Immunotherapy for Infectious Diseases

306 Casadevall
species suggest that optimal immunotherapy may require an individualized approach
to each type of fungal infection. Susceptibility to a particular fungal infection is, in
turn, a function of the specific immunological deficit of the host. Patients with neutropenia
are at high risk for Candida and Aspergillus infections, whereas those with
impaired cellular immunity are at high risk for the endemic mycosis (i.e., histoplasmosis,
coccidioidomycosis, blastomycosis, penicilliosis). Each fungal infection must
be considered in the context of the immunologic deficit of the host, and therapy should
be targeted at restoring or compensating for that particular immunologic impairment.
An important concept is that it may be possible to use immune therapy to compensate
for immunologic deficits by taking advantage of the many defense functions that comprise
the immune system. For example, neutropenic mice can be protected against
experimental candidiasis by administration of specific antibody, even though the role
of natural antibody-mediated immunity in candidiasis is uncertain (8). Hence, it may
be possible to design effective immune therapies that promote eradication of fungal
infections without the vastly more complicated task of having to reverse the underlying
immunologic deficit.
APPROACH TO THE LITERATURE
ON IMMUNOTHERAPY FOR FUNGAL INFECTIONS
The literature on immunotherapies for fungal infections consists of animal studies
and human clinical data. In general, animal studies are usually well controlled and rigorously
performed. In contrast, most of the information available about immunotherapy
in humans comes from case reports and small studies. Hence, the reader must
exercise caution when interpreting the human data and making inferences that are
applicable to specific clinical situations. It is important to consider that the literature
may be biased toward favorable outcomes since these are more likely to be reported
than negative experiences. Firm conclusions about the value of specific types
of immunotherapy for specific fungal infections must await the completion of wellcontrolled
studies. Nevertheless, case reports and small studies provide important clinical
information that can be used to design larger trials or guide heroic therapies in
desperately ill patients with fungal infections refractory to standard therapy.
NONSPECIFIC REPLACEMENT IMMUNE THERAPIES
Granulocyte Transfusions
Granulocyte transfusions were first used in the 1960s for the treatment and prevention
of infection in patients with severe polymorphonuclear (PMN) leukocyte deficiency
(neutropenia) resulting from cancer therapy. Granulocyte transfusions provide mature
PMNs to serve an antimicrobial role. Leukocyte preparations containing primarily
PMNs can be isolated from the blood of healthy donors by centrifugation or leukopharesis.
Although granulocyte transfusions may help neutropenic patients survive a bout of
infection, their use has been controversial because of high cost, significant toxicity, and
lack of evidence that they affect long-term survival (for review, see ref. 9).
The popularity of granulocyte transfusions diminished significantly in the 1980s
because of several developments (reviewed in refs. 10 and 11). First, alternatives to
granulocyte transfusions became available in the form of CSFs that promoted more