Effectiveness of inactivated influenza vaccine in children by vaccine dose, 2013–18

ObjectivesWe assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) by vaccine dose in children aged 6 months to 12 years for whom two doses are recommended in Japan to ascertain the appropriate vaccine doses.MethodsVE was assessed according to a test-negative case-control design based on rapid influenza diagnostic test (RIDT) results. Children aged 6 months to 12 years with a fever ≥38 °C who had received an RIDT in outpatient clinics of 24 hospitals were enrolled for all five seasons since 2013/14. VE by vaccine dose (none vs. once or twice, and once vs. twice) was analyzed.ResultsIn the dose analysis, 20,033 children were enrolled. Both one- and two-dose regimens significantly reduced cases in preventing any influenza, influenza A, and influenza B, but there was no significant difference in adjusted VE between one- and two-dose regimens overall (adjusted OR, 0.560 [95% CI, 0.505–0.621], 0.550 [95% CI, 0.516–0.586]), 0.549 [95% CI, 0.517–0.583], and 1.014 [95% CI, 0.907–1.135], for none vs. once, none vs. twice, none vs. once or twice, and once vs. twice for any influenza, respectively). Both one- and two-dose regimens significantly reduced cases with any influenza and influenza A every season. Also, both regimens significantly reduced cases of any influenza, influenza A, and influenza B among children aged 1–12 years, especially among those aged 1–5 years. In the 2013/14, 2015/16, and 2016/17 seasons, however, only the two-dose regimen was significantly effective in preventing influenza B. Both one- and two-dose regimens significantly reduced cases involving hospitalization due to any influenza and influenza A.ConclusionsBoth one- and two-doses regimens of IIV were effective in preventing influenza for children aged 6 months to 12 years. The two-dose regimen was more effective against influenza B in some seasons.     

Three-season effectiveness of inactivated influenza vaccine in preventing influenza illness and hospitalization in children in Japan, 2013–2016

ObjectivesWe assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children 6 months to 15 years of age in 2015/16 season. In addition, based on the data obtained during the three seasons from 2013 to 2016, we estimated the three-season VE in preventing influenza illness and hospitalization.MethodsOur study was conducted according to a test-negative case-control design (TNCC) and as a case-control study based on influenza rapid diagnostic test results.ResultsDuring 2015/16 season, the quadrivalent IIV was first used in Japan. The adjusted VE in preventing influenza illness was 49% (95% confidence interval [CI]: 42–55%) against any type of influenza, 57% (95% CI: 50–63%) against influenza A and 34% (95% CI: 23–44%) against influenza B. The 3-season adjusted VE was 45% (95% CI: 41–49%) against influenza virus infection overall (N = 12,888), 51% (95% CI: 47–55%) against influenza A (N = 10,410), and 32% (95% CI: 24–38%) against influenza B (N = 9232). An analysis by age groups showed low or no significant VE in infants or adolescents. By contrast, VE was highest in the young group (1–5 years old) and declined with age thereafter. The 3-season adjusted VE in preventing hospitalization as determined in a case-control study was 52% (95% CI: 42–60%) for influenza A and 28% (95% CI: 4–46%) for influenza B, and by TNCC design, it was 54% (95% CI: 41–65%) for influenza A and 34% (95% CI: 6–54%) for influenza B.ConclusionWe demonstrated not only VE in preventing illness, but also VE in preventing hospitalization based on much larger numbers of children than previous studies.     

A real-world study evaluating the relative vaccine effectiveness of a cell-based quadrivalent influenza vaccine compared to egg-based quadrivalent influenza vaccine in the US during the 2017–18 influenza season

BackgroundCell-based influenza vaccine manufacturing reduces egg adaptations that can decrease vaccine effectiveness. We evaluated the relative vaccine effectiveness (rVE) of cell-based quadrivalent influenza vaccine (QIVc) compared to standard-dose egg-based quadrivalent influenza vaccines (QIVe-SD) against influenza-related and serious respiratory events among subjects 4–64 years of age during the 2017–18 influenza season.MethodsA retrospective cohort analysis was conducted using administrative claims data in the US (IQVIA PharMetrics Plus® database). Subjects vaccinated with QIVc or QIVe-SD from 8/2017–1/2018 were identified (date of vaccination termed the index date). Influenza-related hospitalizations/ER visits, all-cause hospitalizations and serious respiratory hospitalizations/ER visits were assessed post-vaccination. Inverse probability of treatment weighting (IPTW) and Poisson regression were used to evaluate the adjusted rVE of QIVc compared to QIVe-SD. In a subgroup analysis, rVE was assessed for several subgroups of interest (4–17, 18–64 and 50–64 years, and subjects with ≥1 high-risk condition). In a secondary economic analysis, annualized all-cause costs over the follow-up were compared using propensity score matching (PSM) and generalized estimating equation (GEE) models.ResultsThe study sample comprised 555,538 QIVc recipients and 2,528,524 QIVe-SD recipients. Prior to adjustment, QIVc subjects were older and had higher total costs in the 6-months pre-index. Following IPTW-adjustment and Poisson regression, QIVc was more effective in reducing influenza-related hospitalizations/ER visits, all-cause hospitalizations, and hospitalizations/ER visits related to asthma/COPD/bronchial events and other respiratory events compared to QIVe-SD. Similar trends were generally observed in the subgroup analysis. Following PSM adjustment and GEE regression, QIVe-SD was associated with significantly higher annualized all-cause total costs compared to QIVc, driven by higher costs for outpatient medical services and inpatient hospitalizations.ConclusionsAfter adjustment for confounders and selection bias, QIVc reduced influenza-related hospitalizations/ER visits, all-cause hospitalizations, and serious respiratory hospitalizations/ER visits compared to QIVe-SD. QIVc was associated with significantly lower all-cause total costs.     

A multi-country investigation of influenza vaccine coverage in pregnant individuals, 2010–2016

BackgroundMany countries recommend influenza vaccination during pregnancy. Despite this recommendation, influenza vaccine among pregnant individuals remains under-utilized and uptake varies by country. Factors associated with influenza vaccine uptake during pregnancy may also vary across countries.MethodsAs members of the Pregnancy Influenza Vaccine Effectiveness Network (PREVENT), five sites from four countries (Australia, Canada, Israel, and the United States) retrospectively identified cohorts of individuals aged 18–50 years who were pregnant during pre-defined influenza seasons. Influenza vaccine coverage estimates were calculated for the 2010–11 through 2015–16 northern hemisphere and the 2012 through 2015 southern hemisphere influenza seasons, by site. Sites used electronic health records, administrative data, and immunization registries to collect information on pregnancy, health history, demographics, and vaccination status. Each season, vaccination coverage was calculated as the percentage of individuals who received influenza vaccine among the individuals in the cohort that season. Characteristics were compared between those vaccinated and unvaccinated, by site.ResultsMore than two million pregnancies were identified over the study period. Influenza vaccination coverage ranged from 5% to 58% across sites and seasons. Coverage increased consistently over the study period at three of the five sites (Western Australia, Alberta, and Israel), and was highest in all seasons at the United States study site (39–58%). Associations with vaccination varied by country and across seasons; where available, parity >0, presence of a high-risk medical condition, and urban residence were consistently associated with increased likelihood of vaccination.ConclusionsThough increasing, uptake of influenza vaccine among pregnant individuals remains lower than recommended. Coverage varied substantially by country, suggesting an ongoing need for targeted strategies to improve influenza vaccine uptake in this population.     

Seasonal influenza vaccine effectiveness against influenza in 2012–2013: A hospital-based case-control study in Lithuania

Background

Due to scarce information on seasonal influenza vaccine effectiveness (SIVE) against severe clinical influenza outcomes in risk populations, we conducted a case-control study to assess its effects against laboratory-confirmed influenza in hospitalized patients during the 2012–2013 influenza season.

Methods

We conducted a test-negative case-control study among ≥18 years old patients with influenza-like illness (ILI) hospitalized in two Lithuanian hospitals. Cases were influenza A(H1N1), A(H3) or influenza B positive by RT-PCR, and controls were influenza negative. Additional demographic and clinical data to assess the role of confounding were collected. SIVE and its confidence intervals (95% CI) were estimated by using multivariate logistic regression as (1 − OR) × 100%.

Results

The sample consisted of 185 subjects. Seasonal influenza vaccine uptake was 5%. Among 111 (60%) influenza positive cases, 24.3% were A(H1N1), 10.8% were A(H3) and 24.3% were influenza B cases. Unadjusted SIVE was 79% (95% CI −6% to 96%) and after the adjustment it increased to 86% (95% CI 19% to 97%).

Conclusions

Seasonal influenza vaccination in 2012–2013 was associated with reduced occurrence of laboratory-confirmed influenza, but due to low sample size the estimate of SIVE is imprecise. Given high prevalence of influenza in hospitalized ILI cases and low influenza vaccination coverage, there is a need to increase influenza vaccination rates.     

Comparison of vaccine effectiveness against influenza hospitalization of cell-based and egg-based influenza vaccines, 2017–2018

Egg-based influenza vaccines could be less effective than cell-based vaccine due to adaptive mutations acquired for growth. We conducted a test-negative case-control study at Kaiser Permanente Southern California to assess vaccine effectiveness (VE) against hospitalization for laboratory-confirmed influenza during 2017–2018. Among the 1186 cases and 6946 controls, 74% and 59%, respectively, were ages ≥ 65 years. For any influenza, the adjusted relative VE of cell-based vaccine versus egg-based vaccines was 43% (95% CI: −45% to 77%) for patients ages < 65 years and 6% (95% CI: −46% to 39%) for patients ages ≥ 65 years. For influenza A(H3N2), the adjusted relative VE was 61% (95% CI: −63% to 91%) for patients ages < 65 years and −4% (95% CI: −70% to 37%) for patients ages ≥ 65 years. Statistically significant protection against influenza hospitalization of cell-based vaccine compared to egg-based vaccines was not observed, but further studies in additional influenza seasons are warranted.     

Safety and immunogenicity of high-dose trivalent inactivated influenza vaccine in adults 50–64 years of age

BackgroundIndividuals 50–64 years of age have reduced immune responses to influenza vaccines. The current study examined whether a high-dose inactivated trivalent influenza vaccine (IIV3-HD) might improve immune responses over a standard-dose inactivated influenza vaccine (IIV3-SD) in this age group.MethodsThis was a multicenter, observer-blinded, randomized, active-controlled phase II trial. Adults 50–64 years of age were randomized 1:1 to receive IIV3-HD or IIV3-SD. Hemagglutination inhibition titers were measured before and 28 days after vaccination. Reactogenicity was recorded for 7 days after vaccination and adverse events for 28 days.Results148 participants received IIV3-HD and 152 received IIV3-SD. For all vaccine strains, day 28 geometric mean hemagglutination inhibition titers were significantly higher in the IIV3-HD group than in the IIV3-SD group (geometric mean titer ratio [95% confidence interval (CI)] = 1.43 [1.04–1.97] for A/H1N1, 1.65 [1.21–2.25] for A/H3N2, and 1.60 [1.23–2.08] for B). Seroconversion rates were significantly higher in the IIV3-HD group than in the IIV3-SD group for strains A/H3N2 and B but not A/H1N1 (difference [95% CI] = 13.5% [4.76–22.0] for A/H3N2, 23.1% [11.7–33.6] for B, and −0.2% [−9.66 to 9.18] for A/H1N1). The post-vaccination seroprotection rate was significantly higher in the IIV3-HD group than in the IIV3-SD group for strain B but not for strains A/H1N1 or A/H3N2 (difference = 9.1% [2.95–15.7] for B, 2.0% [−0.907 to 5.68] for A/H1N1, and 0.6% [−3.14 to 4.43] for A/H3N2). Reactogenicity was higher in the IIV3-HD group than in the IIV3-SD group, but reactions were mostly of low intensity, transient, and self-limited. Rates of unsolicited adverse events were similar between groups. No serious AEs, AEs leading to early withdrawal, or deaths were reported.ConclusionsThe study suggests that in adults 50–64 years of age, IIV3-HD may improve immunogenicity compared to IIV3-SD while maintaining an acceptable safety profile.     

Assessment of influenza vaccine effectiveness in a sentinel surveillance network 2010–13, United States

BackgroundInfluenza vaccines are now widely used to reduce the burden of annual epidemics of influenza virus infections. Influenza vaccine effectiveness (VE) is monitored annually to determine VE against each season's circulating influenza strains in different groups such as children, adults and the elderly. Few prospective surveillance programs are available to evaluate influenza VE against medically attended illness for patients of all ages in the United States.MethodsWe conducted surveillance of patients with acute respiratory illnesses in 101 clinics across the US during three consecutive influenza seasons. We analyzed laboratory testing results for influenza virus, self-reported vaccine history, and patient characteristics, defining cases as patients who tested positive for influenza virus and controls as patients who tested negative for influenza virus. Comparison of influenza vaccination coverage among cases versus controls, adjusted for potential confounders, was used to estimate VE as one minus the adjusted odds ratio multiplied by 100%.ResultsWe included 10,650 patients during three influenza seasons from August 2010 through December 2013, and estimated influenza VE in children 6m–5y of age (58%; 95% CI: 49%–66%), children 6–17y (45%; 95% CI: 34%–53%), adults 18–49y (36%; 95% CI: 24%, 46%), and adults ≥50y (34%, 95% CI: 13%, 51%). VE was higher against influenza A(H1N1) compared to A(H3N2) and B.ConclusionsOur estimates of moderate influenza VE confirm the important role of vaccination in protecting against medically attended influenza virus infection.     

The faces of influenza vaccine recommendation: A Literature review of the determinants and barriers to health providers’ recommendation of influenza vaccine in pregnancy

IntroductionWHO recommends influenza vaccination for pregnant women and health providers (HPs), yet global uptake for both is persistently low. Research suggests that HPs greatly influence uptake of influenza vaccine in pregnant women. Our review studies HPs’ recommendation of influenza vaccine to pregnant women, determinants and barriers to recommendation, and the role that HPs may play in global influenza vaccine coverage.MethodsWe undertook a comprehensive global review of literature relating to HPs’ recommendation of seasonal influenza vaccines to pregnant women and the determinants and barriers to recommendation and how this may vary by country and context. We evaluated data from each study including frequency of HP recommendation, vaccine coverage, determinants and barriers to recommendation, and the odds of recommending. We tracked the frequency of determinants and barriers to recommendation in heat maps and organized data by world regions and income classifications.ResultsFrom 32 studies in 15 countries, we identified 68 determinants or barriers to HPs’ recommendation. Recommendation rates were highest (77%) in the Americas and lowest in South East Asia (18%). A HP’s own influenza vaccine status was a main determinant of recommendation in multiple country contexts and from different provider types. Financial barriers to recommendation were present in higher-income countries and policy-related barriers were highlighted in lower-income countries. HP perceptions of safety, efficacy, and the utility of vaccine were the most frequently cited barriers, relevant in almost every context.ConclusionsHP recommendation is important to influenza vaccine implementation in pregnant women. A HP’s own status is an important recommendation determinant in multiple contexts. Vaccine program implementation plans should consider the impact of HPs' knowledge, awareness and vaccine confidence on their own uptake and recommendation practices, as well as on the uptake among pregnant women. Addressing safety and efficacy concerns is relevant in all contexts for HPs and pregnant women.     

On the bias of estimates of influenza vaccine effectiveness from test–negative studies

Estimates of the effectiveness of influenza vaccines are commonly obtained from a test-negative design (TND) study, where cases and controls are patients seeking care for an acute respiratory illness who test positive and negative, respectively, for influenza infection. Vaccine effectiveness (VE) estimates from TND studies are usually interpreted as vaccine effectiveness against medically-attended influenza (MAI). However, it is also important to estimate VE against any influenza illness (symptomatic influenza (SI)) as individuals with SI are still a public health burden even if they do not seek medical care. We present a numerical method to evaluate the bias of TND-based estimates of influenza VE with respect to MAI and SI. We consider two sources of bias: (a) confounding bias due to a (possibly unobserved) covariate that is associated with both vaccination and the probability of the outcome of interest and (b) bias resulting from the effect of vaccination on the probability of seeking care. Our results indicate that (a) VE estimates may suffer from substantial confounding bias when a confounder has a different effect on the probabilities of influenza and non-influenza ARI, and (b) when vaccination reduces the probability of seeking care against influenza ARI, then estimates of VE against MAI may be unbiased while estimates of VE against SI may be have a substantial positive bias.     

Seasonal influenza vaccine coverage among high-risk populations in Thailand, 2010–2012

BackgroundThe Advisory Committee on Immunization Practice of Thailand prioritizes seasonal influenza vaccinations for populations who are at highest risk for serious complications (pregnant women, children 6 months–2 years, persons ≥65 years, persons with chronic diseases, obese persons), and healthcare personnel and poultry cullers. The Thailand government purchases seasonal influenza vaccine for these groups. We assessed vaccination coverage among high-risk groups in Thailand from 2010 to 2012.MethodsNational records on persons who received publicly purchased vaccines from 2010 to 2012 were analyzed by high-risk category. Denominator data from multiple sources were compared to calculate coverage. Vaccine coverage was defined as the proportion of individuals in each category who received the vaccine. Vaccine wastage was defined as the proportion of publicly purchased vaccines that were not used.ResultsFrom 2010 to 2012, 8.18 million influenza vaccines were publicly purchased (range, 2.37–3.29 million doses/year), and vaccine purchases increased 39% over these years. Vaccine wastage was 9.5%. Approximately 5.7 million (77%) vaccine doses were administered to persons ≥65 years and persons with chronic diseases, 1.4 million (19%) to healthcare personnel/poultry cullers, 82,570 (1.1%) to children 6 months–2 years, 78,885 (1.1%) to obese persons, 26,481 (0.4%) to mentally disabled persons, and 17,787 (0.2%) to pregnant women. Between 2010 and 2012, coverage increased among persons with chronic diseases (8.6% versus 14%; p < 0.01) and persons ≥65 years (12%, versus 20%; p < 0.01); however, coverage decreased for mentally disabled persons (6.1% versus 4.9%; p < 0.01), children 6 months–2 years (2.3% versus 0.9%; p < 0.01), pregnant women (1.1% versus 0.9%; p < 0.01), and obese persons (0.2% versus 0.1%; p < 0.01).ConclusionsFrom 2010 to 2012, the availability of publicly purchased vaccines increased. While coverage remained low for all target groups, coverage was highest among persons ≥65 years and persons with chronic diseases. Annual coverage assessments are necessary to promote higher coverage among high-risk groups in Thailand.     

Intradermally-administered influenza virus vaccine is safe and immunogenic in healthy adults 18–64 years of age

Background

To increase vaccine acceptance, intradermal (ID) influenza vaccine (Fluzone^® Intradermal, Sanofi Pasteur Inc.) may be an attractive alternative to intramuscular (IM) vaccination due to smaller needle and volume injected.

Methods

A multicenter, randomized (2:1 ID vs IM vaccines) study, blinded for ID vaccine lots, was conducted among 4292 adults 18–64 years of age enrolled in October 2008. Three lots of investigational trivalent influenza vaccine containing 9 μg hemagglutinin (HA) per strain in 0.1 mL administered ID with a 30 gauge, 1.5 mm long needle were compared to standard dose vaccine (0.5 mL containing 15 μg HA/strain) given IM.

Results

The post-vaccination antibody geometric mean titers (GMT) for the ID vaccine were similar to the IM vaccine (H1N1: 193.2 vs. 178.3, H3N2: 246.7 vs. 230.7, and B: 102.5 vs. 126.9). Non-inferiority was met for the ID vaccine compared to IM vaccine as assessed by antibody GMT ratios (IM/ID) for all three virus strains (H1N1: 0.92, H3N2: 0.94, and B: 1.24). Seroconversion rates were non-inferior for H1N1 and H3N2, but not for B (ID vs. IM: H1N1: 61.2% vs. 60.5%, H3N2: 75.3% vs. 74.8%, and B: 46.2% vs. 54.2%). Seroprotection (HAI titer ≥1:40) rates were similar between groups (ID vs. IM, H1N1: 91.1% vs. 91.7%, H3N2: 90.7% vs. 91.4%, and B: 87.4% vs. 89.3%). Local injection site reactions overall were more common with ID than IM vaccine (ID vs. IM: 89.2% vs. 60.2%), but were usually grade 1 or 2 and transient. The frequencies of local injection site pain and systemic reactions were similar between vaccine groups, except more myalgia with IM vaccine.

Conclusions

The ID vaccine elicited immune responses comparable to IM vaccine except for the seroconversion rate to B virus. With the exception of pain, local injection site reactions were more common with the ID vaccine, but well-tolerated and of short duration.

Trial registration

ClinicalTrials.gov identifier: NCT00772109.     

Immunogenicity and safety of a trivalent inactivated 2010–2011 influenza vaccine in Taiwan infants aged 6–12 months

This prospective study aimed to investigate the immune responses and safety of an influenza vaccine in vaccine-naïve infants aged 6–12 months, and was conducted from November 2010 to May 2011. Fifty-nine infants aged 6–12 months received two doses of trivalent inactivated influenza vaccine 4 weeks apart. Hemagglutination inhibition titers were measured 4 weeks after the two doses of study vaccine. Based on the assumption that a hemagglutination inhibition titer of 1:40 or greater against the antigen would be protective in adults, two doses of the study vaccine generated a protective immune response of 63.2% against influenza A(H1N1), 82.5% against influenza A(H3N2) and 38.6% against influenza B viruses in infants aged 6–12 months. The geometric mean fold rises against influenza type A and B viruses also met the European Medicines Agency criteria for flu vaccines. The solicited events within 7 days after vaccination were mild in intensity. No deaths or adverse events such as optic neuritis, cranial neuropathy, and brachial neuropathy or Guillain-Barre syndrome were reported. Two doses of inactivated influenza vaccine were well tolerated and induced a protective immune response against influenza in infants aged 6–12 months.     

Does pneumococcal vaccine reduce influenza morbidity in humans?

A retrospective study was conducted to verify the possibility that people immunized with pneumococcal vaccine (PV) show lower morbidity not only for pneumonia but also for influenza. A total of 450 individuals were enrolled between 1999 and 2003 and allocated to one of the following groups: (A) not vaccinated; (B) immunized with PV during 1999; (C) immunized with anti-influenza vaccine (Flu-V) each year; and (D) immunized with PV once in 1999 and Flu-V every consecutive year. People from group B showed significantly lower percentage of influenza-related diseases during the year 2000 in comparison with those from group A (p<0.01), whereas in the course of 2001 the morbidity of patients from group B was lower compared with the other groups (p<0.01). The results point to a way to decrease the morbidity of influenza-related diseases by immunization with PV only, at least for 2-3 years, avoiding Flu-V administration and permitting considerable saving for health care providers. Therefore, it is concluded that PV can reduce the morbidity of influenza at a greater rate than the Flu-V.     

Seasonal influenza vaccine supply and target vaccinated population in China, 2004–2009

To better understand the gap between limited influenza vaccine supply and the target population for vaccination in China, we conducted a retrospective survey to quantify the production capacity, supply and sale of seasonal trivalent inactive vaccine (TIV) from the 2004–2005 through the 2008–2009 season, and estimated the target population who should receive annual influenza vaccine. The maximum domestic capacity to produce TIV was 126 million doses in 2009. A total of 32.5 million doses of TIV were supplied in 2008–2009, with an average annual increase rate of 18% from 16.9 million in 2004–2005. This represents an amount sufficient to vaccinate 1.9% of Chinese population. The average number of doses of TIV for sale by province ranged from <5 to 108 per 1000 people. The differences are explained in part by level of economic development but also influenced by local reimbursement policies in some provinces. Based on national recommendations, we estimated a target population of 570.6 million or 43% of the total population. Supply and domestic production capacity for influenza vaccine is currently insufficient to vaccinate the estimated target population in China. The Government of China should consider measures to improve domestic production capacity of influenza vaccine, expand successful promotional campaigns, and add cost subsidies in high risk groups to further encourage influenza vaccine usage.     

Monitoring of influenza viruses in Western Siberia in 2008–2012

Western Siberia is of great importance in ecology and epidemiology of influenza. This territory is nesting area for great amount of bird species. Territorial relations of Western Siberian birds that are established during seasonal migration are extremely wide since this region is an intersection point of bird migration flows wintering in different regions of the world: Europe, Africa, Middle East, Central Asia, Hindustan, and South East Asia. Reassortant influenza viruses that can cause outbreak among population may emerge in Western Siberia with high probability. Thus, it is extremely important to carry out widespread study of circulated viruses, their molecular biological properties, phylogenetic links in this region, as well as herd immunity to influenza virus serotypes with epidemic potential.     

A postlicensure evaluation of the safety of Ann Arbor strain live attenuated influenza vaccine in children 24–59 months of age

Background

In the United States, live attenuated influenza vaccine (LAIV) was initially approved for use in individuals aged 5–49 years in 2003, which was extended to individuals aged 2–49 years in 2007. At that time, a postlicensure commitment was made to describe the safety of LAIV within a cohort of eligible children aged 2–5 years.

Methods

A prospective observational postmarketing study was conducted to evaluate the safety of LAIV. Rates of medically attended events (MAEs) and serious adverse events (SAEs) in eligible children aged 24–59 months receiving LAIV as part of routine care from October 2007 to March 2010 were compared with rates in a within-cohort self-control, as well as matched unvaccinated and matched trivalent inactivated influenza vaccine (TIV)-vaccinated controls. Children with asthma and other high-risk medical conditions before vaccination were excluded. All MAEs and SAEs through 42 days postvaccination and all hospitalizations and deaths through 6 months postvaccination were analyzed. Statistical significance was declared without multiplicity adjustment.

Results

A total of 28,226 unique LAIV recipients were matched with similar numbers of TIV-vaccinated and unvaccinated children. Of 4696 MAE incidence rate comparisons, 83 (1.8%) were statistically significantly higher and 221 (4.7%) were statistically significantly lower in LAIV recipients versus controls. No pattern of MAE rate differences suggested a safety signal with LAIV. Asthma/wheezing MAEs were not statistically increased in LAIV recipients. No anaphylaxis events occurred within 3 days postvaccination. Rates of SAEs were similar between LAIV and control groups.

Conclusions

Results of this postlicensure evaluation of LAIV safety in US children are consistent with preapproval clinical studies and Vaccine Adverse Event Reporting System reports, both of which demonstrated no significant increase in asthma/wheezing events or other adverse outcomes among eligible children aged 24–59 months who received LAIV.     

Is the adjuvanted influenza vaccine more effective than the trivalent inactivated vaccine in the elderly population? Results of a case–control study

Introduction

Influenza illness is an important public health problem and annual vaccination is globally recommended for high risk populations.

Objective

The aim was to evaluate and compare the effectiveness of influenza vaccines in reducing hospitalizations for influenza or pneumonia during two influenza seasons in the elderly.

Methods

A case–control study was performed, using administrative database of the Local Health Unit Roma-A (LHU RM-A). The included subjects were at least 65 years old and residing in one of the four districts of the LHU. The cases were hospitalized for influenza or pneumonia during influenza season in the years 2010–2011 and 2011–2012. The controls were hospitalized in the same period, but not for influenza or pneumonia. The subjects were immunized with the trivalent inactivated influenza vaccine (TIV) in the first influenza season (2010–2011) and with the adjuvanted influenza vaccine MF59 (ATIV) in the second season (2011–2012).

Results

A total of 269 cases and 1247 controls were included for the 2010–2011 influenza season, and 365 cases and 1227 controls were selected for the 2011–2012 season. Up to 63.6% cases and 53.5% controls in the 2010–2011 season and 78.6% of cases and 64.1% of controls in the 2011–2012 season have not been vaccinated. Female gender and high educational level were protective factors for hospitalization. Subjects over 75 years were at high risk of hospitalization compared to 65–74 years olds. Influenza vaccination reduced significantly hospitalization in both seasons. In subjects with 65–74 years TIV was more effective than ATIV; vice versa for those over 75 years old.

Discussion and conclusion

TIV and ATIV reduce hospitalization for influenza or pneumonia with a variable degree of protection in different age groups. In particular, ATIV is more effective in individuals over 75 years old.     

Association of spontaneous abortion with receipt of inactivated influenza vaccine containing H1N1pdm09 in 2010–11 and 2011–12

IntroductionInactivated influenza vaccine is recommended in any stage of pregnancy, but evidence of safety in early pregnancy is limited, including for vaccines containing A/H1N1pdm2009 (pH1N1) antigen. We sought to determine if receipt of vaccine containing pH1N1 was associated with spontaneous abortion (SAB).MethodsWe conducted a case-control study over two influenza seasons (2010–11, 2011–12) in the Vaccine Safety Datalink. Cases had SAB and controls had live births or stillbirths and were matched on site, date of last menstrual period, and age. Of 919 potential cases identified using diagnosis codes, 485 were eligible and confirmed by medical record review. Exposure was defined as vaccination with inactivated influenza vaccine before the SAB date; the primary exposure window was the 1–28 days before the SAB.ResultsThe overall adjusted odds ratio (aOR) was 2.0 (95% CI, 1.1–3.6) for vaccine receipt in the 28-day exposure window; there was no association in other exposure windows. In season-specific analyses, the aOR in the 1–28 days was 3.7 (95% CI 1.4–9.4) in 2010–11 and 1.4 (95% CI 0.6–3.3) in 2011–12. The association was modified by influenza vaccination in the prior season (post hoc analysis). Among women who received pH1N1-containing vaccine in the previous influenza season, the aOR in the 1–28 days was 7.7 (95% CI 2.2–27.3); the aOR was 1.3 (95% CI 0.7–2.7) among women not vaccinated in the previous season. This effect modification was observed in each season.ConclusionSAB was associated with influenza vaccination in the preceding 28 days. The association was significant only among women vaccinated in the previous influenza season with pH1N1-containing vaccine. This study does not and cannot establish a causal relationship between repeated influenza vaccination and SAB, but further research is warranted.