Exploring the effect of clinical case definitions on influenza vaccine effectiveness estimation at primary care level: Results from the end-of-season 2022-23 VEBIS multicentre study in Europe.

BACKGROUND: Within influenza vaccine effectiveness (VE) studies at primary care level with a laboratory-confirmed outcome, clinical case definitions for recruitment of patients can vary. We used the 2022-23 VEBIS primary care European multicentre study end-of-season data to evaluate whether the clinical case definition affected IVE estimates. METHODS: We estimated VE using a multicentre test-negative case-control design. We measured VE against any influenza and influenza (sub)types, by age group (0-14, 15-64, ≥65 years) and by influenza vaccine target group, using logistic regression. We estimated IVE among patients meeting the European Union (EU) acute respiratory infection (ARI) case definition and among those meeting the EU influenza-like illness (ILI) case definition, including only sites providing information on specific symptoms and recruiting patients using an ARI case definition (as the EU ILI case definition is a subset of the EU ARI one). RESULTS: We included 24 319 patients meeting the EU ARI case definition, of whom 21 804 patients (90 %) meet the EU ILI case definition, for the overall pooled VE analysis against any influenza. The overall and influenza (sub)type-specific VE varied by ≤2 % between EU ILI and EU ARI populations. DISCUSSION: Among all analyses, we found similar VE estimates between the EU ILI and EU ARI populations, with few (10%) additional non-ILI ARI patients recruited. These results indicate that VE in the 2022-23 influenza season was not affected by use of a different clinical case definition for recruitment, although we recommend investigating whether this holds true for next seasons.

Interim 2023/24 influenza A vaccine effectiveness: VEBIS European primary care and hospital multicentre studies, September 2023 to January 2024.

Influenza A viruses circulated in Europe from September 2023 to January 2024, with influenza A(H1N1)pdm09 predominance. We provide interim 2023/24 influenza vaccine effectiveness (IVE) estimates from two European studies, covering 10 countries across primary care (EU-PC) and hospital (EU-H) settings. Interim IVE was higher against A(H1N1)pdm09 than A(H3N2): EU-PC influenza A(H1N1)pdm09 IVE was 53% (95% CI: 41 to 63) and 30% (95% CI: -3 to 54) against influenza A(H3N2). For EU-H, these were 44% (95% CI: 30 to 55) and 14% (95% CI: -32 to 43), respectively.

Influenza vaccine effectiveness in Europe: Results from the 2022-2023 VEBIS (Vaccine Effectiveness, Burden and Impact Studies) primary care multicentre study.

Background: Influenza A(H3N2) viruses dominated early in the 2022-2023 influenza season in Europe, followed by higher circulation of influenza A(H1N1)pdm09 and B viruses. The VEBIS primary care network estimated the influenza vaccine effectiveness (VE) using a multicentre test-negative study. Materials and Methods: Primary care practitioners collected information and specimens from patients consulting with acute respiratory infection. We measured VE against any influenza, influenza (sub)type and clade, by age group, by influenza vaccine target group and by time since vaccination, using logistic regression. Results: We included 38 058 patients, of which 3786 were influenza A(H3N2), 1548 influenza A(H1N1)pdm09 and 3275 influenza B cases. Against influenza A(H3N2), VE was 36% (95% CI: 25-45) among all ages and ranged between 30% and 52% by age group and target group. VE against influenza A(H3N2) clade 2b was 38% (95% CI: 25-49). Overall, VE against influenza A(H1N1)pdm09 was 46% (95% CI: 35-56) and ranged between 29% and 59% by age group and target group. VE against influenza A(H1N1)pdm09 clade 5a.2a was 56% (95% CI: 46-65) and 79% (95% CI: 64-88) against clade 5a.2a.1. VE against influenza B was 76% (95% CI: 70-81); overall, 84%, 72% and 71% were among 0-14-year-olds, 15-64-year-olds and those in the influenza vaccination target group, respectively. VE against influenza B with a position 197 mutation of the hemagglutinin (HA) gene was 79% (95% CI: 73-85) and 90% (95% CI: 85-94) without this mutation. Conclusion: The 2022-2023 end-of-season results from the VEBIS network at primary care level showed high VE among children and against influenza B, with lower VE against influenza A(H1N1)pdm09 and A(H3N2).

Influenza vaccine effectiveness against influenza A subtypes in Europe: Results from the 2021-2022 I-MOVE primary care multicentre study.

BACKGROUND: In 2021-2022, influenza A viruses dominated in Europe. The I-MOVE primary care network conducted a multicentre test-negative study to measure influenza vaccine effectiveness (VE). METHODS: Primary care practitioners collected information on patients presenting with acute respiratory infection. Cases were influenza A(H3N2) or A(H1N1)pdm09 RT-PCR positive, and controls were influenza virus negative. We calculated VE using logistic regression, adjusting for study site, age, sex, onset date, and presence of chronic conditions. RESULTS: Between week 40 2021 and week 20 2022, we included over 11 000 patients of whom 253 and 1595 were positive for influenza A(H1N1)pdm09 and A(H3N2), respectively. Overall VE against influenza A(H1N1)pdm09 was 75% (95% CI: 43-89) and 81% (95% CI: 45-93) among those aged 15-64 years. Overall VE against influenza A(H3N2) was 29% (95% CI: 12-42) and 25% (95% CI: -41 to 61), 33% (95% CI: 14-49), and 26% (95% CI: -22 to 55) among those aged 0-14, 15-64, and over 65 years, respectively. The A(H3N2) VE among the influenza vaccination target group was 20% (95% CI: -6 to 39). All 53 sequenced A(H1N1)pdm09 viruses belonged to clade 6B.1A.5a.1. Among 410 sequenced influenza A(H3N2) viruses, all but eight belonged to clade 3C.2a1b.2a.2. DISCUSSION: Despite antigenic mismatch between vaccine and circulating strains for influenza A(H3N2) and A(H1N1)pdm09, 2021-2022 VE estimates against circulating influenza A(H1N1)pdm09 were the highest within the I-MOVE network since the 2009 influenza pandemic. VE against A(H3N2) was lower than A(H1N1)pdm09, but at least one in five individuals vaccinated against influenza were protected against presentation to primary care with laboratory-confirmed influenza.

Influenza vaccination of school teachers: A scoping review and an impact estimation.

INTRODUCTION: Influenza vaccination, besides protecting traditional risk groups, can protect employees and reduce illness-related absence, which is especially relevant in sectors with staff shortages. This study describes current knowledge of influenza vaccination in teachers and estimates its potential impact. METHODS: We conducted a scoping review of the considerations for and impact of influenza vaccination of schoolteachers (grey and scientific literature up to 2020 March, complemented with interviews). We then estimated the potential impact of teacher vaccination in the Netherlands, with different scenarios of vaccine uptake for 3 influenza seasons (2016-2019). Using published data on multiple input parameters, we calculated potentially averted absenteeism notifications, averted absenteeism duration and averted doctor visits for influenza. RESULTS: Only one scientific paper reported on impact; it showed lower absenteeism in vaccinated teachers, whereas more knowledge of vaccination impact was deemed crucial by 50% of interviewed experts. The impact for the Netherlands of a hypothetical 50% vaccine uptake was subsequently estimated: 74-293 potentially averted physician visits and 11,178-28,896 potentially averted days of influenza absenteeism (on ≈200,000 total teacher population). An estimated 12-32 vaccinations were required to prevent one teacher sick-leave notification, or 3.5-9.1 vaccinations to prevent one day of teacher absenteeism (2016-2019). CONCLUSION: Scientific publications on influenza vaccination in teachers are few, while public interest has increased to reduce teacher shortages. However, school boards and public health experts indicate requiring knowledge of impact when considering this vaccination. Estimations of 3.5-9.1 vaccinated teachers preventing one day of influenza-related sick leave suggest a possible substantial vaccination impact on absenteeism. Financial incentives, more accessible on-site vaccinations at workplaces, or both, are expected to increase uptake, but more research is needed on teachers' views and vaccine uptake potential and its cost-effectiveness. Piloting free on-site influenza vaccination in several schools could provide further information on teacher participation.

Rapidly adapting primary care sentinel surveillance across seven countries in Europe for COVID-19 in the first half of 2020: strengths, challenges, and lessons learned.

As the COVID-19 pandemic began in early 2020, primary care influenza sentinel surveillance networks within the Influenza - Monitoring Vaccine Effectiveness in Europe (I-MOVE) consortium rapidly adapted to COVID-19 surveillance. This study maps system adaptations and lessons learned about aligning influenza and COVID-19 surveillance following ECDC / WHO/Europe recommendations and preparing for other diseases possibly emerging in the future. Using a qualitative approach, we describe the adaptations of seven sentinel sites in five European Union countries and the United Kingdom during the first pandemic phase (March-September 2020). Adaptations to sentinel systems were substantial (2/7 sites), moderate (2/7) or minor (3/7 sites). Most adaptations encompassed patient referral and sample collection pathways, laboratory testing and data collection. Strengths included established networks of primary care providers, highly qualified testing laboratories and stakeholder commitments. One challenge was the decreasing number of samples due to altered patient pathways. Lessons learned included flexibility establishing new routines and new laboratory testing. To enable simultaneous sentinel surveillance of influenza and COVID-19, experiences of the sentinel sites and testing infrastructure should be considered. The contradicting aims of rapid case finding and contact tracing, which are needed for control during a pandemic and regular surveillance, should be carefully balanced.

Dairy Sheep Played a Minor Role in the 2005-2010 Human Q Fever Outbreak in The Netherlands Compared to Dairy Goats.

Q fever is an almost ubiquitous zoonosis caused by Coxiella burnetii. This organism infects several animal species, as well as humans, and domestic ruminants like cattle, sheep and goats are an important animal reservoir of C. burnetii. In 2007, a sudden rise in notified human Q fever cases occurred in The Netherlands, and by the end of 2009, more than 3500 human Q fever patients had been notified. Dairy sheep and dairy goats were suspected to play a causal role in this human Q fever outbreak, and several measures were taken, aiming at a reduction of C. burnetii shedding by infected small ruminants, in order to reduce environmental contamination and thus human exposure. One of the first measures was compulsory notification of more than five percent abortion within thirty days for dairy sheep and dairy goat farms, starting 12 June 2008. After notification, an official farm inspection took place, and laboratory investigations were performed aiming at ruling out or demonstrating a causal role of C. burnetii. These measures were effective, and the number of human Q fever cases decreased; levels are currently the same as they were prior to 2007. The effect of these measures was monitored using a bulk tank milk (BTM) PCR and an antibody ELISA. The percentage PCR positive dairy herds and flocks decreased over time, and dairy sheep flocks tested PCR positive significantly less often and became PCR negative earlier compared to dairy goat herds. Although there was no difference in the percentage of dairy goat and dairy sheep farms with a C. burnetii abortion outbreak, the total number of shedding dairy sheep was much lower than the number of shedding dairy goats. Combined with the fact that Q fever patients lived mainly in the proximity of infected dairy goat farms and that no Q fever patients could be linked directly to dairy sheep farms, although this may have happened in individual cases, we conclude that dairy sheep did not play a major role in the Dutch Q fever outbreak. BTM monitoring using both a PCR and an ELISA is essential to determine a potential C. burnetii risk, not only for The Netherlands but for other countries with small ruminant dairy industries.

Absence of association between 2019-20 influenza vaccination and COVID-19: Results of the European I-MOVE-COVID-19 primary care project, March-August 2020.

BACKGROUND: Claims of influenza vaccination increasing COVID-19 risk are circulating. Within the I-MOVE-COVID-19 primary care multicentre study, we measured the association between 2019-20 influenza vaccination and COVID-19. METHODS: We conducted a multicentre test-negative case-control study at primary care level, in study sites in five European countries, from March to August 2020. Patients presenting with acute respiratory infection were swabbed, with demographic, 2019-20 influenza vaccination and clinical information documented. Using logistic regression, we measured the adjusted odds ratio (aOR), adjusting for study site and age, sex, calendar time, presence of chronic conditions. The main analysis included patients swabbed ≤7 days after onset from the three countries with <15% of missing influenza vaccination. In secondary analyses, we included five countries, using multiple imputation with chained equations to account for missing data. RESULTS: We included 257 COVID-19 cases and 1631 controls in the main analysis (three countries). The overall aOR between influenza vaccination and COVID-19 was 0.93 (95% CI: 0.66-1.32). The aOR was 0.92 (95% CI: 0.58-1.46) and 0.92 (95% CI: 0.51-1.67) among those aged 20-59 and ≥60 years, respectively. In secondary analyses, we included 6457 cases and 69 272 controls. The imputed aOR was 0.87 (95% CI: 0.79-0.95) among all ages and any delay between swab and symptom onset. CONCLUSIONS: There was no evidence that COVID-19 cases were more likely to be vaccinated against influenza than controls. Influenza vaccination should be encouraged among target groups for vaccination. I-MOVE-COVID-19 will continue documenting influenza vaccination status in 2020-21, in order to learn about effects of recent influenza vaccination.

Animal sources for zoonotic transmission of psittacosis: a systematic review.

BACKGROUND: Human psittacosis, caused by Chlamydia (C.) psittaci, is likely underdiagnosed and underreported, since tests for C. psittaci are often not included in routine microbiological diagnostics. Source tracing traditionally focuses on psittacine pet birds, but recently other animal species have been gaining more attention as possible sources for human psittacosis. This review aims to provide an overview of all suspected animal sources of human psittacosis cases reported in the international literature. In addition, for each animal species the strength of evidence for zoonotic transmission was estimated. METHODS: A systematic literature search was conducted using four databases (Pubmed, Embase, Scopus and Proquest). Articles were included when there was mention of at least one human case of psittacosis and a possible animal source. Investigators independently extracted data from the included articles and estimated strength of evidence for zoonotic transmission, based on a self-developed scoring system taking into account number of human cases, epidemiological evidence and laboratory test results in human, animals, and the environment. RESULTS: Eighty articles were included, which provided information on 136 different situations of possible zoonotic transmission. The maximum score for zoonotic transmission was highest for turkeys, followed by ducks, owls, and the category 'other poultry'. Articles reporting about zoonotic transmission from unspecified birds, psittaciformes and columbiformes provided a relatively low strength of evidence. A genotypical match between human and animal samples was reported twenty-eight times, including transmission from chickens, turkeys, guinea fowl, peafowl, pigeons, ducks, geese, songbirds, parrot-like birds and owls. CONCLUSIONS: Strong evidence exists for zoonotic transmission from turkeys, chickens and ducks, in addition to the more traditionally reported parrot-like animal sources. Based on our scoring system, the evidence was generally stronger for poultry than for parrot-like birds. Psittaciformes should not be disregarded as an important source of human psittacosis, still clinicians and public health officials should include poultry and birds species other than parrots in medical history and source tracing.

Cost-effectiveness of Screening Program for Chronic Q Fever, the Netherlands.

In the aftermath of a large Q fever (QF) epidemic in the Netherlands during 2007-2010, new chronic QF (CQF) patients continue to be detected. We developed a health-economic decision model to evaluate the cost-effectiveness of a 1-time screening program for CQF 7 years after the epidemic. The model was parameterized with spatial data on QF notifications for the Netherlands, prevalence data from targeted screening studies, and clinical data from the national QF database. The cost-effectiveness of screening varied substantially among subpopulations and geographic areas. Screening that focused on cardiovascular risk patients in areas with high QF incidence during the epidemic ranged from cost-saving to €31,373 per quality-adjusted life year gained, depending on the method to estimate the prevalence of CQF. The cost per quality-adjusted life year of mass screening of all older adults was €70,000 in the most optimistic scenario.

Impact of influenza vaccination programmes among the elderly population on primary care, Portugal, Spain and the Netherlands: 2015/16 to 2017/18 influenza seasons.

BackgroundTo increase the acceptability of influenza vaccine, it is important to quantify the overall benefits of the vaccination programme.AimTo assess the impact of influenza vaccination in Portugal, Spain and the Netherlands, we estimated the number of medically attended influenza-confirmed cases (MAICC) in primary care averted in the seasons 2015/16 to 2017/18 among those ≥ 65 years.MethodsWe used an ecological approach to estimate vaccination impact. We compared the number of observed MAICC (n) to the estimated number that would have occurred without the vaccination programme (N). To estimate N, we used: (i) MAICC estimated from influenza surveillance systems, (ii) vaccine coverage, (iii) pooled (sub)type-specific influenza vaccine effectiveness estimates for seasons 2015/16 to 2017/18, weighted by the proportion of virus circulation in each season and country. We estimated the number of MAICC averted (NAE) and the prevented fraction (PF) by the vaccination programme.ResultsThe annual average of NAE in the population ≥ 65 years was 33, 58 and 204 MAICC per 100,000 in Portugal, Spain and the Netherlands, respectively. On average, influenza vaccination prevented 10.7%, 10.9% and 14.2% of potential influenza MAICC each season in these countries. The lowest PF was in 2016/17 (4.9-6.1%) with an NAE ranging from 24 to 69 per 100,000.ConclusionsOur results suggest that influenza vaccination programmes reduced a substantial number of MAICC. Together with studies on hospitalisations and deaths averted by influenza vaccination programmes, this will contribute to the evaluation of the impact of vaccination strategies and strengthen public health communication.

Effectiveness of influenza vaccine against influenza A in Europe in seasons of different A(H1N1)pdm09 and the same A(H3N2) vaccine components (2016-17 and 2017-18).

INTRODUCTION: Influenza A(H3N2) viruses predominated in Europe in 2016-17. In 2017-18 A(H3N2) and A(H1N1)pdm09 viruses co-circulated. The A(H3N2) vaccine component was the same in both seasons; while the A(H1N1)pdm09 component changed in 2017-18. In both seasons, vaccine seed A(H3N2) viruses developed adaptations/alterations during propagation in eggs, impacting antigenicity. METHODS: We used the test-negative design in a multicentre primary care case-control study in 12 European countries to measure 2016-17 and 2017-18 influenza vaccine effectiveness (VE) against laboratory-confirmed influenza A(H1N1)pdm09 and A(H3N2) overall and by age group. RESULTS: During the 2017-18 season, the overall VE against influenza A(H1N1)pdm09 was 59% (95% CI: 47-69). Among those aged 0-14, 15-64 and ≥65 years, VE against A(H1N1)pdm09 was 64% (95% CI: 37-79), 50% (95% CI: 28-66) and 66% (95% CI: 42-80), respectively. Overall VE against influenza A(H3N2) was 28% (95% CI: 17-38) in 2016-17 and 13% (95% CI: -15 to 34) in 2017-18. Among 0-14-year-olds VE against A(H3N2) was 28% (95%CI: -10 to 53) and 29% (95% CI: -87 to 73), among 15-64-year-olds 34% (95% CI: 18-46) and 33% (95% CI: -3 to 56) and among those aged ≥65 years 15% (95% CI: -10 to 34) and -9% (95% CI: -74 to 32) in 2016-17 and 2017-18, respectively. CONCLUSIONS: Our study suggests the new A(H1N1)pdm09 vaccine component conferred good protection against circulating strains, while VE against A(H3N2) was <35% in 2016-17 and 2017-18. The egg propagation derived antigenic mismatch of the vaccine seed virus with circulating strains may have contributed to this low effectiveness. A(H3N2) seed viruses for vaccines in subsequent seasons may be subject to the same adaptations; in years with lower than expected VE, recommendations of preventive measures other than vaccination should be given in a timely manner.

Estimating severity of influenza epidemics from severe acute respiratory infections (SARI) in intensive care units.

BACKGROUND: While influenza-like-illness (ILI) surveillance is well-organized at primary care level in Europe, few data are available on more severe cases. With retrospective data from intensive care units (ICU) we aim to fill this current knowledge gap. Using multiple parameters proposed by the World Health Organization we estimate the burden of severe acute respiratory infections (SARI) in the ICU and how this varies between influenza epidemics. METHODS: We analyzed weekly ICU admissions in the Netherlands (2007-2016) from the National Intensive Care Evaluation (NICE) quality registry (100% coverage of adult ICUs in 2016; population size 14 million) to calculate SARI incidence, SARI peak levels, ICU SARI mortality, SARI mean Acute Physiology and Chronic Health Evaluation (APACHE) IV score, and the ICU SARI/ILI ratio. These parameters were calculated both yearly and per separate influenza epidemic (defined epidemic weeks). A SARI syndrome was defined as admission diagnosis being any of six pneumonia or pulmonary sepsis codes in the APACHE IV prognostic model. Influenza epidemic periods were retrieved from primary care sentinel influenza surveillance data. RESULTS: Annually, an average of 13% of medical admissions to adult ICUs were for a SARI but varied widely between weeks (minimum 5% to maximum 25% per week). Admissions for bacterial pneumonia (59%) and pulmonary sepsis (25%) contributed most to ICU SARI. Between the eight different influenza epidemics under study, the value of each of the severity parameters varied. Per parameter the minimum and maximum of those eight values were as follows: ICU SARI incidence 558-2400 cumulated admissions nationwide, rate 0.40-1.71/10,000 inhabitants; average APACHE score 71-78; ICU SARI mortality 13-20%; ICU SARI/ILI ratio 8-17 cases per 1000 expected medically attended ILI in primary care); peak-incidence 101-188 ICU SARI admissions in highest-incidence week, rate 0.07-0.13/10,000 population). CONCLUSIONS: In the ICU there is great variation between the yearly influenza epidemic periods in terms of different influenza severity parameters. The parameters also complement each other by reflecting different aspects of severity. Prospective syndromic ICU SARI surveillance, as proposed by the World Health Organization, thereby would provide insight into the severity of ongoing influenza epidemics, which differ from season to season.

Laboratory methods for case finding in human psittacosis outbreaks: a systematic review.

BACKGROUND: Psittacosis outbreak investigations require rapid identification of cases in order to trace possible sources and perform public health risk assessments. In recent outbreaks in the Netherlands, such investigations were hampered by the non-specificity of laboratory testing methods to identify human Chlamydia psittaci infections. METHOD: A systematic search of PubMed and Scopus databases of literature published between 01 January, 1986 and 03 July, 2017 was done to find best practices of laboratory-testing methods used in psittacosis outbreaks of two or more human cases. Reference lists of included articles were hand searched to identify additional articles. RESULTS: Thirty-seven eligible articles were identified, describing 44 human psittacosis outbreaks in 12 countries. Laboratory tests performed were PCR (with various targets), serologic tests (complement binding reactions, ELISA's, immunofluorescence tests and immuno-peroxidase tests) and culture, in various combinations. The literature provided no 'gold standard' laboratory testing strategy to identify recent human C. psittaci infections. In most psittacosis outbreaks, for a considerable number of cases (or tested individuals in an exposed cohort), C. psittaci infection could not be confirmed, nor excluded as causative pathogen. None of the testing strategies was found to be suitable for (nearly) full case finding. CONCLUSION: PCR enables rapid identification of human psittacosis patients and helps source finding by genotyping but has the disadvantage that sensitivity is high only in the acute phase. In outbreak situations, there is often a time delay and therefore, there is a need for new serologic testing methods next to PCR, with good specificity and sensitivity. Moreover, serum is easier to collect than the preferred diagnostic materials for PCR. A serologic test that can reliably confirm infection status without the necessity of convalescent serum sampling would enhance case finding, source tracing, identification of risk factors and assessment of burden of disease in various settings.

2015/16 I-MOVE/I-MOVE+ multicentre case-control study in Europe: Moderate vaccine effectiveness estimates against influenza A(H1N1)pdm09 and low estimates against lineage-mismatched influenza B among children.

BACKGROUND: During the 2015/16 influenza season in Europe, the cocirculating influenza viruses were A(H1N1)pdm09 and B/Victoria, which was antigenically distinct from the B/Yamagata component in the trivalent influenza vaccine. METHODS: We used the test-negative design in a multicentre case-control study in twelve European countries to measure 2015/16 influenza vaccine effectiveness (VE) against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza. General practitioners swabbed a systematic sample of consulting ILI patients and a random sample of influenza-positive swabs was sequenced. We calculated adjusted VE against influenza A(H1N1)pdm09, A(H1N1)pdm09 genetic group 6B.1 and influenza B overall and by age group. RESULTS: We included 11 430 ILI patients, of which 2272 were influenza A(H1N1)pdm09 and 2901 were influenza B cases. Overall VE against influenza A(H1N1)pdm09 was 32.9% (95% CI: 15.5-46.7). Among those aged 0-14, 15-64 and ≥65 years, VE against A(H1N1)pdm09 was 31.9% (95% CI: -32.3 to 65.0), 41.4% (95% CI: 20.5-56.7) and 13.2% (95% CI: -38.0 to 45.3), respectively. Overall VE against influenza A(H1N1)pdm09 genetic group 6B.1 was 32.8% (95% CI: -4.1 to 56.7). Among those aged 0-14, 15-64 and ≥65 years, VE against influenza B was -47.6% (95% CI: -124.9 to 3.1), 27.3% (95% CI: -4.6 to 49.4) and 9.3% (95% CI: -44.1 to 42.9), respectively. CONCLUSIONS: Vaccine effectiveness (VE) against influenza A(H1N1)pdm09 and its genetic group 6B.1 was moderate in children and adults, and low among individuals ≥65 years. Vaccine effectiveness (VE) against influenza B was low and heterogeneous among age groups. More information on effects of previous vaccination and previous infection is needed to understand the VE results against influenza B in the context of a mismatched vaccine.

Temporal and spatial analysis of psittacosis in association with poultry farming in the Netherlands, 2000-2015.

BACKGROUND: Human psittacosis is a highly under diagnosed zoonotic disease, commonly linked to psittacine birds. Psittacosis in birds, also known as avian chlamydiosis, is endemic in poultry, but the risk for people living close to poultry farms is unknown. Therefore, our study aimed to explore the temporal and spatial patterns of human psittacosis infections and identify possible associations with poultry farming in the Netherlands. METHODS: We analysed data on 700 human cases of psittacosis notified between 01-01-2000 and 01-09-2015. First, we studied the temporal behaviour of psittacosis notifications by applying wavelet analysis. Then, to identify possible spatial patterns, we applied spatial cluster analysis. Finally, we investigated the possible spatial association between psittacosis notifications and data on the Dutch poultry sector at municipality level using a multivariable model. RESULTS: We found a large spatial cluster that covered a highly poultry-dense area but additional clusters were found in areas that had a low poultry density. There were marked geographical differences in the awareness of psittacosis and the amount and the type of laboratory diagnostics used for psittacosis, making it difficult to draw conclusions about the correlation between the large cluster and poultry density. The multivariable model showed that the presence of chicken processing plants and slaughter duck farms in a municipality was associated with a higher rate of human psittacosis notifications. The significance of the associations was influenced by the inclusion or exclusion of farm density in the model. CONCLUSIONS: Our temporal and spatial analyses showed weak associations between poultry-related variables and psittacosis notifications. Because of the low number of psittacosis notifications available for analysis, the power of our analysis was relative low. Because of the exploratory nature of this research, the associations found cannot be interpreted as evidence for airborne transmission of psittacosis from poultry to the general population. Further research is needed to determine the prevalence of C. psittaci in Dutch poultry. Also, efforts to promote PCR-based testing for C. psittaci and genotyping for source tracing are important to reduce the diagnostic deficit, and to provide better estimates of the human psittacosis burden, and the possible role of poultry.

Influenza vaccine effectiveness estimates in the Dutch population from 2003 to 2014: The test-negative design case-control study with different control groups.

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.

Influenza Vaccine Effectiveness in the Netherlands from 2003/2004 through 2013/2014: The Importance of Circulating Influenza Virus Types and Subtypes.

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.

Long-Term Correlation between Influenza Vaccination Coverage and Incidence of Influenza-Like Illness in 14 European Countries.

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.

Comparison of different collection methods for reported adverse events following pandemic and seasonal influenza vaccination.

BACKGROUND: During the 2009/2010 season, information on adverse events after administration of seasonal and pandemic influenza vaccines was collected by different active surveys in the Netherlands. In the present paper, we compared data from a paper-based questionnaire with data from a web-based questionnaire with respect to outcomes and target population, in order to guide future influenza vaccine safety monitoring. METHODS: The paper-based survey collected data from patients who attended primary care practices in the province of Utrecht for influenza vaccination. The web-based survey recruited participants from the general population all provinces of the Netherlands. To analyze the association between study approach and the reported local and systemic adverse events, a generalized estimation equation model was applied. We adjusted for age, gender, comorbidity, previous vaccination and socio-economic status score. RESULTS: No significant differences were found between the two studies approaches in reporting local reactions (OR: 0.98, 95% CI 0.88-1.10) and systemic AEs (OR: 1.12, 95% CI 0.99-1.27). There were important differences in the age groups that responded. The elderly were more represented in the paper-based survey where participants were recruited via GPs (79%⩾60years) compared to 37% in the web-based survey where participants were recruited via internet. CONCLUSION: The paper-based survey with recruitment of participants through GPs is more representative for the target group of influenza vaccination compared to the web-based survey with recruitment of participants via internet. A web-based approach with recruitment of participants via internet seems more suitable for situations where information about adverse events on a national level is desirable. We recommend to recruit participants for a web-based survey during mass vaccinations sessions by GPs to comply with the recommendations of the European Centre for Disease Prevention Control.