Immunotherapy for Infectious Diseases

From: Immunotherapy for Infectious Diseases
Edited by: J. M. Jacobson © Humana Press Inc., Totowa, NJ
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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