Identification of Risk Factors for Chronic Q Fever, the Netherlands

Linda M. Kampschreur; Sandra Dekker; Julia C.J.P. Hagenaars; Peter J. Lestrade; Nicole H.M. Renders; Monique G.L. de Jager-Leclercq; Mirjam H.A. Hermans; Cornelis A.R. Groot; Rolf H.H. Groenwold; Andy I.M. Hoepelman; Peter C. Wever; Jan Jelrik Oosterheert


Emerging Infectious Diseases. 2012;18(4):563-570. 

In This Article

Abstract and Introduction


Since 2007, the Netherlands has experienced a large Q fever outbreak. To identify and quantify risk factors for development of chronic Q fever after Coxiella burnetii infection, we performed a case–control study. Comorbidity, cardiovascular risk factors, medications, and demographic characteristics from 105 patients with proven (n = 44), probable (n = 28), or possible (n = 33) chronic Q fever were compared with 201 patients who had acute Q fever in 2009 but in whom chronic Q fever did not develop (controls). Independent risk factors for development of proven chronic Q fever were valvular surgery, vascular prosthesis, aneurysm, renal insufficiency, and older age.


Q fever, a zoonosis caused by the intracellular gram-negative bacterium Coxiella burnetii, is prevalent worldwide[1,2] and has various acute and chronic clinical manifestations. Acute Q fever is mostly a self-limiting, mild, influenza-like disease, sometimes complicated by severe pneumonia or hepatitis. Asymptomatic acute infection occurs in 50%–60% of patients.[3–5] Among patients infected by C. burnetii, infection progresses to chronic Q fever in 1%–5%, months to years after primary infection.[2,4,6] Previous data, mainly from France, show that endocarditis is the most common clinical manifestation (±75%), followed by infections of aortic aneurysms and vascular prostheses (±10%).[5,7–9] In the Netherlands, however, an equal distribution of endocarditis and vascular infections has been seen.[10]

Chronic Q fever leads to high illness and death rates if untreated, which makes early case finding and preventive measures critical for patients at high risk. Treatment for Q fever consists of long-term antimicrobial drug therapy, preferably a combination of doxycycline and hydroxychloroquine for 18–24 months. Previously identified risk factors for chronic Q fever are preexisting cardiac valvulopathy, vascular grafts and aneurysms, immunosuppression, and pregnancy; however, most published studies have been descriptive, lacked statistical quantification, or included specific high-risk groups only.[6–9,11,12]

Since 2007, a large Q fever outbreak has been ongoing in the Netherlands, with >4,000 acute Q fever cases reported.[13] Because of asymptomatic disease and overlap with other febrile diseases, however, the actual number of Q fever infections is probably much higher. Although the acute Q fever epidemic in the Netherlands has subsided, the number of patients with chronic Q fever is rising.[10,14] In this unique population, we conducted a case–control study to identify and quantify risk factors for development of chronic Q fever after C. burnetii infection.


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