Fast track — ArticlesLong-term outcome of Q fever endocarditis: a 26-year personal survey
Introduction
Q fever is a worldwide zoonosis caused by infection with Coxiella burnetii bacteria. The potential effect of Q fever on public health has been highlighted by the ongoing outbreak in the Netherlands, which is of unprecedented size in a highly industrialised country with 3483 human cases and six deaths since 2007.1, 2 Systematic screening for cardiac valvular abnormalities is particularly important in the treatment of C burnetii infection, because endocarditis is the most severe and potentially fatal form of chronic Q fever.3 1–5% of patients with acute Q fever4, 5 and 60–80% of patients with chronic Q fever4 develop endocarditis. Moreover, C burnetii might cause 5% of all endocarditis cases in some regions6 and more than half of the documented cases of endocarditis with negative blood cultures, making it a more common cause than Bartonella spp, Brucella spp, Tropheryma whipplei, Mycoplasma spp, or Legionella spp.7, 8, 9, 10, 11
C burnetii, strictly intracellular Gram-negative bacteria, live and multiply in the phagolysosomes of infected cells, mainly monocytes and macrophages, in an acidic environment (pH 4·8).12 Another important characteristic of C burnetii is its antigenic variation, called phase variation, which is similar to the rough-smooth phenotype in Enterobacteriaceae due to partial loss of lipopolysaccharide. When isolated from animals or human beings, C burnetii express phase I antigen and are very infectious (a single bacterium is sufficient to infect a person). After subculture in cells or embryonated eggs, modification of the lipopolysaccharide results in an antigenic shift to the non-infectious phase II form. This antigenic shift is valuable in differentiation of acute from chronic Q fever because the serological response of patients with acute Q fever is mainly directed against phase II antigens, whereas patients with chronic Q fever have a serological response directed against phase I and phase II antigens.13, 14 A titre of IgG for phase I antigen greater than 800 suggests chronic infection, with a positive predictive value estimated at 98% and a sensitivity of 100%.15 C burnetii is difficult to eradicate because of its intracellular location, explaining why relapses and deaths were common among patients with the infection in the 1960s and 1970s when as many as two-thirds of the patients died in some studies.16, 17, 18 Since these findings, mortality has been reduced with prolonged treatment with antibiotic combinations,19 and the inclusion of substances that raise the pH of phagolysosomes have been effective in vitro20, 21 and in vivo.22 Therefore, the recommended treatment is a combination of doxycycline and hydroxychloroquine for 18 months to 3 years, but no data are available detailing the optimum duration of treatment.23 Treatment of Q fever endocarditis is among the longest for bacterial diseases, matching that of leprosy and other mycobacterial diseases.24
The purpose of this retrospective cohort study was to assess the long-term outcome of patients with Q fever endocarditis and to identify prognostic factors associated with mortality, surgery, serological cure, and serological relapse. Particular attention was given to the effect of treatment duration.
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Patients
All patients followed for Q fever endocarditis in our centre (French National Referral Centre for Q Fever) by DR from May, 1983, to June, 2006, were assessed. The diagnosis of infective endocarditis was made by use of the modified Duke criteria,25 which include a titre of IgG specific for phase I antigen of 800 or more or a positive blood culture as a major criterion. Transoesophageal echocardiography was done systematically if transthoracic echocardiography was negative. A positive PCR on
Results
104 patients were identified for inclusion in the study. Median follow-up was 100 months (range 37–310 months). One patient was excluded because follow-up was less than 36 months (figure 1). Table 1 summarises the characteristics of the population at diagnosis. Mean age at diagnosis was 53 years (SD 4; median 53, range 15–84); sex at diagnosis did not differ significantly. Table 2 details the clinical and echocardiographic features at diagnosis and the anatomical distribution of affected
Discussion
In our study, overall and endocarditis-related mortality increased with the length of follow-up, and treatment for 18 months made the infection undetectable in most patients. Age, stroke at diagnosis, endocarditis on prosthetic valves, and serological characteristics were associated with mortalitly.
Early mortality of Q fever endocarditis decreased from 60% in the 1970s17, 18 to 5% in the 1990s because of the use of combination therapy and the reduction in the diagnostic delay.19, 22 Since the
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