The cost-effectiveness of trivalent and quadrivalent influenza vaccination in communities in South Africa,Vietnam and Australia

BackgroundTo inform national healthcare authorities whether quadrivalent influenza vaccines (QIVs) provide better value for money than trivalent influenza vaccines (TIVs), we assessed the cost-effectiveness of TIV and QIV in low-and-middle income communities based in South Africa and Vietnam and contrasted these findings with those from a high-income community in Australia.MethodsIndividual based dynamic simulation models were interfaced with a health economic analysis model to estimate the cost-effectiveness of vaccinating 15% of the population with QIV or TIV in each community over the period 2003–2013. Vaccination was prioritized for HIV-infected individuals, before elderly aged 65+ years and young children. Country or region-specific data on influenza-strain circulation, clinical outcomes and costs were obtained from published sources. The societal perspective was used and outcomes were expressed in International$ (I$) per quality-adjusted life-year (QALY) gained.ResultsWhen compared with TIV, we found that QIV would provide a greater reduction in influenza-related morbidity in communities in South Africa and Vietnam as compared with Australia. The incremental cost-effectiveness ratio of QIV versus TIV was estimated at I$4183/QALY in South Africa, I$1505/QALY in Vietnam and I$80,966/QALY in Australia.ConclusionsThe cost-effectiveness of QIV varied between communities due to differences in influenza epidemiology, comorbidities, and unit costs. Whether TIV or QIV is the most cost-effective alternative heavily depends on influenza B burden among subpopulations targeted for vaccination in addition to country-specific willingness-to-pay thresholds and budgetary impact.     

Cost-effectiveness of quadrivalent versus trivalent influenza vaccine for elderly population in China

BackgroundInfluenza-associated excess death occurred most in the elderly. We aimed to assess the cost-effectiveness of quadrivalent influenza vaccine (QIV) versus trivalent influenza vaccine (TIV) for prevention of influenza infection among elderly population in China.MethodsA decision-analytic model was developed to compare 1-year clinical and economic outcomes of three influenza vaccination options (no vaccination, TIV, and QIV) in a hypothetical cohort of Chinese elderly aged 69 years. Outcome measures included cost, influenza infection rate, influenza-related mortality rate, quality-adjusted life-years (QALY) loss, and incremental cost-effectiveness ratio (ICER) from societal perspective. Sensitivity analyses were performed to examine the uncertainty of model inputs.ResultsBase-case results showed no vaccination was dominated (more costly at higher QALY loss) by TIV and QIV. QIV was more costly (USD56.29 versus USD54.28) with lower influenza infection rate (0.608 versus 0.623), mortality rate (0.00199 versus 0.00204), and QALY loss (0.01213 versus 0.01243) than TIV. QIV was cost-effective compared to TIV with ICER of 6,700 USD/QALY below the willingness-to-pay threshold (29,580 USD/QALY). One-way sensitivity analysis found the cost-effectiveness of QIV was subject to the relative risk of vaccine effectiveness of QIV versus TIV, and TIV would be cost-effective if the relative risk was below 1.05. In 10,000 Monte Carlo simulations, the probabilities of QIV, TIV, and no vaccination to be cost-effective were 86.3%, 13.7%, and 0%, respectively.ConclusionQIV appears to be a cost-effective option compared to TIV and no influenza vaccination for elderly population in China.     

Cost-Effectiveness of Quadrivalent Versus Trivalent Influenza Vaccination in the Dutch National Influenza Prevention Program

ObjectivesAs of 2019, quadrivalent influenza vaccine (QIV) has replaced trivalent influenza vaccine (TIV) in the national immunization program in The Netherlands. Target groups are individuals of 60+ years of age and those with chronic diseases. The objective was to estimate the incremental break-even price of QIV over TIV at a threshold of €20 000 per quality-adjusted life-year (QALY).MethodsAn age-structured compartmental dynamic model was adapted for The Netherlands to assess health outcomes and associated costs of vaccinating all individuals at higher risk for influenza with QIV instead of TIV over the seasons 2010 to 2018. Influenza incidence rates were derived from a global database. Other parameters (probabilities, QALYs and costs) were extracted from the literature and applied according to Dutch guidelines. A threshold of €20 000 per QALY was applied to estimate the incremental break-even prices of QIV versus TIV. Sensitivity analyses were performed to test the robustness of the model outcomes.ResultsRetrospectively, vaccination with QIV instead of TIV could have prevented on average 9500 symptomatic influenza cases, 2130 outpatient visits, 84 hospitalizations, and 38 deaths per year over the seasons 2010 to 2018. This translates into 385 QALYs and 398 life-years potentially gained. On average, totals of €431 527 direct and €2 388 810 indirect costs could have been saved each year.ConclusionUsing QIV over TIV during the influenza seasons 2010 to 2018 would have been cost-effective at an incremental price of maximally €3.81 (95% confidence interval, €3.26-4.31). Sensitivity analysis showed consistent findings on the incremental break-even price in the same range.     

Cost-effectiveness analysis of switching from a trivalent to a quadrivalent inactivated influenza vaccine in the Peruvian immunisation programme

BackgroundSeasonal influenza is an acute respiratory infection mostly caused by type A and B influenza viruses. The severe form of the infection can be life-threatening and lead to a significant burden. Vaccination is the most efficient way of preventing influenza infections and limit this burden.ObjectivesTo assess the cost-effectiveness of switching from a trivalent influenza vaccine (TIV) to a quadrivalent influenza vaccine (QIV) in the vaccination programme in Peru, and to evaluate the health and economic impact of reaching the vaccination coverage rate targeted by the Ministry of Health.MethodsA decision-analytic static cost-effectiveness model, was adapted to the Peruvian setting under both payer and societal perspectives.ResultsA switch from TIV to QIV would prevent 29,126 additional cases (including 12,815 consultations), 54 hospitalisations, and 23 deaths related to influenza, mostly in the population <2 years-old and >60 years-old. This would lead to a saving of US $505,206 under the payer perspective, that would partially offset the investment necessary to introduce QIV into the immunisation programme. The resulting incremental cost-effectiveness ratio (ICER) is $16,649 per QALYs gained. The main drivers of the model results were vaccine efficacy against influenza B viruses, degree of match, vaccines prices and proportion of cases attributable to influenza B. The robustness of the results seems satisfactory as QIV has the probability of being a cost-effective strategy of 83.8% (considering a threshold of three GDP per capita). Reaching the coverage targeted by the Ministry of Health would result in health benefits and disease management savings, and lower ICERs.ConclusionIntroducing QIV instead of TIV in the Peruvian immunisation programme is expected to be a cost-effective strategy, especially in younger children and the elderly. The benefit of QIV would be even more important if the coverage targeted by the Ministry of Health would be reached in the most vulnerable groups.     

Systematic Review on the Cost-Effectiveness of Seasonal Influenza Vaccines in Older Adults

ObjectivesOlder adults are at high risk of influenza-related complications or hospitalization. The purpose of this systematic review is to assess the relative cost-effectiveness of all influenza vaccine options for older adults.MethodsThis systematic review identified economic evaluation studies assessing the cost-effectiveness of influenza vaccines in adults ≥65 years of age from 5 literature databases. Two reviewers independently selected, extracted, and appraised relevant studies using the JBI Critical Appraisal Checklist for Economic Evaluations and Heyland’s generalizability checklist. Costs were converted to 2019 Canadian dollars and adjusted for inflation and purchasing power parity.ResultsA total of 27 studies were included. There were 18 comparisons of quadrivalent inactivated vaccine (QIV) versus trivalent inactivated vaccine (TIV): 5 showed QIV dominated TIV (ie, lower costs and higher health benefit), and 13 showed the results depended on willingness to pay (WTP). There were 9 comparisons of high-dose TIV (TIV-HD) versus TIV: 5 showed TIV-HD dominated TIV, and 4 showed the results depended on WTP. There were 8 comparisons of adjuvanted TIV (TIV-ADJ) versus TIV: 4 showed TIV-ADJ dominated TIV, and 4 showed the results depended on WTP. There were few pairwise comparisons among QIV, TIV-HD, and TIV-ADJ.ConclusionsThe evidence suggests QIV, TIV-HD, and TIV-ADJ are cost-effective against TIV for a WTP threshold of $50 000 per quality-adjusted life-year. Future studies should include new and existing vaccine options for broad age ranges and use more robust methodologies—such as real-world evaluations or modeling studies accounting for methodological, structural, and parameter uncertainty.     

Fc functional antibody responses to adjuvanted versus unadjuvanted seasonal influenza vaccination in community-dwelling older adults

BackgroundSeasonal influenza vaccination with a standard trivalent influenza vaccine (TIV) induces a modest, and cross-reactive, Fc functional antibody response in older adults. Recent improvements to influenza vaccines include a quadrivalent influenza vaccine (QIV) and a TIV adjuvanted with the squalene-based oil-in-water emulsion MF59.MethodsPre- and post-vaccination serum samples from older adults vaccinated with QIV (n = 27) and adjuvanted TIV (n = 44) were studied using hemagglutination inhibition (HAI) assays and dimeric Fc-gamma receptor IIIa binding ELISAs, as a surrogate of antibody-dependent cellular cytotoxicity (ADCC).ResultsWe found that the unadjuvanted QIV elicited a stronger HAI response against the H1N1 vaccine virus than the adjuvanted TIV. Post-vaccination levels of HA-specific ADCC antibodies were similar for older adults vaccinated with QIV and adjuvanted TIV. The ADCC response to influenza vaccination was largely determined by pre-vaccination or baseline levels of these antibodies, with older adults with low baseline levels of ADCC activity demonstrating greater post-vaccination rises.ConclusionsIn this cohort of community-dwelling older adults, the QIV was at least as good as the adjuvanted TIV in the induction of ADCC and HAI responses. Further studies on how these antibody responses translate to efficacy in preventing influenza infections are warranted.     

Cost-Effectiveness of Routine Childhood Vaccination Against Seasonal Influenza in Germany

ObjectivesIn Germany, routine influenza vaccination with quadrivalent influenza vaccines (QIV) is recommended and reimbursed for individuals ≥60 years of age and individuals with underlying chronic conditions. The present study examines the cost-effectiveness of a possible extension of the recommendation to include strategies of childhood vaccination against seasonal influenza using QIV.MethodsA dynamic transmission model was used to examine the epidemiological impact of different childhood vaccination strategies. The outputs were used in a health economic decision tree to calculate the costs per quality-adjusted life year (QALY) gained from a societal and a third-party payer (TPP) perspective. Strain-specific epidemiology, vaccine uptake, and vaccine efficacy data from the 10 non-pandemic seasons from 2003/2004 to 2013/2014 were used, and cost data were drawn mainly from a health insurance claims data analysis and supplemented by estimates from literature. Uncertainty is explored via scenario, deterministic, and probabilistic sensitivity analyses.ResultsVaccinating 2- to 9-year-olds with QIV assuming a vaccine uptake of 40% is cost-saving with a benefit–cost ratio of 1.66 from a societal perspective and an incremental cost-effectiveness ratio of €998/QALY from a TPP perspective. Lower and higher vaccine uptakes show marginal effects, while extending the target group to 2- to 17-year-olds further increases the health benefits while still being below the willingness-to-pay (WTP) threshold. Assuming no vaccine-induced herd protection has a negative effect on the cost-effectiveness ratio, but childhood vaccination remains cost-effective.ConclusionRoutine childhood vaccination against seasonal influenza in Germany is most likely to be cost-saving from a societal perspective and highly cost-effective from a TPP perspective.     

Comparison of the immunogenicity and safety of quadrivalent and tetravalent influenza vaccines in children and adolescents

BackgroundChildren and adolescents are susceptible to influenza. Vaccination is the most important strategy for preventing influenza, yet there are few studies on the immunogenicity and safety of quadrivalent inactivated influenza vaccine (QIV) containing two A strains (H1N1 and H3N2) and two B lineages (Victoria and Yamagata). Therefore, to further clarify the immunogenicity and safety of QIV in children and adolescents, a meta-analysis was performed to provide a reference for the development of influenza prevention strategies.MethodsPubMed, EMBASE and Cochrane Library were searched for articles published as of February 12, 2019. Random clinical trials comparing the immunogenicity and safety of QIV and TIV among children and adolescents were selected. The main outcomes were comparisons of immunogenicity (seroprotection rate [SPR] and seroconversion rate [SCR] and adverse events using risk ratios (RRs). The meta-analysis was performed using random-effects models.ResultsAmong the 6 months up to 3 years group, QIV showed a higher SPR for B lineages than for TIV-B/Yamagata, with pooled RRs of 3.07 (95% CI: 2.58–3.66) and 1.06 (95% CI: 1.01–1.11), respectively. For the 3 years through 18 years, QIV had a higher SCR and SPR for the Yamagata lineage than for TIV-B/Victoria, with pooled RRs of 2.30 (95% CI: 1.83–2.88) and 1.16 (95% CI: 1.03–1.30), respectively. Compared to TIV-B/Yamagata, a higher SCR and SPR for the Victoria lineage was found for QIV, with RRs of 3.09 (95% CI: 1.99–4.78) and 1.72 (95% CI: 1.22–2.41), respectively. Regarding adverse events, only pain was more frequently reported for QIV than TIV ; the RR was 1.09 (95% CI: 1.02–1.17).ConclusionsThe immunogenicity of QIV for common ingredients was similar to that of TIV, but the former exhibited significantly higher immunogenicity for the unique lineage. QIV also had the same reliable safety as TIV.     

A cost-effectiveness analysis of South Africa’s seasonal influenza vaccination programme

BackgroundSeasonal influenza imposes a significant health and economic burden in South Africa, particularly in populations vulnerable to severe consequences of influenza. This study assesses the cost-effectiveness of South Africa’s seasonal influenza vaccination strategy, which involves vaccinating vulnerable populations with trivalent inactivated influenza vaccine (TIV) during routine facility visits. Vulnerable populations included in our analysis are persons aged ≥ 65 years; pregnant women; persons living with HIV/AIDS (PLWHA), persons of any age with underlying medical conditions (UMC) and children aged 6–59 months.MethodWe employed the World Health Organisation’s (WHO) Cost Effectiveness Tool for Seasonal Influenza Vaccination (CETSIV), a decision tree model, to evaluate the 2018 seasonal influenza vaccination campaign from a public healthcare provider and societal perspective. CETSIV was populated with existing country-specific demographic, epidemiologic and coverage data to estimate incremental cost-effectiveness ratios (ICERs) by comparing costs and benefits of the influenza vaccination programme to no vaccination.ResultsThe highest number of clinical events (influenza cases, outpatient visits, hospitalisation and deaths) were averted in PLWHA and persons with other UMCs. Using a cost-effectiveness threshold of US$ 3 400 per quality-adjusted life year (QALY), our findings suggest that the vaccination programme is cost-effective for all vulnerable populations except for children aged 6–59 months. ICERs ranged from ~US$ 1 750 /QALY in PLWHA to ~US$ 7 500/QALY in children. In probabilistic sensitivity analyses, the vaccination programme was cost-effective in pregnant women, PLWHA, persons with UMCs and persons aged ≥65 years in >80% of simulations. These findings were robust to changes in many model inputs but were most sensitive to uncertainty in estimates of influenza-associated illness burden.ConclusionSouth Africa's seasonal influenza vaccination strategy of opportunistically targeting vulnerable populations during routine visits is cost-effective. A budget impact analysis will be useful for supporting future expansions of the programme.     

A Phase III randomised trial of the immunogenicity and safety of quadrivalent versus trivalent inactivated subunit influenza vaccine in adult and elderly subjects,assessing both anti-haemagglutinin and virus neutralisation antibody responses

BackgroundTrivalent influenza vaccines (TIVs) offer substantial protection against matching B-strains, however, protection against alternate-lineage B-strains may be enhanced by adding a second B-strain in quadrivalent influenza vaccines (QIVs). In this Phase III, double-blind, multicentre, randomised study, the immunogenicity and safety of subunit inactivated QIV versus TIV was assessed in adult (aged ≥18 to ≤60 years) and elderly (aged ≥61 years) subjects by analysing a combination of haemagglutinin inhibition (HI) and virus neutralisation (VN).MethodsSubjects (n = 1980) were recruited off season (2015/2016) from 20 centres in five European countries and randomised to receive either QIV (n = 1538), TIV with B-strain of the Victoria lineage (n = 221) or TIV with B-strain of the Yamagata lineage (n = 221). The primary aim was to demonstrate non-inferiority of QIV to TIV for immunogenicity against matched influenza strains based on post-vaccination HI titres. Secondary aims were to show superiority of QIV to TIV for immunogenicity against alternate-lineage B-strains and to characterise the immune response by reverse cumulative distribution (RCD) curves of antibody titres and derived serological parameters for HI and VN. Reactogenicity and occurrence of adverse events were assessed post-vaccination.ResultsQIV elicited a non-inferior immune response for matched strains (upper limit of 95% CI for HI geometric mean ratios [GMRs] <1.5) and a superior response for alternate-lineage B-strains (HI GMRs < 1; p < 0.0001) versus TIV. RCD curves demonstrated that post-vaccination HI and VN titres were higher for QIV versus TIV for both alternate-lineage B-strains. Seroconversion rates and geometric mean fold increases of the VN assay were consistent with the HI assay for all strains in QIV. Reporting rates of local and systemic reactions were similar in both vaccine groups.ConclusionsQIV was non-inferior in immunogenicity to TIV for matched strains and superior to the alternate-lineage B-strains in TIV. Safety and tolerability profiles of QIV and TIV were comparable.     

Cost-effectiveness of introducing an MF59-adjuvanted trivalent influenza vaccine for older adults in Argentina

IntroductionInfluenza surveillance in Argentina reported influenza-like illness at a rate of 3500/100,000, a hospitalization rate of 15.5/100,000, and a death rate of 0.32/100,000 annually in adults aged over 65 years. The high burden of disease may be due to a combination of immunosenescence and the suboptimal clinical effectiveness of conventional, non-adjuvanted influenza vaccines in this age group. There is a clinical need for more effective influenza vaccines in this population. This study evaluated the cost-effectiveness of an MF59®-adjuvanted trivalent influenza vaccine (aTIV) in adults aged over 65 years in Argentina compared with the non-adjuvanted trivalent influenza vaccine (TIV) used under the current national vaccination policy.MethodsA decision tree cost-effectiveness model was developed to estimate the cost-effectiveness of switching from TIV to aTIV in Argentinian older adults. The model compared cost and health benefits of vaccination in one influenza season from the payer perspective. The main predictions included survival, quality-adjusted survival, and costs. Model inputs were sourced from Argentina or internationally where local data was considered inaccurate. Vaccine efficacy assumptions were extracted from recently published, peer-reviewed scientific literature.ResultsSwitching from TIV to aTIV would result in 170 deaths averted and 1310 incremental quality-adjusted life years (QALYs) gained. The incremental cost-effectiveness ratio per QALY was US $2660.59 from the payer perspective. In all sensitivity analyses, aTIV remained highly cost-effective. The probabilistic sensitivity analyses showed a 95% CI per QALY of US $113.74–7721.67.ConclusionIntroducing an adjuvanted influenza vaccine in Argentina is potentially beneficial and cost-effective relative to the currently-used TIV through the reduction of disease burden and utilization of healthcare resources.     

Post-marketing surveillance of adverse events following immunization with inactivated quadrivalent and trivalent influenza vaccine in health care providers in Western Australia

In 2015, inactivated quadrivalent influenza vaccine (QIV) was first introduced into the Australian market. A routine vaccine safety surveillance system in Western Australia was used to conduct post-licensure surveillance of adverse events following immunization with inactivated QIV and trivalent influenza vaccines (TIV) in a sample of 1685 healthcare providers (HCPs). A similar percentage of HCPs who received QIV reported having any reaction seven days post-vaccination as HCPs who received TIV (13.6 vs. 12.8%, respectively; p = 0.66). However, a slightly higher percentage of HCPs who received QIV reported pain or swelling at the injection site as compared to HCPs who received TIV (6.9% vs. 4.2%, respectively; p = 0.02). No serious vaccine-associated adverse events were detected during follow-up of either vaccine. Acknowledging the study limitations, the results of this post-marketing surveillance support the safety of QIV, suggesting there is little difference in the reactogenicity of QIV as compared to TIV.     

Immunogenicity,reactogenicity, and safety of inactivated quadrivalent influenza vaccine candidate versus inactivated trivalent influenza vaccine in healthy adults aged ≥18 years: A phase III,randomized trial

Background

Two influenza B lineages have been co-circulating since the 1980s, and because inactivated trivalent influenza vaccine (TIV) contains only one B strain, it provides little/no protection against the alternate B-lineage. We assessed a candidate inactivated quadrivalent influenza vaccine (QIV) containing both B lineages versus TIV in healthy adults.

Methods

Subjects received one dose of QIV (lot 1, 2, or 3) or one of two TIVs (B strain from Victoria or Yamagata lineage); randomization was 2:2:2:1:1. Hemagglutination-inhibition assays were performed 21-days post-vaccination; superiority of QIV versus TIV for the alternate B-lineage was demonstrated if the 95% confidence interval (CI) lower limit for the GMT ratio was ≥1.5, and non-inferiority against the shared strains was demonstrated if the 95% CI upper limit for the GMT ratio was ≤1.5. Reactogenicity and safety were assessed during the post-vaccination period. NCT01196975.

Results

Immunogenicity of QIV lots was consistent, QIV was superior to TIV for the alternate B-lineage strain, and QIV was non-inferior versus TIVs for shared strains (A/H1N1, A/H3N2, B-strain). Reactogenicity and safety profile of the QIV was consistent with seasonal influenza vaccines.

Conclusion

QIV provided superior immunogenicity for the added B strain without affecting the antibody response to the TIV strains, and without compromising safety.     

Quadrivalent influenza vaccines in low and middle income countries: Cost-effectiveness,affordability and availability

In high-income countries, there is an increased tendency to replace inactivated seasonal trivalent influenza (TIV) vaccines with quadrivalent (QIV) vaccines as these are considered to give a greater public health benefit. In addition, several recent studies from the USA and Europe indicate that replacement with QIV might also be cost-effective; however, the situation in low- and middle-income countries (LMIC) is less clear as few studies have investigated this aspect.The paper by de Boer et al. (2018) describes a dynamic modelling study commissioned by WHO that suggests that in LMICs, under certain conditions, QIV might also be more cost-effective than TIV. In this commentary, we discuss some important aspects that policymakers in LMICs might wish to take into account when considering replacing TIV by QIV.Indeed, from the data presented in the paper by de Boer et al. it can be inferred that replacing QIV for TIV would mean a 25–29% budget increase for seasonal influenza vaccination in South Africa and Vietnam, resulting in an incremental influenza-related health impact reduction of only 7–8% when a 10% symptomatic attack rate is assumed. We argue that national health budget considerations in LMIC might lead decision-makers to choose other investments with higher health impact for a budget equivalent to roughly a quarter of the yearly TIV immunization costs.In addition to an increased annual cost that would be associated with a decision to replace TIV with QIV, there would be an increased pressure on manufacturers to produce QIV in time for the influenza season requiring manufacturers to produce some components of the seasonal vaccine at risk prior to the WHO recommendations for influenza vaccines.Unless the current uncertainties, impracticalities and increased costs associated with QIVs are resolved, TIVs are likely to remain the more attractive option for many LMICs. Each country should establish its context-specific process for decision-making based on national data on disease burden and costs in order to determine whether the health gains out-weigh the additional cost of moving to QIV. For example, immunizing more people in the population, especially those in higher risk groups, with TIV might not only provide better value for money but also deliver better health outcomes in LMICs.Countries with local influenza vaccine manufacturing capacity should include in their seasonal influenza vaccine procurement process an analysis of the pros- and cons- of TIV versus QIV, to ensure both feasibility and sustainability of local manufacturing.     

Efficacy and safety of a quadrivalent influenza vaccine in children aged 6–35 months: A global,multiseasonal, controlled,randomized Phase III study

BackgroundChildren are an important target group for influenza vaccination, but few studies have prospectively evaluated influenza vaccine efficacy (VE) in children under 3 years of age. This was a randomized Phase III trial to assess the efficacy, immunogenicity, and safety of an inactivated quadrivalent influenza vaccine (QIV) in young children (EudraCT: 2016–004904–74).MethodsInfluenza-naïve children aged 6–35 months were randomized during three influenza seasons to receive vaccination with QIV or a non-influenza control vaccine. One group of participants was revaccinated with QIV in the subsequent influenza season. The primary efficacy endpoint was the absolute VE of QIV against influenza caused by any circulating strain. Key secondary efficacy endpoints included the absolute VE of QIV against influenza due to antigenically matching strains and immunogenicity. Safety and reactogenicity were also evaluated.ResultsIn total, 1005 children received QIV and 995 received control vaccine. Influenza A/B infection due to any circulating influenza strain occurred less frequently in children who received QIV versus children receiving a control vaccine. The absolute VE of QIV against any circulating influenza strain was 54% (95% confidence interval [CI]: 37%, 66%). The absolute VE of QIV against antigenically matching influenza strains was 68% (95% CI: 45%, 81%). Mean hemagglutination inhibition titers for all influenza strains in the QIV group increased post-vaccination, whereas increases were minimal in the control vaccine group; results from virus neutralization and neuraminidase-inhibition assays were generally consistent with the hemagglutination inhibition assay findings. Approximately 12 months after primary vaccination with QIV, antibody titers remained higher than pre-vaccination titers for most strains. In participants who were revaccinated, QIV elicited strong antibody responses. The overall safety profile and reactogenicity of QIV was comparable with control vaccine.ConclusionPrimary vaccination with QIV was well tolerated and effective in protecting children aged 6–35 months against influenza.     

Modelling the optimal target age group for seasonal influenza vaccination in Japan

BackgroundIn Japan, the current influenza vaccination programme is targeting older individuals. On the other hand, epidemics of influenza are likely to be mainly driven by children. In this study, we consider the most cost-effective target age group for a seasonal influenza vaccination programme in Japan.MethodsWe constructed a deterministic compartmental Susceptible-Exposed-Infectious-Recovered (SEIR) model with data from the 2012/13 to 2014/15 influenza seasons in Japan. Bayesian inference with Markov Chain Monte Carlo method was used for parameter estimation. Cost-effectiveness analyses were conducted from public health care payer’s perspective.ResultsA scenario targeting children under 15 was expected to reduce the number of cases 6,382,345 compared to the current strategy. A scenario targeting elderly population (age over 49 years) was expected to reduce the number of cases 693,206. The children targeted scenario demonstrated negative ICER (incremental cost-effectiveness ratio) value. On the other hand, elderly targeted scenario demonstrated higher ICER value than the willingness to pay (50,000 USD/QALY).ConclusionsA vaccination programme which targets children under 15 is predicted to have much larger epidemiological impact than those targeting elderly.     

四价流感病毒灭活疫苗在18~64岁人群免疫原性和安全性的系统综述和Meta分析

目的 用Meta分析的方法评价四价流感病毒灭活疫苗在18~64岁人群的免疫原性（抗体保护率和抗体阳转率）。方法 检索Medline、Cochrane Library、Science Direct数据库,将近10年内发表的比较18~64岁人群接种四价流感病毒灭活疫苗和三价流感病毒灭活疫苗免疫原性的临床随机对照试验纳入分析。采用Revman 5.3软件对纳入文献数据进行Meta分析。结果 共纳入8篇文献,针对甲型流感株（A/H1N1、A/H3N2）的抗体保护率和抗体阳转率,两种疫苗的反应差异无统计学意义;针对不含乙型流感株B/Victoria的三价流感病毒灭活疫苗,四价流感病毒灭活疫苗抗体保护率的合并RR值为1.28（95% CI：1.08~1.51,P<0.05）,抗体阳转率的合并RR值为1.94（95% CI：1.50~2.50,P<0.05）;针对不含乙型流感株B/Yamagata的三价流感病毒灭活疫苗,四价流感病毒疫苗抗体保护率的合并RR值为1.10（95% CI：1.02~1.18,P<0.05）,抗体阳转率的合并RR值为1.99（95% CI：1.34~2.97,P<0.05）,差异有统计学意义。结论 18~64岁人群中,四价流感病毒灭活疫苗与三价流感病毒灭活疫苗对于相同的疫苗株产生的免疫原性无差异,对于三价流感病毒灭活疫苗中不含的乙型疫苗株能产生良好的免疫效果。     

Cost effectiveness of trivalent and quadrivalent influenza vaccines in 50- to 64-year-old adults in Korea

BackgroundInfluenza causes severe complications in at-risk populations, resulting in significant morbidity and mortality. Vaccination is the most effective measure to prevent infection and complications caused by seasonal influenza. However, no study has analyzed the cost-effectiveness of influenza vaccines in 50- to 64-year-olds in South Korea.ObjectiveWe examined the application of the National Immunization Program (NIP) in 50- to 64-year-olds and compared the cost-effectiveness of quadrivalent influenza vaccine (QIV) with that of trivalent influenza vaccine (TIV) in South Korea.MethodsOne-year static model was assumed by constructing separate decision trees for age subgroups: 50–54, 55–59, and 60–64. Each subgroup was divided into at-risk and not-at-risk groups. Using circulation data from previous studies and Korea Centers for Disease Control and Prevention, we estimated the probabilities of influenza infection, outpatient treatment, hospitalization, and deaths. Medical cost was estimated from 2015 to 2017 National Health Insurance Sharing Service claim data, while productivity losses from work absenteeism or death were estimated from labor and economic surveys of Korean government. Disutility was estimated based on previous studies.ResultsCompared with non-vaccination, incremental cost-effectiveness ratios (ICERs) for the 50–54, 55–59, and 60–64 age groups for TIV were US$2010.90, US$2004.58, and US$1865.55, respectively, while for QIV were US$2187.17, US$2190.89, and US$2074.52, respectively. Compared with TIV, ICERs for QIV were US$4445.66, US$4578.06, and US$4751.93, respectively. All the aforementioned ICER values were lower than the 2017 Korean GDP per capita of US$29,742.839.ConclusionImplementing the NIP in the 50- to 64-year-old age group was found to be cost effective. Since both TIV and QIV were cost effective, we recommend QIV as the preferred option, based on its greater protection against Influenza B.     

Simulation studies to assess the long-term effects of Japan’s change from trivalent to quadrivalent influenza vaccination

BackgroundSince 2013/2014, the WHO has been recommending quadrivalent influenza vaccines (QIV) to prevent seasonal influenza. In 2015, Japan replaced trivalent influenza vaccines (TIV) by QIV. We used computer simulations to calculate how this impacted the epidemiology and to assess its cost-effectiveness.MethodsWe simulated the seasonal transmission of the four influenza strains A(H1N1), A(H3N2), B/Yamagata and B/Victoria with the individual-based simulation tool 4Flu, using official demographic data and Japanese contact patterns. The model considered maternal protection, immunity boosting, new drift variants and different immunity durations for naturally acquired and vaccination-derived immunity. Starting with the 2015/16 season, simulations were evaluated for 20 years, using either TIV or QIV with the reported vaccination coverage. Costs and years of life saved (YOLSs) were calculated and discounted at 2%, using 2015 as base year.ResultsQIV annually prevents on average 548 influenza cases (4.7% of cases which occur when using TIV; 11.9% of influenza B), 1.62 hospitalizations and 0.078 deaths per 100,000 individuals. In Japan’s population of 125.35 million, annually 91.51 YOLSs are gained by QIV and 10.75 million USD are saved (societal perspective). From payer perspective, the ICER is 3698 USD/YOLS.ConclusionsQIV is cost-effective (payer perspective) or even cost-saving (societal perspective) in Japan.     

Immunogenicity and safety of inactivated quadrivalent influenza vaccine in adults: A systematic review and meta-analysis of randomised controlled trials

BackgroundA quadrivalent influenza vaccine (QIV) includes two A strains (A/H1N1, A/H3N2) and two B lineages (B/Victoria, B/Yamagata). The presence of both B lineages eliminate potential B lineage mismatch of trivalent influenza vaccine (TIV) with the circulating strain.MethodsElectronic database searches of Medline, Embase, Cochrane Central Register of Controlled Trials (CCRCT), Scopus and Web of Science were conducted for articles published until June 30, 2015 inclusive. Articles were limited to randomised controlled trials (RCTs) in adults using inactivated intramuscular vaccine and published in English language only. Summary estimates of immunogenicity (by seroprotection and seroconversion rates) and adverse events outcomes were compared between QIV and TIV, using a risk ratio (RR). Studies were pooled using inverse variance weights with a random effect model and the I² statistic was used to estimate heterogeneity.ResultsA total of five RCTs were included in the meta-analysis. For immunogenicity outcomes, QIV had similar efficacy for the three common strains; A/H1N1, A/H3N2 and the B lineage included in the TIV. QIV also showed superior efficacy for the B lineage not included in the TIV; pooled seroprotection RR of 1.14 (95%CI: 1.03–1.25, p = 0.008) and seroconversion RR of 1.78 (95%CI: 1.24–2.55, p = 0.002) for B/Victoria, and pooled seroprotection RR of 1.12 (95%CI: 1.02–1.22, p = 0.01) and seroconversion RR of 2.11 (95%CI: 1.51–2.95, p < 0.001) for B/Yamagata, respectively. No significant differences were found between QIV and TIV for aggregated local and systemic adverse events within 7 days post-vaccination. There were no vaccine-related serious adverse events reported for either QIV or TIV. Compared to TIV, injection-site pain was more common for QIV, with a pooled RR of 1.18 (95%CI: 1.03–1.35, p = 0.02).ConclusionIn adults, inactivated QIV was as immunogenic as seasonal TIV, with equivalent efficacy against the shared three strains included in TIV, and a superior immunogenicity against the non-TIV B lineage.