Correlations between Peripheral Blood Coxiella burnetii DNA Load, Interleukin-6 Levels, and C-Reactive Protein Levels in Patients with Acute Q Fever

Abstract

e From 2007 to 2010, the Netherlands experienced the largest reported Q fever outbreak, with >4,000 notified cases. We showed previously that C-reactive protein is the only traditional infection marker reflecting disease activity in acute Q fever. Interleukin-6 is the principal inducer of C-reactive protein. We questioned whether increased C-reactive protein levels in acute Q fever patients coincide with increased interleukin-6 levels and if these levels correlate with the Coxiella burnetii DNA load in serum. In addition, we studied their correlation with disease severity, expressed by hospital admission and the development of fatigue. Interleukin-6 and C-reactive protein levels were analyzed in sera from 102 patients diagnosed with seronegative PCR-positive acute Q fever. Significant but weak negative correlations were observed between bacterial DNA loads expressed as cycle threshold values and interleukin-6 and C-reactive protein levels, while a significant moderate-strong positive correlation was present between interleukin-6 and C-reactive protein levels. Furthermore, significantly higher interleukin-6 and C-reactive protein levels were observed in hospitalized acute Q fever patients in comparison to those in nonhospitalized patients, while bacterial DNA loads were the same in the two groups. No marker was prognostic for the development of fatigue. In conclusion, the correlation between interleukin-6 and C-reactive protein levels in acute Q fever patients points to an immune activation pathway in which interleukin-6 induces the production of C-reactive protein. Significant differences in interleukin-6 and C-reactive protein levels between hospitalized and nonhospitalized patients despite identical bacterial DNA loads suggest an important role for host factors in disease presentation. Higher interleukin-6 and C-reactive protein levels seem predictive of more severe disease.

Dysregulation of Serum Gamma Interferon Levels in Vascular Chronic Q Fever Patients Provides Insights into Disease Pathogenesis

“…Of these markers, CRP and IL-6 were strongly increased in the acute Q fever group and to a lesser extent in the vascular chronic Q fever group compared to the past resolved Q fever group. Recent findings obtained in acute Q fever patients from the same outbreak also showed correlated responses between these two acute-phase response markers (20). We also show here that a set of CC-type chemokines (MIP1␣, RANTES, and eotaxin-1) shows downregulation in acute Q fever patients and a heterogeneous response in the group of vascular chronic Q fever patients.…”

Persistence of impaired health status of Q fever patients 4 years after the first Dutch outbreak

“…The NCSI has been used in previous studies assessing health status after Q fever infection [5, 6, 11–13]. It is based on an empirical definition of health status, covering ‘physiological functioning’, ‘symptoms’, ‘functional impairment in daily life’, and ‘quality of life’ as main domains.…”

Fatigue following Acute Q-Fever: A Systematic Literature Review

“…Of the 28 articles that contained information on aetiology, 18 were classified in the main table aetiology ( S4 Table ) [ 18 – 21 , 36 – 38 , 45 – 51 , 54 , 55 , 60 , 63 ].…”

“…burnetii antibodies disappeared [ 55 ]. In acute Q-fever IL-6 and CRP seemed predictive of more severe disease, but no support was found that these were associated with prolonged fatigue [ 63 ]. Markers of inflammation and pro-inflammatory cytokine concentrations did not remain altered in patients with post-infective fatigue [ 12 , 18 ].…”

“…No symptoms during the acute Q-fever infection were predictors for persisting symptoms [ 3 ], nor did these determine the long-term health status [ 65 ]. Neither IL-6 and CRP levels nor antibiotic treatment during the acute infection were predictors for the development of prolonged fatigue [ 3 , 63 ]. No relationship was found between fatigue and antibody titres six years after the Q-fever infection [ 49 ].…”