Chronic Q fever diagnosis—consensus guideline versus expert opinion

Chronic Q fever, caused by Coxiella burnetii, has high mortality and morbidity rates if left untreated. Controversy about the diagnosis of this complex disease has emerged recently. We applied the guideline from the Dutch Q Fe­ver Consensus Group and a set of diagnostic criteria pro­posed by Didier Raoult to all 284 chronic Q fever patients included in the Dutch National Chronic Q Fever Database during 2006–2012. Of the patients who had proven cas­es of chronic Q fever by the Dutch guideline, 46 (30.5%) would not have received a diagnosis by the alternative cri­teria designed by Raoult, and 14 (4.9%) would have been considered to have possible chronic Q fever. Six patients with proven chronic Q fever died of related causes. Until results from future studies are available, by which current guidelines can be modified, we believe that the Dutch lit­erature-based consensus guideline is more sensitive and easier to use in clinical practice

Characteristics of hospitalized acute Q fever patients during a large epidemic, The Netherlands.

From 2007 to 2009, The Netherlands experienced a major Q fever epidemic, with higher hospitalization rates than the 2-5% reported in the literature for acute Q fever pneumonia and hepatitis. We describe epidemiological and clinical features of hospitalized acute Q fever patients and compared patients presenting with Q fever pneumonia with patients admitted for other forms of community-acquired pneumonia (CAP). We also examined whether proximity to infected ruminant farms was a risk factor for hospitalization.A retrospective cohort study was conducted for all patients diagnosed and hospitalized with acute Q fever between 2007 and 2009 in one general hospital situated in the high incidence area in the south of The Netherlands. Pneumonia severity scores (PSI and CURB-65) of acute Q fever pneumonia patients (defined as infiltrate on a chest x-ray) were compared with data from CAP patients. Hepatitis was defined as a >twofold the reference value for alanine aminotransferase and for bilirubin.Among the 183 hospitalized acute Q fever patients, 86.0% had pneumonia. Elevated liver enzymes (alanine aminotransferase) were found in 32.3% of patients, although hepatitis was not observed in any of them. The most frequent clinical signs upon presentation were fever, cough and dyspnoea. The median duration of admission was five days. Acute Q fever pneumonia patients were younger, had less co-morbidity, and lower PSI and CURB-65 scores than other CAP patients. Anecdotal information from attending physicians suggests that some patients were admitted because of severe subjective dyspnoea, which was not included in the scoring systems. Proximity to an infected ruminant farm was not associated with hospitalization.Hospitalized Dutch acute Q fever patients mostly presented with fever and pneumonia. Patients with acute Q fever pneumonia were hospitalized despite low PSI and CURB-65 scores, presumably because subjective dyspnoea was not included in the scoring systems

The value of 18F-FDG PET/CT in diagnosis and during follow-up in 273 patients with chronic Q fever

In 1%–5% of all acute Q fever infections, chronic Q fever develops, mostly manifesting as endocarditis, infected aneurysms, or infected vascular prostheses. In this study, we investigated the diagnostic value of 18F-FDG PET/CT in chronic Q fever at diagnosis and during follow-up. Methods: All adult Dutch patients suspected of chronic Q fever who were diagnosed since 2007 were retrospectively included until March 2015, when at least one 18F-FDG PET/CT scan was obtained. Clinical data and results from 18F-FDG PET/CT at diagnosis and during follow-up were collected. 18F-FDG PET/CT scans were prospectively reevaluated by 3 nuclear medicine physicians using a structured scoring system. Results: In total, 273 patients with possible, probable, or proven chronic Q fever were included. Of all 18F-FDG PET/CT scans performed at diagnosis, 13.5% led to a change in diagnosis. Q fever–related mortality rate in patients with and without vascular infection based on 18F-FDG PET/CT was 23.8% and 2.1%, respectively (P 5 0.001). When 18F-FDG PET/CT was added as a major criterion to the modified Duke criteria, 17 patients (1.9-fold increase) had definite endocarditis. At diagnosis, 19.6% of 18F-FDG PET/CT scans led to treatment modification. During follow-up, 57.3% of 18F-FDG PET/CT scans resulted in treatment modification. Conclusion: 18F-FDG PET/CT is a valuable technique in diagnosis of chronic Q fever and during follow-up, often leading to a change in diagnosis or treatment modification and providing important prognostic information on patient survival

Comparison of hospitalized acute Q fever pneumonia patients (n = 154) with patients admitted with a community-acquired pneumonia (CAP) (n = 254) and with CAP patients with bacterial aetiology other than <i>C. burnetii</i> (n = 104).

<p>IQR: interquartile range; COPD: chronic obstructive pulmonary disease.</p>a<p>Chi-square test.</p>b<p>Mann-Whitney U test.</p>c<p>Information missing or unknown for seven Q fever pneumonia patients, 56 CAP patients and 24 bacterial pneumonia patients.</p>d<p>Three CAP patients who died on the same day as visiting the emergency department not included, two patients not included in the bacterial pneumonia group.</p>e<p>Information missing for three Q fever pneumonia patients, 46 CAP patients and 19 bacterial pneumonia patients.</p>f<p>Information missing or unknown for 36 CAP patients and 18 bacterial pneumonia patients.</p>g<p>Information missing or unknown for 31 CAP patients and 13 bacterial pneumonia patients.</p>h<p>Pneumonia Severity Index (PSI): risk class: I–III = low; IV = moderate; V = severe.</p>i<p>Information missing for 29 CAP patients and 13 bacterial pneumonia patients.</p>j<p>Chi-square test for trend.</p>k<p>Confusion, blood Urea nitrogen, Respiratory rate, Blood pressure, age≥65 (CURB-65) score: 0–1 = mild pneumonia; 2 = moderate pneumonia; 3–5 = severe pneumonia.</p>l<p>Information missing for 27 CAP patients and 12 bacterial pneumonia patients.</p>m<p>Severe pneumonia is defined as PSI risk class ≥IV and/or CURB-score ≥2.</p

Symptoms at time of admission of hospitalized acute Q fever patients (n = 183).

<p>Symptoms at time of admission of hospitalized acute Q fever patients (n = 183).</p

Baseline characteristics of hospitalized acute Q fever patients from 2007 to 2009 (n = 183) compared with the general Dutch population in the region and nationwide.

<p>COPD: chronic obstructive pulmonary disease; CVA: cerebrovascular accident; IQR: interquartile range; MHS: Municipal Health Service.</p>a<p>Unless otherwise indicated, data extracted from Statistics Netherlands (CBS), 2008–2011: <a href="http://statline.cbs.nl/statweb/(website" target="_blank">http://statline.cbs.nl/statweb/(website</a> accessed 2013 July 30) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091764#pone.0091764-Statistics1" target="_blank">[27]</a>.</p>b<p>Information missing for nine cases.</p>c<p>Information missing for 18 cases.</p>d<p>Information missing for three cases.</p>e<p>Prevalence in 2007, data extracted from National Public Health Compass: <a href="http://www.nationaalkompas.nl/gezondheid-en-ziekte/ziekten-en-aandoeningen/hartvaatstelsel/hartfalen/cijfers-hartfalen-prevalentie-incidentie-en-sterfte-uit-de-vtv-2010/(website" target="_blank">http://www.nationaalkompas.nl/gezondheid-en-ziekte/ziekten-en-aandoeningen/hartvaatstelsel/hartfalen/cijfers-hartfalen-prevalentie-incidentie-en-sterfte-uit-de-vtv-2010/(website</a> accessed 2013 July 30) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091764#pone.0091764-Gommer1" target="_blank">[26]</a>.</p>f<p>20-years prevalence in 2009, data extracted from Comprehensive Cancer Centre the Netherlands (IKNL): <a href="http://www.cijfersoverkanker.nl/(website" target="_blank">http://www.cijfersoverkanker.nl/(website</a> accessed 2013 July 30) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091764#pone.0091764-Comprehensive1" target="_blank">[25]</a>.</p

Comparison of hospitalized acute Q fever pneumonia patients (n = 154) with patients admitted with a community-acquired pneumonia (CAP) (n = 254) and with CAP patients with bacterial aetiology other than <i>C. burnetii</i> (n = 104).

<p>IQR: interquartile range; COPD: chronic obstructive pulmonary disease.</p>a<p>Chi-square test.</p>b<p>Mann-Whitney U test.</p>c<p>Information missing or unknown for seven Q fever pneumonia patients, 56 CAP patients and 24 bacterial pneumonia patients.</p>d<p>Three CAP patients who died on the same day as visiting the emergency department not included, two patients not included in the bacterial pneumonia group.</p>e<p>Information missing for three Q fever pneumonia patients, 46 CAP patients and 19 bacterial pneumonia patients.</p>f<p>Information missing or unknown for 36 CAP patients and 18 bacterial pneumonia patients.</p>g<p>Information missing or unknown for 31 CAP patients and 13 bacterial pneumonia patients.</p>h<p>Pneumonia Severity Index (PSI): risk class: I–III = low; IV = moderate; V = severe.</p>i<p>Information missing for 29 CAP patients and 13 bacterial pneumonia patients.</p>j<p>Chi-square test for trend.</p>k<p>Confusion, blood Urea nitrogen, Respiratory rate, Blood pressure, age≥65 (CURB-65) score: 0–1 = mild pneumonia; 2 = moderate pneumonia; 3–5 = severe pneumonia.</p>l<p>Information missing for 27 CAP patients and 12 bacterial pneumonia patients.</p>m<p>Severe pneumonia is defined as PSI risk class ≥IV and/or CURB-score ≥2.</p

Additional microbiological tests and outcomes in hospitalized acute Q fever patients.

a<p>No pathogens cultured; in two patients sputum had been sampled which was not suitable for cultivation.</p>b<p><i>Staphylococcus epidermidis</i> (both are probably a contamination of the sample).</p>c<p><i>Mycoplasma pneumoniae</i> antibodies ≥1∶320, 20 additional patients had detectable antibodies: 1∶40 (n = 8), 1∶80 (n = 4), 1∶160 (n = 8).</p

Radiologic findings, laboratory tests, treatment, and follow-up of hospitalized acute Q fever patients (n = 183).

<p>ALT: alanine aminotransferase; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; Gamma GT: Gamma glutamyl transferase; ICU: Intensive Care Unit.</p>a<p>Male <50 years of age: >15 mm/h; male≥50 years of age: >20 mm/h; female <50 years of age: >20 mm/h; female≥50 years of age: >30 mm/h.</p>b<p>Values presented are applicable to male patients. Female: anaemia (hemoglobin): <7.5 mmol/L; elevated ALT: >35 U/L; highly elevated ALT: >70 U/L; Gamma GT: >40 U/L.</p>c<p>Defined as doxycycline, 200 mg/day; moxifloxacin, 400 mg/day; ciprofloxacin, 1,000 mg/day per oral dose <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091764#pone.0091764-Dijkstra2" target="_blank">[22]</a>. Adequate treatment during or after hospitalization (medication used for at least 10 days): 113/155 (72.9%) of patient who started adequate treatment, 15/155 (9.7%) received adequate antibiotics for less than 10 days, in 27/155 (17.4%) duration unknown/not reported in clinical patient files.</p>d<p>Within two years after hospital admission.</p>e<p>All-cause mortality within two years after hospitalization. All patients had underlying disease. Two patients died at the intensive care unit during hospital admission. The eleven deceased patients include one proven and one possible chronic Q fever case. The chronic infection might have contributed to the death in the proven chronic Q fever patient, though also other underlying illnesses were present.</p