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Background Chronic Q fever is accompanied by high mortality and morbidity, and requires prolonged antibiotic treatment. Little is known on long-term quality of life (LQOL) in chronic Q fever patients treated with antibiotics. Aim To identify patient and treatment-related factors associated with impaired LQOL in chronic Q fever patients treated with antibiotics, and to assess patients' perception on treatment. Design Cross-sectional study. Methods LQOL was assessed with a validated questionnaire from the Nijmegen Clinical Screening Instrument. Patients' perception on treatment was measured with three newly developed questions. Results We included 64 patients: LQOL was impaired in 55% (n = 35) after a median follow-up of 5 years. Median treatment duration was 27 months. In multivariable analysis, treatment duration was significantly associated with impaired LQOL (OR 1.07; 95%CI 1.02–1.12, P < 0.01 per month increase). Age, gender, number of antibiotic regimens, surgical intervention, complications, diagnostic classification, focus of infection or registration of side effects during treatment were not associated with impaired LQOL. After start of treatment, 17 patients (27%) perceived improvement of their condition. Disadvantages of treatment were experienced on a daily basis by 24 patients (69%) with impaired LQOL and 13 patients (46%) without impaired LQOL (P = 0.04). Conclusions LQOL in chronic Q fever patients treated with antibiotics is impaired in more than half of patients 5 years after diagnosis. Antibiotic treatment duration was the only variable associated with impaired LQOL. The majority of patients experienced disadvantages on a daily basis, highlighting the high burden of disease and treatment. [ABSTRACT FROM AUTHOR]

Background: First choice treatment for chronic Q fever is doxycycline plus hydroxychloroquine. Serum doxycy- cline concentration (SDC) >5 µg/mL has been associated with a favourable serological response, but the effect on clinical outcomes is unknown. Objectives: To assess the effect of measuring SDC during treatment of chronic Q fever on clinical outcomes. Methods: We performed a retrospective cohort study, to assess the effect of measuring SDC on clinical outcomes in patients treated with doxycycline and hydroxychloroquine for chronic Q fever. Primary outcome was the first disease-related event (new complication or chronic Q fever-related mortality); secondary outcomes were all-cause mortality and PCR-positivity. Multivariable analysis was performed with a Cox proportional hazards model, with shared-frailty terms for different hospitals included. Results: We included 201 patients (mean age 68years, 83% male): in 167 patients (83%) SDC was measured, 34 patients (17%) were treated without SDC measurement. First SDC was >5 µg/mL in 106 patients (63%), all with 200 mg doxycycline daily. In patients with SDC measured, dosage was adjusted in 41% (n = 68), concerning an increase in 64 patients. Mean SDC was 4.1 µg/mL before dosage increase, and 5.9 µg/mL afterwards. SDC measurement was associated with a lower risk for disease-related events (HR 0.51, 95% CI 0.26-0.97, P = 0.04), but not with all-cause mortality or PCR-positivity. Conclusions: SDC measurement decreases the risk for disease-related events, potentially through more optimal dosing or improved compliance. We recommend measurement of SDC and striving for SDC >5 ig/mL and <10 µg/mL during treatment of chronic Q fever. [ABSTRACT FROM AUTHOR]

Background: First choice treatment for chronic Q fever is doxycycline plus hydroxychloroquine. Serum doxycycline concentration (SDC) >5 μg/mL has been associated with a favourable serological response, but the effect on clinical outcomes is unknown.Objectives: To assess the effect of measuring SDC during treatment of chronic Q fever on clinical outcomes.Methods: We performed a retrospective cohort study, to assess the effect of measuring SDC on clinical outcomes in patients treated with doxycycline and hydroxychloroquine for chronic Q fever. Primary outcome was the first disease-related event (new complication or chronic Q fever-related mortality); secondary outcomes were all-cause mortality and PCR-positivity. Multivariable analysis was performed with a Cox proportional hazards model, with shared-frailty terms for different hospitals included.Results: We included 201 patients (mean age 68 years, 83% male): in 167 patients (83%) SDC was measured, 34 patients (17%) were treated without SDC measurement. First SDC was >5 μg/mL in 106 patients (63%), all with 200 mg doxycycline daily. In patients with SDC measured, dosage was adjusted in 41% (n = 68), concerning an increase in 64 patients. Mean SDC was 4.1 μg/mL before dosage increase, and 5.9 μg/mL afterwards. SDC measurement was associated with a lower risk for disease-related events (HR 0.51, 95% CI 0.26-0.97, P = 0.04), but not with all-cause mortality or PCR-positivity.Conclusions: SDC measurement decreases the risk for disease-related events, potentially through more optimal dosing or improved compliance. We recommend measurement of SDC and striving for SDC >5 μg/mL and <10 μg/mL during treatment of chronic Q fever. [ABSTRACT FROM AUTHOR]

Quick detection and recovery of country's freedom status remain a constant challenge in animal health surveillance. The efficacy and cost efficiency of different surveillance components in proving the absence of infection or (early) detection of bluetongue serotype 8 in cattle populations within different countries (the Netherlands, France, Belgium) using surveillance data from years 2006 and 2007 were investigated using an adapted scenario tree model approach. First, surveillance components (sentinel, yearly cross-sectional and passive clinical reporting) within each country were evaluated in terms of efficacy for substantiating freedom of infection. Yearly cross-sectional survey and passive clinical reporting performed well within each country with sensitivity of detection values ranging around 0.99. The sentinel component had a sensitivity of detection around 0.7. Secondly, how effective the components were for (early) detection of bluetongue serotype 8 and whether syndromic surveillance on reproductive performance, milk production and mortality data available from the Netherlands and Belgium could be of added value were evaluated. Epidemic curves were used to estimate the timeliness of detection. Sensitivity analysis revealed that expected within-herd prevalence and number of herds processed were the most influential parameters for proving freedom and early detection. Looking at the assumed direct costs, although total costs were low for sentinel and passive clinical surveillance components, passive clinical surveillance together with syndromic surveillance (based on reproductive performance data) turned out most cost-efficient for the detection of bluetongue serotype 8. To conclude, for emerging or re-emerging vectorborne disease that behaves such as bluetongue serotype 8, it is recommended to use passive clinical and syndromic surveillance as early detection systems for maximum cost efficiency and sensitivity. Once an infection is detected and eradicated, cross-sectional screening for substantiating freedom of infection and sentinel for monitoring the disease evolution are recommended. [ABSTRACT FROM AUTHOR]

Community-acquired pneumonia (CAP) is mostly caused by Streptococcus pneumoniae. Identification of the pathogen causing CAP can be achieved by conventional culture techniques of sputum and/or blood, antigen detection from urine or molecular analysis. However, it remains difficult to determine patients who are at risk of severe disease development (intensive care unit [ICU] admittance and/or death). In this retrospective study, 121 patients admitted to the emergency department with pneumonia symptoms were included. Several markers of infection (pneumococcal DNA load in blood (real-time LytA PCR), white blood cell (WBC) count, C-reactive protein (CRP), procalcitonin (PCT) and soluble urokinase plasminogen activator receptor (suPAR) levels) were assessed for their ability to predict severe disease development. Of 121 patients, 6 were excluded from the study because of an alternative diagnosis, whereas 8 were excluded from biomarker analysis because of the presence of co-morbidities. Of the 115 patients analysed by the LytA PCR, 23 were positive. PCR detected S. pneumoniae DNA in 82% of patients with positive blood culture for S. pneumoniae. PCR missed three samples from patients in which S. pneumoniae was recovered by blood cultures. However, eight additional LytA PCR-positive samples were detected from patients whose blood cultures remained negative. Pneumococcal DNA load was also monitored in time for 31 patients, of whom 11 had positive PCR results. For 10 out of 11 (91%) positive PCR patients, a clear increase in Ct-values was observed, indicating a lower pneumococcal DNA load in the blood as a result of antibiotic therapy. Biomarker analysis was performed in 107 patients, of whom 29 showed severe disease development. Pneumococcal DNA load ( p = 0.026), PCT ( p = 0.046) and suPAR ( p = 0.001) levels most reliably predicted severe disease development. In conclusion, in patients with CAP, higher pneumococcal DNA load, PCT and suPAR values are associated with severe disease development (ICU admission and/or death). These biomarkers may be useful tools for triage of patients suspected of having CAP in the emergency department. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the quality of life in patients with vascular chronic Q fever at time of diagnosis and during follow-up. Based upon the SF-36 questionnaire, the mean physical and mental health of each patient were assessed at 3-month intervals for up to 18 months. A total of 26 patients were included in the study. At time of diagnosis, the mean physical health and mental health score was 50·6 [95% confidence interval (CI) 46·7–54·4] and 44·6 (95% CI 41·6–47·5), respectively. During treatment, the mean physical health score declined significantly by 1·7 points each 3 months (P < 0·001) to 40·8 (95% CI 34·4–45·1). The mean mental health score significantly and steadily increased towards 51·2 (95% CI 46·9–54·3) during follow-up (P = 0·026). A total of 23% of patients were cured after 18 months of follow-up. In conclusion, quality of life at time of diagnosis for patients with vascular chronic Q fever is lower compared to a similar group of patients, matched for age and gender, with an aortic abdominal aneurysmal disease, and physical health decreases further after starting treatment. Considering the low percentage of cure, the current treatment of vascular chronic Q fever patients may require a separate strategy from that of endocarditis in order to increase survival. [ABSTRACT FROM PUBLISHER]

The aim of this study was to provide data on the risk of developing chronic Q fever in patients with aorto-iliac disease and evidence of previous Q fever infection. Patients with an aortic and/or iliac aneurysm or aorto-iliac reconstruction (aorto-iliac disease) and evidence of previous Q fever infection were included. The presence of phase I and II Coxiella burnetii IgG antibodies was assessed periodically using immunofluorescence assay. A total of 111 patients with aorto-iliac disease were divided into three groups, based upon the serological profile [mean follow-up: 16 ± 9 months (mean ± standard deviation)]. Group 1 consisted of 30 patients with a serological trace of C. burnetii infection (negative IgG phase I, IgG phase II titer of 1:32). Of these, 36.7 % converted to serological profile matching past resolved Q fever. Group 2 included 49 patients with negative IgG phase I titer and IgG phase II titer ≥1:64. No patients developed chronic Q fever, but 14.3 % converted to a positive IgG phase I titer. Group 3 consisted of 32 patients with positive IgG phase I and positive IgG phase II titers, of which 9.4 % developed chronic Q fever (significantly different from group 2, p = 0.039). The IgG phase I titer increased in 28.1 % of patients (from 1:64 to 1:4,096). The risk of developing chronic Q fever in patients with aorto-iliac disease and previous Q fever infection with a positive IgG phase I titer was 9.4 %. The IgG phase I titer increases or becomes positive in a substantial number of patients. A standardized serological follow-up is proposed. [ABSTRACT FROM AUTHOR]

The Netherlands experienced an unprecedented outbreak of Q fever between 2007 and 2010. The Jeroen Bosch Hospital (JBH) in 's-Hertogenbosch is located in the centre of the epidemic area. Based on Q fever screening programmes, seroprevalence of IgG phase II antibodies to Coxiella burnetii in the JBH catchment area was 10·7% [785 tested, 84 seropositive, 95% confidence interval (CI) 8·5–12·9]. Seroprevalence appeared not to be influenced by age, gender or area of residence. Extrapolating these data, an estimated 40 600 persons (95% CI 32 200–48 900) in the JBH catchment area have been infected by C. burnetii and are, therefore, potentially at risk for chronic Q fever. This figure by far exceeds the nationwide number of notified symptomatic acute Q fever patients and illustrates the magnitude of the Dutch Q fever outbreak. Clinicians in epidemic Q fever areas should be alert for chronic Q fever, even if no acute Q fever is reported. [ABSTRACT FROM AUTHOR]

Large outbreaks of Q fever in The Netherlands have provided a unique opportunity for studying longitudinal serum antibody responses in patients. Results are presented of a cohort of 344 patients with acute symptoms of Q fever with three or more serum samples per patient. In all these serum samples IgM and IgG against phase 1 and 2 Coxiella burnetii were measured by an immunofluorescence assay. A mathematical model of the dynamic interaction of serum antibodies and pathogens was used in a mixed model framework to quantitatively analyse responses to C. burnetii infection. Responses show strong heterogeneity, with individual serum antibody responses widely different in magnitude and shape. Features of the response, peak titre and decay rate, are used to characterize the diversity of the observed responses. Binary mixture analysis of IgG peak levels (phases 1 and 2) reveals a class of patients with high IgG peak titres that decay slowly and may represent potential chronic cases. When combining the results of mixture analysis into an odds score, it is concluded that not only high IgG phase 1 may be predictive for chronic Q fever, but also that high IgG phase 2 may aid in detecting such putative chronic cases. [ABSTRACT FROM AUTHOR]

Background The pathophysiological mechanisms which contribute to an increased risk of community-acquired pneumonia ( CAP) in patients using proton pump inhibitors are not well established. Aim To examine differences in microbial etiology in patients with CAP between patients with and without proton pump inhibitor ( PPI) therapy and its possible impact on disease severity. Methods All individuals consulting the emergency care unit were prospectively registered and underwent chest radiography. Sputum, urine, nose-throat swabs and blood samples were obtained for microbial evaluation. We evaluated the association between use of proton pump inhibitors, etiology of CAP and severity of illness with multivariate regression analysis. Results The final cohort comprised 463 patients, 29% using proton pump inhibitors ( PPIs). Pathogens regarded as oropharyngeal flora were more common in CAP patients using PPI therapy compared to those who did not (adjusted OR: 2.0; 95% CI: 1.22-3.72). Patients using proton pump inhibitors more frequently had an infection with Streptococcus pneumoniae (28% vs. 14%) and less frequently with Coxiella burnetii (8% vs. 19%) compared to nonuser of PPI. Adjusted for baseline differences, the risk of PPI users being infected with S. pneumonia was 2.23 times (95% CI: 1.28-3.75) higher compared to patients without PPI's. No risk between PPI use and any other microbial pathogen was found. There was no difference in severity of CAP between patients with and without using PPI therapy. Conclusions Proton pump inhibitor therapy was associated with an approximately 2-fold increased risk to develop community-acquired pneumonia possibly as a result of S. pneumoniae infection. [ABSTRACT FROM AUTHOR]

A commercially available enzyme-linked immunosorbent assay (ELISA) detecting Coxiella burnetii phase II-specific IgM for the diagnosis of acute Q fever was compared with indirect immunofluorescent antibody assay (IFA). IFA is the current reference method for the detection of antibodies against C. burnetii, but has disadvantages because the judgment of fluorescence is subjective and tiring, and the test is expensive and automation is not possible. To examine whether phase II IgM ELISA could be used as a screening assay for acute Q fever, we compared the sensitivity and specificity of IFA and ELISA. The sensitivity of the IFA and ELISA tests were 100 and 85.7%, respectively, with a specificity of 95.3 and 97.6%, respectively. Because of the high sensitivity and specificity of the ELISA in combination with the practical disadvantages of the IFA, we introduced a new algorithm to screen samples of patients with symptoms of acute Q fever infection. [ABSTRACT FROM AUTHOR]

Capnocytophaga canimorsus is a common Gram-negative anaerobic bacterium from the oral flora of dogs, typically transmitted to humans by dog bites. We report a case of C. canimorsus meningitis where there was (on presentation) no apparent predisposing risk factor and in whom we used 16S rRNA PCR gene sequencing to identify the pathogen quickly and to switch to appropriate antibiotic therapy. Physicians should be aware of potential C. canimorsus meningitis if conventional cerebrospinal fluid bacterial culture is negative but Gram staining identifies bacteria, especially in patients with a recent dog bite or known immunodeficiency. [ABSTRACT FROM AUTHOR]

Legionella pneumophila DNA can be detected in serum from patients with Legionnaires’ disease (LD). We explored this observation studying the kinetics of L. pneumophila DNA in serum samples in relation to C-reactive protein (CRP). Eleven hospitalized patients with LD were studied. Diagnosis was made by Legionella urinary antigen test in 8 patients and seroconversion in 3 patients. A macrophage infectivity potentiator (MIP) real-time PCR was performed on 31 serum samples, including 20 follow-up serum samples. Serum samples obtained on the day of admission were MIP PCR-positive in 7 (64%) and MIP PCR-negative in 4 (36%) patients. Three (75%) of the 4 patients with a MIP PCR-negative serum sample on the day of admission became positive during follow-up. Overall, L. pneumophila DNA was detected in serum samples from 10 of the 11 patients (91%). CRP levels in the 7 patients with a positive MIP PCR serum sample on day of admission (499 ± 144 mg/l; median ± SD) were significantly higher than those in the 4 patients with a negative MIP PCR serum sample on the day of admission (244 ± 97 mg/l). No difference in the severity of the disease on the day of admission was found between these patients. The presence of L. pneumophila DNA in serum is a common phenomenon in hospitalized patients with LD, although in some cases it is not yet present on the day of admission. L. pneumophila DNA in serum on the day of admission correlates with high CRP levels, but not with the severity of the disease. [ABSTRACT FROM AUTHOR]

Rapid diagnosis of influenza in hospitalised patients is important to prevent the transmission of the infection in the hospital. This prospective observational cohort study was designed to determine the relationship between the clinical diagnosis of influenza made by the physician at admission and the presence of influenza virus in patients with respiratory tract infections. This prospective observational cohort study was conducted in a large Dutch teaching hospital in a period of four weeks during the influenza season 2004/2005. All patients of 18 years and older, admitted with respiratory tract infections were included in the study. Clinical and laboratory parameters, chest radiograph (CR), blood and sputum cultures and nasopharyngeal swab for polymerase chain reaction (PCR) were obtained for each patient. In addition, the physicians opinion at admission whether this patient had influenza was recorded. A total of 78 patients were hospitalized with respiratory tract infections. In 41 (53%) of them influenza virus was detected by PCR. Among the patients that were positive for influenza virus by PCR, a clinical diagnosis of influenza was made in 18 cases (44%). Conversely, clinical diagnosis of influenza was made in 16 out of 37 patients in whom influenza virus was not detected by PCR. Neither C-reactive protein, leucocytes count nor an infiltrate on CR were helpful in determining the cause of the respiratory tract infection. The present findings failed to demonstrate a significant relationship between the clinical diagnosis of influenza and PCR detection of the virus. Also, the virus was present at least twice more often than influenza was clinically diagnosed. As a consequence, the decision to take protective measures to control spread of the virus should not rely on the clinical diagnosis. [ABSTRACT FROM AUTHOR]

Neutrophils have the shortest half-life among circulating leucocytes and rapidly undergo apoptosis in vitro. The homologous Bc1-2 and Bax proteins have opposing effects, with Bc1-2 extending cellular survival and Bax promoting cell death following an apoptotic stimulus. We determined Bc1-2 to Bax expression ratios in peripheral blood lymphocytes, monocyte.s and granulocytes and related them to the susceptibility of these cells to anti-Fas (anti-CD95)-induced apoptosis. Here, we show that Bax/Bc1-2 ratios are high in granulocytes and relatively low in monocytes and lymphocytes. Furthermore, we show a relation between this ratio in the different leucocyte subsets and their susceptibility to anti-Fas-induced apoptosis, with granulocytes showing the highest susceptibility, followed by monocytes and lymphocytes. It is concluded that the balance between Bc1-2 and Bax forms an apoptotic rheostat, which seems to determine sensitivity to apoptosis. [ABSTRACT FROM AUTHOR]

Presents a study on the timing of the onset of fined grained carbonate deposits, the Vigla Limestone, of typical Maiolica facies occurring in the Ionian zone of Western Greece. Details on studies carried out at the lowest beds of the Vigla Limestone, near Kato Kouklessi; Information on the onset of Vigla Limestone sedimentation being diachronous within the Ionian zone.

Presents a letter to the editor about erythema induratum.

Presents a case in which quantitative buffy coat (QBC) analysis facilitated the rapid detection of pneumococcemia. Inoculation of the ethylenediaminetetraacetic acid (EDTA)-anticoagulated blood onto blood agar plates with antibiotic-impregnated disks; Use of EDTA-anticoagulated blood obtained by venepuncture in performing QBC analysis; Efficacy of QBC analysis in facilitating the rapid detection of bacteremia.

Examines the correlation between tumor necrosis factor (TNF) and secretory phospholipase in patients with Crohn's disease. Intravenous infusion of anti-TNF chimeric monoclonal antibody to patients; Significance of TNF for induction of plasma; Inflammatory effects of secretory phospholipase.