Tdap Administration Research Articles

Vaccination uptake for pertussis and influenza vaccines in pregnancy among different practices at a single institution.

The authors investigated tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) and influenza vaccination during pregnancy following Advisory Committee on Immunization Practices' (ACIP's) recommendation for antenatal pertussis vaccination. A retrospective chart review was performed in 2019 of women receiving prenatal care at our institution between January 1, 2014 and December 31, 2018. Receipt of ACIP-recommended vaccines were examined using Current Procedural Terminology codes to identify initiation of prenatal care, then administration of Tdap and influenza vaccines. Data were examined by individual practice (university faculty, community physicians, obstetrics and gynecology (OBGYN) residents, and family medicine residents, practice staff composition, vaccination protocol use, and insurance status. Statistical analyses were performed using χ2 testing and χ2 testing of linear trend. Within our cohort (n = 17 973), highest vaccination uptake occurred in the university-based OBGYN faculty practice (Tdap = 58.2%, influenza = 56.5%) with lowest uptake in the OBGYN resident practice (Tdap = 28.6%, influenza = 18.5%). Higher uptake occurred in practices with standing orders, more advanced practice providers, lower provider to nursing ratios, and lower rates of Medicaid insurance. These data demonstrated higher vaccination uptake with standing orders, more advanced practice providers, and lower provider to nurse ratios. Future work optimizing practice staff composition and vaccination protocols may increase vaccine uptake.

Coverage for pertussis vaccination during pregnancy with 4 models of vaccine delivery: a quasiexperimental, multicentre observational study.

Background:Vaccination of pregnant people with a vaccine containing acellular pertussis (tetanus–diphtheria–acellular pertussis [Tdap]) has been recommended in Canada since 2018, and the evaluation of delivery models for efficient maternal Tdap administration is a priority for the Quebec Ministry of Health. We implemented 3 vaccine delivery models, in addition to the existing standard of practice model, and compared the vaccine coverage achieved by the 4 models in Quebec.Methods:In this quasiexperimental, multicentre observational study, we recruited pregnant people at less than 21 weeks’ gestation in 4 Quebec regions from April to October 2019. We compared 4 vaccine delivery models: local community service centres (centre local de services communautaires [CLSCs], baseline), family medicine groups (FMGs), obstetrics clinic and the oral glucose challenge test (OGCT). In addition to the CLSCs, 3 FMGs, 1 obstetric clinic and a hospital-based OGCT screening program participated. We determined vaccination status from a self-reported questionnaire, the Quebec Immunization Registry or medical charts. We compared model-specific (for participants recruited to a model and subsequently vaccinated within that model) and overall vaccine coverage (considering all vaccine delivery pathways) and used logistic regression to adjust for sociodemographic variables.Results:Overall, 946 of 1000 recruited pregnant people were eligible for analyses. Vaccination via the FMGs achieved the highest model-specific vaccine coverage (67.8%, 95% confidence interval [CI] 60.5%–74.4%), but coverage was not significantly different from the CLSCs (63.8%, 95% CI 57.6%–69.6%). For overall vaccine coverage, the FMG (86.5%, 95% CI 80.6%–90.9%) and obstetrics models (85.9%, 95% CI 80.9%–89.7%) achieved significantly higher vaccine coverage than the CLSCs (66.3%, 95% CI 60.1%–71.9%). The OGCT model did not improve overall vaccine coverage (61.8%, 95% CI 56.1%–67.2%).Interpretation:Compared with CLSCs, overall vaccine coverage was higher when Tdap was offered in FMGs or an obstetrics clinic providing prenatal care. Health professionals involved in pregnancy follow-up recommending and offering the vaccine may be a key factor in optimizing vaccine coverage.

Health Outcomes in Young Children Following Pertussis Vaccination During Pregnancy.

Maternal immunization with tetanus, diphtheria, and acellular pertussis vaccine (Tdap) is routinely recommended in many countries as a strategy to protect young infants against severe pertussis infection; few studies have assessed whether prenatal exposure to the vaccine is associated with any longer-term adverse health effects in children. We evaluated the long-term safety of exposure to Tdap vaccination during pregnancy. Population-based retrospective cohort study conducted in Ontario, Canada using multiple linked province-wide health administrative databases. All live births between April 2012 and March 2017 were included, and children were followed for up to 6 years to ascertain study outcomes. Children exposed to prenatal Tdap were propensity score matched to unexposed children at a 1:5 ratio. Tdap vaccination during pregnancy was ascertained by using vaccine-specific fee codes. Immune-related (infectious diseases, asthma) and nonimmune-related (neoplasm, sensory disorders) outcomes and a nonspecific morbidity outcome (urgent or inpatient health service use) were evaluated from birth to end of follow-up. Of 625 643 live births, 12 045 (1.9%) were exposed to Tdap in utero. There were no significant increased risks of adverse childhood outcomes and prenatal Tdap exposure; however, we observed inverse associations (adjusted incidence rate ratio [95% confidence interval]) with upper respiratory infections (0.94 [0.90-0.99]), gastrointestinal infections (0.85 [0.79-0.91]), and urgent and inpatient health service use (0.93 [0.91-0.96]). Exposure to Tdap vaccination in pregnancy was not associated with any increased risk of adverse health outcomes in early childhood, supporting the long-term safety of Tdap administration in pregnancy.

1483. Maternal Tdap Vaccination During Pregnancy and Immune Response: A Comparison Between Infants Born to Mothers Primed with Acellular or Whole Cell Pertussis Vaccines

BackgroundAcellular pertussis (aP) vaccines replaced whole cell pertussis (wP) vaccines for the recommended childhood primary series in the United States in 1997. As women primed with aP vaccines in childhood enter reproductive age, it is unknown how maternal aP-priming will impact pertussis protection conferred to infants through Tdap (tetanus toxoid, reduced diphtheria toxoid and acellular pertussis) vaccination during pregnancy.MethodsInfants born at term to women who had been vaccinated with Tdap at 27-36 weeks’ gestation and ≥ 14 days prior to delivery were included. Geometric mean concentrations (GMC) of pertussis-specific antibodies (measured in IU/mL) in umbilical cord blood of infants born to women born after 1997 (aP vaccine primed) were compared with those born to women born before 1992 (wP vaccine primed).Results253 and 506 neonates born to aP- and wP-primed women, respectively, were included. Compared with wP-primed women, aP-primed women were younger (19.3 v. 24.5 years), more likely to be Hispanic or non-Hispanic black and to have infants with lower birthweight (3264 v. 3392 grams, p< 0.01 for all). Gestation at Tdap receipt, gestational age at delivery, and interval between Tdap administration and delivery were not statistically different.Antibodies against pertussis toxin (PT) and filamentous hemagglutinin (FHA) were significantly lower among neonates born to aP-primed versus wP-primed mothers (PT: 17.3 v. 36.4, GMC ratio 0.475 (0.408 – 0.552) (Figure); FHA: 104.6 v. 121.4, GMC ratio 0.861 (0.776 – 0.958)). No significant differences were observed between the aP and wP-primed groups for anti- fimbriae (FIM) or anti-pertactin (PRN) antibodies ((FIM: 469.6 v. 577.2, GMC ratio 0.81 (CI 0.65 – 1.01); PRN 338.8 v. 292.6, GMC ratio 1.16 (CI 0.99 – 1.35)).Figure. Distribution of anti-PT antibody levels in cord blood in infants born to women who were primed with whole cell pertussis compared with acellular pertussis vaccines in childhood.* ConclusionThe type of pertussis vaccine a woman received during childhood significantly impacted her response to Tdap vaccination during pregnancy; the largest reduction was in anti-PT antibodies thought to be most important in preventing severe infection in infants. These findings suggest that infants born to aP-primed women who received Tdap during pregnancy may have less passive protection against pertussis during the first months of life than those born to wP-primed women.Disclosures All Authors: No reported disclosures

Arthus Reaction as an Adverse Event Following Tdap Vaccination.

Repeat administration of tetanus toxoid-containing vaccines has rarely been associated with Arthus phenomenon, an immune-complex reaction. In the US, since 2013, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccines (Tdap) have been recommended for administration during each pregnancy. Separately, in 2019, one Tdap was approved for repeat administration in adults in the US. We aimed to describe trends in spontaneously reported Arthus reactions following Tdap in the US and to assess the risk of this phenomenon in persons receiving Tdap repeatedly. We reviewed Arthus reports in the Vaccine Adverse Events Reporting System (VAERS), 1990–2018. Reporting rates were estimated using Tdap doses distributed data. A systematic literature review was conducted in MEDLINE for any Arthus cases reported in Tdap clinical trials and observational studies published between 2000 and 2019. We found 192 Arthus reports in VAERS after any vaccine, of which 36 occurred after Tdap and none were reported during pregnancy. The Arthus reporting rate was estimated at 0.1 per million doses distributed. We identified eight published studies of Tdap administration within five years after a previous dose of tetanus toxoid-containing vaccine; no Arthus cases were reported. We conclude that Arthus reaction following Tdap is extremely rare. Increasing frequency of repeat Tdap administration in adults in the US did not result in a detectable increase in reporting rates of this phenomenon, confirming the favorable safety profile of Tdap.

Initiation of Post-Transplant Vaccination Among Allogeneic and Autologous HCT Recipients: A Single Center, Retrospective Quality Improvement Assessment

<h3>Introduction</h3> Given the significant morbidity from infection after HCT, guidelines have recommended re-vaccination starting at 6 to 12 months post-tx. Guideline adherence, however, has been varied across institutions. <h3>Objectives</h3> We report on a quality improvement initiative at our BMT center aimed at identifying differences in re-vaccination between allogeneic (alloSCT) and autologous (ASCT) HCT pts. <h3>Methods</h3> We performed an analysis of alloSCT pts at our institution from 2015 to 2017 and ASCT pts from 2017; analysis was done in February 2019. Pts were included in the study if they were alive 12 months post-tx and had not had another HCT after the tx of analysis. Charts were reviewed for administration of PCV13, Tdap or DTaP, HiB, inactivated polio, Hep B, Hep A, and meningococcal vaccines. Initiation of re-vaccination was defined as starting at least three separate vaccination series. The percentage of pts initiated on re-vaccination and the median time to vaccine initiation were compared using the Fisher's exact test and the Mann-Whitney U test, respectively. Incidence of chronic GVHD, use of rituximab within one year post-tx, and CAR-T therapy were evaluated by chart review. Incidence of acute GvHD was collected from The Mount Sinai Acute GvHD International Consortium. <h3>Results</h3> Among HCT pts in 2017, significantly more alloSCT pts were initiated on re-vaccination series than ASCT pts (67.5% vs 37.5%; p = 0.0007), although there was no difference in the median time to vaccine initiation among pts who were initiated (Table 1). Among all pts in the cohort, there were no differences in vaccine initiation based on a history of acute or chronic GVHD in alloSCT pts, nor based on post-tx rituximab use in all pts (Table 1). Seven pts subsequently underwent CAR-T therapy, only one of whom started re-vaccination. <h3>Conclusion</h3> This quality initiative demonstrated that our re-vaccination initiation timing was within guideline recommendations for the majority of alloSCT patients. Our study suggests that ASCT pts may have stronger barriers to re-vaccination, such as maintenance therapies or the presence of outside practitioners. We are now using this assessment to standardize the re-vaccination efforts at our BMT center. Potential barriers to re-vaccination should be further evaluated, including the effect of post-tx treatments such as CAR-T therapy.

A Retrospective Cohort Study of Safety Outcomes in New Zealand Infants Exposed to Tdap Vaccine in Utero.

We aimed to evaluate the safety of maternal Tdap; thus, we assessed health events by examining the difference in birth and hospital-related outcomes of infants with and without fetal exposure to Tdap. This was a retrospective cohort study using linked administrative datasets. The study population were all live-born infants in New Zealand (NZ) weighing at least 400 g at delivery and born to women who were eligible for the government funded, national-level vaccination program in 2013. Infants were followed from birth up to one year of age. There were a total of 69,389 eligible infants in the cohort. Of these, 8299 infants were born to 8178 mothers exposed to Tdap (12%), primarily between 28 and 38 weeks gestation as per the national schedule. Among the outcomes, we found a reduced risk for moderate to late preterm birth, low birth weight, small for gestational age, large for gestational age, respiratory distress syndrome, transient tachypnea of newborn, tachycardia or bradycardia, haemolytic diseases, other neonatal jaundice, anaemia, syndrome of infant of mother with gestational diabetes, and hypoglycemia in infants born to vaccinated mothers. There was no association between maternal Tdap, infant Apgar score at 5 min after birth, asphyxia, sepsis or infection, or hypoxic ischemic encephalopathy. Infant exposure to Tdap during pregnancy was associated with a higher mean birthweight (not clinically significant) and higher odds for ankyloglossia and neonatal erythema toxicum diagnoses. There were insufficient observations to allow examination of the effect of Tdap on extreme preterm and very preterm birth, and stillbirth, infant death, or microcephaly. Overall, we found no outcomes of concern associated with the administration of Tdap during pregnancy. NZ Health and Disability Ethics Committee Approval #14/N.T.A/169/AM05.

Immunogenicity of a Quadrivalent Human Papillomavirus Vaccine When Co-Administered with Tetanus-Reduced Diphtheria-Acellular Pertussis and Quadrivalent Meningococcal Conjugate Vaccines in Healthy Adolescents: Results from a Randomized, Observer-Blind, Controlled Trial.

IntroductionVaccines against human papillomavirus (HPV), tetanus, diphtheria, pertussis (Tdap) and Neisseria meningitidis are widely recommended in adolescents. A phase-4 observer-blind study was performed to investigate the impact of concomitant administration of a quadrivalent HPV (HPV4) and Tdap vaccine with a quadrivalent meningococcal CRM197-conjugate vaccine (MenACWY-CRM) in terms of immunogenicity against the different vaccine antigens and overall safety profile. Previous results showed that concomitant administration of the three vaccines did not impact the immunogenicity of Tdap and MenACWY, or safety. This article presents recently released HPV immunogenicity results.MethodsHealthy adolescents aged 11–18 years (801) were randomized to receive either HPV4 + Tdap + MenACWY or HPV4 + Tdap + Placebo and two additional doses of HPV4 at 2 and 6 months after the first dose. Antibody responses to HPV types (HPV-6, -11, -16 and -18) were assessed at baseline and at 1 month post-full vaccination.ResultsPost-third HPV4 dose, non-inferiority of immune responses to HPV4 + Tdap + MenACWY vs. HPV4 + Tdap + Placebo was demonstrated; the lower limits of two-sided 95% CIs of the between-group differences in seroconversion rates were > − 5% (non-inferiority margin) against each HPV type tested. Seroconversion rates ranged between 98.0% (HPV-6) and 99.7% (HPV-11 and HPV-18) in group HPV4 + Tdap + MenACWY and from 99.0% (HPV-11 and HPV-16) to 99.7% (HPV-6 and HPV-18) in group HPV4 + Tdap + Placebo.ConclusionOverall, these data support the concomitant administration of HPV4, Tdap and MenACWY-CRM in adolescents.FundingNovartis Vaccines and Diagnostics Inc., now part of the GSK group of companies.Trial RegistrationClinicalTrials.gov identifier, NCT01424644.

Increasing antepartum Tdap vaccine administration: A quality improvement initiative

The Centers for Disease Control and Prevention (CDC) recommends antepartum Tdap vaccination for women with each pregnancy to protect themselves and their vulnerable infants through transplacental transfer of maternal antibodies. Our aim was to increase the rate of antepartum Tdap vaccine administration by 20%. Obstetricians were surveyed to identify their present approaches and barriers to antepartum Tdap vaccine administration to help guide the development of our intervention. Limited staff training, lack of vaccine on site, and cost were the most commonly identified barriers. Using these survey responses, existing literature, and brainstorming conversations with colleagues, an interdisciplinary workgroup then created a fishbone analysis and developed a 5-step intervention to address these barriers: (1) educate providers and patients on Tdap and pertussis; (2) increase Tdap availability to all pregnant women; (3) remind staff of the established Tdap standing order to facilitate administration; (4) encourage obstetricians to offer Tdap; (5) transfer documentation of Tdap administration from office to hospital. To monitor changes in the process over 15 months of pre- and post-intervention, data were collected from monthly chart audits and a two-phase control chart was created. The main outcome measure was proportion of eligible women who received Tdap during current pregnancy. In the pre-intervention period, 362 of 636 eligible women (56.9%) received Tdap during their current pregnancy; in the post-intervention period, 457 of 708 eligible women (64.5%) received Tdap during their current pregnancy. This absolute difference of 7.6% (64.5% vs. 56.9%, p < 0.01) represents a 13.4% relative increase (64.5%/56.9%) in the proportion of clinically eligible pregnant women who received Tdap. This represents a clinically and statistically significant increase in the rate of antepartum Tdap immunization. More research is needed to further understand obstetric barriers and maternal refusal of antepartum Tdap administration.

Provider group type and Tdap coverage in pregnancy

IntroductionThe Advisory Committee on Immunization Practices (ACIP) has focused on maternal Tdap immunization as an important means to protect neonates from pertussis infections. There is little published data on provider and/or clinic characteristics as predictors of maternal Tdap uptake. This study examined differences in maternal Tdap coverage in women delivering at a single academic institution, but cared for prenatally in different clinical settings, in 2013, 2014, and 2015. Additionally, the accuracy and utilization of Vermont's immunization information system (IIS) was assessed. MethodsThis was a retrospective, multiple time-point cross-sectional analysis of annual maternal Tdap coverage in women delivering at a single academic institution in the 3 years following a fundamental change in national maternal Tdap vaccination guidelines. Tdap administration was examined across different obstetric groups using chart review and data from the state's IIS. ResultsAll obstetric care groups except the resident-staffed clinic significantly increased maternal Tdap coverage in 2014, compared to 2013 coverage, with no further increase in 2015. In contrast, there was no increase in maternal Tdap coverage in 2014 in the resident-staffed clinics, but then a statistically significant increase in 2015. Overall Tdap coverage in 2014 was 80.4%, with variation in Tdap coverage between clinics types. In the subset of women who were cared for by the University-based groups, there was significant variation in Tdap coverage between clinics, despite racial homogeneity, which persisted after adjustment for maternal age and insurance type. The state's IIS was found to be highly accurate, using individual chart review as the “gold standard.” DiscussionWhile we demonstrated high maternal Tdap coverage in women delivering at our institution, differences in clinic type and provider training appeared to impact immunization rates, as well as how quickly evolving national recommendations were adopted. Additionally, the fidelity of the state's IIS data was verified.

Pertussis Immunisation in Pregnancy Safety (PIPS) Study: A retrospective cohort study of safety outcomes in pregnant women vaccinated with Tdap vaccine

BackgroundNew Zealand has funded the administration of tetanus, diphtheria and acellular pertussis (Tdap) vaccine during pregnancy to prevent infant pertussis since 2013. The aim of this study was to assess the safety of Tdap vaccine administered to pregnant women as part of a national maternal immunisation programme. MethodsWe conducted a national retrospective observational study using linked administrative New Zealand datasets. The study population consisted of pregnant women eligible to receive funded Tdap vaccination from 28 to 38 weeks gestation in 2013. Primary study outcomes were based on prioritised adverse events for the assessment of vaccine safety in pregnant women, as defined by WHO and Brighton Collaboration taskforces. We examined the effect of Tdap vaccination on prioritised maternal outcomes using Cox proportional hazard models. Adjusted hazard ratios controlled for key confounding variables. ResultsIn the cohort of 68,550 women eligible to receive funded antenatal Tdap vaccination during 2013, 8178 (11.9%) were vaccinated and 60,372 (88.1%) were unvaccinated. The use of Tdap in pregnancy was not associated with an increase in the rate of primary outcomes, including preterm labour; pre-eclampsia; pre-eclampsia with severe features; eclampsia; gestational hypertension; fetal growth restriction; or post-partum haemorrhage. Tdap also did not increase secondary outcomes, including gestational diabetes mellitus; antenatal bleeding; placental abruption; premature rupture of membranes; preterm delivery; fetal distress; chorioamnionitis; or, maternal fever during or after labour. Lactation disorders was the only secondary maternal outcome with a significantly increased hazard ratio. Tdap vaccine had a protective effect on pre-eclampsia with severe features, preterm labour, preterm delivery, and antenatal bleeding. ConclusionWe did not detect any biologically plausible adverse maternal outcomes following Tdap vaccination during pregnancy. This study provides further assurance that Tdap administration during pregnancy is not associated with unexpected safety risks.

Effectiveness of Prenatal Tetanus, Diphtheria, Acellular Pertussis Vaccination in the Prevention of Infant Pertussis in the U.S.

It is recommended that all pregnant women in the U.S. receive tetanus, diphtheria, acellular pertussis (Tdap) immunization to prevent infant pertussis. This study's objective was to examine the clinical effectiveness of prenatal Tdap, and whether effectiveness varies by gestational age at immunization. A nationwide cohort study of pregnant women with deliveries in 2010-2014 and their infants was performed. Commercial insurance claims data were analyzed in 2016-2017 to identify Tdap receipt by the pregnant women, and hospitalizations and outpatient visits for pertussis in their infants until the infants reached 18 months of age. Pertussis occurrence was compared between infants of mothers who received prenatal Tdap (overall and stratified by gestational age at administration) and infants of unvaccinated mothers. There were 675,167 mother-infant pairs in the cohort. Among infants whose mothers received prenatal Tdap, the rate of pertussis was 43% lower (hazard ratio=0.57, 95% CI=0.35, 0.92) than infants whose mothers did not receive prenatal or postpartum Tdap; this reduction was consistent across pertussis definitions (hazard ratio for inpatient-only pertussis=0.32, 95% CI=0.11, 0.91). Pertussis rates were also lower for infants whose mothers received Tdap during the third trimester. Infants whose mothers received Tdap at <27 weeks of gestation did not experience reductions in pertussis rates (hazard ratio for pertussis=1.10, 95% CI=0.54, 2.25). Infants of mothers who received prenatal Tdap experienced half the rate of pertussis as compared with infants of unimmunized mothers. These results do not provide evidence to support changing the currently recommended timing of Tdap administration in pregnancy.

Effect of Tdap upon antibody response to meningococcal polysaccharide when administered before, with or after the quadrivalent meningococcal TT-conjugate vaccine (coadministered with the 13-valent pneumococcal CRM197-conjugate vaccine) in adult Hajj pilgrims: A randomised controlled trial

Hajj pilgrims are susceptible to several serious infections and are required to receive multiple vaccinations. Polysaccharide-protein conjugate vaccines contain carrier proteins such as tetanus toxoid (TT), diphtheria toxoid or a mutant of diphtheria toxoid (CRM197). These carrier proteins may interact with other conjugate or combination vaccines containing tetanus or diphtheria on concurrent or sequential administration. We examined the immune interaction of separate and concomitant administration of a tetanus/diphtheria/acellular pertussis (Tdap) vaccine with a TT-conjugated quadrivalent meningococcal vaccine (MCV4) (coadministered with 13-valent pneumococcal CRM197-conjugate vaccine [PCV13]) in adult Australian pilgrims before attending Hajj in 2015.We randomly assigned each participant to one of three vaccination schedules. Group 1 received Tdap 3–4 weeks before receiving MCV4 coadministered with PCV13. Group 2 received all three vaccines concomitantly. Group 3 received MCV4 and PCV13 3–4 weeks before Tdap. Blood samples were collected at baseline, at each vaccination visit and 3–4 weeks after vaccination and tested for response to meningococcal serogroups C, W and Y using a serum bactericidal antibody (rSBA) assay with baby rabbit complement, and to diphtheria and tetanus toxoid, measuring IgG antibodies by ELISA. Participants completed symptom diaries after each vaccination. A total of 166 participants aged 18–64 (median 42) years were recruited, of whom 160 completed the study. Compared to the other groups, Group 1 (given Tdap first) had significantly lower proportion of subjects achieving a ≥4-fold rise in rSBA for serogroup W. No difference was detected across the three groups in achieving protection threshold (rSBA ≥8 post vaccination) or SBA geometric mean titre (GMT) post vaccination.Group 3, which was given MCV4/PCV13 first, had high levels of antibody against diphtheria and tetanus than the other groups, when tested prior to receipt of Tdap; Only the anti-tetanus responses remained significantly higher after Tdap administration. No serious adverse events were reported.In conclusion, when multiple vaccination is required for Hajj pilgrims, administering Tdap concurrently with MCV4/PCV13 produces adequate immune responses, and avoids meningococcal immune interference, in the convenience of a single consultation. However, giving Tdap 3–4 weeks after MCV4/PCV13 has the advantage of an enhanced tetanus toxoid response.The trial is Trials Registry (ANZCTR): ACTRN12613000536763.

Immunogenicity and safety of a second booster dose of an acellular pertussis vaccine combined with reduced antigen content diphtheria-tetanus toxoids 10 years after a first booster in adolescence: An open, phase III, non-randomized, multi-center study

ABSTRACTPertussis is a highly contagious disease, for which periodic peaks in incidence and an increasing number of outbreaks have been observed over the last decades. The reduced-antigen-content tetanus-diphtheria-acellular pertussis vaccine (Tdap) can be used to boost individuals aged ≥10 years, vaccinated in infancy with a diphtheria-tetanus-acellular pertussis vaccine (DTaP), to reduce pertussis morbidity and maintain protection against diphtheria and tetanus throughout adolescence and adulthood. This phase III, open-label, non-randomized, multicenter follow-up study (NCT01738477) enrolled 19–30-year-old participants from the United States who had received booster vaccination 10 years earlier with either Tdap (Tdap group) or Td (Td group). In total, 128 (Tdap group) and 37 (Td group) participants received Tdap vaccination. After administration of Tdap, all participants were seroprotected (antibody concentrations ≥0.1 international units [IU]/ml) against diphtheria and tetanus. Immune responses to a second Tdap dose in the Tdap group were shown to be non-inferior to responses elicited by a first Tdap dose in the Td group for diphtheria and tetanus and to a 3-dose DTaP vaccination during infancy for pertussis antigens (primary objectives). Post-booster vaccination, all participants in both groups had antibody concentrations above assay cut-offs and antibody geometric mean concentrations increased by 3.8–15.5-fold compared to pre-booster levels for all antigens. The incidence of adverse events was similar in the Td (80.6%) and Tdap (85.6%) groups (no serious adverse events reported). A Tdap dose administered after previous Td or Tdap vaccination was shown to be immunogenic and well-tolerated in young adults, supporting repeated vaccination with Tdap at 10-year intervals.

Humoral immunity 10 years after booster immunization with an adolescent and adult formulation combined tetanus, diphtheria, and 5-component acellular pertussis vaccine in the USA

BackgroundIn a prospective, randomized pivotal phase III clinical trial, the immunogenicity and reactogenicity of a tetanus-diphtheria-acellular pertussis vaccine (Tdap) and a tetanus-diphtheria vaccine (Td) vaccine were studied in participants aged 11–64 years. Here we report antibody persistence through 10 years after vaccination. MethodsParticipants who received Tdap or Td in the original phase III trial and provided pre- and post-vaccination serum samples were recruited to donate sera at 1, 3, 5 and 10 years post-vaccination. Antibody concentrations were measured using standard assay techniques. ResultsInitially, 1457 Tdap and 1152 Td recipients were included; of these, 175 persons from Tdap group were available at the final study bleed point. Nearly all adolescents in both groups had diphtheria antibody levels ≥0.1 IU/mL 1 month after vaccination, which were maintained in ≥95% of vaccinees at 5 and 10 years. Among adults, ≥94% had diphtheria antibody levels ≥0.1 IU/mL 1 month after vaccination, which were maintained in ≥80% at 5 and 10 years. Nearly all participants had tetanus antibodies ≥0.1 IU/mL throughout the study. PT antibodies declined to pre-vaccination levels approximately 5 years post-vaccination; FHA, PRN and FIM antibodies waned at 5 and 10 years but remained several-fold higher than pre-vaccination levels. ConclusionsTdap and Td provide long-lasting protective immune responses against diphtheria and tetanus. Pertussis antibodies following Tdap generally exceeded pre-vaccination levels throughout the study, but showed substantial waning. These data may inform discussion of the need for repeat Tdap booster vaccinations among adults. Trial registrationThe original phase III clinical trial, as well as the 1-, 3-, and 5-year serology follow-up studies were conducted prior to mandatory registration. The 10-year serology follow-up data collection was performed as part of a repeat Tdap administration clinical trial that was registered under clinicaltrials.gov number NCT01439165.

Effectiveness of Prenatal Tdap Immunization in the Prevention of Infant Pertussis in the United States

BackgroundThe Centers for Disease Control and Prevention recommends that all pregnant women in the United States receive tetanus-diphtheria-acellular pertussis (Tdap) immunization to prevent infant pertussis. While the vaccine may be administered at any time during pregnancy, the recommendations define administration at 27 to 36 weeks of gestation as optimal timing to prevent infant pertussis. These recommendations were primarily based on immunogenicity studies. The objective of this study was to examine the clinical effectiveness of prenatal Tdap, and to understand whether effectiveness varies by gestational age at immunization.MethodsWe performed a nationwide cohort study of pregnant women with deliveries in 2010–2014 and their infants. Commercial insurance claims data were used to identify receipt of Tdap immunization in the pregnant women, and hospitalizations and outpatient visits for pertussis in their infants until 18 months of age. To address the difficulties in diagnosing pertussis, we also employed a “probable pertussis” definition, as an inpatient or outpatient diagnosis of pertussis, plus antibiotic treatment with a macrolide or trimethoprim/sulfamethoxazole within 7 days of diagnosis. Pertussis occurrence was compared between infants of mothers who received prenatal Tdap (overall, and stratified by gestational age at administration) and infants of unvaccinated mothers.ResultsThere were 675,167 mother–infant pairs included in the cohort. Among infants whose mothers received Tdap at any time during pregnancy, the rate of pertussis hospitalization was 50% lower (adjusted hazards ratio (HR) = 0.50, 95% CI: 0.23, 1.09), and the rate of probable pertussis was 42% lower (HR = 0.58, 95% CI: 0.38, 0.89) than infants of unimmunized mothers. Pertussis rates were also lower for infants whose mothers received prenatal Tdap during the third trimester. Infants whose mothers received Tdap before the third trimester also tended to have lower rates of pertussis, but these estimates were imprecise.ConclusionInfants of mothers who received prenatal Tdap experienced half the rate of pertussis as compared with infants of unimmunized mothers. Our results do not provide evidence to support changing the currently recommended timing of Tdap administration in pregnancy.Disclosures S. Becker-Dreps, Pfizer: Consultant and Grant Investigator, Consulting fee and Research grant; A. M. Butler, Astra Zeneca: Consultant, Support to institution; Amgen: Grant Investigator, Investigator initiated grant to institution; D. J. Weber, Merck: Consultant and Speaker’s Bureau, Consulting fee and Speaker honorarium; Pfizer: Consultant, Consulting fee; J. B. Layton, Merck: Member of Center for Pharmacoepidemiology, Support to institution; GlaxoSmithKline: Member of Center for Pharmacoepidemiology, Support to institution; UCB Biosciences: Member of Center for Pharmacoepidemiology, Support to institution

Prenatal Tdap immunization and risk of maternal and newborn adverse events.

Many countries recommend combined tetanus toxoid, reduced diphtheria toxoid and acellular pertussis immunization (Tdap) during pregnancy to stimulate transplacental transmission of pertussis antibodies to newborns. The immune system can be altered during pregnancy, potentially resulting in differing immunization risks in pregnant women. The safety of widespread Tdap immunization during pregnancy needs to be established. Our objective was to assess whether prenatal Tdap immunization was associated with adverse birth outcomes, and to evaluate the effect of timing of Tdap administration on these outcomes. We identified pregnancies at delivery in a large insurance claims database (2010-2014). Tdap immunization was categorized as optimal prenatal (27+weeks), early prenatal (<27weeks), postpartum (≤7days post-delivery), or none. Medical claims were searched to identify maternal adverse immunization reactions (e.g. anaphylaxis, fever, Guillian-Barre syndrome [GBS]), adverse birth outcomes (e.g. preeclampsia/eclampsia, premature rupture or membranes, chorioamnionitis) and newborn outcomes (e.g. respiratory distress, pulmonary hypertension, neonatal jaundice). Women with optimal or early prenatal Tdap were compared to those not immunized in pregnancy, using propensity score-weighted log-binomial regression and Cox proportional hazards models to estimate risk ratios (RR) and hazard ratios (HR). We identified 1,079,034 deliveries and 677,075 linked newborns; 11.5% were immunized optimally and 2.3% immunized early. There were 1 case of post-immunization anaphylaxis, and 12 cases of maternal encephalopathy (all post- delivery); there were no cases of GBS. Optimally-timed immunization was associated with small increased relative risks of: chorioamnionitis [RR=1.11, (95% CI: 1.07-1.15), overall risk=2.8%], and postpartum hemorrhage [RR=1.23 (95% DI: 1.18-1.28), overall risk=2.4%]; however, these relative increases corresponded to low absolute risk increases. Tdap was not associated with increased risk of any adverse newborn outcome. Overall, prenatal Tdap immunization was not associated with newborn adverse events, but potential associations with chorioamnionitis consistent with one previous study and postpartum hemorrhage require further investigation.

Safety of Tdap vaccine in pregnant women: an observational study

ObjectivesActively recruit and intensively follow pregnant women receiving a dose of acellular pertussis vaccine for 4 weeks after vaccination.Design and settingsA prospective observational study conducted in 2 New Zealand regions.ParticipantsWomen...

Immunisation schedule of the Spanish Association of Paediatrics: 2016 recommendations

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV-AEP) annually publishes the immunisation schedule which, in our opinion, estimates optimal for children resident in Spain, considering available evidence on current vaccines. We acknowledge the effort of the Ministry of Health during the last year in order to optimize the funded unified Spanish vaccination schedule, with the recent inclusion of pneumococcal and varicella vaccination in early infancy. Regarding the funded vaccines included in the official unified immunization schedule, taking into account available data, CAV-AEP recommends 2+1 strategy (2, 4 and 12 months) with hexavalent (DTPa-IPV-Hib-HB) vaccines and 13-valent pneumococcal conjugate vaccine. Administration of Tdap and poliomyelitis booster dose at the age of 6 is recommended, as well as Tdap vaccine for adolescents and pregnant women, between 27-36 weeks gestation. The two-dose scheme should be used for MMR (12 months and 2-4 years) and varicella (15 months and 2-4 years). Coverage of human papillomavirus vaccination in girls aged 11-12 with a two dose scheme (0, 6 months) should be improved. Information for male adolescents about potential beneficial effects of this immunisation should be provided as well. Regarding recommended unfunded immunisations, CAV-AEP recommends the administration of meningococcal B vaccine, due to the current availability in Spanish communitary pharmacies, with a 3+1 scheme (3, 5, 7 and 13-15 months). CAV-AEP requests the incorporation of this vaccine in the funded unified schedule. Vaccination against rotavirus is recommended in all infants. Annual influenza immunisation and vaccination against hepatitis A are indicated in population groups considered at risk.

Tdap vaccination during pregnancy—no signal of safety concerns for infants

Taking advantage of a robust electronic medical record system at Intermountain Healthcare facilities in Utah, Shakib et al performed a retrospective cohort study assessing pregnancy, birth, and infancy outcomes for 138 women who were given tetanus and reduced-content diphtheria toxoids and reduced-content acellular pertussis vaccine (Tdap) compared with 552 randomly selected nonvaccinated pregnant women controls. The study, ending in 2009, was performed before routine recommendation for Tdap administration during pregnancy. The most common reason for Tdap was prophylaxis for open wounds or during acute care visits for trauma. Of pregnant women receiving Tdap, 63% received the vaccine during the first trimester. For all outcomes assessed (ie, preterm delivery, low gestational age or weight, congenital anomaly, or diagnosis of complex conditions in the first 12 months of life), there was no signal of excess occurrence in vaccinated versus unvaccinated cohorts. In light of nationwide increase of pertussis and deaths in infants too young to be protected by the current Tdap schedule, the Centers for Disease Control and Prevention now recommends Tdap administration during every pregnancy. Implementation, however, has been woefully poor to date. This study provides reassurance regarding safety for mothers, their pregnancy, and their infants—even when Tdap was given earlier than the optimal window currently recommended (for maximized antibody level in offspring at birth) of 27 to 36 weeks of gestation. We pediatricians need to encourage obstetricians, family physicians, and internists to immunize pregnant women in order to extend lifesaving vaccines, such as for influenza for mothers and pertussis for neonates, to all people. Article page 1422▶ Tetanus, Diphtheria, Acellular Pertussis Vaccine during Pregnancy: Pregnancy and Infant Health OutcomesThe Journal of PediatricsVol. 163Issue 5PreviewTo assess pregnancy and birth outcomes in infants born to women who did or did not receive tetanus, diphtheria, acellular pertussis (Tdap) vaccine during pregnancy. Full-Text PDF