Descriptive characteristics of the study population.

<p>Descriptive characteristics of the study population.</p

Boxplot of IgG phase I antibodies in two samples obtained from veterinarians (n = 78) and Q fever patients (n = 98) in a three-year time period.

<p>The horizontal dark lines within the boxes represent the median antibody titer, the lower and upper boundaries of the boxes represent the 25^th and 75^th percentiles, and the T-bars represent the 2.5^th and 97.5^th percentiles. Outliers are indicated with dots, extreme outliers (more than three times the height of the box) with asterisks. First serum sample: veterinarians in 2009 or 2010; patients in 2008 or 2009 (twelve months after acute Q fever diagnosis in 2007 or 2008). Follow-up sample: veterinarians in 2013 (three to four years after first sample); patients in 2011 or 2012 (four years after acute Q fever diagnosis in 2007 or 2008). When no end titration available: >1:2,048 categorized as 1:4,096, and >1:4,096 categorized as 1:8,912.</p

Regional differences in reported serological follow-up practices by GPs in regions with a Laboratory of Medical Microbiology (LMM) with or without an automatic follow-up system.

<p>Municipalities in the service area of a LMM with follow-up: Heusden, Oss, Maasdonk, Uden, Bernheze, Lith, Landerd, Vught, 's-Hertogenbosch (Den Bosch), Sint Michielsgestel, Veghel, Schijndel, Boekel, Boxtel.</p><p>Municipalities in the service area of a LMM without follow-up: Dongen, Waalwijk, Tilburg, Oisterwijk, Gilze Rijen, Loon op Zand, Sint Oedenrode, Cuijk, Boxmeer, Mill en Sint Hubert, Hilvarenbeek, Sint Anthonis, Haaren, Grave.</p

Cumulative Q fever incidence in the Netherlands from 2007 up to and including 2010, marking the Municipal Health Service regions, highlighting the Municipal Health Service region Hart voor Brabant and the Laboratories of Medical Microbiology, A in 's-Hertogenbosch, B in Tilburg, and C in Veldhoven.

<p>Cumulative Q fever incidence in the Netherlands from 2007 up to and including 2010, marking the Municipal Health Service regions, highlighting the Municipal Health Service region Hart voor Brabant and the Laboratories of Medical Microbiology, A in 's-Hertogenbosch, B in Tilburg, and C in Veldhoven.</p

Diagnosis and serological follow-up up to 15 months (450 days) after diagnosis of Q fever for three Laboratories of Medical Microbiology (LMM).

*<p>A sample taken within 60 days after diagnosis was not considered as a follow-up sample.</p>†<p>For 13 samples the applicant was unknown (request by an external laboratory).</p><p>NA: not applicable.</p

Answers to knowledge and practice questions of medical practitioners (MPs) comparing those with few (≤10) and many (>10) Q fever patients.

*<p>Excluded are medical practitioners without Q fever patients (n = 30), those who never request serological follow-up (n = 70) or gave not applicable (NA) answers.</p

Long-Term Serological Follow-Up of Acute Q-Fever Patients after a Large Epidemic

<div><p>Background</p><p>Serological follow-up of acute Q-fever patients is important for detection of chronic infection but there is no consensus on its frequency and duration. The 2007–2009 Q-fever epidemic in the Netherlands allowed for long-term follow-up of a large cohort of acute Q-fever patients. The aim of this study was to validate the current follow-up strategy targeted to identify patients with chronic Q-fever.</p><p>Methods</p><p>A cohort of adult acute Q-fever patients, diagnosed between 2007 and 2009, for whom a twelve-month follow-up sample was available, was invited to complete a questionnaire and provide a blood sample, four years after the acute episode. Antibody profiles, determined by immunofluorescence assay in serum, were investigated with a special focus on high titres of IgG antibodies against phase I of <i>Coxiella burnetii</i>, as these are considered indicative for possible chronic Q-fever.</p><p>Results</p><p>Of the invited 1,907 patients fulfilling inclusion criteria, 1,289 (67.6%) were included in the analysis. At any time during the four-year follow-up period, 58 (4.5%) patients were classified as possible, probable, or proven chronic Q-fever according to the Dutch Q-fever Consensus Group criteria (which uses IgG phase I ≥1:1,024 to as serologic criterion for chronic Q-fever). Fifty-two (89.7%) of these were identified within the first year after the acute episode. Of the six patients that were detected for the first time at four-year follow-up, five had an IgG phase I titre of 1:512 at twelve months.</p><p>Conclusions</p><p>A twelve-month follow-up check after acute Q-fever is recommended as it adequately detects chronic Q-fever in patients without known risk factors. Additional serological and clinical follow-up is recommended for patients with IgG phase I ≥1:512, as they showed the highest risk to progress to chronic Q-fever.</p></div

Recommendations for serological and clinical follow-up in acute Q-fever patients regardless of compatible clinical presentation.

<p>^a Heart valve/vascular disease or prosthesis. ^b See [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131848#pone.0131848.ref021" target="_blank">21</a>].</p

Response at four-year follow-up: received questionnaires and blood samples for each year of diagnosis and total numbers.

<p>^a Percentages calculated with number of invited as denominator.</p><p>^b Including three questionnaires with the majority of answers missing (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131848#pone.0131848.g001" target="_blank">Fig 1</a>).</p><p>Response at four-year follow-up: received questionnaires and blood samples for each year of diagnosis and total numbers.</p

Boxplot of IgG phase I and II antibodies at twelve months and four years after acute Q-fever diagnosis (n = 1,289).

<p>The horizontal dark lines within the boxes represent the median antibody titre, the lower and upper boundaries of the boxes represent the 25^th and 75^th percentiles, and the T-bars represent the 2.5^th and 97.5^th percentiles. Outliers are indicated with dots, extreme outliers (more than three times the height of the box) with asterisks. Because there is less variation in the IgG phase I titres at four years compared to the other three boxes shown, this is the only one of the four boxes that shows extreme outliers.</p