Impact analysis of rotavirus vaccination in various geographic regions in Western Europe.

BACKGROUND: Universal mass vaccination (UMV) against rotavirus has been implemented in many but not all European countries. This study investigated the impact of UMV on rotavirus incidence trends by comparing European countries with UMV: Belgium, England/Wales and Germany versus countries without UMV: Denmark and the Netherlands. METHODS: For this observational retrospective cohort study, time series data (2001-2016) on rotavirus detections, meteorological factors and population demographics were collected. For each country, several meteorological and population factors were investigated as possible predictors of rotavirus incidence. The final set of predictors were incorporated in negative binomial models accounting for seasonality and serial autocorrelation, and time-varying incidence rate ratios (IRR) were calculated for each age group and country separately. The overall vaccination impact two years after vaccine implementation was estimated by pooling the results using a random effects meta-analyses. Independent t-tests were used to compare annual epidemics in the pre-vaccination and post-vaccination era to explore any changes in the timing of rotavirus epidemics. RESULTS: The population size and several meteorological factors were predictors for the rotavirus epidemiology. Overall, we estimated a 42% (95%-CI 23;56%) reduction in rotavirus incidence attributable to UMV. Strongest reductions were observed for age-groups 0-, 1- and 2-years (IRR 0.47, 0.48 and 0.63, respectively). No herd effect induced by UMV in neighbouring countries was observed. In all UMV countries, the start and/or stop and corresponding peak of the rotavirus season was delayed by 4-7 weeks. CONCLUSIONS: The introduction of rotavirus UMV resulted in an overall reduction of 42% in rotavirus incidence in Western European countries two years after vaccine introduction and caused a change in seasonal pattern. No herd effect induced by UMV neighbouring countries was observed for Denmark and the Netherlands.

Atmospheric dispersion and transmission of Legionella from wastewater treatment plants: A 6-year case-control study.

Legionnaires Disease incidence has risen in the Netherlands in recent years. For the majority of the cases, the source of infection is never identified. Two Dutch wastewater treatment plants (WWTPs) have previously been identified as source of outbreaks of Legionnaires Disease (LD) among local residents. The objective of this study is to examine if LD patients in the Netherlands are more exposed to aerosols originating from WWTPs than controls. METHODS: An atmospheric dispersion model was used to generate nationwide exposure maps of aerosols from 776 WWTPs in the Netherlands. Municipal sewage treatment plants and industrial WWTPs were both included. Exposure of LD cases and controls at the residential address was compared, in a matched case-control design using a conditional logistic regression. Cases were notified LD cases with onset of disease in the period 2013-2018 in the Netherlands (n = 1604). RESULTS: Aerosols dispersed over a large part of the Netherlands, but modelled concentrations are estimated to be elevated in close proximity to WWTPs. A statistically significant association was found between LD and the calculated annual average aerosol concentrations originating from WWTPs (odds-ratio: 1.32 (1.06-1.63)). This association remained significant when the two outbreak-related WWTPs were removed from the analysis (odds-ratio: 1.28 (1.03-1.58)). CONCLUSION: LD cases were more exposed to aerosols from WWTPs than controls. This indicates that exposure to aerosols dispersed from WWTPs caused Legionnaires Disease in residents living near WWTPs in the period 2013-2018. In order to investigate which characteristics of WWTPs are associated with an increased LD risk, the WWTP database should be updated and more data is needed on the presence and survival of aerosolized Legionella bacteria to improve the Legionella dispersion modelling. Furthermore, it is recommended to further investigate how aerosol dispersion of WWTPs can effectively be reduced in order to reduce the potential health risk.

Spatial Effects of Livestock Farming on Human Infections With Shiga Toxin-Producing Escherichia coli O157 in Small but Densely Populated Regions: The Case of the Netherlands.

The role of environmental transmission of typically foodborne pathogens like Shiga toxin-producing Escherichia coli (STEC) O157 is increasingly recognized. To gain more insights into spatially restricted risk factors that play a role in this transmission, we assessed the spatial association between sporadic STEC O157 human infections and the exposure to livestock (i.e. small ruminants, cattle, poultry, and pigs) in a densely populated country: the Netherlands. This was done for the years 2007-2016, using a state-of-the-art spatial analysis method in which hexagonal areas with different sizes (90, 50, 25 and 10 km2) were used in combination with a novel probability of exposure metric: the population-weighted number of animals per hexagon. To identify risk factors for STEC O157 infections and their population attributable fraction (PAF), a spatial regression model was fitted using integrated nested Laplace approximation (INLA). Living in hexagonal areas of 25, 50 and 90 km2 with twice as much population-weighted small ruminants was associated with an increase of the incidence rate of human STEC O157 infections in summer (RR of 1.09 [95%CI;1.01-1.17], RR of 1.17 [95%CI;1.07-1.28] and RR of 1.13 [95%CI;1.01-1.26]), with a PAF of 49% (95%CI;8-72%). Results suggest exposure to small ruminants to be a risk factor, although no evidence on the mode of transmission is provided. Therefore, the underlying mechanisms warrant further investigation and could offer new targets for control. The newly proposed exposure metric has potential to improve existing spatial modeling studies on infectious diseases related to livestock exposure, especially in densely populated countries like the Netherlands.

Familiarity of general practitioners with Q fever decreases hospitalisation risk.

INTRODUCTION: Between 2007 and 2010, the Netherlands experienced large outbreaks of Q fever with over 4000 cases. There were unexplained geographical differences in hospitalisation rates of notified patients. We examined the extent of this geographic variation in Q fever hospitalisation and its potential association with general practitioner (GP) experience with Q fever. METHODS: We included Q fever cases notified by GPs in 2008 and 2009 in the affected public health region. We used linear regression to describe trends of hospitalisation over time and tested for statistical differences in hospitalisation between municipalities with the chi-square test. We used the number of previously diagnosed Q fever cases of an individual GP as a proxy for Q fever experience, grouped into four categories of GP experience (1; 2; 3-7 and 8 or more cases). We calculated adjusted odds ratios (OR) using logistic regression, taking into account clustering at the GP level. RESULTS: The proportion of hospitalised cases was highly variable between municipalities (range 0-56%, p-value < 0.001). The proportion of hospitalised cases decreased monthly by 0.7% (95% confidence interval (CI): 0.03-1.3%). The risk of hospitalisation was lower when GPs had seen eight or more Q fever cases compared with GPs who had seen only one case (OR 0.4 [95% CI: 0.2-0.8]). DISCUSSION: Our findings suggest that increased GP experience was associated with a reduction in hospitalisations. This supports the public health initiatives to disseminate epidemiological updates and information regarding diagnostic and therapeutic options for Q fever to GPs to reduce Q fever related hospitalisation.

Impact of infant pneumococcal conjugate vaccination on community acquired pneumonia hospitalization in all ages in the Netherlands.

BACKGROUND: The long-term impact of pneumococcal conjugate vaccines on pneumonia hospitalizations in all age-groups varies between countries. In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV7) was implemented for newborns in 2006 and replaced by PCV10 in 2011. We assessed the impact of PCVs on community-acquired pneumonia (CAP) hospitalization rates in all age-groups. METHODS: A time series analysis using Poisson regression was performed on 155,994 CAP hospitalizations. Hospitalization rates were calculated using the total number of hospitalizations as denominator. The time trend in the pre-PCV period (1999-2006) was extrapolated to predict the hospitalization rate in the post-PCV period (2006-2014) if PCV had not been implemented. Rate ratios over time were calculated by comparing observed and predicted time trends. RESULTS: In children <5 years of age, the observed hospitalization rates during the post-PCV period were significantly lower than predicted if PCV had not been implemented (0-6 months: 0.62, 95% CI: 0.41-0.96; 6 months - 1 year: 0.67, 95% CI: 0.50-0.90; 2-4 years: 0.78, 95% CI: 0.61-0.97). In all other age-groups, rate ratios declined over time but did not reach statistical significance. CONCLUSIONS: After introduction of PCV, CAP hospitalizations declined in young children but no clear impact of PCV on CAP hospitalizations was seen in other age-groups.

Human Q fever incidence is associated to spatiotemporal environmental conditions.

Airborne pathogenic transmission from sources to humans is characterised by atmospheric dispersion and influence of environmental conditions on deposition and reaerosolisation. We applied a One Health approach using human, veterinary and environmental data regarding the 2009 epidemic in The Netherlands, and investigated whether observed human Q fever incidence rates were correlated to environmental risk factors. We identified 158 putative sources (dairy goat and sheep farms) and included 2339 human cases. We performed a high-resolution (1 × 1 km) zero-inflated regression analysis to predict incidence rates by Coxiella burnetii concentration (using an atmospheric dispersion model and meteorological data), and environmental factors - including vegetation density, soil moisture, soil erosion sensitivity, and land use data - at a yearly and monthly time-resolution. With respect to the annual data, airborne concentration was the most important predictor variable (positively correlated to incidence rate), followed by vegetation density (negatively). The other variables were also important, but to a less extent. High erosion sensitive soils and the land-use fractions "city" and "forest" were positively correlated. Soil moisture and land-use "open nature" were negatively associated. The geographical prediction map identified the largest Q fever outbreak areas. The hazard map identified highest hazards in a livestock dense area. We conclude that environmental conditions are correlated to human Q fever incidence rate. Similar research with data from other outbreaks would be needed to more firmly establish our findings. This could lead to better estimations of the public health risk of a C. burnetii outbreak, and to more detailed and accurate hazard maps that could be used for spatial planning of livestock operations.

Geographical association between livestock density and human Shiga toxin-producing Escherichia coli O157 infections.

Shiga toxin-producing Escherichia coli (STEC) bacteria can cause outbreaks and sporadic cases of gastroenteritis in humans. Ruminants are seen as the main reservoir. The aim of this study was to evaluate the spatial association between reported human STEC O157 infections in The Netherlands and different livestock densities. Data were collected at the municipality level and a spatial regression analysis was performed. Between April 1999 and December 2008, 409 symptomatic sporadic cases were registered. Adding an interaction term between season, age, and livestock density showed an increased risk of STEC cases in summer for living in areas with cattle, in particular for young children. In conclusion, cattle, but not pigs or poultry, are indicated as an important source for human STEC O157 infections in rural areas. The association is probably due to direct or indirect contact with cattle, resulting in symptomatic infections, especially in young children.

Evaluation of the "testing and scheduling" strategy for control of Campylobacter in broiler meat in The Netherlands.

"Testing and scheduling" has been proposed as a strategy for control of Campylobacter in broiler meat. By this strategy, flocks with high numbers of Campylobacter in fecal samples would be diverted away from fresh meat production at the entrance of the broiler meat processing plant. Risk assessment studies suggest that this would effectively decrease human health risks, if these flocks are responsible for the meat products with the highest Campylobacter numbers. To investigate the effect of this control strategy, the numbers of Campylobacter were determined in fecal samples from transport containers, and in cecal and breast meat samples from birds in 62 broiler chicken flocks. Results from direct plating and enrichment were combined by a statistical method that allows the inclusion of censored data. As the implementation of "testing and scheduling" requires a rapid on-site test to detect high numbers of Campylobacter, a lateral flow immuno-assay (LFA) was developed and applied to the fecal samples collected from containers. The Campylobacter prevalence in broiler flocks in the autumn of 2007 was found to be 85.4% by traditional microbiological methods. Campylobacter could be isolated from breast meat samples from 42% of the flocks. There was limited agreement between Campylobacter results for the three types of samples and weak correlation between the quantitative results for fecal or cecal samples and meat samples. Agreement between the results of LFA and traditional methods was poor. These findings do not support the implementation of "testing and scheduling" as a practical control strategy, because of both measurement uncertainties and shortcomings in understanding the dynamics of transmission and survival of Campylobacter in the broiler meat processing plant. The limited correlation between Campylobacter contamination of cecal samples and breast meat samples, as observed in this study, suggests that cecal samples are no good indicator for human exposure to Campylobacter.

The use of Bartonella henselae-specific age dependent IgG and IgM in diagnostic models to discriminate diseased from non-diseased in Cat Scratch Disease serology.

Cat Scratch Disease (CSD) is caused by Bartonella henselae infection and is a common cause of regional lymphadenopathy. The diagnosis of CSD largely depends on serology, but is hampered by both low sensitivity and specificity of the applied IgG and IgM assays. Using an in-house ELISA, we detected a significant age-dependent increase in the IgG levels in the general population compared to CSD patients. With this knowledge, we developed diagnostic models to differentiate diseased from non-diseased persons. Evaluation of these models using samples from PCR-positive patients (n=155) and age-matched controls (n=244) showed an important increase in the assay performance if the combination of the IgG and IgM results were taken into account. If the specificity was set at 98% the sensitivity was only 45% and 32% for the IgM and IgG ELISA, respectively but increased to 59% when these results were combined. Also the use of age-dependent factors further improved the clinical relevance of the outcome raising the sensitivity to 64%. Although the sensitivity of the ELISA remains low we conclude that the use of models using the combination of both IgM and IgG test results and age-depending factors can be a useful diagnostic tool in the serodiagnosis of CSD.