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Introduction: Influenza vaccination, besides protecting traditional risk groups, can protect employees and reduce illness-related absence, which is especially relevant in sectors with staff shortages. This study describes current knowledge of influenza vaccination in teachers and estimates its potential impact., Methods: We conducted a scoping review of the considerations for and impact of influenza vaccination of schoolteachers (grey and scientific literature up to 2020 March, complemented with interviews). We then estimated the potential impact of teacher vaccination in the Netherlands, with different scenarios of vaccine uptake for 3 influenza seasons (2016-2019). Using published data on multiple input parameters, we calculated potentially averted absenteeism notifications, averted absenteeism duration and averted doctor visits for influenza., Results: Only one scientific paper reported on impact; it showed lower absenteeism in vaccinated teachers, whereas more knowledge of vaccination impact was deemed crucial by 50% of interviewed experts. The impact for the Netherlands of a hypothetical 50% vaccine uptake was subsequently estimated: 74-293 potentially averted physician visits and 11,178-28,896 potentially averted days of influenza absenteeism (on ≈200,000 total teacher population). An estimated 12-32 vaccinations were required to prevent one teacher sick-leave notification, or 3.5-9.1 vaccinations to prevent one day of teacher absenteeism (2016-2019)., Conclusion: Scientific publications on influenza vaccination in teachers are few, while public interest has increased to reduce teacher shortages. However, school boards and public health experts indicate requiring knowledge of impact when considering this vaccination. Estimations of 3.5-9.1 vaccinated teachers preventing one day of influenza-related sick leave suggest a possible substantial vaccination impact on absenteeism. Financial incentives, more accessible on-site vaccinations at workplaces, or both, are expected to increase uptake, but more research is needed on teachers' views and vaccine uptake potential and its cost-effectiveness. Piloting free on-site influenza vaccination in several schools could provide further information on teacher participation., Competing Interests: The authors have declared that no competing interests exist.

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., Competing Interests: The authors have declared that no competing interests exist.

[This corrects the article DOI: 10.1371/journal.pone.0195413.].

Background: Patients with Mycobacterium tuberculosis isolates sharing identical DNA fingerprint patterns can be epidemiologically linked. However, municipal health services in the Netherlands are able to confirm an epidemiological link in only around 23% of the patients with isolates clustered by the conventional variable number of tandem repeat (VNTR) genotyping. This research aims to investigate whether whole genome sequencing (WGS) is a more reliable predictor of epidemiological links between tuberculosis patients than VNTR genotyping., Methods: VNTR genotyping and WGS were performed in parallel on all Mycobacterium tuberculosis complex isolates received at the Netherlands National Institute for Public Health and the Environment in 2016. Isolates were clustered by VNTR when they shared identical 24-loci VNTR patterns; isolates were assigned to a WGS cluster when the pair-wise genetic distance was ≤ 12 single nucleotide polymorphisms (SNPs). Cluster investigation was performed by municipal health services on all isolates clustered by VNTR in 2016. The proportion of epidemiological links identified among patients clustered by either method was calculated., Results: In total, 535 isolates were genotyped, of which 25% (134/535) were clustered by VNTR and 14% (76/535) by WGS; the concordance between both typing methods was 86%. The proportion of epidemiological links among WGS clustered cases (57%) was twice as common than among VNTR clustered cases (31%)., Conclusion: When WGS was applied, the number of clustered isolates was halved, while all epidemiologically linked cases remained clustered. WGS is therefore a more reliable tool to predict epidemiological links between tuberculosis cases than VNTR genotyping and will allow more efficient transmission tracing, as epidemiological investigations based on false clustering can be avoided.

Community acquired pneumonia is a major global public health problem. In the Netherlands there are 40,000-50,000 hospital admissions for pneumonia per year. In the large majority of these hospital admissions the etiologic agent is not determined and a real-time surveillance system is lacking. Localised and temporal increases in hospital admissions for pneumonia are therefore only detected retrospectively and the etiologic agents remain unknown. Here, we perform spatio-temporal analyses of pneumonia hospital admission data in the Netherlands. To this end, we scanned for spatial clusters on yearly and seasonal basis, and applied wavelet cluster analysis on the time series of five main regions. The pneumonia hospital admissions show strong clustering in space and time superimposed on a regular yearly cycle with high incidence in winter and low incidence in summer. Cluster analysis reveals a heterogeneous pattern, with most significant clusters occurring in the western, highly urbanised, and in the eastern, intensively farmed, part of the Netherlands. Quantitatively, the relative risk (RR) of the significant clusters for the age-standardised incidence varies from a minimum of 1.2 to a maximum of 2.2. We discuss possible underlying causes for the patterns observed, such as variations in air pollution.

Previous research conducted in 2009 found a significant positive association between pneumonia in humans and living close to goat and poultry farms. However, as this result might have been affected by a large goat-related Q fever epidemic, the aim of the current study was to re-evaluate this association, now that the Q-fever epidemic had ended. In 2014/15, 2,494 adults (aged 20-72 years) living in a livestock-dense area in the Netherlands participated in a medical examination and completed a questionnaire on respiratory health, lifestyle and other items. We retrieved additional information for 2,426/2,494 (97%) participants from electronic medical records (EMR) from general practitioners. The outcome was self-reported, physician-diagnosed pneumonia or pneumonia recorded in the EMR in the previous three years. Livestock license data was used to determine exposure to livestock. We quantified associations between livestock exposures and pneumonia using odds ratios adjusted for participant characteristics and comorbidities (aOR). The three-year cumulative frequency of pneumonia was 186/2,426 (7.7%). Residents within 2,000m of a farm with at least 50 goats had an increased risk of pneumonia, which increased the closer they lived to the farm (2,000m aOR 1.9, 95% CI 1.4-2.6; 500m aOR 4.4, 95% CI 2.0-9.8). We found no significant associations between exposure to other farm animals and pneumonia. However, when conducting sensitivity analyses using pneumonia outcome based on EMR only, we found a weak but statistically significant association with presence of a poultry farm within 1,000m (aOR: 1.7, 95% CI 1.1-2.7). Living close to goat and poultry farms still constitute risk factors for pneumonia. Individuals with pneumonia were not more often seropositive for Coxiella burnetii, indicating that results are not explained by Q fever. We strongly recommend identification of pneumonia causes by the use of molecular diagnostics and investigating the role of non-infectious agents such as particulate matter or endotoxins.

Background: Brucellosis is a worldwide zoonosis with significant impact on rural livelihoods and a potentially underestimated contributor to febrile illnesses. The aim of this study was to estimate the seroprevalence of brucellosis in humans and small ruminants in The Gambia., Methods: The study was carried out in rural and urban areas. In 12 rural villages in Kiang West district, sera were collected from humans (n = 599) and small ruminants (n = 623) from the same compounds. From lactating small ruminants, milk samples and vaginal swabs were obtained. At the urban study sites, sera were collected from small ruminants (n = 500) from slaughterhouses and livestock markets. Information on possible risk factors for seropositivity was collected through questionnaires. Sera were screened for antibodies against Brucella spp. with the Rose Bengal Test, ELISA and Micro Agglutination Test (human sera only). PCR was performed on 10 percent of the milk samples and vaginal swabs from small ruminants., Results: One human and 14 sheep sera were positive by the Rose Bengal Test. The rest were negative in all serological tests used. The PCR results were all negative., Conclusions: The results suggest that brucellosis is currently not a generalized problem in humans or small ruminants in The Gambia., Competing Interests: The authors have declared that no competing interests exist.

We aimed to examine the long-term correlation between influenza vaccination coverage and the incidence of influenza-like illness (ILI) in the total and elderly populations of European countries for which data was available on at least six consecutive influenza seasons. We graphically visualised vaccination coverage and ILI incidence trends and calculated Spearman rank correlation coefficients. Additionally, we fitted a negative binomial regression model to estimate the change in ILI incidence per percentage point change in vaccination coverage. We found significant negative correlations for the total population of the Netherlands (ρ = -0.60, p-value = 0.003) and for the elderly populations of England (ρ = -0.80, p-value < 0.001) and Germany (ρ = -0.57, p-value = 0.04). However, results were not consistent, and for some countries we observed significant positive correlations. Only for the elderly in England was there a significant decline in incidence rate per percentage point increase in vaccination coverage (incidence rate ratio = 0.93; 95% confidence interval 0.88-0.99). Based on this ecological study it is not possible to provide evidence for a negative correlation between influenza vaccination coverage and ILI incidence. For future, aetiological studies to assess impact of influenza vaccinations on the population, there is a need for high quality data over long periods of time, on proportion of ILI caused by influenza virus infection, on severe outcome measures such as hospitalisation for influenza, and on other factors that potentially affect influenza transmission., Competing Interests: The authors have declared that no competing interests exist.

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.

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.

In 2007, Q fever started to become a major public health problem in the Netherlands, with small ruminants as most probable source. In order to reduce environmental contamination, control measures for manure were implemented because of the assumption that manure was highly contaminated with Coxiella burnetii. The aims of this study were 1) to clarify the role of C. burnetii contaminated manure from dairy goat farms in the transmission of C. burnetii to humans, 2) to assess the impact of manure storage on temperature profiles in dunghills, and 3) to calculate the decimal reduction time of the Nine Mile RSA 493 reference strain of C. burnetii under experimental conditions in different matrices. For these purposes, records on distribution of manure from case and control herds were mapped and a potential relation to incidences of human Q fever was investigated. Additionally, temperatures in two dunghills were measured and related to heat resistance of C. burnetii. Results of negative binomial regression showed no significant association between the incidence of human Q fever cases and the source of manure. Temperature measurements in the core and shell of dunghills on two farms were above 40°C for at least ten consecutive days which would result in a strong reduction of C. burnetii over time. Our findings indicate that there is no relationship between incidence of human Q fever and land applied manure from dairy goat farms with an abortion wave caused by C. burnetii. Temperature measurements in dunghills on two farms with C. burnetii shedding dairy goat herds further support the very limited role of goat manure as a transmission route during the Dutch human Q fever outbreak. It is very likely that the composting process within a dunghill will result in a clear reduction in the number of viable C. burnetii.

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.

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.

Background: Q fever is a zoonosis caused by Coxiella burnetii, a Gram negative bacterium present worldwide. Small ruminants are considered the main reservoirs for infection of humans. This study aimed to estimate the extent of C. burnetii infection among sheep and goats in part of The Gambia., Methodology/principal Findings: This survey was carried out from March to May 2012 at two areas in The Gambia. The first area comprised a cluster of seven rural villages situated 5-15 km west of Farafenni as well as the local abattoir. A second sampling was done at the central abattoir in Abuko (30 km from the capital, Banjul) in the Western Region. Serum samples were obtained from 490 goats and 398 sheep. In addition, 67 milk samples were obtained from lactating dams. Sera were tested with a Q fever ELISA kit. C. burnetii DNA was extracted from milk samples and then detected using a specific quantitative multiplex PCR assay, targeting the IS1111a element. A multivariable mixed logistic regression model was used to examine the relationship between seropositivity and explanatory variables. An overall seroprevalence of 21.6% was found. Goats had a significantly higher seroprevalence than sheep, respectively 24.2% and 18.5%. Seropositive animals were significantly older than seronegative animals. Animals from the villages had a significantly lower seroprevalence than animals from the central abattoir (15.1% versus 29.1%). C. burnetii DNA was detected in 2 out of 67 milk samples, whereas 8 samples gave a doubtful result., Conclusion/significance: A substantial C. burnetii seroprevalence in sheep and goats in The Gambia was demonstrated. People living in close proximity to small ruminants are exposed to C. burnetii. Q fever should be considered as a possible cause of acute febrile illness in humans in The Gambia. Future studies should include a simultaneous assessment of veterinary and human serology, and include aetiology of febrile illness in local clinics.

Objectives: Severe influenza can lead to Intensive Care Unit (ICU) admission. We explored whether ICU data reflect influenza like illness (ILI) activity in the general population, and whether ICU respiratory infections can predict influenza epidemics., Methods: We calculated the time lag and correlation between ILI incidence (from ILI sentinel surveillance, based on general practitioners (GP) consultations) and percentages of ICU admissions with a respiratory infection (from the Dutch National Intensive Care Registry) over the years 2003-2011. In addition, ICU data of the first three years was used to build three regression models to predict the start and end of influenza epidemics in the years thereafter, one to three weeks ahead. The predicted start and end of influenza epidemics were compared with observed start and end of such epidemics according to the incidence of ILI., Results: Peaks in respiratory ICU admissions lasted longer than peaks in ILI incidence rates. Increases in ICU admissions occurred on average two days earlier compared to ILI. Predicting influenza epidemics one, two, or three weeks ahead yielded positive predictive values ranging from 0.52 to 0.78, and sensitivities from 0.34 to 0.51., Conclusions: ICU data was associated with ILI activity, with increases in ICU data often occurring earlier and for a longer time period. However, in the Netherlands, predicting influenza epidemics in the general population using ICU data was imprecise, with low positive predictive values and sensitivities.

Background: Source identification in areas with outbreaks of airborne pathogens is often time-consuming and expensive. We developed a model to identify the most likely location of sources of airborne pathogens., Methods: As a case study, we retrospectively analyzed three Q fever outbreaks in the Netherlands in 2009, each with suspected exposure from a single large dairy goat farm. Model input consisted only of case residential addresses, day of first clinical symptoms, and human population density data. We defined a spatial grid and fitted an exponentially declining function to the incidence-distance data of each grid point. For any grid point with a fit significant at the 95% confidence level, we calculated a measure of risk. For validation, we used results from abortion notifications, voluntary (2008) and mandatory (2009) bulk tank milk sampling at large (i.e. >50 goats and/or sheep) dairy farms, and non-systematic vaginal swab sampling at large and small dairy and non-dairy goat/sheep farms. In addition, we performed a two-source simulation study., Results: Hotspots--areas most likely to contain the actual source--were identified at early outbreak stages, based on the earliest 2-10% of the case notifications. Distances between the hotspots and suspected goat farms varied from 300-1500 m. In regional likelihood rankings including all large dairy farms, the suspected goat farms consistently ranked first. The two-source simulation study showed that detection of sources is most clear if the distance between the sources is either relatively small or relatively large., Conclusions: Our model identifies the most likely location of sources in an airborne pathogen outbreak area, even at early stages. It can help to reduce the number of potential sources to be investigated by microbial testing and to allow rapid implementation of interventions to limit the number of human infections and to reduce the risk of source-to-source transmission.

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.

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.

Background: Q fever is an occupational risk for veterinarians, however little is known about the risk for veterinary medicine students. This study aimed to assess the seroprevalence of Coxiella burnetii among veterinary medicine students and to identify associated risk factors., Methods: A cross-sectional study with questionnaire and blood sample collection was performed among all veterinary medicine students studying in The Netherlands in 2006. Serum samples (n = 674), representative of all study years and study directions, were analyzed for C. burnetii IgG and IgM phase I and II antibodies with an immunofluorescence assay (IFA). Seropositivity was defined as IgG phase I and/or II titer of 1:32 and above., Results: Of the veterinary medicine students 126 (18.7%) had IgG antibodies against C. burnetii. Seropositivity associated risk factors identified were the study direction 'farm animals' (Odds Ratio (OR) 3.27 [95% CI 2.14-5.02]), advanced year of study (OR year 6: 2.31 [1.22-4.39] OR year 3-5 1.83 [1.07-3.10]) having had a zoonosis during the study (OR 1.74 [1.07-2.82]) and ever lived on a ruminant farm (OR 2.73 [1.59-4.67]). Stratified analysis revealed study direction 'farm animals' to be a study-related risk factor apart from ever living on a farm. In addition we identified a clear dose-response relation for the number of years lived on a farm with C. burnetii seropositivity., Conclusions: C. burnetii seroprevalence is considerable among veterinary medicine students and study related risk factors were identified. This indicates Q fever as an occupational risk for veterinary medicine students.

Background: Although syndromic surveillance is increasingly used to detect unusual illness, there is a debate whether it is useful for detecting local outbreaks. We evaluated whether syndromic surveillance detects local outbreaks of lower-respiratory infections (LRIs) without swamping true signals by false alarms., Methods and Findings: Using retrospective hospitalization data, we simulated prospective surveillance for LRI-elevations. Between 1999-2006, a total of 290762 LRIs were included by date of hospitalization and patients place of residence (>80% coverage, 16 million population). Two large outbreaks of Legionnaires disease in the Netherlands were used as positive controls to test whether these outbreaks could have been detected as local LRI elevations. We used a space-time permutation scan statistic to detect LRI clusters. We evaluated how many LRI-clusters were detected in 1999-2006 and assessed likely causes for the cluster-signals by looking for significantly higher proportions of specific hospital discharge diagnoses (e.g. Legionnaires disease) and overlap with regional influenza elevations. We also evaluated whether the number of space-time signals can be reduced by restricting the scan statistic in space or time. In 1999-2006 the scan-statistic detected 35 local LRI clusters, representing on average 5 clusters per year. The known Legionnaires' disease outbreaks in 1999 and 2006 were detected as LRI-clusters, since cluster-signals were generated with an increased proportion of Legionnaires disease patients (p:<0.0001). 21 other clusters coincided with local influenza and/or respiratory syncytial virus activity, and 1 cluster appeared to be a data artifact. For 11 clusters no likely cause was defined, some possibly representing as yet undetected LRI-outbreaks. With restrictions on time and spatial windows the scan statistic still detected the Legionnaires' disease outbreaks, without loss of timeliness and with less signals generated in time (up to 42% decline)., Conclusions: To our knowledge this is the first study that systematically evaluates the performance of space-time syndromic surveillance with nationwide high coverage data over a longer period. The results show that syndromic surveillance can detect local LRI-outbreaks in a timely manner, independent of laboratory-based outbreak detection. Furthermore, since comparatively few new clusters per year were observed that would prompt investigation, syndromic hospital-surveillance could be a valuable tool for detection of local LRI-outbreaks.