Efficacy and immunogenicity of high-dose influenza vaccine in older adults by age,comorbidities, and frailty

BackgroundA randomized trial demonstrated that a high-dose inactivated influenza vaccine (IIV-HD) was 24.2% more efficacious than a standard-dose vaccine (IIV-SD) against laboratory-confirmed influenza illness in adults ≥65 years. To evaluate the consistency of IIV-HD benefits, supplemental analyses explored efficacy and immunogenicity by baseline characteristics of special interest.MethodsDouble-blind, randomized, active-controlled, multicenter trial. Adults ≥65 years were randomized 1:1 to receive IIV-HD or IIV-SD and followed for 6–8 months postvaccination for the occurrence of influenza. One third of participants were randomly selected to provide sera for measurement of hemagglutination inhibition antibody (HAI) titers. Efficacy (IIV-HD vs. IIV-SD) against laboratory-confirmed, protocol-defined influenza-like illness (PD-ILI) and HAI geometric mean titer (GMT) ratios (IIV-HD/IIV-SD) were evaluated by age, and number of high-risk comorbid and frailty conditions.ResultsEfficacy (95% confidence intervals) of IIV-HD relative to IIV-SD against laboratory-confirmed PD-ILI was 19.7% (0.4%; 35.4%) for participants 65–74 years, 32.4% (8.1%; 50.6%) for those ≥75 years, 22.1% (3.9%; 37.0%) for participants with ≥1 high-risk comorbidity, 23.6% (−3.2%; 43.6%) for those with ≥2 high-risk comorbidities, 27.5% (0.4%; 47.4%) for persons with 1 frailty condition, 23.9% (−9.0%; 47.2%) for those with 2 frailty conditions, and 16.0% (−16.3%; 39.4%) for those with ≥3 frailty conditions. There was no evidence of vaccine efficacy heterogeneity within age, comorbidity, and frailty strata (P-values 0.351, 0.875, and 0.838, respectively). HAI GMT ratios were significantly higher among IIV-HD recipients for all strains and across all subgroups.ConclusionsEstimates of relative efficacy consistently favored IIV-HD over IIV-SD. There was no significant evidence that baseline age, comorbidity, or frailty modified the efficacy of IIV-HD relative to IIV-SD. IIV-HD significantly improved HAI responses for all strains and in all subgroups. IIV-HD is likely to provide benefits beyond IIV-SD for adults ≥65 years, irrespective of age and presence of comorbid or frailty conditions.     

Effectiveness of 2009 pandemic influenza A(H1N1) vaccines: A systematic review and meta-analysis

BackgroundThe clinical effectiveness of monovalent influenza A(H1N1)pdm09 vaccines has not been comprehensively summarised. We undertook a systematic review and meta-analysis to assess vaccine effectiveness (VE) for adjuvanted and unadjuvanted vaccines.MethodsWe searched healthcare databases and grey literature from 11 June 2009 to 12 November 2014. Two researchers independently assessed titles and abstracts to identify studies for full review. Random effects meta-analyses estimated the pooled effect size of vaccination compared to placebo or no vaccination for crude and adjusted odds ratios (OR) to prevent laboratory confirmed influenza illness (LCI) and related hospitalization. VE was calculated as (1-pooled OR) 1 100. Narrative synthesis was undertaken where meta-analysis was not possible.ResultsWe identified 9229 studies of which 38 at moderate risk of bias met protocol eligibility criteria; 23 were suitable for meta-analysis. Pooled adjusted VE against LCI with adjuvanted and unadjuvanted vaccines both reached statistical significance (adjuvanted: VE = 80%; 95% confidence interval [CI] 59–90%; unadjuvanted: VE = 66%; 95% CI 47–78%); in planned secondary analyses, VE in adults often failed to reach statistical significance and pooled point estimates were lower than observed in children. Overall pooled adjusted VE against hospitalization was 61% (95% CI 14–82%); in planned secondary analyses, adjusted VE attained statistical significance in adults aged 18–64 years and children for adjuvanted vaccines. Adjuvanted vaccines were significantly more effective in children compared to adults for both outcomes.ConclusionsAdjuvanted and unadjuvanted monovalent influenza A(H1N1)pdm09 vaccines were both effective in preventing LCI. Overall, the vaccines were also effective against influenza-related hospitalization. For both outcomes adjuvanted vaccines were more effective in children than in adults.     

Parental perceptions of childhood seasonal influenza vaccination in Singapore: A cross-sectional survey

PurposeSeasonal influenza vaccination is recommended in children aged 6–59 months, but little is known about child vaccination coverage and determinants in Asian settings. We report the results of a survey of knowledge, attitudes, practices, and determinants of child influenza vaccination in Singapore.MethodsIn December 2015-March 2016, we conducted a survey of 332 parents of children aged 6 months to 5 years attending pre-schools. We assessed child influenza vaccine coverage and parental knowledge, attitudes, and practices of child influenza vaccination. We used multivariable regression and structural equation models to identify factors associated with child influenza vaccination.ResultsKnowledge about influenza, perceived benefit of vaccination, and willingness to vaccinate were high. However, only 32% of children had ever received influenza vaccine, and only 15% in the past year. Factors independently associated with child influenza vaccination included: being recommended influenza vaccine by a child’s doctor (prevalence ratio (PR) = 2.47, 95% CI: 1.75–3.48); receiving influenza vaccine information from a private general practitioner (PR = 1.47, 95% CI: 1.05–2.04); regularly receiving pre-travel influenza vaccine (PR = 1.64, 95% CI: 1.19–2.25); higher willingness to vaccinate (PR = 1.58, 95% CI:1.24–2.04 per unit increase in willingness score); and feeling well-informed about influenza vaccine (PR = 1.44, 95% CI: 1.04–1.99). Parents who obtained influenza vaccine information from television were less likely to have vaccinated their child (PR = 0.44, 95% CI: 0.23–0.85). Path analysis indicated that being recommended vaccination by a child's doctor increased willingness to vaccinate and self-efficacy (feeling well-informed about influenza vaccine). Median willingness-to-pay for a dose of influenza vaccine was SGD30 (interquartile range: SGD20-SGD50), and was higher in parents of vaccinated compared with unvaccinated children (SGD45 vs SGD30, p = 0.0012).ConclusionKnowledge and willingness to vaccinate was high in this parent population, but influenza vaccine uptake in children was low. Encouraging medical professionals to recommend vaccination of eligible children is key to improving uptake.     

Efficacy and safety of high-dose influenza vaccine in elderly adults: A systematic review and meta-analysis

IntroductionOlder adults are prioritized for influenza vaccination but also have lowered antibody responses to the vaccine. Higher-doses of influenza antigen may increase immune response and thus be more effective. Our objectives were to compare the efficacy and safety of the high-dose influenza vaccine to the standard-dose influenza vaccine in the elderly (age > 65).MethodsData sources: Randomized trials (RCTs) from Medline (Ovid), EMBASE (Ovid), Cochrane Library (Wiley), ClinicalTrials.gov, reference lists of relevant articles, and gray literature.Study selection: Two reviewers independently identified RCTs comparing high-dose influenza vaccine (60 μg of hemagglutinin per strain) to standard-dose influenza vaccine (15 μg of hemagglutinin per strain) in adults over the age of 65 years.Data extraction: Two reviewers independently extracted trial-level data including population characteristics, interventions, outcomes, and funding sources. Risk of bias was assessed using the Cochrane Risk of Bias tool.ResultsWe included seven eligible trials; all were categorized as having a low (n = 3) or unclear (n = 4) risk of bias. Patients receiving the high-dose vaccine had significantly less risk of developing laboratory-confirmed influenza infections (Relative Risk 0.76, 95%CI 0.65 to 0.90; I² 0%, 2 trials, 41,141 patients). Post-vaccination geometric mean titres and seroprotection rates were also higher in high-dose vaccine recipients. There were no protocol-defined serious adverse events in the included trials in either group.ConclusionsIn elderly adults, the high-dose influenza vaccine was well-tolerated, more immunogenic, and more efficacious in preventing influenza infections than the standard-dose vaccine. Further pragmatic trials are needed to determine if the higher efficacy translates into higher vaccine effectiveness in adults over the age of 65.     

Safety of Russian-backbone seasonal trivalent,live-attenuated influenza vaccine in a phase II randomized placebo-controlled clinical trial among children in urban Bangladesh

IntroductionLive-attenuated influenza vaccines (LAIVs) have the potential to be affordable, effective, and logistically feasible for immunization of children in low-resource settings.Material and methodsWe conducted a phase II, randomized, double-blind, parallel group, placebo-controlled trial on the safety of the Russian-backbone, seasonal trivalent LAIV among children aged 24 through 59 months in Dhaka, Bangladesh in 2012. After vaccination, we monitored participants for six months with weekly home visits and study clinic surveillance for solicited and unsolicited adverse events, protocol-defined wheezing illness (PDWI), and serious adverse events (SAEs), including all cause hospitalizations.ResultsThree hundred children were randomized and administered LAIV (n = 150) or placebo (n = 150). No immediate post-vaccination reactions occurred in either group. Solicited reactions were similar between vaccine and placebo groups during the first 7 days post-vaccination and throughout the entire trial. There were no statistically significant differences in participants experiencing PDWI between LAIV and placebo groups throughout the trial (n = 13 vs. n = 16, p = 0.697). Of 131 children with a history of medical treatment or hospitalization for asthma or wheezing at study entry, 65 received LAIV and 66 received placebo. Among this subset, there was no statistical difference in PDWI occurring throughout the trial between the LAIV or placebo groups (7.7% vs. 19.7%, p = 0.074). While there were no related SAEs, LAIV recipients had six unrelated SAEs and placebo recipients had none. These SAEs included three due to traumatic injury and bone fracture, and one each due to accidental overdose of paracetamol, abdominal pain, and acute gastroenteritis. None of the participants with SAEs had laboratory-confirmed influenza, wheezing illness, or other signs of acute respiratory illness at the time of their events.ConclusionsIn this randomized, controlled trial among 300 children aged 24 through 59 months in urban Bangladesh, Russian-backbone LAIV was safe and well tolerated. Further evaluation of LAIV safety and efficacy in a larger cohort is warranted.     

Efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RV5) in healthy Chinese infants: A randomized,double-blind,placebo-controlled trial

BackgroundA randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RotaTeq™, RV5) against rotavirus gastroenteritis (RVGE).Methods4040 participants aged 6–12 weeks were enrolled and randomly assigned to either 3 oral doses of RV5 (n = 2020) or placebo (n = 2020), administered ∼4 weeks apart. The participants also received OPV and DTaP in a concomitant or staggered fashion. The primary objective was to evaluate vaccine efficacy (VE) against naturally-occurring RVGE at least 14 days following the third dose. Key secondary objectives included: VE against naturally-occurring severe RVGE and VE against severe and any-severity RVGE caused by rotavirus serotypes contained in the vaccine, occurring at least 14 days after the third dose. All adverse events (AEs) were collected for 30 days following each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. (ClinicalTrials.gov registry: NCT02062385).ResultsVE against RVGE of any-severity caused by any serotype was 69.3% (95% CI: 54.5, 79.7). The secondary efficacy analysis showed an efficacy of: 78.9% (95% CI: 59.1, 90.1) against severe RVGE caused by any serotype; 69.9% (95% CI: 55.2, 80.3) and 78.9% (95% CI: 59.1, 90.1) against any-severity and severe RVGE caused by serotypes contained in the vaccine, respectively. Within 30 days following any vaccination, 53.5% (1079/2015) and 53.3% (1077/2019) of participants reported at least one AE, and 5.8% (116/2015) and 5.7% (116/2019) reported SAEs in the vaccine and placebo groups, respectively. No SAEs were considered vaccine-related in recipients of RV5. Two intussusception cases were reported in recipients of RV5 who recovered after receiving treatment. Neither was considered vaccine-related.ConclusionsIn Chinese infants, RV5 was efficacious against any-severity and severe RVGE caused by any serotype and generally well-tolerated with respect to AEs.     

Safety and immunogenicity of an inactivated cell culture-derived H7N9 influenza vaccine in healthy adults: A phase I/II,prospective, randomized,open-label trial

BackgroundWe conducted a phase I/II clinical trial to evaluate the safety and immunogenicity of a Madin-Darby canine kidney (MDCK) cell-grown inactivated H7N9 influenza vaccine for pandemic preparedness purposes.MethodsBetween April 7, 2015 and May 27, 2016, healthy adults aged 20–60 years were enrolled sequentially in phase I (n = 40) and phase II (n = 160) from three hospitals in Taiwan and randomized to receive 2 doses of whole-virus H7N9 vaccine (15 or 30 μg hemagglutinin antigen (HA) with or without an aluminum hydroxide adjuvant) at 21-day intervals. Safety up to 180 days and changes in hemagglutinin inhibition (HI) titers at 21 days after each vaccination were determined.ResultsOf the 200 randomized subjects, 193 (96.5%) received 2 doses of the study vaccine and were included in the intention-to-treat analysis for safety, and 190 (95%) were included in the per-protocol analysis for immunogenicity. Most adverse events were mild and transient; no death or vaccine-related serious adverse events were reported. Overall, higher immune responses were observed in the groups administered with 30 μg HA formulation than in the other two groups administered with 15 μg HA formulation. The highest immune response was observed in subjects who received 2 doses of the adjuvanted vaccine containing 30 μg HA with HI titer, seroprotection rate, seroconversion rate, and seroconversion factor of 36.2, 64.6%, 64.6% and 5.7, respectively.ConclusionsOur study demonstrated that the H7N9 influenza vaccine containing 30 µg HA with aluminum hydroxide adjuvant was immunogenic and safe in adults aged 20–60 years.CLINICALTRIALS.GOV identifier: NCT02436928.     

Birth outcomes for Australian mother-infant pairs who received an influenza vaccine during pregnancy, 2012–2014: The FluMum study

IntroductionIn Australia, influenza vaccination is recommended for all women who will be pregnant during the influenza season. Vaccine safety and effectiveness are key concerns and influencers of uptake for both vaccine providers and families. We assessed the safety of receiving an influenza vaccination during any trimester of pregnancy with respect to preterm births and infant birthweight.MethodsWe conducted a nested retrospective cohort study of ‘FluMum’ participants (2012–2014). Our primary exposure of interest was influenza vaccination during pregnancy. The primary outcomes of interest were infant birthweight and weeks’ gestation at birth for live singleton infants. Analyses included comparisons of these birth outcomes by vaccination status and trimester of pregnancy an influenza vaccine was given. We calculated means, proportions, and relative risks and performed multivariable logistic regression for potential confounding factors.ResultsIn the 7126 mother-infant pairs enrolled in this study, mean maternal age at infant birth was 31.7 years. Influenza vaccine uptake in pregnancy was 34%. Most mothers with a known date of vaccination received a vaccine in the second trimester (51%). Those mothers with a co-morbidity or risk factor were 13% more likely to have influenza vaccine during pregnancy compared to other mothers (RR 1.13, 95% CI 1.04–1.24, p = 0.007). Mean weeks’ gestation at birth was 38.7 for the vaccinated and 38.8 for the unvaccinated group (p = 0.051). Infants in the vaccinated group weighed 15 g less in birthweight compared to the unvaccinated infants (95% CI −12.8 to 42.2, p = 0.29).ConclusionResults arising from this large Australian cohort study are reassuring with respect to two critical safety outcomes; preterm births and low infant birthweights. Studies examining a broader range of birth outcomes following influenza vaccination during pregnancy are required, particularly now that maternal vaccination in pregnancy has expanded to include pertussis as well as influenza.     

Efectividad de la vacuna de la gripe para prevenir casos graves. Temporada 2018/2019

ObjectiveTo know the effectiveness of the 2018/2019 flu vaccine for the prevention of severe cases of flu in a tertiary hospital.MethodCase-control study. We included all patients hospitalized with influenza confirmed by laboratory during 2018/2019 season. Those who met the criteria of severe case of influenza (pneumonia, multiorgan failure, septic shock, ICU admission or death) were considered as cases. Non severe cases of influenza were included in the control group. We calculated the effectiveness of the raw and adjusted vaccine (to prevent severe cases of influenza) and its 95% confidence interval using formula VE = (1 − odds ratio) × 100.ResultsEffectiveness of flu vaccine adjusted by age group and comorbidities was 60.7% (20.5-80.5). In the analysis adjusted and restricted to each sex, age group and presence of comorbidities, the influenza vaccine had a positive effect in all groups and categories, with effectiveness in the age group 65 years or more being 55.0% (2.6-79.2).ConclusionsFlu vaccination reduced the severity of influenza in hospitalized patients. These findings should be taken into account to improve vaccination strategies and achieve better vaccination coverage in the high-risk population in order not only to decrease flu cases, but also their severity.     

Effectiveness of adenovirus type 5 vectored and inactivated COVID-19 vaccines against symptomatic COVID-19, COVID-19 pneumonia,and severe COVID-19 caused by the B.1.617.2 (Delta) variant: Evidence from an outbreak in Yunnan,China, 2021

BackgroundIn partial response to the coronavirus disease 2019 (COVID-19) pandemic, countries around the world are conducting large-scale vaccination campaigns. Real-world estimates of vaccine effectiveness (VE) against the B.1.617.2 (Delta) variant are still limited. An outbreak in Ruili city of China provided an opportunity to evaluate VE against the Delta variant of two types of COVID-19 vaccines in use in China and globally – inactivated (CoronaVac and BBIBP-CorV) and adenovirus type 5 vectored (Convidecia) vaccines.MethodsWe estimated VE using a retrospective cohort study two months after the Ruili vaccination campaign (median: 63 days). Close contacts of infected people (Chinese nationality, 18 years and above) were included to assess VE against symptomatic Covid-19, COVID-19 pneumonia, and severe COVID-19. We calculated the relative risks (RR) of the outcomes for unvaccinated compared with fully vaccinated individuals. We used logistic regression analyses to estimate adjusted VEs, controlling for gender and age group (18–59 years and 60 years and over).We compared unvaccinated and fully vaccinated individuals on duration of RT-PCR positivity and Ct value.FindingsThere were 686 close contacts eligible for VE estimates. Adjusted VE of ad5-vectored vaccine was 61.5% (95% CI, 9.5–83.6) against symptomatic COVID-19, 67.9% (95%CI: 1.7–89.9) against pneumonia, and 100% (95%CI: 36.6–100) against severe/critical illness. For the two inactivated vaccines, combined VE was 74.6% (95% CI, 36.0–90.0) against symptomatic COVID-19, 76.7% (95% CI: 19.3–93.3) against pneumonia, and 100% (95% CI: 47.6–100) against severe/critical COVID-19. There were no statistically significant differences in VE between two inactivated vaccines for symptomatic COVID-19 and for pneumonia, nor were there statistically significant differences between inactivated and ad5-vectored VE in any of the three outcomes. The median durations of RT-PCR positivity were 17 days for fifteen people vaccinated with an inactivated vaccine, 18 days for forty-four people vaccinated with the Ad5 vectored vaccine, and 26 days for eleven unvaccinated individuals. InterpretationThese results provide reassuring evidence that the three vaccines are effective at preventing Delta-variant COVID-19 in short term following vaccination campaign, and are most effective at preventing more serious illness. The findings of reduced duration of RT-PCR positivity and length of hospital stay associated with full vaccination suggests potential saving of health-care system resources.     

Improving influenza and Tdap vaccination during pregnancy: A cluster-randomized trial of a multi-component antenatal vaccine promotion package in late influenza season

BackgroundEvidence-based interventions to improve influenza vaccine coverage among pregnant women are needed, particularly among those who remain unvaccinated late into the influenza season. Improving rates of antenatal tetanus, diphtheria and acellular pertussis (Tdap) vaccination is also needed.PurposeTo test the effectiveness of a practice-, provider-, and patient-focused influenza and Tdap vaccine promotion package on improving antenatal influenza and Tdap vaccination in the obstetric setting.MethodsA cluster-randomized trial among 11 obstetric practices in Georgia was conducted in 2012–2013. Intervention practices adopted the intervention package that included identification of a vaccine champion, provider-to-patient talking points, educational brochures, posters, lapel buttons, and iPads loaded with a patient-centered tutorial. Participants were recruited from December 2012–April 2013 and included 325 unvaccinated pregnant women in Georgia. Random effects regression models were used to evaluate primary and secondary outcomes.ResultsData on antenatal influenza and Tdap vaccine receipt were obtained for 300 (92.3%) and 291 (89.5%) women, respectively. Although antenatal influenza and Tdap vaccination rates were higher in the intervention group than the control group, improvements were not significant (For influenza: risk difference (RD) = 3.6%, 95% confidence interval (CI): −4.0%, 11.2%; for Tdap: RD = 1.3%, 95% CI: −10.7%, 13.2%). While the majority of intervention package components were positively associated with antenatal vaccine receipt, a provider's recommendation was the factor most strongly associated with actual receipt, regardless of study group or vaccine.ConclusionsThe intervention package did not significantly improve antenatal influenza or Tdap vaccine coverage. More research is needed to determine what motivates women remaining unvaccinated against influenza late into the influenza season to get vaccinated. Future research should quantify the extent to which clinical interventions can bolster a provider's recommendation for vaccination. This study is registered with clinicaltrials.gov, study ID NCT01761799.     

Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine and an MF59-adjuvanted influenza vaccine after concomitant vaccination in ⩾60-year-old adults

BackgroundConcomitant administration of influenza and pneumococcal vaccines could be an efficient strategy to increase vaccine uptake among older adults. Nevertheless, immune interference and safety issues have been a concern when more than one vaccines are administered at the same time.MethodsSubjects aged ⩾60 years were randomized in a 1:1:1 ratio to receive MF59-adjuvanted trivalent inactivated influenza vaccine (MF59-aTIV) + 13-valent pneumococcal conjugate vaccine (PCV13) (Group 1), PCV13 alone (Group 2), or MF59-aTIV alone (Group 3). Hemagglutination inhibition (HI) and opsonophagocytic activity (OPA) assays were used to compare immunogenicity after single or concomitant vaccination.ResultsA total of 1149 subjects (Group 1, N = 373; Group 2, N = 394; Group 3, N = 382) were available for the assessment of immunogenicity and safety. All groups met immunogenicity criteria for the influenza vaccine in older adults with similar seroprotection rates, seroconversion rates, and geometric mean titer (GMT) fold-increases, irrespective of concomitant vaccination. For each pneumococcal serotype, OPA titers increased markedly after the PCV13 vaccination, irrespective of the concomitant influenza vaccination. After concomitant administration, the non-inferiority criteria of GMT ratios were met for all three influenza subtypes and 13 pneumococcal serotypes. No vaccine-related serious adverse events occurred.ConclusionsConcomitant MF59-aTIV and PCV13 administration showed no interference with antibody response and showed good safety profiles.(Clinical Trial Number – NCT02215863).     

Lot-to-lot consistency,safety and immunogenicity of 3 lots of Haemophilus influenzae type b conjugate vaccine: results from a phase III randomized,multicenter study in infants

BackgroundVaccination against Haemophilus influenzae type b (Hib) is included in routine pediatric immunization schedule in the United States. Previous vaccine shortages have created the need for additional options for Hib vaccination.MethodsThis phase III, randomized, multi-centered study (NCT01000974) evaluated the safety and immunogenicity of a monovalent tetanus toxoid-conjugate Hib vaccine (Hib-TT) compared to a monovalent (Hib-TT control) and a combination Hib-TT vaccine. We hierarchically assessed lot-to-lot consistency of 3 Hib-TT lots and non-inferiority of Hib-TT to Hib-TT control. We co-administered routine pediatric vaccines with Hib-TT vaccines at 2, 4, 6 months (primary vaccination) and 15–18 months of age (booster vaccination). We recorded adverse events (AEs) for 4 (solicited) and 31 days (unsolicited) post-vaccination and serious AEs (SAEs) throughout the study.ResultsOf 4009 enrolled children, 3086 completed booster phase. Lot-to-lot consistency was not demonstrated. The study met statistical criteria for non-inferiority of Hib-TT to Hib-TT control in terms of immune responses to Hib and co-administered vaccines’ antigens, but not in terms of participants achieving post-primary vaccination anti-PRP levels ≥1 µg/mL. Because of the hierarchical nature of the objectives, non-inferiority could not be established. In all groups, 92.5–96.7% and 99.6–100% of participants achieved anti-PRP levels ≥0.15 µg/mL, while 78.3–89.8% and 97.9–99.1% had anti-PRP levels ≥1 µg/mL, post-primary and post-booster vaccination, respectively. Immune responses to co-administered vaccines and reported incidence of AEs were comparable among groups. We recorded SAEs for 107/2963 (3.6%), 24/520 (4.6%), and 21/520 (4.0%) children post-primary vaccination, and 29/2337 (1.2%), 4/435 (0.9%), and 2/400 (0.5%) children post-booster vaccination with Hib-TT, Hib-TT control and combination Hib-TT vaccine, respectively; 6/5330 (0.1%) SAEs in the Hib-TT groups were considered vaccine-related.ConclusionHib-TT induced seroprotective antibody concentrations in the majority of participants and was well-tolerated when co-administered with routine pediatric vaccines according to a 3 + 1 schedule.     

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.     

Seasonal influenza vaccine effectiveness against medically attended influenza illness among children aged 6–59 months,October 2011–September 2012: A matched test-negative case–control study in Suzhou,China

BackgroundSeasonal influenza infections among young children in China lead to substantial numbers of hospitalizations and financial burden. This study assessed the seasonal influenza vaccine effectiveness (VE) against laboratory confirmed medically attended influenza illness among children in Suzhou, China, from October 2011–September 2012.MethodsWe conducted a test-negative case–control study among children aged 6–59 months who sought care at Soochow University Affiliated Children's Hospital (SCH) from October 2011–September 2012. A case was defined as a child with influenza-like illness (ILI) or severe acute respiratory infection (SARI) with an influenza-positive nasopharyngeal swab by rRT-PCR. Controls were selected from children presenting with ILI or SARI without laboratory confirmed influenza. We conducted 1:1 matching by age and admission date. Vaccination status was verified from the citywide immunization system database. VE was calculated with conditional logistic regression: (1 − OR) × 100%.ResultDuring the study period, 2634 children aged 6–59 months presented to SCH with ILI (1975) or SARI (659) and were tested for influenza. The vaccination records were available for 69% (1829; ILI: 1354, SARI: 475). Among those, 23% (427) tested positive for influenza, and were included as cases. Among influenza positive cases, the vaccination rates were 3.2% for SARI and 4.5% for ILI. Among controls, the vaccination rates were 13% for SARI, and 11% for ILI. The overall VE against lab-confirmed medically attended influenza virus infection was 67% (95% CI: 41–82). The VE for SARI was 75% (95% CI: 11–93) and for ILI was 64% (95% CI: 31–82).ConclusionsThe seasonal influenza vaccine was effective against medically attended lab-confirmed influenza infection in children aged 6–59 months in Suzhou, China in the 2011–12 influenza season. Increasing seasonal influenza vaccination among young children in Suzhou may decrease medically attended influenza-associated ILI and SARI cases in this population.     

Risk factors of ICU or high dependency requirements amongst hospitalized pediatric pertussis cases: A 10 year retrospective series,Singapore

IntroductionPertussis causes the highest complication rates and deaths in the infant group. Our study explored risk factors for ICU/high dependency (HD) admissions and intubation/non-invasive ventilation (NIV).MethodsA retrospective review of pertussis admissions over 10 years from 2007 to 2016 was done at KK Women's and Children's Hospital, Singapore. To understand risk factors for severe pertussis infection, we compared cases requiring ICU/HD care with controls admitted to the general ward. Risk factors for intubation/NIV were also studied. Vaccine efficacy for protection against ICU/HD admission or intubation/NIV was also calculated.ResultsThere were 200 pertussis patients with a median age of 2.75 months. Sixty-one % were ≤3 months and 14.5% were <6 weeks old. Majority of patients (77%) had no prior pertussis vaccination. After removing 3 patients with missing vaccination records, 20 cases were compared with 177 controls. On univariate analysis, risk factors for ICU/HD admission comprised: Age ≤3 months, contact history, underlying co-morbidity, prematurity, absent DTaP vaccination, lymphocytosis, hyperleukocytosis (wbc ≥50 × 10⁹/L), thrombocytosis (platelet ≥500 × 10⁹/L), and pneumonia. Multivariate analysis revealed that age ≤3 months (OR 40, 95% CI 4.57–1111.11, p = .007), co-morbidity (OR 8.46 (95% CI 1.47–56.89, p = .019), pneumonia (OR 18.08, 95% CI 3.22–132.15, p = .002), white cell count (OR 1.07, 95% CI 1.01–1.14, p = .023) and cyanosis (OR 5.09, 95% CI 1.31–24.71, p = .026) were risk factors for ICU/HD admission. Prior DTaP vaccination had a vaccine effectiveness of 86.5% in preventing ICU/HD admission and 82.1% in preventing intubation/NIV.ConclusionsAs the majority of pertussis patients were infants ≤3 months old who are at high risk for ICU/HD admission and intubation/NIV, prevention is key to reducing pertussis morbidity. Even though not statistically significant, DTaP vaccination had a role in preventing ICU/HD admission and intubation/NIV.