Potential value of an ELISPOT interferon gamma release assay as a diagnostic tool in Q fever infection

Rationale: Q fever is an emerging zoonosis in the Netherlands, atypical pneumonia being the most common clinical manifestation. Acute disease is followed by resolution in the majority of cases, 10-20% will exhibit the post-Q fever fatigue syndrome (QFS) and 1-5% of patients progresses to chronic disease. Current tests measuring humoral immune response to Coxiella burnetii have considerable limitations in diagnosing these different outcomes. We conducted an exploratory study to determine T cell response to C. burnetii specific antigens using an ELISPOT interferon gamma release assay (Coxiella ELISPOT). Methods: An in-house developed Coxiella ELISPOT interferon gamma release assay, using both phase I and phase II antigens was performed on blood samples of Q fever patients. Results: Coxiella ELISPOT was performed for 7 patients reconvalesced after acute Q fever and 2 chronic Q fever patients (n=1 newly diagnosed, n=1 after completion of treatment). Mean (± SE) spot count for reconvalesced patients was 11±5 (range 1-42) for phase I and 31±15 (range 1-120) for phase II. One patient was diagnosed with QFS and had the highest spot count in both phase I (42 spots) and phase II (120 spots). The newly diagnosed chronic Q fever patient (male, 64 ys) showed a predominant responsiveness to phase I antigen (spot count Phase I 209, Phase II 177). The other chronic Q fever patient (male, 67 ys) had finished a 18 month antibiotic treatment for Q fever endocarditis. Coxiella ELISPOT showed a marked T cell unresponsiveness to both phase I (3 spots) and phase II antigens (0 spots). Conclusion: Different clinical Q fever outcomes are associated with marked differences in Coxiella ELISPOT results.