Immunotherapy for Infectious Diseases

314 Casadevall
effective in achieving cures in horses with recent infection (58). This therapeutic vaccine
apparently mediates its effects by eliciting strong inflammatory responses that
result in eradication of infection (58). There is one case report of the use of this vaccine
in humans that describes the case of a 14-year-old Thai boy with P. insidiosum arteritis
who was apparently cured by vaccine therapy (59). The efficacy of this vaccine in horses
suggests that for some fungal infections, it may be possible to develop vaccine therapy
with specific antigen preparations that stimulate the immune system to control infection.
Transfer Factor
Transfer factor is an extract from lymphoid cells sensitized with antigen that can
transfer cell-mediated reactivity in the form of delayed cutaneous hypersensitivity
response (reviewed in ref. 60). Although many aspects of this phenomenon remain controversial,
transfer factor has been used for the treatment of refractory fungal infections
(60–62). Chronic mucocutaneous candidiasis in patients without HIV infection is a rare
disease characterized by chronic C. albicans infections of the nails, skin, and mucous
membranes (63). Several remarkable remissions of candidal infection have been
reported in some patients with chronic mucocutaneous candidiasis treated with transfer
factor (60). Graybill et al. (64) reported three patients with disseminated coccidioidomycosis
who were treated with transfer factor and amphotericin B. All three
patients displayed increased cellular responses to C. immitis antigens after receiving
transfer factor, and two manifested significant improvement with prolonged remissions
(64). Transfer factor was also used successfully in patients with histoplasmosis (65)
and cryptococcosis (66) in conjunction with amphotericin B.
For these case reports, it is difficult to separate the potential therapeutic contribution
of transfer factor from that of standard antifungal therapy. The use of transfer factor
has been plagued by inconsistent results in clinical trials, and its use remains experimental.
In fact, interest in transfer factor therapy has waned in recent years, as indicated
by the relative paucity of new studies in the literature. Guidelines for
the preparation of dialyzable leukocyte extracts containing transfer factor have been
proposed (62).
Fungal Antigens
Although not a classic fungal infection, brief mention will be made of the use of
fungal antigens to treat allergic fungal sinusitis. Allergic fungal sinusitis has histologic
features resembling those of allergic bronchopulmonary aspergillosis and is characterized
by association with asthma, nasal polyps, and allergic mucin, a viscous secretion
that contains degenerating eosinophils and Charcot-Leyden crystals (67,68). Aspergillus
species are frequently cultured from mucin, but a variety of other fungal species have
been cultured from patients with allergic fungal sinusitis including Bipolaris, Curvelaria,
Alternaria, and Cladosporium (69). The standard therapy for allergic fungal
sinusitis is surgical drainage and corticosteroid administration, but relapses are common
(67). Because of the immunologic nature of this disease, immunotherapy has been
suggested to be potentially beneficial (69). Immunotherapy for allergic fungal sinusitis
involves the injection of fungal antigens to which an individual shows a positive
reaction to intradermal testing (69). Although there have been concerns about whether