Abstract
Diagnosis of ongoing or past infection with Coxiella burnetii, the causative agent of Q fever, relies heavily on serology: the measurement of C. burnetii-specific antibodies, reflecting the host’s humoral immune response. However, cell-mediated immune responses play an important, probably even more relevant, role in infections caused by the intracellular C. burnetii bacterium. Recent studies have investigated interferon-gamma (IFN-γ) based assays, including a whole-blood IFN-γ production assay and a Coxiella enzyme-linked immunospot (Coxiella ELISPOT), as potential diagnostic tools for Q fever diagnosis. Both are in-house developed assays using stimulating antigens of different origin. The main objective of this study was to compare the test performance of the IFN-γ production assay and the Coxiella ELISPOT for detecting a cellular immune response to C. burnetii in Q fever patients, and to assess the correlation between both assays. To that end, both tests were performed in a well-defined patient group of chronic Q fever patients (n = 16) and a group of healthy seronegative individuals (n = 17). Among patients, both the Coxiella ELISPOT and the IFN-γ production assay detected positive response in 14/16. Among controls, none were positive in the Coxiella ELISPOT, whereas the IFN-γ production assay detected positive results in 1/17 and 3/17, when using Henzerling and Nine Mile as stimulating antigens, respectively. These results suggest the Coxiella ELISPOT has a somewhat higher specificity than the IFN-γ production assay when Nine Mile is used as antigen stimulus. The assays showed moderate correlation: the Spearman correlation coefficient r ranged between 0.37–0.60, depending on the antigens used. Further investigation of the diagnostic potential for C. burnetii infection of both assays is warranted.
Highlights
Q fever is a zoonotic disease that occurs worldwide and is caused by the gram-negative, intracellular bacterium Coxiella burnetii
Measurement of serum antibodies against C. burnetii is currently the ‘gold standard’ for Q fever diagnosis [3]
Fever relies heavily on detection of high IgG antibody titers against phase 1 C. burnetii. This serological criterion is combined with PCR for C. burnetii DNA on blood or tissue and clinical assessment of any nidus of chronic infection [4,5]
Summary
Q fever is a zoonotic disease that occurs worldwide and is caused by the gram-negative, intracellular bacterium Coxiella burnetii. Chronic Q fever is a rare but serious complication that occurs in approximately 5% of all patients following the acute infection. This persisting infection typically presents with endocarditis or vascular infection, and has significant mortality rates, especially in case of diagnostic and therapeutic delay [3]. Diagnosis of chronic Q fever relies heavily on detection of high IgG antibody titers against phase 1 C. burnetii. This serological criterion is combined with PCR for C. burnetii DNA on blood or tissue (if available) and clinical assessment of any nidus of chronic infection [4,5]
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