Cost-effectiveness analysis of catch-up hepatitis A vaccination among unvaccinated/partially-vaccinated children

BackgroundSince 2006, the US Centers for Disease Control and Prevention has recommended hepatitis A (HepA) vaccination routinely for children aged 12–23 months to prevent hepatitis A virus (HAV) infection. However, a substantial proportion of US children are unvaccinated and susceptible to infection. We present results of economic modeling to assess whether a one-time catch-up HepA vaccination recommendation would be cost-effective.MethodsWe developed a Markov model of HAV infection that followed a single cohort from birth through death (birth to age 95 years). The model compared the health and economic outcomes from catch-up vaccination interventions for children at target ages from two through 17 years vs. outcomes resulting from maintaining the current recommendation of routine vaccination at age one year with no catch-up intervention.ResultsOver the lifetime of the cohort, catch-up vaccination would reduce the total number of infections relative to the baseline by 741 while increasing doses of vaccine by 556,989. Catch-up vaccination would increase net costs by $10.2 million, or $2.38 per person. The incremental cost of HepA vaccine catch-up intervention at age 10 years, the midpoint of the ages modeled, was $452,239 per QALY gained. Across age-cohorts, the cost-effectiveness of catch-up vaccination is most favorable at age 12 years, resulting in an Incremental Cost-Effectiveness Ratio of $189,000 per QALY gained.ConclusionsGiven the low baseline of HAV disease incidence achieved by current vaccination recommendations, our economic model suggests that a catch-up vaccination recommendation would be less cost-effective than many other vaccine interventions, and that HepA catch-up vaccination would become cost effective at a threshold of $50,000 per QALY only when incidence of HAV rises about 5.0 cases per 100,000 population.     

Improved immunogenicity of high-dose influenza vaccine compared to standard-dose influenza vaccine in adult oncology patients younger than 65 years receiving chemotherapy: A pilot randomized clinical trial

PurposePatients undergoing chemotherapy often fail to develop robust responses to influenza vaccination. Compared to standard-dose influenza vaccine (SD), high-dose influenza vaccine (HD) has shown improved immunogenicity and protection against influenza illness in adults 65 years and older. This study compared the immunogenicity and tolerability of HD to SD in adults younger than 65 years of age receiving chemotherapy.MethodsThis double-blind study randomized patients receiving chemotherapy to vaccination with either SD or HD influenza vaccine. Hemagglutination inhibition assays (HAI) were performed prior to and 4 weeks after vaccination. HAI were summarized as geometric mean titers (GMT), seroconversion rates, and seroprotection rates.ResultsA total of 105 subjects were enrolled in the trial (51 received SD and 54 received HD). Subjects were well matched for demographic and medical conditions. Both vaccines were well tolerated with no SAEs. Of the 100 subjects with evaluable data, seroconversion rates for all 3 influenza antigens & post-vaccination GMTs for H3N2 & B strains were significantly improved with HD compared to SD. Seroprotection was excellent and equivalent in both groups.ConclusionsTrivalent high-dose influenza vaccine can be safely administered to patients receiving chemotherapy with improved immunogenicity and seroconversion compared to standard-dose vaccine. Post-vaccination seroprotection rates were similar in both groups. A larger study is needed to show clinical benefits with HD in this population.This study was registered at ClinicalTrials.gov as NCT01666782.     

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.     

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine compared with two trivalent inactivated influenza vaccines containing alternate B strains in adults: A phase 3, randomized noninferiority study

BackgroundVaccination is the most effective means of influenza prevention. Efficacy of trivalent vaccines may be enhanced by including both B strain lineages. This phase 3, double-blind study assessed the immunogenicity and safety/tolerability of a quadrivalent inactivated influenza vaccine (IIV4) versus the United States (US)-licensed 2014–2015 trivalent inactivated influenza vaccine (IIV3-Yamagata [IIV3-YAM]; Afluria) and IIV3 containing the alternate Victoria B strain (IIV3-VIC) in adults ≥18 years.MethodsParticipants (n = 3484) were randomized 2:1:1 and stratified by age to receive IIV4 (n = 1741), IIV3-YAM (n = 871), or IIV3-VIC (n = 872). The primary objective was to demonstrate noninferiority of the immunological response to IIV4 versus IIV3-YAM and IIV3-VIC. Noninferiority was assessed by hemagglutination inhibition geometric mean titer (GMT) ratio (IIV3/IIV4; upper bound of two-sided 95% confidence interval [CI] ≤ 1.5) and seroconversion rate (SCR) difference (IIV3 – IIV4; upper bound of two-sided 95% CI ≤ 10%) for vaccine strains. Solicited local and systemic adverse events (AEs) were assessed for 7 days postvaccination, AEs recorded for 28 days postvaccination, and serious AEs for 6 months postvaccination.ResultsIIV4 elicited a noninferior immune response for matched strains, and superior response for unmatched B strains not contained in IIV3 comparators. Adjusted GMT ratios (95% CI) for A/H1N1, A/H3N2, B/YAM, and B/VIC strains were 0.93 (0.88, 0.99), 0.93 (0.88, 0.98), 0.87 (IIV3-YAM; 0.82, 0.93), and 0.95 (IIV3-VIC; 0.88, 1.03), respectively. Corresponding values for SCR differences (95% CI) were −1.1 (−4.5, 2.3), −1.7 (−5.0, 1.7), −3.2 (IIV3-YAM; −7.4, 0.9), and −1.6 (IIV3-VIC; −5.8, 2.5). AEs were generally mild and experienced by 52.9% of participants. Serious AEs were reported with a slightly higher frequency with IIV4 (2.3%) versus IIV3-YAM (1.6%) and IIV3-VIC (1.5%).ConclusionsIIV4 demonstrated immunological noninferiority to the US-licensed IIV3, and superiority for unmatched B strains not contained in IIV3 comparators. Safety/tolerability profiles were similar across vaccine groups.Funding: Seqirus; Clinicaltrials.gov: NCT02214225.     

Predictors of influenza vaccination in the U.S. among children 9–13 years of age

Background and objectivesU.S. estimates of seasonal influenza (flu) vaccine uptake in 2014–2015 were 62% for 5–12 year olds, dropping to 47% for 13–17 year olds. The Healthy People 2020 goal for these age groups is 80%. It is important to understand factors associated with influenza vaccination, especially for those ages where rates begin to decline. The objective of this study was to identify factors associated with influenza vaccination acceptance in 9–13 year old children.MethodsAn online U.S. survey of mothers of children aged 9–13 assessed children's influenza vaccine uptake in the previous season, healthcare utilization, sociodemographics, and vaccine attitudes. Multivariable logistic regression identified independent predictors of influenza vaccine status.ResultsThere were 2363 respondents (Mean age = 38 years old). Referent children were 57% female and 66% non-minority race/ethnicity with a mean age of 10.6 years. By maternal report, 59% of children had received an influenza vaccine in the previous season. Predictors of influenza vaccine uptake included a recommendation or strong recommendation from a health care provider, seeing a health care provider in the past year, positive attitudes regarding the influenza vaccine, and being a minority race. Child gender, age, insurance coverage, and whether the child had a regular healthcare provider were not associated with influenza vaccine uptake (p = n.s.).ConclusionsThis sample reported overall rates of influenza vaccine uptake similar to national surveillance data, but still lower than national goals. Provider recommendations along with health attitudes and seeing a health care provider were associated with vaccine uptake. Promising interventions may include more directive physician messaging for influenza vaccine uptake in youth, encouraging more regular well-child visits during the adolescent years, and promoting influenza vaccination at alternative sites.     

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.     

The European I-MOVE Multicentre 2013–2014 Case-Control Study. Homogeneous moderate influenza vaccine effectiveness against A(H1N1)pdm09 and heterogenous results by country against A(H3N2)

BackgroundIn the first five I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe) influenza seasons vaccine effectiveness (VE) results were relatively homogenous among participating study sites. In 2013–2014, we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in six European Union (EU) countries to measure 2013–2014 influenza VE against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. Influenza A(H3N2) and A(H1N1)pdm09 viruses co-circulated during the season.MethodsPractitioners systematically selected ILI patients to swab within eight days of symptom onset.We compared cases (ILI positive to influenza A(H3N2) or A(H1N1)pdm09) to influenza negative patients. We calculated VE for the two influenza A subtypes and adjusted for potential confounders. We calculated heterogeneity between sites using the I² index and Cochrane's Q test. If the I² was <50%, we estimated pooled VE as (1 minus the OR) × 100 using a one-stage model with study site as a fixed effect. If the I² was >49% we used a two-stage random effects model.ResultsWe included in the A(H1N1)pdm09 analysis 531 cases and 1712 controls and in the A(H3N2) analysis 623 cases and 1920 controls. For A(H1N1)pdm09, the Q test (p = 0.695) and the I² index (0%) suggested no heterogeneity of adjusted VE between study sites. Using a one-stage model, the overall pooled adjusted VE against influenza A(H1N1)pdm2009 was 47.5% (95% CI: 16.4–67.0).For A(H3N2), the I² was 51.5% (p = 0.067). Using a two-stage model for the pooled analysis, the adjusted VE against A(H3N2) was 29.7 (95% CI: −34.4–63.2).ConclusionsThe results suggest a moderate 2013–2014 influenza VE against A(H1N1)pdm09 and a low VE against A(H3N2). The A(H3N2) estimates were heterogeneous among study sites. Larger sample sizes by study site are needed to prevent statistical heterogeneity, decrease variability and allow for two-stage pooled VE for all subgroup analyses.     

Reduced schedules of 4CMenB vaccine in infants and catch-up series in children: Immunogenicity and safety results from a randomised open-label phase 3b trial

BackgroundThis study evaluated the immunogenicity and safety of a licensed meningococcal serogroup B vaccine (4CMenB) administered alone according to reduced schedules in infants or catch-up series in children.MethodsIn this open-label, multicentre, phase 3b study (NCT01339923), infants randomised 1:1:1 received 4CMenB: 2 + 1 doses at 3½–5–11 months or 6–8–11 months of age, 3 + 1 doses at ages 2½–3½–5–11 months. Children aged 2–10 years received 2 catch-up doses administered 2 months apart. Immune responses were measured by hSBA assays against 4 strains specific for vaccine components fHbp, NadA, PorA and NHBA. Sufficiency of immune responses was defined in groups with 2 + 1 doses schedules as a lower limit ≥70% for the 97.5% confidence interval of the percentage of infants with hSBA titres ≥4, 1 month post-dose 2 for fHbp, NadA, PorA. Adverse events were collected for 7 days post-vaccination; serious adverse events (SAEs) throughout the study.Results754 infants and 404 children were enrolled. Post-primary vaccination, 98–100% of infants across all groups developed hSBA titres ≥4 for fHbp, NadA, PorA, and 48–77% for NHBA. Sufficiency of immune responses in infants receiving 2 + 1 schedules was demonstrated for fHbp, NadA, PorA after 2 doses of 4CMenB, as pre-specified criteria were met. Following receipt of 2 catch-up doses, 95–99% of children developed hSBA titres ≥4 for 4CMenB components. Similar safety profiles were observed across groups. A total of 45 SAEs were reported, 3 of which were related to vaccination.ConclusionReduced infant schedules and catch-up series in children were immunogenic and safe, having the potential to widen 4CMenB vaccine coverage.FundingGlaxoSmithKline Biologicals SA.     

Adolescent confidence in immunisation: Assessing and comparing attitudes of adolescents and adults

IntroductionThere is limited knowledge of adolescent views and attitudes towards immunisation. Our study investigated adolescent attitudes to immunisation and compared differences in vaccination attitudes between adolescents and adults.MethodsThis study was a cross-sectional, national online survey. Recruitment was stratified by state and gender to ensure findings were nationally representative. Regression analyses were performed to assess and compare adolescent and adult views on vaccine benefits, community protection, risks, side effects, sources of information, and decision-making preference.ResultsIn 2013, 502 adolescents and 2003 adults completed the online survey. Lower levels of vaccine confidence were observed in adolescents with adolescents less likely to believe vaccines are beneficial and/or safe compared to adults (p = 0.043). Compared to females, males were less confident of vaccine benefits (p < 0.05) but less concern about vaccine side effects (p < 0.05). Adolescents were more concerned about vaccine side effects than adults for pain (p < 0.001), redness or swelling (p < 0.001), and fever (p = 0.006). Adolescents were less likely than adults to consider health professionals (p < 0.001) and the media (e.g. internet) (p = 0.010) as important sources of information, and were more likely to seek information from social networks (p < 0.001) including families and schools. Although 62.0% of adolescents agreed that parents should make the decision about vaccination for them, adolescents were more likely to prefer a joint decision with parents (p < 0.001) or by themselves (p = 0.007) compared with adults.ConclusionAdolescents have a lesser understanding of vaccine safety and benefits than adults and have higher concerns about potential vaccine reactions. Improving adolescent awareness and knowledge of the benefits and risks of vaccination through school-based educational programs may improve confidence in and uptake of vaccines for adolescents and increase vaccine confidence in the next generation of parents.     

Public health impact of Rotarix vaccination among commercially insured children in the United States

BackgroundThis study (NCT01915888) assessed public health impact of Rotarix, GSK [RV1] vaccination.MethodsChildren born between 2007–2011 were identified from Truven Commercial Claims and Encounters Databases and observed until earlier of plan disenrollment or five years old. Children receiving one or two doses of RV1 during the vaccination window were assigned to incomplete and complete vaccination cohorts, respectively. Children without rotavirus (RV) vaccination (RV1 OR RotaTeq, Merck & Co., Inc. [RV5]) were assigned to the unvaccinated cohort. Claims with International Classification of Disease 9th edition (ICD-9) codes for diarrhea and RV infections were identified. First RV episode incidence, RV-related and diarrhea-related healthcare resource utilization were compared. Multivariate Poisson regression with generalized estimating equations was used to generate 95% confidence intervals (CIs) around incidence rate ratios (IRR) between cohorts while adjusting for gender, age and calendar year. Mean costs for first RV and diarrhea episodes were calculated with adjustment for gender and birth year; bootstrapping was used to determine statistically significant differences between cohorts.ResultsIncidence of first RV episodes was significantly reduced in complete and incomplete vaccination cohorts compared to the unvaccinated cohort (IRR = 0.17 [95%CI: 0.09–0.30] and IRR = 0.19 [95%CI: 0.06–0.58], respectively). RV-related inpatient, outpatient and emergency room (ER) visits were significantly lower for complete vaccination versus unvaccinated cohort. Diarrhea-related inpatient and ER visit rates were significantly lower for complete vaccination versus unvaccinated cohorts; outpatient rates were similar. RV-related and diarrhea-related resource utilization rates were significantly lower or no different for incomplete vaccination versus unvaccinated cohort. Compared with unvaccinated children, adjusted mean cost for first RV episode and first diarrhea episode per 1000 persons was $11,511 (95%CI: $9855-$12,024) and $46,772 (95%CI: $26,268-$66,604) lower, respectively, for completely vaccinated children.ConclusionsRV1 vaccination confers benefits in reduction of RV incidence, RV- and diarrhea-related healthcare resource utilization, and RV- and diarrhea-related healthcare costs.     

Methotrexate reduces vaccine-specific immunoglobulin levels but not numbers of circulating antibody-producing B cells in rheumatoid arthritis after vaccination with a conjugate pneumococcal vaccine

BackgroundTreatment with methotrexate (MTX) in patients with rheumatoid arthritis (RA) leads to decreased total immunoglobulin (Ig) levels and impairs vaccine-specific IgG antibody levels following pneumococcal vaccination. The mechanisms by which MTX exerts these effects in RA are unknown. We aimed to evaluate whether MTX reduces vaccine-specific serum Ig levels and their functionality in RA patients following vaccination with pneumococcal conjugate vaccine, and if numbers of antigen-specific circulating plasmablasts are affected.MethodsTen patients with RA on MTX and 10 RA patients without disease modifying anti-rheumatic drug (DMARD) were immunized with a dose 13-valent pneumococcal conjugate vaccine (Prevenar13). Circulating plasmablasts producing total IgG and IgA as well as specific IgG and IgA against two pneumococcal capsular serotypes (6B and 23F) were enumerated using ELISPOT 6 days after vaccination. IgG levels against both these serotypes were determined with ELISA before and 4–6 weeks after vaccination. Positive antibody response was defined as ⩾2-fold increase of pre-vaccination antibody levels. The functionality of vaccine specific antibodies to serotype 23F was evaluated by measuring their ability to opsonize bacteria using opsonophagocytic assay (OPA) in 4 randomly chosen RA patients on MTX and 4 RA patients without DMARD.ResultsAfter vaccination, RA patients on MTX showed significant increase in pre- to postvaccination antibody levels for 6B (p < 0.05), while patients without DMARD had significant increases for both 6B and 23F (p < 0.05 and p < 0.01, respectively). Only 10% of RA on MTX and 40% of RA patients without DMARD showed positive post-vaccination antibody responses for both serotypes. Increased opsonizing ability after vaccination was detected in 1 of 4 RA patients on MTX and 3 of 4 patients on RA without DMARD. However, numbers of circulating total and vaccine-specific IgG- or IgA-producing plasmablasts did not differ between RA patients with or without MTX.ConclusionsMTX treatment in RA leads to reduced vaccine-specific antibody responses and their functionality compared to untreated RA following pneumococcal vaccination using polysaccharide-protein conjugate vaccine. However, since there was no reduction in numbers of circulating total or vaccine-specific antibody-producing plasmablasts after vaccination this effect is probably not due to reduced activation of B cells in lymphoid tissue.Clinical trial registration: NCT02240888.     

Immunogenicity and safety of an AS03-adjuvanted H7N1 vaccine in adults 65 years of age and older: A phase II,observer-blind,randomized, controlled trial

BackgroundH7 influenza strains can cause severe and often fatal human infections, especially in the elderly. This phase II, observer-blind, randomized trial (www.ClinicalTrials.gov: NCT01949090) assessed the immunogenicity and safety of a novel AS03-adjuvanted H7N1 vaccine that may serve as a model H7-subtype vaccine.Methods360 adults ≥65 years of age in stable health received either 1 of 4 adjuvanted A/mallard/Netherlands/12/2000 split virion vaccine formulations (3.75 μg or 7.5 μg hemagglutinin adjuvanted with either AS03_A or AS03_B) or saline placebo, given as a 2-dose series. Immunogenicity was assessed using hemagglutination-inhibition (HI) and microneutralization (MN) assays for the per-protocol cohort, comprising 332 participants at 21 days post-each dose, 332 at month 6, and 309 at month 12 (HI assay only). Safety was assessed up to month 12 for all participants who had received ≥1 dose (360 participants).ResultsFor H7N1 HI antibody assessment at day 42 (21 days post-dose 2), seroprotection rates (SPR) in the vaccinated groups were 69.6%–88.7%, seroconversion rates (SCR) 69.6%–88.5%, mean geometric increase (MGI) 11.0–18.9, and HI geometric mean titers (GMTs) 55.0–104.8. These parameters declined by month 6 and month 12. Microneutralization GMTs were 46.2–74.7 in the vaccinated groups at day 42, while vaccine response rate (VRR; proportion with ≥4-fold increase in MN titer) was 46.4%–81.5%. For the cross-reactive H7N9 strain, at day 42, HI GMT were 64.3–201.3, SPR 78.6%–96.3%, SCR 79.3%–96.3%, and MGI 14.1–37.7; MN GMTs were 44.0–85.6, and VRR 46.4–85.2%.The most frequent solicited symptom was injection site pain (41.7%–65.0% of vaccine recipients). In total, 40 participants reported 67 serious adverse events; none were considered causally related to vaccination.ConclusionsIn adults aged ≥65 years, the adjuvanted H7N1 vaccine was immunogenic after 2 doses, and had an acceptable safety profile.www.ClinicalTrials.gov: NCT01949090.     

The free vaccination policy of influenza in Beijing,China: The vaccine coverage and its associated factors

BackgroundIn order to improve influenza vaccination coverage, the coverage rate and reasons for non-vaccination need to be determined. In 2007, the Beijing Government published a policy providing free influenza vaccinations to elderly people living in Beijing who are older than 60. This study examines the vaccination coverage after the policy was carried out and factors influencing vaccination among the elderly in Beijing.MethodsA cross-sectional survey was conducted through the use of questionnaires in 2013. A total of 1673 eligible participants were selected by multistage stratified random sampling in Beijing using anonymous questionnaires in-person. They were surveyed to determine vaccination status and social demographic information.ResultsThe influenza vaccination coverage was 38.7% among elderly people in Beijing in 2012. The most common reason for not being vaccinated was people thinking they did not need to have a flu shot. After controlling for age, gender, income, self-reported health status, and the acceptance of health promotion, the rate in rural areas was 2.566 (95% confidence interval [CI], 1.801–3.655, P < 0.010) times greater than that in urban areas. Different mechanisms of health education and health promotion have different influences on vaccination uptake. Those whom received information through television, community boards, or doctors were more likely to get vaccinated compared to those who did not (Odds Ratio [OR] = 1.403, P < 0.010; OR = 1.812, P < 0.010; OR = 2.647, P < 0.010).ConclusionThe influenza vaccine coverage in Beijing is much lower than that of developed countries with similar policies. The rural–urban disparity in coverage rate (64.1% versus 33.5%), may be explained by differing health provision systems and personal attitudes toward free services due to socioeconomic factors. Methods for increasing vaccination levels include increasing the focus on primary care and health education programs, particularly recommendations from doctors, to the distinct target populations, especially with a focus on expanding these efforts in urban areas.     

Evaluating the effectiveness of the universal immunization program against varicella in Japanese children

ObjectiveMatched case control study was conducted to elucidate the effectiveness of the Oka/Biken vaccine immediately after implementation of the universal immunization program in Japan.MethodsCases were laboratory confirmed varicella patient under 15 years of age diagnosed at 14 designated pediatric clinics between September 2015 and September 2016. Controls were selected from patients who visited the same practice for different reasons as the varicella case within 2 weeks. Swab samples were collected from varicella suspected patients and molecular diagnostic assays were used to confirm varicella cases. Matched odds ratio were used to calculate vaccine effectiveness (VE).ResultsVaricella zoster virus DNA was detected in 183 (81.3%) of 225 suspected cases. One sample was excluded because it was positive for the Oka vaccine strain (182/225, 80.9%). Three hundred twenty-three control subjects were enrolled. The effectiveness of 1 dose of the Oka/Biken vaccine compared with no vaccine was 76.7% (95% confidence interval [CI]: 58.6–86.9%; P < 0.001). The effectiveness of 2 doses of the Oka/Biken vaccine was 94.2% (95% CI: 85.7–97.6%; P < 0.001). After adjusting for potential confounding effects, the adjusted VE of 1 and 2 doses of varicella vaccine were 76.9% (95% CI: 58.1–87.3%; P < 0.001) and 94.7% (95% CI: 86.0–98.0%; P < 0.001), respectively.ConclusionsVE of one dose of Oka/Biken varicella vaccine was insufficient to control varicella. Therefore, two doses of Oka/Biken varicella vaccine is significant for controlling varicella in Japan.     

Humoral,T-cell and B-cell immune responses to seasonal influenza vaccine in solid organ transplant recipients receiving anti-T cell therapies

BackgroundWe analyzed the impact of the anti-T-cell agents basiliximab and antithymocyte globulins (ATG) on antibody and cell-mediated immune responses after influenza vaccination in solid-organ transplant recipients.Methods71 kidney and heart transplant recipients (basiliximab [n = 43] and ATG [n = 28]) received the trivalent influenza vaccine. Antibody responses were measured at baseline and 6 weeks post-vaccination by hemagglutination inhibition assay; T-cell responses were measured by IFN-γ ELISpot assays and intracellular cytokine staining (ICS); and influenza-specific memory B-cell (MBC) responses were evaluated using ELISpot.ResultsMedian time of vaccination from transplantation was 29 months (IQR 8–73). Post-vaccination seroconversion rates were 26.8% for H1N1, 34.1% for H3N2 and 4.9% for influenza B in the basiliximab group and 35.7% for H1N1, 42.9% for H3N2 and 14.3% for influenza B in the ATG group (p = 0.44, p = 0.61, and p = 0.21, respectively). The number of influenza-specific IFN-γ-producing cells increased significantly after vaccination (from 35 to 67.5 SFC/10⁶ PBMC, p = 0.0007), but no differences between treatment groups were observed (p = 0.88). Median number of IgG-MBC did not increase after vaccination (H1N1, p = 0.94; H3N2 p = 0.34; B, p = 0.79), irrespective of the type of anti-T-cell therapy.ConclusionsAfter influenza vaccination, a significant increase in antibody and T-cell immune responses but not in MBC responses was observed in transplant recipients. Immune responses were not significantly different between groups that received basiliximab or ATG.     

The 2015 global production capacity of seasonal and pandemic influenza vaccine

A global shortage and inequitable access to influenza vaccines has been cause for concern for developing countries who face dire consequences in the event of a pandemic. The Global Action Plan for Influenza Vaccines (GAP) was launched in 2006 to increase global capacity for influenza vaccine production to address these concerns. It is widely recognized that well-developed infrastructure to produce seasonal influenza vaccines leads to increased capacity to produce pandemic influenza vaccines. This article summarizes the results of a survey administered to 44 manufacturers to assess their production capacity for seasonal influenza and pandemic influenza vaccine production. When the GAP was launched in 2006, global production capacity for seasonal and pandemic vaccines was estimated to be 500 million and 1.5 billion doses respectively. Since 2006 there has been a significant increase in capacity, with the 2013 survey estimating global capacity at 1.5 billion seasonal and 6.2 billion pandemic doses. Results of the current survey showed that global seasonal influenza vaccine production capacity has decreased since 2013 from 1.504 billion doses to 1.467 billion doses. However, notwithstanding the overall global decrease in seasonal vaccine capacity there were notable positive changes in the distribution of production capacity with increases noted in South East Asia (SEAR) and the Western Pacific (WPR) regions, albeit on a small scale. Despite a decrease in seasonal capacity, there has been a global increase of pandemic influenza vaccine production capacity from 6.2 billion doses in 2013 to 6.4 billion doses in 2015. This growth can be attributed to a shift towards more quadrivalent vaccine production and also to increased use of adjuvants. Pandemic influenza vaccine production capacity is at its highest recorded levels however challenges remain in maintaining this capacity and in ensuring access in the event of a pandemic to underserved regions.     

Evaluation of anthrax vaccine safety in 18 to 20 year olds: A first step towards age de-escalation studies in adolescents

Background/objectivesAnthrax vaccine adsorbed (AVA, BioThrax^®) is recommended for post-exposure prophylaxis administration for the US population in response to large-scale Bacillus anthracis spore exposure. However, no information exists on AVA use in children and ethical barriers exist to performing pre-event pediatric AVA studies. A Presidential Ethics Commission proposed a potential pathway for such studies utilizing an age de-escalation process comparing safety and immunogenicity data from 18 to 20 year-olds to older adults and if acceptable proceeding to evaluations in younger adolescents. We conducted exploratory summary re-analyses of existing databases from 18 to 20 year-olds (n = 74) compared to adults aged 21 to 29 years (n = 243) who participated in four previous US government funded AVA studies.MethodsData extracted from studies included elicited local injection-site and systemic adverse events (AEs) following AVA doses given subcutaneously at 0, 2, and 4 weeks. Additionally, proportions of subjects with ≥4-fold antibody rises from baseline to post-second and post-third AVA doses (seroresponse) were obtained.ResultsRates of any elicited local AEs were not significantly different between younger and older age groups for local events (79.2% vs. 83.8%, P = 0.120) or systemic events (45.4% vs. 50.5%, P = 0.188). Robust and similar proportions of seroresponses to vaccination were observed in both age groups.ConclusionsAVA was safe and immunogenic in 18 to 20 year-olds compared to 21 to 29 year-olds. These results provide initial information to anthrax and pediatric specialists if AVA studies in adolescents are required.     

An accelerated rabies vaccine schedule based on toll-like receptor 3 (TLR3) agonist PIKA adjuvant augments rabies virus specific antibody and T cell response in healthy adult volunteers

BackgroundRabies is a fatal disease where post-exposure prophylaxis (PEP) is crucial in preventing infection. However, deaths even after appropriate PEP, have been reported. The PIKA Rabies vaccine adjuvant is a TLR3 agonist that activates B and T cells leading to a robust immune response.MethodsWe conducted a phase I, open label, randomized study in healthy adults to assess the safety and immunogenicity of the PIKA Rabies vaccine and an accelerated vaccine regimen. Thirty-seven subjects were randomized into 3 groups: control vaccine classic regimen, PIKA vaccine classic regimen and PIKA vaccine accelerated regimen. Subjects were followed up for safety, rabies virus neutralizing antibodies (RVNA) and T cell responses.ResultsBoth the control and PIKA Rabies vaccine were well tolerated. All adverse events (AEs) were mild and self-limiting. Seventy-five percent of subjects in the PIKA accelerated regimen achieved a RVNA titer ⩾0.5 IU/mL on day 7, compared to 53.9% in the PIKA classic regimen (p = 0.411) and 16.7% in control vaccine classic regimen (p = 0.012). The PIKA rabies vaccine elicited multi-specific rabies CD4 mediated T cell response already detectable ex vivo at day 7 after vaccination and that was maintained at day 42.ConclusionThe investigational PIKA rabies vaccine was well tolerated and more immunogenic than the commercially available vaccine in healthy adults.Clinical trial registry: The study was registered with clinicaltrials.gov NCT02657161.     

Clinician knowledge,clinician barriers,and perceived parental barriers regarding human papillomavirus vaccination: Association with initiation and completion rates

PurposeWe tested the hypothesis that clinician knowledge, clinician barriers, and perceived parental barriers relevant to the human papillomavirus (HPV) vaccination account for the variation in vaccine delivery at the practice-site level.MethodsWe conducted a survey from October 2015 through January 2016 among primary care clinicians (n = 280) in a 27-county geographic region to assess clinician knowledge, clinician barriers, and perceived parental barriers regarding HPV vaccination. Primary care clinicians included family medicine physicians, general pediatricians, and family and pediatric nurse-practitioners. We also used the Rochester Epidemiology Project to measure HPV vaccination delivery. Specifically we used administrative data to measure receipt of at least one valid HPV vaccine dose (initiation) and receipt of three valid HPV vaccine doses (completion) among 9–18 year old patients residing in the same 27-county geographic region. We assessed associations of clinician survey data with variation in vaccine delivery at the clinical site using administrative data on patients aged 9–18 years (n = 68,272).ResultsConsistent with our hypothesis, we found that greater knowledge of HPV and the HPV vaccination was associated with higher rates of HPV vaccination initiation (Incidence rate ratio [IRR] = 1.05) and completion of three doses (IRR = 1.28). We also found support for the hypothesis that greater perceived parental barriers to the HPV vaccination were associated with lower rates of initiation (IRR = 0.94) and completion (IRR = 0.90). These IRRs were statistically significant even after adjustment for site-level characteristics including percent white, percent female, percent ages 9–13, and percent with government insurance or self-pay at each site.ConclusionsClinician knowledge and their report of the frequency of experiencing parental barriers are associated with HPV vaccine delivery rates—initiation and completion. Higher measures of knowledge correlated with higher rates. Fewer perceived occurrences of parental barriers correlated with lower rates. These data can guide efforts to improve HPV vaccine delivery in clinical settings.