Salvage agents and future therapies

Interferon Gamma Therapy

In-vitro studies have demonstrated interferon gamma (IFN-γ) production by peripheral blood mononuclear cells is reduced in patients with chronic coccidioidomycosis (1-3) and defects within the IL-12/IFN-γ have been reported in several patients with disseminated coccidioidal infection (4, 5). These findings have encouraged the use of adjunctive exogenous IFN-γ along with antifungal use in patients with refractory disseminated coccidioidomycosis although use is limited by patient tolerability, expense, and a lack of a clear benefit in the absence of compelling clinical data(6).

Future Therapies

Future innovative ways to target this disease are in development. Nikkomycin Z has shown promise with a possibility of cure in murine models of infection. Safety trials have been conducted and clinical trials are anticipated in 2016 or shortly thereafter.

As this organism is capable of eliciting a wide range of immunologic reactions, further research in the areas of immunotherapy and vaccination will be of great importance. It is well known that some hosts are able to effectively control infection, while others develop severe complications. The current knowledge of host risk factors and immunogenetics is in the early stages and a better understanding of the mechanisms for effective host control of disease may allow the possibility of intervention (7, 8).

REFERENCES

1. Ampel NM, Kramer LA. In vitro modulation of cytokine production by lymphocytes in human coccidioidomycosis. Cell Immunol 2003; 221(2): 115-21.
2. Ampel NM, Christian L. In vitro modulation of proliferation and cytokine production by human peripheral blood mononuclear cells from subjects with various forms of coccidioidomycosis. Infect Immun 1997; 65(11): 4483-7.
3. Corry DB, Ampel NM, Christian L, Locksley RM, Galgiani JN. Cytokine production by peripheral blood mononuclear cells in human coccidioidomycosis. The Journal of infectious diseases 1996; 174(2): 440-3.
4. Vinh DC, Masannat F, Dzioba RB, Galgiani JN, Holland SM. Refractory disseminated coccidioidomycosis and mycobacteriosis in interferon-gamma receptor 1 deficiency. Clin Infect Dis 2009; 49(6): e62-5.
5. Vinh DC. Coccidioidal Meningitis: Disseminated Disease in Patients Without HIV/AIDS. Medicine (Baltimore) 2011; 90(1): 87.
6. Kuberski TT, Servi RJ, Rubin PJ. Successful treatment of a critically ill patient with disseminated coccidioidomycosis, using adjunctive interferon-gamma. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2004; 38(6): 910-2.
7. Thompson GR, 3rd, Stevens DA, Clemons KV, et al. Call for a California coccidioidomycosis consortium to face the top ten challenges posed by a recalcitrant regional disease. Mycopathologia 2015; 179(1-2): 1-9.
8. Thompson GR, 3rd, Bays D, Taylor SL, Cohen SH, Pappagianis D. Association between serum 25-hydroxyvitamin D level and type of coccidioidal infection. Medical mycology 2013; 51(3): 319-23.