Enhanced surveillance of tetanus toxoid,reduced diphtheria toxoid,and acellular pertussis (Tdap) vaccines in pregnancy in the Vaccine Adverse Event Reporting System (VAERS), 2011–2015

BackgroundIn October 2011, the Advisory Committee on Immunization Practices (ACIP) issued updated recommendations that all pregnant women routinely receive a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine.ObjectivesWe characterized reports to the Vaccine Adverse Event Reporting System (VAERS) in pregnant women who received Tdap after this updated recommendation (2011–2015) and compared the pattern of adverse events (AEs) with the period before the updated recommendation (2005–2010).MethodsWe searched the VAERS database for reports of AEs in pregnant women who received Tdap vaccine after the routine recommendation (11/01/2011–6/30/2015) and compared it to published data before the routine Tdap recommendation (01/01/2005–06/30/2010). We conducted clinical review of reports and available medical records. The clinical pattern of reports in the post-recommendation period was compared with the pattern before the routine Tdap recommendation.ResultsWe found 392 reports of Tdap vaccination after the routine recommendation. One neonatal death but no maternal deaths were reported. No maternal or neonatal deaths were reported before the recommendation. We observed an increase in proportion of reports for stillbirths (1.5–2.8%) and injection site reactions/arm pain (4.5–11.9%) after the recommendation compared to the period before the routine recommendation for Tdap during pregnancy. We noted a decrease in reports of spontaneous abortion (16.7–1%). After the 2011 Tdap recommendation, in most reports, vaccination (79%) occurred during the third trimester compared to 4% before the 2011 Tdap recommendation. Twenty-six reports of repeat Tdap were received in VAERS; 13 did not report an AE. One medical facility accounted for 27% of all submitted reports.ConclusionsNo new or unexpected vaccine AEs were noted among pregnant women who received Tdap after routine recommendations for maternal Tdap vaccination. Changes in reporting patterns would be expected, given the broader use of Tdap in pregnant women in the third trimester.     

Randomized study of immune responses to two Tdap vaccines among adolescents primed with DTaP and comparison with results among adolescents primed with DTwP

BackgroundIt has been reported that persons primed with acellular (DTaP) pertussis vaccines have reduced duration of pertussis protection compared with those primed with whole-cell (DTwP) vaccines. However, due to the rapid transition to acellular vaccines, studies attempting directly to compare protection among DTaP-primed vs DTwP-primed individuals are subject to confounding by age and other limitations of ecological studies. Using validated assay results and stored sera from multiple Tdap studies, we evaluated two licensed Tdap vaccines among DTaP-primed adolescents to allow comparison with results obtained in the same laboratory from earlier studies involving DTwP-primed adolescents.MethodsParticipants 11–12 years of age who had received exactly 5 doses of DTaP vaccine prior to 7 years of age were randomly assigned in 2012 to receive one of two licensed Tdap vaccines. Serum specimens obtained pre- and post-vaccination were assayed for responses to the vaccines. Current results were then compared to results obtained in the same laboratory from prior randomized Tdap studies conducted among adolescents primed with DTwP or DTaP.ResultsBoth Tdap vaccines produced strong antibody responses to diphtheria and tetanus; responses to contained pertussis antigens were consistent with the differing levels of those antigens in each Tdap vaccine. However, postvaccination pertussis antibody responses were as much as 71% lower in these DTaP-primed adolescents compared with responses among DTwP-primed adolescents in a prior study of the same two Tdap vaccines. In contrast, results from the present study were similar to those seen in another study of Tdap among DTaP-primed adolescents.DiscussionTaken together, these results from randomized clinical trials provide direct evidence of reduced antibody responses to both licensed Tdap vaccines among adolescents primed with DTaP vaccine, compared with adolescents primed with DTwP vaccine.Clinical trial registry number: ClinicalTrials.gov, NCT01629589.     

Predictors of tetanus,diphtheria, acellular pertussis and influenza vaccination during pregnancy among full-term deliveries in a medically underserved population

ObjectiveTo evaluate predictors of vaccination among women who received tetanus, diphtheria, and acellular pertussis vaccination (Tdap), influenza vaccination, and Tdap and influenza vaccinations.Study DesignIn a retrospective cohort study of all full-term (≥37 weeks gestation) deliveries between July 1, 2016 and June 30, 2018 at a single, safety-net institution, we used multinomial logistic regression models to compare predictors of vaccination among women who received Tdap only, influenza only, and both Tdap and influenza vaccines.ResultsAmong 3132 full-term deliveries, women were primarily non-Hispanic black (67.5%), between the ages of 21–34 (65.3%), and multiparous (76.0%). The rates of only influenza or Tdap vaccination were 10.3% and 21.6%, respectively; 43.3% of women received both vaccines, and 24.9% of women did not receive either vaccine. In the adjusted models, Hispanic ethnicity was positively associated with receipt of all types of vaccination and non-Spanish language interpreter use was positively associated with receipt of Tdap vaccination and Tdap and influenza vaccination. A parity of greater than three and inadequate and unknown prenatal care adequacy were negative predictors of all types of vaccination. Pre-existing hypertension was negatively associated with Tdap vaccination, and HIV-positive status was negatively associated with influenza vaccination and Tdap and influenza vaccination.ConclusionCompared to the national rate of both Tdap and influenza vaccination (32.8%), a higher proportion of women received both vaccines in our study population. Vaccine uptake may be affected by race/ethnicity, use of interpreter services, parity, pre-existing comorbidities, and prenatal care adequacy. The lower rate of influenza vaccination compared to Tdap vaccination suggests that other factors, such as vaccine hesitancy and mistrust, may be differentially impacting influenza vaccination uptake in our predominantly minority population. Future provider and public health approaches to vaccine promotion should incorporate culturally appropriate strategies that address vaccine-related beliefs and misconceptions.     

Impact of Tdap vaccine during pregnancy on the incidence of pertussis in children under one year in Brazil – A time series analysis

Pertussis is a globally distributed infectious disease that is a significant cause of morbidity and mortality, especially in infants who are too young to be immunized. This disease is common in childhood, and when it occurs during the first few months of life, it leads to hospitalization and, sometimes, death. Brazil has adopted the strategy of maternal immunization against pertussis in late 2014. This study aims to analyze public data on the disease to determine whether there was an impact on the disease burden following the introduction of the vaccine Tdap in pregnant women and its magnitude. We performed a time-series analysis of the incidence of pertussis between October 2010 and January 2019. We stratified the population of interest into three groups: infants aged less than two months old, infants aged two to six months, and infants aged six months to one year, according to Brazil's vaccination schedule. We found a protective effect of maternal vaccination in all age groups, more prominent on the first group. Before the intervention, infants under two months had a higher risk of getting pertussis in comparison with infants two to six months old (HR 1.15, CI 95%: 1.11–1.19). After the intervention, age under two months is a protective factor compared with two to six months (HR 0.90, CI 95%: 0.82–0.98). The pertussis incidence reduced in all age groups and all Brazil's Regions.     

Chorioamnionitis following vaccination in the Vaccine Adverse Event Reporting System

BackgroundIn October 2012, the Advisory Committee on Immunization Practices (ACIP) recommended a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) during each pregnancy, irrespective of the woman's prior history of receiving Tdap. A retrospective cohort study to assess the safety of Tdap vaccination in pregnant women in two Vaccine Safety Datalink (VSD) sites during 2010–2012 found a small but statistically significant increased risk of chorioamnionitis.ObjectiveWe conducted a review of the VAERS database to describe reports of chorioamnionitis following receipt of any vaccines.MethodsWe searched the VAERS database for reports of chorioamnionitis after any vaccine in the United States during the period from July 1, 1990 through February 2, 2014.ResultsVAERS received 31 reports of chorioamnionitis out of 3389 pregnancy reports in 24 years. The three most common vaccines in these reports were 2009 H1N1 inactivated influenza, quadrivalent human papillomavirus (HPV4), and Tdap vaccines in 32%, 29% and 26% of reports, respectively. Fifty-eight percent of reports had at least one reported risk factor for chorioamnionitis. Chorioamnionitis was identified in 3 reports of spontaneous abortions and 6 stillbirths, 6 reports of preterm birth (two of whom died) and 16 reports of term birth; maternal outcomes included two reports of postpartum hemorrhage and one report of maternal admission to the intensive care unit. No maternal deaths were reported.ConclusionChorioamnionitis was found to be uncommonly reported, representing 1% of pregnancy reports to VAERS. A majority of reports had at least one risk factor for chorioamnionitis.     

Relationship between patient copayments in Medicare Part D and vaccination claim status for herpes zoster and tetanus-diphtheria-acellular pertussis

Objective: To assess the relationship between copay amount and vaccination claim submission status for tetanus-diphtheria-acellular pertussis (Tdap) and herpes zoster (GSK study identifier: HO-14-14319).

Methods: Retrospective analyses were performed using vaccination administrative claims data in patients aged ≥65 years with ≥1 claim for Tdap or zoster vaccines between 2012 and 2014. To avoid confounding by other financial responsibility, analyses were conducted among patients in the copayment phase of insurance. The impact of patient copay amount on vaccination claim status (“canceled” vs. “paid”) was evaluated by logistic regression separately for Tdap and zoster, adjusting for patient and provider characteristics.

Results: A total of 81,027 (39.2% with canceled claims) and 346,417 patients (56.8% with canceled claims) were included in the Tdap and zoster analyses, respectively. Mean (standard deviation) copay for canceled vs. paid claims was $37.2 (18.4) vs. $31.1 (20.1) for Tdap and $64.9 (36.9) vs. $53.5 (38.8) for zoster. The adjusted odds ratios (ORs) for a canceled Tdap vaccine claim, compared with Objective: To assess the relationship between copay amount and vaccination claim submission status for tetanus-diphtheria-acellular pertussis (Tdap) and herpes zoster (GSK study identifier: HO-14-14319).

Methods: Retrospective analyses were performed using vaccination administrative claims data in patients aged ≥65 years with ≥1 claim for Tdap or zoster vaccines between 2012 and 2014. To avoid confounding by other financial responsibility, analyses were conducted among patients in the copayment phase of insurance. The impact of patient copay amount on vaccination claim status (“canceled” vs. “paid”) was evaluated by logistic regression separately for Tdap and zoster, adjusting for patient and provider characteristics.

Results: A total of 81,027 (39.2% with canceled claims) and 346,417 patients (56.8% with canceled claims) were included in the Tdap and zoster analyses, respectively. Mean (standard deviation) copay for canceled vs. paid claims was $37.2 (18.4) vs. $31.1 (20.1) for Tdap and $64.9 (36.9) vs. $53.5 (38.8) for zoster. The adjusted odds ratios (ORs) for a canceled Tdap vaccine claim, compared with $0 copay, were 1.19 ($1–25 copay), 1.76 ($26–50 copay), 2.42 ($51–75 copay) and 2.40 ($76–100 copay), all p?<?.001. The adjusted ORs for a canceled zoster vaccine claim, compared with $0 copay, were 1.02 ($1–25), 1.39 ($26–50), 1.66 ($51–75), 2.07 ($76–100) and 2.71 (>$100), all p?<?.001 except for $1–25 (p?=?.172).

Conclusions: High patient copay is a barrier to Tdap and zoster vaccinations in Medicare Part D patients. Providing vaccines at low or no copay may improve vaccination rates in these adults.

GSK study identifier: HO-14-14319.     

Antibody persistence and safety and immunogenicity of a second booster dose nine years after a first booster vaccination with a reduced antigen diphtheria-tetanus-acellular pertussis vaccine (Tdap) in adults

BackgroundOver the last decades, pertussis showed periodic increases in its incidence among adults, despite being a vaccine-preventable disease.MethodsThis phase III, multicenter, extension study (NCT00489970) was conducted in adults from the United States, followed at Year (Y) 5 and Y9 post-vaccination with a dose of reduced-antigen-content tetanus-diphtheria-acellular pertussis vaccine containing either 3 (Tdap-B group) or 5 pertussis components (Tdap-A group). Willing participants in Tdap groups and newly-recruited participants (Control group) received one Tdap-B dose at Y9. Antibody persistence (at Y5 and Y9) and safety of Tdap-B at Y9 were assessed. Non-inferiority of immune response elicited by 2 Tdap doses was evaluated at Y9: (i) versus one Tdap-B dose for diphtheria and tetanus in terms of seroprotection rates; (ii) for all antigens in terms of booster response rates (Tdap-B and Tdap-A groups versus Control group); and (iii) for pertussis antigens in terms of geometric mean concentrations (GMCs) versus a 3-dose series of a combined diphtheria-tetanus-acellular pertussis vaccine (DTPa) administered during infancy.Results1257 participants were enrolled at Y5 and 809 participants were vaccinated at Y9. Seroprotection rates in both Tdap groups were ≥98.4% and ≥98.0% (Y5) and ≥98.3% and ≥98.1% (Y9) for diphtheria and tetanus, respectively. For pertussis antigens, antibody concentrations above assay cut-offs were observed for ≥76.6% (Y5) and ≥84.9% (Y9) of participants in Tdap groups. At Y9, one month post-Tdap vaccination, comparable seroprotection/seropositivity rates and antibody GMCs were observed among groups. Non-inferiority of immune responses in both Tdap groups was demonstrated when compared to the Control group for diphtheria and tetanus and to a 3-dose DTPa series for pertussis antigens. Non-inferiority criteria in terms of booster response were not met for all antigens. No safety concerns were raised.ConclusionA second dose of Tdap-B administered in adults, 9 years after initial Tdap vaccination, is immunogenic and well-tolerated.     

Cost-effectiveness analysis of pertussis vaccination during pregnancy in Japan

BackgroundBoth re-emergence of pertussis outbreak among adolescents/adults and recent approval of the extended use of DTaP vaccine for boosting adolescents/adults against pertussis in Japan, have raised the possibility of using aP-containing vaccine in pregnant women to protect neonates and unvaccinated infants. There is a need, therefore, to evaluate the value for money of such possibility.MethodsWe evaluated the cost-effectiveness of conducting antepartum maternal vaccination (AMV) strategy in Japan. Considering the duration of vaccine effectiveness for infant (single year) and for mother (multiple years), the decision tree model and Markov model was adapted for infant and mother, respectively. Incremental cost-effectiveness ratio (ICER) compared with current no AMV strategy from societal perspective were calculated. The transition probabilities, utility weights to estimate quality-adjusted life year (QALY), and disease treatment costs were either calculated or extracted from literature. Costs per vaccination was assumed at ¥6000/US$54.5. Markov model for mothers with one-year cycle runs up to year four after vaccination, based on the waning of vaccine effectiveness. Infant who survived from pertussis was assumed to live until to his/her life expectancy.ResultsAMV strategy reduces disease treatment costs, while the reduction cannot offset the vaccination cost. Incremental QALYs were at 0.0002802, among them 79.5% were from infants, and others from mothers. ICER was ¥9,149,317/US$83,176 per QALY gained. One-way sensitivity analyses identified that the incidence rate and costs per shot were the two main key variables to impact the ICER.ConclusionWe found that vaccinating pregnant women with aP-containing vaccine to prevent neonatal and unvaccinated infants from pertussis-associated disease in Japan can be cost-effective from societal perspective, under the WHO-suggested “cost-effective” criteria (1 to 3 times of GDP). Pertussis is expected be designated as a notifiable disease in 2018, re-analysis should be conducted when straightforward incidence data is available.