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Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis

Nature Microbiology volume 1, Article number: 15008 (2016) Cite this article

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Abstract

Burkholderia pseudomallei, a highly pathogenic bacterium that causes melioidosis, is commonly found in soil in Southeast Asia and Northern Australia1,2. Melioidosis can be difficult to diagnose due to its diverse clinical manifestations and the inadequacy of conventional bacterial identification methods3. The bacterium is intrinsically resistant to a wide range of antimicrobials, and treatment with ineffective antimicrobials may result in case fatality rates (CFRs) exceeding 70%4,5. The importation of infected animals has, in the past, spread melioidosis to non-endemic areas6,7. The global distribution of B. pseudomallei and the burden of melioidosis, however, remain poorly understood. Here, we map documented human and animal cases and the presence of environmental B. pseudomallei and combine this in a formal modelling framework8–10 to estimate the global burden of melioidosis. We estimate there to be 165,000 (95% credible interval 68,000–412,000) human melioidosis cases per year worldwide, from which 89,000 (36,000–227,000) people die. Our estimates suggest that melioidosis is severely underreported in the 45 countries in which it is known to be endemic and that melioidosis is probably endemic in a further 34 countries that have never reported the disease. The large numbers of estimated cases and fatalities emphasize that the disease warrants renewed attention from public health officials and policy makers.

Melioidosis is a disease of public health importance in areas of Southeast Asia and Australia, and is considered a potential emerging infectious disease in many tropical developing countries11. In northeast Thailand, there are around 2,000 culture-confirmed melioidosis cases per year, with a case fatality rate (CFR) of 40%12. In Singapore, 550 melioidosis cases have occurred during the last ten years, of which a fifth resulted in death13. Skin inoculation is considered the main route of infection in agricultural workers in developing countries14. Recent evidence also suggests that inhalation of Burkholderia pseudomallei during extreme weather events15,16 and ingestion of B. pseudomallei contaminated water are also important routes of infection17. High-risk groups include patients with diabetes mellitus, chronic kidney disease and excessive alcohol intake12,18. Developed countries are also observing an emergence of melioidosis related to travelling and importation of cases11. No licensed vaccine for melioidosis is currently available. Strengthening of microbiological laboratories and research facilities often results in the discovery of B. pseudomallei in new areas, with recent national additions including India, southern China, Brazil and Malawi11,19. Given diagnostic limitations3, it is likely that B. pseudomallei is present in many other tropical countries but has not yet been detected.

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Figure 1: Global evidence consensus and geographic locations of occurrence data from 1910 to 2014.
Figure 2: Predicted environmental suitability for B. pseudomallei persistence at 5 × 5 km2 spatial resolution.
Figure 3: Priority countries where microbiological diagnostic facilities and disease reporting systems for melioidosis should be strengthened.

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Acknowledgements

The authors thank P. Wannapinij for technical support and N. J. White and K. Schaecher for comments on the final draft. The authors also thank M. Devine for proofreading. This work was funded by the Wellcome Trust (grant no. 101103). S.I.H. is funded by a Senior Research Fellowship from the Wellcome Trust (grant no. 095066) and grants from the Bill & Melinda Gates Foundation (nos. OPP1119467, OPP1106023 and OPP1093011). S.I.H. acknowledges funding support from the RAPIDD programme of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health.

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Authors and Affiliations

  1. Wellcome Trust Centre for Human Genetics, University of Oxford, OX3 7BN, Oxford, UK

    Direk Limmathurotsakul, Nick Golding, David M. Pigott, Catherine L. Moyes & Simon I. Hay

  2. Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 10400, Bangkok, Thailand

    Direk Limmathurotsakul, Nicholas P. J. Day & Sharon J. Peacock

  3. Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, 10400, Bangkok, Thailand

    Direk Limmathurotsakul

  4. Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Vientiane, Lao PDR

    David A. B. Dance

  5. Centre for Tropical Medicine and Global Health, University of Oxford, Old Road Campus, OX3 7FZ, Oxford, UK

    David A. B. Dance & Nicholas P. J. Day

  6. Department of Zoology, University of Oxford, South Parks Road, OX1 3PS, Oxford, UK

    Jane P. Messina

  7. Universidade de Fortaleza, 60811-905, Fortaleza, Brazil

    Dionne B. Rolim

  8. Department of Pandemic and Epidemic Diseases, World Health Organization, 27, Geneva, Switzerland

    Eric Bertherat

  9. Department of Medicine, University of Cambridge, Addenbrooke's Hospital, CB2 0QQ, Cambridge, UK

    Sharon J. Peacock

  10. London School of Hygiene and Tropical Medicine, WC1E 7HT, London, UK

    Sharon J. Peacock

  11. Institute of Health Metrics and Evaluation, University of Washington, Seattle, 98121, Washington, USA

    Simon I. Hay

  12. Fogarty International Center, National Institutes of Health, Bethesda, 20892-2220, Maryland, USA

    Simon I. Hay

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  1. Direk Limmathurotsakul
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Contributions

D.L., D.D., E.B., N.P.J.D., S.J.P. and S.I.H. conceived the research. D.L. and S.I.H. drafted the manuscript. D.L. and D.D. reviewed all the occurrence data. D.L. and N.G. carried out the modelling and analysis with advice from S.I.H. D.L., N.G., J.M. and D.P. created the maps and figures. All authors discussed the results and contributed to the revision of the final manuscript.

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Correspondence to Direk Limmathurotsakul.

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Supplementary Information

Supplementary Methods, References, Table 1 and Figures 1–9. (PDF 8877 kb)

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Limmathurotsakul, D., Golding, N., Dance, D. et al. Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis. Nat Microbiol 1, 15008 (2016). https://doi.org/10.1038/nmicrobiol.2015.8

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