Melioidosis: Epidemiology, Pathophysiology, and Management Melioidosis: Epidemiology, Pathophysiology,

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  • CLINICAL MICROBIOLOGY REVIEWS, Apr. 2005, p. 383–416 Vol. 18, No. 2 0893-8512/05/$08.00�0 doi:10.1128/CMR.18.2.383–416.2005 Copyright © 2005, American Society for Microbiology. All Rights Reserved.

    Melioidosis: Epidemiology, Pathophysiology, and Management Allen C. Cheng1,2 and Bart J. Currie1,2,3*

    Menzies School of Health Research, Charles Darwin University,1 Northern Territory Clinical School, Flinders University,2 and Department of Medicine, Royal Darwin Hospital,3 Darwin, Australia

    INTRODUCTION .......................................................................................................................................................384 Background and History........................................................................................................................................384

    EPIDEMIOLOGY.......................................................................................................................................................384 Melioidosis in the Australia-Pacific Region........................................................................................................384 Distribution of Melioidosis in Asia ......................................................................................................................385

    Thailand ...............................................................................................................................................................385 PDR Laos .............................................................................................................................................................386 Vietnam ................................................................................................................................................................386 Malaysia and Indonesia.....................................................................................................................................386 Singapore .............................................................................................................................................................387 China, Hong Kong Special Administrative Region, and Taiwan .................................................................387 Other parts of Asia.............................................................................................................................................387

    Areas outside Asia ..................................................................................................................................................389 Animals and Melioidosis .......................................................................................................................................389

    BACTERIOLOGY AND PATHOGENESIS.............................................................................................................389 General Bacteriology ..............................................................................................................................................389 Environmental Microbiology and Epidemiology ................................................................................................389 Bacterial Virulence Factors ...................................................................................................................................390

    Secretory antigens...............................................................................................................................................390 Cell-associated antigens.....................................................................................................................................391

    Molecular Epidemiology ........................................................................................................................................392 Genome Sequence of B. pseudomallei and Comparison with That of B. mallei ..............................................392 Role of Host Immune Responses..........................................................................................................................393

    Innate immunity..................................................................................................................................................393 Role of macrophages in immunity....................................................................................................................393 Role of T cells in immunity ...............................................................................................................................394 Antibody responses .............................................................................................................................................394 Other host factors...............................................................................................................................................394

    Prospects for Vaccine .............................................................................................................................................394 CLINICAL FEATURES .............................................................................................................................................395

    Risk Factors.............................................................................................................................................................395 Clinical Syndromes.................................................................................................................................................396 Modes of Acquisition and Incubation Period .....................................................................................................397 Melioidosis as a Potential Bioweapon .................................................................................................................398

    DIAGNOSIS AND MANAGEMENT OF MELIOIDOSIS ....................................................................................399 Diagnosis..................................................................................................................................................................399

    Culture-based methods ......................................................................................................................................400 Antigen detection ................................................................................................................................................400 Antibody detection ..............................................................................................................................................400 Molecular methods .............................................................................................................................................401

    Antibiotic Resistance ..............................................................................................................................................401 Antibiotic Treatment ..............................................................................................................................................403 Management of Sepsis Syndrome.........................................................................................................................405

    CONCLUSIONS .........................................................................................................................................................406 ACKNOWLEDGMENTS ...........................................................................................................................................406 REFERENCES ............................................................................................................................................................406

    * Corresponding author. Mailing address: Menzies School of Health Research, P.O. Box 41096, Casuarina, NT 0811, Darwin, Australia. Phone: 61 8 8922 8196. Fax: 61 8 8927 5187. E-mail: bart@menzies .edu.au.

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  • INTRODUCTION

    Background and History

    The pathologist Alfred Whitmore and his assistant C. S. Krishnaswami first described melioidosis as a “glanders-like” disease among morphia addicts in Rangoon, Burma, in 1911 (474, 475). They recognized a new organism that fulfilled Koch’s postulates for causation of disease. This bacterium, which could be isolated from autopsy specimens on peptone agar and potato slopes, could be distinguished from the organ- ism causing glanders by its relatively rapid growth, its motility, and the lack of the Strauss reaction when it was injected into guinea pigs. Based on these characteristics, “. . . sufficiently peculiar to distinguish it from all pathogenic bacteria previ- ously known to us” (475), they correctly surmised that this new bacterium was closely related to that which caused glanders, a finding that has only recently been confirmed by molecular studies (170, 197, 313).

    This disease, now termed melioidosis, was named from the Greek “melis” (distemper of asses) and “eidos” (resemblance) by Stanton and Fletcher in 1932 (405). During the last century this gram-negative environmental bacterium has been vari- ously known as Bacillus pseudomallei, Bacillus whitmorii (or Bacille de Whitmore), Malleomyces pseudomallei, Pseudomonas pseudomallei, and, since 199

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