Fluoride excess in coccidioidomycosis patients receiving long-term antifungal therapy: an assessment of currently available triazoles.

The use of voriconazole, a trifluorinated antifungal, has been associated with the development of fluoride excess and periostitis/exostoses. We evaluated a cohort of patients on long-term triazole therapy and found that other fluorinated triazoles (fluconazole and posaconazole) conferred no risk for the development of hyperfluorosis and its complications in our cohort.

Coccidioidomycosis in California state correctional institutions.

Coccidioidomycosis (CM) has been recognized in inmates of California State prisons since 1919, where it has been diagnosed in inmates of various correctional facilities inside and outside the known endemic areas. In recent years construction of new prisons within endemic areas has led to an increase in the number of cases of CM. In 2005 and 2006, the Pleasant Valley State Prison (PVSP) near Coalinga and Avenal State Prison (ASP) near Avenal on the western side of the San Joaquin Valley have been particularly affected. In 2005, our serologic testing yielded 150 new cases from PVSP and 30 from ASP. The incidence rate in 2005 for PVSP (population approximately 5,000) was at least 3,000 per 100,000, and this will be exceeded in 2006. Some cases diagnosed in early 2006 likely were infections that were acquired in 2005. Some cases are medically managed on site, but very ill inmates have had care in nonprison facilities. Precise numbers of patients who were hospitalized were not made available to the author. Estimates of the cost per patient have varied from $8,000 in the 1990s to $30,000 more recently. Thus, this disease has important medical, demographic, and financial implications for the state.

Preliminary evaluation of whole-blood gamma interferon release for clinical assessment of cellular immunity in patients with active coccidioidomycosis.

Assessment of the cellular immune response in coccidioidomycosis has epidemiologic and prognostic importance. Measurement of delayed-type hypersensitivity to skin testing has been used in the past to determine cellular immunity in coccidioidomycosis. However, no skin tests are currently available in the United States. Assay of gamma interferon (IFN-gamma) release in whole blood in response to incubation with antigen has been used to assess cellular immunity in tuberculosis. We used a similar assay using the coccidioidal antigen preparation T27K to measure the in vitro cellular immune responses among a cohort of 69 subjects with active coccidioidomycosis. IFN-gamma release was bimodal, with concentrations above and below 5 IU/ml. Using multivariate logistic regression, underlying disease and disseminated or chronic pulmonary coccidioidomycosis was significantly associated with the release of IFN-gamma at a concentration of <5 IU/ml (P = 0.02 or 0.05, respectively). In addition, the release IFN-gamma concentration was <5 IU/ml in all subjects with a clinical severity score of > or =6 (P = 0.02). The release IFN-gamma concentration correlated with expression of CD69 on T lymphocytes in an in vitro assay using T27K as the antigen (Spearman's rho = 0.59; P < 0.01). These results suggest that the IFN-gamma release assay with T27K as the antigen may be a useful clinical test for assessing cellular immunity in patients with active coccidioidomycosis.