Immunogenicity and Safety of a Newly Developed Tetanus-Diphtheria Toxoid (Td) in Healthy Korean Adolescents: a Multi-center, Randomized, Double-blind, Active-Controlled Phase 3 Trial.

BACKGROUND: Although the combination tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) is recommended at adolescence in developed countries, the tetanus and diphtheria toxoid vaccine (Td), which is less costly, is recommended instead in some parts of the world. A new Td, BR-TD-1001, was developed by a Korean manufacturer for distribution to endemic regions and for use in the initial step of novel Tdap development. METHODS: This phase 3, randomized, double-blind, multi-center trial, conducted in Korea, aimed to evaluate the immunogenicity and safety of BR-TD-1001. Healthy children aged 10 to 12 years were randomized 1:1 to receive either BR-TD-1001 or the control Td (Td-pur, GlaxoSmithKline). Antibodies were measured using enzyme-linked immunosorbent assay. RESULTS: A total of 218 subjects (BR-TD-1001, n = 108; control, n = 110) were enrolled and included in the safety analysis. Vaccine-mediated antibody responses were similar in both groups. We confirmed the non-inferiority of BR-TD-1001 against the control, Td; 100% of both groups achieved seroprotection against diphtheria and tetanus. Furthermore, there was no significant difference between groups in the proportion of participants who demonstrated boost responses against diphtheria and tetanus toxoids. The incidence of solicited local and systemic adverse events (AEs), unsolicited AEs, and serious AEs did not differ significantly between groups. CONCLUSION: The BR-TD-1001 satisfied the immunological non-inferiority criterion against diphtheria and tetanus, with a clinically acceptable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04618939.

Safety and immunogenicity of tetanus/diphtheria vaccination in patients with rheumatic diseases-a prospective multi-centre cohort study.

OBJECTIVES: We aimed to assess the safety and immunogenicity of a diphtheria/tetanus vaccine booster dose in three different patient groups with rheumatic diseases on a variety of immunosuppressive/immunomodulatory medications compared with healthy controls (HCs). METHODS: We conducted a multi-centre prospective cohort study in Switzerland. We enrolled patients with RA, axial SpA/PsA, vasculitis (Behçet's disease, ANCA-associated vasculitis) and HCs. Diphtheria/tetanus vaccination was administered according to the Swiss vaccination recommendations. Blood samples were drawn before vaccination, and 1 month and 3 months afterwards. Antibody concentrations against vaccine antigens were measured by ELISA. Immunogenicity was compared between patient and medication groups. A mixed model was applied for multivariate analysis. Missing data were dealt with using multiple imputation. RESULTS: Between January 2014 and December 2015, we enrolled 284 patients with rheumatic diseases (131 RA, 114 SpA/PsA, 39 vasculitis) and 253 HCs. Of the patients, 89% were on immunosuppressive/immunomodulatory medication. Three months post-vaccination 100% of HCs vs 98% of patients were protected against tetanus and 84% vs 73% against diphtheria. HCs and SpA/PsA patients had significantly higher responses than RA and vasculitis patients. Assessing underlying diseases and medications in a multivariate model, rituximab was the only factor negatively influencing tetanus immunogenicity, whereas only MTX treatment had a negative influence on diphtheria antibody responses. No vaccine-related serious adverse events were recorded. CONCLUSION: Diphtheria/tetanus booster vaccination was safe. Tetanus vaccination was immunogenic; the diphtheria component was less immunogenic. Vaccine responses were blunted by rituximab and MTX. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, Identifier: NCT01947465.

Immunogenicity and safety of a tetanus-diphtheria vaccine and a 13-valent pneumococcal conjugate vaccine after concomitant vaccination in ≥ 50-year-old adults.

BACKGROUND: When two or more vaccines are administered concurrently, there is concern about safety and immunogenicity from vaccine interaction. METHODS: Subjects aged ≥50 years were randomized 1:1:1 to receive tetanus-diphtheria (Td) + 13-valent pneumococcal conjugate vaccine (PCV13; Group 1), PCV13 alone (Group 2), or Td alone (Group 3). After single or concomitant vaccination, enzyme-linked immunosorbent assay and opsonophagocytic assay (OPA) were performed to compare immunogenicity for Td and PCV13, respectively. RESULTS: A total of 448 subjects were available for the assessment. After concomitant administration, the non-inferiority criteria of geometric mean titer (GMT) ratios were met for tetanus, diphtheria, and all four pneumococcal serotypes (1, 5, 18C, and 19A). However, subjects in Group 3 (Td alone) were more likely to have a high IgG anti-tetanus antibody titer (≥ 0.5 U/mL) than those in Group 1 (Td + PCV13) (p <  0.01). As for the pneumococcal serotype 1, the OPA GMT was significantly higher in Group 1 (PCV13 + Td) compared to Group 2 (PCV13 alone) (p = 0.02). No serious adverse event occurred. CONCLUSIONS: Concomitant Td and PCV13 administration induced sufficient immunity without significant interference and showed good safety profiles. TRIALS REGISTRATION: NCT03552445 registered at http://www.clinicaltrials.gov on June 11, 2018 (retrospectively registered).

Safety of repeated doses of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine in adults and adolescents.

In light of waning immunity to pertussis following receipt of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine, maintaining protection may require repeated Tdap vaccination. We evaluated the safety of repeated doses of tetanus-containing vaccine in 68 915 nonpregnant adolescents and adults in the Vaccine Safety Datalink population who had received an initial dose of Tdap. Compared with 7521 subjects who received a subsequent dose of tetanus toxoid, reduced diphtheria (Td) vaccine, the 61 394 subjects who received a subsequent dose of Tdap did not have significantly elevated risk of medical visits for seizure, cranial nerve disorders, limb swelling, pain in limb, cellulitis, paralytic syndromes, or encephalopathy/encephalitis/meningitis. These results suggest that repeated Tdap vaccination has acceptable safety relative to Tdap vaccination followed by Td vaccination.

Safety of vaccinations in patients with cryopyrin-associated periodic syndromes: a prospective registry based study.

Objectives: Pneumococcal, tetanus and influenza vaccinations are recommended for patients with cryopyrin-associated periodic syndromes (CAPS) when treated with immunosuppressive medication. The aim of this publication is to report the safety of pneumococcal and other vaccinations in CAPS patients. Methods: All CAPS patients followed in the ß-CONFIDENT (Clinical Outcomes and Safety Registry study of Ilaris patients) registry were analysed if they had received a vaccination. The ß-CONFIDENT registry is a global, long-term, prospective, observational registry, capturing and monitoring patients treated with canakinumab. Results: Sixty-eight CAPS patients had received a total of 159 vaccine injections, 107 injections against influenza, 19 pneumococcal vaccinations, 12 against tetanus/diphtheria antigens and 21 other vaccinations. Fourteen per cent of injections had elicited at least one vaccine reaction. All five vaccine-related serious adverse events were associated with pneumococcal vaccination. Vaccine reactions were observed in 70% of pneumococcal vaccinations, compared with 7% in influenza and 17% in tetanus/diphtheria vaccinations. The odds ratios to react to the pneumococcal vaccines compared with influenza and tetanus/diphtheria vaccines were 31.0 (95% CI: 8, 119) and 10.8 (95% CI: 2, 74). Vaccine reactions after pneumococcal vaccinations were more severe and lasted significantly longer (up to 3 weeks) compared with other vaccinations. In two patients, pneumococcal vaccination also elicited symptoms consistent with systemic inflammation due to CAPS reactivation. Conclusion: Pneumococcal vaccines, unlike other vaccines, frequently trigger severe local and systemic inflammation in CAPS patients. Clinicians must balance potential benefits of pneumococcal immunization against safety concerns. The 13-valent pneumococcal conjugate vaccine might be favourable over the polysaccharide vaccine in CAPS patients.

Optic neuritis and mydriasis after vaccination: a case report.

BACKGROUND: Optic neuritis (ON) is an inflammatory demyelinating condition of the optic nerve, with various causes. Its incidence is higher in children and young adults than in older adults of both genders, but is more common in women than in men. ON is rarely associated with mydriasis, and it is seldom triggered by vaccines against tetanus and diphtheria. CASE REPORT: A 36-year-old Caucasian woman presented with bilateral ON that had started 18 days after administration of a booster dose of the double adult vaccine (dT) against diphtheria and tetanus. Bilateral mydriasis persisted after treatment and clinical resolution of the ON. She experienced severe headache, blurred vision, decreased visual acuity in the right eye and bilateral mydriasis, a diagnosis confirmed by imaging tests. Treatment with oral corticosteroids resulted in rapid resolution of the neuritis; however, mydriasis persisted for several months. CONCLUSION: This study describes a very unusual case of bilateral ON associated with prolonged mydriasis after vaccination against tetanus and diphtheria that regressed after treatment with oral corticosteroids. Prolonged mydriasis was the manifestation that differed from the other cases previously described.

Evaluation of immunogenicity and safety of the new tetanus-reduced diphtheria (Td) vaccines (GC1107) in healthy Korean adolescents: a phase II, double-blind, randomized, multicenter clinical trial.

This phase II clinical trial was conducted to compare the immunogenicity and safety of a newly developed tetanus-reduced diphtheria (Td) vaccine (GC1107-T5.0 and GC1107-T7.5) and control vaccine. This study was also performed to select the proper dose of tetanus toxoid in the new Td vaccines. Healthy adolescents aged between 11 and 12 yr participated in this study. A total of 130 subjects (44 GC1107-T5.0, 42 GC1107-T7.5 and 44 control vaccine) completed a single dose of vaccination. Blood samples were collected from the subjects before and 4 weeks after the vaccination. In this study, all subjects (100%) in both GC1107-T5.0 and GC1107-T7.5 groups showed seroprotective antibody levels (≥ 0.1 U/mL) against diphtheria or tetanus toxoids. After the vaccination, the geometric mean titer (GMT) against diphtheria was significantly higher in Group GC1107-T5.0 (6.53) and GC1107-T7.5 (6.11) than in the control group (3.96). The GMT against tetanus was 18.6 in Group GC1107-T5.0, 19.94 in GC1107-T7.5 and 19.01 in the control group after the vaccination. In this study, the rates of local adverse reactions were 67.3% and 59.1% in GC1107-T5.0 and GC1107-7.5, respectively. No significant differences in the number of adverse reactions, prevalence and degree of severity of the solicited and unsolicited adverse reactions were observed among the three groups. Thus, both newly developed Td vaccines appear to be safe and show good immunogenicity. GC1107-T5.0, which contains relatively small amounts of tetanus toxoid, has been selected for a phase III clinical trial.

Psoriasis triggered by tetanus-diphtheria vaccination.

Psoriasis is a common inflammatory disease with multiple known triggers. We report the case of a patient whose psoriasis was triggered by tetanus and diphtheria immunization (Td vaccine). To the best of our knowledge, this is the first reported case of psoriasis triggered by the Td vaccine. Authors speculate about the involved mechanisms.

Two rare cases of retinal vasculitis following vaccination.

We write to report two rare cases of retinal vasculitis following administration of vaccinations. Both patients received recent vaccinations (within 4 weeks and 2 months respectively) and presented with unilateral visual loss due to retinal arteriolar vasculitis. Investigations did not reveal any other causes of vasculitis. The first patient's ocular inflammation settled following periocular steroid injection, whereas the second patient required the additional use of oral corticosteroid. Both patients had improved vision following treatment. Vaccinations can cause an autoimmune reaction. Systemic vasculitis has previously been described, whereas ocular vasculitic involvement is also possible but extremely rare. When seeing a patient with visual loss due to retinal vasculitis of unknown aetiology, a history of any recent vaccinations should be elicited.

Complex regional pain syndrome type I after diphtheria-tetanus (Di-Te) vaccination.

Complex regional pain syndrome type I (CRPS I) is a disorder of one or more extremities characterized by pain, abnormal sensitivity (allodynia), swelling, limited range of motion, vasomotor instability, fatigue and emotional distress. The symptoms may be aggravated by even minor activity or weather change. It is usually provoked by injury, surgery or injection but in a small proportion of patients CRPS I develops without a clear causative event. There are several literature reports on CRPS after rubella and hepatitis B vaccination. We present a case of CRPS I affecting the left arm after diphtheria and tetanus (Di-Te) vaccination in the left deltoid muscle in a young girl having experienced profound emotional stress before the vaccination procedure. History data on previous minor trauma at the site of vaccination or emotional stress may necessitate temporary vaccination delay due to their proneness to impaired local or systemic immune response and CRPS as a complication of vaccination. If a child or an adult has prominent swelling and severe pain after vaccination, the diagnosis of CRPS I should be considered and if confirmed, the multidisciplinary treatment should start as soon as possible.

Parental reports of adverse events following simultaneously given dT-IPV and MMR vaccines in healthy 9-year-old children.

In the Netherlands, children at 9 years of age receive a booster dT-IPV together with their second measles, mumps, and rubella (MMR) vaccination within the national immunization program. Safety is monitored continuously by enhanced passive surveillance. This population-based study was conducted to obtain more information on adverse events after vaccination at 9 years of age. Questionnaires on local and systemic reactions were distributed 1 and 3 weeks after vaccination, respectively, to parents of 1,250 healthy children who received their MMR and diphtheria, tetanus, and inactivated poliovirus injection (dT-IPV) vaccination as scheduled. Response to the questionnaires was 57.0% and 46.5%, respectively. Local reactions occurred in 86.5% of the children within 7 days after vaccination, more often at the dT-IPV (83.4%) than at the MMR site (32.7%). Pain was the most reported symptom (80.8% at the dT-IPV site; 29.1% at the MMR site). Systemic events occurred in 33.4% children within 7 days after vaccination, with headache as the most frequently reported (20.8%). Systemic events occurred in 20.8% children 8-21 days after vaccination. Children with local reactions at only the dT-IPV site had significantly more systemic events (19.3%) than those without local reactions (3.4%, p < 0.01). Such difference was not found for the MMR site. No serious adverse events were reported. Medical intervention was applied to 133 children (130 used analgesics and for three children the GP was consulted by phone). In conclusion, the frequency of reported local reactions is high, especially at the dT-IPV site, but all symptoms were transient. However, the use of reduced antigen content vaccines in association with the occurrence of adverse events is meaningful to explore. Furthermore, the overall rates are useful for monitoring variations in adverse events rates in the general population.

[Prognostic value of allergic reaction indicators in the vaccination of children with chronic diseases].

To define the likelihood of development of adverse reactions and complications due to vaccination, the authors conducted clinical and laboratory studies of 115 children aged 1 to 15 years with chronic pathology (allergic diseases, pyelonephritis, immunodeficiency states), vaccinated with diphtheria and tetanus toxoids and pertussis vaccine and diphtheria and tetanus-M anatoxin and revaccinated with diphtheria and tetanus-M anatoxin. The results of the study suggested the prognostic value of allergic reaction indicators (total IgE, DA- and CA-specific IgE, vaccine sensitization detected by the basophil degranulation test) against adverse events and complications of immunization. Vaccination in children with chronic pathology in the presence of higher parameters of allergic reactions, by using hyposensitization therapy, was followed by to the formation of tense antidiphtheria and antitetanus immunity. The given data support the immunological efficiency and safety of immunization of children with chronic diseases against diphtheria and tetanus provided that hyposensitization therapy is performed, by keeping in mind the results of prior clinical and laboratory studies.

Characterising the Phenotypic Diversity of Antigen-Specific Memory B Cells Before and After Vaccination.

The diversity of B cell subsets and their contribution to vaccine-induced immunity in humans are not well elucidated but hold important implications for rational vaccine design. Prior studies demonstrate that B cell subsets distinguished by immunoglobulin (Ig) isotype expression exhibit divergent activation-induced fates. Here, the antigen-specific B cell response to tetanus toxoid (TTd) booster vaccination was examined in healthy adults, using a dual-TTd tetramer staining flow cytometry protocol. Unsupervised analyses of the data revealed that prior to vaccination, IgM-expressing CD27+ B cells accounted for the majority of TTd-binding B cells. 7 days following vaccination, there was an acute expansion of TTd-binding plasmablasts (PB) predominantly expressing IgG, and a minority expressing IgA or IgM. Frequencies of all PB subsets returned to baseline at days 14 and 21. TTd-binding IgG+ and IgA+ memory B cells (MBC) exhibited a steady and delayed maximal expansion compared to PB, peaking in frequencies at day 14. In contrast, the number of TTd-binding IgM+IgD+CD27+ B cells and IgM-only CD27+ B cells remain unchanged following vaccination. To examine TTd-binding capacity of IgG+ MBC and IgM+IgD+CD27+ B cells, surface TTd-tetramer was normalised to expression of the B cell receptor-associated CD79b subunit. CD79b-normalised TTd binding increased in IgG+ MBC, but remained unchanged in IgM+IgD+CD27+ B cells, and correlated with the functional affinity index of plasma TTd-specific IgG antibodies, following vaccination. Finally, frequencies of activated (PD-1+ICOS+) circulating follicular helper T cells (cTFH), particularly of the CXCR3-CCR6- cTFH2 cell phenotype, at their peak expansion, strongly predicted antigen-binding capacity of IgG+ MBC. These data highlight the phenotypic and functional diversity of the B cell memory compartment, in their temporal kinetics, antigen-binding capacities and association with cTFH cells, and are important parameters for consideration in assessing vaccine-induced immune responses.

Immunogenicity and safety of diphtheria-tetanus vaccine in adults.

This study was conducted to evaluate the immunogenicity and safety of diphtheria-tetanus (Td) vaccine in adults over 40 yr old who had never received a diphtheria-tetanus-pertussis (DTP) vaccination. A total of 242 subject completed three-doses of Td vaccination and subsequent assays for immunogenicity. Before vaccination, 33.9% and 96.7% participants showed antibody levels of diphtheria and tetanus, respectively, which were below protective level (<0.1 U/mL). After the first dose of Td vaccine, 92.6% and 77.6% of subjects gained protective antibody concentrations (≥ 0.1 U/mL) for diphtheria and tetanus, with an increase to 99.6% and 100% after the third dose. Local and systemic adverse events occurred in 37.9% and 15.5% of the subjects. No serious adverse event requiring an unscheduled hospital visit occurred. In conclusion, three-doses of Td vaccination to unimmunized adults are safe and effective in inducing protective immunity against diphtheria and tetanus.

[Immunization of patients with chronic obstructive pulmonary disease with vaccines of Bubo-M and hepatitis B].

AIM: To assess tolerability and immunological activity of Bubo-M vaccine and hepatitis B vaccine in patients with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Sixty-three patients with moderate and severe COPD aged 35-65 years were immunized against diphtheria, tetanus, and hepatitis B. Bubo-M vaccine as well as vaccine against hepatitis B were used for immunization. Immunologic effect of vaccination was assessed by measurement of serum antibody level to HBsAg as well as to diphtheria and tetanus toxoids. Assessment of antibody level to HBsAg was performed by ELISA, and levels of antibodies to diphtheria and tetanus toxoids--by micromethod in direct hemagglutination assay. Reactogenicity of Bubo-M vaccine was measured according to duration and intensity of local and systemic reactions. RESULTS: The local and systemic reactions were infrequent, serious adverse events after vaccination were not observed. Six months after vaccination, protective antibody titers to hepatitis B, diphtheria and tetanus were determined in all immunized persons--either healthy, or with COPD. During completion of vaccination schedule, significant reduction of acute respiratory infections rate and main disease exacerbations was noted in patients with COPD. CONCLUSION: Good tolerability and high immunogenicity of Bubo-M and hepatitis B vaccines were demonstrated in both groups of vacinees. These vaccines could be recommended for booster vaccination of adults with COPD.

A randomized controlled trial [corrected] administration of tetanus toxoid (TT) versus tetanus and reduced diphtheria (Td) in pregnant women.

INTRODUCTION: The present study was designed as a randomized clinical trial to compare the immunogenicity, reactogenicity, and efficacy of tetanus toxoid (TT) and the combined tetanus and reduced diphtheria (Td) in pregnant women in four rural communities in Egypt. The pregnant women in each four villages received either TT or Td randomly. Both TT and Td vaccines are manufactured by the Egyptian Company for Biological Products & Vaccines (VACSERA) in Egypt. A total of 131 pregnant women were enrolled during the time of antenatal care visit (at 20 weeks gestational age of pregnancy) in one of four health units in Abu Homos district, Beheira Governorate, Egypt. DISCUSSION: Unimmunized women received two random doses of either TT or Td 8 weeks apart during their pregnancy. Outpatient follow-up for adverse reactions occurred at the third day after each vaccine dose as either local effects such as pain, redness, and swelling or systematic effects such as fever, malaise, and headache or body aches which was served as primary safety endpoint. Blood was collected three times from each woman for determination of antibody titer against tetanus and diphtheria by using enzyme-linked immunosorbent assay technique. The first sample was collected immediately before the first dose, the second before the second dose, and the third sample 1 week after delivery. Active surveillance home visits to all study participants were done twice: the first home visit during the first week after delivery and the second 1 month after labor to report the health status of the mother and the baby. A total of 122 pregnant women received two ordinary doses with interdose intervals within the allowable range and three blood samples were collected in each protocol analysis (62 in the TT group and 60 in the Td group). There was no statistically significant difference between groups in the percentage of reporting a primary safety endpoint (fever, malaise, body ache, headache) or local reactions at the site of injection as redness and swelling, at third day after each dose. While in the Td group, after doses I and II, there was significant reporting pain at injection site as compared with TT group, home visits clinical examination revealed that the mothers and children were normal on in both groups. However, in the TT group, some children suffered from physiological jaundice. In all women in the two groups, protective immunity for tetanus was acquired, which reflected in neutralization of antibodies at titer (>0.10 IU/ml) after complete vaccination; however, the tetanus geometric mean titers postdoses I and II were significantly higher in TT vaccines group (P < 0.001). The postvaccination seroprotection titer (>0.10 IU/ml) in diphtheria was significantly higher in Td group than the TT group; diphtheria geometric mean titers of postdose II were significantly higher in Td vaccines as compared to the other group (P < 0.0001). From this results, we can conclude that the use of Td vaccine improves immunogenicity for both tetanus and diphtheria more than the use of TT vaccine alone and we can recommend to replace TT in immunization of pregnant women.

Prevention of pertussis, tetanus, and diphtheria among pregnant and postpartum women and their infants recommendations of the Advisory Committee on Immunization Practices (ACIP).

In 2005, two tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines were licensed and recommended for use in adults and adolescents in the United States: ADACEL (sanofi pasteur, Swiftwater, Pennsylvania), which is licensed for use in persons aged 11--64 years, and BOOSTRIX (GlaxoSmithKline Biologicals, Rixensart, Belgium), which is licensed for use in persons aged 10-18 years. Both Tdap vaccines are licensed for single-dose use to add protection against pertussis and to replace the next dose of tetanus and diphtheria toxoids vaccine (Td). Available evidence does not address the safety of Tdap for pregnant women, their fetuses, or pregnancy outcomes sufficiently. Available data also do not indicate whether Tdap-induced transplacental maternal antibodies provide early protection against pertussis to infants or interfere with an infant's immune responses to routinely administered pediatric vaccines. Until additional information is available, CDC's Advisory Committee on Immunization Practices recommends that pregnant women who were not vaccinated previously with Tdap: 1) receive Tdap in the immediate postpartum period before discharge from hospital or birthing center, 2) may receive Tdap at an interval as short as 2 years since the most recent Td vaccine, 3) receive Td during pregnancy for tetanus and diphtheria protection when indicated, or 4) defer the Td vaccine indicated during pregnancy to substitute Tdap vaccine in the immediate postpartum period if the woman is likely to have sufficient protection against tetanus and diphtheria. Although pregnancy is not a contraindication for receiving Tdap vaccine, health-care providers should weigh the theoretical risks and benefits before choosing to administer Tdap vaccine to a pregnant woman. This report 1) describes the clinical features of pertussis, tetanus, and diphtheria among pregnant and postpartum women and their infants, 2) reviews available evidence of pertussis vaccination during pregnancy as a strategy to prevent infant pertussis, 3) summarizes Tdap vaccination policy in the United States, and 4) presents recommendations for use of Td and Tdap vaccines among pregnant and postpartum women.

Frequency of medically attended adverse events following tetanus and diphtheria toxoid vaccine in adolescents and young adults: a Vaccine Safety Datalink study.

BACKGROUND: Local reactions are the most commonly reported adverse events following tetanus and diphtheria toxoid (Td) vaccine and the risk of local reactions may increase with number of prior Td vaccinations. METHODS: To estimate the risk of medically attended local reactions following Td vaccination in adolescents and young adults we conducted a six-year retrospective cohort study assessing 436,828 Td vaccinations given to persons 9 through 25 years of age in the Vaccine Safety Datalink population from 1999 through 2004. RESULTS: Overall, the estimated risk of a medically attended local reaction was 3.6 events per 10,000 Td vaccinations. The lowest risk (2.8 events per 10,000 vaccinations) was found in the 11 to 15 year old age group. In comparison with that group, the event risks were significantly higher in both the 9 to 10 and 21 to 25 year old age groups. The risk of a local reaction was significantly higher in persons who had received another tetanus and diphtheria toxoid containing vaccine (TDCV) in the previous five years (incidence rate ratio, 2.9; 95% confidence interval, 1.2 to 7.2). Twenty-eight percent of persons with a local reaction to Td vaccine were prescribed antibiotics. CONCLUSION: Medically attended local reactions were uncommon following Td vaccination. The risk of those reactions varied by age and by prior receipt of TDCVs. These findings provide a point of reference for future evaluations of the safety profile of newer vaccines containing tetanus or diphtheria toxoid.

Changes in DT vaccine frequency and indications for use following introduction of DTaP vaccine.

Our population-based study among HMO members under seven years of age in 1993-2000 showed that frequency of diphtheria and tetanus toxoid vaccine (DT) use declined significantly following the introduction of acellular pertussis-containing (DTaP) vaccine. We also observed changes in indications for DT following the transition to DTaP among children under two years of age; notably, a decline in the proportion of children receiving DT due to a reported prior vaccine reaction and an increase in the proportion of children receiving DT due to parental request and a history of pertussis.