Coccidioidomycosis Complement Fixation Titer Trends in the Age of Antifungals

Background: Coccidioidomycosis is associated with a broad spectrum of illness severity, ranging from asymptomatic or self-limited pulmonary infection to life-threatening manifestations of disseminated disease. Serologic studies before the widespread availability of antifungals established current understanding of serologic kinetics and dynamics. Methods: Chart history and complement fixation (CF) titer trends were analyzed for 434 antifungal-treated coccidioidomycosis patients classified by three infectious disease physicians as having either pulmonary uncomplicated coccidioidomycosis (PUC) (n=248), pulmonary chronic coccidioidomycosis (PCC) (n=64), disseminated coccidioidomycosis not including meningitis (DC) (n=86), or coccidioidal meningitis (CM) (n=36). Results: The median maximum CF titer was 1:4 for PUC, 1:24 for PCC, 1:128 for DC, and 1:32 for CM patients. Approximately 25.4% of PUC, 6.2% of PCC, 2.3% of DC, and 8.3% of CM patients did not develop a detectable titer during the study period. Maximum titers developed a mean of 31 (95% CI 13-50) days after initial serologic positivity with no significant differences between groups. Serologic recurrence occurred in 9% of PUC, 36% of PCC, 50% of DC, and 52% of CM patients. Median titer improvement rate was 91 days/dilution for PUC, 112 days/dilution for PCC, 136 days/dilution for DC, and 146 days/dilution for CM patients. ROC analysis revealed that complement fixation retains moderate classification value for disseminated (AUC=0.82, 95% CI: 0.78-0.87) and complicated (AUC of 0.82, 95% CI: 0.77-0.86) infections. A suitable cutoff for complicated infections is ≥1:32. Conclusion: Findings update serologic parameters that are relevant for clinical assessment of coccidioidomycosis patients in the triazole era.