Vaccine effectiveness against medically attended, laboratory-confirmed influenza in the I-MOVE primary care network in Europe, VEBIS project, 2024/25

BackgroundInfluenza 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 MethodsPrimary 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.ResultsWe 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 mutationConclusionThe 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).

BackgroundThe 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.MethodsWe 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.ResultsDepending 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.ConclusionUp 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.

The 2024/25 influenza season in Hungary experienced a major surge in cases, the largest since the COVID-19 pandemic. We evaluated influenza vaccine effectiveness (VE) in primary care settings among adults and vaccination target groups, and also according to time since vaccination, prior seasonal vaccination, and influenza type. A test-negative case-control study was conducted in Hungary. Data and specimens were collected from primary care patients with an acute respiratory infection (ARI). Patients with positive PCR test results for influenza were classified as cases, while those with negative test results for influenza were classified as controls. Adjusted VEs were calculated using logistic regression as (1 - odds ratio of vaccination) × 100. Between November 2024 and May 2025, 2074 patients were included in the analysis, of whom 395 cases had influenza. Of the 129 vaccinated patients, 123 (95%) received trivalent inactivated adjuvanted whole-cell vaccine (TIAV), and 6 (5%) received quadrivalent split-virion vaccine. The VE against any influenza was 53% (95% CI: 13-74) in the 18+ age group and 52% (95% CI: 7-75) in the target group for vaccination. The VE against any influenza was 63% (95% CI: 17-84) 14-89 days after vaccination, and 27% (95% CI: -67-68) 90 days or more after vaccination. The VE against any influenza was 56% (95% CI: 1-80) with both current and prior seasonal vaccination, and 5% (95% CI: -64-45) with only prior seasonal vaccination. The VE against influenza A was 39% (95% CI: -16-68), and against influenza B was 80% (95% CI: 2-96). We observed moderate vaccine effectiveness against any influenza, with higher protection within three months after vaccination. Our research findings provide evidence to inform the development of vaccines and the scheduling of vaccination campaigns, with the aim of maximizing the level of protection provided by vaccines throughout the entire influenza season.

Antimicrobial resistance is one of the most significant causes of morbidity and mortality worldwide, including in the paediatric population. Its primary cause is the excessive and inappropriate use of antibacterial agents. In children, the most common reason for prescribing antibacterial therapy is upper and lower respiratory tract infections, which are most often self-limiting viral illnesses. However, up to 80% of these infections are treated with antibacterial therapy, although antibiotic treatment is generally not beneficial. The factors underlying extensive antibiotic prescribing are complex and multifactorial. The most significant problems are related to difficulties in differentiating viral and bacterial etiology based solely on clinical signs, as well as concerns about missing severe bacterial infections. The situation is worsened by physician workload, restricted consultation times, and parental or patient pressure to obtain antibacterial therapy. To reduce the prescription of antibacterial therapy, it is necessary to improve the diagnosis of acute illnesses and enhance physicians’ knowledge about prudent antibiotic use. The aim of the study was to investigate antibiotic prescribing habits and the use of diagnostic tests in children with acute infections in primary care in Latvia, and to evaluate the effect of multifactorial interventions (general practitioner education training and access to the use of C-reactive protein point-of-care testing (CRP POCT), as well as the long-term impact of the educational intervention on prescribing practices. Until now, there has been limited research on antibacterial prescribing and diagnostic practices in the paediatric population in Latvia, and no intervention studies focusing on education and diagnostic strategies to decrease antibiotic use in primary care for children have been carried out. A randomized controlled intervention study was carried out, during which 80 general practitioners from different regions of Latvia recorded data on paediatric patients with acute illnesses who attended in-person consultations. The study consisted of two phases, during which general practitioners were randomly divided into two groups. In the first phase, one group received a combined intervention—participation in an educational seminar and the introduction of CRP POCT into practice—while the other group continued routine practice without interventions and served as the control group. After three months, the groups were switched: the control group then received an equivalent combined intervention, while the other group continued routine practice without access to CRP POCT. Since the latter group had previously received the educational intervention, the long-term effect of education was assessed. A total of 3317 patients with a median age of 4.0 years were included in the study. The majority of patients (95.6%) presented with acute respiratory tract infections, most frequently acute upper respiratory tract infections. Antibacterial therapy was prescribed to 29.3% of patients, and in approximately one-third of cases broad-spectrum antibacterial agents were chosen. Therapy was often initiated within the first days of illness or for potentially self-limiting infections. The lowest frequency of antibacterial prescribing was observed in the long-term education group. In both intervention groups, there was a tendency to use delayed prescriptions more frequently compared to the control group. However, overall, the effect of combined and educational interventions on the frequency of antibacterial prescribing was not statistically significant. Decisions regarding the prescription of antibacterial therapy were predominantly based on clinical signs rather than objective test results when such tests were unavailable during the consultation. The availability of CRP POCT substantially increased the use of diagnostic testing in children with acute infections. In both intervention groups, the number of patients prescribed antibacterial therapy at low CRP values (<20 mg/L), which are rarely associated with severe bacterial infections, decreased. Although overall rates of antibacterial prescribing were relatively low, further improvements are necessary. The integration of POCT with clinical assessment has the potential to improve the diagnostic process and reduce inappropriate use of antibacterial therapy; however, the availability of CRP POCT alone is insufficient. Further research is required to develop standardized criteria for test interpretation and indications. While general practitioner education is essential in promoting prudent antibiotic use, a single passive educational session is insufficient and may need to be supplemented with interactive seminars, individualized practice improvement recommendations, or patient education to enhance its effectiveness. The Doctoral Thesis was developed at Rīga Stradiņš University, Latvia. Defence of the Doctoral Thesis will take place at the public session of the Promotion Council of Clinical Medicine on 26 February 2026 at 15.00 in the 2nd Auditorium, 16 Dzirciema Street, Rīga Stradiņš University. 3.2. Clinical Medicine; Sub-Sector – Paediatrics. Keywords: Acute infection; antibacterial treatment; children; primary care; physician education; CRO POCT.

BackgroundIn the third season of I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe), we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in eight European Union (EU) member states to estimate 2010/11 influenza vaccine effectiveness (VE) against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza.MethodsUsing systematic sampling, practitioners swabbed ILI/ARI patients within seven days of symptom onset. We compared influenza-positive to influenza laboratory-negative patients among those meeting the EU ILI case definition. A valid vaccination corresponded to > 14 days between receiving a dose of vaccine and symptom onset. We used multiple imputation with chained equations to estimate missing values. Using logistic regression with study as fixed effect we calculated influenza VE adjusting for potential confounders. We estimated influenza VE overall, by influenza type, age group and among the target group for vaccination.ResultsWe included 2019 cases and 2391 controls in the analysis. Adjusted VE was 52% (95% CI 30-67) overall (N = 4410), 55% (95% CI 29-72) against A(H1N1) and 50% (95% CI 14-71) against influenza B. Adjusted VE against all influenza subtypes was 66% (95% CI 15-86), 41% (95% CI -3-66) and 60% (95% CI 17-81) among those aged 0-14, 15-59 and ≥60 respectively. Among target groups for vaccination (N = 1004), VE was 56% (95% CI 34-71) overall, 59% (95% CI 32-75) against A(H1N1) and 63% (95% CI 31-81) against influenza B.ConclusionsResults suggest moderate protection from 2010-11 trivalent influenza vaccines against medically-attended ILI laboratory-confirmed as influenza across Europe. Adjusted and stratified influenza VE estimates are possible with the large sample size of this multi-centre case-control. I-MOVE shows how a network can provide precise summary VE measures across Europe.

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

The Development and Validation of a Multidimensional Sum-Scaling Questionnaire to Measure Patient-Reported Outcomes in Acute Respiratory Tract Infections in Primary Care: The Acute Respiratory Tract Infection Questionnaire

Acute Infections in Primary Care: Accuracy of Electronic Diagnoses and Electronic Antibiotic Prescribing

In previous trials, point-of-care testing of C-reactive protein (CRP) concentrations safely reduced antibiotic use in non-severe acute respiratory infections in primary care. However, these trials were done in a research-oriented context with close support from research staff, which could have influenced prescribing practices. To better inform the potential for scaling up point-of-care testing of CRP in respiratory infections, we aimed to do a pragmatic trial of the intervention in a routine care setting. We did a pragmatic, cluster-randomised controlled trial at 48 commune health centres in Viet Nam between June 1, 2020, and May 12, 2021. Eligible centres served populations of more than 3000 people, handled 10-40 respiratory infections per week, had licensed prescribers on site, and maintained electronic patient databases. Centres were randomly allocated (1:1) to provide point-of-care CRP testing plus routine care or routine care only. Randomisation was stratified by district and by baseline prescription level (ie, the proportion of patients with suspected acute respiratory infections to whom antibiotics were prescribed in 2019). Eligible patients were aged 1-65 years and visiting the commune health centre for a suspected acute respiratory infection with at least one focal sign or symptom and symptoms lasting less than 7 days. The primary endpoint was the proportion of patients prescribed an antibiotic at first attendance in the intention-to-treat population. The per-protocol analysis included only people who underwent CRP testing. Secondary safety outcomes included time to resolution of symptoms and frequency of hospitalisation. This trial is registered with ClinicalTrials.gov, NCT03855215. 48 commune health centres were enrolled and randomly assigned, 24 to the intervention group (n=18 621 patients) and 24 to the control group (n=21 235). 17 345 (93·1%) patients in the intervention group were prescribed antibiotics, compared with 20 860 (98·2%) in the control group (adjusted relative risk 0·83 [95% CI 0·66-0·93]). Only 2606 (14%) of 18 621 patients in the intervention group underwent CRP testing and were included in the per-protocol analysis. When analyses were restricted to this population, larger reductions in prescribing were noted in the intervention group compared with the control group (adjusted relative risk 0·64 [95% CI 0·60-0·70]). Time to resolution of symptoms (hazard ratio 0·70 [95% CI 0·39-1·27]) and frequency of hospitalisation (nine in the intervention group vs 17 in the control group; adjusted relative risk 0·52 [95% CI 0·23-1·17]) did not differ between groups. Use of point-of-care CRP testing efficaciously reduced prescription of antibiotics in patients with non-severe acute respiratory infections in primary health care in Viet Nam without compromising patient recovery. The low uptake of CRP testing suggests that barriers to implementation and compliance need to be addressed before scale-up of the intervention. Australian Government, UK Government, and the Foundation for Innovative New Diagnostics.

The 2016-2017 influenza season in Israel was dominated by the circulation of influenza A(H3N2). Influenza vaccine is recommended for the entire population in Israel aged >6 months. The inactivated influenza vaccine was chosen for use this season. We estimated the 2016-2017 end-of-season influenza vaccine effectiveness (VE) in preventing influenza-like illness due to influenza A(H3N2), using the test-negative design. Age-specific VE was estimated using a moving age window and weekly analysis. During the 2016-2017 season, 1267 samples were collected; 467 (36.9%) were positive for influenza, with 97.9% A(H3N2), 0.2% A(H1N1)pdm09, and 1.9% B. A total of 1088 individuals were found eligible to be included in VE assessment. All vaccinated individuals included in the VE assessment received the inactivated influenza vaccine. Adjusted VE against influenza A(H3N2) was 29.0% (95% confidence interval [CI], 0.3%-49.5%). Age group-specific adjusted VE was 69.2% (95% CI, 19.4%-88.3%) for children aged 5-17 years and 58.8% (95% CI, .8%-82.9%) for adults aged 45-64 years. Other age groups demonstrated lower VE estimates that were not statistically significant. Adjusted VE estimates using a moving window of 15 years and weekly VE analyses provided a more defined understanding of age-specific VE during the 2016-2017 season. Estimating VE using a moving age window as well as weekly VE analysis may provide more detailed information regarding the relationship between VE and age.

BackgroundIn 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).MethodsPrimary 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.ResultsBetween 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.DiscussionDespite 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.

BackgroundWith the emergence of SARS‐CoV‐2, influenza surveillance systems in Spain were transformed into a new syndromic sentinel surveillance system. The Acute Respiratory Infection Surveillance System (SiVIRA in Spanish) is based on a sentinel network for acute respiratory infection (ARI) surveillance in primary care and a network of sentinel hospitals for severe ARI (SARI) surveillance in hospitals.MethodsUsing a test‐negative design and data from SARI admissions notified to SiVIRA between January 1 and October 3, 2021, we estimated COVID‐19 vaccine effectiveness (VE) against hospitalization, by age group, vaccine type, time since vaccination, and SARS‐CoV‐2 variant.ResultsVE was 89% (95% CI: 83–93) against COVID‐19 hospitalization overall in persons aged 20 years and older. VE was higher for mRNA vaccines, and lower for those aged 80 years and older, with a decrease in protection beyond 3 months of completing vaccination, and a further decrease after 5 months. We found no differences between periods with circulation of Alpha or Delta SARS‐CoV‐2 variants, although variant‐specific VE was slightly higher against Alpha.ConclusionsThe SiVIRA sentinel hospital surveillance network in Spain was able to describe clinical and epidemiological characteristics of SARI hospitalizations and provide estimates of COVID‐19 VE in the population under surveillance. Our estimates add to evidence of high effectiveness of mRNA vaccines against severe COVID‐19 and waning of protection with time since vaccination in those aged 80 or older. No substantial differences were observed between SARS‐CoV‐2 variants (Alpha vs. Delta).

Within the Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) project we conducted a multicentre case–control study in eight European Union (EU) Member States to estimate the 2011/12 influenza vaccine effectiveness against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza A(H3) among the vaccination target groups. Practitioners systematically selected ILI / acute respiratory infection patients to swab within seven days of symptom onset. We restricted the study population to those meeting the EU ILI case definition and compared influenza A(H3) positive to influenza laboratory-negative patients. We used logistic regression with study site as fixed effect and calculated adjusted influenza vaccine effectiveness (IVE), controlling for potential confounders (age group, sex, month of symptom onset, chronic diseases and related hospitalisations, number of practitioner visits in the previous year). Adjusted IVE was 25% (95% confidence intervals (CI): -6 to 47) among all ages (n=1,014), 63% (95% CI: 26 to 82) in adults aged between 15 and 59 years and 15% (95% CI: -33 to 46) among those aged 60 years and above. Adjusted IVE was 38% (95%CI: -8 to 65) in the early influenza season (up to week 6 of 2012) and -1% (95% CI: -60 to 37) in the late phase. The results suggested a low adjusted IVE in 2011/12. The lower IVE in the late season could be due to virus changes through the season or waning immunity. Virological surveillance should be enhanced to quantify change over time and understand its relation with duration of immunological protection. Seasonal influenza vaccines should be improved to achieve acceptable levels of protection.

Inhaled antibiotics for acute lower respiratory tract infections in primary care: a hypothesis

The early experience of the United Kingdom (UK) is that influenza B has dominated the influenza 2012/13 season. Overall trivalent influenza vaccine (TIV) adjusted vaccine effectiveness (VE) against all laboratory-confirmed influenza in primary care was 51% (95% confidence interval (CI): 27% to 68%); TIV adjusted VE against influenza A alone or influenza B alone was 49% (95% CI: -2% to 75%) and 52% (95% CI: 23% to 70%) respectively. Vaccination remains the best protection against influenza.