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Background: The burden of severe influenza virus infections is poorly known, for which surveillance of severe acute respiratory infection (SARI) is encouraged. Hospitalized SARI patients are however not always tested for influenza virus infection. Thus, to estimate the impact of influenza circulation we studied how influenza in primary care relates to intensive care unit (ICU) admissions using a modelling approach. Methods: We used time‐series regression modelling to estimate a) the number of SARI admissions to ICU associated with medically attended influenza infections in primary care; b) how this varies by season; and c) the time lag between SARI and influenza time series. We analysed weekly adult ICU admissions (registry data) and adult influenza incidence (primary care surveillance data) from July 2007 through June 2016. Results: Depending on the year, 0% to 12% of annual SARI admissions were associated with influenza (0‐554 in absolute numbers; population rate: 0/10 000‐0.39/10 000 inhabitants), up to 27% during influenza epidemics. The average optimal fitting lag was +1 week (SARI trend preceding influenza by 1 week), varying between seasons (−1 to +4) with most seasons showing positive lags. Conclusion: Up to 12% of yearly SARI admissions to adult ICU are associated with influenza, but with large year‐to‐year variation and higher during influenza epidemics. In most years, SARI increases earlier than medically attended influenza infections in the general population. SARI surveillance could thus complement influenza‐like illness surveillance by providing an indication of the season‐specific burden of severe influenza infections and potential early warning of influenza activity and severity. [ABSTRACT FROM AUTHOR]

Ambulance dispatches for respiratory syndromes reflect incidence of influenza-like illness in primary care. Associations are highest in children (15%-34% of respiratory calls attributable to influenza), out-of-office hours (9%), and highest urgency-level calls (9%-11%). Ambulance dispatches might be an additional source of data for severe influenza surveillance. [ABSTRACT FROM AUTHOR]

Influenza vaccine effectiveness (IVE) varies over different influenza seasons and virus (sub)types/lineages. To assess the association between IVE and circulating influenza virus (sub)types/lineages, we estimated the overall and (sub)type specific IVE in the Netherlands. We conducted a test-negative case control study among subjects with influenza-like illness or acute respiratory tract infection consulting the Sentinel Practices over 11 influenza seasons (2003/2004 through 2013/2014) in the Netherlands. The adjusted IVE was estimated using generalized linear mixed modelling and multiple logistic regression. In seven seasons vaccine strains did not match the circulating viruses. Overall adjusted IVE was 40% (95% CI 18 to 56%) and 20% (95% CI -5 to 38%) when vaccine (partially)matched and mismatched the circulating viruses, respectively. When A(H3N2) was the predominant virus, IVE was 38% (95% CI 14 to 55%). IVE against infection with former seasonal A(H1N1) virus was 83% (95% CI 52 to 94%), and with B virus 67% (95% CI 55 to 76%). In conclusion IVE estimates were particularly low when vaccine mismatched the circulating viruses and A(H3N2) was the predominant influenza virus subtype. Tremendous effort is required to improve vaccine production procedure and to explore the factors that influence the IVE against A(H3N2) virus. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background We assessed the impact of two major modifications of the Dutch National Influenza Prevention Programme - the introduction in 1997 of free-of-charge vaccination to persons aged ≥65 years and to high-risk groups (previously only advised, and not free of charge), and the lowering of the eligible age to 60 years in 2008 - on the estimated incidence of influenza infection leading to influenza-like illness ( ILI). Methods Additive negative-binomial segmented regression models were fitted to ILI data from GP sentinel surveillance in two-eight-season intervals (1993/4 to 2000/1, 2004/5 to 2011/12, comparing pre- and post-policy-change periods within each interval), with laboratory virological reporting of samples positive for influenza or other ILI-causing pathogens as covariates. Results For the 2008 policy change, there was a significant step decrease in influenza contribution considering all ages (=−111 per 100 positives; 95% CI: −162, −65·0), <60 years and 60-64 years age groups ( B = −92·1 per 100; 95% CI: −134, −55·5; B = −5·2; 95% CI: −10·3, −1·2, respectively). There was no evidence for a decrease associated with the 1997 policy change targeting the ≥65 years age group. Conclusions In the Netherlands, a 56% reduction in influenza contribution was associated with the 2008 policy targeting 60-64 year-olds, but there was no effect of the earlier policy targeting ≥65-year-olds, for whom vaccination coverage was already rising before the policy change. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: During the 2009 influenza pandemic period, routine surveillance of influenza-like-illness (ILI) was conducted in The Netherlands by a network of sentinel general practitioners (GPs). In addition during the pandemic period, four other ILI/influenza surveillance systems existed. For pandemic preparedness, we evaluated the performance of the sentinel system and the others to assess which of the four could be useful additions in the future. We also assessed whether performance of the five systems was influenced by media reports during the pandemic period. Methods: The trends in ILI consultation rates reported by sentinel GPs from 20 April 2009 through 3 January 2010 were compared with trends in data from the other systems: ILI cases self-reported through the web-based Great Influenza Survey (GIS); influenza-related web searches through Google Flu Trends (GFT); patients admitted to hospital with laboratory-confirmed pandemic influenza, and detections of influenza virus by laboratories. In addition, correlations were determined between ILI consultation rates of the sentinel GPs and data from the four other systems. We also compared the trends of the five surveillance systems with trends in pandemic-related newspaper and television coverage and determined correlation coefficients with and without time lags. Results: The four other systems showed similar trends and had strong correlations with the ILI consultation rates reported by sentinel GPs. The number of influenza virus detections was the only system to register a summer peak. Increases in the number of newspaper articles and television broadcasts did not precede increases in activity among the five surveillance systems. Conclusions: The sentinel general practice network should remain the basis of influenza surveillance, as it integrates epidemiological and virological information and was able to maintain stability and continuity under pandemic pressure. Hospital and virological data are important during a pandemic, tracking the severity, molecular and phenotypic characterization of the viruses and confirming whether ILI incidence is truly related to influenza virus infections. GIS showed that web-based, self-reported ILI can be a useful addition, especially if virological self-sampling is added and an epidemic threshold could be determined. GFT showed negligible added value. [ABSTRACT FROM AUTHOR]

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 lowerrespiratory 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. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the general practitioner (GP) consultation rate attributable to influenza in The Netherlands.Methods: Regression analysis was performed on the weekly numbers of influenza-like illness (ILI) GP consultations and laboratory reports for influenza virus types A and B and 8 other pathogens over the period 2003-2014 (11 influenza seasons; week 40-20 of the following year).Results: In an average influenza season, 27% and 11% of ILI GP consultations were attributed to infection by influenza virus types A and B, respectively. Influenza is therefore responsible for approximately 107 000 GP consultations (651/100 000) each year in The Netherlands. GP consultation rates associated with influenza infection were highest in children under 5 years of age, at 667 of 100 000 for influenza A and 258 of 100 000 for influenza B. Influenza virus infection was found to be the predominant cause of ILI-related GP visits in all age groups except children under 5, in which respiratory syncytial virus (RSV) infection was found to be the main contributor.Conclusions: The burden of influenza in terms of GP consultations is considerable. Overall, influenza is the main contributor to ILI. Although ILI symptoms in children under 5 years of age are most often associated with RSV infection, the majority of visits related to influenza occur among children under 5 years of age. [ABSTRACT FROM AUTHOR]

Information about influenza vaccine effectiveness (IVE) is important for vaccine strain selection and immunization policy decisions. The test-negative design (TND) case-control study is commonly used to obtain IVE estimates. However, the definition of the control patients may influence IVE estimates. We have conducted a TND study using the Dutch Sentinel Practices of NIVEL Primary Care Database which includes data from patients who consulted the General Practitioner (GP) for an episode of acute influenza-like illness (ILI) or acute respiratory infection (ARI) with known influenza vaccination status. Cases were patients tested positive for influenza virus. Controls were grouped into those who tested (1) negative for influenza virus (all influenza negative), (2) negative for influenza virus, but positive for respiratory syncytial virus, rhinovirus or enterovirus (non-influenza virus positive), and (3) negative for these four viruses (pan-negative). We estimated the IVE over all epidemic seasons from 2003/2004 through 2013/2014, pooled IVE for influenza vaccine partial/full matched and mismatched seasons and the individual seasons using generalized linear mixed-effect and multiple logistic regression models. The overall IVE adjusted for age, GP ILI/ARI diagnosis, chronic disease and respiratory allergy was 35% (95% CI: 15–48), 64% (95% CI: 49–75) and 21% (95% CI: −1 to 39) for all influenza negative, non-influenza virus positive and pan-negative controls, respectively. In both the main and subgroup analyses IVE estimates were the highest using non-influenza virus positive controls, likely due to limiting inclusion of controls without laboratory-confirmation of a virus causing the respiratory disease. [ABSTRACT FROM AUTHOR]

Abstract: Enhanced surveillance of infections due to the pandemic A(H1N1) influenza virus, which included monitoring for antiviral resistance, was carried out in the Netherlands from late April 2009 through late May 2010. More than 1100 instances of infection with the pandemic A(H1N1) influenza virus from 2009 and 2010 [A(H1N1) 2009] distributed across this period were analyzed. Of these, 19 cases of oseltamivir-resistant virus harboring the H275Y mutation in the neuraminidase (NA) were detected. The mean 50% inhibitory concentration (IC50) levels for oseltamivir- and zanamivir-susceptible A(H1N1) 2009 viruses were 1.4-fold and 2-fold, respectively, lower than for the seasonal A(H1N1) influenza viruses from 2007/2008; for oseltamivir-resistant A(H1N1) 2009 virus the IC50 was 2.9-fold lower. Eighteen of the 19 patients with oseltamivir-resistant virus showed prolonged shedding of the virus and developed resistance while on oseltamivir therapy. Sixteen of these 18 patients had an immunodeficiency, of whom 11 had a hematologic disorder. The two other patients had another underlying disease. Six of the patients who had an underlying disease died; of these, five had received cytostatic or immunosuppressive therapy. No indications for onward transmission of resistant viruses were found. This study showed that the main association for the emergence of cases of oseltamivir-resistant A(H1N1) 2009 virus was receiving antiviral therapy and having drug-induced immunosuppression or an hematologic disorder. Except for a single case of a resistant virus not linked to oseltamivir therapy, the absence of detection of resistant variants in community specimens and in specimens from contacts of cases with resistant virus suggested that the spread of resistant A(H1N1) 2009 virus was limited. Containment may have been the cumulative result of impaired NA function, successful isolation of the patients, and prophylactic measures to limit exposure. [Copyright &y& Elsevier]