Diphtheria-tetanus-acellular Pertussis Research Articles

Maternal Recall of Obstetric Office-Based Activities That Promote Antepartum Tetanus–Diphtheria–Acellular–Pertussis Vaccination

Maternal Recall of Obstetric Office-Based Activities That Promote Antepartum Tetanus–Diphtheria–Acellular–Pertussis Vaccination

Vaccination during pregnancy and modulation of IgG response to pertussis vaccines in infants: The impact of different vaccine formulations

The IgG response following infant diphtheria-tetanus-acellular pertussis (DTaP) immunization is influenced by the formulation of the infant and/or the adult vaccine (Tdap) given during pregnancy. DTaP vaccines containing either 3 (DTaP3) or 5 (DTaP5) pertussis antigens are commonly used. By conducting a secondary analysis of a large randomized controlled trial, we compared IgG levels against pertussis vaccine antigens in children of Td- and Tdap5-vaccinated mothers, after stratifying by infant vaccine formulation. After immunization with a primary series of DTaP5, but not DTaP3, IgG GMCs against pertussis antigens were significantly lower in infants of Tdap-immunized mothers compared with infants of Td-vaccinated mothers (pertussis toxin: GMC = 52.3[Tdap5] vs 83.5[Td], p < 0.001). Before and after the DTaP booster dose, IgG GMCs were similar in infants of Tdap- and Td-immunized mothers specifically when infants received the DTaP3 vaccine. The combination of the TdaP5 vaccine for mothers and the DTaP3 vaccine for children could attenuate Tdap-associated immunomodulation.

Cost-effectiveness analysis of pertussis booster vaccination for adolescents in Japan

IntroductionIn Japan, the introduction of a fifth diphtheria–tetanus–acellular pertussis (DTaP) vaccination has been considered, and adolescents aged 11–12 years old who are currently receiving the diphtheria–tetanus (DT) vaccine are one candidate group. We analyze the cost-effectiveness of replacing the DT vaccine with the DTaP vaccine for 11-year-old adolescents and investigate the indirect effect of vaccinated adolescents on unvaccinated infant siblings. We undertake two analyses using high- and low-morbidity pertussis cases, and based on the results, present suggestions for pertussis prevention in the post-COVID-19 pandemic era. MethodWe used the number of pertussis cases in 2019 as the high-morbidity case and the average number of cases in 2020–2021 as the low-morbidity case, and evaluated the incremental cost-effectiveness ratio (ICER) of the DTaP strategy to the DT strategy based on quality-adjusted life years (QALYs). The economic model contained adolescent and infant sub-models. The indirect effect for infants was considered as the probability of unvaccinated infants avoiding pertussis infection from their vaccinated siblings. ResultsThe ICER from the payers’ perspective was Japanese yen (JPY) 4,254,515 per QALY gained in the high-morbidity case and JPY 62,546,776 per QALY gained in the low-morbidity case. The sensitivity analysis showed that the utility of pertussis had the greatest impact on the ICER, with a 60.58% and 0% probability that the ICER was less than JPY 5 million per QALY gained in the high-morbidity case and low-morbidity case, respectively. ConclusionThe cost-effectiveness of replacing the DT vaccine with the DTaP vaccine is affected by the level of pertussis morbidity, with the ICER becoming more favorable in the high-morbidity case. The indirect effect has little impact on the ICER. Thus, policy-makers should continue to monitor the pertussis epidemic in the post-COVID-19 era, and determine the need to introduce a booster based on perceived trends.

Attitudes Toward Routine Vaccines and COVID-19 Vaccines Among Parents of Infants and Toddlers in an Urban Safety-Net Setting.

This study explores attitudes toward diphtheria-tetanus-acellular pertussis (DTaP), measles-mumps-rubella (MMR), influenza, and coronavirus disease 2019 (COVID-19) vaccines among English-speaking and Spanish-speaking parents of infants in a safety-net setting. Parents aged 18 years or older were recruited from outpatient clinics between December 2020 and December 2021. The interviews were then recorded, transcribed, translated, and qualitatively analyzed using the modified grounded theory. Thirty-two individuals participated (18 English-speaking and 14 Spanish-speaking). Almost all supported receiving routine childhood vaccines, DTaP, influenza, and MMR and believed that vaccines promote health. Vaccine concerns differed by each vaccine. Few participants expressed concerns about DTaP and MMR vaccines. Concerns around influenza vaccines often stemmed from personal experience and perceived increased risk of flu-like illnesses. Participants expressed the most concerns related to COVID-19 vaccinations, including age-based immunity of their infants. Based on these findings, future interventions to improve vaccine uptake may focus on benefits common to all vaccines, while addressing vaccine-specific concerns.

Safety assessments of recombinant DTaP vaccines developed in South Korea.

Pertussis bacteria have many pathogenic and virulent antigens and severe adverse reactions have occurred when using inactivated whole-cell pertussis vaccines. Therefore, inactivated acellular pertussis (aP) vaccines and genetically detoxified recombinant pertussis (rP) vaccines are being developed. The aim of this study was to assess the safety profile of a novel rP vaccine under development in comparison to commercial diphtheria-tetanus-acellular pertussis (DTaP) vaccines. The two positive control DTaP vaccines (two- and tri-components aP vaccines) and two experimental recombinant DTaP (rDTaP) vaccine (two- and tri-components aP vaccines adsorbed to either aluminum hydroxide or purified oat beta-glucan) were used. Temperature histamine sensitization test (HIST), indirect Chinese hamster ovary (CHO) cell cluster assay, mouse-weight-gain (MWG) test, leukocytosis promoting (LP) test, and intramuscular inflammatory cytokine assay of the injection site performed for safety assessments. HIST results showed absence of residual pertussis toxin (PTx) in both control and experimental DTaP vaccine groups, whereas in groups immunized with tri-components vaccines, the experimental tri-components rDTaP absorbed to alum showed an ultra-small amount of 0.0066 IU/mL. CHO cell clustering was observed from 4 IU/mL in all groups. LP tests showed that neutrophils and lymphocytes were in the normal range in all groups immunized with the two components vaccine. However, in the tri-components control DTaP vaccine group, as well as two- and tri-components rDTaP with beta-glucan group, a higher monocyte count was observed 3 days after vaccination, although less than 2 times the normal range. In the MWG test, both groups showed changes less than 20% in body temperature and body weight before the after the final immunizations. Inflammatory cytokines within the muscle at the injection site on day 3 after intramuscular injection revealed no significant response in all groups. There were no findings associated with residual PTx, and no significant differences in both local and systemic adverse reactions in the novel rDTaP vaccine compared to existing available DTaP vaccines. The results suggest that the novel rDTaP vaccine is safe.

Australian vaccine preventable disease epidemiological review series: tetanus 2003-2019.

Background We examined trends in tetanus notification, hospitalisation and death data from 2003-2019 to assess the impact of adult tetanus booster recommendations in Australia. Methods Tetanus notifications and deaths from the National Notifiable Diseases Surveillance System; hospitalisations from the Australian Institute of Health and Welfare National Hospital Morbidity Database; and deaths from the Australian Coordinating Registry were analysed by age group, sex, Aboriginal and Torres Strait Islander status and state/territory. Annual rates were calculated using Australian Bureau of Statistics mid-year estimated resident populations from 2003-2019 as denominators. To assess the impact of a recommended booster dose of reduced antigen content diphtheria-tetanus-acellular pertussis (dTpa) vaccine for adults aged ≥ 65 years, notification, hospitalisation and death rates of tetanus per 100,000 population were compared pre (2003-2012) and post (2013-2019) the recommendation's introduction. Results There were 63 notifications of tetanus from 2003-2019 with an average annual incidence rate of 0.02/100,000. Similar to previous studies, the burden of tetanus in the Australian population continues to disproportionately affect the elderly, with those aged ≥ 65 years encompassing 63% (40/63) of notifications and 100% (11/11) of the deaths observed in this timeframe. Following the introduction of a recommendation for those aged ≥ 65 years to receive a dTpa booster, average annual notification and hospitalisation rates in those aged ≥ 65 years were significantly lower (notifications: 0.11/100,000 in 2003-2012 and 0.05/100,000 in 2013-2019, p = 0.01; hospitalisations: 0.24/100,000 in 2003-2012 and 0.10/100,000 in 2013-2019, p = 0.01]). The average annual death rate was similar in the two periods (0.002/100,000), although based on small numbers. Conclusions The findings of this analysis suggest a positive impact from the 2013 recommendation. However, the burden is still disproportionately higher in those aged ≥ 65 years and strategies to improve vaccination coverage in older Australians are recommended.

Impact of national recommendations for routine pertussis vaccination during pregnancy on infant pertussis in Ontario, Canada: a population-based time-series study

BackgroundIn February 2018, Canada’s National Advisory Committee on Immunization (NACI) recommended antenatal tetanus–diphtheria–acellular pertussis (Tdap) immunization in every pregnancy regardless of previous Tdap immunization history. We examined the impact of the NACI recommendation on rates of infant pertussis in Ontario, Canada.MethodsWe conducted a population-based time-series study of all live births in Ontario between August 1, 2011 and February 28, 2020. We used interventional autoregressive integrated moving average models to examine the impact of the NACI recommendation on monthly rates of pertussis among infants ≤ 3 months of age.ResultsWe observed 675 incident cases of pertussis among 1,368,024 infants 3 months of age or less between August 2011 and February 2020. The average monthly percent change in infant pertussis during the period up to and including publication of the NACI guidance and the period following publication were 0.0% (95% CI: -0.4–0.3%) and − 0.8% (95% CI -2.3% to -0.1%), respectively. Following interventional ARIMA modelling, publication of the NACI guidance was not associated with a statistically significant decrease in the monthly pertussis incidence trend (-0.67 cases per 100,000 infants; p = 0.73).ConclusionPublication of national recommendations for antenatal Tdap immunization in every pregnancy did not significantly reduce infant pertussis rates. This may reflect the persistently low rate of antenatal vaccination following publication of the recommendations. Expanding the scope of practice of allied health care providers to include antenatal Tdap immunization and patient education regarding antenatal pertussis immunization should be considered to further optimize uptake of vaccination.

Association between pertussis vaccination coverage and other sociodemographic factors and pertussis incidence using surveillance data

Routine vaccination with pertussis vaccines has been successful in driving down pertussis mortality and morbidity globally. Despite high vaccination coverage, countries such as Australia, USA, and UK have experienced increase in pertussis activity over the last few decades. This may be due to local pockets of low vaccination coverage that result in persistence of pertussis in the population and occasionally lead to large outbreaks. The objective of this study was to characterize the association between pertussis vaccination coverage and sociodemographic factors and pertussis incidence at the school district level in King County, Washington, USA. We used monthly pertussis incidence data for all ages reported to the Public Health Seattle and King County between January 1, 2010 and December 31, 2017 to obtain school district level pertussis incidence. We obtained immunization data from the Washington State Immunization Information System to estimate school-district level vaccination coverage as proportion of 19–35 month old children fully vaccinated with ≥4 doses of the Diphtheria-Tetanus-acellular-Pertussis (DTaP) vaccine in a school district. We used two methods to quantify the effects of vaccination coverage on pertussis incidence: an ecological vaccine model and an endemic–epidemic model. Even though the effect of vaccination is modeled differently in the two approaches, both models can be used to estimate the association between vaccination coverage and pertussis incidence. Using the ecological vaccine model, we estimated the vaccine effectiveness of 4 doses of Diphtheria-Tetanus-acellular-Pertussis vaccine to be 83% (95% credible interval: 63%, 95%). In the endemic–epidemic model, under-vaccination was statistically significantly associated with epidemic risk of pertussis (adjusted Relative Risk, aRR: 2.76; 95% confidence interval: 1.44, 16.6). Household size and median income were statistically significantly associated with endemic pertussis risk. The endemic–epidemic model suffers from ecological bias, whereas the ecological vaccine model provides less biased and more interpretable estimates of epidemiological parameters, such as DTaP vaccine effectiveness, for each school district.

Immunogenicity and safety of BPZE1, an intranasal live attenuated pertussis vaccine, versus tetanus–diphtheria–acellular pertussis vaccine: a randomised, double-blind, phase 2b trial

Bordetella pertussis epidemics persist as transmission remains unabated despite high acellular pertussis vaccination rates. BPZE1, a live attenuated intranasal pertussis vaccine, was designed to prevent B pertussis infection and disease. We aimed to assess the immunogenicity and safety of BPZE1 compared with the tetanus-diphtheria-acellular pertussis vaccine (Tdap). In this double-blind, phase 2b trial at three research centres in the USA, healthy adults aged 18-50 years were randomly assigned (2:2:1:1) via a permuted block randomisation schedule to receive BPZE1 vaccination followed by BPZE1 attenuated challenge, BPZE1 vaccination followed by placebo challenge, Tdap followed by BPZE1 attenuated challenge, or Tdap followed by placebo challenge. On day 1, lyophilised BPZE1 was reconstituted with sterile water and given intranasally (0·4 mL delivered to each nostril), whereas Tdap was given intramuscularly. To maintain masking, participants in the BPZE1 groups received an intramuscular saline injection, and those in the Tdap groups received intranasal lyophilised placebo buffer. The attenuated challenge took place on day 85. The primary immunogenicity endpoint was the proportion of participants achieving nasal secretory IgA seroconversion against at least one B pertussis antigen on day 29 or day 113. Reactogenicity was assessed up to 7 days after vaccination and challenge, and adverse events were recorded for 28 days after vaccination and challenge. Serious adverse events were monitored throughout the study. This trial is registered with ClinicalTrials.gov, NCT03942406. Between June 17 and Oct 3, 2019, 458 participants were screened and 280 were randomly assigned to the main cohort: 92 to the BPZE1-BPZE1 group, 92 to the BPZE1-placebo group, 46 to the Tdap-BPZE1 group, and 50 to the Tdap-placebo group. Seroconversion of at least one B pertussis-specific nasal secretory IgA was recorded in 79 (94% [95% CI 87-98]) of 84 participants in the BPZE1-BPZE1 group, 89 (95% [88-98]) of 94 in the BPZE1-placebo group, 38 (90% [77-97]) of 42 in the Tdap-BPZE1 group, and 42 (93% [82-99]) of 45 in the Tdap-placebo group. BPZE1 induced broad and consistent B pertussis-specific mucosal secretory IgA responses, whereas Tdap did not induce consistent mucosal secretory IgA responses. Both vaccines were well tolerated, with mild reactogenicity and no serious adverse events related to study vaccination. BPZE1 induced nasal mucosal immunity and produced functional serum responses. BPZE1 has the potential to avert B pertussis infections, which ultimately could lead to reduced transmission and diminished epidemic cycles. These results should be confirmed in large phase 3 trials. ILiAD Biotechnologies.

Pertussis, diphtheria, and tetanus antibodies seroprevalence in pregnant women and neonates, as a preliminary data for introduction of preconception or prenatal DTaP vaccination among Japanese society

An increasing number of countries have been introducing acellular pertussis vaccination during pregnancy for the prevention of neonatal pertussis. In response to the fact that infantile pertussis cases of 0–5 months age groups remained unchanged despite the universal vaccination program, prenatal pertussis vaccination has been a rising issue in Japan. Hence, we investigated the seroprevalence of pertussis, diphtheria, and tetanus antibodies in Japanese pregnant women and neonates, and evaluated the necessity of diphtheria-tetanus-acellular pertussis (DTaP) vaccination during the preconception or prenatal period. Maternal PT-IgG (EIA) and FHA-IgG (EIA) for the first trimester, within 1 week after delivery, and cord blood were collected, along with colostrum pertussis-IgA (ELISA), diphtheria-IgG (EIA), tetanus-IgG (EIA), and blood samples from the first trimester. The maternal seroprevalence of PT-IgG and FHA-IgG was 69 % and 75 %, respectively. All tested participants were positive for diphtheria-IgG and tetanus-IgG (100 %). First trimester PT-IgG/FHA-IgG antibody titers were significantly associated with cord blood PT-IgG/FHA-IgG titers (P < 0.001). We found that pertussis seroprevalence among pregnant Japanese women was approximately 70 %. The antibody seropositivity rate of pertussis was lower than that of diphtheria and tetanus. Fetal acquired passive immunity against pertussis is higher when the level of maternal antibody in the first trimester is sufficient. At least 30 % of study population did not reach to the threshold value to provide sufficient pertussis immunity for the neonates and themselves. The acellular pertussis vaccine (DTaP) approved in Japan lacks safety information for pregnancy, hence, a solution for prompt administration of prenatal acellular pertussis vaccination might be introducing DTaP in the preconception period.

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 pointConsidering 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.BackgroundThe 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.MethodsThe 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.ResultsThis 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.ConclusionsThe 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.

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

ABSTRACT 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.

Timing of Monovalent Vaccine Administration in Infants Receiving DTaP-based Combination Vaccines in the United States.

Background:The recommended US infant immunization schedule includes doses of diphtheria, tetanus, acellular pertussis (DTaP), inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib) and hepatitis B virus (HepB) during the first 6 months of life. Little information is available about the timing of associated, complementary monovalent vaccine administration in infants receiving DTaP-based pentavalent combination vaccines.Methods:This was a retrospective cohort study of infants born between July 1, 2010, and June 30, 2018, in the US MarketScan commercial claims and encounters database. Descriptive statistics were used to assess vaccine administration patterns. Multivariate logistic regression was performed to explore factors associated with coadministration of DTaP-IPV/Hib and HepB.Results:Among infants who received DTaP-HepB-IPV (n = 129,885), 93.7% had claims for at least 2 Hib doses; most (91.5%‐98.3%) of these doses were administered on the same day as DTaP-HepB-IPV doses. Among infants who received DTaP-IPV/Hib (n=214,172), 95.3% had claims for ≥2 doses of HepB. Although coverage was high, 59.2% received the second HepB dose on the same day as the first DTaP-IPV/Hib dose, and 44.6% received the third dose of HepB on the same day as the third DTaP-IPV/Hib dose. Differences in coadministration of the second and third HepB doses with DTaP-IPV/Hib were associated with the region of residence, provider type, health plan type and coadministration of pneumococcal conjugate vaccine and rotavirus vaccine.Conclusions:Almost all infants received the appropriate, complementary monovalent vaccine series. However, this study found variability in the timing of HepB doses in relation to DTaP-IPV/Hib doses with many infants not completing the HepB series until 9 months of age.

True, true, and unrelated: Stop routine testing to vaccine excipients for suspected vaccine allergy

Vaccines for infectious diseases contain multiple minor ingredients called excipients, such as egg ovalbumin, polysorbate (PS), polyethylene glycol (PEG), neomycin, thimerosal, and other contaminants (eg, lactose, yeast, formaldehyde, gelatin, latex).1,2 Allergic reactions occurring to vaccines are rare, but focus on vaccine excipients as the provoking cause.3 Examples of this include egg ovalbumin in yellow fever (YF), gelatin in measles, mumps, and rubella (MMR) and several other vaccines, yeast in hepatitis B vaccines, and casein with diphtheria tetanus acellular pertussis (DTaP).

Antibiotic Use and Vaccine Antibody Levels.

The majority of children are prescribed antibiotics in the first 2 years of life while vaccine-induced immunity develops. Researchers have suggested a negative association of antibiotic use with vaccine-induced immunity in adults, but data are lacking in children. From 2006 to 2016, children aged 6 to 24 months were observed in a cohort study. A retrospective, unplanned secondary analysis of the medical record regarding antibiotic prescriptions and vaccine antibody measurements was undertaken concurrently. Antibody measurements relative to diphtheria-tetanus-acellular pertussis (DTaP), inactivated polio (IPV), Haemophilus influenzae type b (Hib), and pneumococcal conjugate (PCV) vaccines were made. In total, 560 children were compared (342 with and 218 without antibiotic prescriptions). Vaccine-induced antibody levels to several DTaP and PCV antigens were lower (P < .05) in children given antibiotics. A higher frequency of vaccine-induced antibodies below protective levels in children given antibiotics occurred at 9 and 12 months of age (P < .05). Antibiotic courses over time was negatively associated with vaccine-induced antibody levels. For each antibiotic course the child received, prebooster antibody levels to DTaP antigens were reduced by 5.8%, Hib by 6.8%, IPV by 11.3%, and PCV by 10.4% (all P ≤ .05), and postbooster antibody levels to DTaP antigens were reduced by 18.1%, Hib by 21.3%, IPV by 18.9%, and PCV by 12.2% (all P < .05). Antibiotic use in children <2 years of age is associated with lower vaccine-induced antibody levels to several vaccines.

Cost-effectiveness of pertussis booster vaccination for preschool children in Japan

Introduction: Japan currently recommends four doses of the diphtheria-tetanus-acellular pertussis (DTaP) vaccine in its routine vaccination program, but the introduction of a fifth dose is currently under consideration. An objective of the booster vaccination is to prevent severe cases of pertussis in infants through herd immunity. Thus, the aim of this analysis was to demonstrate the cost-effectiveness of a fifth-dose of the DTaP vaccine for 6-year-old children, taking herd immunity for unvaccinated infants into account. MethodAn economic model analysis was conducted comparing the cost and effectiveness of the two strategies based on quality-adjusted life years (QALYs). We evaluated the incremental cost-effectiveness ratio (ICER) of the booster strategy to the no booster strategy. This model contained two sub-models: one for children aged 6 years or older and one for infants under 3 months old. Herd immunity for infants is modeled as when siblings in the same family are infected. ResultsThe ICER was JPY 71,605,491 (USD 656,931) per QALY gained from the societal perspective, and 7.10% of incremental QALYs (0.0000934) were from a reduction in infant infection. In the sensitivity analysis, no variables moved the ICER under the threshold (JPY 5,000,000 per QALY gained), and the duration of pertussis disease and the incidence rate of pertussis had a significant impact on the ICER. When the disease burden of pertussis decreased, the booster strategy resulted in fewer QALYs gained and greater costs compared with the no booster strategy. ConclusionThe introduction of a DTaP booster vaccination to the routine immunization schedule can be expected to reduce the number of pertussis cases in the target population. However, our study showed that adding a booster vaccination for 6-year-old children to the schedule in Japan would not be cost-effective in terms of achieving herd immunity among unvaccinated infants.

Factors Impacting Vaccine Uptake during Pregnancy: A Retrospective Analysis.

Background and Objective:Vaccine uptake rates during pregnancy remain below target goals due to a convergence of factors. In particular, women of lower socioeconomic means and racial minorities typically have reduced rates of vaccine acceptance. This study aims to identify additional factors contributing to vaccine acceptance within a sample population of women receiving prenatal care in Houston, Texas, United States of America.Methods:We performed a retrospective cross-sectional analysis of 11,500 pregnant women covered by Medicaid or ChipPerinate who received prenatal care during 2013-2021, assessing influenza (flu) and combined Tetanus, Diphtheria, Acellular Pertussis (TDAP) vaccine acceptance in the patient population. We examined temporal trends in flu and TDAP vaccination rates using Joinpoint regression analyses and evaluated the factors associated with single or concomitant vaccine acceptance during the study period and during the COVID-19 pandemic using adjusted log-binomial regression models.Results:In our population, 54% of patients received flu vaccination, and 76.1% received TDAP. TDAP rates increased from 2013-2015 but have shown an overall decline since then, as with the flu vaccine. Earlier entry to prenatal care (Prevalence Ratio [PR] 6.32; Confidence Interval [CI] 3.28-12.24) and pregnancy comorbidity such as gestational diabetes (PR 1.32; CI 0.82-2.19) were positively associated with uptake. In contrast, the NH-Black race was negatively associated with vaccine acceptance (PR 0.51 CI; 0.25-0.99). Otherwise, age and history of pre-pregnancy comorbidities were not significant predictors.Conclusion and Global Health Implications:Within demographic groups identified as at-risk for vaccine refusal, modifying factors further impact vaccine hesitancy. Identifying these elements will guide targeted patient efforts to promote vaccine uptake, both for routine prenatal recommendations and for COVID vaccination.

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.

Immunogenicity of a new enhanced tetanus-reduced dose diphtheria-acellular pertussis (Tdap) vaccine against Bordetella pertussis in a murine model

BackgroundThe necessity of the tetanus-reduced dose diphtheria-acellular pertussis (Tdap) vaccine in adolescence and adults has been emphasized since the resurgence of small-scale pertussis in Korea and worldwide due to the waning effect of the vaccine and variant pathogenic stains in the late 1990s. GreenCross Pharma (GC Pharma), a Korean company, developed the Tdap vaccine GC3111 in 2010. Recently, they enhanced the vaccine, GC3111, produced previously in 2010 to reinforce the antibody response against filamentous hemagglutinin (FHA). In this study, immunogenicity and efficacy of the enhanced Tdap vaccine compared and evaluated with two Tdap vaccines, GC3111 vaccine produced in 2010 previously and commercially available Tdap vaccine in a murine model.MethodsTwo tests groups and positive control group of Balb/c mice were primed with two doses of the diphtheria-tetanus-acellular pertussis (DTaP) vaccine followed by a single booster Tdap vaccine at 9 week using the commercially available Tdap vaccine or 2 Tdap vaccines from GC Pharma (GC3111, enhanced GC3111). Humoral response was assessed 1 week before and 2 and 4 weeks after Tdap booster vaccination. The enhanced GC3111 generated similar humoral response compare to the commercial vaccine for filamentous hemagglutinin (FHA). The interferon gamma (IFN-γ) (Th1), interleukin 5 (IL-5) (Th2) and interleukin 17 (IL-17) (Th17) cytokines were assessed 4 weeks after booster vaccination by stimulation with three simulators: heat inactivated Bordetella pertussis (hBp), vaccine antigens, and hBp mixed with antigens (hBp + antigen). A bacterial challenge test was performed 4 weeks after booster vaccination.ResultsRegarding cell-mediated immunity, cytokine secretion differed among the three simulators. However, no difference was found between two test groups and positive control group. All the vaccinated groups indicated a Th1 or Th1/Th2 response. On Day 5 post-bacterial challenge, B. pertussis colonies were absent in the lungs in two test groups and positive control group.ConclusionsOur results confirmed the immunogenicity of GC Pharma’s Tdap vaccine; enhanced GC3111 was equivalent to the presently used commercial vaccine in terms of humoral response as well as cell-mediated cytokine expression.

Association of Diphtheria-Tetanus–Acellular Pertussis Vaccine Timeliness and Number of Doses With Age-Specific Pertussis Risk in Infants and Young Children

In most countries, the diphtheria-tetanus-acellular pertussis (DTaP) vaccine is administered as a 3-dose infant series followed by additional booster doses in the first 5 years of life. Short-term immunity from the DTaP vaccine can depend on the number, timing, and interval between doses. Not receiving doses in a timely manner might be associated with a higher pertussis risk. To examine the association between number and timeliness of vaccine doses and age-specific pertussis risk. This population-based, retrospective cohort study used Washington State Immunization Information System data and pertussis surveillance data from Public Health Seattle and King County, Washington. Included participants were children aged 3 months to 9 years born or living in King County, Washington, between January 1, 2008, and December 31, 2017. Data were analyzed from June 30 to December 1, 2019. Being undervaccinated (receiving fewer than recommended doses at a given age) or delayed vaccination (not receiving doses within time frames recommended by Centers for Disease Control and Prevention). Suspected, probable, and confirmed pertussis diagnosis. A total of 316 404 children (median age, 65.2 months [interquartile range, 35.3-94.1 months]; 162 025 boys [51.2%]) as of December 31, 2017, with 17.4 million person-months of follow-up were included in the analysis. A total of 19 943 children (6.3%) had no vaccines recorded in the Immunization Information System, 116 193 (36.7%) received a vaccine with a delay, and 180 268 (56.9%) were fully vaccinated with no delay. Delayed vaccination and undervaccination rates were higher for older children (17.6% delayed or undervaccinated at age 2 months for dose 1 at 3 months vs 41.6% at age 5 years for dose 5) but improved for successive birth cohorts (52.2% for 2008 birth cohort vs 32.3% for 2017 birth cohort). Undervaccination was significantly associated with higher risk of pertussis for the 3-dose primary series (adjusted relative risk [aRR], 4.8; 95% CI, 3.1-7.6), the first booster (aRR, 3.2; 95% CI, 2.3-4.5), and the second booster (aRR, 4.6; 95% CI, 2.6-8.2). However, delay in vaccination among children who received the recommended number of vaccine doses was not associated with pertussis risk. The results of this cohort study suggest that undervaccination is associated with higher pertussis risk. Short delays in vaccine receipt may be less important if the age-appropriate number of doses is administered, but delaying doses is not recommended. Ensuring that children receive all doses of pertussis vaccine, even if there is some delay, is important.