Aspergillus fumigatus and Aspergillosis It sporulates abundantly, with every conidial head producing

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  • CLINICAL MICROBIOLOGY REVIEWS, 0893-8512/99/$04.0010

    Apr. 1999, p. 310–350 Vol. 12, No. 2

    Copyright © 1999, American Society for Microbiology. All Rights Reserved.

    Aspergillus fumigatus and Aspergillosis JEAN-PAUL LATGÉ*

    Laboratoire des Aspergillus, Institut Pasteur, 75015 Paris, France

    INTRODUCTION .......................................................................................................................................................310 TAXONOMY OF A. FUMIGATUS ...........................................................................................................................311

    Species Identification .............................................................................................................................................311 Culture and morphological characteristics .....................................................................................................311 Biochemical and molecular characterizations used in species determination...........................................311

    Molecular Analyses in Strain Typing ..................................................................................................................312 CLINICAL SYMPTOMS AND DIAGNOSIS OF RESPIRATORY ASPERGILLOSIS ....................................314

    Allergic Bronchopulmonary Aspergillosis ...........................................................................................................314 Aspergilloma............................................................................................................................................................314 Invasive Aspergillosis .............................................................................................................................................314

    ANTIGENS AND LABORATORY DIAGNOSIS ....................................................................................................316 Antigens....................................................................................................................................................................316 Serodiagnosis in the Immunocompetent Patient................................................................................................318 Serodiagnosis in the Immunocompromised Host...............................................................................................318

    Circulating antigens ...........................................................................................................................................318 Detection of DNA in specimens ........................................................................................................................320

    ARE THERE VIRULENCE FACTORS IN A. FUMIGATUS? ..............................................................................320 Strategies..................................................................................................................................................................320 Animal Models ........................................................................................................................................................321 Putative Virulence Factors ....................................................................................................................................323

    Adhesins ...............................................................................................................................................................323 Pigments...............................................................................................................................................................323 Toxic Molecules...................................................................................................................................................323 Enzymes................................................................................................................................................................324

    HOST DEFENSE MECHANISMS AGAINST A. FUMIGATUS...........................................................................326 Innate Immunity .....................................................................................................................................................326

    Anatomical barriers............................................................................................................................................326 Humoral components .........................................................................................................................................326 Phagocytic cells ...................................................................................................................................................326

    (i) Macrophages ..............................................................................................................................................327 (ii) Neutrophils ...............................................................................................................................................327 (iii) Platelets ....................................................................................................................................................327

    Acquired Immunity.................................................................................................................................................327 T-cell immunity ...................................................................................................................................................327 Protective immunity............................................................................................................................................329

    Role of Immunosuppression in the Development of Invasive Aspergillosis...................................................329 Immunosuppressive drugs .................................................................................................................................329 Immunosuppressive molecules of fungal origin .............................................................................................330

    MOLECULAR EPIDEMIOLOGY AND PROPHYLAXIS OF INVASIVE ASPERGILLOGIS........................330 TREATMENT OF ASPERGILLOSIS......................................................................................................................332

    Amphotericin B .......................................................................................................................................................332 Itraconazole .............................................................................................................................................................333 Outcome and Trends..............................................................................................................................................333

    CONCLUSION............................................................................................................................................................335 ACKNOWLEDGMENTS ...........................................................................................................................................335 REFERENCES ............................................................................................................................................................335

    INTRODUCTION

    Aspergillus fumigatus is a saprophytic fungus that plays an essential role in recycling environmental carbon and nitrogen (235, 506, 676). Its natural ecological niche is the soil, wherein

    it survives and grows on organic debris. Although this species is not the most prevalent fungus in the world, it is one of the most ubiquitous of those with airborne conidia (443, 444, 466). It sporulates abundantly, with every conidial head producing thousands of conidia. The conidia released into the atmo- sphere have a diameter small enough (2 to 3 mm) to reach the lung alveoli (518, 577). A. fumigatus does not have an elaborate mechanism for releasing its conidia into the air; dissemination simply relies on disturbances of the environment and strong air

    * Mailing address: Laboratoire des Aspergillus, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France. Phone: 01 40 61 35 18. Fax: 01 40 61 34 19. E-mail: jplatge@pasteur.fr.

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  • currents. Once the conidia are in the air, their small size makes them buoyant, tending to keep them airborne both indoors and outdoors. Environmental surveys indicate that all humans will inhale at least several hundred A. fumigatus conidia per day (99, 222, 271). For most patients, therefore, disease occurs predominantly in the lungs, although dissemination to virtually any organ occurs in the most severely predisposed.

    Inhalation of conidia by immunocompetent individuals rarely has any adverse effect, since the conidia are eliminated relatively efficiently by innate immune mechanisms. Thus, until recent years, A. fumigatus was viewed as a weak pathogen responsible for allergic forms of the disease, such as farmer’s lung, a clinical condition observed among individuals exposed repeatedly to conidia, or aspergilloma, an overgrowth of the fungus on the surface of preexisting cavities in the lungs of patients treated successfully for tuberculosis (169, 341, 500). Because of the increase in the number of immunosuppressed patients, however, and the degree of severity of modern im- munosuppressive therapies, the situation has changed dramat- ically in recent years (114, 5