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HARRISON’S Infectious Diseases Derived from Harrison’s Principles of Internal Medicine, 17th Edition Editors ANTHONY S. FAUCI, EUGENE BRAUNWALD, MD MD Chief,Laboratory of Immunoregulation; Distinguished Hersey Professor of Medicine, Director,National Institute of Allergy and Infectious Diseases, Harvard Medical School;Chairman,TIMI Study Group, National Institutes of Health,Bethesda Brigham and Women’s Hospital,Boston DENNIS L. KASPER, STEPHEN L. HAUSER, MD MD William Ellery Channing Professor of Medicine,Professor of Robert A.Fishman Distinguished Professor and Chairman, Microbiology and Molecular Genetics,Harvard Medical School; Department of Neurology,University of California,San Francisco Director,Channing Laboratory,Department of Medicine, Brigham and Women’s Hospital,Boston J. LARRY JAMESON, , MD PhD Professor of Medicine; DAN L. LONGO, MD Vice President for Medical Affairs and Scientific Director,National Institute on Aging, Lewis Landsberg Dean,Northwestern University National Institutes of Health,Bethesda and Baltimore Feinberg School of Medicine,Chicago JOSEPH LOSCALZO, , MD PhD Hersey Professor of the Theory and Practice of Medicine, Harvard Medical School;Chairman,Department of Medicine; Physician-in-Chief,Brigham and Women’s Hospital,Boston HARRISON’S Infectious Diseases Editors Dennis L. Kasper, MD William Ellery Channing Professor of Medicine,Professor of Microbiology and Molecular Genetics,Harvard Medical School;Director,Channing Laboratory, Department of Medicine,Brigham and Women’s Hospital,Boston Anthony S. Fauci, MD Chief,Laboratory of Immunoregulation;Director,National Institute of Allergy and Infectious Diseases,National Institutes of Health,Bethesda New York Chicago San Francisco Lisbon London Madrid Mexico City Milan New Delhi San Juan Seoul Singapore Sydney Toronto Copyright © 2010 by The McGraw-Hill Companies, Inc. All rights reserved. Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a database or retrieval system, without the prior written permission of the publisher. ISBN: 978-0-07-170294-2 MHID: 0-07-170294-6 The material in this eBook also appears in the print version of this title: ISBN: 978-0-07-170293-5, MHID: 0-07-170293-8. All trademarks are trademarks of their respective owners. Rather than put a trademark symbol after every occurrence of a trademarked name, we use names in an editorial fashion only, and to the benefi t of the trademark owner, with no intention of infringement of the trademark. Where such designations appear in this book, they have been printed with initial caps. McGraw-Hill eBooks are available at special quantity discounts to use as premiums and sales promotions, or for use in corporate training programs. To contact a representative please e-mail us at [email protected]. This book was set in Bembo by Glyph International.The editors were James F. Shanahan and Kim J. Davis. The production supervisor was Catherine H. Saggese. Project management was provided by Arushi Chawla of Glyph International.The cover design was by Thomas DePierro. Cover, section, and chapter opener illustrations © MedicalRF.com. All rights reserved. TERMS OF USE This is a copyrighted work and The McGraw-Hill Companies, Inc. (“McGrawHill”) and its licensors reserve all rights in and to the work. Use of this work is subject to these terms. Except as permitted under the Copyright Act of 1976 and the right to store and retrieve one copy of the work, you may not decompile, disassemble, reverse engineer, reproduce, modify, create derivative works based upon, transmit, distribute, disseminate, sell, publish or sublicense the work or any part of it without McGraw-Hill’s prior consent. You may use the work for your own noncommercial and personal use; any other use of the work is strictly prohibited. Your right to use the work may be terminated if you fail to comply with these terms. THE WORK IS PROVIDED “AS IS.” McGRAW-HILL AND ITS LICENSORS MAKE NO GUARANTEES OR WARRANTIES AS TO THE ACCURACY, ADEQUACY OR COMPLETENESS OF OR RESULTS TO BE OBTAINED FROM USING THE WORK, INCLUDING ANY INFORMATION THAT CAN BE ACCESSED THROUGH THE WORK VIA HYPERLINK OR OTHERWISE, AND EXPRESSLY DISCLAIM ANY WARRANTY, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. McGraw-Hill and its licensors do not warrant or guarantee that the functions contained in the work will meet your requirements or that its operation will be uninterrupted or error free. Neither McGraw-Hill nor its licensors shall be liable to you or anyone else for any inaccuracy, error or omission, regardless of cause, in the work or for any damages resulting therefrom. McGraw-Hill has no responsibility for the content of any information accessed through the work. Under no circumstances shall McGraw-Hill and/ or its licensors be liable for any indirect, incidental, special, punitive, consequential or similar damages that result from the use of or inability to use the work, even if any of them has been advised of the possibility of such damages. This limitation of liability shall apply to any claim or cause whatsoever whether such claim or cause arises in contract, tort or otherwise. CONTENTS Contributors . . . . . . . . . . . . . . . . . . . . . . . . xi 14 Approach to the Acutely Ill Infected Febrile Patient. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153 Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . xvii Tamar F.Barlam,Dennis L.Kasper 15 Severe Sepsis and Septic Shock . . . . . . . . . . . 162 SECTION I Robert S.Munford INTRODUCTION TO INFECTIOUS DISEASES SECTION III 1 Introduction to Infectious Diseases: INFECTIONS IN ORGAN SYSTEMS Host-Pathogen Interactions. . . . . . . . . . . . . . . . 2 16 Pharyngitis,Sinusitis,Otitis,and Other Lawrence C.Madoff,Dennis L.Kasper Upper Respiratory Tract Infections . . . . . . . . 174 2 Molecular Mechanisms of Microbial Michael A.Rubin,Ralph Gonzales, Pathogenesis. . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Merle A.Sande Gerald B.Pier 17 Pneumonia. . . . . . . . . . . . . . . . . . . . . . . . . . 188 3 Immunization Principles and Vaccine Use . . . . 20 Lionel A.Mandell,Richard Wunderink Gerald T.Keusch,Kenneth J.Bart,Mark Miller 18 Bronchiectasis and Lung Abscess . . . . . . . . . . 202 4 Health Advice for International Travel. . . . . . . 43 Gregory Tino,Steven E.Weinberger Jay S.Keystone,Phyllis E.Kozarsky 19 Infective Endocarditis . . . . . . . . . . . . . . . . . . 206 5 Laboratory Diagnosis of Infectious Diseases . . . 54 Adolf W.Karchmer Alexander J.McAdam,Andrew B.Onderdonk 20 Pericardial Disease . . . . . . . . . . . . . . . . . . . . 220 6 Microbial Bioterrorism. . . . . . . . . . . . . . . . . . 66 Eugene Braunwald H.Clifford Lane,Anthony S.Fauci 21 Infections of the Skin,Muscle,and Soft Tissues. . . . . . . . . . . . . . . . . . . . . . . . . . 230 Dennis L.Stevens SECTION II FEVER AND APPROACH TO THE 22 Osteomyelitis. . . . . . . . . . . . . . . . . . . . . . . . 237 FEBRILE PATIENT Jeffrey Parsonnet 7 Fever and Hyperthermia. . . . . . . . . . . . . . . . . 82 23 Infectious Arthritis . . . . . . . . . . . . . . . . . . . . 244 Charles A.Dinarello,Reuven Porat Lawrence C.Madoff 8 Fever and Rash . . . . . . . . . . . . . . . . . . . . . . . 87 24 Intraabdominal Infections and Abscesses. . . . . 252 Elaine T.Kaye,Kenneth M.Kaye Miriam J.Baron,Dennis L.Kasper 9 Fever of Unknown Origin . . . . . . . . . . . . . . 100 25 Acute Infectious Diarrheal Diseases and Jeffrey A.Gelfand,Michael V.Callahan Bacterial Food Poisoning . . . . . . . . . . . . . . . 260 Joan R.Butterton,Stephen B.Calderwood 10 Atlas of Rashes Associated with Fever . . . . . . 108 Kenneth M.Kaye,Elaine T.Kaye 26 Acute Appendicitis and Peritonitis. . . . . . . . . 268 Susan L.Gearhart,William Silen 11 Infections in Patients with Cancer. . . . . . . . . 118 27 Urinary Tract Infections,Pyelonephritis, Robert Finberg and Prostatitis. . . . . . . . . . . . . . . . . . . . . . . . 272 12 Infections in Transplant Recipients. . . . . . . . . 130 Walter E.Stamm Robert Finberg,Joyce Fingeroth 28 Sexually Transmitted Infections:Overview and 13 Health Care–Associated Infections. . . . . . . . . 144 Clinical Approach. . . . . . . . . . . . . . . . . . . . . 283 Robert A.Weinstein King K.Holmes v vi Contents 29 Meningitis,Encephalitis,Brain Abscess,and Part 3 Diseases Caused by Gram-Negative Bacteria Empyema. . . . . . . . . . . . . . . . . . . . . . . . . . . 303 44 Meningococcal Infections. . . . . . . . . . . . . . . 450 Karen L.Roos,Kenneth L.Tyler Lee M.Wetzler 30 Chronic and Recurrent Meningitis . . . . . . . . 333 45 Gonococcal Infections . . . . . . . . . . . . . . . . . 459 Walter J.Koroshetz,Morton N.Swartz Sanjay Ram,Peter A.Rice 31 Chronic Fatigue Syndrome. . . . . . . . . . . . . . 341 46 Moraxella Infections. . . . . . . . . . . . . . . . . . . . 469 Stephen E.Straus Daniel M.Musher 32 Infectious Complications of Burns and Bites . . . 343 47 Haemophilus Infections . . . . . . . . . . . . . . . . . 472 Lawrence C.Madoff,Florencia Pereyra Timothy F.Murphy 48 Infections Due to the HACEK Group and Miscellaneous Gram-Negative Bacteria . . . . . 477 SECTION IV Tamar F.Barlam,Dennis L.Kasper BACTERIAL INFECTIONS 49 Legionella Infection . . . . . . . . . . . . . . . . . . . . 481 Part 1 Approach to Therapy for Bacterial Diseases Miguel Sabria,Victor L.Yu 33 Treatment and Prophylaxis of Bacterial 50 Pertussis and Other Bordetella Infections. . . . . 487 Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . 354 Scott A.Halperin Gordon L.Archer,Ronald E.Polk 51 Diseases Caused by Gram-Negative Part 2 Diseases Caused by Gram-Positive Bacteria Enteric Bacilli . . . . . . . . . . . . . . . . . . . . . . . 493 Thomas A.Russo,James R.Johnson 34 Pneumococcal Infections . . . . . . . . . . . . . . . 374 Daniel M.Musher 52 Helicobacter Pylori Infections. . . . . . . . . . . . . . 506 John C.Atherton,Martin J.Blaser 35 Staphylococcal Infections . . . . . . . . . . . . . . . 386 Franklin D.Lowy 53 Infections Due to Pseudomonas Species and Related Organisms. . . . . . . . . . . . . . . . . 512 36 Streptococcal and Enterococcal Infections . . . 399 Reuben Ramphal Michael R.Wessels 54 Salmonellosis . . . . . . . . . . . . . . . . . . . . . . . . 521 37 Acute Rheumatic Fever . . . . . . . . . . . . . . . . 412 David A.Pegues,Samuel I.Miller Jonathan R.Carapetis 55 Shigellosis . . . . . . . . . . . . . . . . . . . . . . . . . . 530 38 Diphtheria and Other Infections Caused by Philippe Sansonetti,Jean Bergounioux Corynebacteria and Related Species . . . . . . . 418 56 Infections Due to Campylobacter and William R.Bishai,John R.Murphy Related Species . . . . . . . . . . . . . . . . . . . . . . 536 39 Infections Caused by Listeria Monocytogenes. . . 426 Martin J.Blaser Elizabeth L.Hohmann,Daniel A.Portnoy 57 Cholera and Other Vibrioses. . . . . . . . . . . . . 540 40 Tetanus . . . . . . . . . . . . . . . . . . . . . . . . . . . . 429 Matthew K.Waldor,Gerald T.Keusch Elias Abrutyn 58 Brucellosis . . . . . . . . . . . . . . . . . . . . . . . . . . 547 Michael J.Corbel,Nicholas J.Beeching 41 Botulism . . . . . . . . . . . . . . . . . . . . . . . . . . . 434 Elias Abrutyn 59 Tularemia. . . . . . . . . . . . . . . . . . . . . . . . . . . 552 Richard F.Jacobs,Gordon E.Schutze 42 Gas Gangrene and Other Clostridial Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . 438 60 Plague and Other Yersinia Infections . . . . . . . 558 Dennis L.Kasper,Lawrence C.Madoff David T.Dennis,Grant L.Campbell 43 Clostridium Difficile–Associated Disease, 61 Bartonella Infections,Including Including Pseudomembranous Colitis . . . . . . 445 Cat-Scratch Disease . . . . . . . . . . . . . . . . . . . 569 Dale N.Gerding,Stuart Johnson David H.Spach,Emily Darby Contents vii 62 Donovanosis. . . . . . . . . . . . . . . . . . . . . . . . . 574 SECTION V Gavin Hart VIRAL INFECTIONS Part 4 Miscellaneous Bacterial Infections Part 1 Viral Diseases:General Considerations 63 Nocardiosis . . . . . . . . . . . . . . . . . . . . . . . . . 576 78 Medical Virology . . . . . . . . . . . . . . . . . . . . . 706 Gregory A.Filice Fred Wang,Elliott Kieff 64 Actinomycosis . . . . . . . . . . . . . . . . . . . . . . . 581 79 Antiviral Chemotherapy,Excluding Thomas A.Russo Antiretroviral Drugs . . . . . . . . . . . . . . . . . . . 717 Lindsey R.Baden,Raphael Dolin 65 Infections Due to Mixed Anaerobic Organisms . . . . . . . . . . . . . . . . . . . . . . . . . . 586 Part 2 Infections Due to DNA Viruses Dennis L.Kasper,Ronit Cohen-Poradosu 80 Herpes Simplex Viruses. . . . . . . . . . . . . . . . . 730 Lawrence Corey Part 5 Mycobacterial Diseases 81 Varicella-Zoster Virus Infections . . . . . . . . . . 740 66 Tuberculosis. . . . . . . . . . . . . . . . . . . . . . . . . 596 Richard J.Whitley Mario C.Raviglione,Richard J.O’Brien 82 Epstein-Barr Virus Infections,Including 67 Leprosy (Hansen’s Disease) . . . . . . . . . . . . . . 617 Infectious Mononucleosis . . . . . . . . . . . . . . . 745 Robert H.Gelber Jeffrey I.Cohen 68 Nontuberculous Mycobacteria . . . . . . . . . . . 627 83 Cytomegalovirus and Human C.Fordham von Reyn Herpesvirus Types 6,7,and 8. . . . . . . . . . . . . 751 69 Antimycobacterial Agents . . . . . . . . . . . . . . . 635 Martin S.Hirsch Richard J.Wallace,Jr.,David E.Griffith 84 Molluscum Contagiosum,Monkeypox, Part 6 Spirochetal Diseases and Other Poxviruses,Excluding Smallpox Virus . . . . . . . . . . . . . . . . . . . . . . . 757 70 Syphilis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 644 Fred Wang Sheila A.Lukehart 85 Parvovirus Infections. . . . . . . . . . . . . . . . . . . 759 71 Endemic Treponematoses . . . . . . . . . . . . . . . 656 Kevin E.Brown Sheila A.Lukehart 86 Human Papillomavirus Infections . . . . . . . . . 762 72 Leptospirosis. . . . . . . . . . . . . . . . . . . . . . . . . 660 Richard C.Reichman Peter Speelman,Rudy Hartskeerl Part 3 Infections Due to DNA and RNA Respiratory 73 Relapsing Fever . . . . . . . . . . . . . . . . . . . . . . 665 Viruses David T.Dennis 87 Common Viral Respiratory Infections and Severe 74 Lyme Borreliosis. . . . . . . . . . . . . . . . . . . . . . 670 Acute Respiratory Syndrome (SARS) . . . . . . 766 Allen C.Steere Raphael Dolin Part 7 Diseases Caused by Rickettsiae,Mycoplasmas, 88 Influenza . . . . . . . . . . . . . . . . . . . . . . . . . . . 776 and Chlamydiae Raphael Dolin 75 Rickettsial Diseases. . . . . . . . . . . . . . . . . . . . 676 Part 4 Infections Due to Human Immunodeficiency David H.Walker,J.Stephen Dumler, Virus and Other Human Retroviruses Thomas Marrie 89 The Human Retroviruses . . . . . . . . . . . . . . . 785 76 Infections Due to Mycoplasmas. . . . . . . . . . . 688 Dan L.Longo,Anthony S.Fauci William M.McCormack 90 Human Immunodeficiency Virus Disease: 77 Chlamydial Infections. . . . . . . . . . . . . . . . . . 692 AIDS and Related Disorders. . . . . . . . . . . . . 792 Walter E.Stamm Anthony S.Fauci,H.Clifford Lane viii Contents Part 5 Infections Due to RNA Viruses 107 Candidiasis. . . . . . . . . . . . . . . . . . . . . . . . . 1017 John E.Edwards,Jr. 91 Viral Gastroenteritis . . . . . . . . . . . . . . . . . . . 887 Umesh D.Parashar,Roger I.Glass 108 Aspergillosis. . . . . . . . . . . . . . . . . . . . . . . . 1021 David W.Denning 92 Acute Viral Hepatitis. . . . . . . . . . . . . . . . . . . 893 Jules L.Dienstag 109 Mucormycosis . . . . . . . . . . . . . . . . . . . . . . 1028 Alan M.Sugar 93 Chronic Hepatitis. . . . . . . . . . . . . . . . . . . . . 917 Jules L.Dienstag 110 Miscellaneous Mycoses and Algal Infections . . . 1031 Stanley W.Chapman,Donna C.Sullivan 94 Enteroviruses and Reoviruses . . . . . . . . . . . . 939 Jeffrey I.Cohen 111 Pneumocystis Infection . . . . . . . . . . . . . . . . . 1037 A.George Smulian,Peter D.Walzer 95 Measles (Rubeola) . . . . . . . . . . . . . . . . . . . . 947 Anne Gershon 96 Rubella (German Measles) . . . . . . . . . . . . . . 952 SECTION VIII Anne Gershon PROTOZOAL AND 97 Mumps . . . . . . . . . . . . . . . . . . . . . . . . . . . . 956 HELMINTHIC INFECTIONS Anne Gershon Part 1 Parasitic Infections:General Considerations 98 Rabies and Other Rhabdovirus Infections . . . 959 112 Laboratory Diagnosis of Parasitic Alan C.Jackson,Eric C.Johannsen Infections. . . . . . . . . . . . . . . . . . . . . . . . . . 1042 99 Infections Caused by Arthropod- and Sharon L.Reed,Charles E.Davis Rodent-Borne Viruses . . . . . . . . . . . . . . . . . 965 113 Agents Used to Treat Parasitic Clarence J.Peters Infections. . . . . . . . . . . . . . . . . . . . . . . . . . 1050 100 Ebola and Marburg Viruses . . . . . . . . . . . . . . 985 Thomas A.Moore Clarence J.Peters 114 Pharmacology of Agents Used SECTION VI to Treat Parasitic Infections . . . . . . . . . . . . . 1059 PRION DISEASES Thomas A.Moore Part 2 Protozoal Infections 101 Prion Diseases . . . . . . . . . . . . . . . . . . . . . . . 990 Stanley B.Prusiner,Bruce L.Miller 115 Amebiasis and Infection With Free-Living Amebas . . . . . . . . . . . . . . . . . . 1070 SECTION VII Sharon L.Reed FUNGAL AND ALGAL INFECTIONS 116 Malaria. . . . . . . . . . . . . . . . . . . . . . . . . . . . 1077 102 Diagnosis and Treatment of Fungal Nicholas J.White,Joel G.Breman Infections. . . . . . . . . . . . . . . . . . . . . . . . . . 1000 John E.Edwards,Jr. 117 Babesiosis. . . . . . . . . . . . . . . . . . . . . . . . . . 1097 Jeffrey A.Gelfand,Edouard Vannier 103 Histoplasmosis . . . . . . . . . . . . . . . . . . . . . . 1003 Chadi A.Hage,L.Joseph Wheat 118 Atlas of Blood Smears of Malaria and Babesiosis. . . . . . . . . . . . . . . . . . . . . . . 1100 104 Coccidioidomycosis . . . . . . . . . . . . . . . . . . 1007 Nicholas J.White,Joel G.Breman Neil M.Ampel 119 Leishmaniasis . . . . . . . . . . . . . . . . . . . . . . . 1104 105 Blastomycosis. . . . . . . . . . . . . . . . . . . . . . . 1011 Barbara L.Herwaldt Stanley W.Chapman,Donna C.Sullivan 106 Cryptococcosis. . . . . . . . . . . . . . . . . . . . . . 1013 120 Trypanosomiasis. . . . . . . . . . . . . . . . . . . . . 1111 Arturo Casadevall Louis V.Kirchhoff Contents ix 121 Toxoplasma Infections . . . . . . . . . . . . . . . . . 1118 126 Schistosomiasis and Other Lloyd H.Kasper Trematode Infections . . . . . . . . . . . . . . . . . 1154 Adel A.F.Mahmoud 122 Protozoal Intestinal Infections and Trichomoniasis. . . . . . . . . . . . . . . . . . . 1127 127 Cestodes. . . . . . . . . . . . . . . . . . . . . . . . . . . 1163 Peter F.Weller A.Clinton White,Jr.,Peter F.Weller Part 3 Helminthic Infections Appendix Laboratory Values of Clinical Importance . . . . 1173 123 Trichinella and Other Tissue Nematodes . . . . 1133 Alexander Kratz,Michael A.Pesce,Daniel J.Fink Peter F.Weller Review and Self-Assessment. . . . . . . . . . . . . . 1195 124 Intestinal Nematodes . . . . . . . . . . . . . . . . . 1139 Charles Wiener,Gerald Bloomfield, Peter F.Weller,Thomas B.Nutman Cynthia D.Brown,Joshua Schiffer,Adam Spivak 125 Filarial and Related Infections. . . . . . . . . . . 1145 Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1231 Thomas B.Nutman,Peter F.Weller

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ANTHONY S. FAUCI, MD. Chief, Laboratory of Immunoregulation;. Director, National Institute of Allergy and Infectious Diseases,. National Institutes of
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