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.

COVID-19 vaccine effectiveness against symptomatic infection with SARS-CoV-2 BA.1/BA.2 lineages among adults and adolescents in a multicentre primary care study, Europe, December 2021 to June 2022.

BackgroundScarce European data in early 2021 suggested lower vaccine effectiveness (VE) against SARS-CoV-2 Omicron lineages than previous variants.AimWe aimed to estimate primary series (PS) and first booster VE against symptomatic BA.1/BA.2 infection and investigate potential biases.MethodsThis European test-negative multicentre study tested primary care patients with acute respiratory symptoms for SARS-CoV-2 in the BA.1/BA.2-dominant period. We estimated PS and booster VE among adults and adolescents (PS only) for all products combined and for Comirnaty alone, by time since vaccination, age and chronic condition. We investigated potential bias due to correlation between COVID-19 and influenza vaccination and explored effect modification and confounding by prior SARS-CoV-2 infection.ResultsAmong adults, PS VE was 37% (95% CI: 24-47%) overall and 60% (95% CI: 44-72%), 43% (95% CI: 26-55%) and 29% (95% CI: 13-43%) < 90, 90-179 and ≥ 180 days post vaccination, respectively. Booster VE was 42% (95% CI: 32-51%) overall and 56% (95% CI: 47-64%), 22% (95% CI: 2-38%) and 3% (95% CI: -78% to 48%), respectively. Primary series VE was similar among adolescents. Restricting analyses to Comirnaty had little impact. Vaccine effectiveness was higher among older adults. There was no signal of bias due to correlation between COVID-19 and influenza vaccination. Confounding by previous infection was low, but sample size precluded definite assessment of effect modification.ConclusionPrimary series and booster VE against symptomatic infection with BA.1/BA.2 ranged from 37% to 42%, with similar waning post vaccination. Comprehensive data on previous SARS-CoV-2 infection would help disentangle vaccine- and infection-induced immunity.

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).

Interim 2022/23 influenza vaccine effectiveness: six European studies, October 2022 to January 2023.

BackgroundBetween October 2022 and January 2023, influenza A(H1N1)pdm09, A(H3N2) and B/Victoria viruses circulated in Europe with different influenza (sub)types dominating in different areas.AimTo provide interim 2022/23 influenza vaccine effectiveness (VE) estimates from six European studies, covering 16 countries in primary care, emergency care and hospital inpatient settings.MethodsAll studies used the test-negative design, but with differences in other study characteristics, such as data sources, patient selection, case definitions and included age groups. Overall and influenza (sub)type-specific VE was estimated for each study using logistic regression adjusted for potential confounders.ResultsThere were 20,477 influenza cases recruited across the six studies, of which 16,589 (81%) were influenza A. Among all ages and settings, VE against influenza A ranged from 27 to 44%. Against A(H1N1)pdm09 (all ages and settings), VE point estimates ranged from 28% to 46%, higher among children (< 18 years) at 49-77%. Against A(H3N2), overall VE ranged from 2% to 44%, also higher among children (62-70%). Against influenza B/Victoria, overall and age-specific VE were ≥ 50% (87-95% among children < 18 years).ConclusionsInterim results from six European studies during the 2022/23 influenza season indicate a ≥ 27% and ≥ 50% reduction in disease occurrence among all-age influenza vaccine recipients for influenza A and B, respectively, with higher reductions among children. Genetic virus characterisation results and end-of-season VE estimates will contribute to greater understanding of differences in influenza (sub)type-specific results across studies.

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.

High syphilis prevalence and incidence in people living with HIV and Preexposure Prophylaxis users: A retrospective review in the French Dat'AIDS cohort.

BACKGROUND: In the past years, we observed a sharp increase of Syphilis, especially among male who have sex with male (MSM), either HIV-infected, or on pre-exposure prophylaxis (PrEP). Our aim was to assess syphilis prevalence and incidence among people living with HIV (PLWH) and PrEP users. METHODS: PLWH were included from 2010 to 2020 and PrEP users from 2016 to 2020 from the Dat'AIDS French cohort. We calculated syphilis prevalence and incidences for first infections, re-infections, and iterative infections (> 2 times). T-Tests, Wilcoxon tests and Chi2 test were used for descriptive analysis and multivariate logistic regression models were used to estimate Odds ratios (OR) and 95% confidence intervals (95% CI) for factors associated with syphilis. RESULTS: Among the 8 583 PLWH, prevalence of subject with past or present syphilis was 19.9%. These subjects were more likely MSM or transgender and aged over 35 years, but prevalence was lower in AIDS subjects. Same pattern was seen for incident infection and re-infection. Incidence was 3.8 per 100 person-years for infection and 6.5 per 100 person-years for re-infection. Among 1 680 PrEP users, syphilis prevalence was 25.8%, with an estimated 7.2% frequency of active syphilis. Risk of syphilis infection was higher in male and increased with age. Incidence was 11.2 per 100 person-years for infection and 11.1 per 100 person-years for re-infection. CONCLUSION: Syphilis prevalence and incidence were high, especially in older MSM with controlled HIV infection and PrEP users, enhancing the need to improve syphilis screening and behavioral risk reduction counseling among high-risk subjects.

The effect of social deprivation on the dynamic of SARS-CoV-2 infection in France: a population-based analysis.

BACKGROUND: Data on health inequalities related to the dynamic of SARS-CoV-2 infection in France are scarce. The aim of this study was to analyse the association between an area-based deprivation indicator and SARS-CoV-2 incidence, positivity, and testing rates between May 2020 and April 2021. METHODS: We analysed data reported to the Système d'Information de Dépistage Populationnel surveillance system between May 14, 2020 and April 29, 2021, which records the results of all SARS-CoV-2 tests in France. Residential addresses of tested individuals were geocoded to retrieve the associated aggregated units for the statistical information (IRIS) scale, corresponding to an area comprising 2000 inhabitants relatively homogenous in terms of socioeconomic characteristics. A social deprivation score was assigned to each area using the European Deprivation Index (EDI). We fitted negative binomial generalised additive models to model the age-standardised and sex-standardised ratios for SARS-CoV-2 incidence, positivity rates, and testing rates, and to estimate incidence rate ratios (IRRs) and 95% CIs of their association with EDI quintiles, using the first quintile (least deprived) as the reference category, adjusted for week, population density, and region. FINDINGS: Analyses were based on 70 990 478 SARS-CoV-2 tests, of which 5 000 972 were positive. SARS-CoV-2 incidence was higher in the most deprived areas than the least deprived areas (IRR 1·148 [95% CI 1·138-1·158]) and positivity rates were also higher (IRR 1·283 [1·273-1·294]), whereas testing rates were lower in the most deprived areas than the least deprived areas (IRR 0·905 [0·904-0·907]). SARS-CoV-2 incidence and positivity rates remained higher in the most deprived areas than the least deprived areas during the second and third national lockdowns, and variation in testing rate was observed according to population density. INTERPRETATION: Our results highlight a positive social gradient between deprivation and the risk of testing positive for SARS-CoV-2, with the highest risk among individuals living in the most deprived areas and a negative social gradient for testing rate. These findings might reflect structural barriers to health-care access in France and lower capacity of deprived populations to benefit from protective measures. FUNDING: None.

Depressive Symptoms and Cigarette Smoking in Adolescents and Young Adults: Mediating Role of Friends Smoking.

INTRODUCTION: We examined the mediating role of friends smoking in the association between depressive symptoms and daily/weekly cigarette smoking from adolescence into adulthood. METHODS: Data were drawn from the Nicotine Dependence In Teens study (NDIT, Canada) and the Avon Longitudinal Study of Parents and Children (ALSPAC, UK) studies. Three age groups were investigated in NDIT: age 13-14 (n = 1189), 15-16 (n = 1107), and 17-18 (n = 1075), and one in ALSPAC (n = 4482, age 18-21). Multivariable mediation models decomposed the total effect (TE) of depressive symptoms on smoking into a natural direct effect (NDE) and natural indirect effect (NIE) through friends smoking. RESULTS: The odds ratios (ORs) for the TE were relatively constant over time with estimates ranging from 1.12 to 1.35. Friends smoking mediated the association between depressive symptoms and smoking in the two youngest samples (OR [95% confidence interval [CI] 1.09 [1.01,1.17] in 13- to 14-year-olds; 1.10 [1.03,1.18] in 15- to 16-year-olds). In the two older samples, NDE of depressive symptoms was close to the TE, suggestive that mediation was absent or too small to detect. CONCLUSION: Friends smoking mediates the association between depressive symptoms and daily/weekly cigarette smoking in young adolescents. IMPLICATIONS: If young adolescents use cigarettes to self-medicate depressive symptoms, then interventions targeting smoking that ignore depressive symptoms may be ineffective. Our results also underscore the importance of the influence of friends in younger adolescents, suggestive that preventive intervention should target the social environment, including social relationships.

Patterning of educational attainment across inflammatory markers: Findings from a multi-cohort study.

BACKGROUND: Evidence suggests that the inflammatory reaction, an adaptive response triggered by a variety of harmful stimuli and conditions involved in the risk and development of many chronic diseases, is a potential pathway through which the socioeconomic environment is biologically embedded. Difficulty in interpreting the role of the inflammatory system in the embodiment dynamic arises because of heterogeneity across studies that use a limited but varied number of inflammatory markers. There is no consensus in the literature as to which inflammatory markers beyond the C-reactive protein and to a lesser extent interleukin 6 are related to the social environment. Accordingly, we aimed to investigate the association between educational attainment, and several markers of inflammation - C-reactive protein, fibrinogen, interleukin 6, interleukin 1ß and tumor necrosis factor α- in 6 European cohort studies. METHODS: Up to 17,470 participants from six European cohort studies with data on educational attainment, health behaviors and lifestyle factors, and at least two different inflammatory markers. Four sub-datasets were drawn with varying numbers of participants to allow pairwise comparison of the social patterning of C-reactive protein and any other inflammatory markers. To evaluate within each sub-dataset the importance of the context and cohort specificities, linear regression-based analyses were performed separately for each cohort and combined in a random effect meta-analysis to determine the relationship between educational attainment and inflammation. RESULTS: We found that the magnitude of the relationship between educational attainment and five inflammatory biomarkers (C-reactive protein, fibrinogen, interleukin 6 and 1ß and tumor necrosis factor α) was variable. By far the most socially patterned biomarker was C-reactive protein, followed by fibrinogen and to lesser extent interleukin 6, where a low educational attainment was associated with higher inflammation even after adjusting for health behaviours and body mass index. No association was found with interleukin 1ß and tumor necrosis factor α. CONCLUSIONS: Our study suggests different educational patterning of inflammatory biomarkers. Further large-scale research is needed to explore social differences in the inflammatory cascade in greater detail and the extent to which these differences contribute to social inequalities in health.

Incidence of diabetes in HIV-infected patients treated with first-line integrase strand transfer inhibitors: a French multicentre retrospective study.

BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are increasingly used in patients living with HIV due to their safety, effectiveness and high genetic barrier. However, an association with weight gain has recently been suggested and several cases of diabetes mellitus have been reported with raltegravir and dolutegravir. The long-time metabolic impact of these recent molecules remains unclear. OBJECTIVES: To assess if an INSTI as a third agent is statistically associated with new-onset diabetes mellitus compared with an NNRTI or a PI. PATIENTS AND METHODS: Patients undergoing first-line combined ART (cART) without diabetes at baseline were retrospectively included from the Dat'AIDS French cohort study (ClinicalTrials.gov NCT02898987). Incident diabetes mellitus was defined as a notification of new diabetes in the medical history, a glycated haemoglobin (HbA1c) level superior to 7.5% or the start of a diabetes therapy following the initiation of ART. RESULTS: From 2009 to 2017, 19 462 patients were included, among which 265 cases of diabetes mellitus occurred. Multivariate and survival analyses did not highlight an increase in new-onset diabetes in patients undergoing cART with an INSTI as a third agent compared with an NNRTI or a PI. BMI >30 kg/m2, age >37 years old (in survival analysis), black race or Hispanic ethnicity, arterial hypertension and AIDS were associated with a higher proportion of incident diabetes. CONCLUSIONS: INSTIs were not statistically associated with new-onset diabetes. However, clinicians should remain aware of this possible metabolic comorbidity, particularly in patients with a high BMI and older patients.