Tetanus Toxoid-containing Vaccine Research Articles

Reporting Case Study Results for Neonatal Tetanus Case Investigations

Developing countries are facing numerous health challenges. One of the greatest challenges in this regards is the existence of neonatal tetanus disease. Dera Ismail Khan is educationally backward, and the majority of the population lives in rural areas without proper access to health facilities. This study was aimed to intestate the neonatal tetanus cases. Literature review was undertaken, which suggested the use of case approach; therefore, the study used a case method of investigation. The case setting was District Headquarters Zanana (Women) Hospital Dera Ismail Khan, which is the only mother-child hospital in the southern districts of DIKhan, Tank, and Waziristan. The study reported that Tetanus remains a significant public health concern in the areas, with a high mortality rate and a need for improved prevention and management efforts. The majority of tetanus cases in the area occur among unvaccinated individuals, particularly among those who have not received tetanus toxoid-containing vaccine as part of routine immunization. There are significant disparities in tetanus vaccination coverage by region and socioeconomic status, which contribute to the burden of tetanus in vulnerable populations. Improving tetanus vaccination coverage and strengthening surveillance and management systems are important steps to lessen the burden of tetanus in Pakistan.

Prevalence and determinants of two or more doses of tetanus toxoid-containing vaccine immunization among pregnant women in sub-Saharan Africa: Evidence from recent demographic and health survey data

IntroductionTetanus is a major public health problem in low and middle income countries including in sub-Saharan Africa. Tetanus toxoid vaccine immunization during pregnancy is a global strategy against mortality due to maternal and neonatal tetanus. Recent data on tetanus toxoid-containing vaccination during pregnancy provides insight to policymakers for better implementation of the vaccine. Hence, this study aimed to determine prevalence and determinants of immunization with tetanus toxoid containing vaccine among pregnant women in sub-Saharan Africa. MethodsSecondary analysis of the recent demographic and health survey data was done using a sample of 173,032 pregnant women. Stata 14 statistical software was used for analysis and multilevel logistic regression model was applied to determine associated factors of two or more tetanus toxoid-containing vaccine immunization. P-value less than 0.05 for adjusted odds ratio was used to identify factors significantly associated with the outcome. ResultThe prevalence of immunization with two and more doses of tetanus toxoid-containing vaccine in sub-Saharan Africa was found to be 49.8 %. Women’s age 36–49, women’s education, poor household wealth index, unwanted pregnancy, women’s occupation, husband education, and community illiteracy were significantly associated with two or more doses of tetanus toxoid-containing vaccine immunization in sub-Saharan Africa. ConclusionIn sub-Saharan Africa, less than half of pregnant women were immunized with two or more doses of tetanus toxoid-containing vaccine. Women's education and women's employment positively affected immunization with two or more doses of tetanus toxoid-containing vaccine. Women’s age group of 36–49 years, unwanted pregnancy, poor household wealth index, husbands having no formal education, and community illiteracy negatively affected receipt of two or more doses of tetanus toxoid-containing vaccine. Therefore, policymakers should take into account the determinants of tetanus toxoid immunization throughout its implementation so as to boost the coverage of tetanus toxoid immunization in sub-Saharan Africa.

Characteristics of preventive intervention acceptance for international travel among clients aged 60 years and older from a Japanese multicenter pretravel consultation registry

ObjectivesPretravel consultation (PTC) is important for older adults owing to health problems associated with overseas travel. Although older adults in Japan, their PTC characteristics are less known. This study aimed to investigate the epidemiology of clients aged ≥ 60 years based on data from the Japan Pre-travel Consultation Registry (J-PRECOR). MethodsClients aged ≥ 60 years who visited J-PRECOR cooperative hospitals from February 1, 2018, to May 31, 2022, were included. The primary endpoint was a comparison of prescriptions for vaccines for hepatitis A, tetanus toxoid, and malaria prophylaxis in travelers to high-risk malaria countries in yellow fever vaccination (YFV)-available facilities with and without YFV. ResultsIn total, 1000 clients (median age: 67 years) were included. Although 523 clients were immunized with YFV, only 38.6% of the 961 unimmunized clients were vaccinated with the tetanus toxoid-containing vaccine. Malaria chemoprophylaxis was prescribed to 25.7% of clients traveling for ≤55 days. At YFV-capable institutes, 557 clients traveling to yellow fever risk countries took PTC, 474 of whom received YFV and 83 were unvaccinated. Lower age (odds rate 0.85 per 1 year; 95% CI 0.80–0.90) and lower hepatitis A vaccination rate (0.29; 95% CI 0.14–0.63) were significantly associated with YFV. ConclusionsPreventive interventions other than YFV should be offered to older adults.

Validation of the Vaccination Trust Indicator (VTI) in a multi-country survey of adult vaccination attitudes.

Improved uptake of adult vaccinations could substantially reduce the burden of infectious disease worldwide, however very few countries achieve high coverage of recommended adult vaccinations. Vaccine hesitancy is an important driver of low vaccine uptake among adults but no measure currently exists to capture general vaccination attitudes in this population accurately and efficiently. We utilize data from two surveys of adult vaccine attitudes and uptake conducted in fifteen countries to evaluate the Vaccination Trust Indicator (VTI). The VTI is a six-item measure intended to capture general vaccine attitudes. We utilized multivariable logistic regression to examine the association between VTI scores and self-reported receipt of the seasonal influenza vaccine, receipt of a tetanus toxoid-containing vaccine and intent to receive the flu vaccine in the next season. In the five countries with self-reported vaccine receipt data, we found that a ten-point increase in VTI score was associated with a 50% increase in odds of influenza vaccine receipt (OR = 1.55, 95% CI = 1.48, 1.62) and 25% increase in the odds of tetanus vaccine receipt (OR = 1.26, 95% CI = 1.21, 1.30). Strong associations between VTI score and vaccine receipt were found in each country except China. A strong association between VTI score and intent to receive the influenza vaccine was found in all fifteen countries. The VTI is a promising tool for assessing adult immunization attitudes with clear and immediate uses for immunization programs globally.

Factors associated with maternal tetanus vaccination in Myanmar: An analysis of demographic and health survey data

BackgroundTetanus toxoid vaccination is a life-saving maternal and child health intervention. Understanding gaps in maternal vaccination coverage is key to informing progress towards universal health coverage. We assessed the vaccination coverage in Myanmar and investigated factors associated with being unvaccinated. MethodIn this cross-sectional analysis of 2015–16 Demographic and Health Survey data including women aged 15–49 years with at least one childbirth in the last five years. The outcome maternal tetanus vaccination during her last pregnancy, defined as protected against neonatal tetanus based on the Myanmar National Guidelines for Antenatal Care. We also examined mothers who missed a second dose of tetanus toxoid containing vaccine (TTCV) by states and regions. We used logistic regression models to assess factors associated with being unvaccinated. ResultsOverall maternal tetanus vaccination coverage was 72%. At subnational level, the percent unvaccinated was highest in Shan State (42%), followed by Magway Region (33%), Kayin State (33%), and Sagaing Region (32%). The percentage of mothers who missed a second dose of TTCV was high predominantly in regions, rather than states. We found that the percentage of unvaccinated mothers was higher among younger mothers, and mothers with lower educational attainment. No antenatal care (ANC) or receiving ANC in non-public healthcare facilities were strongly associated with being unvaccinated. Differences in percent unvaccinated by maternal age were largely mediated through their healthcare access, particularly ANC services. InterpretationWe identified regional, structural, and individual differences in maternal tetanus vaccination coverage. Factors influencing mothers who missed a second dose of TTCV warrant further investigation. Achieving universal coverage of maternal tetanus vaccination will largely depend on the ability to provide accessible antenatal care to most women who do not currently receive it.

Surveillance of Vaccination Coverage Among Adult Populations -United States, 2018.

Surveillance of Vaccination Coverage Among Adult Populations -United States, 2018.

The association between area of residence and sufficient antenatal tetanus vaccination in women ages 15\u201349 in Afghanistan: an analysis of the 2015 DHS dataset

BackgroundNeonatal tetanus (NT) is a deadly nervous system disorder that is endemic to Afghanistan. Administering sufficient doses of tetanus toxoid containing vaccine (TTCV) during pregnancy can pass antibodies to the fetus and therefore prevent NT. Using survey data, we investigated the association between area of residence (urban or rural) and sufficient antenatal TTCV coverage among women aged 15–49 years in Afghanistan during their most recent pregnancy in the past 5 years that resulted in a live birth. Mother’s education level was also assessed as a potential effect modifier.MethodsSecondary analysis was performed on data from the 2015 Afghanistan Demographic and Health Survey (AfDHS). The 2015 AfDHS was a nationally representative survey with participants selected in a stratified two-stage sample design from urban and rural areas across Afghanistan’s 34 provinces. Data were analyzed on 19,737 women ages 15–49 that had a live birth in the 5 years preceding the survey. The relationship between area of residence and sufficient antenatal TTCV was assessed in a multivariable logistic regression model, adjusting for several confounding variables.Results55.1% (95% CI = 51.6–58.5%) of urban women and 53.9% (95% CI = 49.7–57.9%) of rural women had sufficient tetanus vaccination coverage in their most recent pregnancy. In multivariate analysis, there was strong evidence for greater odds of sufficient antenatal tetanus vaccination in rural areas (OR = 1.62; 95% CI = 1.18–2.24, p = 0.003). There was no effect modification on this association by mother’s education level.ConclusionsWomen in rural areas of Afghanistan have greater odds of receiving sufficient antenatal tetanus vaccination than women in urban areas. Further study into factors contributing to this urban-rural disparity is needed. Targeted antenatal tetanus vaccination strategies for urban and rural women will be necessary as Afghanistan continues to work towards NT eradication.

Arthus Reaction as an Adverse Event Following Tdap Vaccination.

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

Vaccine implementation factors affecting maternal tetanus immunization in low- and middle-income countries: Results of the Maternal Immunization and Antenatal Care Situational Analysis (MIACSA) project

ObjectivesTo examine the characteristics of existing maternal tetanus immunization programmes for pregnant women in low- and middle-income countries (LMICs) and to identify and understand the challenges, barriers and facilitators associated with maternal vaccine service delivery that may impact the introduction and implementation of new maternal vaccines in the future. DesignA mixed methods, cross sectional study with four data collection phases including a desk review, online survey, telephone and face-to-face interviews and in country visits. SettingLMICs. ResultsThe majority of countries (84/95; 88%) had a maternal tetanus immunization policy. Countries with high protection at birth (PAB) were more likely to report tetanus toxoid-containing vaccine (TTCV) coverage targets > 90%. Less than half the countries included in this study had a TTCV coverage target of > 90%. Procurement and distribution of TTCV was nearly always the responsibility of the Expanded Programme on Immunization (EPI), however planning and management of maternal immunization was often shared between EPI and Maternal, Newborn and Child Health (MNCH) programmes. Receipt of TTCV at the same time as the antenatal care visit correlated with high PAB. Most countries (81/95; 85%) had an immunization safety surveillance system in place although only 11% could differentiate an adverse event following immunization (AEFI) in pregnant and non-pregnant women. ConclusionsRecommendations arising from the MIACSA project to strengthen existing services currently delivering maternal tetanus immunization in LMICs include establishing and maintaining vaccination targets, clearly defining responsibilities and fostering collaborations between EPI and MNCH, investing in strengthening the health workforce, improving the design and use of existing record keeping for immunization, adjusting current AEFI reporting to differentiate pregnant women and endeavoring to integrate the provision of TTCV within ANC services where appropriate.

Progress Toward Maternal and Neonatal Tetanus Elimination - Worldwide, 2000-2018.

Maternal and neonatal tetanus* (MNT) remains a major public health problem, with an 80%-100% case-fatality rate among neonates, especially in areas with poor immunization coverage and limited access to clean deliveries (i.e., delivery in a health facility or assisted by medically trained attendants in sanitary conditions) and umbilical cord care (1). In 1989, the World Health Assembly endorsed the elimination† of neonatal tetanus (NT), and in 1999, the initiative was relaunched and renamed the MNT elimination§ initiative, targeting 59¶ priority countries (1). Elimination strategies include 1) achieving ≥80% coverage with ≥2 doses of tetanus toxoid-containing vaccine (TTCV) among women of reproductive age through routine immunization of pregnant women and supplementary immunization activities (SIAs)** in high-risk areas and districts††; 2) achieving care at ≥70% of deliveries by a skilled birth attendant (SBA)§§; and 3) enhancing surveillance for NT cases (1). This report summarizes progress toward achieving MNT elimination during 2000-2018. Coverage with ≥2 doses of TTCV (2 doses of tetanus toxoid [TT2+] or 2 doses of tetanus-diphtheria toxoid [Td2+]) among women of reproductive age increased by 16%, from 62% in 2000 to 72% in 2018. By December 2018, 52 (88%) of 59 priority countries had conducted TTCV SIAs, vaccinating 154 million (77%) of 201 million targeted women of reproductive age with TT2+/Td2+. Globally, the percentage of deliveries assisted by SBAs increased from 62% during 2000-2005 to 81% during 2013-2018, and estimated neonatal tetanus deaths decreased by 85%, from 170,829 in 2000 to 25,000 in 2018. By December 2018, 45 (76%) of 59 priority countries were validated by WHO as having achieved MNT elimination. To achieve elimination in the remaining 14 countries and sustain elimination in countries that have achieved it, implementation of MNT elimination strategies needs to be maintained and strengthened, and TTCV booster doses need to be included in country immunization schedules as recommended by the World Health Organization (WHO) (2). In addition, integration of maternal, newborn, and child health services with vaccination services is needed, as well as innovative approaches to target hard-to-reach areas for tetanus vaccination and community engagement to strengthen surveillance.

Improving immunization strategy and promoting the development of tetanus prevention and control in China

Neonatal tetanus has been basically eliminated in China, but the incidence of non-neonatal tetanus is still high. Tetanus after trauma is the main type of non-neonatal tetanus. The correct application of tetanus toxoid containing vaccine (TTCV) has been neglected in the prevention of tetanus after trauma in China. On May 9, 2019, National Advisory Committee of Experts on Immunization Planning (NIAC) reviewed and approved the first guidelines for the use of TTCV and passive immune preparation after trauma, which clarified the basic process of treatment of tetanus after trauma, as well as the pointer to the use of TTCV and passive immune preparation after trauma. The main measure to prevent tetanus after trauma is to use TTCV for active immunization, and to use passive immune preparation for those without TTCV immune history. Through the construction of the top-down control and prevention system of tetanus, the change of the concept of tetanus immunoprophylaxis of medical staff is promoted. Active immunization is the main measure, but passive immunization is an added measure for the prevention of tetanus after trauma, which is of great significance to reverse the mistake of prevention of tetanus in China.

Single doses of diphtheria-tetanus-pertussis and poliomyelitis vaccines are sufficient to generate a booster-type response to tetanus in most migrant children

BackgroundImmunization coverage for three doses of the diphtheria-tetanus-pertussis and poliomyelitis vaccines in infants is high worldwide, therefore despite the lack of documentation of past vaccinations, most migrant children do not require complete revaccination. Our strategy was to administer a single dose of a tetanus toxoid containing vaccine (TTCV) to migrant children followed by anti-tetanus toxoid (TT) serology to determine whether additional vaccine doses were required. Our goal was to estimate the basic TTCV coverage and to identify potential determinants of the vaccination response. MethodsNewly arrived migrant children were prospectively enrolled between October 2014 and August 2017. We included patients aged 1–18 years with no proof of past vaccinations who accepted a single dose of TTCV. Anti-TT serology was performed after 4–6 weeks, and an anti-TT level ≥ 1 IU/mL was considered a booster-type antibody response with no need for additional doses of TTCV. Potential determinants of the vaccination response were identified using univariate and multivariate linear regression analyses. ResultsTwo hundred and eight children were eligible for analysis. The mean age of the children was 9 (±4.5) years and 100 (48%) were female. The majority (n = 129, 62%) of the children came from the WHO Eastern Mediterranean region. Only three patients (1.4%) required additional vaccine doses. A Syrian origin (p < 0.001) and direct arrival primarily by airplane into Switzerland without transiting through other European countries (p = 0.029) associated with higher anti-TT levels in a multivariate regression model (multiple r2 = 0.210, p < 0.001). ConclusionA single dose of TTCV is enough to generate long-term protection in most migrant children. In the context of high basic vaccination coverage, the strategy, which consists of administration of a single dose of TTCV followed by anti-TT serology, can be considered where serotesting is available and economical.

Impact of tetanus, diphtheria, and acellular pertussis (Tdap) vaccine use in wound management on health care costs and pertussis cases.

The Advisory Committee on Immunization Practices (ACIP) recommends the use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine for routine wound management in adolescents and adults who require a tetanus toxoid-containing vaccine who were vaccinated ≥ 5 years earlier with tetanus toxoid, reduced diphtheria toxoid (Td) vaccine, and who have not previously received Tdap. To estimate the overall budget and health impact of vaccinating individuals presenting for wound management with Tdap instead of Td vaccine, the current standard of care in practices that do not use Tdap for purposes of wound management. A decision-analytic economic model was developed to estimate the expected increase in direct medical costs and the expected number of cases of pertussis avoided associated with the use of Tdap instead of Td vaccine in the wound management setting. Patients eligible for Tdap were aged 10+ years and required a tetanus-containing vaccine. Age-specific wound incidence data and Td and Tdap vaccination rates were taken from the National Health Interview Survey and the National Immunization Survey for the most recent available year. Age-specific pertussis incidence used in this analysis (151 per 100,000 for adolescents, 366 per 100,000 for those aged 20-64 years, and 176 per 100,000 for those aged 65+ years) used reported incidence rates adjusted by a factor of 10 for adolescents and by a factor of 100 for adults, based on assumptions previously made by ACIP to account for underreporting. Vaccine wholesale acquisition costs without federal excise tax were assumed in the base case. Efficacy of vaccination with Tdap in preventing pertussis was based on clinical trial data. Possible herd immunity effects of vaccination were not included in the model. Costs associated with vaccination and treatment of pertussis cases were reported as total annual costs and per-member-per-month (PMPM) costs for hypothetical health plans and for the U.S. population. Aggregate and incremental costs and pertussis cases avoided were presented undiscounted (as recommended for budget-impact analyses) annually and cumulatively over a 3-year time horizon in 2012 U.S. dollars. Scenario analyses were conducted on key parameters, including wound incidence, pertussis incidence, vaccine efficacy and waning protection against pertussis, uptake rates for Tdap, and vaccine prices using alternative data sources or alternative clinically relevant assumptions. For a health plan with 1 million covered lives aged < 65 years, vaccination with Tdap instead of Td was estimated to cost an additional $132,364 ($0.01 PMPM) in the first year and an additional $368,640 ($0.01 PMPM) cumulatively over 3 years. For a health plan with 1 million covered lives aged 65+ years, vaccination with Tdap instead of Td was estimated to cost an additional $201,165 ($0.02 PMPM) in the first year and an additional $549,568 ($0.02 PMPM) cumulatively over 3 years. For the U.S. population aged 10+ years, vaccination with Tdap instead of Td was estimated to result in protection against pertussis for an additional 2.7 million patients with wounds annually and was estimated to cost an additional $121,101,671 to avoid 42,104 cases of pertussis over the 3-year time horizon. Results were sensitive to input parameter values, particularly parameters associated with the number of patients with wounds vaccinated with Tdap (range 2.7 to 5.1 million patients). However, for all of the alternative scenarios tested, the expected increase in PMPM costs ranged from < $0.01 to $0.03. Vaccination of adolescents and adults with Tdap for wound management may result in an increase in PMPM costs for health plans of < $0.01 to $0.03. Given the potential reduction in pertussis cases at the population level, vaccination with Tdap for routine wound management could be considered as another strategy to help address the pertussis public health concern in the United States.

Shortened Interval between Tetanus Vaccines

To identify the minimum safe interval between tetanus-diphtheria (Td) and tetanus-diphtheria-acellular pertussis (Tdap) vaccines. Literature was retrieved through a review of ImmunoFacts, the Centers for Disease Control and Prevention (CDC) Web site, MEDLINE (1966-February 2012) and International Pharmaceutical Abstracts (1970-February 2012) using the terms Tdap, Td, and interval. In addition, reference citations from publications identified were reviewed. All English-language articles identified from the data sources were evaluated. Studies addressing an interval of 2 years or less between Td and Tdap vaccines were included. Two observational noninferiority studies have evaluated the safety of an interval of 2 years or less. The first involved a school-based immunization program to compare the safety of a single dose of Tdap given 18 months to 9 years after a tetanus and diphtheria toxoid-containing vaccine versus an interval of 10 or more years. Injection site erythema and swelling were increased among participants with shortened intervals between vaccines; however, no serious adverse events, entire limb swelling, or Arthus-like reactions were reported. The second study involved health care workers who received Tdap during a pertussis outbreak with the objective to compare safety of intervals less than 2 years between prior tetanus vaccination and Tdap with intervals 2 years or more. Criteria for noninferiority were met overall between the 2 intervals in terms of moderate and severe injection site reactions. Fever was more common with the shortened interval, as was any redness or any swelling. No serious adverse events were reported among the group with an interval of less than 2 years between vaccine administration. Although well-designed randomized controlled trials are lacking, the current observational evidence and CDC provisional recommendations support a shortened interval between Td and Tdap vaccines to protect health care workers from pertussis. Intervals less than 2 years may be associated with an increased incidence of local injection site reactions.

Pertussis and Patient Safety: Implementing Tdap Vaccine Recommendations in Hospitals

Despite the availability of pediatric vaccines against pertussis ("whooping cough"), the disease is poorly controlled. Adolescents and adults with waning immunity, especially immediate family members, are responsible for 76%-83% of pertussis transmission to infants. Adolescent/adult tetanus, diphtheria, and acellular pertussis (Tdap) booster vaccines were licensed in the United States in 2005, but their use has been low and hospitals' implementation of immunization recommendations suboptimal. Efforts were implemented at two hospitals in Chicago to increase postpartum use of Tdap vaccine and to replace the tetanus and diphtheria toxoids (Td) booster with Tdap vaccine in emergency department (ED) settings. Postpartum Pertussis Vaccination Program at Prentice Women's Hospital: In the program's first 18 months (June 2008-November 2009) 9,540 doses of Tdap vaccine were administered to 78.87% of the postpartum patients. Children's Memorial Hospital: Tdap Use in Emergency Settings: In 2007, uptake of Tdap was slow. During 2008, of 43 ED patients receiving a tetanus toxoid-containing vaccine as part of wound management, 10 were given Tdap (20 had previously received a dose of Tdap vaccine). Hospital-based Tdap initiatives in postpartum and ED settings can be successfully implemented, provided that support is obtained not only from key decision makers at the hospital but also the health care providers who will be directly involved in implementing those initiatives. It is imperative that hospitals implement programs that increase the use of Tdap vaccine among postpartum women, in emergency settings, and among health care personnel.

How Soon After a Prior Tetanus-Diphtheria Vaccination Can One Give Adult Formulation Tetanus-Diphtheria-Acellular Pertussis Vaccine?

Adult formulation tetanus and diphtheria toxoids and acellular pertussis vaccines (Tdap) have been developed to prevent pertussis in adolescents and adults. There are concerns that unacceptable rates of severe injection site reactions, including Arthus-type reactions might occur if Tdap is administered too soon after a previous tetanus and diphtheria toxoid-containing vaccine formulated for infants and younger children (TD) or older children and adults (Td). To evaluate whether adverse reactions after Tdap might be related to time since last receipt of TD/Td, we performed an open label, province-wide, clinical trial comparing the reactogenicity of Tdap given 18 months-9 years versus > or = 10 years after a previous TD/Td. Seven thousand one hundred fifty-six children and adolescents were enrolled in the study (464-963 subjects per cohort), and 7001 had documented dates of the previous immunization within the specified intervals; adverse event data were provided by 5931 (84.7%). No whole limb swelling, Arthus-like reactions or serious adverse events related to vaccination were reported. No differences in reports of fever were found by interval since last immunization. Injection site erythema and swelling were slightly and statistically significantly increased among those participants with most recent prior TD/Td. Compared with the 10-year interval group, the maximum increase for any other group was < or = 8.6% for any erythema, < or = 6% for erythema > 10 mm, < or = 10.3% for any swelling, < or = 6.9% for swelling > 10 mm, < or = 5.2% for any pain and < or = 3.7% for moderate/severe pain. Although there is a slight increase in injection site events with decreasing interval since a previous immunization, Tdap can be safely administered at intervals of > or = 18 months since a previous TD/Td vaccine.