Coccidioidomycosis in Immunocompromised Patients

Patients with impaired immune function are at risk for both symptomatic infection as well as reactivation of latent disease. The risks of novel infection are often presumed higher in such a group, but definitive incidence data is limited. In a study of 2,246 solid organ transplant (SOT) recipients in Arizona, 239 (10.6%) had positive serologic testing with nearly all (212/239) showing evidence of coccidioidomycosis prior to transplantation (1). Post-transplant, an additional 27 of the 2,246 patients (1.2%) developed newly acquired, active disease. In a study of allogeneic hematopoietic cell transplantation (allo-HCT) patients, 11/426 (2.6%) developed active coccidioidomycosis post-transplant (2). In these groups, the rates of dissemination and mortality are higher than in the general population, with up to 55% mortality observed in allo-HCT recipients and 28% in SOT recipients(1-3). Observation of such outcomes has led many clinicians to recommend prophylaxis in high-risk transplant recipients. Due to suboptimal testing sensitivities, achieving a diagnosis can be challenging, and may require multiple testing modalities [62].

Further studies have demonstrated that patients with serologic evidence of prior coccidioidomycosis before organ transplantation have higher rates of post-transplant coccidioidomycosis than others, suggesting that Coccidioides may reactivate from latency, with some risk factors including high dose prednisone, and treatment for rejection(4). In the aforementioned study of allo-HCT patients, 8 of 426 (1.9%) had asymptomatic positive serologic tests prior to transplantation, and two (25%) had reactivation following transplantation. While antifungal prophylaxis has been evaluated and appears effective in some studies, it may not be a panacea. In a study of 100 patients with coccidioidomycosis who underwent SOT, 94% received antifungal prophylaxis and of this group, five patients experienced reactivated infection (5). Notably, all patients survived with modified ongoing antifungal therapies.

It should also be noted that donor derived coccidioidomycosis is possible (6). Transmission rates are difficult to determine, but onset of disease has a high mortality in these patients. Pre-transplant recipient and donor screening in endemic areas or with a history of travel to endemic areas is recommended. Multiple testing modalities may be considered depending on clinical presentation and may include serology, pathology, culture, PCR, and in the future, skin-testing and an excellent review has been recently published (1). In patients with HIV, coccidioidomycosis may be considered an opportunistic infection. While primary prophylaxis has not been demonstrated to be effective, treatment of primary pulmonary coccidioidomycosis is warranted, especially if CD4+ lymphocyte counts are <250 cells/μL (7). Secondary prophylaxis may be considered until counts rise >250 cells/μL.

The advent of biologic therapies and targeted chemotherapeutics has resulted in further questions regarding their use in endemic areas. At present, the exact risks of acquiring coccidioidomycosis on any given biologic agent are unknown. In a convenience sample in an endemic area 1.9% of patients in a rheumatology center had evidence of coccidioidomycosis (8). The prevalence in rheumatoid arthritis patients was ~3.1%, but use of TNF-α inhibitors could not be proven to have association in this study. In contrast, a prior study of patients receiving infliximab and etanercept found 13 cases of coccidioidomycosis (7/247 in the infliximab group vs. 4/738 treated with other modalities, RR 5.23, p < 0.01) (9). Screening may be employed, but the benefit is unclear. Antifungal prophylaxis is not currently recommended.

REFERENCES

1. Mendoza N, Blair JE. The utility of diagnostic testing for active coccidioidomycosis in solid organ transplant recipients. American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2013; 13(4): 1034-9.
2. Mendoza N, Noel P, Blair JE. Diagnosis, treatment, and outcomes of coccidioidomycosis in allogeneic stem cell transplantation. Transplant infectious disease: an official journal of the Transplantation Society 2015; 17(3): 380-8.
3. Vucicevic D, Carey EJ, Blair JE. Coccidioidomycosis in liver transplant recipients in an endemic area. American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2011; 11(1): 111-9.
4. Blair JE, Kusne S, Carey EJ, Heilman RL. The prevention of recrudescent coccidioidomycosis after solid organ transplantation. Transplantation 2007; 83(9): 1182-7.
5. Keckich DW, Blair JE, Vikram HR, Seville MT, Kusne S. Reactivation of coccidioidomycosis despite antifungal prophylaxis in solid organ transplant recipients. Transplantation 2011; 92(1): 88-93.
6. Engelthaler DM, Chiller T, Schupp JA, et al. Next-generation sequencing of Coccidioides immitis isolated during cluster investigation. Emerging infectious diseases 2011; 17(2): 227-32.
7. Masannat FY, Ampel NM. Coccidioidomycosis in patients with HIV-1 infection in the era of potent antiretroviral therapy. Clin Infect Dis 2010; 50(1): 1-7.
8. Mertz LE, Blair JE. Coccidioidomycosis in rheumatology patients: incidence and potential risk factors. Ann N Y Acad Sci 2007; 1111: 343-57.
9. Bergstrom L, Yocum DE, Ampel NM, et al. Increased risk of coccidioidomycosis in patients treated with tumor necrosis factor alpha antagonists. Arthritis and rheumatism 2004; 50(6): 1959-66.