Immunotherapy for Infectious Diseases

Fungal Infections 313
randomized controlled trials to evaluate the efficacy of M-CSF as adjunctive therapy for
invasive fungal infections (47). M-CSF administration is well tolerated. The major side
effects are a transient dose-related thrombocytopenia that may be caused by enhanced
function of splenic phagocytic cells (45).
Interferon-�
IFN-� is a T-cell-derived cytokine that has powerful effects on macrophage cell activation
(48). Since macrophages are critically important for the control of many fungal
infections, there has been considerable interest in the potential usefulness of INF-� for
therapy of fungal infections. IFN-� has been used with some success in combination
with conventional therapy for patients with mycobacterial infections (49). Studies in
animals provide encouragement for the use of IFN-� as an adjunct to antifungal therapy
(reviewed in refs. 1 and 5). For example, a single dose of IFN-� enhanced the efficacy
of amphotericin B against Cryptococcus neoformans in mice (50). However, at
this time there is relatively little clinical information available regarding the usefulness
of IFN-� in the treatment of fungal infections. IFN-� administration has been used successfully
as adjunctive therapy for infection in a few patients with unusual fungal infections
in the setting of chronic granulomatous disease (CGD) (reviewed in ref. 51)
(Table 3). CGD is an inherited immunodeficiency that results from a diminished ability
of PMNs to produce the microbicidal respiratory burst. Patients with CGD are susceptible
to a variety of pathogens including fungi, and IFN-� can reduce the frequency
of fungal infections, including Aspergillus (52). The cases of Paecilomyces varioti
infection in patients with CGD were cured with a combination of IFN-� and amphotericin
B (Table 4). A 10-year-old boy with CGD and disseminated Pseudallescheria
boydii infection was cured with combination of miconazole and IFN-� (53). Administration
of IFN-� is generally well tolerated. Most of the clinical adverse reactions consist
of fever, chills, headache, and injection site erythema (49,52).
INTRAVENOUS IMMUNE GLOBULIN
Passive antibody administration modifies the course of several fungal infections
(54). The only antibody preparation available for clinical use is immunoglobulin. Since
antibodies to fungal antigens are sometimes found in normal human sera, the administration
of immunoglobulin could, in theory, be useful in therapy. However, there are
very few data to support the routine use of intravenous immunoglobulin (IVIG) for
treatment or prevention of fungal infections. Combination therapy of amphotericin B
and IVIG for experimental C. albicans in mice resulted in a modest improvement in
survival (55). Prophylactic IVIG administration was associated with a reduction in fungal
infections in liver transplant recipients (56) but not in bone marrow recipients (57).
PATHOGEN-SPECIFIC IMMUNE THERAPY
Therapeutic Vaccine for Pythium insidisum
Pythiosis insidiosi is a rare human fungal infection caused by Pythium insidisum. In
horses, pythiosis is a relatively common infection that is treated with surgery, antifungal
agents, and a therapeutic vaccine composed of Pythium antigens. Mendoza et al.
have described Two vaccines for pythiosis have been described made from either
P. insidiosum whole cells or soluble concentrated antigens (59). Both vaccines are