Combined tetanus-diphtheria and pertussis vaccine during pregnancy: transfer of maternal pertussis antibodies to the newborn

Background and objectivesPertussis is currently an emerging public health concern in some countries with high vaccination coverage. It is expected that maternal pertussis immunization could provide newborn protection. We compared pertussis toxin antibody (anti-PT) levels in women during pregnancy (pre- and post-vaccination) with respect to levels in the newborn at delivery in women vaccinated during pregnancy. We also estimated anti-PT titers at primary infant vaccination.MethodsObservational study of pregnant women vaccinated with Tdap (≥20 weeks gestation) and their newborns between May 2012 and August 2013. Anti-PT levels were determined by ELISA in maternal (pre- and post-vaccination) and newborn blood.ResultsPre-vaccination, post-vaccination maternal and newborn samples were available in 132 subjects. Mean maternal age was 34.2 (SD 4.3) years. Median weeks of gestation at vaccination were 27.2 (Q1–Q3 21.7–30.8). Anti-PT (≥10 IU/ml) levels were found in 37.1% of maternal pre-vaccination samples (geometric mean titer (GMT) 7.9 IU/ml (95% CI 6.8–9.2)), 90.2% of post-vaccination samples (GMT 31.1 IU/ml (95% CI 26.6–36.3)) and 94.7% of newborns (GMT 37.8 IU/ml (95% CI 32.3–44.1)). The Lin concordance index between post-vaccination maternal and newborn samples was 0.8 (95% CI 0.8–0.9). Transplacental transfer ratio was 146.6%. At two months of age, 66% of newborns had estimated anti-PT levels ≥10 IU/ml.ConclusionsThere was a high correlation between anti-PT levels in mothers and newborns, with higher levels in newborns, which should be sufficient to provide protection against pertussis during the first months of life. Vaccination of pregnant women seems to be an immunogenic strategy to protect newborns until primary infant immunization.     

The antibody response to influenza vaccination is not impaired in type 2 diabetics

BackgroundDiabetics are considered to be at high risk for complications from influenza infection and type 2 diabetes is a significant comorbidity of obesity. Obesity is an independent risk factor for complications from infection with influenza. Annual vaccination is considered the best strategy for protecting against influenza infection and it's complications. Our previous study reported intact antibody responses 30 days post vaccination in an obese population. This study was designed to determine the antibody response to influenza vaccination in type 2 diabetics.MethodsSubjects enrolled were 18 or older without immunosuppressive diseases or taking immunosuppressive medications. A pre-vaccination blood draw was taken at time of enrollment, the subjects received the influenza vaccine and returned 28–32 days later for a post-vaccination blood draw. Height and weight were also obtained at the first visit and BMI was calculated. Antibody levels to the vaccine were determined by both ELISA and hemagglutination inhibition (HAI) assays.ResultsAs reported in our previous work, obesity positively correlates with the influenza antibody response (p = 0.02), while age was negatively correlated with antibody response (p < 0.001). In both year 1 and year 2 of our study there was no significant difference in the percentage of the type 2 diabetic subjects classified as seroprotected or a responder to the influenza vaccine compared to the non-diabetic subjects.ConclusionsThese data are important because they demonstrate that diabetics, considered a high risk group during influenza season, are able to mount an antibody response to influenza vaccination that may protect them from influenza infection.     

The humoral immune response to high-dose influenza vaccine in persons with monoclonal B-cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL)

BackgroundLimited data are available regarding the immunogenicity of high-dose influenza vaccine among persons with chronic lymphocytic leukemia (CLL) and monoclonal B cell lymphocytosis (MBL).MethodsA prospective pilot study of humoral immune responses to 2013–2014 and 2014–2015 high-dose trivalent influenza vaccine (HD IIV; Fluzone® High-Dose; Sanofi Pasteur) was conducted among individuals with MBL and previously untreated CLL. Serum hemagglutination inhibition (HAI) antibody titers were measured at baseline and Day 28 after vaccination; seroprotection and seroconversion rates were determined. Memory B cell responses were assessed by B-cell enzyme-linked immune absorbent spot assays.ResultsThirty subjects (17 CLL and 13 MBL) were included. Median age was 69.5 years. Day 28 seroprotection rates for the cohort were 19/30 (63.3%) for A/H1N1; 21/23 (91.3%) for A/H3N2; and 13/30 (43.3%) for influenza B. Those with MBL achieved higher day 28 HAI geometric mean titers (54.1 [4.9, 600.1] vs. 12.1 [1.3, 110.1]; p = 0.01) and higher Day 28 seroprotection rates (76.9% vs. 17.6%; p = 0.002) against the influenza B-vaccine strain virus than those with CLL.ConclusionsImmunogenicity of the HD IIV3 in patients with CLL and MBL is lower than reported in healthy adults. Immunogenicity to influenza B was greater in those with MBL than CLL.     

Brief education to promote maternal influenza vaccine uptake: A randomized controlled trial

BackgroundAlthough pregnant women are the highest priority group for seasonal influenza vaccination, maternal influenza vaccination rates remain suboptimal. The purpose of this study was to evaluate the effect of a brief education intervention on maternal influenza vaccine uptake.MethodsDuring the 2013–14 and 2014–15 influenza seasons, we recruited 321 pregnant women from the antenatal clinics of 4 out of 8 public hospitals in Hong Kong with obstetric services. Hospitals were geographically dispersed and provided services to pregnant women with variable socioeconomic backgrounds. Participants were randomized to receive either standard antenatal care or brief one-to-one education. Participants received telephone follow-up at 2 weeks postpartum. The primary study outcome was self-reported receipt of influenza vaccination during pregnancy. The secondary outcomes were the proportion of participants who initiated discussion about influenza vaccination with a health care professional and the proportion of participants who attempted to get vaccinated.ResultsCompared with participants who received standard care, the vaccination rate was higher among participants who received brief education (21.1% vs. 10%; p = 0.006). More participants in the education group initiated discussion about influenza vaccination with their HCP (19.9% vs. 13.1%; p = 0.10), but the difference was not statistically significant. Of participants who did not receive the influenza vaccine (n = 271), 45 attempted to get vaccinated. A significantly higher proportion of participants who attempted to get vaccinated were in the intervention group (82.2% vs. 17.8%; p < 0.001). If participants who had attempted vaccination had received the vaccine, vaccination rates would have been substantially higher (44.1% vs. 15%; p < 0.001). Twenty-six participants were advised against influenza vaccination by a healthcare professional, including general practitioners, obstetricians, and nurses.ConclusionAlthough brief education was effective in improving vaccination uptake among pregnant women, overall vaccination rates remain suboptimal. Multicomponent approaches, including positive vaccination recommendations by healthcare professionals, are needed to promote maternal influenza vaccination.Clinical Trial Registration: www.clinicaltrials.gov (NCT01772901).     

Vitamin D levels and influenza vaccine immunogenicity among HIV-infected and HIV-uninfected adults

BackgroundVaccination is the most important preventive strategy against influenza, however post-vaccination antibody responses are often inadequate especially among HIV-infected persons. Vitamin D deficiency has been suggested to adversely influence immune responses and is highly prevalent among HIV-infected adults. Therefore, we evaluated the association between 25-hydroxyvitamin D [25(OH)D] levels and post-influenza vaccination responses.MethodsWe conducted a prospective cohort study evaluating the immunogenicity of monovalent influenza A (H1N1) vaccination among both HIV-infected and HIV-uninfected adults (18–50 years of age) during the 2009–2010 influenza season. Antibody titers were evaluated at baseline, day 28, and 6 months post-vaccination using hemagluttination inhibition assays. Serum 25(OH)D levels were measured at day 28. Univariate and multivariate regression analyses examined the association between 25(OH)D levels [categorized as <20 ng/ml (deficiency) vs. ⩾20 ng/ml] with the primary outcome of seroconversion. Secondary outcomes included seroprotection; a ⩾4-fold increase in titers; and geometric mean titers post-vaccination. Analyses were repeated using 25(OH)D levels as a continuous variable.ResultsA total of 128 adults [64 HIV-infected (median CD4 count 580 cells/mm³) and 64 HIV-uninfected] were included. Seroconversion at day 28 post-vaccination was achieved in fewer HIV-infected participants compared with HIV-uninfected participants (56% vs. 74%, p = 0.03). Vitamin D deficiency was more prevalent among HIV-infected persons vs. HIV-uninfected persons (25% vs. 17%), although not significantly different (p = 0.39). There were no associations found between lower 25(OH)D levels and poorer antibody responses at day 28 or 6 months for any of the study outcomes among either HIV-infected or HIV-uninfected adults.ConclusionVitamin D deficiency was common among both HIV-infected and HIV-uninfected adults, but lower levels did not predict antibody responses after H1N1 (2009) influenza vaccination. Low 25(OH)D levels do not explain poorer post-vaccination responses among HIV-infected persons.     

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.     

Effects of Repeated Annual Inactivated Influenza Vaccination among Healthcare Personnel on Serum Hemagglutinin Inhibition Antibody Response to A/Perth/16/2009 (H3N2)-like virus during 2010-11

BackgroundRecently, lower estimates of influenza vaccine effectiveness (VE) against A(H3N2) virus illness among those vaccinated during the previous season or multiple seasons have been reported; however, it is unclear whether these effects are due to differences in immunogenicity.MethodsWe performed hemagglutination inhibition antibody (HI) assays on serum collected at preseason, ∼30 days post-vaccination, and postseason from a prospective cohort of healthcare personnel (HCP). Eligible participants had medical and vaccination records for at least four years (since July, 2006), including 578 HCP who received 2010-11 trivalent inactivated influenza vaccine [IIV3, containing A/Perth/16/2009-like A(H3N2)] and 209 HCP who declined vaccination. Estimates of the percentage with high titers (≥40 and > 100) and geometric mean fold change ratios (GMRs) to A/Perth/16/2009-like virus by number of prior vaccinations were adjusted for age, sex, race, education, household size, hospital care responsibilities, and study site.ResultsPost-vaccination GMRs were inversely associated with the number of prior vaccinations, increasing from 2.3 among those with 4 prior vaccinations to 6.2 among HCP with zero prior vaccinations (F[4,567] = 9.97, p < .0005). Thirty-two percent of HCP with 1 prior vaccination achieved titers >100 compared to only 11% of HCP with 4 prior vaccinations (adjusted odds ratio = 6.8, 95% CI = 3.1 – 15.3).ConclusionOur findings point to an exposure-response association between repeated IIV3 vaccination and HI for A(H3N2) and are consistent with recent VE observations. Ultimately, better vaccines and vaccine strategies may be needed in order to optimize immunogenicity and VE for HCP and other repeated vaccinees.     

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).     

Body mass index and vaccine responses following influenza vaccination during pregnancy

Background and AimsInfluenza vaccination is recommended by the World Health Organisation for pregnant women, offering the dual benefit of protecting pregnant women and their newborn infants against influenza infection. Various factors can influence vaccine immunogenicity, with obesity being one factor implicated in varied responses. This study aimed to investigate the impact of body mass index (BMI) on vaccine responses following influenza vaccination during pregnancy.MethodsPregnant women attending the Women’s and Children’s Hospital in South Australia during 2014–2016 were invited to participate. Participant’s clinical and demographic factors were recorded prior to administration of licensed seasonal influenza vaccination. Blood samples were collected before and one month post-vaccination to measure antibody responses by haemagglutination inhibition (HI) assay. Seroprotection was defined as a post-vaccination HI titre ≥ 1:40. Regression models assessed associations with failure to achieve seroprotective antibodies to H1, H3, and B influenza strains.ResultsA total of 96 women were enrolled in the study at a median gestation of 22 weeks with a BMI range of 18–49 kg/m². Paired sera samples were available for 90/96 (94%). Most pregnant women (72/90, 80%) demonstrated seroprotective antibody titres to all three influenza vaccine antigens (A(H1N1)pdm09, A(H3N2), B/Yamagata) following vaccination. Compared with women with BMI < 30 kg/m², those with high BMI were less likely to fail to achieve seroprotective antibodies, however this was not statistically significant (RR 0.42, 95% CI 0.11–1.68; p = 0.22). A greater proportion of women vaccinated during their second (47/53, 93%) or third trimester (18/25, 72%) demonstrated seroprotection to all three vaccine antigens following vaccination compared with women vaccinated during their first trimester (7/12, 58%).ConclusionHigh BMI did not impair seroprotection levels following influenza vaccination in pregnant women. Gestation at vaccination may be an important consideration for optimising vaccine protection for pregnant women and their newborns. Further assessment of first trimester influenza vaccine responses is warranted.     

Immunogenicity of influenza vaccines administered to pregnant women in randomized clinical trials in Mali and South Africa

BackgroundA key consideration for expanding recommendations for influenza vaccination is a robust assessment of immunogenicity and efficiency of transplacental antibody transfer after maternal vaccination.MethodsWe pooled data from two trials of maternal influenza vaccination to analyze vaccine immunogenicity with more power than either trial had alone. We compared hemagglutination-inhibition (HAI) titers and titer factor change for women and their infants between trial arms using t-tests; maternal and infant putative seroprotective titers (HAI ≥ 1:40) within each trial arm and maternal seroconversion between trial arms using exact tests; and transplacental antibody transfer between trial arms using t-tests. We used marginal linear models and generalized estimating equations to examine the impact of time between maternal vaccination and delivery on transplacental antibody transfer, infant titers, and infant seroprotection.ResultsFor all vaccine components (A/H1N1, A/H3N2, and Type B), >80% of vaccinated women had seroprotective titers, >60% of them seroconverted, and >50% of their infants were born with seroprotective titers. These immunogenicity outcomes occurred more often in vaccine recipients and their infants than in controls. No difference in efficiency of transplacental antibody transfer was observed between vaccine recipients and controls.ConclusionsOur results provide robust support for further expansion of maternal influenza vaccination recommendations.Clinical Trials Registration: NCT01430689 and NCT01306669.     

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.     

Interventions to increase the uptake of seasonal influenza vaccination among pregnant women: A systematic review

BackgroundPregnant women and their infants under 6 months of age infected with influenza have a high risk of serious morbidity and mortality. Influenza vaccine during pregnancy offers 3-for-1 benefits to pregnant women, fetuses and newborn infants. Current vaccination uptake rates during pregnancy, however, are often lower than other high-risk groups and the general population.MethodsWe systematically reviewed evidence on the effectiveness of interventions to improve influenza vaccination coverage in pregnant women. Risk differences (RDs) were calculated from the included studies.ResultsEleven studies were included in the review, of which four were randomized controlled trials (RCTs). Three cohort studies assessed provider-focused interventions while four RCTs and one cohort study evaluated pregnant women-focused interventions. Two cohort studies and a prospective intervention study assessed the effectiveness of bundled interventions. No study solely assessed the effectiveness of interventions to enhance access to influenza vaccination. One moderate quality RCT showed that an influenza pamphlet, with or without a verbalized benefit statement, improved the vaccination rate (RD = 0.26; RD = 0.39). The other reviewed RCTs showed discordant results, with RDs ranging from −0.15 to 0.03. Although all observational studies significantly improved vaccination rates (RDs ranged from 0.03 to 0.44), the quality of the evidence varied.ConclusionsThere is a lack of effective interventions to increase the influenza vaccination rate in pregnant women. Based on the existing research, we recommend that clinicians provide influenza pamphlets to pregnant women with a verbalized statement about the benefits of influenza vaccine to newborns. Further high-quality RCTs are needed to develop successful maternal influenza vaccination programs. Increased clarity in reporting the content of interventions would help to improve the comparability and generalizability of the published studies.     

Proinflammatory cytokine responses correspond with subjective side effects after influenza virus vaccination

BackgroundThough typically mild, side effects to the influenza virus vaccine are common and may contribute to negative perceptions including the belief that the vaccine can cause the flu. However, the extent to which subjective symptoms correspond with biological response indicators is poorly understood.MethodsThis study examined associations among subjective side effects (soreness at the site of injection and illness-like symptoms), serum proinflammatory cytokines and body temperature a baseline, 1, 2, and 3 days following receipt of trivalent inactivated influenza vaccine (IIV3) in a sample of 56 women 18–40 years in age.ResultsIn relation to local reactions, women reporting being very sore at the injection site at 1 day post-vaccination exhibited greater increases in serum TNF-α and MIF in the days following vaccination compared to those with no or mild soreness. In addition, higher basal body temperature was observed in this group compared to other groups (98.7 °F versus 98.0–98.1°). In relation to systemic reactions, women endorsing illness-like symptoms (headache, fatigue, nausea, sore throat, dizziness, achiness, or mild fever) exhibited marginally higher IL-6 at baseline (p = 0.055) and greater increases in serum MIF at 2 days post-vaccination than those reporting no systemic symptoms. Associations of systemic symptoms with inflammatory responses were not accounted for by concomitant local reactions. As expected, antibody responses to the vaccine were highly similar in women regardless of local or systemic symptoms.ConclusionsThese results are consistent with the notion that subjective reports of local and systemic reactions following vaccination may be predicted by and correspond with biological indicators of inflammatory status, but are not meaningful predictors of antibody responses. To improve adherence to vaccine recommendations, clinicians should provide assurance that such symptoms may be related to normal mild inflammatory responses to the vaccine and do not reflect immunogenicity.     

Rubella specific cell-mediated and humoral immunity following vaccination in college students with low antibody titers

ObjectiveThis study measured cell-mediated immunity (CMI) and antibodies to clarify the basis of rubella reinfection after vaccination.MethodsIn a pool of 65 college students, 39 who exhibited hemagglutination–inhibition (HI) antibody titers against rubella of ≤1:16 were vaccinated with a rubella vaccine. The CMI was assessed with interferon-gamma release assay.ResultsThere was low correlation (r = 0.24) between the antibody titers and interferon-gamma levels at pre-vaccination status. Preexisting interferon-gamma levels were low in some subjects with low HI antibody titers of 1:8 and 1:16. Fifty-seven percent (4/7) of the subjects who were antibody-negative with past history of rubella vaccination at entry onto the study exhibited CMI. And 57% (4/7) of the subjects remained antibody-negative following a second vaccination, despite exhibiting CMI. HI antibody titers increased significantly after vaccination, whereas post-vaccination interferon-gamma levels did not exhibit significant increases. When subjects were divided (based on their past history of vaccination and antibody values) into natural infection and vaccination groups, HI antibody titers (mean ± SD) increased to 1:2^4.4 ± 1.4 from 1: 2^3.2 ± 0.4 (p = 0.065) in the natural infection group and to 1:2^4.4 ± 1.0 from 1:2^3.0 ± 0.8 (p < 0.00001) in the vaccination group following vaccination. The same classification revealed that interferon-gamma values did not increase significantly in either group following vaccination, but the interferon-gamma values at pre- and post-vaccination in the natural infection group were significantly higher than those at pre- and post-vaccination in the vaccination group (p < 0.05 and p < 0.05, respectively).ConclusionPre-vaccination interferon-gamma levels in each HI antibody titer group were similar. And there were some subjects with antibody-positive exhibited CMI-negative. These data may explain why rubella reinfection can occur in vaccinated seropositive individuals.     

Long-term follow-up of Japanese encephalitis chimeric virus vaccine: Immune responses in children

BackgroundA single dose of live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) was shown to be immunogenic and well tolerated when given either as a booster to formalin-inactivated Japanese encephalitis (JE)-vaccine (mouse brain-derived vaccine [MBDV])-primed 2–5-year-olds, or as a primary vaccination to JE-vaccine-naïve 12–24-month-old toddlers in Thailand. A 5-year follow-up assessment of immune response persistence over time was conducted.MethodsFour additional visits (at 2, 3, 4, and 5 years) for immunologic assessments were added to the original 12-month open-label crossover study, in which 100 healthy children aged 2–5 years with a history of two-dose primary vaccination with MBDV (according to the Thai Expanded Program for Immunization schedule), and 200 healthy JE-vaccine-naïve 12–24-month-old toddlers, were randomized 1:1 to receive JE-CV, containing ⩾4 log₁₀ plaque forming units, 1 month before or after hepatitis A control vaccine.ResultsIn MBDV-primed 2–5-year-olds (n = 78), the immune response to the JE-CV vaccine persisted up to at least 5 years after vaccination with a single dose of JE-CV, with all (n = 78) children seroprotected at the year 5 visit (geometric mean titers [GMT]: 252 1/dil). There was no decrease of seroprotection rate over time (100% at 6 months post-vaccination and 96.8% (90.3–98.9) at 5 years post-vaccination). In JE-vaccine-naïve toddlers, a protective immune response persisted up to at least 5 years in 58.8% (50.9–66.4) after a single-dose administration of JE-CV (GMT 26.7 1/dil; sensitivity analysis).ConclusionsA single-dose of JE-CV as a booster following MBDV administration provided long-lasting immunity. In JE-vaccine-naïve toddlers, despite relatively high seroprotection rates persisting over time, a subsequent booster dose is recommended following a JE-CV primary vaccination for long-term protection.This study was registered on www.clinicaltrials.gov (NCT00621764).     

Comparing the rubella seronegativity in pregnant women who received one dose of rubella vaccine at different ages in Taiwan

IntroductionVaccination is the best strategy to prevent rubella and congenital rubella. The aim of our study was to assess the immunity to rubella and determine rubella virus antibody titers in pregnant women who were offered a single dose of rubella vaccine at different ages of their lives.MethodsA total 15,067 rubella IgG antibody test results for Taiwanese pregnant women who received routine prenatal checkup at Fooyin University Hospital from 1999 to 2014 were analyzed in this study. The women were divided into five birth cohorts in order to compare their rubella seronegativities and antibody titers according to the different period of rubella vaccination policy in Taiwan.ResultsThe total rubella seronegativity rate was 11.2% (95% CI: 10.7–11.7%) and the mean rubella antibody titers was 51.0 IU/mL (SD = 54.7 IU/mL). The junior school cohort has the lowest rubella seronegativity of 7.6% (95% CI: 6.9–8.2%). The seronegativities were significantly high in the preschool cohort and in the 15-month-old cohort, 14.9% (95% CI: 13.2–16.6%) and 14.8% (95% CI: 11.5–18.1%), respectively. The OR values were 2.1 (95% CI: 1.8–2.5, p < 0.001) in the preschool cohort and 2.2 (95% CI: 1.6–2.8, p < 0.001) in the 15-month-old cohort, respectively, against the junior school cohort. Women in the 15-month-old cohort have lowest average rubella IgG titer, 25.4 IU/mL.ConclusionThe total rubella seronegativity rate was 11.2% in all native pregnant women. Women who received one dose rubella vaccine at preschool and 15-month-old have highest seronegativities. The 15-month-old cohort has the lowest average rubella IgG titer. We recommend a revised catch-up immunization policy to women who received one dose rubella vaccine at a younger age.     

Increasing seasonal influenza vaccination among high risk groups in China: Do community healthcare workers have a role to play?

BackgroundSeasonal influenza vaccine uptake in China is low. This study aims to assess the role of community healthcare workers (HCWs) in increasing vaccination among high risk groups in China.MethodsWe analyzed data from four knowledge, attitude and practice (KAP) studies on seasonal influenza vaccination in China targeting guardians of young children, pregnant women, adults aged ≥60 years, and HCWs from 2012 to 2014.ResultsThirty-one percent of pregnant women and 78% adults aged ≥60 years reported willingness to follow HCWs’ recommendations for influenza vaccination. Guardians were more likely to vaccinate their children if they received HCWs’ recommendations (35% vs. 17%, p < 0.001). Community HCWs were more likely to recommend seasonal influenza vaccination than hospital HCWs (58% vs. 28%, p < 0.001).ConclusionStudy results suggest the value of incorporating community HCWs’ recommendation for seasonal influenza vaccination into existing primary public health programs to increase vaccination coverage among high risk groups in China.     

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.     

Influenza vaccine acceptance among pregnant women in urban slum areas,Karachi, Pakistan

BackgroundFacilitators and barriers to influenza vaccination among pregnant women in the developing world are poorly understood, particularly in South Asia. We assessed intention to accept influenza vaccine among ethnically diverse low-income pregnant women in Pakistan.MethodsFrom May to August 2013, we conducted a cross-sectional survey of pregnant women who visited health centers in urban slums in Karachi city. We assessed intention to accept influenza vaccine against socio-demographic factors, vaccination history, vaccine recommendation sources, and other factors.ResultsIn an unvaccinated study population of 283 respondents, 87% were willing to accept the vaccine, if offered. All except two participants were aware of symptoms typically associated with influenza. Perceived vaccine safety, efficacy, and disease susceptibility were significantly associated with intention to accept influenza vaccine (p < 0.05). Regardless of intention to accept influenza vaccine, 96% rated healthcare providers as highly reliable source of vaccine information. While a recommendation from a physician was critical for influenza vaccine acceptance, parents-in-law and husbands were often considered the primary decision-makers for pregnant women seeking healthcare including vaccination.ConclusionsMaternal influenza vaccination initiatives in South Asia should strongly consider counseling of key familial decision-makers and inclusion of healthcare providers to help implement new vaccination programs.