Blastomycosis

CURRENT TOPICS IN INFECTIOUS DISEASE

Series Editors:

William B. Greenough III Division of Geographic Medicine The Johns Hopkins University School

of Medicine Baltimore. Maryland

Thomas C. Merigan Head. Division of Infectious Disease Stanford University Medical Center Stanford. California

The Atypical Mycobacteria and Human Mycobacteriosis

John S. Chapman

Blastomycosis

Edited by Youse! Al-Doory and Arthur F. DiSalvo

Cholera

Edited by Dhiman Barua and William B. Greenough III

Coccidioidomycosis: A Text

Edited by David A. Stevens

Infections of the Gastrointestinal Tract: Microbiology, Pathophysiology, and Clinical Features

Herbert L. DuPont and Larry K. Pickering

Infective Endocarditis and Other Intravascular Infections

Lawrence R. Freedman

Plague and Other Yersinia Infections

Thomas Butler

A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual ship­ment. For further information please contact the publisher.

Blastomycosis

Edited by

Yousef AI-Doory, Ph. D. George Washington University

School of Medicine and Health Sciences Washington, D.e.

and

Arthur F. DiSalvo, M. D. Nevada State Health Laboratory Reno, Nevada

SPRINGER SCIENCE+BUSINESS MEDIA, LLC

Llbrary of Congress Cataloglng-ln-Publlcatlon Data

Blastomycosis I edited by Yousef Al-Doory and Arthur F. DiSalvo. p. cm. -- (Current top i cs in infect i ous d i sease)

Include bibliographical references and index. ISBN 978-1-4613-6455-9 ISBN 978-1-4615-3306-1 (eBook) DOI 10.1007/978-1-4615-3306-1 1. Blastomycosis. '2. Blastomyces dermatitidis.

Yousef, 1924- II. DiSalvo, Arthur F., 1932-1. Al-Doory,

III. Series. [DNLM, 1. Blastomyces. 2. Blastomycosis.

OR201.B55B53 1992 616.9'69--dc20 DNLM/DLC for Library of Congress

ISBN 978-1-4613-6455-9

WC 450 B6441

© 1992 Springer Science+Business Media New York Origina1ly published by Plenum Publishing Corporation in 1992

91-39241 CIP

Plenum Medical Book Company is an imprint of Plenum Publishing Corporation

AII rights reserved

No part ofthis book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher.

To

J. Fred Denton, M.D.

and

Norman F. Conant, Ph.D.

Contributors

Yousef Al-Doory, Ph.D., 12150 Long Ridge Lane, Bowie, Maryland

Robert W. Bradsher, M.D., Division of Infectious Diseases, Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas

Elmer Brummer, Ph.D., Department of Medicine, Santa Clara Valley Medi­cal Center, San Jose, California

Guy D. Campbell, M.D., Clinical Professor of Medicine, University of Mis­sissippi, School of Medicine, Jackson, Mississippi

William A. Causey, M.D., Clinical Associate Professor of Medicine, Univer­sity of Mississippi, School of Medicine, Jackson, Mississippi

Francis W. Chandler, D.V.M., Ph.D., Department of Pathology, Medical College of Georgia, Augusta, Georgia

George C. Cozad, Ph.D., Department of Botany and Microbiology, Univer­sity of Oklahoma, Norman, Oklahoma

Arthur F. DiSalvo, M.D., Nevada State Health Laboratory, Reno, Nevada

Norman L. Goodman, Ph.D., Department of Pathology, Albert B. Chandler Medical Center, University of Kentucky, Lexington, Kentucky

Leo Kaufman, Ph.D., Division of Mycotic Diseases, Centers for Disease Control, Atlanta, Georgia

Bruce S. Klein, M.D., Departments of Pediatrics and Internal Medicine, University of Wisconsin at Madison, Madison, Wisconsin

vii

viii Contributors

Alfred M. Legendre, D.V.M., University of Tennessee, Department ofUr­ban Practice, College of Veterinary Medicine, Knoxville, Tennessee

Alan M. Sugar, M.D., Department of Medicine, Boston University Medical Center, Boston, Massachusetts

John C. Watts, M.D., Division of Surgical Pathology, Department of Ana­tomic Pathology, William Beaumont Hospital, Royal Oak, Michigan

Foreword

Blastomycosis remains the most enigmatic of human mycotic infections. The enigmas encompass the natural habitat of the etiologic agent, extent of exposure and subclinical infections in endemic areas, distribution of en­demic foci throughout the world, inconsistency of serologic evaluation of infected patients, and varying response of such patients to standard treat­ment regimens.

In spite of diligent investigations by many competent investigators, we still do not know the ecological niche inhabited by the etiologic agent. We have many tantalizing clues but no definite answers. Nor do we know the extent of the endemic areas in the world for this disease. Skin testing, so useful in defining the distribution of histoplasmosis and coccidioidomycosis, has been of no value in mapping endemic areas for blastomycosis. Even the serologic evaluation of known cases of the disease has been too erratic in results to be useful as a diagnostic or prognostic procedure.

The enigmas of blastomycosis go straight to the disease itself. There is an extensive literature on the debate concerning the presence and extent of subclinical infections. Case report series demonstrate that such transient infections do occur but, unlike other mycoses, the extent to which this phe­nomenon is common in the general population still cannot be assessed. Even the diagnosis of established disease is a major clinical problem. Serologic procedures are unreliable: the organism may take from 2 days to 12 weeks to grow out in culture (and then be difficult to identify positively), so that observing the fungus in tissue is the only "rapid" procedure, although the latter is fraught with difficulties as well.

It becomes apparent from looking at the list of unknowns regarding blastomycosis that a compendium of known information and evaluations of evidence relevant to these enigmas is greatly needed. This present volume will fill the gap in our appreciation of this disease.

ix

x Foreword

A study of the Contents demonstrates that all major aspects of blasto­mycosis are covered: history, taxonomy and biology, clinical aspects ofnatu­ral infections in humans and animals as well as experimental infections, the very complex immunological responses elicited by infection, the variation in -virulence of different isolates, the great enigmas of distribution and endemic­ity in human and animal infections, and, finally, the frustratingly contradic­tory pathology and clinical types of disease are analyzed and clarified. Each of the authors is an experienced and recognized expert in the field. The editors of this volume are experienced not only in medical mycology but also in the writing and communication of that science so the resulting consis­tency of style contributes greatly to the quality of the volume. This book is therefore a most valuable summation of present knowledge of the subject and will be a reference of great worth for years to come.

John W. Rippon

Preface

Blastomycosis is one of the major systemic mycotic diseases, with a world­wide distribution and a significant rate of mortality. At the same time, it is the most difficult mycotic disease to identify. The causative fungus, Blasto­myces dermatitidis, is the most difficult agent to isolate from sources in nature where it is expected to be found.

The expansion of scientific research, the accumulation of data, and the increased number of medical, veterinary, and microbiological journals in various languages make it cumbersome for an interested professional to gain comprehensive knowledge of specific mycotic diseases by referring to the few general texts available in medical mycology. For this reason, we believe that a monograph on each major mycotic disease is needed. This need has been recognized, and separate monographs have been published on coccidioido­mycosis, histoplasmosis, paracoccidioidomycosis, cryptococcosis, aspergil­losis, candidiasis, chromomycosis, and mycetoma. Furthermore, with the rate of accumulation of information regarding certain diseases, we believe that such monographs should be updated periodically. No monograph, how­ever, has been available for blastomycosis.

Our aim is to bring together in this volume all accessible data on B. dermatitidis and blastomycosis. We believe this can best be accomplished by having each chapter written by an authority in the field.

Our thanks are extended to the chapter authors as well as to those who permitted the reproduction of photographs and/or quoted material as indi­cated in source lines accompanying the material.

Endorsement of products or manufacturers named in the text is dis­claimed by the editors and the authors. These names are used for identifica­tion purposes only.

Yousef AI-Doory, Ph.D. Arthur F. DiSalvo, M.D.

xi

Publisher's note: The spelling "mold" has been used throughout this volume, as it is our policy to employ American spelling in all our titles. We do acknowledge that many authorities in the fields of microbiology and medicine, including the editors of this volume, prefer the spelling "mould."

Contents

Chapter 1

INTRODUCTION ................................................... 1

Youse! Al-Doory

1. History ........................................................... . 2. The Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 3 3. The Fungus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 5 References ............................................................ 6

Chapter 2 TAXONOMY AND BIOLOGY OF BLASTOMYCES DERMATITIDIS ..................................................... 9

Alan M. Sugar

1. Introduction ....................................................... 9 2. Taxonomy ....................................................... 10 3. Morphology ...................................................... 12

3.1. Teleomorph (Perfect or Sexual State) ......................... 12 3.2. Anamorph (Imperfect or Asexual State) ...................... 13 3.3. Summary .................................................... 14

4. Ultrastructure .................................................... 15 4.1. Cytoplasm ................................................... 17 4.2. Ribosomes................................................... 17 4.3. Nuclear Cytology ............................................ 17 4.4. Yeast-to-Mycelia Conversion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 19 4.5. Summary .................................................... 19

xiii

xiv Contents

5. Genetics and Reproduction ....................................... 19 5.1. Teleomorph .............................................. " ... 20 5.2. Anamorph ................................................... 20 5.3. Summary .................................................... 20

6. Physiology........................................................ 21 6.1. Growth Requirements ....................................... 21 6.2. Chemical Composition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 21 6.3. Summary .................................................... 25

7. Dimorphic Phase Transition ...................................... 26 8. Summary ......................................................... 26 References ........................................................... 27

Chapter 3

VIRULENCE OF BLASTOMYCES DERMATITIDIS ............... 31

Elmer Brummer

1. In Vivo ........................................................... 31 1.1. Measurement of Virulence ................................... 31 1.2. Basis of Pathogenicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 32 1.3. Virulence ofIsolates ......................................... 32 1.4. Stability of Virulence ........................................ 33 1.5. Correlates of Virulence ....................................... 35

2. In Vitro .......................................................... 36 2.1. Macrophages ................................................ 36 2.2. PMNs ....................................................... 37

3. Virulence Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 39 3.1. Lipids and Phospholipids .................................... 39 3.2. Cell Wall Composition ....................................... 39

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 40

Chapter 4

THE ECOLOGY OF BLASTOMYCES DERMATITIDIS ........... 43

Arthur F. DiSalvo

1. Introduction .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 43 2. Source in Nature ................................................. 44

Contents xv

3. Experimental Ecology ............................................ 46 4. Geographic Distribution .......................................... 47

4.1. North America .............................................. 48 4.2. South America. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 52 4.3. Africa ....................................................... 53 4.4. Europe ...................................................... 55 4.5. Middle East ................................................. 56 4.6. India ........................................................ 57 4.7. South Pacific ................................................ 59

5. Conidia as Infectious Particles .................................... 60 6. Isolation from Nature ............................................. 60

6.1. Reports . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 60 6.2. Methods of Isolation ......................................... 65 6.3. Environmental Characteristics ............................... 66

7. Summary......................................................... 68 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 69

Chapter 5 THE EPIDEMIOLOGY OF BLASTOMYCOSIS ............. '" ..... 75

Arthur F. DiSalvo

1. Introduction .................................................... 75 2. Transmission .................................................... 76 3. Incubation Period ............................................... 77 4. Skin Testing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 79 5. Demographic Aspects ........................................... 80

5.1. Age ........................................................ 80 5.2. Sex ......................................................... 82 5.3. Race ....................................................... 82

6. Outbreaks ....................................................... 83 7. Possible Hosts ................................................... 90

7.1. The Canine Surrogate ...................................... 90 7.2. Bat ......................................................... 92

8. Occupational Mycosis ........................................... 92 9. Seasonality ...................................................... 95

10. Strain Synonyms ................................................ 96 11. Summary ....................................................... 98 References ......................................................... 100

xvi Contents

Chapter 6 DIAGNOSIS OF BLASTOMYCOSIS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 105

Norman L. Goodman

1. Specimen Selection .............................................. 105 2. Specimen Collection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 106

2.1. Pulmonary Secretions ...................................... 106 2.2. Exudates and Pus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 107 2.3. Tissue ...................................................... 107 2.4. Urine ...................................................... 108 2.5. Cerebrospinal Fluid (CSF) .................................. 108 2.6. Blood ...................................................... 109

3. Direct Microscopic Examination ................................. 109 4. Processing and Culturing Clinical Specimens .......... " ......... III

4.1. Specimen Processing ........................................ 112 4.2. Medium Selection .......................................... 114 4.3. Culture Procedure .......................................... 116

5. Identification .................................................... 118 5.1. Culture..................................................... 118 5.2. Exoantigen ................................................. 119 5.3. DNA Probes ................................................ 120

References ......................................................... 121

Chapter 7

IMMUNODIAGNOSIS OF BLASTOMYCOSIS .................... 123

Leo Kaufman

1. Introduction .................................................... 123 2. Diagnostic Tests. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 124

2.1. Complement Fixation Test ................................. 124 2.2. Immunodiffusion Test ...................................... 125 2.3. Enzyme Immunosorbent Assay (EIA) ....................... 126 2.4. Western Blot ............................................... 127 2.5. Immunofluorescence ....................................... 128 2.6. Radioimmunoassay ......................................... 128 2.7. Cell-Mediated Immunity .................................... 129

3. Summary ....................................................... 130 References ......................................................... 130

Contents xvii

Chapter 8 IMMUNOLOGY OF BLASTOMYCOSIS .......................... 133

Bruce S. Klein

1. Introduction .................................................... 133 2. Inflammatory Response to B. dermatitidis ....................... 133 3. Antigens of B. dermatitidis ...................................... 135 4. Genetic Factors in Resistance to B. dermatitidis Infection ........ 136 5. Natural Resistance to B. dermatitidis Infection ................... 139

5.1. Natural Cellular Resistance ................................. 140 5.2. Complement ............................................... 146 5.3. Summary .................................................. 146

6. Acquired Resistance to B. dermatitidis Infection ................. 146 6.1. Humoral Immunity ........................................ 146 6.2. Cell-Mediated Immunity .................................... 149 6.3. Summary .................................................. 154

7. Immunomodulation ............................................. 154 7.1. Augmentation .............................................. 154 7.2. Suppression ................................................ 156

8. Summary ...................................................... 158 References ......................................................... 158

Chapter 9 CLINICAL ASPECTS OF BLASTOMYCOSIS ..................... 165

William A. Causey and Guy D. Campbell

1. Introduction .................................................... 165 2. Pulmonary Blastomycosis ....................................... 166

2.1. Primary Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 166 2.2. Chronic Blastomycosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 167

3. Extrapulmonary Infections ...................................... 168 3.1. Cutaneous Blastomycosis ................................... 170 3.2. Bone and Joint ............................................. 175 3.3. Genitourinary .............................................. 176 3.4. Larynx ..................................................... 179 3.5. Central Nervous System (CNS) ............................. 180 3.6. Adrenal Gland ............................................. 181 3.7. Other Manifestations of Blastomycosis ...................... 181

xviii Contents

4. Blastomycosis in Pregnancy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 182 5. Combined Fungal Infections ..................................... 182 6. Blastomycosis in Children ....................................... 183 7. Compromised Host .............................................. 183 References ......................................................... 185

Chapter 10 PATHOLOGIC FEATURES OF BLASTOMyCOSIS ............... 189

Francis W Chandler and John C. Watts

1. Clinicopathologic Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 190 2. Gross Pathology ................................................. 194 3. Morphologic and Tinctorial Features of B. dermatitidis in Tissue

Sections ......................................................... 199 4. Microscopic Pathology .......................................... 204 5. Immunohistologic Diagnosis: Applications and Current Status .... 208 6. Differential Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 211 References ......................................................... 215

Chapter 11 EXPERIMENTAL BLASTOMYCOSIS ............................ 221

George C. Cozad

1. Introduction .................................................... 221 2. Experimental Infection and Pathogenicity . . . . . . . . . . . . . . . . . . . . . . .. 221 3. Importance of Cellular Immunity in Blastomycosis. . . . . . . . . . . . . .. 223 4. Cell-Mediated Immunoprotection in Blastomycosis (Whole

Animal Study) ................................................... 225 5. Immune Monitoring in Blastomycosis ........................... 227 6. Thymosin, Lymphotoxin, and Immune Reaction ................ 228 7. B. dermatitidis as a Biologic Response Modulator ................ 231 8. Immunoadjuvant Effects of B. dermatitidis against EL4

Lymphoma ..................................................... 232 References ......................................................... 233

Contents xix

Chapter 12 PROGNOSIS AND THERAPY OF BLASTOMYCOSIS ............ 237

Robert W Bradsher

1. Introduction .................................................... 237 2. Initiation of Therapy ............................................ 238 3. Amphotericin B ................................................. 239 4. Ketoconazole.................................................... 241 5. Itraconazole ..................................................... 243 6. Other Modes of Therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 244 7. Summary ....................................................... 245 References ......................................................... 245

Chapter 13

BLASTOMYCOSIS IN ANIMALS ................................. 249

Alfred M. Legendre

1. Introduction .................................................... 249 2. Epidemiology of Blastomycosis in Animals. . . . . . . . . . . . . . . . . . . . . .. 250 3. Clinical Aspects of Animal Blastomycosis ........................ 252 4. Diagnostic Procedures ........................................... 255 5. Therapy ......................................................... 256 6. Prognostic Factors ............................................... 258 7. Public Health Aspects of Animal Blastomycosis .................. 258 References ......................................................... 259

INDEX ............................................................ 265