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Melioidosis

Nature Reviews Disease Primers volume 4, Article number: 17107 (2018) Cite this article

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Abstract

Burkholderia pseudomallei is a Gram-negative environmental bacterium and the aetiological agent of melioidosis, a life-threatening infection that is estimated to account for ∼89,000 deaths per year worldwide. Diabetes mellitus is a major risk factor for melioidosis, and the global diabetes pandemic could increase the number of fatalities caused by melioidosis. Melioidosis is endemic across tropical areas, especially in southeast Asia and northern Australia. Disease manifestations can range from acute septicaemia to chronic infection, as the facultative intracellular lifestyle and virulence factors of B. pseudomallei promote survival and persistence of the pathogen within a broad range of cells, and the bacteria can manipulate the host's immune responses and signalling pathways to escape surveillance. The majority of patients present with sepsis, but specific clinical presentations and their severity vary depending on the route of bacterial entry (skin penetration, inhalation or ingestion), host immune function and bacterial strain and load. Diagnosis is based on clinical and epidemiological features as well as bacterial culture. Treatment requires long-term intravenous and oral antibiotic courses. Delays in treatment due to difficulties in clinical recognition and laboratory diagnosis often lead to poor outcomes and mortality can exceed 40% in some regions. Research into B. pseudomallei is increasing, owing to the biothreat potential of this pathogen and increasing awareness of the disease and its burden; however, better diagnostic tests are needed to improve early confirmation of diagnosis, which would enable better therapeutic efficacy and survival.

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Figure 1: Milestones in the history of melioidosis.
Figure 2: Estimated mortality and reported cases of melioidosis.
Figure 3: Schematic model of host–pathogen interactions and pathophysiology of melioidosis.
Figure 4: Clinical manifestations of melioidosis.
Figure 5: Identification of Burkholderia pseudomallei colonies on three common types of agar.

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Acknowledgements

W.J.W. received a Vidi grant (91716475) from the Netherlands Organisation for Scientific Research (NWO) and Marie Curie Skledowska Innovative Training Network (MC-ITN) European Sepsis Academy, funded by the European Union's Horizon 2020 programme. H.S.V. received a Marie Curie Skledowska fellowship under the European Sepsis Academy, funded by the European Union's Horizon 2020 programme. A.G.T. is supported by the NIH and the National Institute of Allergy and Infectious Diseases (NIAID) R01 grant AI12660101. B.J.C. is supported by Australian National Health and Medical Research Council grants, including the HOT NORTH initiative. S.J.P. is an NIH Research Senior Investigator. D.A.B.D. is supported by The Wellcome Trust of Great Britain (grant number 106698/Z/14/Z). D.L. is supported by The Wellcome Trust Public Health and Tropical Medicine Intermediate Fellowship (grant number 101103/Z/13/Z). The authors thank G. Wongsuvan, P. Amornchai, P. Wannapinij and V. Wuthiekanun for their assistance with the images in Fig. 5.

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Authors and Affiliations

  1. Department of Medicine, Division of Infectious Diseases, Academic Medical Center, Meibergdreef 9, Rm. G2-132, Amsterdam, 1105 AZ, The Netherlands

    W. Joost Wiersinga

  2. Centre for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands

    W. Joost Wiersinga & Harjeet S. Virk

  3. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA

    Alfredo G. Torres

  4. Menzies School of Health Research, Charles Darwin University and Royal Darwin Hospital, Darwin, Australia

    Bart J. Currie

  5. Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK

    Sharon J. Peacock & David A. B. Dance

  6. Department of Medicine, University of Cambridge, Cambridge, UK

    Sharon J. Peacock

  7. Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit, Vientiane, Lao People's Democratic Republic

    David A. B. Dance

  8. Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK

    David A. B. Dance & Direk Limmathurotsakul

  9. Department of Tropical Hygiene and Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand

    Direk Limmathurotsakul

Authors
  1. W. Joost Wiersinga
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  2. Harjeet S. Virk
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  3. Alfredo G. Torres
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  4. Bart J. Currie
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  5. Sharon J. Peacock
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Contributions

Introduction (H.S.V. and W.J.W.); Epidemiology (D.L. and D.A.B.D.); Mechanisms/pathophysiology (H.S.V., W.J.W., A.G.T. and S.J.P.); Diagnosis, screening and prevention (D.A.B.D., D.L. and B.J.C.); Management (B.J.C.); Quality of life (B.J.C.); Outlook (A.G.T., H.S.V., D.A.B.D., D.L. and W.J.W.); Overview of Primer (all authors).

Corresponding authors

Correspondence to W. Joost Wiersinga or Direk Limmathurotsakul.

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Competing interests

D.A.B.D. acted as a consultant to Soligenix, Inc. All other authors declare no competing interests.

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Wiersinga, W., Virk, H., Torres, A. et al. Melioidosis. Nat Rev Dis Primers 4, 17107 (2018). https://doi.org/10.1038/nrdp.2017.107

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