Notification data and criteria during a large Q-fever epidemic reassessed.

From 2007 to 2010, the largest reported Q-fever epidemic occurred in the Netherlands with 4026 notified laboratory-confirmed cases. During the course of the epidemic, health-seeking behaviour changed and awareness among health professionals increased. Changes in laboratory workflows were implemented. The aim of this study was to analyse how these changes instigated adjustments of notification criteria and how these adjustments affected the monitoring and interpretation of the epidemic. We used the articles on laboratory procedures related to the epidemic and a description of the changes that were made to the notification criteria. We compared the output of a regional laboratory with notifications to the regional Public Health Service and the national register of infectious diseases. We compared the international notification criteria for acute Q-fever. Screening with ELISA IgM phase II and PCR was added to the diagnostic workflow. In the course of the epidemic, serology often revealed a positive IgG/IgM result although cases were not infected recently. With increasing background seroprevalence, the presence of IgM antibodies can only be suggestive for acute Q-fever and has to be confirmed either by seroconversion of IgG or a positive PCR result. Differences in sero-epidemiology make it unlikely that full harmonisation of notification criteria between countries is feasible.

Disease burden of psittacosis in the Netherlands.

Psittacosis (infection with Chlamydia psittaci) can have diverse presentations in humans, ranging from asymptomatic infection to severe systemic disease. Awareness of psittacosis and its presentations are low among clinicians and the general public. Therefore, underdiagnosis and thereby underestimation of the incidence and public health importance of psittacosis is very likely. We used the methodology developed for the Burden of communicable diseases in Europe toolkit of the European Centre for Disease Prevention and Control, to construct a model to estimate disease burden in disability-adjusted life years (DALYs) attributable to psittacosis. Using this model, we estimated the disease burden caused by psittacosis in the Netherlands to have been 222 DALY per year (95% CI 172-280) over the period 2012-2014. This is comparable with the amount of DALYs estimated to be due to rubella or shigellosis in the same period in the Netherlands. Our results highlight the public health importance of psittacosis and identify evidence gaps pertaining to the clinical presentations and prognosis of this disease.

The incidence of symptomatic infection with influenza virus in the Netherlands 2011/2012 through 2016/2017, estimated using Bayesian evidence synthesis.

Due to differences in the circulation of influenza viruses, distribution and antigenic drift of A subtypes and B lineages, and susceptibility to infection in the population, the incidence of symptomatic influenza infection can vary widely between seasons and age-groups. Our goal was to estimate the symptomatic infection incidence in the Netherlands for the six seasons 2011/2012 through 2016/2017, using Bayesian evidence synthesis methodology to combine season-specific sentinel surveillance data on influenza-like illness (ILI), virus detections in sampled ILI cases and data on healthcare-seeking behaviour. Estimated age-aggregated incidence was 6.5 per 1000 persons (95% uncertainty interval (UI): 4.7-9.0) for season 2011/2012, 36.7 (95% UI: 31.2-42.8) for 2012/2013, 9.1 (95% UI: 6.3-12.9) for 2013/2014, 41.1 (95% UI: 35.0-47.7) for 2014/2015, 39.4 (95% UI: 33.4-46.1) for 2015/2016 and 27.8 (95% UI: 22.7-33.7) for season 2016/2017. Incidence varied substantially between age-groups (highest for the age-group <5 years: 23 to 47/1000, but relatively low for 65+ years: 2 to 34/1000 over the six seasons). Integration of all relevant data sources within an evidence synthesis framework has allowed the estimation - with appropriately quantified uncertainty - of the incidence of symptomatic influenza virus infection. These estimates provide valuable insight into the variation in influenza epidemics across seasons, by virus subtype and lineage, and between age-groups.

Childhood infections and common carotid intima media thickness in adolescence.

Atherosclerotic changes can be measured as changes in common carotid intima media thickness (CIMT). It is hypothesised that repeated infection-associated inflammatory responses in childhood contribute to the atherosclerotic process. We set out to determine whether the frequency of infectious diseases in childhood is associated with CIMT in adolescence. The study is part of the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) population-based birth cohort. At age 16 years, common CIMT was measured. We collected general practitioner (GP) diagnosed infections and prescribed antibiotics. Parent-reported infections were retrieved from annual questionnaires. Linear regression analysis assessed the association between number of infections during the first 4 years of life and common CIMT. Common CIMT measurement, GP and questionnaire data were available for 221 participants. No association was observed between the infection measures and CIMT. In a subgroup analysis, significant positive associations with CIMT were observed in participants with low parental education for 2-3 or ⩾7 GP diagnosed infections (+26.4 µm, 95% CI 0.4-52.4 and +26.8 µm, 95% CI 3.6-49.9, respectively) and ⩾3 antibiotic prescriptions (+35.5 µm, 95%CI 15.8-55.3). Overall, early childhood infections were not associated with common CIMT in adolescence. However, a higher number of childhood infections might contribute to the inflammatory process of atherosclerosis in subgroups with low education, this needs to be confirmed in future studies.

Chlamydia psittaci (psittacosis) as a cause of community-acquired pneumonia: a systematic review and meta-analysis.

Psittacosis is a zoonotic infectious disease caused by the transmission of the bacterium Chlamydia psittaci from birds to humans. Infections in humans mainly present as community-acquired pneumonia (CAP). However, most cases of CAP are treated without diagnostic testing, and the importance of C. psittaci infection as a cause of CAP is therefore unclear. In this meta-analysis of published CAP-aetiological studies, we estimate the proportion of CAP caused by C. psittaci infection. The databases MEDLINE and Embase were systematically searched for relevant studies published from 1986 onwards. Only studies that consisted of 100 patients or more were included. In total, 57 studies were selected for the meta-analysis. C. psittaci was the causative pathogen in 1·03% (95% CI 0·79-1·30) of all CAP cases from the included studies combined, with a range between studies from 0 to 6·7%. For burden of disease estimates, it is a reasonable assumption that 1% of incident cases of CAP are caused by psittacosis.

Estimated incidence and number of outpatient visits for seasonal influenza in 2015-2016 in Beijing, China.

Information on morbidity burden of seasonal influenza in China is limited. A multiplier model was used to estimate the incidence and number of outpatient visits for seasonal influenza by age group for the 2015-2016 season in Beijing, the capital of China, based on reported numbers of influenza-like illness consultations and proportions of positive cases from influenza surveillance systems in Beijing, general consultation rates and other parameters from previous studies, surveys and surveillance systems. An estimated total of 1 190 200 (95% confidence interval (CI) 830 400-1 549 900) cases of influenza virus infections occurred in Beijing, 2015-2016 season, with an attack rate of 5·5% (95% CI 3·9-7·2%). These infections resulted in an estimated 468 280 (95% CI 70 700-606 800) outpatient visits, with an attack rate of 2·2% (95% CI 0·3-2·8%). The attack rate of influenza virus infections was highest among children aged 0-4 years (31·9% (95% CI 21·9-41·9%)), followed by children aged 5-14 years (18·7% (95% CI 12·9-24·5%)). Our study demonstrated a substantial influenza-related morbidity in Beijing, China, especially among the preschool- and school-aged children. This suggests that development or modification of seasonal influenza targeted vaccination strategies need to recognize that incidence is highest in children.

Prevalence and risk factors for colonization of Clostridium difficile among adults living near livestock farms in the Netherlands.

A cross-sectional study was performed among 2494 adults not living or working on a farm to assess prevalence of Clostridium difficile (CD) colonization and risk factors in a livestock dense area. CD prevalence was 1·2%. Twenty-one persons were colonized with a toxigenic strain and nine with a non-toxigenic strain. CD-positive persons did not live closer to livestock farms than individuals negative for CD. Antibiotic exposure in the preceding 3 months was a risk factor for CD colonization (odds ratio 3·70; 95% confidence interval 1·25-10·95).

The health status of a village population, 7 years after a major Q fever outbreak.

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.

Waning population immunity prior to a large Q fever epidemic in the south of The Netherlands.

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.

Severely impaired health status of non-notified Q fever patients leads to an underestimation of the true burden of disease.

Q fever patients are often reported to experience a long-term impaired health status, including fatigue, which can persist for many years. During the large Q fever epidemic in The Netherlands, many patients with a laboratory-confirmed Coxiella burnetii infection were not notified as acute Q fever because they did not fulfil the clinical criteria of the acute Q fever case definition (fever, pneumonia and/or hepatitis). Our study assessed and compared the long-term health status of notified and non-notified Q fever patients at 4 years after onset of illness, using the Nijmegen Clinical Screening Instrument (NCSI). The study included 448 notified and 193 non-notified Q fever patients. The most severely affected subdomain in both patient groups was 'Fatigue' (50·5% of the notified and 54·6% of the non-notified patients had severe fatigue). Long-term health status did not differ significantly between the notified and non-notified patient groups, and patients scored worse on all subdomains compared to a healthy reference group. Our findings suggest that the magnitude of the 2007-2009 Q fever outbreak in The Netherlands was underestimated when only notified patients according to the European Union case definition are considered.

Summer increase of Legionnaires' disease 2010 in The Netherlands associated with weather conditions and implications for source finding.

During August and September 2010 an unexpected high number of domestic cases of Legionnaires' disease (LD) were reported in The Netherlands. To examine this increase, patient characteristics and results of source finding and environmental sampling during the summer peak were compared to other domestic cases in 2008-2011. This analysis did not provide an explanation for the rise in cases. A similar increase in LD cases in 2006 was shown to be associated with warm and wet weather conditions, using an extended Poisson regression model with adjustment for long-term trends. This model was optimized with the new data from 2008 to 2011. The increase in 2010 was very accurately described by a model, which included temperature in the preceding 4 weeks, and precipitation in the preceding 2 weeks. These results confirm the strong association of LD incidence with weather conditions, but it remains unclear which environmental sources contributed to the 2010 summer increase.

Comparing the impact of two concurrent infectious disease outbreaks on The Netherlands population, 2009, using disability-adjusted life years.

In 2009 two notable outbreaks, Q fever and the novel influenza A(H1N1)pdm09, occurred in The Netherlands. Using a composite health measure, disability-adjusted life years (DALYs), the outbreaks were quantified and compared. DALYs were calculated using standardized methodology incorporating age- and sex-stratified data in a disease progression model; years lost due to disability and years of life lost were computed by outcome. Nationally, influenza A(H1N1)pdm09 caused more DALYs (24 484) than Q fever (5797). However, Q fever was 8·28 times more severe [497 DALYs/1000 symptomatic cases (DP1SC)] than A(H1N1)pdm09 (60 DP1SC). The A(H1N1)pdm09 burden is largely due to mortality while the Q fever burden is due primarily to long-term sequelae. Intervention prioritization for influenza should support patients in a critical condition while for Q fever it should target immediate containment and support for patients with long-term sequelae. Burden estimates provide guidance for focusing intervention options during outbreaks of infectious diseases.

Particulate matter strongly associated with human Q fever in The Netherlands: an ecological study.

There are still questions about the importance of different animal reservoirs and environmental factors that played a role in the large Q fever epidemic in The Netherlands. We therefore investigated the spatial association between reported Q fever cases and different livestock and environmental factors at the national level. A spatial regression analysis was performed, with four-digit postal code areas as the unit of analysis. High level of particulate matter (< 24.5 µg/m³) with an aerodynamic diameter <10 µm (PM10) was by far the strongest risk factor for human Q fever with an odds ratio of 10.4 (95% confidence interval 7.0-15.6) using PM10 <24.5 µg/m³ as reference, in logistic regression analysis, controlling for differences in animal densities, vegetation and other risk factors. Particulate matter seems to play an important role in the transmission of Q fever from infected animals to humans and should be a focus for further studies on zoonotic infectious diseases and decision-making.

Routine screening for Coxiella burnetii infection during pregnancy: a clustered randomised controlled trial during an outbreak, the Netherlands, 2010.

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 in humans and farm animals in four European countries, 1982 to 2010.

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.

The 2009 influenza A (H1N1) pandemic. Management and vaccination strategies in The Netherlands.

Prior to 2009, The Netherlands had prepared itself extensively for a potential pandemic. Multidisciplinary guidelines had been drafted to control transmission and limit adverse outcomes for both a phase of early incidental introduction and for a phase with widespread transmission. The Ministry of Health had ensured a supply and distribution schedule for antivirals and negotiated a contract for vaccine purchases. During the pandemic, existing surveillance was expanded, the established infectious disease response structure was activated, and the previously prepared protocols for communication, diagnostics, use of antivirals, and vaccination implementation were operationalized and implemented. When the pandemic turned out to be less severe than many had anticipated, risk communication and rapid modification of guidelines and communication became a major challenge. Antivirals and pandemic vaccines were reserved for those at high risk for severe outcomes only. Overall, the impact of the pandemic was comparable to the impact of an average seasonal influenza epidemic, but with a shift in (severe) outcomes from the very young and elderly toward young adults. Established prepared protocols enabled timely coordinated responses. In preparing for the worst, sufficient attention must be given to preparing for a mild scenario as well.

Detection of phase I IgG antibodies to Coxiella burnetii with EIA as a screening test for blood donations.

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.

Visits on 'lamb-viewing days' at a sheep farm open to the public was a risk factor for Q fever in 2009.

Between February and May 2009, 347 laboratory-confirmed cases of acute Q fever were reported in a southern municipal health service region in The Netherlands. Commercial dairy-goat farms were implicated and control measures were initially targeted there. A preliminary investigation also implicated a non-dairy sheep farm, open to the public on 'lamb-viewing days'. This study tested the association between visiting the non-dairy sheep farm and developing Q fever in residents of the region between February and May 2009. A case-control study of 146 cases and 431 address-matched controls was conducted. Multivariable logistic regression analysis confirmed the association between visiting to the sheep farm and Q fever disease (matched odds ratio 43, 95% confidence interval 9-200). Other risk factors were being a smoker, having a past medical history and being aged >40 years. Vaccination of sheep and goats on farms open to the public should help to reduce the number of future human cases.

The burden of 2009 pandemic influenza A(H1N1) in the Netherlands.

BACKGROUND: The disease burden of the 2009 influenza pandemic has been debated but reliable estimates are lacking. To guide future policy and control, these estimates are necessary. This study uses burden of disease measurements to assess the contribution of the pandemic influenza A(H1N1) virus to the overall burden of disease in the Netherlands. METHODS: The burden of disease caused by 2009 pandemic influenza was estimated by calculating Disability Adjusted Life Years (DALY), a composite measure that combines incidence, sequelae and mortality associated with a disease, taking duration and severity into account. Available influenza surveillance data sources (primary care sentinel surveillance, notification data on hospitalizations and deaths and death registries) were used. Besides a baseline scenario, five alternative scenarios were used to assess effects of changing values of input parameters. RESULTS: The baseline scenario showed a loss of 5800 DALY for the Netherlands (35 DALY per 100 000 population). This corresponds to 0.13% of the estimated annual disease burden in the Netherlands and is comparable to the estimated disease burden of seasonal influenza, despite a different age distribution in incidence and mortality of the pandemic compared to seasonal influenza. CONCLUSIONS: This disease burden estimate confirmed that, although there was a higher mortality observed among young people, the 2009 pandemic was overall a mild influenza epidemic. The disease burden of this pandemic was comparable to the burden of seasonal influenza in the Netherlands.

Relation between Q fever notifications and Coxiella burnetii infections during the 2009 outbreak in The Netherlands.

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 cost­benefit analyses of screening options.