Immunotherapy for Infectious Diseases
Immunotherapy for Infectious Diseases Immunotherapy for Infectious Diseases
From: Immunotherapy for Infectious Diseases Edited by: J. M. Jacobson © Humana Press Inc., Totowa, NJ 303 18 Immunotherapy for Fungal Infections Arturo Casadevall INTRODUCTION Most fungal pathogens are low-virulence organisms that seldom cause serious infections in individuals with intact immune function. However, fungal infections have emerged as a major medical problem in the second half of the 20th century. Factors that have contributed to this phenomenon are: (1) the development of therapies for cancer and autoimmune disorders that produce immune suppression as a consequence of their therapeutic effects; (2) increased use of indwelling vascular devices and invasive surgical techniques that compromise the integrity of the skin; (3) the use of broad spectrum antibacterial drugs that disrupt the host microbial flora and predispose to fungal superinfection; and (4) the epidemic of HIV infection that has resulted in many individuals with impaired immunologic function at risk for fungal infection. Fungi are notorious for producing chronic infections requiring prolonged therapy. The problems posed by fungal infections are compounded by the availability of only a few antifungal drugs that are relatively ineffective in patients with impaired immunity. In fact, many types of fungal infections in patients with impaired immune function cannot be eradicated with antifungal therapy. For example, cryptococcosis, coccidioidomycosis, and histoplasmosis are generally considered to be incurable in patients with advanced HIV infection. The major fungal infections and the conditions that predispose to them are listed in Table 1. Since most life-threatening fungal infections occur in patients with impaired immunity, therapies designed to reconstitute or activate the immune system are logical adjuncts to antifungal chemotherapy. Immunotherapy can be used to correct the underlying immunologic defect or to recruit additional resources of the immune system to fight the infection. Examples of immunotherapies designed to correct or compensate for immunologic defects are neutrophil transfusions and immunoglobulin administration in patients with neutropenia and hypogammaglobulinemia, respectively. Examples of immunotherapies designed to provide additional immunologic resources include the administration of cytokines to stimulate immune function or passive antibody therapy. Immunotherapy can be nonspecific or pathogen-specific. Nonspecific immunotherapy is designed to enhance general immune function by administration of immune modulators such as cytokines and growth factors. Pathogen-specific immunotherapy is designed to
304 Table 1 Major Fungal Infections and Risk Factors Major predisposing Infection Pathogen immunologic deficit Major risk factors Aspergillosis Aspergillus sp. Neutropenia Antineoplastic chemotherapy, late stage HIV infection Blastomycosis Blastomyces dermatitides Defects in cell-mediated immunity Immunosuppressive therapy, late stage HIV infection; can occur in normal individuals Candidiasis Candida sp. Neutropenia Immunosuppressive therapy, HIV infection, antibiotic use, surgical procedures, indwelling catheters Coccidioidomycosis Coccidioides immitis Defects in cell-mediated immunity Late stage HIV infection, pregnancy, certain ethnic groups; may occur in normal individuals Cryptococcosis Cryptococcus neoformans Defects in cell-mediated immunity Late stage HIV infection, corticosteroid use, lymphoproliferative malignancies; may occur in normal individuals Histoplasmosis Histoplasma capsulatum Defects in cell-mediated immunity Late stage HIV infection, corticosteroid therapy; may occur in normal individuals Mucormycosis Rhizopus sp. Diabetic ketoacidosis, neutropenia Diabetes mellitus, antineoplastic chemotherapy Paracoccidioidomycosis Paracoccidioides brasiliensis Defects in cell-mediated immunity Late stage HIV infection; may occur in normal individuals Penicilliosis Penicillium marneffei Defects in cell-mediated immunity Late stage HIV infection, immunosuppressive therapy Sporotrichosis Sporothrix schenckii Defects in cell-mediated immunity Late stage HIV infection; may occur in normal individuals
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Table 1<br />
Major Fungal Infections and Risk Factors<br />
Major predisposing<br />
Infection Pathogen immunologic deficit Major risk factors<br />
Aspergillosis Aspergillus sp. Neutropenia Antineoplastic chemotherapy, late stage HIV<br />
infection<br />
Blastomycosis Blastomyces dermatitides Defects in cell-mediated immunity Immunosuppressive therapy, late stage HIV<br />
infection; can occur in normal individuals<br />
Candidiasis Candida sp. Neutropenia Immunosuppressive therapy, HIV infection,<br />
antibiotic use, surgical procedures, indwelling<br />
catheters<br />
Coccidioidomycosis Coccidioides immitis Defects in cell-mediated immunity Late stage HIV infection, pregnancy, certain<br />
ethnic groups; may occur in normal<br />
individuals<br />
Cryptococcosis Cryptococcus neo<strong>for</strong>mans Defects in cell-mediated immunity Late stage HIV infection, corticosteroid use,<br />
lymphoproliferative malignancies; may<br />
occur in normal individuals<br />
Histoplasmosis Histoplasma capsulatum Defects in cell-mediated immunity Late stage HIV infection, corticosteroid<br />
therapy; may occur in normal individuals<br />
Mucormycosis Rhizopus sp. Diabetic ketoacidosis, neutropenia Diabetes mellitus, antineoplastic chemotherapy<br />
Paracoccidioidomycosis Paracoccidioides brasiliensis Defects in cell-mediated immunity Late stage HIV infection; may occur in<br />
normal individuals<br />
Penicilliosis Penicillium marneffei Defects in cell-mediated immunity Late stage HIV infection, immunosuppressive<br />
therapy<br />
Sporotrichosis Sporothrix schenckii Defects in cell-mediated immunity Late stage HIV infection; may occur in<br />
normal individuals