Challenges in diagnosis and follow-up of chronic Q fever

Coxiella burnetii is the causative pathogen of the zoonosis Q fever. Upon primary infection, patients can remain asymptomatic or experience the disease called acute Q fever. After primary infection, 1-5% develop chronic Q fever, which is a persistent infection with C. burnetii causing vascular (prosthesis) infection and/or endocarditis. Diagnosis of chronic Q fever is based on clinical symptoms, radiologic, and microbiological results and is further classified into proven, probable, and possible chronic Q fever, based on the likelihood of infection. Antibiotic treatment for chronic Q fever is advised for at least 18 months and can be stopped when clinical, microbiological, and radiologic criteria are met. Part one of this thesis described the diagnosis and prognosis of Q fever. The diagnostic value of C. burnetii polymerase chain reaction (PCR) on throat swabs for Q fever pneumonia is evaluated in chapter two. As a low diagnostic value was found, diagnosis of Q fever pneumonia should be based on C. burnetii serology, and not on throat swab analysis alone. Chapter three outlines methods for detecting C. burnetii in tissue samples of chronic Q fever patients. This is routinely performed with PCR and should remain so, as fluorescence in situ hybridization (FISH) for C. burnetii detection in tissue samples was inferior to it. In chapter four the long-term follow-up of Dutch chronic Q fever patients is described. Many years after the 2007-2010 Q fever outbreak patients are still being diagnosed with chronic Q fever, with an incidence of ~20 cases per year. There is a considerable diagnostic delay between acute Q fever and the diagnosis of chronic Q fever, with intervals reaching up to nine years. Performing serological follow-up after acute Q fever resulted in patients being diagnosed within a shorter interval. The prognostic value of serological titres on clinical outcome during treatment and follow-up of patients with chronic Q fever is investigated in chapter five. Serological titres were found to have no prognostic value for clinical endpoints. Treatment decisions in chronic Q fever patients should be based on other factors. Chapter six analyses the association between genetic variations in genes encoding for pattern recognition receptors, for phagolysosomal pathways components, and for matrix metalloproteinases with clinical outcomes. Two genetic variations of interest were found, but these results need to be reproduced before treatment decisions can be based upon them. In part two of this thesis, the focus lies on vascular chronic Q fever. Chapter seven reevaluated patients with vascular risk factors for chronic Q fever that were already screened after the epidemic. Still, one patient was identified as having chronic Q fever. This finding warrants clinicians to stay vigilant for chronic Q fever, especially in high risk patients, even for so many years after the epidemic. Chapter eight addresses the growing concerns of vascular complications following quinolone exposure. In a high risk study population of patients with vascular chronic Q fever, no association was found between quinolone exposure and vascular complications. Therefore, quinolone therapy should not be withheld when indicated.