ReviewChronic Q fever: Review of the literature and a proposal of new diagnostic criteria
Introduction
Q fever is a zoonosis, caused by the Gram-negative coccobacillus Coxiella burnetii. There is a large animal reservoir, with goats, sheep and cattle being the most common source of human infections.1, 2, 3 After primary infection, an estimated 1–5% of patients progress to chronic Q fever, which can become manifest years after initial infection. Endocarditis and infections of aneurysms or vascular prostheses are the most common manifestations.4, 5 Arthritis, osteomyelitis or hepatitis are rare manifestations of chronic Q fever. In a small number of patients no focus can be found.6, 7, 8 Pre-existent cardiac valvular disease, aortic aneurysm, vascular grafts, immunocompromised state, and pregnancy are reported risk factors for the development of chronic Q fever.7, 9, 10
If left untreated, chronic Q fever leads to considerable morbidity and a mortality up to 60%.5 Long-term antibiotic treatment, preferably consisting of hydroxychloroquine and doxycycline, and sometimes aggressive surgery are required in patients with established chronic Q fever.4, 5, 11 The consequences of an adequate diagnosis are therefore of major impact for suspected chronic Q fever patients. However, the diagnosis of chronic Q fever is challenging: culture of C. burnetii is difficult and time-consuming, requires a level 3 biosafety laboratory and lacks sensitivity.12 The diagnosis of chronic Q fever currently relies on serology and detection of DNA in blood or tissue with polymerase chain reaction (PCR). Chronic Q fever is proven when C. burnetii DNA is detected by PCR in blood or tissue in the absence of acute infection, although sensitivity of these techniques is low.13 Serological diagnosis is based on antigenic variation of C. burnetii, in which after culture in cells, a virulent variant phase I antigen, shifts to an avirulent phase II variant. During acute infection, antibodies to phase II antigens are detected first, followed by phase I antibodies. Persisting high levels of antibodies to phase I and phase II antigens, are thought to be caused by continuous antigenic stimulation and considered indicative for chronic Q fever.2, 14. A cutoff for phase I IgG of ≥1:800 has been internationally accepted for the serological diagnosis of chronic Q fever, which is based on an in house produced immunofluorescence assay (IFA).15 Due to a high number of false-positive tests with a cut-off of 1:800 and development of other (commercial) IFA-assays, discussions about the optimal cut-off values and suggestions of the incorporation of clinical characteristics in the diagnosis of chronic Q fever have emerged.8, 16, 17
Since 2007, the southern parts of the Netherlands suffered from a major Q fever outbreak, with more than 4000 reported symptomatic cases. As the majority of patients have mild or asymptomatic acute infection, the actual incidence is probably much higher.18 Due to hygienic measures, vaccination of goats and culling of pregnant goats, the acute Q fever epidemic in the Netherlands has subsided. Nevertheless, chronic Q fever is seen in a rising number of patients.19 Uniformity in the assays and interpretation of test results is necessary for good patient care. Given the uncertainties in diagnostic algorithms for chronic Q fever, the impact of an adequate diagnosis on the prognosis and treatment, and the increasing number of patients, we performed a review of the available literature on the clinical aspects and diagnostic tools for chronic Q fever. Based on this available evidence, a new proposal for the diagnosis of chronic Q fever was formulated in a consensus meeting of clinicians and microbiologists which combines clinical, radiological and microbiological factors.
Section snippets
Search strategy
A literature search was conducted in Pubmed to identify publications on the diagnostic features of chronic Q fever. We used the MESH-terms “Q fever” and “Coxiella burnetii” in combination with the subheading “diagnosis” and “microbiology”, and the MESH terms “radiography” OR “ultrasonography” OR “echocardiography” OR “Positron-Emission Tomography” OR “Immunology” OR “PCR” OR “fluorescent antibody technique” OR “serologic test” OR “diagnostic imaging”. Language was restricted to “English” only.
Selection
We initially identified 607 unique publications describing features of chronic Q fever. Based on title and abstract, 553 articles were excluded because they did not describe diagnostic accuracy or clinical manifestations. An additional eight publications were detected through the reference lists. After reviewing the 62 remaining papers, 45 articles were excluded because they were case reports or series describing less than five patients (16), they described acute Q fever only (6), pathogenesis
Discussion
With this review, we aimed to summarize the available knowledge on clinical presentation, microbiological diagnosis, and imaging techniques for the diagnosis of chronic Q fever and to provide a basis for uniformity in the work-up of patients suspected of having this infection. Due to the relative rarity of the disease, studies that have evaluated the diagnostic value of clinical, laboratory, imaging and microbiological parameters for chronic Q fever are limited to case reports and are mainly
Acknowledgement
We would like to thank all members of the Dutch Q fever Consensus group for their support and cooperation with this review and the development of the new diagnostic guideline for chronic Q fever.
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Cited by (0)
- i
Both authors contributed equally.
- j
See Members of the Dutch Q fever Consensus Group Section.