Surveillance for adverse events following immunization with DTaP-containing combination vaccines in Linping, China, 2019-2022.

Background: The DTaP-Hib and DTaP-IPV/Hib combination vaccine can be used as a substitute for the diphtheria, tetanus, and acellular pertussis combined vaccine (DTaP). We aimed to evaluate the safety of multi-component vaccines containing DTaP by analyzing the reporting rates and characteristics of adverse events following immunization (AEFIs) in Linping District during the years 2019 to 2022. Methods: We obtained data of AEFI and vaccination from the National AEFI Surveillance System of China and Zhejiang Municipal Immunization Information Management System, respectively, during 2019-2022 for a descriptive, epidemiological analysis. Results: The total number of AEFI reported following vaccinations with DTaP-containing combination vaccines was 802 in Linping District from 2019 to 2022. The overall reporting rates of AEFIs following DTaP, DTaP-Hib, and DTaP-IPV/Hib vaccinations were 445.72 (537 cases), 536.29 (45 cases), and 306.13 (220 cases) per 100,000 doses in Linping District from 2019 to 2022, respectively. Only one case of a serious AEFI following DTaP vaccination, with a reporting rate of 0.83 per 100,000 doses. The composition ratio of vaccine product-related reactions for DTaP, DTaP-Hib, and DTaP-IPV/Hib were 99.81, 97.78, and 100.00%, respectively. The composition ratio of coincidental events for DTaP and DTaP-Hib were 0.19 and 2.22%, respectively. The reporting rates of total AEFIs for DTaP-IPV/Hib were lower than for DTaP. The reporting rate of local induration for DTaP-Hib was lower than for DTaP, and the reporting rates of local redness & swelling and local induration for DTaP-IPV/Hib were both lower than for DTaP. DTaP-IPV/Hib had a higher proportion of AEFIs in first quarter compared to DTaP. The reporting rate after the second dose of DTaP-Hib was higher than that of DTaP, and the reporting rates of AEFIs after the first dose and third dose of DTaP-IPV/Hib were lower than DTaP. Conclusion: The reported AEFIs to multi-component vaccines containing DTaP components during 2019-2022 in Linping District were mainly mild vaccine reactions. DTaP-containing combination vaccines demonstrated a good safety profile.

Phase 3 Safety and Immunogenicity Study of a Three-dose Series of Twenty-valent Pneumococcal Conjugate Vaccine in Healthy Infants and Toddlers.

BACKGROUND: Global pediatric immunization programs with pneumococcal conjugate vaccines (PCVs) have reduced vaccine-type pneumococcal disease, but a substantial disease burden of non-PCV serotypes remains. METHODS: This phase 3, randomized (1:1), double-blind study evaluated safety and immunogenicity of 20-valent PCV (PCV20) relative to 13-valent PCV (PCV13) in healthy infants. Participants received 2 infant doses and a toddler dose of PCV20 or PCV13, with diphtheria-tetanus-acellular pertussis combination vaccine at all doses and measles, mumps, rubella and varicella vaccines at the toddler dose. Primary pneumococcal immunogenicity objectives were to demonstrate noninferiority (NI) of PCV20 to PCV13 for immunoglobulin G geometric mean concentrations after infant and toddler doses and percentages of participants with predefined serotype-specific immunoglobulin G concentrations after infant doses. Safety endpoints included local reactions, systemic events and adverse events. RESULTS: Overall, 1204 participants were vaccinated (PCV20, n = 601; PCV13, n = 603). One month after the toddler dose, 19/20 serotypes met NI for immunoglobulin G geometric mean concentrations; serotype 6B narrowly missed NI [PCV20/PCV13 geometric mean ratio: 0.57 (2-sided 95% confidence interval: 0.48-0.67); NI criterion: lower 2-sided 95% confidence interval >0.5]. Sixteen/twenty serotypes met NI for ≥1 primary objective after 2 infant doses. PCV20 induced robust opsonophagocytic activity, and boosting responses were observed for all vaccine serotypes, including those missing statistical NI. The safety/tolerability profile of PCV20 was like that of PCV13. CONCLUSIONS: PCV20 3-dose series in infants was safe and elicited robust immune responses. Based on these results and PCV13 experience, PCV20 3-dose series is expected to be protective for all 20 vaccine serotypes. NCT04546425.

Immunogenicity and safety of concomitant administration of the sabin-strain-based inactivated poliovirus vaccine, the diphtheria-tetanus-acellular pertussis vaccine, and measles-mumps-rubella vaccine to healthy infants aged 18 months in China.

OBJECTIVES: During the COVID-19 pandemic, there was a decline in vaccine coverage, and the implementation of combined vaccines and co-administration strategies emerged as potential solutions to alleviate this predicament. Our objective is to delve into the concurrent administration of the sabin-strain-based inactivated poliovirus vaccine (sIPV), the diphtheria-tetanus-acellular pertussis vaccine (DTaP), and measles-mumps-rubella vaccine (MMR), with the intention of bridging the evidentiary gap pertaining to vaccine co-administration in Chinese infants, and to ensure a safe and effective vaccination strategy, ultimately leading to an augmentation in immunization coverage. METHODS: This study was a follow-up trial of the "Immunogenicity and safety of concomitant administration of the sIPV with the DTaP vaccine in children: a multicenter, randomized, non-inferiority, controlled trial." Blood samples were collected on day 0 and day 30, and serum antibody levels were detected to measure antibody responses to each of the antigens. Local and systemic adverse events were monitored and compared among groups. This study is the first to fill the knowledge gap in China regarding the safe and effective combined vaccination of sIPV, DTaP, and MMR vaccines. RESULTS: The geometric mean titer of the poliovirus types I, II, and III neutralizing antibodies were 1060.22 (95% CI: 865.73-1298.39), 1537.06 (95% CI: 1324.27-1784.05), and 1539.10 (95% CI: 1296.37-1827.29) in group I on day 30; geometric mean titer of antibodies against DTaP and MMR in the simultaneous vaccination group was non-inferior to those in the DTaP alone and MMR alone group. Reporting rates of local and systemic adverse reactions were similar between groups and no serious adverse events were reported throughout the clinical study period. CONCLUSION: Co-administration of the sIPV, DTaP, and MMR was safe and did not impact immunogenicity, which would help to mitigate administrative costs and enhance vaccine coverage rates.

Immunogenicity of tetanus, diphtheria and acellular pertussis vaccination among pregnant women living with and without HIV.

OBJECTIVE: Vaccination during pregnancy with tetanus-diphtheria-acellular pertussis (Tdap) vaccine is recommended to protect the young infants against pertussis. There is a paucity of data on immune responses to Tdap in pregnant women with HIV (PWWH), and its impact on the protection of their infants has not been described. METHODS: In an open label phase IV clinical trial in South Africa, we evaluated the immunogenicity and safety of Tdap in PWWH compared with HIV-uninfected women. Antigen-specific immunoglobulin G (IgG) to pertussis toxoid, filamentous haemagglutinin, pertactin, fimbriae, diphtheria and tetanus were measured by electrochemiluminescence-based multiplex assay. RESULTS: Overall, 91 PWWH and 136 HIV-uninfected pregnant women were enrolled. All PWWH were on antiretroviral treatment and 94.5% had HIV viral loads <40 copies per millilitre. Antibody levels prevaccination were lower among PWWH compared with HIV-uninfected women for all antigens. At 1 month postvaccination PWWH compared with HIV-uninfected women had lower fold-increase and antibody concentrations for all epitopes. Also, a lower proportion of PWWH achieved ≥4-fold increase from pre to postvaccination for pertussis toxoid and pertactin, or diphtheria IgG levels ≥0.1 IU/ml and ≥1 IU/ml postvaccination. Adverse events postvaccination were similar in PWWH and HIV-uninfected. CONCLUSION: Tdap vaccination was safe and immunogenic. PWHW had, however, attenuated humoral immune responses, which could affect the effectiveness of protecting their infants against pertussis compared with those born to women without HIV.ClinicalTrials.gov identifier: NCT05264662.

Tetanus, diphtheria, and acellular pertussis vaccine coverage in adults with chronic respiratory conditions.

BACKGROUND: Pertussis is a highly contagious respiratory disease, and those with chronic respiratory illnesses may be at higher risk of infection and severe pertussis. Acellular pertussis-containing vaccines (Tdap) are recommended in the United States for those with risk factors, such as asthma and chronic obstructive pulmonary disease (COPD). OBJECTIVE: To determine Tdap vaccination rates among people with asthma or COPD compared with matched controls with type 2 diabetes and the general population. METHODS: This observational database study identified adults with asthma or COPD, and their matched controls, from a large US administrative health claims system between January 2008 and December 2014. Vaccination with Tdap was identified using current procedural terminology and national drug codes, and vaccination rates per 1000 patient-years and adjusted rate ratios (RR) were calculated using a generalized linear model with a Poisson distribution and 95% confidence intervals (CI). RESULTS: Vaccination rates were low overall; however, they were slightly higher in asthma than the general population cohort, with vaccination incidence RRs of 1.12 (95% CI, 1.08-1.17), 1.09 (95% CI, 1.06-1.11), and 1.11 (95% CI, 1.07-1.16) in those aged 18 to 44, 45 to 64, and 65 years and older, respectively. However, Tdap vaccination rates were lower in the COPD than in the general population cohort, with vaccination incidence RRs of 0.72 (95% CI, 0.60-0.86), 0.87 (95% CI, 0.83-0.91), and 0.94 (95% CI, 0.92-0.96), respectively. CONCLUSION: Pertussis vaccination rates were suboptimal among adults in general and adults with asthma or COPD. Work is needed to boost Tdap vaccination uptake among people with chronic respiratory conditions.

Tdap vaccination during pregnancy and risk of chorioamnionitis and related infant outcomes.

INTRODUCTION: An increased risk of chorioamnionitis in people receiving tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during pregnancy has been reported. The importance of this association is unclear as additional study has not demonstrated increased adverse infant outcomes associated with Tdap vaccination in pregnancy. METHODS: We conducted a retrospective observational cohort study of pregnant people ages 15-49 years with singleton pregnancies ending in live birth who were members of 8 Vaccine Safety Datalink (VSD) sites during October 2016-September 2018. We used a time-dependent covariate Cox model with stabilized inverse probability weights applied to evaluate associations between Tdap vaccination during pregnancy and chorioamnionitis and preterm birth outcomes. We used Poisson regression with robust variance with stabilized inverse probability weights applied to evaluate the association of Tdap vaccination with adverse infant outcomes. We performed medical record reviews on a random sample of patients with ICD-10-CM-diagnosed chorioamnionitis to determine positive predictive values (PPV) of coded chorioamnionitisfor "probable clinical chorioamnionitis," "possible clinical chorioamnionitis," or "histologic chorioamnionitis." RESULTS: We included 118,211 pregnant people; 103,258 (87%) received Tdap vaccine during pregnancy; 8098 (7%) were diagnosed with chorioamnionitis. The adjusted hazard ratio for chorioamnionitis in the Tdap vaccine-exposed group compared to unexposed was 0.96 (95% CI 0.90-1.03). There was no association between Tdap vaccine and preterm birth or adverse infant outcomes associated with chorioamnionitis. Chart reviews were performed for 528 pregnant people with chorioamnionitis. The PPV for clinical (probable or possible clinical chorioamnionitis) was 48% and 59% for histologic chorioamnionitis. The PPV for the combined outcome of clinical or histologic chorioamnionitis was 81%. CONCLUSIONS AND RELEVANCE: Tdap vaccine exposure during pregnancy was not associated with chorioamnionitis, preterm birth, or adverse infant outcomes. ICD-10 codes for chorioamnionitis lack specificity for clinical chorioamnionitis and should be a recognized limitation when interpreting results.

Effect of maternal immunisation with multivalent vaccines containing inactivated poliovirus vaccine (IPV) on infant IPV immune response: A phase 4, multi-centre randomised trial.

Multivalent diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine (DTaP/IPV) has been offered to pregnant women in the United Kingdom since 2012. To assess the impact of maternal DTaP/IPV immunisation on the infant immune response to IPV, we measured poliovirus-specific neutralising antibodies at 2, 5 and 13 months of age in a randomised, phase 4 study of Repevax or Boostrix/IPV in pregnancy and in a non-randomised group born to women not given DTaP/IPV in pregnancy. Infants whose mothers received DTaP/IPV were less likely to seroconvert after three IPV doses than those whose mothers did not receive DTaP/IPV. At 13 months of age, 63/110 (57.2 %), 46/108 (42.6 %) and 40/108 (37.0 %) were seropositive to types 1 to 3, compared with 20/22 (90.9 %), 20/22 (90.9 %) and 14/20 (70.0 %) (p-values 0.003, <0.001 and 0.012). UK infants whose mothers are given DTaP/IPV in pregnancy may be insufficiently protected against poliomyelitis until their pre-school booster.

Reactogenicity and safety of second trimester maternal tetanus, diphtheria and acellular pertussis vaccination in the Netherlands.

BACKGROUND: Maternal tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccination is offered to all pregnant women during their second trimester in the Netherlands since December 2019. We assessed second trimester Tdap vaccination reactogenicity and compared with third trimester data from a similar study. For safety assessment, adverse pregnancy outcomes were compared with national data from 2018, before Tdap vaccine-introduction. METHODS: Pregnant women were included between August 2019-December 2021 and received Tdap vaccination between 20 and 24w gestational age (GA). Participants completed a questionnaire on solicited local reactions and systemic adverse events (AEs) within one week after vaccination. Results were compared with historical data on reactogenicity from women vaccinated between 30 and 33w GA (n = 58). Regarding safety-related outcomes, each participant was matched to four unvaccinated pregnant women from the Dutch Perinatal Registry, based on living area, parity and age. RESULTS: Among 723 participants who completed the questionnaire, 488 (67.5 %) experienced ≥ 1 local reaction with pain at the injection site as most reported reaction (62.3 %), and 460 (63.6 %) experienced ≥ 1 systemic AE with stiffness in muscles/joints (38.9 %), fatigue (28.9 %), headache (14.5 %) and common cold-like symptoms (11.0 %) most frequently reported. 4 women (0.6 %) reported fever (≥38.0˚C). Symptoms were considered mild and transient within days. No difference in AEs were found between vaccination at 20-24w versus 30-33w GA. 723 participants were matched to 2,424 unvaccinated pregnant women with no increased rates of premature labor, small-for-gestational-age, or other adverse pregnancy outcomes. CONCLUSIONS: Second trimester maternal Tdap vaccination appears safe and well-tolerated. Comparison between second versus third trimester vaccination yielded no reactogenicity concerns.

Maternal vaccination-current status, challenges, and opportunities.

AIM: Maternal vaccination is a promising strategy for protecting pregnant women and newborns against severe infections. This review aims to describe the current status and challenges associated with maternal vaccination against seasonal influenza, tetanus-diphtheria-pertussis (Tdap/DTaP), and novel coronavirus disease of 2019 (COVID-19) in Japan and other countries, mainly the United States and the United Kingdom. METHODS: A literature search was conducted in PubMed and other public websites (e.g., Centers for Disease Control and Prevention) to obtain information on maternal vaccination. RESULTS: Inactivated vaccines are recommended for pregnant women by gynecologic societies in Japan, the United States, and the United Kingdom. Among pregnant Japanese women, the influenza and COVID-19 (two doses) vaccine coverage rates were 27.0%-53.5% (six studies) and 73.6% (one study), respectively; there are no studies on maternal vaccination with DTaP. Concerns regarding vaccine safety are a major barrier to maternal vaccination across countries. Maternal vaccination is effective in preventing severe disease in pregnant women and protecting infants aged <6 months, is generally safe, and does not increase the risk of adverse maternal and fetal outcomes. Providing accurate information regarding vaccination through healthcare providers and the government and government funding for vaccines may help improve maternal vaccination rates in Japan. CONCLUSION: Current coverage for maternal vaccination is still low globally mainly because of vaccine hesitancy among pregnant women. The government, drug-regulatory authorities, and healthcare professionals must educate pregnant women about the effectiveness and safety of maternal vaccines and encourage vaccination when the benefits outweigh the risks.

Lack of association between febrile seizures and vaccines containing diphtheria, tetanus, and acellular pertussis in Chinese children.

BACKGROUND: The association between the administration of vaccines containing diphtheria, tetanus, and acellular pertussis (DTaP) and febrile seizures (FSs) is unclear. This study aimed to evaluate the risk of FSs after the administration of DTaP-containing vaccines in Chinese children aged 1 to 23 months. RESEARCH DESIGN AND METHODS: A self-controlled case series (SCCS) design was adopted based on data from the Ningbo Regional Health Information Platform (NRHIP). The observation period was from 1 to 23 months of age. The relative incidences (RIs) within 0 to 3 days, 4 to 7 days, and 0 to 7 days after the administration of DTaP-containing vaccines were estimated. The remaining observation period was the control period. RESULTS: The RIs within 0 to 3 days, 4 to 7 days, and 0 to 7 days after any dose of DTaP-containing vaccines were 1.14 (95% CI 0.86 to 1.52), 0.89 (95% CI 0.65 to 1.23), and 1.02 (95% CI 0.82 to 1.26), respectively. CONCLUSIONS: This study provides reassuring evidence that there is no increased risk of FSs immediately after the administration of DTaP-containing vaccines, which might serve to reassure both professionals and families with regard to the risk of FSs associated with DTaP-containing vaccines.

Genetic predisposition to adverse events in Chinese children aged 3-24 months after diphtheria, tetanus, acellular pertussis and haemophilus influenzae type b combined vaccination.

BACKGROUND: Post-vaccination safety is a major public health concern. The genetic predisposition on immune response has not been clearly identified. Clarifying whether individual genetic predisposition plays a role on adverse events (AEs) is critical for the prevention of AEs. METHODS: From July 2019 to June 2020, we performed a case-control study among children aged 3-24 months in seven Chinese provinces. Each child received a combination vaccination against diphtheria, tetanus, acellular pertussis, and Haemophilus influenzae type b (DTaP-Hib). Through daily telephone follow-up, we collected AEs within seven days. Oral swab samples were collected to investigate the effects of single nucleotide polymorphisms (SNPs) on the risk of AEs. RESULTS: 304 participants were included in the study. In univariate analysis, we discovered three protective SNPs (rs452204, OR = 0.67, P = 0.0352; rs9282763 and rs839, OR = 0.64, P = 0.0256) and one risk SNP (rs9610, OR = 2.20, P = 0.0397). In multivariate analysis, the effects of rs452204 and rs839 were found to be stable. The interaction between rs452204 and rs9610 was observed (OR = 7.25, 95% CI: 1.44-36.58, P = 0.0165). CONCLUSION: Genetic predisposition was associated with the risk of AEs after DTaP-Hib vaccination, emphasizing the potential application in the prevention of AEs.

Immunogenicity and safety of concomitant administration of the chinese inactivated poliovirus vaccine with the diphtheria-tetanus-acellular pertussis (DTaP) vaccine in children: A multicenter, randomized, non-inferiority, controlled trial.

Key point: Considering that vaccination with the sIPV and DTaP overlap at the ages of 3 and 4 months in China, to reduce the burden of treatment on parents and increase vaccination coverage rates, we designed a postmarket clinical study of co-administration. Background: The Sabin-strain-based inactivated poliovirus vaccine (sIPV) and the diphtheria-tetanus-acellular pertussis vaccine (DTaP) have been licensed in China for many years. To conduct a clinical study on the safety and immunogenicity of the sIPV when administered concomitantly with the DTaP. Methods: The study population was divided into three groups: group 1 was the sIPV+ DTaP concomitant administration group, group 2 was the sIPV inoculation group, and group 3 was the DTaP inoculation group. Blood samples were collected prevaccination and 30 days postvaccination, and serum antibody levels were detected. Results: This study showed that the seropositive and seroconversion rates of type 1, 2 and 3 poliovirus in group 1 were higher than those in group 2, with no statistically significant difference after vaccination (P>0.05). Groups 1 and 3 also showed similar responses for all vaccine antigens except anti-FHA (97.65 (94.09-99.36) vs. 100 (97.89-100)). The geometric mean titers (GMTs) for the DTaP and sIPV among the groups were comparable, and the non-inferiority t test result was P<0.001. The number of local adverse events (AEs) reported in group 1 (29.91%) were larger than those in group 2 (12.39%) and group 3 (21.93%), among which the most common was redness. Similarly, the most common systemic AE was fever. All 5 severe AE (SAE) cases were determined by experts to be unrelated to the vaccines during the study. Conclusions: The evidence of similar seroconversion and safety with co-administered DTaP and sIPV supports the co-administration supports the introduction of a strategy of simultaneous administration of both vaccines into routine infant immunization, and it could increase vaccination coverage and protect more infants from morbidity and mortality from these related diseases. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04054882?term=NCT04054882&cntry=CN&draw=2&rank=1, identifier NCT04054882.

A combined DTaP-IPV vaccine (Tetraxim®/Tetravac®) used as school-entry booster: a review of more than 20 years of clinical and post-marketing experience.

INTRODUCTION: Routine infant primary series and toddler booster vaccination are associated with waning of antibody levels over time, which can lead to an increased incidence of vaccine-preventable diseases. A diphtheria-tetanus-pertussis (DTP) booster vaccination at school-entry (aged 4-7 years) allows continued protection against these diseases and is included in many national immunization programs. AREAS COVERED: The available immunogenicity and safety data from 6 clinical studies of a diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine (DTaP-IPV [Tetraxim®]) used as a school-entry booster vaccination were identified using a PubMed search or on file at Sanofi. The studies spanned a 15-year period (1995-2010) and were performed in different populations using different study designs, so all data were reviewed descriptively (no meta-analyses were conducted). Additionally, post-marketing experience was reviewed. EXPERT OPINION: Each vaccine antigen is highly immunogenic, and the safety profile of the vaccine is satisfactory. Post-marketing evaluations have shown the effectiveness of a school-age booster, particularly against increased pertussis disease incidence around the time of school entry and the associated risk of spreading the disease through contact with younger vulnerable infants. School-entry provides an ideal opportunity to implement DTaP-IPV vaccination to close the gap between waning immunity from the previous infant/toddler vaccination and future adolescent vaccination.

Kawasaki disease following immunization reported to the Canadian Immunization Monitoring Program ACTive (IMPACT) from 2013 to 2018.

Kawasaki disease (KD) is an acute systemic vasculitis primarily affecting children younger than 5 y of age that has been reported as an adverse event following immunization (AEFI). The Canadian Immunization Monitoring Program ACTive (IMPACT) conducts active surveillance for KD following immunization across Canada. We characterized KD cases reported to IMPACT between 2013 and 2018. Cases admitted to an IMPACT hospital with a physician diagnosis of complete or incomplete KD with onset 0-42 d following vaccination were reviewed. Cases meeting the Brighton Collaboration case definition (BCCD) levels of diagnostic certainty levels 1 a/b, 2a/b or 3a-e were defined as KD cases. Demographic and vaccination characteristics were compared between KD cases and non-cases. Of 84 cases reviewed, 58 met the BCCD: 47 (81%) cases met level 1a (Complete KD), 8 (14%) met level 1b (Incomplete KD), 2 (3%) met level 2a, and 1 (2%) met level 2c (Probable KD). Median age at admission was 13 months (interquartile range 7-26 months). A median of 9.5 cases were reported per year (range 4-14). Thirty-one (53%) KD cases were temporally associated with diphtheria-tetanus acellular pertussis containing vaccinations, followed by 21 (36%) cases with pneumococcal conjugate vaccines. Symptom onset was 0-14 d after vaccination in 32 (55%) cases. Echocardiogram results were available for 43 (74%) cases with 22 reported as abnormal. Age, sex, interval to symptom onset, and vaccines received were similar between KD cases and non-cases. No safety signals were detected in these data.

Surveillance of adverse events following immunisation in Australia annual report, 2020.

This report summarises Australian spontaneous surveillance data for adverse events following immunisation (AEFI) for 2020, reported to the Therapeutic Goods Administration (TGA), and describes reporting trends over the 21-year period from 1 January 2000 to 31 December 2020. There were 3,827 AEFI records for vaccines administered in 2020, an annual AEFI reporting rate of 14.9 per 100,000 population. There was a slight (3.8%) decrease in the overall AEFI reporting rate in 2020 compared with 2019 (15.5 per 100,000 population). This decrease in the AEFI reporting rate in 2020 is potentially due to the impact of coronavirus disease 2019 (COVID-19) and was mainly from a decline in reported adverse events related to HPV, dTpa, and seasonal influenza vaccines. AEFI reporting rates for most individual vaccines in 2020 were similar to 2019. The most commonly reported adverse events were injection site reaction (37.1%); pyrexia (18.1%); rash (15.8%); vomiting (7.6%); pain (7.4%); headache (5.7%); and urticaria (5.1%). There were six deaths reported to the TGA. In one of the reports, the timing and clinical findings were consistent with a causal association with vaccination. In the remaining five reports, no clear causal relationship with vaccination was found.

Safety of tetanus, diphtheria, acellular pertussis (Tdap) vaccination during pregnancy.

The objective of this study was to evaluate the safety of prenatal tetanus, diphtheria, acellular pertussis (Tdap) vaccination. This cohort study was conducted among pregnant members at Kaiser Permanente Southern California (KPSC). The exposed cohort consisted of women who received Tdap vaccine on or after the 27th week of pregnancy between January 2018 and January 2019. The unexposed cohort consisted of matched women who were pregnant between January 2012 and December 2014 and were not vaccinated with any Tdap vaccine throughout their pregnancy. Maternal and infant characteristics and pre-specified endpoints were collected through automated data and review of the electronic health records. Unadjusted and adjusted relative risks (aRRs) with confidence intervals (CIs) were estimated by Poisson regression. Non-inferiority testing (i.e., to rule out a two-fold increase) was conducted for primary endpoints with adjustment for multiplicity. Superiority testing was conducted without multiplicity adjustment for secondary endpoints. The analysis consisted of 16,606 pairs of Tdap recipients and unexposed pregnant women. For the primary endpoints, the aRR for preeclampsia/eclampsia was 1.38 (98.75% CI:1.21-1.58) and the aRR for intrauterine infection was 1.28 (98.75% CI:1.12-1.47). These increases were consistent with the background increasing trend of these diagnoses among all pregnant women at KPSC since 2011, and the upper limit of the 98.75% CI of both aRRs did not exceed the pre-specified threshold of 2. No increased risks of small for gestational age (aRR = 1.04, 98.75% CI:0.94-1.16) or preterm delivery (aRR = 0.71, 98.75% CI:0.64-0.78) were observed. No evidence of increased risks for secondary endpoints, including poor fetal growth, preterm pre-labor rupture of membranes, stillbirth/fetal death, placental abruption, transfusion during delivery hospitalization, and neonatal death, was observed. Prenatal Tdap vaccination after the 27th week of pregnancy was not associated with increased risks of pre-specified maternal and infant outcomes, supporting the safety of Tdap vaccination during pregnancy.

Severe immune thrombocytopenia following diphtheria, tetanus, pertussis and polio vaccination in a 36-year-old Caucasian woman: a case report.

BACKGROUND: Immune thrombocytopenia (ITP) is a rare autoimmune disorder characterized by low platelet counts and increased bleeding risk. The disease may be induced by other disorders, including malignancies, autoimmune diseases, infectious agents or drugs. However, ITP has also been described following vaccinations, such as the measles-mumps-rubella vaccination. In rare cases, ITP may occur in children who received a DTaP-IP (diphtheria, tetanus, acellular pertussis vaccine and inactivated poliovirus) vaccine. Hereinafter, we report the first well-documented cases of ITP in an adult patient in the temporal context of a DTaP-IP vaccination. CASE PRESENTATION: This case report attempts to capture the life-threatening picture of a 36-year-old otherwise healthy Caucasian woman with newly diagnosed severe immune thrombocytopenia in the temporal context of a DTaP-IP vaccination. Four days after receiving the vaccine, the women presented to her primary care physician with malaise, fever and recurrent epistaxis. Clinical examination revealed oral petechiae, ecchymoses, and non-palpable petechiae on both legs. The patient was immediately referred to a local hematology unit where she developed hematuria and an intestinal bleeding (WHO Bleeding Grade III) requiring multiple transfusions. After receiving oral corticosteroids and intravenous immunoglobulins, her platelets gradually recovered. Common causes of secondary ITP were ruled out by laboratory investigations, bone marrow and peripheral blood examinations. This raises the possibility of a (secondary) vaccination-associated thrombocytopenia. To the best of our knowledge, this is the first well-documented case of a DTaP-IP vaccination-related ITP in an adult patient in the English literature. CONCLUSION: Although a causal connection between both entities may not be established, we would like to raise awareness in clinicians that ITP following DTaP-IP vaccinations is potentially not limited to children, but may also occur in adults. Users of DTaP-IP booster vaccines should be alert of the possibility of such adverse reactions.

A decade of data: Adolescent vaccination in the vaccine safety datalink, 2007 through 2016.

BACKGROUND: Between May 2005 and March 2007, three vaccines were recommended by the Advisory Committee on Immunization Practices for routine use in adolescents in the United States: quadrivalent meningococcal conjugate vaccine (MenACWY), tetanus, diphtheria and acellular pertussis vaccine (Tdap), and human papillomavirus vaccine (HPV). Understanding historical adolescent vaccination patterns may inform future vaccination coverage efforts for these and emerging adolescent vaccines, including COVID-19 vaccines. METHODS: This was a descriptive, retrospective cohort study. All vaccines administered to adolescents aged 11 through 18 years in the Vaccine Safety Datalink population between January 1, 2007 and December 31, 2016 were examined. Vaccination coverage was assessed by study year for ≥1 dose Tdap or Td, ≥1 dose Tdap, ≥1 dose MenACWY, ≥1 dose HPV, and ≥3 dose HPV. The proportion of vaccine visits with concurrent vaccination (≥2 vaccines administered at the same visit) was calculated by sex and study year. The most common vaccine combinations administered in the study population were described by sex for two time periods: 2007-2010 and 2011-2016. RESULTS: The number of 11-18-year-olds in the study population averaged 522,565 males and 503,112 females per study year. Between January 2007 and December 2016 there were 4,884,553 vaccine visits in this population (45% among males). The overall proportion of concurrent vaccine visits among males was 43% (33-61% by study year). Among females, 39% of all vaccine visits included concurrent vaccination (32-48% by study year). Vaccine coverage for Tdap, MenACWY, and 1- and 3-dose HPV increased across the study period. A wide variety of vaccine combinations were administered among both sexes and in both time periods. CONCLUSIONS: The high vaccine uptake and multitude of vaccine combinations administered concurrently in the adolescent population of the Vaccine Safety Datalink provide historical patterns with which to compare future adolescent vaccination campaigns.

Fourteen years of the Pregnancy Registry on maternal immunisation with a reduced-antigen-content tetanus-diphtheria-acellular pertussis (Tdap) vaccine.

BACKGROUND: GSK initiated a Pregnancy Registry in the United States (US) for the reduced-antigen-content tetanus-diphtheria-acellular pertussis (Tdap; Boostrix, GSK) vaccine with the aim to detect and describe pregnancy outcomes in women vaccinated with Boostrix 28 days before estimated conception or during pregnancy. METHODS: Voluntary reports of pregnancy exposure to Boostrix received from spontaneous and post-marketing surveillance sources in the US were assessed. Reports were classified as prospective or retrospective based on the knowledge of pregnancy outcomes at the time of reporting. For completeness, reports of exposure to Boostrix or to the Tdap-inactivated poliovirus vaccine (Boostrix-IPV, GSK) reported to the global safety database from countries outside the US were also evaluated. RESULTS: From May 2005 to August 2019, 1517 (1455 prospective and 62 retrospective) pregnancy reports were received in the Boostrix US Pregnancy Registry. Of the prospective reports, 250 had known outcomes: 244 live infants with no apparent birth defects (BDs), three live infants with BDs, and three spontaneous abortions with no apparent BDs. Of the retrospective reports, 55 had known outcomes: 33 live infants with no apparent BDs, 16 live infants with BDs, one spontaneous abortion with no apparent BDs, four stillbirths with no apparent BDs, and one stillbirth with BDs. Cumulatively, 1321 pregnancy reports (1006 for Boostrix; 315 for Boostrix-IPV) were received from countries outside the US. Of these, 163 prospective reports and 551 retrospective reports had known outcomes. Results were in line with those from the Boostrix US Pregnancy Registry. CONCLUSIONS: Data currently available from the Boostrix US Pregnancy Registry and from countries outside the US suggested that exposure to Boostrix or Boostrix-IPV during pregnancy does not raise safety concerns related to adverse pregnancy outcomes or BDs.

The optimal strategy for pertussis vaccination: a systematic review and meta-analysis of randomized control trials and real-world data.

OBJECTIVE: Severe pertussis infection has been reported in infants before receiving routine immunization series. This problem could be solved by vaccinating mothers during pregnancy or children at birth. This study aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) and real-world evidence to evaluate the optimal strategy for pertussis vaccination. DATA SOURCES: PubMed, Embase, and the Cochrane Library databases were searched until December 2020. STUDY ELIGIBILITY CRITERIA: RCTs, cohort studies, case-control studies, and case series were included if they investigated the efficacy, immunogenicity, and safety of acellular pertussis vaccine during pregnancy and at birth. METHODS: Number of pertussis cases, severe adverse events (SAEs), and pertussis antibody concentration in infants before and after they receive routine vaccination series were extracted and random-effect model was used to pool the analyses. RESULTS: Overall, 29 studies were included. Our meta-analysis revealed that pertussis immunization during pregnancy significantly increased the concentrations of 3 pertussis antibodies and reduced the incidence rates of infected infants below 3 months of age (odds ratio, 0.22; 95% confidence interval, 0.14-0.33). Similarly, infants vaccinated at birth had higher levels of pertussis antibody than those who were not. No significant difference in rates of severe adverse events was seen in all vaccination groups (during pregnancy [risk ratio, 1.18; 95% confidence interval, 0.76-1.82] and at birth [risk ratio, 0.72; 95% confidence interval, 0.34-1.54]). CONCLUSION: Pertussis vaccination during pregnancy could protect infants against pertussis disease before the routine vaccination. Pertussis immunization at birth would be an alternative for infants whose mothers did not receive pertussis vaccines during pregnancy.