Diphtheria And Tetanus Toxoids And Acellular Pertussis Research Articles

Recommendation for use of diphtheria and tetanus toxoids and acellular pertussis, inactivated poliovirus, Haemophilus influenzae type b conjugate, and hepatitis B vaccine in infants.

In April 2020, the Ministry of Food and Drug Safety licensed a hexavalent combined diphtheria and tetanus toxoids and acellular pertussis (DTaP), inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib) conjugated to tetanus protein, and hepatitis B (HepB) (recombinant DNA) vaccine, DTa-PIPV-Hib-HepB (Hexaxim, Sanofi Pasteur), for use as a 3-dose primary series in infants aged 2, 4, and 6 months. The DTaP-IPV-Hib-HepB vaccine is highly immunogenic and safe and provides a long-term immune response based on studies performed in a variety of settings in many countries, including Korea. This report summarizes the Committee on Infectious Diseases of the Korean Pediatric Society guidelines for the use of this newly introduced hexavalent combination vaccine.

The recombinant protein combined vaccine based on the fragment C of tetanus toxin and the cross-reacting material 197.

Diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccines were widely used since 1940s. The exceptional success of childhood vaccination is undisputed. However, the anti-diphtheria and tetanus antibody will decrease with the increase of age in human body. A boosting vaccine for tetanus and diphtheria in adult is recommended by WHO. Recombinant protein vaccine has the advantages of single component and high safety, which is one of the directions to develop boosting vaccines. Therefore, in this study, we evaluated a recombinant TTc and CRM197 combination vaccine (RTCV) that uses the fragment C (TTc) of tetanus toxin and the cross-reacting material 197 (CRM197) of the diphtheria toxin mutant. Our results displayed that RTCV (composed of 10 μg/mL TTc, 20 μg/mL CRM197 antigens, and 500 μg/mL aluminum adjuvants) could induce high levels of IgG and IgG1 antibody in mice, which were similar as those induced by DTaP. These results will provide technical support for a novel boosting vaccine against diphtheria and tetanus. KEY POINTS: • We successfully expressed CRM197 protein in E. coli BL21 (DE3) using pET26b (+) vector. • The anti-TTc and anti-CRM197 antibody titer (IgG) of RTCV was similar with DTaP.

Safety of Diphtheria and Tetanus Toxoids and Acellular Pertussis (DTaP) Vaccine in Adults in Japan.

Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine is generally used for booster vaccination of infants in Europe and the United States to avoid increased reactogenicity after diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccination. However, Japan has extended the use of additional DTaP vaccination without reducing the antigen dose for diphtheria and pertussis in adolescents and adults, despite limited reports on its safety in adults. This prospective, observational, questionnaire-based study investigated the occurrence of adverse events (AEs) following DTaP vaccination between June 2018 and June 2019 in participants aged 10 years or older. Of the 250 eligible participants, 235 (94%) responded regarding AEs. Among them, 133 (56.6%) reported AEs, of which 39 reported systemic AEs (16.6%) and 120 reported local AEs (51.1%) attributed to DTaP vaccination. The incidence of local AEs was markedly higher with DTaP vaccination than with non-DTaP vaccination (51.1% vs. 10.5%), and AEs appeared later (P < 0.01) and lasted longer (P < 0.01) with DTaP vaccination. However, more than 75% of these AEs resolved within 7 days. DTaP vaccination was not associated with any serious AEs. These results indicate that the DTaP vaccine can be widely used as a booster in adults as an alternative to the Tdap vaccine.

Vaccines—Autism Toolkit

Vaccines—Autism Toolkit

Licensure of a Diphtheria and Tetanus Toxoids and Acellular Pertussis, Inactivated Poliovirus, Haemophilus influenzae Type b Conjugate, and Hepatitis B Vaccine, and Guidance for Use in Infants.

On December 21, 2018 the Food and Drug Administration (FDA) licensed a hexavalent combined diphtheria and tetanus toxoids and acellular pertussis (DTaP) adsorbed, inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib) conjugate (meningococcal protein conjugate) and hepatitis B (HepB) (recombinant) vaccine, DTaP-IPV-Hib-HepB (Vaxelis; MCM Vaccine Company),* for use as a 3-dose series in infants at ages 2, 4, and 6 months (1). On June 26, 2019, after reviewing data on safety and immunogenicity, the Advisory Committee on Immunization Practices (ACIP)† voted to include DTaP-IPV-Hib-HepB in the federal Vaccines for Children (VFC) program.§ This report summarizes the indications for DTaP-IPV-Hib-HepB and provides guidance for its use.

Safety of Co-Administration Versus Separate Administration of the Same Vaccines in Children: A Systematic Literature Review.

The growing number of available vaccines that can be potentially co-administered makes the assessment of the safety of vaccine co-administration increasingly relevant but complex. We aimed to synthesize the available scientific evidence on the safety of vaccine co-administrations in children by performing a systematic literature review of studies assessing the safety of vaccine co-administrations in children between 1999 and 2019, in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Fifty studies compared co-administered vaccines versus the same vaccines administered separately. The most frequently studied vaccines included quadrivalent meningococcal conjugate (MenACWY) vaccine, diphtheria and tetanus toxoids and acellular pertussis (DTaP) or tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines, diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B, inactivated poliovirus and Haemophilus influenzae type b conjugate (DTaP-HepB-IPV/Hib) vaccine, measles, mumps, and rubella (MMR) vaccine, and pneumococcal conjugate 7-valent (PCV7) or 13-valent (PCV13) vaccines. Of this, 16% (n = 8) of the studies reported significantly more adverse events following immunization (AEFI) while in 10% (n = 5) significantly fewer adverse events were found in the co-administration groups. Statistically significant differences between co-administration and separate administration were found for 16 adverse events, for 11 different vaccine co-administrations. In general, studies briefly described safety and one-third of studies lacked any statistical assessment of AEFI. Overall, the evidence on the safety of vaccine co-administrations compared to separate vaccine administrations is inconclusive and there is a paucity of large post-licensure studies addressing this issue.

Prevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP).

SummaryThis report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of tetanus, diphtheria, and pertussis in the United States. As a comprehensive summary of previously published recommendations, this report does not contain any new recommendations and replaces all previously published reports and policy notes; it is intended for use by clinicians and public health providers as a resource. ACIP recommends routine vaccination for tetanus, diphtheria, and pertussis. Infants and young children are recommended to receive a 5-dose series of diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccines, with one adolescent booster dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine. Adults who have never received Tdap also are recommended to receive a booster dose of Tdap. Women are recommended to receive a dose of Tdap during each pregnancy, which should be administered from 27 through 36 weeks’ gestation, regardless of previous receipt of Tdap. After receipt of Tdap, adolescents and adults are recommended to receive a booster tetanus and diphtheria toxoids (Td) vaccine every 10 years to assure ongoing protection against tetanus and diphtheria.

Advisory Committee on Immunization Practices Recommended Immunization Schedules for Persons Aged 0 Through 18 Years—United States, 2016

Each year, the Advisory Committee on Immunization Practices (ACIP)* reviews the recommended immunization schedules for persons aged 0 through 18 years to ensure that the schedules reflect current recommendations for Food and Drug Administration-licensed vaccines. In October 2015, ACIP approved the recommended immunization schedules for persons aged 0 through 18 years for 2016; the 2016 schedules include several changes from the 2015 immunization schedules. For 2016, the figures, footnotes, and tables will be published on the CDC immunization schedule website (http://www.cdc.gov/vaccines/schedules/index.html). This provides readers electronic access to the most current version of the schedules and footnotes on the CDC website. Health care providers are advised to use figures, tables, and the combined footnotes together. Printable versions of the 2016 immunization schedules for persons aged 0 through 18 years in several formats (e.g., portrait, landscape, and pocket-sized versions) and ordering instructions for laminated versions and "parent-friendly" schedules are available at the immunization schedule website.

Risk Factors Associated with Children Missing the Fourth Dose of DTaP Vaccination.

Background:In 2012, reported pertussis reached the highest number of cases (48,277) in the United States since 1955.Objectives:Estimate the prevalence of children who missed the fourth dose of DTaP (Diphtheria and Tetanus toxoids and acellular Pertussis vaccine) by parents’ confidences in vaccines and influences from providers, the timeliness of the first through the third dose of DTaP, and selected socio-demographic characteristics; identify the significant risk factors for non-receipt of the fourth dose of DTaP; and evaluate the unadjusted and adjusted risk ratios for missing the fourth dose of DTaP.Methods:Data from 16,919 children 19–35 months living in the United States included in the 2011 National Immunization Survey were analyzed. Weighted categorical data analysis and multivariable regression in the context of complex sample survey were applied to assess the prevalence and to determine the independent risk factors.Results:Overall, 14.7% of children missed the fourth dose of DTaP. Children who were late in receiving the third dose of DTaP had significantly higher risk of missing the fourth dose of DTaP than children who were on-time in receiving the third dose of DTaP (adjusted risk ratio (RR) 2.48; 95%CI (1.92, 3.20)). The risk of missing the fourth dose of DTaP was 62% higher among children whose parents reported they didn’t have a good relationship with their child’s health-care providers than children whose parents reported having good relationship. Compared with the risk of missing the fourth dose of DTaP among children whose parents were confident in the value of vaccines, the risk was significantly higher for the children whose parents lacked confidence (adjusted RR 1.41; 95%CI (1.05, 1.89)).Conclusions:Timeliness in receiving the first through the third dose of DTaP, influences from providers, and parents’ confidence in the value of vaccines are the five significant risk factors for missing the fourth dose of DTaP vaccination. They are all modifiable. Future interventions to improve parental relationships with providers and attitudes toward vaccines could help improve pertussis vaccination coverage.

Why Do Pertussis Vaccines Fail?

* Abbreviations: DTaP — : pediatric diphtheria and tetanus toxoids and acellular pertussis vaccine DTP — : pediatric diphtheria and tetanus toxoids and whole-cell pertussis vaccine FHA — : filamentous hemagglutinin FIM — : fimbriae PCR — : polymerase chain reaction PRN — : pertactin PT — : pertussis toxin WHO — : World Health Organization During the 2010 pertussis epidemic in California, there was considerable concern in the press and in public health communications about the possible contribution of vaccine failures to the problem.1,2 In this commentary, I examine why pertussis vaccines fail and Table 1 lists 8 possible reasons. View this table: TABLE 1 Possible Reasons Why DTP, DTaP, and Adolescent- and Adult-Formulated Tetanus and Diphtheria Toxoids and Acellular Pertussis Vaccines Fail The first reason, and perhaps the most important one, is that our estimates of vaccine efficacy have been inflated because of case definition.3–11 At the time of the pediatric diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine efficacy trials in the early 1990s, it was hoped that a universal case definition could be developed so that the results of the various trials could be compared. To this end, the World Health Organization (WHO) case definition was developed.3 The primary case definition required laboratory confirmation and ≥21 days of paroxysmal cough. I was a member of the WHO committee and disagreed with the primary case definition because it was clear at that time that this definition would eliminate a substantial number of cases and therefore inflate reported efficacy values.4–11 Nevertheless, the Center for Biologics Evaluation and Research of the Food and Drug Administration accepted this definition, and package inserts of the US-licensed DTaP vaccines reflect this. For example, Infanrix (containing 25 μg pertussis toxin [PT], 25 μg filamentous hemagglutinin [FHA], and 8 μg pertactin [PRN]) and Daptacel (containing 10 μg PT, 5 μg FHA, 5 μg fimbriae [FIM]-2/3, and 3 μg … Address correspondence to James D. Cherry, MD, MSc, Department of Pediatrics, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, MDCC 22-442, Los Angeles, CA 90095-1752. E-mail: jcherry{at}mednet.ucla.edu

Injection Site and Risk of Medically Attended Local Reactions to Acellular Pertussis Vaccine

To assess whether the risk of medically attended local reactions to the fifth dose of the diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine varies according to injection site (arm versus thigh). We conducted a retrospective cohort study of children aged 4 through 6 years in the Vaccine Safety Datalink population who received a DTaP vaccination during the period from 2002 through 2006. Medically attended local reactions to the DTaP vaccine were presumptively identified from administrative data and were confirmed by medical record review. Among the 233,616 children in the study population, 1017 (0.4%) had a confirmed medically attended local reaction to the fifth dose of the DTaP vaccine. The rate of those reactions was significantly higher with vaccinations given in the arm (47.4 per 10,000 vaccinations) compared with vaccinations given in the thigh (32.1 per 10,000 vaccinations) (P < .001). In a multivariable analysis adjusted for age, gender, and study site, children vaccinated in the arm had a 78% higher risk of a local reaction (relative risk: 1.78 [95% confidence interval: 1.43-2.21]). Local reactions to the fifth dose of the DTaP vaccine that require medical evaluation are uncommon, but the risk of those reactions is significantly higher when the vaccine is injected in the arm. These findings suggest that the thigh should be considered as an acceptable site of injection for this vaccination.

Prevention of Pertussis Among Adolescents: Recommendations for Use of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis (Tdap) Vaccine

The purpose of this statement is to provide the rationale and recommendations for adolescent use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines. Despite universal immunization of children with multiple doses of pediatric diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine, pertussis remains endemic with a steady increase in the number of reported cases. Two peaks in the incidence of pertussis occur in pediatric patients: infants younger than 6 months of age who are inadequately protected by the current immunization schedule and adolescents 11 through 18 years of age whose vaccine-induced immunity has waned. Significant medical and public health resources are being consumed in postexposure management of adolescent cases, contacts, and outbreaks with little beneficial effect on individuals or the epidemiology of disease. Two Tdap products were licensed in 2005 for use in people 10 through 18 years of age (Boostrix) and 11 through 64 years of age (Adacel). The American Academy of Pediatrics recommends the following: 1. Adolescents 11 to 18 years of age should receive a single dose of Tdap instead of tetanus and diphtheria toxoids (Td) vaccine for booster immunization. The preferred age for Tdap immunization is 11 to 12 years. 2. Adolescents 11 to 18 years of age who have received Td but not Tdap are encouraged to receive a single dose of Tdap. An interval of at least 5 years between Td and Tdap is suggested to reduce the risk of local and systemic reactions; however, intervals of less than 5 years can be used, particularly in settings of increased risk of acquiring pertussis, having complicated disease, or transmitting infection to vulnerable contacts. Data support acceptable safety with an interval as short as approximately 2 years. 3. Tdap and tetravalent meningococcal conjugate vaccine (MCV4 [Menactra]) should be administered during the same visit if both vaccines are indicated. If this is not feasible, MCV4 and Tdap can be administered using either sequence. When not administered simultaneously, the American Academy of Pediatrics suggests a minimum interval of 1 month between vaccines. The rationale for this strategy is to provide direct protection of immunized adolescents. With implementation of vaccine recommendations, indirect benefitalso is likely to extend to unimmunized peers and other age groups. The strategy of universal Tdap immunization at 11 to 12 years of age is cost-effective.

Effect of a national vaccine shortage on vaccine coverage for American Indian/Alaska Native children.

We determined the effect of national vaccine shortages on coverage with 4 doses of diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine for American Indian/Alaska Native (AIAN) children. Data on DTaP coverage for children aged 19 to 27 months were abstracted from Indian Health Service (IHS) immunization reports. Coverage with the fourth DTaP dose (DTaP4) was compared for different periods to determine coverage levels before, during, and after the shortage. Data were stratified geographically to determine regional variation. AIAN children experienced a significant decline (14.8%) in DTaP4 coverage during the shortage. Considerable variation was seen among IHS regions (declines ranged from 4.5% to 26.5%). AIAN children included in IHS immunization reports experienced a greater decline in DTaP4 coverage during the shortage than the decline reported nationally for children receiving vaccine at public clinics (14.8% vs 6%). Variations in the decline in coverage highlight possible inequities in vaccine supply and distribution and in implementation of vaccine shortage recommendations. We must identify ways to ensure more equitable vaccine distribution and consistent implementation of vaccine recommendations to protect all children from vaccine-preventable diseases.

Predictors of age-appropriate receipt of DTaP Dose 4

Background In the United States, the national childhood immunization schedule calls for children to receive four doses of DTaP (diphtheria and tetanus toxoids and acellular pertussis) vaccine administered at 2, 4, 6, and 15 to 18 months. Dose 4 of DTaP is among the most frequently missed vaccines for children who are not adequately immunized. Methods Using the 2001 National Immunization Survey, the effect of the timeliness of the first three DTaP doses was assessed on completion of the four-dose series by age 24 months and on time by age 12 to 18 months. Results Missing Dose 4 was more prevalent among children who received Dose 3 late (but <16 months) than among children who received Dose 3 on time (24% vs 10%). Similarly, receiving Dose 4 late (or not at all) was more prevalent among children who received Dose 3 late (but <9 months) (39% vs 22%). An invalid Dose 4 was administered to 4.6% of those with Dose 3 late but before 9 months and to 10.6% of those with no Dose 3 before 9 months, compared to 1.2% of those with Dose 3 on time. Conclusion Physicians and staff can identify children at risk for missing the fourth DTaP dose or receiving it late by assessing timeliness of receipt of DTaP Dose 3 and implementing steps to ensure that at-risk children receive Dose 4 as recommended.

Assessing efficacy of Haemophilus influenzae type b combination vaccines.

Regulatory approval of diphtheria and tetanus toxoids and acellular pertussis (DTaP)-based combination vaccines containing Haemophilus influenzae type b (Hib) has been delayed in the US because of difficulty in assessing the effect of lower Hib immunogenicity on vaccine efficacy compared with the immunogenicity of the specific Hib component administered separately. Hib conjugate vaccines confer protection by eliciting serum anticapsular antibody and priming for immunologic memory. Therefore, compelling proof of efficacy would be demonstration that a combination vaccine primes for memory and elicits antibody responses that are not inferior to those elicited by other US-licensed Hib conjugate vaccines, not necessarily the specific Hib component used in the combination. Vaccinated infants also can be considered protected if their serum anticapsular antibody concentrations are > or =0.15 microg/mL immediately before the booster dose given in the second year of life, when antibody concentrations are lowest. These alternative serologic approaches offer a strong scientific and regulatory rationale for licensure of effective DTaP-based Hib combination vaccines.