Diphtheria-tetanus-acellular Pertussis Research Articles

Obstetric and perinatal health outcomes after pertussis vaccination during pregnancy in Ontario, Canada: a retrospective cohort study

Background:In February 2018, Canada’s National Advisory Committee on Immunization recommended maternal vaccination with tetanus–diphtheria–acellular pertussis (Tdap) vaccine during pregnancy to prevent severe pertussis infection in young infants. This study assessed the relation between maternal Tdap vaccination and obstetric and perinatal outcomes in Ontario.Methods:We performed a population-based cohort study of all births from April 2012 to March 2017 using multiple linked health administrative databases. We used Cox regression with a time-dependent exposure variable to estimate adjusted hazard ratios (HRs) for preterm birth (< 37 wk), very preterm birth (< 32 wk) and stillbirth. We assessed remaining outcomes (gestational hypertension, chorioamnionitis, postpartum hemorrhage, severe postpartum hemorrhage, being small for gestational age, neonatal intensive care unit stay > 24 h, composite neonatal morbidity) using log-binomial regression to generate adjusted risk ratios (RRs). We adjusted estimates for potential confounding using propensity score weighting.Results:Of 615 213 infants (live births and stillbirths), 11 519 were exposed to Tdap vaccination in utero. There was no increased risk for preterm birth (adjusted HR 0.98, 95% confidence interval [CI] 0.91–1.06), very preterm birth (adjusted HR 1.10, 95% CI 0.86–1.41), stillbirth (adjusted HR 1.15, 95% CI 0.82–1.60) or being small for gestational age (adjusted RR 0.96, 95% CI 0.90–1.02). The risks of a neonatal intensive care unit stay exceeding 24 hours (adjusted RR 0.82, 95% CI 0.76–0.88) and neonatal morbidity (adjusted RR 0.81, 95% CI 0.75–0.87) were decreased. There was no association with chorioamnionitis (adjusted RR 1.17, 95% CI 0.99–1.39), postpartum hemorrhage (adjusted RR 1.01, 95% CI 0.91–1.13) or severe postpartum hemorrhage (adjusted RR 0.79, 95% CI 0.55–1.13), but we observed a reduced risk of gestational hypertension (adjusted RR 0.87, 95% CI 0.78–0.96).Interpretation:Our results complement evidence that maternal Tdap vaccination is not associated with adverse outcomes in mothers or infants. Ongoing evaluation in Canada is needed as maternal Tdap vaccination coverage increases in coming years.

Newborn antibodies to SARS-CoV-2 detected in cord blood after maternal vaccination \u2013 a case report

BackgroundMaternal vaccination for Influenza and Tetanus, Diphtheria, acellular Pertussis (TDaP) have been well studied in terms of safety and efficacy for protection of the newborn by placental passage of antibodies. Similar newborn protection would be expected after maternal vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). There is a significant and urgent need for research regarding safety and efficacy of vaccination against SARS-CoV-2 during pregnancy.Case presentationA vigorous, healthy, full-term female was born to a COVID-19 naïve mother who had received a single dose of messenger RNA (mRNA) vaccine for SARS-CoV-2 3 weeks prior to delivery. IgG cord blood antibodies were detected to SARS-CoV-2 at the time of birth.ConclusionHere, we report the first known case of an infant with SARS-CoV-2 IgG antibodies detectable in cord blood after maternal vaccination.

1383. Characterizing Real-world Patterns of Early Childhood Vaccination

BackgroundVaccine hesitancy is increasingly common, but more information is needed on patterns of childhood vaccination. We characterized patterns of vaccine delay among commercially-insured children in the U.S.MethodsUsing the IBM MarketScan Commercial Database, we identified infants who received a timely first dose of diphtheria-tetanus-acellular pertussis (DTaP) vaccine from October 2009 to June 2017. We used CPT codes to collect vaccine administration history on antigen, formulation, dose, and date. We ascertained injectable and oral vaccine antigens (DTaP, polio, pneumococcal conjugate, rotavirus, Haemophilus influenza type b (Hib), measles, mumps, rubella, varicella). Timely receipt was defined as concomitant administration of the CDC-recommended number of antigens during the following time windows: 2, 4, 6, and 12-15 months of age (grace period: -7, +21 days). We generated heat maps to illustrate age distributions at receipt of specific antigens and doses. We created Sankey diagrams to illustrate the number of antigens received concomitantly during each time window and depict transitions to different states over time (e.g., no vaccine delay to vaccine delay). For each antigen and dose, we estimated the cumulative incidence of receipt.ResultsAmong 1,066,216 eligible infants, the majority (84%) concomitantly received all 5 CDC-recommended antigens at 2 months of age while others only received 1 (1%), 2 (2%), 3 (4%) or 4 (9%) antigens. Many vaccinations were delayed – 30% and 39% of children did not receive all recommended antigens concomitantly at 4 and 6 months, respectively. The heat map shows wide variation in age at vaccination. For several antigens including Hib, measles, mumps, rotavirus, rubella, and varicella, the cumulative incidence increased steeply at ≥2 time points, suggesting vaccine delay for some infants (e.g., the first dose of Hib was administered to 85% of infants by 2 months of age, with subsequent small but distinct increases at 4, 6, 12, and 15 months of age).ConclusionUsing real-world data to study early childhood vaccination patterns, we observed evidence of substantial deviation from the CDC-recommended schedule. These results expand current knowledge on the magnitude and timing of antigen- and dose-specific vaccine delay on a population level.Disclosures Jason Newland, MD, MEd, FPIDS, Merck (Grant/Research Support)Pfizer (Other Financial or Material Support, Industry funded clinical trial) Leah McGrath, PhD, NoviSci, Inc. (Employee)

Fever After Influenza, Diphtheria-Tetanus-Acellular Pertussis, and Pneumococcal Vaccinations

EB Walter, NP Klein, AP Wodi. Pediatrics . 2020;145(3):e20191909 To determine if administration of the quadrivalent inactivated influenza vaccine (IIV4) at a separate visit from the 13-valent pneumococcal conjugate vaccine (PCV13) and diphtheria–tetanus–acellular pertussis vaccine (DTaP) would affect the occurrence of postvaccination fever. The study included 221 children aged 12 to 16 months (median age 14.6 months) who were fully up-to-date on vaccinations as per the Advisory Committee on Immunization Practices (ACIP). 93.2% of patients were receiving either their first or only dose of influenza vaccine for the season, …

Reducing the Risk of Vaccine Preventable Diseases During the COVID-19 Pandemic

Reducing the Risk of Vaccine Preventable Diseases During the COVID-19 Pandemic

Levels of antibodies specific to diphtheria toxoid, tetanus toxoid, and Haemophilus influenzae type b in healthy children born to Tdap-vaccinated mothers

IntroductionVaccination of pregnant women protects both women and their newborns against some infectious diseases. Thailand implemented tetanus toxoid (TT) vaccination of pregnant women in 1977, which was replaced by tetanus–diphtheria toxoid (dT) vaccination in 2005. The tetanus–diphtheria–acellular pertussis (Tdap) vaccine has been recommended for pregnant women at 27–36 weeks of gestation since 2012 in several countries. Data on antibody responses to diphtheria toxoid (DT), TT, and Hemophilus influenzae type b (Hib) induced by combined vaccines in children born to TT-vaccinated and/or Tdap-vaccinated mothers are limited. Material and methodsWe investigated anti-DT, anti-TT, and anti-Hib IgG responses in a cohort of Thai children (ClinicalTrial.gov NCT02408926) born to mothers who received a TT-containing and/or the Tdap vaccine during pregnancy. Children born to Tdap-vaccinated mothers were randomized to receive either a hexavalent (Infanrix-hexa) or pentavalent (Quinvaxem) vaccine, whereas children born to TT-vaccinated mothers received only Quinvaxem vaccine at 2, 4, 6, and 18 months of age. IgG levels were evaluated at birth (cord blood), 2 (pre-primary), 7 (post-primary), 18 (pre-booster), and 19 months of age (post-booster) using a commercially available enzyme-linked immunoassay. ResultsSeroprotective concentrations of anti-DT, anti-TT, and anti-Hib IgG were achieved in >90% and >99% of children following primary and booster vaccination, respectively. Among children born to Tdap-vaccinated mothers, the pentavalent vaccine induced higher levels of anti-Hib IgG than the hexavalent vaccine after primary and booster vaccination. Significantly higher anti-Hib IgG levels were observed among children receiving the pentavalent vaccine and who were born to TT-vaccinated mothers than among children receiving the pentavalent vaccine and born to Tdap-vaccinated mothers after primary and booster vaccination. ConclusionsVaccination with a TT-containing and/or the Tdap vaccine during pregnancy did not compromise the seroprotection rate achieved following primary and booster immunization in individuals receiving either the pentavalent or hexavalent vaccine.

Interference With Pertussis Vaccination in Infants After Maternal Pertussis Vaccination.

* Abbreviations: aP — : acellular pertussis DTaP — : diphtheria-tetanus-acellular pertussis DTwP — : diphtheria, tetanus, and whole-cell pertussis HIC — : high-income country LMICs — : low- and middle-income countries WHO — : World Health Organization Pertussis is a major public health concern. In 2014, 24 million cases and 160 000 deaths from pertussis in children <5 years were estimated worldwide, with nearly one-third of the cases occurring in Africa.1 Vaccination with an acellular pertussis (aP)–containing vaccine in pregnancy prevents severe pertussis in young infants and has been recommended in an increasing number of high-income countries (HICs). We have recently discussed optimal strategies for vaccination in pregnancy to maximize protection against infections in infancy.2 However, pertussis vaccination in pregnancy reduces infants’ primary immune responses to diphtheria-tetanus-acellular pertussis (DTaP) vaccines, leading to lower antibody levels to some pertussis antigens, when compared with infants of unvaccinated mothers.3 This is termed “interference” and has been shown primarily in studies from HICs that used DTaP formulations for infant immunization, but its clinical implications are unknown. Fewer data are available on the potential interference with diphtheria, tetanus, and whole-cell pertussis (DTwP) vaccines for infant immunization, the vaccines used almost exclusively in low- and middle-income countries (LMICs). An earlier study that we conducted in the United States revealed interference with DTwP vaccines, but not with DTaP vaccines, in infants with higher maternally derived antibody levels before primary vaccination.4 In a recent study conducted in Pakistan, the authors found no correlation between preexisting anti-pertussis antibody levels at delivery and infants’ anti-pertussis antibody levels after primary vaccination with DTwP vaccines.5 However, women in these 2 studies did … Address correspondence to Bahaa Abu-Raya, MD, British Columbia Children’s Hospital Research Institute, The University of British Columbia, 950 W 28th Ave, Vancouver, BC V5Z 4H4, Canada. E-mail: baburaya{at}bcchr.ubc.ca

Determining Which of Several Simultaneously Administered Vaccines Increase Risk of an Adverse Event.

Childhood immunization schedules often involve multiple vaccinations per visit. When increased risk of an adverse event is observed after simultaneous (same-day) vaccinations, it can be difficult to ascertain which triggered the adverse event. This methods paper discusses a systematic process to determine which of the simultaneously administered vaccine(s) are most likely to have caused an observed increase in risk of an adverse event. We use an example from the literature where excess risk of seizure was observed 1day after vaccination, but same-day vaccination patterns made it difficult to discern which vaccine(s) may trigger the adverse event. We illustrate the systematic identification process using a simulation that retained the observed pattern of simultaneous vaccination in an empirical cohort of vaccinated children. We simulated "true" effects for diphtheria-tetanus-acellular pertussis (DTaP) and pneumococcal conjugate (PCV) on risk of seizure the day after vaccination. We varied the independent and interactive effects of vaccines (on the multiplicative scale). After applying the process to simulated data, we evaluated risk of seizure 1day after vaccination in the empirical cohort. In all simulations, we were able to determine which vaccines contributed to excess risk. In the empirical data, we narrowed the association with seizure from all vaccines in the schedule to three likely candidates, DTaP, PCV, and/or Haemophilus influenzae type B (HiB) (p < 0.01, attributable risk when all three were administered together: five per 100,000). Disentangling their associations with seizure would require a larger sample or more variation in the combinations administered. When none of these three were administered, no excess risk was observed. The process outlined could provide valuable information on the magnitude of potential risk from individual and simultaneousvaccinations. Associations should be further investigated with independent data as well as biologically based, statistically independent hypotheses.

Antibodies to measles, mumps, and rubella virus in Thai children after two-dose vaccination at 9 months and 2.5 years: A longitudinal study

IntroductionThailand changed the schedule of childhood measles–mumps–rubella (MMR) vaccination in 2014, moving the second dose from the age of 6 years to 2.5 years. There are currently no data on antibody responses to the MMR vaccine since this recommendation. Material and methodsWe investigated antibody responses in a cohort of children who received two doses of MMR vaccine at the ages of 9 months and 2.5 years that was originally established to evaluate antibody levels to Bordetella pertussis antigens (ClinicalTrials.gov no. NCT02408926). Infants were born to mothers who previously received tetanus–diphtheria–acellular pertussis vaccine at 27–36 weeks of gestation. Anti-measles, -mumps, and -rubella virus IgG levels were measured at birth (cord blood) and the ages of 2 and 7 months (before the first MMR vaccination); 18 and 24 months (9 and 15 months, respectively, after the first dose); and 36 months (6 months after the second dose) using commercially available enzyme-linked immunosorbent assay kits. ResultsAt 7 months of age, 96.2%, 99.6%, and 98.8% of infants had no protection against measles, mumps, and rubella, respectively. Levels of antibody against all three antigens increased significantly after the first but not the second dose. At 6 months after two-dose vaccination, 97.4%, 84.8%, and 78.7% of children remained seroprotected against measles, mumps, and rubella, respectively. ConclusionsMaternally derived antibodies to measles, mumps, and rubella virus disappeared by the age of 7 months in Thai children. Two-dose MMR vaccination at 9 months and 2.5 years of age induced robust immune responses against these viruses.

Fever After Influenza, Diphtheria-Tetanus-Acellular Pertussis, and Pneumococcal Vaccinations.

Administering inactivated influenza vaccine (IIV), 13-valent pneumococcal conjugate vaccine (PCV13), and diphtheria-tetanus-acellular pertussis (DTaP) vaccine together has been associated with increased risk for febrile seizure after vaccination. We assessed the effect of administering IIV at a separate visit from PCV13 and DTaP on postvaccination fever. In 2017-2018, children aged 12 to 16 months were randomly assigned to receive study vaccines simultaneously or sequentially. They had 2 study visits 2 weeks apart; nonstudy vaccines were permitted at visit 1. The simultaneous group received PCV13, DTaP, and quadrivalent IIV (IIV4) at visit 1 and no vaccines at visit 2. The sequential group received PCV13 and DTaP at visit 1 and IIV4 at visit 2. Participants were monitored for fever (≥38°C) and antipyretic use during the 8 days after visits. There were 110 children randomly assigned to the simultaneous group and 111 children to the sequential group; 90% received ≥1 nonstudy vaccine at visit 1. Similar proportions of children experienced fever on days 1 to 2 after visits 1 and 2 combined (simultaneous [8.1%] versus sequential [9.3%]; adjusted relative risk = 0.87 [95% confidence interval 0.36-2.10]). During days 1 to 2 after visit 1, more children in the simultaneous group received antipyretics (37.4% vs 22.4%; P = .020). In our study, delaying IIV4 administration by 2 weeks in children receiving DTaP and PCV13 did not reduce fever occurrence after vaccination. Reevaluating this strategy to prevent fever using an IIV4 with a different composition in a future influenza season may be considered.

Vaccines are underused in pregnancy: what about knowledge, attitudes and practices of providers?

Introduction.To investigate actual knowledge of official recommendations towards seasonal influenza (SID), and Tetanus-diphtheria acellular-pertussis (Tdap) vaccines in obstetrics/gynecologists (OBGYN).Methods.PubMed and EMBASE databases were searched. A meta-analysis was performed to calculate odds ratio (OR) and 95% confidence interval (CI) among case controls, cross-sectional studies, either questionnaire or laboratory exams based.Results.A total of 6 studies met inclusion criteria, including 1323 OBGYN from 5 different countries. Overall, around 99% of sampled professionals were aware that official recommendations towards SID in pregnancy do exist, compared to 92% for Tdap, with significant heterogeneity (I2 > 95%, p < 0.001). Concerns about vaccine safety was reported by 10% of respondents for Tdap, and by 6.0% for SID, but again available studies were substantially heterogenous (I2 = 86.7% and 86.0%, p < 0.001). Eventually, 93% of respondents actively recommended SID in pregnancy, compared to 88% for Tdap (I2 98.8% and I2 95.9%, respectively p < 0.001). The evidence of significant publication bias was initially subjectively identified from the funnel plot, and then objectively confirmed through the regression test for all analyses.Conclusions.These results suggest an appropriated understanding of official recommendation among sampled OBGYN, with high shares of professionals actively promoting vaccination practices among their patients. Despite the high heterogeneity and the significant publication bias we identified, our results also hint towards extensive knowledge gaps of OBGYN, and particularly regarding unmotivated concerns about vaccine safety. As a consequence, appropriate information and formation campaigns should be appropriately tailored. (www.actabiomedica.it)

Challenges to Pertussis Control.

* Abbreviations: DTaP — : diphtheria-tetanus-acellular pertussis DTwP — : diphtheria, tetanus toxoids, and whole-cell pertussis KPNC — : Kaiser Permanente Northern California In this issue of Pediatrics , the vaccine research group at Kaiser Permanente Northern California (KPNC) contributed another important article outlining the challenges of pertussis control in a highly vaccinated population.1 Nearly one-half million children born between 1999 and 2016 and managed at KPNC from 2006 to 2017 were evaluated. Of those immunized children, all had received only diphtheria-tetanus-acellular pertussis (DTaP) vaccine. In total, 738 polymerase chain reaction–confirmed pertussis cases were diagnosed. Pertussis risk was 13 times higher among unvaccinated and nearly 2 times higher among undervaccinated children when compared with those who were fully vaccinated. However, >80% of the total pertussis cases were seen in children who had received all their recommended DTaP vaccine doses. Pertussis risk increased with increasing time since vaccination, clearly demonstrating waning immunity, which the KPNC group and others had previously reported.2,3 Those individuals who began their medical career after 1997, when DTaP totally replaced the conventional diphtheria, tetanus toxoids, and whole-cell pertussis (DTwP) vaccines, may question why DTaP replaced DTwP in the first place. When I began my academic career at Vanderbilt University School of Medicine in 1980, pertussis disease appeared to be well controlled.4 Rarely would cases present to the medical center, and generally … Address correspondence to Kathryn M. Edwards, MD, Division of Infectious Diseases, Department of Pediatrics, Vanderbilt University School of Medicine, 1161 21st Ave South, D-7227 Medical Center North, Nashville, TN 37232. E-mail: kathryn.edwards{at}vumc.org

Acellular Pertussis Vaccine Effectiveness Over Time.

To determine pertussis risk by diphtheria-tetanus-acellular pertussis (DTaP) vaccination status and time since last DTaP dose. Children born at Kaiser Permanente Northern California between 1999 and 2016 were followed from 3 months of age until they tested positive for pertussis; disenrolled from Kaiser Permanente Northern California; received the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed vaccine; turned 11 years of age, or the end of the study period. DTaP vaccination status was categorized on the basis of the number of doses received in relation to the number of doses expected according to the Advisory Committee on Immunization Practice-recommended ages. Among 469 982 children ages 3 months to 11 years, we identified 738 pertussis cases. A total of 99 cases were unvaccinated, 36 were undervaccinated, 515 were fully vaccinated, and 88 were fully vaccinated plus 1 dose. Pertussis risk was 13 times higher among unvaccinated (adjusted hazard ratio [aHR] = 13.53; 95% confidence interval [CI] 10.64-17.21) compared with fully vaccinated children and 1.9 times higher (aHR = 1.86; 95% CI 1.32-2.63) among undervaccinated children. Among vaccinated children ages 19 to <84 months, pertussis risk was 5 times higher (aHR = 5.04; 95% CI 1.84-13.80) ≥3 years vs <1 year after vaccination. Among children ages 84 to 132 months, risk was 2 times higher (aHR = 2.32; 95% CI 0.97-5.59) ≥6 years vs <3 years after vaccination. Undervaccinated and especially unvaccinated children were at greater risk of pertussis. However, most pertussis cases occurred among children age-appropriately vaccinated who were further away from their last DTaP dose, suggesting that suboptimal vaccine effectiveness played a major role in recent pertussis epidemics.

Duration of Immunity and Effectiveness of Diphtheria-Tetanus–Acellular Pertussis Vaccines in Children

ImportanceThe United States has experienced a nationwide resurgence of pertussis since the mid-1970s, despite high estimated vaccine coverage. Short-lived immunity induced by diphtheria-tetanus–acellular pertussis (DTaP) vaccines in young children is widely believed to be responsible for this growing burden, but the duration of protection conferred by DTaP vaccines remains incompletely quantified.ObjectiveTo assess the duration of immunity and the effectiveness of DTaP vaccines in US children.Design, Setting, and ParticipantsA mathematical, age-structured model of pertussis transmission, previously validated empirically on incidence data in Massachusetts, was used in this simulation study to assess the duration of DTaP immunity most consistent with the empirical values of the relative increase in the odds of acquiring pertussis from recent epidemiologic studies in the United States. The study included 5 simulated cohorts of children born between January 1, 2001, and December 31, 2005, followed up between the ages of 5 and 9 years (study period, January 1, 2006, to December 31, 2014). Statistical analysis was performed from May 1 to December 1, 2017.InterventionsVaccination with DTaP according to the US immunization schedule, with a range of assumptions regarding the degree of waning immunity.Main Outcomes and MeasuresVaccine effectiveness and relative change in the odds of acquiring pertussis (odds ratio) in children aged 5 to 9 years, duration of DTaP immunity, and vaccine population-level impact.ResultsThis study found a marked association between the degree of waning immunity, vaccine effectiveness, and the odds ratio. Counterintuitively, the odds ratio was positively associated with vaccine effectiveness, as a consequence of nonlinear, age-assortative transmission dynamics. Based on the empirical odds ratios (1.33; 95% CI, 1.23-1.43), it was estimated that vaccine effectiveness exceeded 75% in children aged 5 to 9 years and that more than 65% of children remained immune to pertussis 5 years after the last DTaP dose.Conclusions and RelevanceThe results of this study suggest that temporal trends in the odds of acquiring pertussis are an unreliable measure of the durability of vaccine-induced protection. They further demonstrate that DTaP vaccines confer imperfect, but long-lived protection. Control strategies should be based on the best available estimates of vaccine properties and the age structure of the transmission network.

Midwives’ role in the provision of maternal and childhood immunisation information

ProblemInactivated influenza vaccine and diphtheria-tetanus acellular pertussis vaccine are routinely recommended during pregnancy to protect women and their babies from infection. Additionally, the hepatitis B vaccine is recommended for infants within the first week of life; however, little is known about midwives’ experiences of recommending and delivering these immunisations. BackgroundMidwives are a trusted source of vaccine information for parents and the confident provision of information about immunisation during antenatal clinic visits has been found to increase the uptake of antenatal and childhood vaccines. AimThis study aims to explore midwives’ experiences of discussing maternal and childhood immunisation with women and their partners and their confidence in answering parent’s questions. MethodsWe conducted 23 semi-structured interviews with registered Australian midwives working in public and private hospital settings, and in private practice. FindingsMidwives find negotiating the requirement to recommend immunisation within a women-centred framework challenging at times. The vast majority of midwives described their education on immunisation as inadequate and workplace issues, such as time pressure, were identified as further barriers to effective communication about immunisation. Discussion/conclusionThe provision of immunisation training within midwifery education and continued professional development is critical. Appropriately resourcing midwives with the necessary infrastructure, education and resources to fully inform parents about immunisation may have a positive impact on vaccine uptake.

Quantitative determination of bioactive proteins in diphtheria tetanus acellular pertussis (DTaP) vaccine by liquid chromatography tandem mass spectrometry

A liquid chromatography tandem mass spectrometry method (LC–MS/MS) was developed to determine simultaneously the bioactive proteins including pertussis toxin (PT) subunits, filamentous hemagglutinin (FHA), pertactin (PRN) and fimbriae (FIM) in diphtheria, tetanus and acellular pertussis combined vaccine (DTaP). The trypsin digestion conditions were investigated in detail using PT reference to achieve satisfactory results in detection of the peptides on LC–MS/MS with a Bio-C18 column. The performance of the described method was evaluated using reference proteins and the results showed a wide linear range (0.15–24 ng μL−1), a high sensitivity (0.038 ng. μL-1 for FHA) and a good precision (RSD of peak area <3.3%). This novel LC–MS/MS method was applied to determine PT subunits, FHA, PRN and FIM in DTaP vaccines, a total of ten batches, obtained from five manufacturers. The results revealed clearly that batch-to-batch consistency of the DTaP vaccines in terms of the protein amounts was stable, while those from manufacturers were varied significantly. On the other hand, the amount of bioactive proteins in component DTaP vaccines was generally higher than those in co-purified DTaP vaccines. The described LC–MS/MS method was compared with Chinese Pharmacopeia method (Lowry method) and it was found that FHA and PRN amounts measured by the two methods were in good agreement. The LC–MS/MS method could provide the amounts of PT subunits. However, the Lowry method could not differentiate the subunits. The LC–MS/MS method was not only more selective and sensitive, but it can be used to determine simultaneously different bioactive proteins in complex matrix-formulated vaccines. The method was extended successfully in other purposes, such as the effect of detoxification on bioactive proteins and characterization of PT references from four organizations worldwide.

Factors Associated With Rotavirus Vaccine Coverage.

Rotavirus vaccines (RVVs) were included in the US immunization program in 2006 and are coadministered with the diphtheria-tetanus-acellular pertussis (DTaP) vaccine, yet their coverage lags behind DTaP. We assessed timing, initiation, and completion of the RVV series among children enrolled in active gastroenteritis surveillance at 7 US medical institutions during 2014-2016. We compared coverage and timing of each vaccine series and analyzed characteristics associated with RVV initiation and completion. We report odds ratios (ORs) and 95% confidence intervals (CIs) from multivariable logistic regression models. We enrolled 10 603 children. In 2015, ≥1 dose coverage was 91% for RVV and 97% for DTaP. Seven percent of children received their first DTaP vaccine at age ≥15 weeks versus 4% for RVV (P ≤ .001). Recent birth years (2013-2016) were associated with higher odds of RVV initiation (OR = 5.72; 95% CI 4.43-7.39), whereas preterm birth (OR = 0.32; 95% CI 0.24-0.41), older age at DTaP initiation (OR 0.85; 95% CI 0.80-0.91), income between $50 000 and $100 000 (OR = 0.56; 95% CI 0.40-0.78), and higher maternal education (OR = 0.52; 95% CI 0.36-0.74) were associated with lower odds. Once RVV was initiated, recent birth years (2013-2016; OR = 1.57 [95% CI 1.32-1.88]) and higher maternal education (OR = 1.31; 95% CI 1.07-1.60) were associated with higher odds of RVV completion, whereas preterm birth (OR = 0.76; 95% CI 0.62-0.94), African American race (OR = 0.82; 95% CI 0.70-0.97) and public or no insurance (OR = 0.75; 95% CI 0.60-0.93) were associated with lower odds. Regional differences existed. RVV coverage remains lower than that for the DTaP vaccine. Timely DTaP administration may help improve RVV coverage.

Determination of tracheal cytotoxin in pertussis and diphtheria tetanus acellular pertussis vaccines using liquid chromatography-tandem mass spectrometry

Tracheal cytotoxin (TCT) is a toxic glycopeptide, which contribute to the adverse effects of pertussis toxin (PT) and related vaccines. Although pharmacopeias limit the amount of TCT in PT product, there is no recommended TCT determination method in any pharmacopeia. In this study, a liquid chromatography-tandem mass spectrometry method was developed to determine TCT. Chromatographic conditions, including column-type and mobile-phase composition, were optimized. According to the literature reports, both reversed-phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC) can provide a good retention for TCT. A large amount of organic solvent is usually used for protein precipitation, which may affect the RPLC mode, leading to peak distortion, while such effects were not observed in HILIC mode. Thus, HILIC mode was used to analyze TCT in this study. The developed method had a wide linear range (5.76-369 ng/L), good precision (no more than 3.9%), satisfied recoveries in various matrices (96.4%-102.5%). The limit of quantification (LOQ) of the developed method was 1279 times lower than the one required by Chinese Pharmacopeia, wherein the required amount of TCT should be less than 2 pmol per dose. The developed method was used to detect TCT in pertussis vaccine (acellular component), pertussis vaccine (acellular, co-purified), co-purified diphtheria tetanus pertussis vaccine, and component diphtheria tetanus acellular pertussis vaccine. As a result, TCT was not detected in any of the selected samples indicating the safety of these vaccines and PT products.

Comparisons of immunization records between a community pharmacy, a regional registry, and a health system

ObjectivesTo compare the completeness of immunization records for 6 vaccines between a community pharmacy database, a regional immunization information system (IIS), and a health system’s electronic health record (EHR). MethodsIn a community pharmacy immunization program, 2 pharmacists and a community pharmacy resident performed a needs assessment for 6 vaccines (tetanus–diphtheria–acellular pertussis vaccine for adults or diphtheria–tetanus–acellular pertussis vaccine for children and adolescents, zoster vaccine live, 13-valent pneumococcal conjugate vaccine, 23-valent pneumococcal polysaccharide vaccine, hepatitis B vaccine series, and human papillomavirus vaccine) for more than 2400 patients from August 2016 to March 2017. This was a retrospective study to review immunization records for 243 patients. Inclusion criteria included patients from the community pharmacy immunization program who also had at least 1 medication prescribed by an academic health system provider. Immunization records for 6 vaccines were collected from the community pharmacy database, the regional IIS, and the EHR. ResultsA total of 186 of 243 patients (77%) had additional immunization records in the regional IIS or EHR that were not found in the community pharmacy database. Among those 186 patients, 108 (58%) had additional immunization records for 2 or more unique vaccines. In total, 378 additional immunization records were identified for the 6 vaccines. For all 6 vaccines, the regional IIS and EHR possessed more complete immunization records than the community pharmacy database (P < 0.05 for HPV and P < 0.001 for the remaining 5 vaccines). ConclusionOur study showed that immunization records were more complete in a regional IIS and health system EHR compared with a community pharmacy database. If all 3 sources were used by the pharmacist during the needs assessment, the community pharmacy team would have made fewer vaccine recommendations, which would have reduced the potential for duplicate or inappropriate vaccines.

Safety Surveillance of Diphtheria and Tetanus Toxoids and Acellular Pertussis (DTaP) Vaccines.

To assess the safety of currently licensed diphtheria-tetanus-acellular pertussis (DTaP) vaccines in the United States by using data from the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system. We searched VAERS for US reports of DTaP vaccinations occurring from January 1, 1991, through December 31, 2016, and received by March 17, 2017. We reviewed available medical records for all death reports and a random sample of reports classified as nondeath serious. We used Empirical Bayesian data mining to identify adverse events that were disproportionally reported after DTaP vaccination. VAERS received 50 157 reports after DTaP vaccination; 43 984 (87.7%) of them reported concomitant administration of other vaccines, and 5627 (11.2%) were serious. Median age at vaccination was 19 months (interquartile range 35 months). The most frequently reported events were injection site erythema (12 695; 25.3%), pyrexia (9913; 19.8%), injection site swelling (7542; 15.0%), erythema (5599; 11.2%), and injection site warmth (4793; 9.6%). For 3 of the DTaP vaccines, we identified elevated values for vaccination errors using Empirical Bayesian data mining. No new or unexpected adverse events were detected. The observed disproportionate reporting for some nonserious vaccination errors calls for better education of vaccine providers on the specific indications for each of the DTaP vaccines.