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Background: A causative role of Coxiella burnetii (the causative agent of Q fever) in the pathogenesis of B-cell non-Hodgkin lymphoma (NHL) has been suggested, although supporting studies show conflicting evidence. We assessed whether this association is present by performing a detailed analysis on the risk of mature B-cell NHL after Q fever during and after the largest Q fever outbreak reported worldwide in the entire Dutch population over a 16-year period., Methods: We performed an ecological analysis. The incidence of mature B-cell NHL in the entire Dutch population from 2002 until 2017 was studied and modelled with reported acute Q fever cases as the determinant. The adjusted relative risk of NHL after acute Q fever as the primary outcome measure was calculated using a Poisson regression., Results: Between January 2002 and December 2017, 266 050 745 person-years were observed, with 61 424 diagnosed with mature B-cell NHL. In total, 4310 persons were diagnosed with acute Q fever, with the highest incidence in 2009. The adjusted relative risk of NHL after acute Q fever was 1.02 (95% CI 0.97-1.06, P = 0.49) and 0.98 (95% CI 0.89-1.07, P = 0.60), 0.99 (95% CI 0.87-1.12, P = 0.85) and 0.98 (95% 0.88-1.08, P = 0.67) for subgroups of diffuse large B-cell lymphoma, follicular lymphoma or B-cell chronic lymphocytic leukaemia, respectively. Modelling with lag times (1-4 years) did not change interpretation., Conclusion: We found no evidence for an association between C. burnetii and NHL after studying the risk of mature B-cell NHL after a large Q fever outbreak in Netherlands., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Early detection of and treatment for chronic Q fever might prevent potentially life-threatening complications. We performed a chronic Q fever screening program in general practitioner practices in the Netherlands 10 years after a large Q fever outbreak. Thirteen general practitioner practices located in outbreak areas selected 3,419 patients who had specific underlying medical conditions, of whom 1,642 (48%) participated. Immunofluorescence assay of serum showed that 289 (18%) of 1,642 participants had a previous Coxiella burnetii infection (IgG II titer >1:64), and 9 patients were suspected of having chronic Q fever (IgG I y titer >1:512). After medical evaluation, 4 of those patients received a chronic Q fever diagnosis. The cost of screening was higher than estimated earlier, but the program was still cost-effective in certain high risk groups. Years after a large Q fever outbreak, targeted screening still detected patients with chronic Q fever and is estimated to be cost-effective.

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.

Background/aim: From 2007 through 2010, the Netherlands experienced the largest recorded Q fever outbreak to date. People living closer to Coxiella burnetii infected goat farms were at increased risk for acute Q fever. Time spent outdoors near infected farms may have contributed to exposure to C. burnetii. The aim of this study was to retrospectively evaluate whether hours/week spent outdoors, in the vicinity of previously C. burnetii infected goat farms, was associated with presence of antibodies against C. burnetii in residents of a rural area in the Netherlands., Methods: Between 2014-2015, we collected C. burnetii antibody serology and self-reported data about habitual hours/week spent outdoors near the home from 2494 adults. From a subgroup we collected 941 GPS tracks, enabling analyses of active mobility in the outbreak region. Participants were categorised as exposed if they spent time within specified distances (500m, 1000m, 2000m, or 4000m) of C. burnetii infected goat farms. We evaluated whether time spent near these farms was associated with positive C. burnetii serology using spline analyses and logistic regression., Results: People that spent more hours/week outdoors near infected farms had a significantly increased risk for positive C. burnetii serology (time spent within 2000m of a C. burnetii abortion-wave positive farm, OR 3.6 (1.2-10.6)), compared to people spending less hours/week outdoors., Conclusions: Outdoor exposure contributed to the risk of becoming C. burnetii serology positive. These associations were stronger if people spent more time near C. burnetii infected farms. Outdoor exposure should, if feasible, be included in outbreak investigations., Competing Interests: Declaration of Competing Interest All authors declare they have no conflicts of interest., (Copyright © 2020. Published by Elsevier Ltd.)

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.

Background: Prior to the 2007-2010 Q fever epidemic in the Netherlands, the seroprevalence of antibodies against Coxiella burnetii in the general population was 1.5%, which is low compared to other countries. We aimed to determine the seroprevalence after the Q fever epidemic among people living in the affected area, compare the seroprevalence with the incidence of Q fever notifications during the 2007-2010 Q fever epidemic, and to identify farm exposures associated with having antibodies against C. burnetii., Methods: During the period March 2014-February 2015, residents aged 18-70 years from two provinces were invited by general practitioners to complete a questionnaire on their symptoms and personal characteristics and to submit a blood sample. We used the mandatory provincial database of livestock licences to calculate distance to farms/farm animals for each participant. To compare ELISA-positive participants for C. burnetii antibodies with those who were negative, we calculated prevalence ratios (PR) using binominal regression. We compared the C. burnetii seroprevalence in the period March 2014-February 2015 with the incidence of Q fever notifications during the 2007-2010 Q fever epidemic at municipal level by calculating the Spearman correlation coefficient., Results: Of the 2296 participants (response rate: 34%), 6.1% (n = 139, 95% CI 5.1-7.1%) had C. burnetii antibodies (range in municipalities: 1.7-14.1%). C. burnetii seroprevalence was higher in individuals living within 1000 m of goat farms (PR 3.0; 95% CI 1.4-6.4) or within 1000 m of > 50 goats (PR 1.9; 95% CI 1.2-3.0). Seroprevalence increased with decreasing distance to the closest goat farm that was infected during the epidemic years (< 500 m, PR 9.5, 95% CI 2.8-32; 500-1000 m, PR 4.5, 95% CI 2.6-7.7; 1000-1500 m, PR 2.2, 95% CI 1.1-4.3, 1500-2000 m, PR 1.2, 95% CI 0.6-2.5; > 2000 reference group). There was no significant correlation between C. burnetii seroprevalence and Q fever incidence during the 2007-2010 epidemic (r s  = 0.42, p = 0.156)., Conclusions: Results showed a remarkable spatial variation in C. burnetii seroprevalence in a relatively small livestock dense area. It confirms previous evidence that the Q fever epidemic was primarily the result of airborne C. burnetii transmission from Q fever affected goat farms.

Objectives: To simultaneously estimate the prevalence of antibodies against Coxiella burnetii (Q fever) among adults and small ruminants, and C. burnetii shedding prevalence among small ruminants in households in the Kiang West district of The Gambia, and to assess associated risk factors., Methods: Sera of 599 adults and 615 small ruminants from 125 compounds within 12 villages were tested for antibodies against C. burnetii using ELISA. Vaginal swabs and milk samples of 155 small ruminants were tested using PCR to investigate shedding of C. burnetii., Results: A total of 3.8-9.7% of adults, depending on ELISA test cut-off, and 24.9% of small ruminants in Kiang West were seropositive. Having at least one seropositive animal in one's compound was a risk factor for human seropositivity (OR: 3.35, 95% CI: 1.09-14.44). A grazing area within a village was a risk factor for seropositivity in small ruminants (OR: 2.07, 95% CI: 1.26-3.50); others were having lambed (OR: 2.75, 95% CI: 1.37-5.76) and older age of the animals (OR: 2.75, 95% CI: 1.37-5.76 for 1-3 years and OR 5.84, 95% CI: 3.10-11.64 for >3 years); 57.4% of sampled small ruminants were shedding C. burnetii., Conclusion: Coxiella burnetii infection is endemic among both humans and small ruminants in this area of The Gambia. Human and animal exposure to C. burnetii were related at compound level. Further research into the clinical relevance of C. burnetii infection in West Africa is needed., (© 2016 John Wiley & Sons Ltd.)

Historical survey data suggest that the seroprevalence of antibodies against Coxiella burnetii in the general population of The Netherlands decreased from more than 40% in 1983 to 2·4% in 2007, just before the start of the large 2007-2010 Q fever epidemic. To assess whether the sharp decline in seroprevalence was real, we performed a cross-sectional study using historical samples. We tested samples using a contemporary commercial indirect immunofluorescence assay. In plasma samples from the south of The Netherlands from 1987, we found an age- and sex-standardized seroprevalence of 14·4% (95% confidence interval 11·2-18·3). This was significantly lower than a 1983 estimate from the same area (62·5%), but significantly higher than 2008 (1·0%) and 2010 (2·3%) estimates from the same area. The study suggests that there was a steady and sharp decline in Q fever seroprevalence in the south of The Netherlands from 1987 to 2008. We assume that seroprevalence has decreased in other parts of The Netherlands as well and seroprevalence surveys in other European countries have shown a similar declining trend. Waning population immunity in The Netherlands may have contributed to the scale of the 2007-2010 Q fever epidemic. For a better understanding of the infection dynamics of Q fever, we advocate an international comparative study of the seroprevalence of C. burnetii.

From 2007 to 2010, The Netherlands experienced a major Q fever outbreak with more than 4000 notifications. Previous studies suggested that Q fever patients could suffer long-term post-infection health impairments, especially fatigue. Our objective was to assess the Coxiella burnetii antibody prevalence and health status including fatigue, and assess their interrelationship in Herpen, a high-incidence village, 7 years after the outbreak began. In 2014, we invited all 2161 adult inhabitants for a questionnaire and a C. burnetii indirect fluorescence antibody assay (IFA). The health status was measured with the Nijmegen Clinical Screening Instrument (NCSI), consisting of eight subdomains including fatigue. Of the 70·1% (1517/2161) participants, 33·8% (513/1517) were IFA positive. Of 147 participants who were IFA positive in 2007, 25 (17%) seroreverted and were now IFA negative. Not positive IFA status, but age <50 years, smoking and co-morbidity, were independent risk factors for fatigue. Notified participants reported significantly more often fatigue (31/49, 63%) than non-notified IFA-positive participants (150/451, 33%). Although fatigue is a common sequel after acute Q fever, in this community-based survey we found no difference in fatigue levels between participants with and without C. burnetii antibodies.

Q fever is an almost ubiquitous zoonosis caused by Coxiella burnetii, which is able to infect several animal species, as well as humans. Cattle, sheep and goats are the primary animal reservoirs. In small ruminants, infections are mostly without clinical symptoms, however, abortions and stillbirths can occur, mainly during late pregnancy. Shedding of C. burnetii occurs in feces, milk and, mostly, in placental membranes and birth fluids. During parturition of infected small ruminants, bacteria from birth products become aerosolized. Transmission to humans mainly happens through inhalation of contaminated aerosols. In the last decade, there have been several, sometimes large, human Q fever outbreaks related to sheep and goats. In this review, we describe C. burnetii infections in sheep and goats, including both advantages and disadvantages of available laboratory techniques, as pathology, different serological tests, PCR and culture to detect C. burnetii. Moreover, worldwide prevalences of C. burnetii in small ruminants are described, as well as possibilities for treatment and prevention. Prevention of shedding and subsequent environmental contamination by vaccination of sheep and goats with a phase I vaccine are possible. In addition, compulsory surveillance of C. burnetii in small ruminant farms raises awareness and hygiene measures in farms help to decrease exposure of people to the organism. Finally, this review challenges how to contain an infection of C. burnetii in small ruminants, bearing in mind possible consequences for the human population and probable interference of veterinary strategies, human risk perception and political considerations., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Atmospheric dispersion models (ADMs) may help to assess human exposure to airborne pathogens. However, there is as yet limited quantified evidence that modelled concentrations are indeed associated to observed human incidence., Methods: We correlated human Q fever (caused by the bacterium Coxiella burnetii) incidence data in the Netherlands to modelled concentrations from three spatial exposure models: 1) a NULL model with a uniform concentration distribution, 2) a DISTANCE model with concentrations proportional to the distance between the source and residential addresses of patients, and 3) concentrations modelled by an ADM using three simple emission profiles. We used a generalized linear model to correlate the observed incidences to modelled concentrations and validated it using cross-validation., Results: ADM concentrations generally correlated the best to the incidence data. The DISTANCE model always performed significantly better than the NULL model. ADM concentrations based on wind speeds exceeding threshold values of 0 and 2 m/s performed better than those based on 4 or 6 m/s. This might indicate additional exposure to bacteria originating from a contaminated environment., Conclusions: By adding meteorological information the correlation between modelled concentration and observed incidence improved, despite using three simple emission profiles. Although additional information is needed - especially regarding emission data - these results provide a basis for the use of ADMs to predict and to visualize the spread of airborne pathogens during livestock, industry and even bio-terroristic related outbreaks or releases to a surrounding human population.

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 2010, (the southern part of) the Netherlands experienced a large Q fever epidemic, with more than 4,000 reported symptomatic cases. Approximately 1 - 5% of the acute Q fever patients develop chronic Q fever. A high IgG antibody titre against phase I of Coxiella burnetii during follow-up is considered a marker of chronic Q fever. However, there is uncertainty about the significance and cause of persistence of high IgG phase I antibody titres in patients that do not have any additional manifestations of chronic Q fever. We studied whether continued or repeated exposure to the source of infection could explain elevated IgG phase I antibody levels., Methods: A case-control study was performed to analyze predictors for possible chronic Q fever. Possible chronic Q fever cases (n = 53) are patients with phase I IgG antibody titre ≥1:1,024 at any point in the 9 - 18 months after acute Q fever diagnosis, with a negative PCR test result for C. burnetii DNA and without other disease manifestations. Controls (n = 110) are acute Q fever patients that did not develop chronic Q fever, and who consistently had phase I IgG antibody titre <1:1,024 during the 9 - 18 months follow-up. Binary logistic regression was performed to analyze the effect of living close to an infected farm on the high antibody titres. A longitudinal analysis described the serological profiles of cases and controls., Results: Proximity to infected farms and contact with animal placental material were not associated with an increased risk for possible chronic Q fever. Possible chronic Q fever patients have high IgG phase II as well as IgG phase I antibody titres, even after 48 months of follow-up., Conclusion: We were unable to explain the cause of persistent high IgG phase I titres among possible chronic Q fever patients by being continuously exposed to the source of infection.

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.

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.

Objective: To estimate the prevalence of antibodies against Coxiella burnetii (Q fever) among children in eight villages in The Gambia, West Africa., Methods: Sera of 796 children aged 1-15 years were tested for presence of antibodies against phase II of C. burnetii by ELISA., Results: IgG and/or IgM phase II antibodies against C. burnetii were detectable in 8.3% (66/796) of all serum samples analysed with significant differences in seroprevalence between villages. Highest prevalence was found in the age group 1-4 years., Conclusions: Exposure to C. burnetii is considerable in the early years of life in The Gambia, and further studies are warranted to estimate the role of Q fever in acute febrile illness in The Gambia and elsewhere in Africa., (© 2013 Blackwell Publishing Ltd.)

Between 2007 and 2010, the Netherlands experienced one of the largest outbreaks of Q fever. Since asymptomatic Coxiella burnetii infection has been associated with maternal and obstetric complications, evidence about the effectiveness of routine screening during pregnancy in outbreak areas is needed. We performed a clustered randomised controlled trial during the Dutch outbreak, in which 55 midwife centres were randomised to recruit pregnant women for an intervention or control strategy. In both groups a serum sample was taken between 20 and 32 weeks of gestation. In the intervention group (n=536), the samples were analysed immediately by indirect immunofluorescence assay for the presence of IgM and IgG (phase I/II) and treatment was given during pregnancy in case of an acute or chronic infection. In the control group (n=693), sera were frozen for analysis after delivery. In both groups 15% were seropositive. In the intervention group 2.2% of the women were seropositive and had an obstetric complication, compared with 1.4% in the control group (Odds ratio: 1.54 (95% confidence interval 0.60-3.96)). During a large Q fever outbreak, routine C. burnetii screening starting at 20 weeks of gestation was not associated with a relevant reduction in obstetric complications and should therefore not be recommended.

Q fever is a disease of humans, caused by Coxiella burnetii, and a large range of animals can be infected. This paper presents a review of the epidemiology of Q fever in humans and farm animals between 1982 and 2010, using case studies from four European countries (Bulgaria, France, Germany and the Netherlands). The Netherlands had a large outbreak between 2007 and 2010, and the other countries a history of Q fever and Q fever research. Within all four countries, the serological prevalence of C. burnetii infection and reported incidence of Q fever varies broadly in both farm animals and humans. Proximity to farm animals and contact with infected animals or their birth products have been identified as the most important risk factors for human disease. Intrinsic farm factors, such as production systems and management, influence the number of outbreaks in an area. A number of disease control options have been used in these four countries, including measures to increase diagnostic accuracy and general awareness, and actions to reduce spillover (of infection from farm animals to humans) and human exposure. This study highlights gaps in knowledge, and future research needs.

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.

The presence of a high phase I IgG antibody titre may indicate chronic infection and a risk for the transmission of Coxiella burnetii through blood transfusion. The outbreak of Q fever in the Netherlands allowed for the comparison of an enzyme immunoassay (EIA) with the reference immunofluorescence assay (IFA) in a large group of individuals one year after acute Q fever. EIA is 100 % sensitive in detecting high (≥1:1,024) phase I IgG antibody titres. The cost of screening with EIA and confirming all EIA-positive results with IFA is much lower than screening all donations with IFA. This should be taken into account in cost-effectiveness analyses of screening programmes.

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 Coxiella 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.

From 2007 to 2009, the Netherlands faced large seasonal outbreaks of Q fever, in which infected dairy goat farms were identified as the primary sources. Veterinary measures including vaccination of goats and sheep and culling of pregnant animals on infected farms seem to have brought the Q fever problem under control. However, the epidemic is expected to result in more cases of chronic Q fever among risk groups in the coming years. In the most affected area, in the south of the country, more than 12% of the population now have antibodies against Coxiella burnetii. Questions remain about the follow-up of acute Q fever patients, screening of groups at risk for chronic Q fever, screening of donors of blood and tissue, and human vaccination. There is a considerable ongoing research effort as well as enhanced veterinary and human surveillance.

Large outbreaks of Q fever in the Netherlands from 2007 to 2009 were monitored using notification data of acute clinical Q fever. However, the notification system provides no information on infections that remain subclinical or for which no medical attention is sought. The present study was carried out immediately after the peak of the 2009 outbreak to estimate the ratio between Coxiella burnetii infections and Q fever notifications. In 23 postcode areas in the high-incidence area, notification rates were compared with seroconversion rates in blood donors from whom serial samples were available. This resulted in a ratio of one Q fever notification to 12.6 incident infections of C. burnetii. This ratio is time and place specific and is based on a small number of seroconversions, but is the best available factor for estimating the total number of infections. In addition, as subclinical C. burnetii infection may lead to chronic Q fever, the ratio can be used to estimate the expected number of chronic Q fever patients in the coming years and as input for cost–benefit analyses of screening options.

In 2005, Q fever was diagnosed on two dairy goat farms and 2 years later it emerged in the human population in the south of the Netherlands. From 2007 to 2010, more than 4,000 human cases were notified with an annual seasonal peak. The outbreaks in humans were mainly restricted to the south of the country in an area with intensive dairy goat farming. In the most affected areas, up to 15% of the population may have been infected. The epidemic resulted in a serious burden of disease, with a hospitalisation rate of 20% of notified cases and is expected to result in more cases of chronic Q fever among risk groups in the coming years. The most important risk factor for human Q fever is living close (<5 km) to an infected dairy goat farm. Occupational exposure plays a much smaller role. In 2009 several veterinary control measures were implemented including mandatory vaccination of dairy goats and dairy sheep, improved hygiene measures, and culling of pregnant animals on infected farms. The introduction of these drastic veterinary measures has probably ended the Q fever outbreak, for which the Netherlands was ill-prepared.

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: 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)., (© 2011 American Association of Blood Banks.)

In 2009, dairy goat farms in the Netherlands were implicated in >2,300 cases of Q fever; in response, 51,820 small ruminants were culled. Among 517 culling workers, despite use of personal protective equipment, 17.5% seroconverted for antibodies to Coxiella burnetii. Vaccination of culling workers could be considered.

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.

Background: Q fever has become a major public health problem in The Netherlands. Infection with Coxiella burnetii (Q fever) during pregnancy has resulted in adverse pregnancy outcome in the majority of reported cases. Therefore, we aimed to quantify this risk by examining the earliest periods corresponding to the epidemic in The Netherlands., Methods: Serum samples that had been collected from the area of highest incidence by an existing national prenatal screening programme and data from the Netherlands Perinatal Registry (PRN) on diagnosis and outcome were used. We performed indirect immunofluorescence assay to detect the presence of IgM and IgG antibodies against C. burnetii in the samples. The serological results were analyzed to determine statistical association with recorded pregnancy outcome., Results: Evaluation of serological results for 1174 women in the PRN indicated that the presence of IgM and IgG antibodies against phase II of C. burnetii was not significantly associated with preterm delivery, low birth weight, or several other outcome measures., Conclusion: The present population-based study showed no evidence of adverse pregnancy outcome among women who had antibodies to C. burnetii during early pregnancy.

Background From 2007 to 2009, the Netherlands experienced a major Q fever epidemic. Long-term serological follow-up of acute Q fever patients enabled the investigation of longitudinal antibody responses and estimating the onset of the seroresponse in individual patients. Methods All available IgG and IgM phase I and II antibody measurements determined by immunofluorescence assay at month 3, 6, 12, and 48 from 2321 acute Q fever patients were retrospectively analyzed. Characteristic features of the antibody response were calculated. To model the seroresponse onset, serological data from patients diagnosed with a positive C. burnetii PCR test ( n = 364), and therefore with a known time of infection, were used as reference. Results In 9083 IgG samples and 3260 IgM samples large heterogeneity in shape and magnitude of antibody responses was observed. Phase II reached higher levels than phase I, and IgG antibodies were more persistent than IgM. The estimated seroresponse latency allowed for determining the time since start of the seroresponse from the concentrations of the different antibodies against C. burnetii . Conclusions The extraordinary large serological dataset provides new insight into the kinetics of the immunoglobulins against C. burnetii antigens. This knowledge is useful for seroprevalence studies and helps to better understand infection dynamics. [ABSTRACT FROM AUTHOR]

Q fever is a zoonosis caused by Coxiella burnetii with a presentation ranging from asymptomatic seroconversion to possibly fatal chronic Q fever. The Netherlands faced an exceptionally large outbreak of Q fever from 2007 to 2010: 4026 human cases were notified, which makes it the largest Q fever outbreak ever reported. This outbreak, because of its size, allowed collecting a wide range of information on the natural history of Q fever, as well as on its transmission and clinical presentation. It also posed unprecedented public healthcare problems, especially for the concomitant management of the epizootic by veterinarian authorities and public health authorities, but also for the management of transmission risk related to blood donation. The need for cost efficient measures emerged rapidly because of the great number of infected individuals or at risk of infection, with a need for guidance on follow-up of acute Q fever patients, screening of pregnant women, or implementation of diagnostic algorithms. The acute outbreak was controlled by drastic veterinarian measures but chronic Q fever will remain a problem for the coming years. [ABSTRACT FROM AUTHOR]

Chronic infection with Coxiella burnetii (chronic Q fever) can cause life-threatening conditions such as endocarditis, infected vascular prostheses, and infected arterial aneurysms. We aimed to assess prognosis of chronic Q fever patients in terms of complications and mortality. A large cohort of chronic Q fever patients was assessed to describe complications, overall mortality and chronic Q fever-related mortality. Chronic Q fever-related mortality was expressed as a case fatality rate (number of chronic Q fever-related deaths/number of chronic Q fever patients). Complications occurred in 166 of 439 (38%) chronic Q fever patients: in 61% of proven (153/249), 15% of probable (11/74), and 2% of possible chronic Q fever patients (2/116). Most frequently observed complications were acute aneurysms (14%), heart failure (13%), and non-cardiac abscesses (10%). Overall mortality was 38% (94/249) for proven chronic Q fever patients (median follow-up 3.6 years) and 22% (16/74) for probable chronic Q fever patients (median follow-up 4.7 years). The case fatality rate was 25% for proven (63/249) chronic Q fever patients and 4% for probable (3/74) chronic Q fever patients. Overall survival was significantly lower in patients with complications, compared to those without complications (p <0.001). In chronic Q fever patients, complications occur frequently and contribute to the mortality rate. Patients with proven chronic Q fever have the highest risk of complications and chronic Q fever-related mortality. Prognosis for patients with possible chronic Q fever is favourable in terms of complications and mortality. [ABSTRACT FROM AUTHOR]