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Background: The echinocandins are lipopeptides that can be employed as antifungal drugs that inhibit the synthesis of 1,3- β-glucans within the fungal cell wall. Anidulafungin and caspofungin are echinocandins used in the treatment of Candida infections and have activity against other fungi including Aspergillus fumigatus. The echinocandins are generally considered fungistatic against Aspergillus species. Methods: Culture of A. fumigatus from conidia to microcolonies on a support of porous aluminium oxide (PAO), combined with fluorescence microscopy and scanning electron microscopy, was used to investigate the effects of anidulafungin and caspofungin. The PAO was an effective matrix for conidial germination and microcolony growth. Additionally, PAO supports could be moved between agar plates containing different concentrations of echinocandins to change dosage and to investigate the recovery of fungal microcolonies from these drugs. Culture on PAO combined with microscopy and image analysis permits quantitative studies on microcolony growth with the flexibility of adding or removing antifungal agents, dyes, fixatives or osmotic stresses during growth with minimal disturbance of fungal microcolonies. Significance: Anidulafungin and caspofungin reduced but did not halt growth at the microcony level; additionally both drugs killed individual cells, particularly at concentrations around the MIC. Intact but not lysed cells showed rapid recovery when the drugs were removed. The classification of these drugs as either fungistatic or fungicidal is simplistic. Microcolony analysis on PAO appears to be a valuable tool to investigate the action of antifungal agents. [ABSTRACT FROM AUTHOR]

Background: To make proper evaluation of prevention policies possible, data on the incidence and associated medical costs of occupational blood exposure accidents in the Netherlands are needed. Methods: Descriptive analysis of blood exposure accidents and risk estimates for occupational groups. Costs of handling accidents were calculated. Results: Each year, an estimated 13 000–15 000 blood exposure accidents are reported in the Netherlands, 95% in occupational settings. Hepatitis B (HBV) vaccination is offered free of charge only to people in risk groups, the seroprevalence of HBV, hepatitis C (HCV) and human immunodeficiency virus (HIV) is low and few infections are related to blood exposure accidents. High-risk accidents occur mainly in hospitals. In nursing homes and home care settings, the majority of the accidents are low-risk. Limited data are available about occurrence of accidents in other occupational groups. Associated medical costs from occupational blood exposure accidents are mainly determined by the initial risk management. Conclusions: Accidents must be managed effectively to prevent infection and reduce anxiety in injured employees. While strategies to reduce HCV and HIV infection should be primarily aimed at reducing the occurrence of high-risk accidents, vaccination can prevent HBV infection and cut the costs of handling low-risk accidents. The implementation of vaccination strategies, safe working policies and the proper use of safe equipment should be monitored better. [ABSTRACT FROM PUBLISHER]

The object of our study was to determine the proportion of atypical respiratory pathogens among patients hospitalized with a community-acquired respiratory infection. From September 1997 to May 1999, 159 patients (57% male, median age 55, range 1–88 y) admitted to 3 regional hospitals for a community acquired respiratory infection, were enrolled in the study. Microbiological diagnosis for the atypical pathogens Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila was performed with PCR on a throat swab, sputum and/or broncho alveolar lavage (BAL). In addition, Legionella species other than L. pneumophila (L. non-pneumophila species) were detected by PCR. Two serum samples were collected and processed forM. pneumoniae and C. pneumoniae serology. In total, 27 patients (17%) were diagnosed with an atypical pathogen. Infection with M. pneumoniae was detected in 19 patients (12%) (PCR positive n = 7), with C. pneumoniae in 5 patients (3%) (PCR positive n = 0) and with L. pneumophila in 4 patients (2.5%) (PCR positive n = 4). In 54 (34%) patients routine microbiological investigations revealed aetiological agents other than the 3 atypical pathogens, the most frequently diagnosed pathogens being Streptococcus pneumoniae (n = 18), Haemophilus influenzae (n = 17), Gram-negative rods (n = 13), Moraxella catarrhalis (n = 6) and Staphylococcus aureus (n = 6). More than 1 pathogen was found in 13 patients. Atypical pathogens were found more often in the young age group (0–18 y), in contrast to bacterial pathogens that were found more often in the older age groups (≥65 y). Atypical pathogens were found less often in patients with a clinical presentation of atypical pneumonia. Legionella species other than L. pneumophila were found by PCR in 13 patients (8%), and in 6 patients in combination with another pathogen. An atypical pathogen (M. pneumoniae, C. pneumoniae or L. pneumophila) was found in 17% of the patients hospitalized with a community acquired respiratory infection, predominantly in the young age group. The role of Legionella nonpneumophila species as pathogen in community acquired respiratory infection needs to be determined. The clinical presentation does not predict the type of pathogen found. [ABSTRACT FROM AUTHOR]

Reports on the prevalence and incidence of hepatitis C virus (HCV) infections among dialysis patients in the Netherlands. Testing of patients recruited from dialysis centers for antibodies and HCV RNA in 1995 and 1997. Analysis of seronegative serum samples by reverse-transcriptase polymerase chain reaction; Indications of nosocomial transmission; Interdependent risk factors.

We examined Coxiella burnetii seroconversion rates by measuring C. burnetii IgG among 2 cohorts of veterinary students. During follow-up of 118 seronegative veterinary students, 23 students seroconverted. Although the clinical importance of the presence of antibodies is unknown, veterinary students should be informed about the potential risks for Q fever. [ABSTRACT FROM AUTHOR]

Since 2007, Q fever has become a major public health problem in the Netherlands and goats were the most likely source of the human outbreaks in 2007, 2008 and 2009. Little was known about the consequences of these outbreaks for those professional care providers directly involved. The aim of this survey was to estimate the seroprevalence of antibodies against C. burnetii among Dutch livestock veterinarians and to determine possible risk factors. Single blood samples from 189 veterinarians, including veterinary students in their final year, were collected at a veterinary conference and a questionnaire was filled in by each participant. The blood samples were screened for IgG antibodies against phase I and phase II antigen of C. burnetii using an indirect immunofluorescent assay, and for IgM antibodies using an ELISA. Antibodies against C. burnetii were detected in 123 (65.1%) out of 189 veterinarians. Independent risk factors associated with seropositivity were number of hours with animal contact per week, number of years graduated as veterinarian, rural or sub urban living area, being a practicing veterinarian, and occupational contact with swine. Livestock veterinarians should be aware of this risk to acquire an infection with C. burnetii. Physicians should consider potential infection with C. burnetii when treating occupational risk groups, bearing in mind that the burden of disease among veterinarians remains uncertain. Vaccination of occupational risk groups should be debated. [ABSTRACT FROM AUTHOR]

In the aftermath of a large Q fever (QF) epidemic in the Netherlands during 2007-2010, new chronic QF (CQF) patients continue to be detected. We developed a health-economic decision model to evaluate the cost-effectiveness of a 1-time screening program for CQF 7 years after the epidemic. The model was parameterized with spatial data on QF notifications for the Netherlands, prevalence data from targeted screening studies, and clinical data from the national QF database. The cost-effectiveness of screening varied substantially among subpopulations and geographic areas. Screening that focused on cardiovascular risk patients in areas with high QF incidence during the epidemic ranged from cost-saving to €31,373 per quality-adjusted life year gained, depending on the method to estimate the prevalence of CQF. The cost per quality-adjusted life year of mass screening of all older adults was €70,000 in the most optimistic scenario. [ABSTRACT FROM AUTHOR]

Background: From 2007 through 2010, a large epidemic of acute Q fever occurred in the Netherlands. Patients with cardiac valvulopathy are at high risk to develop chronic Q fever after an acute infection. This patient group was not routinely screened, so it is unknown whether all their chronic infections were diagnosed. This study aims to investigate how many chronic Q fever patients can be identified by routinely screening patients with valvulopathy and to establish whether the policy of not screening should be changed. Methods: In a cross-sectional study (2016–2017) in a hospital at the epicentre of the Q fever epidemic, a blood sample was taken from patients 18 years and older who presented with cardiac valvulopathy. The sample was tested for IgG antibodies against phase I and II of Coxiella burnetii using an immunofluorescence assay. An IgG phase II titre of ≥1:64 was considered serological evidence of a previous Q fever infection. An IgG phase I titre of ≥1:512 was considered suspicious for a chronic infection, and these patients were referred for medical examination. Results: Of the 904 included patients, 133 (15%) had evidence of a previous C. burnetii infection, of whom 6 (5%) had a chronic infection on medical examination. Conclusions: In a group of high-risk patients with a heart valve defect, we diagnosed new chronic Q fever infections seven years after the epidemic, emphasizing the need for screening of this group to prevent complications in those not yet diagnosed in epidemic areas. [ABSTRACT FROM AUTHOR]

Background Echocardiographic screening of acute Q-fever patients and antibiotic prophylaxis for patients with cardiac valvulopathy is considered an important approach to prevent chronic Q-fever-related endocarditis. During a large Q-fever epidemic in the Netherlands, routine screening echocardiography was discontinued, raising controversy in the international literature. We followed a cohort of acute Q-fever patients to estimate the risk for developing chronic Q-fever, and we evaluated the impact of screening in patients who were not yet known to have a valvulopathy. Methods The study population consisted of patients diagnosed with acute Q-fever in 2007 and 2008. We retrospectively reviewed all screening echocardiographs and checked for development of chronic Q-fever 8 years after the acute episode. Risks of developing chronic Q-fever in relation to the presence or absence of valvulopathy were analyzed with logistic regression. Results The cohort included 509 patients, of whom 306 received echocardiographic screening. There was no significant difference (P -value =.22) in occurrence of chronic Q-fever between patients with a newly detected valvulopathy (2/84, 2.4%) and those with no valvulopathy (12/202, 5.9%). Two patients with a newly detected valvulopathy, who did not receive antibiotic prophylaxis, developed chronic Q-fever at a later stage. Conclusions We found no difference in outcome between patients with and without a valvulopathy newly detected by echocardiographic screening. In retrospect, the 2 above-mentioned patients could have benefitted from antibiotic prophylaxis, but its omission must be weighed against the unnecessary large-scale and long-term use of antibiotics that would have resulted from universal echocardiographic screening. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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 Coxiella burnetii, as these are considered indicative for possible chronic Q-fever. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Introduction: From 2007 through 2010, the Netherlands experienced a large Q-fever epidemic, with 4,107 notifications. The most serious complication of Q-fever is chronic Q-fever. Method: In 2014, we contacted all 2,161 adult inhabitants of the first village in the Netherlands affected by the Q-fever epidemic and offered to test for antibodies against Coxiella burnetii using immunofluorescence assay (IFA) to screen for chronic infections and assess whether large-scale population screening elsewhere is warranted. Results: Of the 1,517 participants, 33.8% were IFA-positive. Six IFA-positive participants had an IgG phase I titer ≥1:512. Two of these six participants were previously diagnosed with chronic Q-fever. Chronic infection was diagnosed in one of the other four participants after clinical examination. Conclusions: Seven years after the initial outbreak, seroprevalence remains high, but the yield of screening the general population for chronic Q-fever is low. A policy of screening known high-risk groups for chronic Q-fever in outbreak areas directly following an outbreak might be more efficient than population screening. A cost-effectiveness analysis should also be performed before initiating a population screening program for chronic Q-fever. [ABSTRACT FROM AUTHOR]

Background: Little is known about the development of chronic Q fever in occupational risk groups. The aim of this study was to perform long-term follow-up of Coxiella burnetii seropositive veterinarians and investigate the course of IgG phase I and phase II antibodies against C. burnetii antigens and to compare this course with that in patients previously diagnosed with acute Q fever. Methods: Veterinarians with IgG phase I ≥1:256 (immunofluorescence assay) that participated in a previous seroprevalence study were asked to provide a second blood sample three years later. IgG antibody profiles were compared to a group of acute Q fever patients who had IgG phase I ≥1:256 twelve months after diagnosis. Results: IgG phase I was detected in all veterinarians (n = 76) and in 85% of Q fever patients (n = 98) after three years (p<0.001). IgG phase I ≥1:1,024, indicating possible chronic Q fever, was found in 36% of veterinarians and 12% of patients (OR 3.95, 95% CI: 1.84–8.49). Conclusions: IgG phase I persists among veterinarians presumably because of continuous exposure to C. burnetii during their work. Serological and clinical follow-up of occupationally exposed risk groups should be considered. [ABSTRACT FROM AUTHOR]

Background: The extracellular domains of cytokine receptors are released during inflammation, but little is known about the shedding of Toll-like receptors (TLR) and whether they can be used as diagnostic biomarkers. Methods: The release of sTLR2 and sTLR4 was studied in in-vitro stimulations, as well as in-vivo during experimental human endotoxemia (n = 11, 2 ng/kg LPS), and in plasma of 394 patients with infections (infectious mononucleosis, measles, respiratory tract infections, bacterial sepsis and candidemia) or non-infectious inflammation (Crohn’s disease, gout, rheumatoid arthritis, autoinflammatory syndromes and pancreatitis). Using C-statistics, the value of sTLR2 and sTLR4 levels for discrimination between infections and non-infectious inflammatory diseases, as well as between viral and bacterial infections was analyzed. Results: In-vitro, peripheral blood mononuclear cells released sTLR2 and sTLR4 by exposure to microbial ligands. During experimental human endotoxemia, plasma concentrations peaked after 2 hours (sTLR4) and 4 hours (sTLR2). sTLR4 did not correlate with cytokines, but sTLR2 correlated positively with TNFα (rs = 0.80, P < 0.05), IL-6 (rs = 0.65, P < 0.05), and IL-1Ra (rs = 0.57, P = 0.06), and negatively with IL-10 (rs = -0.58, P = 0.06), respectively. sTLR4 had a similar area under the ROC curve [AUC] for differentiating infectious and non-infectious inflammation compared to CRP: 0.72 (95% CI 0.66-0.79) versus 0.74 (95% CI 0.69-0.80) [P = 0.80], while sTLR2 had a lower AUC: 0.60 (95% CI 0.54-0.66) [P = 0.0004]. CRP differentiated bacterial infections better from viral infections than sTLR2 and sTLR4: AUC 0.94 (95% CI 0.90-0.96) versus 0.58 (95% CI 0.51-0.64) and 0.75 (95% CI 0.70-0.80), respectively [P < 0.0001 for both]. Conclusions: sTLrs are released into the circulation, and suggest the possibility to use sTLrs as diagnostic tool in inflammatory conditions. [ABSTRACT FROM AUTHOR]

During October-December 2015, 29 patients in a hospital in the Netherlands acquired nosocomial infection with a multidrug-resistant, New Delhi-metallo-β-lactamase-positive Klebsiella pneumoniae strain. Extensive infection control measures were needed to stop this outbreak. The estimated economic impact of the outbreak was $804,263; highest costs were associated with hospital bed closures. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background Chronic Q-fever, a condition with high morbidity and mortality, may develop after an acute infection with Coxiella burnetii (acute Q-fever). Several strategies have been suggested for early detection of chronic Q-fever, focusing on follow-up of known acute Q-fever patients and detection of asymptomatic or unknown chronic infections. As there is no international standard or consensus, the aims of this study were to summarise the available literature and assess the evidence for different follow-up and screening strategies. Design We conducted a systematic review by searching PubMed and Embase. Twenty articles were included, of which fourteen only provided information on follow-up of known acute Q-fever cases, four presented data on identification of previously unknown C. burnetii infections, and two had information on both topics. Results The conversion rate of acute to chronic Q-fever ranged from 0 to 5·0%. Most studies advised serological follow-up of acute Q-fever patients, but without consistent advice on optimum timing and duration. The recommendation to use echocardiography for all acute Q-fever patients to detect valvular damage remains controversial. Screening of high-risk patients in an outbreak setting is advised by studies investigating such strategy. Conclusions There is sufficient evidence to support serological follow-up of all known acute Q-fever patients at least once during the first year following the acute infection, and more frequently in patients with known risk factors for chronic disease, such as heart valve- or vascular prosthesis. Screening of risk groups should be considered in outbreaks of Q-fever. [ABSTRACT FROM AUTHOR]

Background: During the Dutch Q fever epidemic more than 4,000 Q fever cases were notified. This provided logistical challenges for the organisation of serological follow-up, which is considered mandatory for early detection of chronic infection. The aim of this study was to investigate the proportion of acute Q fever patients that received serological follow-up, and to identify regional differences in follow-up rates and contributing factors, such as knowledge of medical practitioners. Methods: Serological datasets of Q fever patients diagnosed between 2007 and 2009 (N = 3,198) were obtained from three Laboratories of Medical Microbiology (LMM) in the province of Noord-Brabant. One LMM offered an active follow-up service by approaching patients; the other two only tested on physician's request. The medical microbiologist in charge of each LMM was interviewed. In December 2011, 240 general practices and 112 medical specialists received questionnaires on their knowledge and practices regarding the serological follow-up of Q fever patients. Results: Ninety-five percent (2,226/2,346) of the Q fever patients diagnosed at the LMM with a follow-up service received at least one serological follow-up within 15 months of diagnosis. For those diagnosed at a LMM without this service, this was 25% (218/852) (OR 54, 95% CI 43–67). Although 80% (162/203) of all medical practitioners with Q fever patients reported informing patients of the importance of serological follow-up, 33% (67/203) never requested it. Conclusions: Regional differences in follow-up are substantial and range from 25% to 95%. In areas with a low follow-up rate the proportion of missed chronic Q fever is potentially higher than in areas with a high follow-up rate. Medical practitioners lack knowledge regarding the need, timing and implementation of serological follow-up, which contributes to patients receiving incorrect or no follow-up. Therefore, this information should be incorporated in national guidelines and patient information forms. [ABSTRACT FROM AUTHOR]

Background: In The Netherlands, 1168 Q-fever patients were notified in 2007 and 2008. Patients and general practitioners (GPs) regularly reported persisting symptoms after acute Q-fever, especially fatigue and long periods of sick leave, to the public health authorities. International studies on smaller Q-fever outbreaks demonstrate that symptoms may persist years after acute illness. Data for the Dutch outbreaks were unavailable. The aim of this study is to quantify sick leave after acute Q-fever and long-term symptoms. Methods: Our study targeted 898 acute Q-fever patients, notified in 2007 and 2008 residing in the Province Noord-Brabant. Patients from the 2008 cohort were mailed a questionnaire at 12 months and those of the 2007 cohort at 12–26 months after onset of illness. Patients reported underlying illness, Q-fever-related symptoms and sick leave. Results: The response rate was 64%. Forty percent of the working patients reported long-term (>1 month) sick leave. Pre-existent heart disease odds ratio (OR) 4.50; confidence interval (CI) 1.27–16.09), hospitalization in the acute phase (OR 3.99; 95% CI 2.15–7.43) and smoking (OR 1.69; 95% CI 1.01–2.84) were significant predictors for long-term absence. Of the patients who resumed work, 9% were—at the time of completing the questionnaire—still unable to function at pre-infection levels due to fatigue or concentration problems. Of the respondents, 40% reported persisting physical symptoms at the time of follow-up. Fatigue (20%) was most frequently reported. Daily activities were affected in 30% of cases. Conclusions: Q-fever poses a serious persisting long-term burden on patients and society. [ABSTRACT FROM PUBLISHER]

Epstein Barr virus (EBV)–related diseases encompass both acute infections that result in acute infectious mononucleosis and chronic infections that result in lymphoproliferative malignant diseases. While classical inflammatory parameters such as C-reactive protein (CRP) have proven their usefulness during bacterial and fungal infections, they are often low and nondiscriminatory in viral infections. Here, we show that IL-18 is markedly elevated during acute EBV infections and EBV-associated diseases, while ferritin concentrations are also elevated during acute EBV infection and correlate with IL-18. Therefore, IL-18 and ferritin may represent infection markers for viral infections such as EBV, similar to CRP for bacterial infections. [ABSTRACT FROM AUTHOR]

Background: Acquired resistance to antifungal agents now supports the introduction of susceptibility testing for speciesdrug combinations for which this was previously thought unnecessary. For pathogenic yeasts, conventional phenotypic testing needs at least 24 h. Culture on a porous aluminum oxide (PAO) support combined with microscopy offers a route to more rapid results. Methods: Microcolonies of Candida species grown on PAO were stained with the fluorogenic dyes Fun-1 and Calcofluor White and then imaged by fluorescence microscopy. Images were captured by a charge-coupled device camera and processed by publicly available software. By this method, the growth of yeasts could be detected and quantified within 2 h. Microcolony imaging was then used to assess the susceptibility of the yeasts to amphotericin B, anidulafungin and caspofungin (3.5 h culture), and voriconazole and itraconazole (7 h culture). Significance: Overall, the results showed good agreement with EUCAST (86.5% agreement; n = 170) and E-test (85.9% agreement; n = 170). The closest agreement to standard tests was found when testing susceptibility to amphotericin B and echinocandins (88.2 to 91.2%) and the least good for the triazoles (79.4 to 82.4%). Furthermore, large datasets on population variation could be rapidly obtained. An analysis of microcolonies revealed subtle effects of antimycotics on resistant strains and below the MIC of sensitive strains, particularly an increase in population heterogeneity and cell densitydependent effects of triazoles. Additionally, the method could be adapted to strain identification via germ tube extension. We suggest PAO culture is a rapid and versatile method that may be usefully adapted to clinical mycology and has research applications [ABSTRACT FROM AUTHOR]

We describe the Q fever epidemic in the Netherlands with emphasis on the epidemiological characteristics of acute Q fever patients and the association with veterinary factors. Data from 3264 notifications for acute Q fever in the period from 2007 through 2009 were analysed. The patients most affected were men, smokers and persons aged 40-60 years. Pneumonia was the most common clinical presentation (62% in 2007 and 2008). Only 3.2% of the patients were working in the agriculture sector and 0.5% in the meat-processing industry including abattoirs. Dairy goat farms with C oxiella burnetii-induced abortion waves were mainly located in the same area where human cases occurred. Airborne transmission of contaminated dust particles from commercial dairy goat farms in densely populated areas has probably caused this epidemic. In 2010, there was a sharp decline in the number of notified cases following the implementation of control measures on dairy goat and sheep farms such as vaccination, hygiene measures and culling of pregnant animals on infected farms. In combination with a rise in the human population with antibodies against C . burnetii, these have most likely ended the outbreak. Development of chronic Q fever in infected patients remains an important problem for years to come. [ABSTRACT FROM AUTHOR]

BACKGROUND: In 2007, 2008, and 2009 outbreaks of Q-fever occurred in the Netherlands with increasing magnitude. The 2009 outbreak with 2354 reported cases is the largest human Q-fever outbreak ever recorded. To assess the extent of infection and the safety of donated blood, we tested local blood donations for presence of Coxiella burnetii antibodies and DNA. STUDY DESIGN AND METHODS: Starting May 2009, more than 40,000 serum samples were collected from all consenting blood donors in the areas with high Q-fever incidence. The 1004 samples from the areas with the highest number of reported cases were tested for C. burnetii DNA by polymerase chain reaction; seroprevalence and incidence were determined using enzyme-linked immunosorbent assay and immunofluorescence assays (IFAs) in the subset of 543 donors of whom a follow-up sample was available. RESULTS: A total of 6 of 1004 donor samples tested reactive for C. burnetii DNA. Confirmatory testing (IFA) on the index and follow-up samples demonstrated seroconversion in two donors, high-level preexisting antibodies in one donor, and no seroconversion in three donors. Immunoglobulin (Ig)G testing of the 543 serum pairs showed that 66 were reactive in the latest sample, of which 10 represented seroconversions. CONCLUSION: In the area with highest incidence during a large Q-fever outbreak, 3 of 1004 blood donations contained C. burnetii DNA (0.3%; 95% confidence interval, 0.1%-1.0%). A total of 66 of 543 (12.2%) donors tested positive for anti- Coxiella IgG. Ten seroconversions were detected, resulting in an incidence of 5.7% per year, which is more than 10-fold higher than the local number of reported clinical cases (0.47% per year). [Correction added after online publication 14-Jul-11: high-level existing antibodies has been updated to highlevel preexisting antibodies.] [ABSTRACT FROM AUTHOR]

Background. Recent outbreaks in the Netherlands allowed for laboratory follow-up of a large series of patients with acute Q fever and for evaluation of test algorithms to detect chronic Q fever, a condition with considerable morbidity and mortality. Methods. For 686 patients with acute Q fever, IgG antibodies to Coxiella burnetii were determined using an immunofluorescence assay at 3, 6, and 12 months of follow-up. Polymerase chain reaction (PCR) was performed after 12 months and on earlier serum samples with an IgG phase I antibody titer $1:1024. Results. In 43% of patients, the IgG phase II antibody titers remained high ($1:1024) at 3, 6, and 12 months of follow-up. Three months after acute Q fever, 14% of the patients had an IgG phase I titer $1:1024, which became negative later in 81%. IgG phase I antibody titers were rarely higher than phase II titers. Eleven cases of chronic Q fever were identified on the basis of serological profile, PCR results, and clinical presentation. Six of these patients were known to have clinical risk factors at the time of acute Q fever. In a comparison of various serological algorithms, IgG phase I titer$1:1024 at 6 months had the most favorable sensitivity and positive predictive value for the detection of chronic Q fever. Conclusions. The wide variation of serological and PCR results during the follow-up of acute Q fever implies that the diagnosis of chronic Q fever, necessitating long-term antibiotic treatment, must be based primarily on clinical grounds. Different serological follow-up strategies are needed for patients with and without known risk factors for chronic Q fever. [ABSTRACT FROM AUTHOR]

Background: A Q-fever outbreak occurred in an urban area in the south of the Netherlands in May 2008. The distribution and timing of cases suggested a common source. We studied the spatial relationship between the residence locations of human cases and nearby small ruminant farms, of which one dairy goat farm had experienced abortions due to Q-fever since mid April 2008. A generic geographic information system (GIS) was used to develop a method for source detection in the still evolving major epidemic of Q-fever in the Netherlands. Methods: All notified Q-fever cases in the area were interviewed. Postal codes of cases and of small ruminant farms (size >40 animals) located within 5 kilometres of the cluster area were geo-referenced as point locations in a GIS-model. For each farm, attack rates and relative risks were calculated for 5 concentric zones adding 1 kilometre at a time, using the 5-10 kilometres zone as reference. These data were linked to the results of veterinary investigations. Results: Persons living within 2 kilometres of an affected dairy goat farm (>400 animals) had a much higher risk for Q-fever than those living more than 5 kilometres away (Relative risk 31.1 [95% CI 16.4-59.1]). Conclusions: The study supported the hypothesis that a single dairy goat farm was the source of the human outbreak. GIS-based attack rate analysis is a promising tool for source detection in outbreaks of human Q-fever. [ABSTRACT FROM AUTHOR]

Background: In The Netherlands the largest human Q fever outbreak ever reported in the literature is currently ongoing with more than 2300 notified cases in 2009. Pregnant women are particularly at risk as Q fever during pregnancy may cause maternal and obstetric complications. Since the majority of infected pregnant women are asymptomatic, a screening strategy might be of great value to reduce Q fever related complications. We designed a trial to assess the (cost-)effectiveness of a screening program for Q fever in pregnant women living in risks areas in The Netherlands. Methods/design: We will conduct a clustered randomized controlled trial in which primary care midwife centres in Q fever risk areas are randomized to recruit pregnant women for either the control group or the intervention group. In both groups a blood sample is taken around 20 weeks postmenstrual age. In the intervention group, this sample is immediately analyzed by indirect immunofluorescence assay for detection of IgG and IgM antibodies using a sensitive cut-off level of 1:32. In case of an active Q fever infection, antibiotic treatment is recommended and serological follow up is performed. In the control group, serum is frozen for analysis after delivery. The primary endpoint is a maternal (chronic Q fever or reactivation) or obstetric complication (low birth weight, preterm delivery or fetal death) in Q fever positive women. Secondary aims pertain to the course of infection in pregnant women, diagnostic accuracy of laboratory tests used for screening, histo-pathological abnormalities of the placenta of Q fever positive women, side effects of therapy, and costs. The analysis will be according to the intention-to-screen principle, and cost-effectiveness analysis will be performed by comparing the direct and indirect costs between the intervention and control group. Discussion: With this study we aim to provide insight into the balance of risks of undetected and detected Q fever during pregnancy. Trial registration: ClinicalTrials.gov, protocol record NL30340.042.09. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Chlamydia antibody test (CAT) has been proposed to predict tubal disease. A correlation between CA-125 and the extent of endometriosis has been found by others. In this study we explored whether a combination of the two tests adds to the predictive value of the individual tests for predicting tubal disease or endometriosis. We also used the combination of tests as a new index test to screen for severe pelvic pathology. Study design: This retrospective study compares the findings of 240 laparoscopies with the serological test results. Findings were classified according to the existing ASRM scoring systems for adnexal adhesions, distal tubal occlusion and endometriosis. Severe pelvic pathology was defined as the presence of ASRM classes III and IV tubal disease or ASRM classes III and IV endometriosis. The predictive value was calculated for both tests separately and for the combined test. The combined test was positive if at least one test result was abnormal (CAT positive and/or CA-125 ≥35IU/ml). Results: 67/240 women had tubal disease, 81/240 had some degree of endometriosis. The odds ratios (ORs) of the CAT and the combined test to diagnose severe tubal disease were 6.6 (2.6–17.0) and 7.3 (2.9–19.3), respectively. The ORs of the CA-125 and the combined test to diagnose severe endometriosis were 15.6 (6.2–40.2) and 3.0 (1.2–8.0), respectively. Severe pelvic pathology was present in 65/240 women (27%). The ORs for severe pelvic pathology of the CAT, CA-125 and the combined test were 2.5 (1.4–5.3), 4.9 (1.9–9.6) and 6.6 (3.3–13.4), respectively. If the combined test was normal 15 out 131 women (11%) were shown to have severe pelvic pathology. Conclusions: The combined test adds hardly anything to the predictive value of CAT alone to diagnose severe tubal disease. The combined test is better than the CAT to predict severe pelvic pathology, but is not significantly better than the CA-125. If both the CAT and CA-125 are normal one could consider not performing a laparoscopy. [Copyright &y& Elsevier]

OBJECTIVE -- Women with diabetes have a high incidence and complication rate of urinary tract infections (UTIs). Our aims were to compare current treatment strategies with respect to recurrence rates in women with diabetes with those without diabetes. RESEARCH DESIGN AND METHODS -- We used a Dutch registration database containing pharmacy dispensing data. A total of 10,366 women with diabetes (17.5% premenopausal) (aged ≤55 years) and 200,258 women without diabetes (68% premenopausal) who received a first course of trimethoprim, nitrofurantoin, fosfomycin, or norfloxacin between January 1999 and January 2006 were included. We compared short (≤5 days) with long (>5 days) prescriptions and norfloxacin with trimethoprim, nitrofurantoin, and fosfomycin. A recurrence was defined as a second prescription for one of the above-mentioned agents or a first with amoxicillin (clavulanic acid), fluoroquinolones, or trimethoprim/sulfamethoxazole between 6 and 30 days after inclusion. RESULTS-- Premenopausal women with diabetes more often received a long (26.5 vs. 19.2%; P < 0.001) treatment with norfloxacin (10.7 vs. 6.2%; P < 0.001) but still had a higher recurrence rate (16.1 vs. 12.2%; P = 0.003) compared with those without diabetes. Similarly, postmenopausal women with diabetes more often received a longer (32.8 vs. 28.8%; P < 0.001) treatment with norfloxacin (15.2 vs. 12.7%; P < 0.001) but had a higher recurrence rate (19.1 vs. 16.4%; P < 0.001) compared with those without diabetes. CONCLUSIONS -- Despite the fact that patients with diabetes more often received longer and more potent initial treatment than patients without diabetes, pre- and postmenopausal women with diabetes more often had recurrences of their UTIs. [ABSTRACT FROM AUTHOR]

The article discusses results of a study on the long-term consequences of asymptomatic bacteria (ASB) in women with type 1 or type 2 diabetes mellitus (DM). Urine culture specimens showed 17% prevalence of ASB. In women with DM and ASB, the decline of creatine clearance was from 87 milliliter per minute to 76 milliliter per minute. Women with ASB developed hypertension more often than women without ASB.

A highly porous inorganic material (Anopore) was shown to be an effective support for culturing and imaging a wide range of microorganisms. An inert barrier grid was printed on the rigid surface of Anopore to create a "living chip" of 336 miniaturized compartments (200/cm²) with broad applications in microbial culture. [ABSTRACT FROM AUTHOR]

Compares the development of asymptomatic urinary tract infection (UTI) in women with diabetes mellitus (DM) versus asymptomatic bacteriuria (ASB). Prevalence of UTI for women with DM versus ASB; Risk of developing UTI in women with DM versus ASB; Renal function and serum creatinine levels in women with ASB versus DM.

A 15-year-old girl was admitted with a high fever and progressive malaise, vomiting, anorexia and abdominal complaints. She previously had a sore throat and unilateral painful swollen lymph nodes in the neck. Laboratory investigation indicated a bacterial infection. Blood cultures were taken. There was infiltrate in the left lung. Pneumonia complicated with sepsis was suspected and ceftriaxone was started. The patient's condition deteriorated. Computed tomography (CT) scan showed progressive infiltrates in both lungs and pleural effusion. Blood culture led to the diagnosis. After changing antibiotics the patient slowly improved. Antibiotics were continued for several weeks. [ABSTRACT FROM AUTHOR]