Persistence of DNA in a Cured Patient and Positive Culture in Cases with Low Antibody Levels Bring into Question Diagnosis of Q Fever Endocarditis

Edouard, Sophie; Million, Matthieu; Lépidi, Hubert; Rolain, Jean‐Marc; Fournier, Pierre‐Edouard; Scola, Bernard La; Grisoli, Dominique; Raoult, Didier

doi:10.1128/jcm.00812-13

Cited by 21 publications

(21 citation statements)

References 29 publications

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“…Similar results demonstrating the high value of RT-PCR on valves in the diagnosis of Bartonella endocarditis were recently reported by Chaloner et al (30), with positive results in 13 of 14 patients. Furthermore, as previously reported (19,31), RT-PCR is significantly more sensitive than 16S rRNA gene amplification for the diagnosis of Bartonella endocarditis in valvular tissues and blood.…”

Section: Discussionmentioning

confidence: 50%

Bartonella, a Common Cause of Endocarditis: a Report on 106 Cases and Review

et al. 2015

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Bartonella spp. are fastidious bacteria that cause blood culture-negative endocarditis and have been increasingly reported. In this study, we included all patients retrospectively and prospectively diagnosed with Bartonella endocarditis in our French reference center between 2005 and 2013. Our diagnosis was based on the modified Duke criteria and microbiological findings, including serological and PCR results. To review the published literature, we searched all human Bartonella endocarditis cases published in the PubMed database between January 2005 and October 2013. We report here a large series of 106 cases, which include 59 cases that had not previously been reported or mentioned. Indirect immunofluorescence assays, Western blotting, and realtime PCR from total blood, serum, and valve tissue exhibited sensitivities of 58%, 100%, 33%, 36%, and 91%, respectively. The number of cases reported in the literature between 2005 and 2013 increased to reach a cumulative number of 196 cases. The number of cases reported in the literature by other centers is increasing more rapidly than that reported by our French reference center (P < 10 ؊2 ). Currently, there is a lack of criteria for the diagnosis of Bartonella endocarditis. We suggest that a positive PCR result from a cardiac valve or blood specimen, an IgG titer of >800 using an immunofluorescence assay, or a positive Western blot assay be considered major Duke criteria for Bartonella endocarditis. There is no real increase in the incidence of these infections but rather a better understanding and interest in the disease resulting from the improvement of diagnostic tools.

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Section: Discussionmentioning

confidence: 50%

Bartonella, a Common Cause of Endocarditis: a Report on 106 Cases and Review

et al. 2015

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“…A positive PCR in serum or blood is considered as a major criterion for the diagnosis of endocarditis, vascular or osteoarticular infection, and can directly affect the management and treatment of the patient in conjunction with clinical symptoms, qPCR and serologic results and the evidence of focal infection by echocardiography or PET-scan Raoult, 2012). qPCR is particularly useful when some criteria are missing, such as for patients presenting with endocarditis or vascular infection with low antibody titers (Edouard et al, 2013). Indeed, positive PCR on serum allowed us to reduce the delay to certain diagnosis of persistent infection.…”

Section: Discussionmentioning

confidence: 99%

Lyophilization to improve the sensitivity of qPCR for bacterial DNA detection in serum: the Q fever paradigm

Edouard

Raoult

2016

Journal of Medical Microbiology

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Quantitative real-time PCR (qPCR) on serum provides significant added value to the diagnosis of Q fever, mainly at the acute stage of the disease in seronegative patients and in patients with endocarditis. We evaluated the benefits of Coxiella burnetii DNA concentration in serum by lyophilization to improve qPCR sensitivity. The detection limit of qPCR was determined by comparing six 10-fold dilutions of serum (calibrated with 10 4 bacteria ml À1 ) with and without lyophilization. We also tested, after lyophilization, 73 sera from patients with acute Q fever and 10 sera from patients with endocarditis for which specific qPCR for C. burnetii performed under our usual conditions remained negative. Lyophilization of DNA was found to improve sensitivity of the qPCR; the limit of detection of C. burnetii DNA by qPCR was 100-fold lower in lyophilized sera (1 bacterium ml À1 ) than in non-lyophilized sera (10 2 bacteria ml À1 ). Among the 73 sera from patients with acute Q fever, 26 (36 %) were positive after lyophilization, demonstrating a sensitivity gain of 44 % for early negative sera and 30 % for positive sera compared to our usual qPCR conditions. Sensitivity was also higher in sera from patients with endocarditis for which 8/ 10 (80 %) were positive after lyophilization. Our results serve as a proof of concept that lyophilization increases the sensitivity of qPCR in serum by concentrating bacterial DNA. This technique may be applied for the earlier diagnosis of other fastidious bacteria or viruses and extended to other clinical samples.

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“…This is because C.burnetii can participate in two M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 8 main pathophysiological mechanisms (cardioembolic and atherothrombotic) involved in its development [1]. The First in the context of valvular endocarditis [13,14], and the other by infection of vascular atherosclerotic plaques. This second mechanism has not been tested, but this action is not only biologically plausible [16][17][18], but also probable [15].…”

Section: Discusionmentioning

confidence: 99%

“…In humans, it can cause a self-limited flu-like illness, pneumonia, and hepatitis, but a large proportion of cases is asymptomatic [13]. Chronic Q fever infections are frequently associated with cardiovascular complications, mainly valvular endocarditis [13,14], but can also be associated with aortic aneurysms and vasculargraft infection [15]. This addition to the group of potential pathogens involved in cerebrovascular disease is fully justified.…”

Section: Introductionmentioning

confidence: 96%

“…This addition to the group of potential pathogens involved in cerebrovascular disease is fully justified. If it is due to a germ of intracellular growth [16], it can persist in the body for long periods of time [14], reactivated in case of immunosuppression [16] or pregnancy [17], and promote inflammation, thrombosis and embolus in vascular beds [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

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Persistent Q fever and ischaemic stroke in elderly patients

González-Quijada

Salazar-Thieroldt

Mora-Simón

2015

Clinical Microbiology and Infection

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Whether persistent or chronic Q fever may act as a risk factor for stroke is unknown. A case-control study was conducted in the Hospital Universitario de Burgos (Spain) between February 2011 and December 2012. A total of 803 samples from 634 consecutive hospitalized patients ≥65 years old were tested, of whom 111 were cases (patients with prevalent or incident ischaemic stroke and/or transient ischaemic attack) and 523 were controls (patients without ischaemic stroke and/or transient ischaemic attack). Immunoglobulin G (IgG) antibody titres phase I and II against Q fever, and IgG antibodies levels against Chlamydia pneumoniae and cytomegalovirus (CMV), were determined using immunofluorescence assay and ELISA methods, respectively. Phase I IgG titres against Coxiella burnetii ≥1:256 (compatible with chronic or persistent Q fever) were detected in 16 of 110 (14.5%) cases and in 32 of 524 (6.1%) controls; P = .004, odds ratio (OR) 2.6, 95% confidence interval (CI) 1.3 to 4.9. This ratio was maintained after adjusting for age, sex, hypertension, dyslipidaemia, cardioembolic focus, smoking, diabetes, other cardiovascular diseases, C-reactive protein, and leukocyte count (OR 2.6, 95% CI 1.3 to 5.3). High-titre IgG antibodies (top quartile) against CMV (OR 2.1, 95% CI 1.3 to 3.5), but not against C. pneumoniae (OR 0.9, 95% CI 0.5 to 1.6), also were associated with ischaemic stroke after adjustment for risk factors. In conclusion, serology compatible with persistent or chronic Q fever is associated with ischaemic stroke in elderly patients. High levels of IgG antibodies against CMV, but not against C. pneumoniae, also are associated with ischaemic stroke in these patients.

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Persistence of DNA in a Cured Patient and Positive Culture in Cases with Low Antibody Levels Bring into Question Diagnosis of Q Fever Endocarditis

Cited by 21 publications

References 29 publications

Bartonella, a Common Cause of Endocarditis: a Report on 106 Cases and Review

Bartonella, a Common Cause of Endocarditis: a Report on 106 Cases and Review

Lyophilization to improve the sensitivity of qPCR for bacterial DNA detection in serum: the Q fever paradigm

Persistent Q fever and ischaemic stroke in elderly patients

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