Chronic Q fever in The Netherlands

Abstract

From 2007-2010, during the recent Q fever epidemic in the Netherlands, over 4000 cases of acute Q fever were registered, which is an underestimation of the total amount of Coxiella burnetii infections due to a high amount of asymptomatic primary infections. In the literature it is stated that 1-5% of patients develop chronic Q fever after acute Q fever. We demonstrated that the risk for development of chronic Q fever after a known acute Q fever episode is approximately 2.5% for all chronic Q fever cases, and 1.5% if limited to proven and probable chronic Q fever cases. We have also demonstrated that the majority of patients with chronic Q fever did not recall an acute Q fever episode. From the Dutch National Chronic Q Fever Database we identified 284 chronic Q fever patients of whom 151 (53.7%) had proven, 64 (22.5%) probable and 69 (24.3%) possible chronic Q fever. The majority of proven and probable chronic Q fever patients had a vascular focus of infection (56.7%), while endocarditis (34.9%) was less prevalent. We described that most patients who died of chronic Q fever-related complications, had a vascular focus of infection (79%). Previously proposed risk factors for the development of chronic Q fever consist of pre-existing cardiac valvulopathy, vascular grafts and aneurysms, immunosuppression and pregnancy. Identified risk factors for chronic Q fever in this thesis were previous cardiac valvular surgery, vascular prosthesis, aneurysms, renal insufficiency, and increasing age. An association between immunosuppression and pregnancy, and chronic Q fever could not be confirmed in this study. A novel finding was the association between mild renal insufficiency and chronic Q fever. Increasing age also predisposed for the development of chronic Q fever. The diagnostic criteria of chronic Q fever have recently led to debate in the international literature. A positive C. burnetii PCR, in the absence of signs of acute Q fever, proves chronic Q fever, but this method has low sensitivity in blood. Until now, diagnosis of chronic Q fever relied mainly on serological examination. In this thesis, we have demonstrated that high phase I IgG titres have a high positive predictive value (PPV) to differentiate proven chronic Q fever from possible chronic Q fever, especially if titres exceed 1:4096. Nevertheless, sensitivity of high phase I IgG titres is low: 60% in case of phase I IgG titres >1:4096. In contrast, phase I IgG titres between 1:1024 and 1:4096 have high sensitivity (98-81%), but a low PPV (62-77%). These results emphasizes that serology is not a diagnostic tool on its own, but should be interpreted in relation with the clinical background. The diagnostic guideline of the Dutch Q fever Consensus Group combines PCR, serology, clinical data and radiological data. In this guideline, suspected chronic Q fever cases are divided in three groups in decreasing likelihood of chronic Q fever: proven, probable and possible. We have demonstrated that the guideline of the Dutch Q fever Consensus Group has better sensitivity and also takes more rare manifestations of chronic Q fever into account