INFECTIONS IN THE IMMUNOCOMPROMISED HOST Laboratory Diagnosis and Treatment

Transcription

1 INFECTIONS IN THE IMMUNOCOMPROMISED HOST Laboratory Diagnosis and Treatment

2 ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY Editorial Board: NATHAN BACK, State University of New York at Buffalo NICHOLAS R. DI LUZIO, Tulane University School of Medicine EPHRAIM KATCHALSKI-KATZIR, The Weizmann Institute of Science DAVID KRITCHEVSKY, Wistar Institute ABEL LAJTHA, Rockland Research Institute RODOLFO PAOLETTI, University of Milan Recent Volumes in this Series Volume 196 STEROID HORMONE RESISTANCE: Mechanisms and Clinical Aspects Edited by George P. Chrousos, D. Lynn Loriaux, and Mortimer B. Lipsett Volume 197 BIOLOGICAL REACTIVE INTERMEDIATES III: Mechanisms of Action in Animal Models and Human Disease Edited by James J. Kocsis, David J. Jollow, Charlotte M. Witmer, Judd o. Nelson, and Robert Snyder Volume 198A KININS IV, Part A Edited by Lowell M. Greenbaum and Harry S. Margolius Volume 198B KININS IV, Part B Edited by Lowell M: Greenbaum and Harry S. Margolius Volume 199 NUTRITIONAL AND TOXICOLOGICAL SIGNIFICANCE OF ENZYME INHIBITORS IN FOODS Edited by Mendel Friedman Volume 200 OXYGEN TRANSPORT TO TISSUE VIII Edited by Ian S. Longmuir Volume 201 LIPOPROTEIN DEFICIENCY SYNDROMES Edited by Aubie Angel and Jiri Frohlich Volume 202 INFECTIONS IN THE IMMUNOCOMPROMISED HOST Laboratory Diagnosis and Treatment Edited by Paul Actor, Alan Evangelista, James Poupard, and Eileen Hinks 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.

3 INFECTIONS IN THE IMMUNOCOMPROMISED HOST Laboratory Diagnosis and Treatment Edited by Paul Actor Smith Kline and French Laboratories Philadelphia, Pennsylvania Alan Evangelista Cooper Hospital University Medical Center Camden, New Jersey J ames Poupard Bryn Mawr Hospital Bryn Mawr, Pennsylvania and Eileen Rinks Rolling Hill Hospital Elkins Park, Pennsylvania PLENUM PRESS NEW YORK AND LONDON

4 Library of Congress Cataloging in Publication Data Eastern Pennsylvania Branch of the American Society for Microbiology Symposium on Infections in the Compromised Host: Laboratory Diagnosis and Treatment: (1983: Philadelphia, Pa.) Infections in the immunocompromosed host. (Advances in experimental medicine and biology; v. 202) "Proceedings of the Eastern Pennsylvania Branch of the American Society for Microbiology Symposium on Infections in the Compromised Host: Laboratory Diagnosis and Treatment, held November 17-18, 1983, in Philadelphia, Pennsylvania"-T.p. verso. Includes bibliographies and index. 1. Immunological deficiency syndromes - Complications and sequelae - Congresses. 2. Communicable diseases-congresses. 3. Infection-Congresses. I. Actor, Paul. II. American Society for Microbiology. Eastern Pennsylvania Branch. III. Title. IV. Series. [DNLM: 1. Immunologic Deficiency Syndromes-complications-congresses. 2. Infection-immunology-congresses. WI AD559/QW 700 E13i 1983] RC606.E ISBN-13: e-isbn-13: DOl: Proceedings of the Eastern Pennsylvania Branch of the American Society for Microbiology Symposium on Infections in the Compromised Host: Laboratory Diagnosis and Treatment, held November 17-18, 1983, in Philadelphia, Pennsylvania 1986 Plenum Press, New York softcover reprint of the hardcover 1 st edition 1986 A Division of Plenum Publishing Corporation 233 Spring Street, New York, N.Y All rights reserved No part of this 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

5 PREFACE The subject matter of this volume, the basis for which was a conference held in Philadelphia which focused on the subject of infections, including their diagnosis and treatment, in immunocompromised individuals. The material is of particular importance today when placed against the background of the rapid spread of acquired immunodeficiency syndrome (AIDS). The first section dealt with the general subject of the immunocompromised host. Here, reviewed in detail, were the epidemiological and clinical aspects of opportunistic infections in patients with defective immune responses. It is widely acknowledged that infections are a major complication of the neoplastic process. Cancer-bearing patients are more prone to certain kinds of infectious and cancer chemotherapy almost always increases susceptibility to such infections. Depending upon the basic disease process of the cancer, a specific array of infectious diseases can be predicted. Patients altered in thymus-derived lymphocyte populations or mononuclear phagocyte capabilities resulting in defects in cell mediated immunity or delayed hypersensitivity become highly susceptible to certain groups of organisms, whereas, profoundly neutropenic patients usually become infected with different organisms. The types of infections noted are relatively predictable for the type of immune defect, with some variations according to epidemiological factors. Major advances have been made in the early diagnosis and treatment of infectious complications with increasingly effective antimicrobial agents and increasing knowledge of their use. The application of so-called preventive procedures has had limited value to date, including immunotherapy, which appears to hold much promise. Covered also was the immunomodulatory effects of microorgani.sms and their products. Infectious agents including bacteria, viruses, fungi and parasites can stimulate the nonspecific proliferation and activation of the immune system or specifically stimulate the antimicrobial immune response resulting in humoral antibody or specific sensitized cells. Various microorganisms and their products, especially those derived from mycobacteria, and other intracellular bacteria, can stimulate v

6 vi PREFACE nonspecific responses and activate macrophages. The perturbation of the immune response observed during experimental and human infections is well-documented. For the most part, this is brought about by either generalized anergy or a selective deregulation of immune responses. Additionally, bacterial, viral and fungal infections have been shown to cause alterations in macrophage function. Parasites can alter the immune response by enhancing polyclonal antibody responses or inducing excessive number of suppressor cells, which inhibit both specific and non-specific immune responses. Viral infections, in man and animals are known to depress existing immune responses including delayed hypersensitivity. Onchogenic viruses may selectively depress certain immune effector cells. Leukemia viruses, in particular, have been widely studied in regards to their effects on immune parameters. These latter studies have direct relevance to AIDS with the demonstration that a human T-cell virus is the etiological agent. A wide variety of immunomodulatory agents have been studied experimentally in terms of their ability to reverse immunodeficiency induced by tumor viruses. The immunomodulatory properties of products derived from bacteria, including endotoxins, lipoteichoic acids and exotoxins have been shown to be due to selective effects on certain classes of immunocompetent cells. The interaction of bacteria or their products with macrophages results in the release of immunomodulatory mediators. Induction of small molecular weight substances such as prostaglandins also may occur in response to microorganisms or their products on immune response mechanisms. Subsequent sessions of the Symposium dealt with laboratory aspects of diagnosis of infectious diseases in compromised patients, as well as the description of various opportunistic infections in such patients. Non-tuberculous mycobacterial species are found in increasing numbers in compromised patients. Among these are Mycobacterium marinum and M. intracellulari. Various aspects of Herpesvirus infections in immunocompromised hosts were covered in detail as were laboratory diagnosis and treatment. Fungal infections continue to be an important pathogen in immunocompromised patients. The role of Pneumocystis carinii and other parasitic infections in compromised hosts was discussed as was Cryptosporidium, another protozoan parasite. The effects of various biologically-active agents and immunostimulants on host immune response were covered in the concluding session. Liposomes and other particulate drug carriers can serve as models for localizing drugs predominantly in the mononuclear phagocytic cells of the reticuloendothelial system. Liposomes containing natural and synthetic immunomodulatory or anti-infective drugs (e.g. amphotericin B) have been shown

7 PREFACE effective in both animal and human infections as well as in animal tumor systems. The potential utility of this approach is compromised by toxicity problems encountered during extended treatment with liposomes with and without immunomodulators. Impairment of RES function and significant bone marrow pathology has been observed in animals treated i.v. with liposomes. These problems are a serious potential limiting factor in the future development of liposomes as a drug delivery system. The use of lymphokines and other biological response modifiers in the treatment of cancer was reviewed. Attempts to stimulate immune responses with a variety of non-specific immunomodulators in the form of bacterial extracts, viruses and chemicals have been largely unsuccessful in man. The rapid advances with genetically engineered biological products such as lymphokines and ctyokines and monoclonal antibodies may prove useful for cancer treatment, but here again, early results have not been highly successful. Such agents may act directly on tumor cells and/or stimulate the patient to produce an anti-tumor response. The topics of infectious disease and malignancy in immunocompromised hosts and the immunological defects underlying such conditions are being examined with greater frequency by many scientists. Cooperative efforts among immunologists, microbiologists, tumor biologists and clinicians in exploring the nature and mechanism of immunodeficiency in various disease states and the types and frequency of infectious diseases in such patients should provide valuable new knowledge in the future for treating and, perhaps, even preventing such diseases. Paul Actor Eileen Hinks Alan Evangelista James Poupard

8 ACKNOHLEDGEMENTS The editors are grateful to the Eastern Pennsylvania Branch of the American Society for Microbiology under whose sponsorships this Conference was held, and to the members of the organizing committee who worked diligently to make the symposium possible. He would like to acknowledge the support and sponsorship of Temple University School of Medicine, Hahnemann Medical College, Thomas Jefferson Medical College, and the School of Medicine of the University of Pennsylvania. The Conference would not have been possible without the generous financial support of Smith, Kline and French Laboratories whose contributions we gratefully acknowledge. Special thanks is offered to Dr. Toby K. Eisenstein, the branch President, for her encouragement and support of this endeavor. The Pennsylvania Department of Health--Bureau of Laboratories generously provided help with mailing and registrations. Thanks and appreciation to Cat Hebert for his assistance in layout, proof-reading and preparation of the camera-ready copy of the manuscripts. ix

9 ORGANIZING COMMITTEE Program Chairman Paul Actor, Ph.D. Smith Kline & French Laboratories Program Co-Chairmen Alan Evangelista, Ph.D. Cooper Hospitall Univ. Medical Center Camden, NJ James Poupard, Ph.D. Bryn Mawr Hospital Bryn Mawr, PA Carl Abramson, Ph.D. Pennsylvania College of Podiatric Medicine Josephine Bartola, J.D. Pennsylvania Department of Health Lionvi 11 e, PA Helen R.. Buckley, Ph.D. Temple University School of Medicine Halter Ceglowski, Ph.D. Temple University School of Medicine Committee Members Kenneth R. Cundy, Ph.D. Temple University School of Medicine Toby K. Eisenstein, Ph.D. Temple Univesity School of Medicine Linda Ann Miller, M.S., M.T. (A.S.C.P.) Bryn Mawr Hospital Bryn Mawr, PA Louis Nisbet, Ph.D. Smith Kline & French Labs. x

10 CONTENTS THE IMMUNOCOMPROMISED HOST - AN OVERVIEW Epidemiologic and Clinical Aspects of Opportunistic Infections.... Donald Armstrong Immunomodulating Effects of Microorganisms and Their Products on the Immune Response Mechanisms. 35 Herman Friedman The Diagnosis and Definition of the Acquired Immunodeficiency Syndrome. James A. Hoxie BACTERIAL AND VIRAL INFECTIONS IN THE COMPROMISED HOST M.I.D.A.S. - An On-Line Microbiology Information System Timothy E. Kiehn Opportuni sti c Mycobacteri a 1 Infections.. Robert Good Laboratory Diagnosis of Herpes Viruses in the Immunocompromised Host Harvey M. Friedman Herpesvirus Infections in the Immunocompromised Host: Diagnosis and Management Richard J. Whitley xi

11 xii CONTENTS FUNGAL AND PARASITIC INFECTIONS IN THE IMMUNOCOMPROMISED HOST - AN OVERVIEW Fungal Infections in the Compromised Host Richard D. Diamond Susceptibility Testing of Medically Important Fungi. Wi 11 i am G. Merz Cryptosporidium - Biology and Diagnosis. Pearl Ma Pneumocystis Garinii Pneumonia. David L. Kaufman IMMUNOTHERAPY Liposome Targeting to Macrophages: Opportunities for Treatment of Infectious Diseases. 171 Richard Kirsh and George Poste Biologicals and Other Biological Response Modifiers: Pre c 1 i n i cal and C 1 i n i cal Ass e s s me n tin Cancer Treatment Robert K. Oldham Index 205