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, and Jan Jelrik Oosterheert

Author affiliations: University Medical Centre Utrecht, Utrecht, the Netherlands (L.M. Kampschreur, R.H.H. Groenwold, A.I.M Hoepelman, J.J. Oosterheert); VU University, Amsterdam, the Netherlands (S. Dekker); Jeroen Bosch Hospital, ’s-Hertogenbosch, the Netherlands (J.C.J.P. Hagenaars, P.J. Lestrade, N.H.M. Renders, M.H.A. Hermans, P.C. Wever); Bernhoven Hospital, Oss/Veghel, the Netherlands (M.G.L. de Jager-Leclercq, C.A.R. Groot)

Abstract

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.