JA1 aTay EL1 aJohnson PD1 aWindecker SM1 aGolding N1 aStinear TP00aStatistical modelling based on structured surveys of Australian native possum excreta harbouring Mycobacterium ulcerans predicts Buruli ulcer occurrence in humans uhttps://elifesciences.org/download/aHR0cHM6Ly9jZG4uZWxpZmVzY2llbmNlcy5vcmcvYXJ0aWNsZXMvODQ5ODMvZWxpZmUtODQ5ODMtdjEucGRmP2Nhbm9uaWNhbFVyaT1odHRwczovL2VsaWZlc2NpZW5jZXMub3JnL2FydGljbGVzLzg0OTgz/elife-84983-v1.pdf?_hash=w%2FQF%2BNwAVQhyH8b0%2Fo7gZq4iQkyf00ON0 v123 a

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).

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