Systematic review of the efficacy, effectiveness and safety of recombinant haemagglutinin seasonal influenza vaccines for the prevention of laboratory-confirmed influenza in individuals ≥18 years of age.

The most effective means of preventing seasonal influenza is through vaccination. In this systematic review, we investigated the efficacy, effectiveness and safety of recombinant haemagglutinin (HA) seasonal influenza vaccines to prevent laboratory-confirmed influenza. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials and non-randomised studies of interventions were eligible for inclusion. The search returned 28,846 records, of which 10 studies on recombinant HA influenza vaccine met our inclusion criteria. One study found that the quadrivalent recombinant HA influenza vaccine had higher relative vaccine efficacy (rVE) in preventing laboratory-confirmed influenza during the 2014-15 season compared with traditional quadrivalent vaccination in adults aged ≥50 years (rVE = 30%, 95% CI 10%-47%, moderate-certainty evidence). In a subgroup analysis, higher rVE was reported for influenza A (rVE = 36%, 95% CI 14% to 53%), but not for B (non-significant). Another study reported higher efficacy for the trivalent recombinant HA vaccine compared with placebo (VE = 45%, 95% CI 19-63, 1 RCT, low-certainty evidence) in adults aged 18-55 years. With the exception of a higher rate of chills (RR = 1.33, 95% CI 1.03-1.72), the safety profile of recombinant HA vaccines was comparable to that of traditional influenza vaccines. The evidence base for the efficacy and effectiveness of recombinant HA influenza vaccines is limited at present, although one study found that the quadrivalent recombinant HA influenza vaccine had higher rVE compared with traditional quadrivalent vaccination in adults aged ≥50 years.

Systematic review of the efficacy, effectiveness and safety of high-dose seasonal influenza vaccines for the prevention of laboratory-confirmed influenza in individuals ≥18 years of age.

This review sought to assess the efficacy, effectiveness and safety of high-dose inactivated influenza vaccines (HD-IIV) for the prevention of laboratory-confirmed influenza in individuals aged 18 years or older. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) were included. The search returned 28,846 records, of which 36 studies were included. HD-IIV was shown to have higher relative vaccine efficacy in preventing influenza compared with standard-dose influenza vaccines (SD-IIV3) in older adults (Vaccine effectiveness (VE) = 24%, 95% CI 10-37, one RCT). One NRSI demonstrated significant effect for HD-IIV3 against influenza B (VE = 89%, 95% CI 47-100), but not for influenza A(H3N2) (VE = 22%, 95% CI -82 to 66) when compared with no vaccination in older adults. HD-IIV3 showed significant relative effect compared with SD-IIV3 for influenza-related hospitalisation (VE = 11.8%, 95% CI 6.4-17.0, two NRSIs), influenza- or pneumonia-related hospitalisation (VE = 13.7%, 95% CI 9.5-17.7, three NRSIs), influenza-related hospital encounters (VE = 13.1%, 95% CI 8.4-17.7, five NRSIs), and influenza-related office visits (VE = 3.5%, 95% CI 1.5-5.5, two NRSIs). For safety, HD-IIV were associated with significantly higher rates of local and systemic adverse events compared with SD-IIV (combined local reactions, pain at injection site, swelling, induration, headache, chills and malaise). From limited data, compared with SD-IIV, HD-IIV were found to be more effective in the prevention of laboratory-confirmed influenza, for a range of proxy outcome measures, and associated with more adverse events.

Systematic review of the efficacy, effectiveness and safety of cell-based seasonal influenza vaccines for the prevention of laboratory-confirmed influenza in individuals ≥18 years of age.

The most effective means of preventing seasonal influenza is through strain-specific vaccination. In this study, we investigated the efficacy, effectiveness and safety of cell-based trivalent and quadrivalent influenza vaccines. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) were eligible for inclusion. Two reviewers independently screened, extracted data and assessed the risk of bias of included studies. Certainty of evidence for key outcomes was assessed using the GRADE methodology. The search returned 28,846 records, of which 868 full-text articles were assessed for relevance. Of these, 19 studies met the inclusion criteria. No relative efficacy data were identified for the direct comparison of cell-based vaccines compared with traditional vaccines (egg-based). Efficacy data were available comparing cell-based trivalent influenza vaccines with placebo in adults (aged 18-49 years). Overall vaccine efficacy was 70% against any influenza subtype (95% CI 61%-77%, two RCTS), 82% against influenza A(H1N1) (95% CI 71%-89%, 2 RCTs), 72% against influenza A(H3N2) (95% CI 39%-87%, 2 RCTs) and 52% against influenza B (95% CI 30%-68%, 2 RCTs). Limited and heterogeneous data were presented for effectiveness when compared with no vaccination. One NRSI compared cell-based trivalent and quadrivalent vaccination with traditional trivalent and quadrivalent vaccination, finding a small but significant difference in favour of cell-based vaccines for influenza-related hospitalisation, hospital encounters and physician office visits. The safety profile of cell-based trivalent vaccines was comparable to traditional trivalent influenza vaccines. Compared with placebo, cell-based trivalent influenza vaccines have demonstrated greater efficacy in adults aged 18-49 years. Overall cell-based vaccines are well-tolerated in adults, however, evidence regarding the effectiveness of these vaccines compared with traditional seasonal influenza vaccines is limited.

Systematic review of the efficacy, effectiveness and safety of MF59® adjuvanted seasonal influenza vaccines for the prevention of laboratory-confirmed influenza in individuals ≥18 years of age.

The most effective means of preventing seasonal influenza is through vaccination. In this systematic review, we investigated the efficacy, effectiveness and safety of MF59® adjuvanted trivalent and quadrivalent influenza vaccines to prevent laboratory-confirmed influenza. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials and non-randomised studies of interventions (NRSIs) were eligible for inclusion. The search returned 28,846 records, of which 48 studies on MF59® adjuvanted vaccines met our inclusion criteria. No efficacy trials were identified. In terms of vaccine effectiveness (VE), MF59® adjuvanted trivalent influenza vaccines were effective in preventing laboratory-confirmed influenza in older adults (aged ≥65 years) compared with no vaccination (VE = 45%, 95% confidence interval (CI) 23%-61%, 5 NRSIs across 3 influenza seasons). By subtype, significant effect was found for influenza A(H1N1) (VE = 61%, 95% CI 44%-73%) and B (VE = 29%, 95% CI 5%-46%), but not for A(H3N2). In terms of relative VE, there was no significant difference comparing MF59® adjuvanted trivalent vaccines with either non-adjuvanted trivalent or quadrivalent vaccines. Compared with traditional trivalent influenza vaccines, MF59® adjuvanted trivalent influenza vaccines were associated with a greater number of local adverse events (RR = 1.90, 95% CI 1.50-2.39) and systemic reactions (RR = 1.18, 95% CI 1.02-1.38). In conclusion, MF59® adjuvanted trivalent influenza vaccines were found to be more effective than 'no vaccination'. Based on limited data, there was no significant difference comparing the effectiveness of MF59® adjuvanted vaccines with their non-adjuvanted counterparts.

Effectiveness of historical smallpox vaccination against mpox clade II in men in Denmark, France, the Netherlands and Spain, 2022.

BackgroundIn 2022, a global monkeypox virus (MPXV) clade II epidemic occurred mainly among men who have sex with men. Until early 1980s, European smallpox vaccination programmes were part of worldwide smallpox eradication efforts. Having received smallpox vaccine > 20 years ago may provide some cross-protection against MPXV.AimTo assess the effectiveness of historical smallpox vaccination against laboratory-confirmed mpox in 2022 in Europe.MethodsEuropean countries with sufficient data on case vaccination status and historical smallpox vaccination coverage were included. We selected mpox cases born in these countries during the height of the national smallpox vaccination campaigns (latest 1971), male, with date of onset before 1 August 2022. We estimated vaccine effectiveness (VE) and corresponding 95% CI for each country using logistic regression as per the Farrington screening method. We calculated a pooled estimate using a random effects model.ResultsIn Denmark, France, the Netherlands and Spain, historical smallpox vaccination coverage was high (80-90%) until the end of the 1960s. VE estimates varied widely (40-80%, I2 = 82%), possibly reflecting different booster strategies. The pooled VE estimate was 70% (95% CI: 23-89%).ConclusionOur findings suggest residual cross-protection by historical smallpox vaccination against mpox caused by MPXV clade II in men with high uncertainty and heterogeneity. Individuals at high-risk of exposure should be offered mpox vaccination, following national recommendations, regardless of prior smallpox vaccine history, until further evidence becomes available. There is an urgent need to conduct similar studies in sub-Saharan countries currently affected by the MPXV clade I outbreak.

Relative vaccine effectiveness against COVID-19 hospitalisation in persons aged ≥ 65 years: results from a VEBIS network, Europe, October 2021 to July 2023.

To monitor relative vaccine effectiveness (rVE) against COVID-19-related hospitalisation of the first, second and third COVID-19 booster (vs complete primary vaccination), we performed monthly Cox regression models using retrospective cohorts constructed from electronic health registries in eight European countries, October 2021-July 2023. Within 12 weeks of administration, each booster showed high rVE (≥ 70% for second and third boosters). However, as of July 2023, most of the relative benefit has waned, particularly in persons ≥ 80-years-old, while some protection remained in 65-79-year-olds.

Effectiveness of the adapted bivalent mRNA COVID-19 vaccines against hospitalisation in individuals aged ≥ 60 years during the Omicron XBB lineage-predominant period: VEBIS SARI VE network, Europe, February to August, 2023.

We conducted a multicentre hospital-based test-negative case-control study to measure the effectiveness of adapted bivalent COVID-19 mRNA vaccines against PCR-confirmed SARS-CoV-2 infection during the Omicron XBB lineage-predominant period in patients aged ≥ 60 years with severe acute respiratory infection from five countries in Europe. Bivalent vaccines provided short-term additional protection compared with those vaccinated > 6 months before the campaign: from 80% (95% CI: 50 to 94) for 14-89 days post-vaccination, 15% (95% CI: -12 to 35) at 90-179 days, and lower to no effect thereafter.

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.

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Alpha- and Delta-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021.

IntroductionTwo large multicentre European hospital networks have estimated vaccine effectiveness (VE) against COVID-19 since 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in hospitalised severe acute respiratory illness (SARI) patients ≥ 20 years, combining data from these networks during Alpha (March-June)- and Delta (June-December)-dominant periods, 2021.MethodsForty-six participating hospitals across 14 countries follow a similar generic protocol using the test-negative case-control design. We defined complete primary series vaccination (PSV) as two doses of a two-dose or one of a single-dose vaccine ≥ 14 days before onset.ResultsWe included 1,087 cases (538 controls) and 1,669 cases (1,442 controls) in the Alpha- and Delta-dominant periods, respectively. During the Alpha period, VE against hospitalisation with SARS-CoV2 for complete Comirnaty PSV was 85% (95% CI: 69-92) overall and 75% (95% CI: 42-90) in those aged ≥ 80 years. During the Delta period, among SARI patients ≥ 20 years with symptom onset ≥ 150 days from last PSV dose, VE for complete Comirnaty PSV was 54% (95% CI: 18-74). Among those receiving Comirnaty PSV and mRNA booster (any product) ≥ 150 days after last PSV dose, VE was 91% (95% CI: 57-98). In time-since-vaccination analysis, complete all-product PSV VE was > 90% in those with their last dose < 90 days before onset; ≥ 70% in those 90-179 days before onset.ConclusionsOur results from this EU multi-country hospital setting showed that VE for complete PSV alone was higher in the Alpha- than the Delta-dominant period, and addition of a first booster dose during the latter period increased VE to over 90%.

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Omicron-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021 to 2022.

IntroductionThe I-MOVE-COVID-19 and VEBIS hospital networks have been measuring COVID-19 vaccine effectiveness (VE) in participating European countries since early 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in patients ≥ 20 years hospitalised with severe acute respiratory infection (SARI) from December 2021 to July 2022 (Omicron-dominant period).MethodsIn both networks, 46 hospitals (13 countries) follow a similar test-negative case-control protocol. We defined complete primary series vaccination (PSV) and first booster dose vaccination as last dose of either vaccine received ≥ 14 days before symptom onset (stratifying first booster into received < 150 and ≥ 150 days after last PSV dose). We measured VE overall, by vaccine category/product, age group and time since first mRNA booster dose, adjusting by site as a fixed effect, and by swab date, age, sex, and presence/absence of at least one commonly collected chronic condition.ResultsWe included 2,779 cases and 2,362 controls. The VE of all vaccine products combined against hospitalisation for laboratory-confirmed SARS-CoV-2 was 43% (95% CI: 29-54) for complete PSV (with last dose received ≥ 150 days before onset), while it was 59% (95% CI: 51-66) after addition of one booster dose. The VE was 85% (95% CI: 78-89), 70% (95% CI: 61-77) and 36% (95% CI: 17-51) for those with onset 14-59 days, 60-119 days and 120-179 days after booster vaccination, respectively.ConclusionsOur results suggest that, during the Omicron period, observed VE against SARI hospitalisation improved with first mRNA booster dose, particularly for those having symptom onset < 120 days after first booster dose.

Estimation of COVID-19 vaccine effectiveness against hospitalisation in individuals aged ≥ 65 years using electronic health registries; a pilot study in four EU/EEA countries, October 2021 to March 2022.

By employing a common protocol and data from electronic health registries in Denmark, Navarre (Spain), Norway and Portugal, we estimated vaccine effectiveness (VE) against hospitalisation due to COVID-19 in individuals aged ≥ 65 years old, without previous documented infection, between October 2021 and March 2022. VE was higher in 65-79-year-olds compared with ≥ 80-year-olds and in those who received a booster compared with those who were primary vaccinated. VE remained high (ca 80%) between ≥ 12 and < 24 weeks after the first booster administration, and after Omicron became dominant.

Risk reduction of severe outcomes in vaccinated COVID-19 cases: an analysis of surveillance data from Estonia, Ireland, Luxembourg and Slovakia, January to November 2021.

Despite high COVID-19 vaccine coverage in the EU/EEA, there are increasing reports of SARS-CoV-2 infections and hospitalisations in vaccinated individuals. Using surveillance data from Estonia, Ireland, Luxembourg and Slovakia (January-November 2021), we estimated risk reduction of severe outcomes in vaccinated cases. Increasing age remains the most important driver of severity, and vaccination significantly reduces risk in all ages for hospitalisation (adjusted relative risk (aRR): 0.32; 95% confidence interval (CI): 0.26-0.39) and death (aRR: 0.20; 95% CI: 0.13-0.29).

Estimated number of deaths directly averted in people 60 years and older as a result of COVID-19 vaccination in the WHO European Region, December 2020 to November 2021.

Since December 2019, over 1.5 million SARS-CoV-2-related fatalities have been recorded in the World Health Organization European Region - 90.2% in people ≥ 60 years. We calculated lives saved in this age group by COVID-19 vaccination in 33 countries from December 2020 to November 2021, using weekly reported deaths and vaccination coverage. We estimated that vaccination averted 469,186 deaths (51% of 911,302 expected deaths; sensitivity range: 129,851-733,744; 23-62%). Impact by country ranged 6-93%, largest when implementation was early.

Initial assessment of the COVID-19 vaccination's impact on case numbers, hospitalisations and deaths in people aged 80 years and older, 15 EU/EEA countries, December 2020 to May 2021.

Prioritisation of elderly people in COVID-19 vaccination campaigns aimed at reducing severe outcomes in this group. Using EU/EEA surveillance and vaccination uptake, we estimated the risk ratio of case, hospitalisation and death notifications in people 80 years and older compared with 25-59-year-olds. Highest impact was observed for full vaccination uptake 80% or higher with reductions in notification rates of cases up to 65% (IRR: 0.35; 95% CI: 0.13-0.99), hospitalisations up to 78% (IRR: 0.22; 95% CI: 0.13-0.37) and deaths up to 84% (IRR: 0.16; 95% CI: 0.13-0.20).

A description of a hepatitis A outbreak in men who have sex with men and public health measures implemented in Seine-Maritime department, Normandy, France, 2017.

BACKGROUND: In 2016-2017, a European-wide circulation of genotype IA hepatitis A virus was responsible for hepatitis A outbreaks in men who have sex with men (MSM). This study aimed to describe the outbreak investigation in Seine-Maritime department (France) and the control measures implemented accordingly. METHODS: Outbreak description used data from mandatory reporting and enhanced surveillance of male cases. Confirmed case was genotype IA isolated, possible cases had no reported genotype information. Targeted control measures included communication on sexual practices at risk of hepatitis A transmission and two vaccination campaigns in April 2017 and January 2018. Characteristics of cases and vaccinees were described. We reported the best communication channel for relaying outbreak information and control measures based on the monitoring of social network activities and feedback from vaccinees. RESULTS: During the outbreak period (December 2016 to December 2017), a total of 48 confirmed outbreak cases and 30 possible outbreak cases were notified. Among them, 69 were male (88%). Two epidemic waves were observed. Cases encountered their partners through gay-dating apps (54%) and in one specific sauna (62%). In response to the outbreak, two vaccination campaigns were deployed. A total of 156 MSM were vaccinated, of whom 56 in a truck parked beside the sauna. Most of the vaccinees had been informed about the campaign through dating apps (44%). Community-based organizations involved in sexual health promotion and other gay social media were very proactive in sharing information about the outbreak and promoting the vaccination campaign through their social media account and also on site (gay venues). Vaccinees reported the same sexual practices at risk of hepatitis A transmission as cases. CONCLUSIONS: In response to this massive hepatitis A outbreak that affected mostly MSM in Seine-Maritime department, vaccination campaign remained the cornerstone of prevention. Prevention officers from the community-based organization played a key role in vaccination promotion. Gay-dating apps and outdoor sessions of vaccination allowed to effectively reach MSM. Cost-effectiveness studies might analyze the interest of a continuous sexual health promotion including vaccination against hepatitis A in MSM through dating apps and social networks.

Epidemiology of measles during the COVID-19 pandemic, a description of the surveillance data, 29 EU/EEA countries and the United Kingdom, January to May 2020.

The number of measles cases declined in European Union/European Economic Area countries and the United Kingdom in 2020. Reported cases to The European Centre for Disease Prevention and Control decreased from 710 to 54 between January and May. Epidemic intelligence screening observed a similar trend. Under-diagnoses and under-reporting during the coronavirus disease (COVID-19) pandemic should be ruled out before concluding reduced measles circulation is because of social distancing and any community control measures taken to control COVID-19.

Mortality and clinical outcomes in children treated with antiretroviral therapy in four African vertical programmes during the first decade of paediatric HIV care, 2001-2010.

OBJECTIVE: To assess mortality and clinical outcomes in children treated with antiretroviral therapy (ART) in four African vertical programmes between 2001 and 2010. METHODS: Cohort analysis of data from HIV-infected children (<15 years old) initiating ART in four sub-Saharan HIV programmes in Kenya, Uganda and Malawi, between December 2001 and December 2010. Rates of mortality, programme attrition and first-line clinico-immunological failure were calculated by age group (<2, 2-4 and 5-14 years), 1 or 2 years after ART initiation, and risk factors were examined. RESULTS: A total of 3949 children, 22.7% aged <2 years, 32.2% 2-4 years and 45.1% 5-14 years, were included. At ART initiation, 60.8% had clinical stage 3 or 4, and 46.5% severe immunosuppression. Overall mortality, attrition and 1-year failure rates were 5.1, 10.8 and 9.0 per 100 person-years, respectively. Immunosuppression, stage 3 or 4, and underweight were associated with increased rates of mortality, attrition and treatment failure. Adjusted estimates showed lower mortality hazard ratios (HR) among children aged 2-4 years (HR = 0.57, 95% CI 0.42-0.77 than children aged 5-14 years). One-year treatment failure incidence rate ratios (IRR) were similar regardless of age (IRR = 0.91, 95% CI 0.67-1.25 for <2 years; 1.01, 95% CI 0.83-1.23 for 2-4 years, vs. 5-14 years). CONCLUSIONS: Good treatment outcomes were achieved during the first decade of HIV paediatric care despite the late start of therapy. Encouraging early HIV infant diagnosis in and outside prevention of mother-to-child transmission programmes, and linkage to care services for early ART initiation, is needed to reduce mortality and delay treatment failure.

Effectiveness of XBB.1.5 Monovalent COVID-19 Vaccines During a Period of XBB.1.5 Dominance in EU/EEA Countries, October to November 2023: A VEBIS-EHR Network Study.

Using a common protocol across seven countries in the European Union/European Economic Area, we estimated XBB.1.5 monovalent vaccine effectiveness (VE) against COVID-19 hospitalisation and death in booster-eligible ≥ 65-year-olds, during October-November 2023. We linked electronic records to construct retrospective cohorts and used Cox models to estimate adjusted hazard ratios and derive VE. VE for COVID-19 hospitalisation and death was, respectively, 67% (95%CI: 58-74) and 67% (95%CI: 42-81) in 65- to 79-year-olds and 66% (95%CI: 57-73) and 72% (95%CI: 51-85) in ≥ 80-year-olds. Results indicate that periodic vaccination of individuals ≥ 65 years has an ongoing benefit and support current vaccination strategies in the EU/EEA.

Early COVID-19 XBB.1.5 Vaccine Effectiveness Against Hospitalisation Among Adults Targeted for Vaccination, VEBIS Hospital Network, Europe, October 2023-January 2024.

We conducted a multicentre test-negative case-control study covering the period from October 2023 to January 2024 among adult patients aged ≥ 18 years hospitalised with severe acute respiratory infection in Europe. We provide early estimates of the effectiveness of the newly adapted XBB.1.5 COVID-19 vaccines against PCR-confirmed SARS-CoV-2 hospitalisation. Vaccine effectiveness was 49% overall, ranging between 69% at 14-29 days and 40% at 60-105 days post vaccination. The adapted XBB.1.5 COVID-19 vaccines conferred protection against COVID-19 hospitalisation in the first 3.5 months post vaccination, with VE > 70% in older adults (≥ 65 years) up to 1 month post vaccination.

Vaccine effectiveness against influenza hospitalisation in adults during the 2022/2023 mixed season of influenza A(H1N1)pdm09, A(H3N2) and B circulation, Europe: VEBIS SARI VE hospital network.

We conducted a multicentre hospital-based test-negative case-control study to measure vaccine effectiveness (VE) against PCR-confirmed influenza in adult patients with severe acute respiratory infection (SARI) during the 2022/2023 influenza season in Europe. Among 5547 SARI patients ≥18 years, 2963 (53%) were vaccinated against influenza. Overall VE against influenza A(H1N1)pdm09 was 11% (95% CI: -23-36); 20% (95% CI: -4-39) against A(H3N2) and 56% (95% CI: 22-75) against B. During the 2022/2023 season, while VE against hospitalisation with influenza B was >55%, it was ≤20% for influenza A subtypes. While influenza vaccination should be a priority for future seasons, improved vaccines against influenza are needed.