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).

Inference of age-dependent case-fatality ratios for seasonal influenza virus subtypes A(H3N2) and A(H1N1)pdm09 and B lineages using data from the Netherlands.

Background: Despite the known relatively high disease burden of influenza, data are lacking regarding a critical epidemiological indicator, the case-fatality ratio. Our objective was to infer age-group and influenza (sub)type specific values by combining modelled estimates of symptomatic incidence and influenza-attributable mortality. Methods: The setting was the Netherlands, 2011/2012 through 2019/2020 seasons. Sentinel surveillance data from general practitioners and laboratory testing were synthesised to supply age-group specific estimates of incidence of symptomatic infection, and ecological additive modelling was used to estimate influenza-attributable deaths. These were combined in an Bayesian inferential framework to estimate case-fatality ratios for influenza A(H3N2), A(H1N1)pdm09 and influenza B, per 5-year age-group. Results: Case-fatality estimates were highest for influenza A(H3N2) followed by influenza B and then A(H1N1)pdm09 and were highest for the 85+ years age-group, at 4.76% (95% credible interval [CrI]: 4.52-5.01%) for A(H3N2), followed by influenza B at 4.08% (95% CrI: 3.77-4.39%) and A(H1N1)pdm09 at 2.51% (95% CrI: 2.09-2.94%). For 55-59 through 85+ years, the case-fatality risk was estimated to double with every 3.7 years of age. Conclusions: These estimated case-fatality ratios, per influenza sub(type) and per age-group, constitute valuable information for public health decision-making, for assessing the retrospective and prospective value of preventative interventions such as vaccination and for health economic evaluations.

Increase in invasive group A streptococcal (Streptococcus pyogenes) infections (iGAS) in young children in the Netherlands, 2022.

In 2022, a sevenfold increase in the number of notifiable invasive Streptococcus pyogenes (iGAS) infections among children aged 0-5 years was observed in the Netherlands compared with pre-COVID-19 pandemic years. Of 42 cases in this age group, seven had preceding or coinciding varicella zoster infections, nine were fatal. This increase is not attributable to a specific emm type. Vigilance for clinical deterioration as iGAS sign is warranted in young children, especially those with varicella zoster infection.

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.

Impact of influenza vaccination on GP-diagnosed COVID-19 and all-cause mortality: a Dutch cohort study.

OBJECTIVES: As clinical presentation and complications of both viruses overlap, it was hypothesised that influenza vaccination was associated with lower general practitioner (GP)-diagnosed COVID-19 rates and lower all-cause mortality rates. STUDY DESIGN: From a primary care population-based cohort in the Netherlands, GP-diagnosed COVID-19 (between 10 March and 22 November 2020) and all-cause mortality events (between 30 December 2019 and 22 November 2020) were recorded. 223 580 persons were included, representing the influenza vaccination 2019 target group (all aged ≥60 years, and those <60 years with a medical indication). Proportional hazards regression analyses evaluated associations between influenza vaccination in 2019 and two outcomes: GP-diagnosed COVID-19 and all-cause mortality. Covariables were sex, age, comorbidities and number of acute respiratory infection primary care consultations in 2019. RESULTS: A slightly positive association (HR 1.15; 95% CI 1.08 to 1.22) was found between influenza vaccination in 2019 and GP-diagnosed COVID-19, after adjusting for covariables. A slightly protective effect for all-cause mortality rates (HR 0.90; 95% CI 0.83 to 0.97) was found for influenza vaccination, after adjusting for covariables. A subgroup analysis among GP-diagnosed COVID-19 cases showed no significant association between influenza vaccination in 2019 and all-cause mortality. CONCLUSIONS: Our hypothesis of a possibly negative association between influenza vaccination in 2019 and GP-diagnosed COVID-19 was not confirmed as we found a slightly positive association. A slightly protective effect on all-cause mortality was found after influenza vaccination, possibly by a wider, overall protective effect on health. Future research designs should include test-confirmed COVID-19 cases and controls, adjustments for behavioural, socioeconomic and ethnic factors and validated cause-specific mortality cases.

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.

Increasing incidence of reported scabies infestations in the Netherlands, 2011-2021.

INTRODUCTION: Several Public Health Services and general practitioners in the Netherlands observed an increase in scabies in the Netherlands. Since individual cases of scabies are not notifiable in the Netherlands, the epidemiological situation is mostly unknown. To investigate the scabies incidence in the Netherlands, we described the epidemiology of scabies between 2011 and 2021. METHODS: Two national data sources were analysed descriptively. One data source obtained incidence data of scabies (per 1,000 persons) of persons consulting in primary care from 2011-2020. The other data source captured the number of prescribed scabicides in the Netherlands from 2011-2021. To describe the correlation between the incidence of diagnoses and the number of dispensations between 2011 and 2020, we calculated a correlation coefficient. RESULTS: The incidence of reported scabies has increased by more than threefold the last decade (2011-2020), mainly affecting adolescents and (young) adults. This was also clearly reflected in the fivefold increase in dispensations of scabicide medication during 2011-2021. The incidence and dispensations were at an all-time high in 2021. We found a strong correlation between the reported incidence and the number of dispensations between 2011 and 2020. CONCLUSIONS: More awareness on early diagnosis, proper treatment and treatment of close contacts is needed.

Effectiveness of complete primary vaccination against COVID-19 at primary care and community level during predominant Delta circulation in Europe: multicentre analysis, I-MOVE-COVID-19 and ECDC networks, July to August 2021.

IntroductionIn July and August 2021, the SARS-CoV-2 Delta variant dominated in Europe.AimUsing a multicentre test-negative study, we measured COVID-19 vaccine effectiveness (VE) against symptomatic infection.MethodsIndividuals with COVID-19 or acute respiratory symptoms at primary care/community level in 10 European countries were tested for SARS-CoV-2. We measured complete primary course overall VE by vaccine brand and by time since vaccination.ResultsOverall VE was 74% (95% CI: 69-79), 76% (95% CI: 71-80), 63% (95% CI: 48-75) and 63% (95% CI: 16-83) among those aged 30-44, 45-59, 60-74 and ≥ 75 years, respectively. VE among those aged 30-59 years was 78% (95% CI: 75-81), 66% (95% CI: 58-73), 91% (95% CI: 87-94) and 52% (95% CI: 40-61), for Comirnaty, Vaxzevria, Spikevax and COVID-19 Vaccine Janssen, respectively. VE among people 60 years and older was 67% (95% CI: 52-77), 65% (95% CI: 48-76) and 83% (95% CI: 64-92) for Comirnaty, Vaxzevria and Spikevax, respectively. Comirnaty VE among those aged 30-59 years was 87% (95% CI: 83-89) at 14-29 days and 65% (95% CI: 56-71%) at ≥ 90 days between vaccination and onset of symptoms.ConclusionsVE against symptomatic infection with the SARS-CoV-2 Delta variant varied among brands, ranging from 52% to 91%. While some waning of the vaccine effect may be present (sample size limited this analysis to only Comirnaty), protection was 65% at 90 days or more between vaccination and onset.

Health and economic impact of seasonal influenza mass vaccination strategies in European settings: A mathematical modelling and cost-effectiveness analysis.

INTRODUCTION: Despite seasonal influenza vaccination programmes in most countries targeting individuals aged ≥ 65 (or ≥ 55) years and high risk-groups, significant disease burden remains. We explored the impact and cost-effectiveness of 27 vaccination programmes targeting the elderly and/or children in eight European settings (n = 205.8 million). METHODS: We used an age-structured dynamic-transmission model to infer age- and (sub-)type-specific seasonal influenza virus infections calibrated to England, France, Ireland, Navarra, The Netherlands, Portugal, Scotland, and Spain between 2010/11 and 2017/18. The base-case vaccination scenario consisted of non-adjuvanted, non-high dose trivalent vaccines (TV) and no universal paediatric vaccination. We explored i) moving the elderly to "improved" (i.e., adjuvanted or high-dose) trivalent vaccines (iTV) or non-adjuvanted non-high-dose quadrivalent vaccines (QV); ii) adopting mass paediatric vaccination with TV or QV; and iii) combining the elderly and paediatric strategies. We estimated setting-specific costs and quality-adjusted life years (QALYs) gained from the healthcare perspective, and discounted QALYs at 3.0%. RESULTS: In the elderly, the estimated numbers of infection per 100,000 population are reduced by a median of 261.5 (range across settings: 154.4, 475.7) when moving the elderly to iTV and by 150.8 (77.6, 262.3) when moving them to QV. Through indirect protection, adopting mass paediatric programmes with 25% uptake achieves similar reductions in the elderly of 233.6 using TV (range: 58.9, 425.6) or 266.5 using QV (65.7, 477.9), with substantial health gains from averted infections across ages. At €35,000/QALY gained, moving the elderly to iTV plus adopting mass paediatric QV programmes provides the highest mean net benefits and probabilities of being cost-effective in all settings and paediatric coverage levels. CONCLUSION: Given the direct and indirect protection, and depending on the vaccine prices, model results support a combination of having moved the elderly to an improved vaccine and adopting universal paediatric vaccination programmes across the European settings.

An unusual outbreak in the Netherlands: community-onset impetigo caused by a meticillin-resistant Staphylococcus aureus with additional resistance to fusidic acid, June 2018 to January 2020.

In this retrospective observational study, we analysed a community outbreak of impetigo with meticillin-resistant Staphylococcus aureus (MRSA), with additional resistance to fusidic acid (first-line treatment). The outbreak occurred between June 2018 and January 2020 in the eastern part of the Netherlands with an epidemiological link to three cases from the north-western part. Forty nine impetigo cases and eight carrier cases were identified, including 47 children. All but one impetigo case had community-onset of symptoms. Pharmacy prescription data for topical mupirocin and fusidic acid and GP questionnaires suggested an underestimated outbreak size. The 57 outbreak isolates were identified by the Dutch MRSA surveillance as MLVA-type MT4627 and sequence type 121, previously reported only once in 2014. Next-generation sequencing revealed they contained a fusidic acid resistance gene, exfoliative toxin genes and an epidermal cell differentiation inhibitor gene. Whole-genome multilocus sequence typing revealed genetic clustering of all 19 sequenced isolates from the outbreak region and isolates from the three north-western cases. The allelic distances between these Dutch isolates and international isolates were high. This outbreak shows the appearance of community-onset MRSA strains with additional drug resistance and virulence factors in a country with a low prevalence of antimicrobial resistance.

Patients with tinnitus use more primary healthcare compared to people without tinnitus.

Tinnitus is a heterogeneous condition not only in terms of nature of the sound, but also in co-morbidities such as mental health issues. Prevalence number range widely between 5 and 43%. Even though the etiologic pathway between tinnitus and its comorbidities remains unclear, in this study we aim to assess whether people with tinnitus use more primary health care than people without tinnitus. To compare primary healthcare consumption between patients with tinnitus and people without tinnitus. In this cross-sectional study, data on number of consultations with the general practitioner or nurse practitioner mental health services were obtained from Nivel (Netherlands Institute for Health Service Research) Primary Care Database in 2018 (n = 963,880 people). People with an open tinnitus episode (n = 8050) were defined as a patient with tinnitus and compared to all other people. Percentages, means, ranges and mean differences were calculated for the total number of consultations and for organ specific diagnoses registered as ICPC-1 code on the day of consultation. Secondary, the total number of referrals to medical specialists and number of drug prescriptions was collected. Logistic regressions were performed to predict having one or more contacts, referrals, and prescriptions,with having tinnitus, this was corrected for age and gender. Patients with tinnitus had a mean of 9.8 (SD 10.9) primary care consultations in 2018, compared to 5.7 (SD 7.9) for people without tinnitus. More patients with tinnitus had more than one referral to medical specialists (47%) compared to people without tinnitus (25%). Patients with tinnitus have 1.2 (mean difference) more drug prescriptions than people without tinnitus. Compared to people without tinnitus, patients with tinnitus were more likely to have one or more of primary healthcare contact, independent of age group and gender. Patients with tinnitus had more consultations in primary health care than people without tinnitus. They are more often referred to medical specialists and receive more drug prescriptions. The causal relationship between tinnitus and the higher healthcare consumption remains to be researched.

The Global Epidemiology of RSV in Community and Hospitalized Care: Findings From 15 Countries.

BACKGROUND: Respiratory syncytial virus (RSV) is one of the leading causes of acute respiratory tract infections. To optimize control strategies, a better understanding of the global epidemiology of RSV is critical. To this end, we initiated the Global Epidemiology of RSV in Hospitalized and Community care study (GERi). METHODS: Focal points from 44 countries were approached to join GERi and share detailed RSV surveillance data. Countries completed a questionnaire on the characteristics of their surveillance system. RESULTS: Fifteen countries provided granular surveillance data and information on their surveillance system. A median (interquartile range) of 1641 (552-2415) RSV cases per season were reported from 2000 and 2020. The majority (55%) of RSV cases occurred in the <1-year-olds, with 8% of cases reported in those aged ≥65 years. Hospitalized cases were younger than those in community care. We found no age difference between RSV subtypes and no clear pattern of dominant subtypes. CONCLUSIONS: The high number of cases in the <1-year-olds indicates a need to focus prevention efforts in this group. The minimal differences between RSV subtypes and their co-circulation implies that prevention needs to target both subtypes. Importantly, there appears to be a lack of RSV surveillance data in the elderly.

Vaccine effectiveness against symptomatic SARS-CoV-2 infection in adults aged 65 years and older in primary care: I-MOVE-COVID-19 project, Europe, December 2020 to May 2021.

We measured COVID-19 vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection at primary care/outpatient level among adults ≥ 65 years old using a multicentre test-negative design in eight European countries. We included 592 SARS-CoV-2 cases and 4,372 test-negative controls in the main analysis. The VE was 62% (95% CI: 45-74) for one dose only and 89% (95% CI: 79-94) for complete vaccination. COVID-19 vaccines provide good protection against COVID-19 presentation at primary care/outpatient level, particularly among fully vaccinated individuals.

Defining the seasonality of respiratory syncytial virus around the world: National and subnational surveillance data from 12 countries.

BACKGROUND: Respiratory syncytial virus (RSV) infections are one of the leading causes of lower respiratory tract infections and have a major burden on society. For prevention and control to be deployed effectively, an improved understanding of the seasonality of RSV is necessary. OBJECTIVES: The main objective of this study was to contribute to a better understanding of RSV seasonality by examining the GERi multi-country surveillance dataset. METHODS: RSV seasons were included in the analysis if they contained ≥100 cases. Seasonality was determined using the "average annual percentage" method. Analyses were performed at a subnational level for the United States and Brazil. RESULTS: We included 601 425 RSV cases from 12 countries. Most temperate countries experienced RSV epidemics in the winter, with a median duration of 10-21 weeks. Not all epidemics fit this pattern in a consistent manner, with some occurring later or in an irregular manner. More variation in timing was observed in (sub)tropical countries, and we found substantial differences in seasonality at a subnational level. No association was found between the timing of the epidemic and the dominant RSV subtype. CONCLUSIONS: Our findings suggest that geographical location or climatic characteristics cannot be used as a definitive predictor for the timing of RSV epidemics and highlight the need for (sub)national data collection and analysis.

Impact of influenza vaccination in the Netherlands, 2007-2016: Vaccinees consult their general practitioner for clinically diagnosed influenza, acute respiratory infections, and pneumonia more often than non-vaccinees.

INTRODUCTION: We aimed to develop an innovative population-based method to estimate the health effect of influenza vaccination based on electronic medical records collected within a general practitioner (GP)-based influenza surveillance system in the Netherlands. METHODS: In each season between 2006/07 and 2015/16, we fitted multilevel Poisson regression models to compare GP consultation rates for clinically diagnosed influenza, acute respiratory infections (ARI), pneumonia, and lower back pain (as a control) between vaccinated vs. unvaccinated individuals. Season-specific relative risks and 95% confidence intervals (CI) were pooled into summary risk ratio (SRR) through random-effects meta-analysis models. Analyses were stratified by patient age (<45, 45-59, 60-74, ≥75 years) and medical indication for the vaccine (any vs. none, subjects aged ≤60 years only). RESULTS: Overall, 12.6% and 21.4% of study subjects were vaccinated because of their age only or because of an underlying medical condition. Vaccine uptake declined over time, especially among subjects aged ≤74 years with medical indications for vaccination. Vaccinated individuals had significantly higher GP consultation rates for clinically diagnosed influenza (SRR 1.24, 95% CI 1.12-1.38, p-value <0.001), ARI (SRR 1.33, 95% CI 1.27-1.39, p-value <0.001), pneumonia (SRR 1.27, 95% CI 1.19-1.36, p-value <0.001), and lower back pain (SRR 1.21, 95% CI 1.14-1.28, p-value <0.001) compared to unvaccinated individuals. DISCUSSION: Contrary to expectations, influenza vaccinees have GP consultation rates for clinically diagnosed influenza, ARI and pneumonia that are 24-33% higher compared to unvaccinated individuals. The lower back pain finding suggests that the increase in consultation rates is partially caused by confounding. Importantly, considering the data are not laboratory-confirmed, our results cannot be linked directly to influenza, but only to respiratory illnesses in general.

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.

Partial Protective Effect of Bivalent Human Papillomavirus 16/18 Vaccination Against Anogenital Warts in a Large Cohort of Dutch Primary Care Patients.

BACKGROUND: There is ongoing debate about the possible protective effect of the bivalent human papillomavirus (2vHPV) vaccine, targeting oncogenic types HPV-16/18, against anogenital warts (AGWs), commonly attributed to HPV-6/11. We performed a retrospective registry-based open cohort study to assess the effect of 2vHPV vaccination on AGWs. METHODS: We linked general practice (ie, primary care) data from women born between 1993 and 2002, who had been eligible for HPV vaccination in the Netherlands, to the Dutch national immunization registry on an individual level. Women were followed until their first AGW diagnosis or end of follow-up. Adjusted incidence rate ratios (aIRRs) were estimated using Poisson regression with vaccination status as a time-dependent exposure. RESULTS: We linked data of 96 468 women with a total of 328 019 years observation time and 613 AGW diagnoses (incidence: 1.87/1000 person-years). At the end of follow-up, 61% were 2vHPV vaccinated (≥ 1 dose) of whom 91% were fully vaccinated. The AGW incidence was lower among those with ≥ 1 dose vs 0 doses (aIRR, 0.75 [95% confidence interval {CI}, .64-.88]). The effect of vaccination was stronger after full vaccination (aIRR, 0.72 [95% CI, .61-.86]) and for women who were offered vaccination at 12-13 years of age (aIRR, 0.69 [95% CI, .51-.93]) vs those at 13-16 years of age (aIRR, 0.77 [95% CI, .64-.93]). CONCLUSIONS: This is the largest population-based study so far to examine the effect of 2vHPV vaccination on AGWs, with reliable individual information on AGW diagnoses and vaccination status. The results indicate that 2vHPV vaccination partially protects against AGWs, especially when administered in early adolescence.

Estimating Transmission Parameters for Respiratory Syncytial Virus and Predicting the Impact of Maternal and Pediatric Vaccination.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of respiratory tract illness in young children and a major cause of hospital admissions globally. METHODS: Here we fit age-structured transmission models with immunity propagation to data from the Netherlands (2012-2017). Data included nationwide hospitalizations with confirmed RSV, general practitioner (GP) data on attendance for care from acute respiratory infection, and virological testing of acute respiratory infections at the GP. The transmission models, equipped with key parameter estimates, were used to predict the impact of maternal and pediatric vaccination. RESULTS: Estimates of the basic reproduction number were generally high (R0 > 10 in scenarios with high statistical support), while susceptibility was estimated to be low in nonelderly adults (<10% in persons 20-64 years) and was higher in older adults (≥65 years). Scenario analyses predicted that maternal vaccination reduces the incidence of infection in vulnerable infants (<1 year) and shifts the age of first infection from infants to young children. CONCLUSIONS: Pediatric vaccination is expected to reduce the incidence of infection in infants and young children (0-5 years), slightly increase incidence in 5 to 9-year-old children, and have minor indirect benefits.