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Diphtheria Tetanus Pertussis (DTaP) Vaccine

Editor: Khalid Alsayouri Updated: 10/7/2022 8:15:19 PM

Indications

The DTaP vaccine series is recommended to help protect against diphtheria, tetanus, and pertussis in infants and young children. Individuals susceptible to these vaccine-preventable diseases can develop life-threatening complications and even death. Since the development of universal vaccines in the 1940s, the number of reported cases of diphtheria, tetanus, and pertussis has declined in the United States. 

Tetanus is an infectious disease caused by neurotoxins produced by the gram-positive bacillus, Clostridium tetani. The heat-resistant spores of the bacteria enter the body at mucous membranes or a breach in the skin. Toxins are formed, including a highly potent toxin called tetanospasmin. This toxin interferes with the release of neurotransmitters in the central nervous system leading to unopposed muscle contraction and spasms. There is no person-to-person transmission of C. tetani.[1][2]

Moreover, diphtheria results from infection with toxin-producing strains of Corynebacterium diphtheriae, a gram-positive bacillus. The disease is transmissible from person to person by droplets or close contact. The bacteria can multiply and produce the diphtheria toxin in the nasopharynx region, mucous membranes, or skin lesions. Early symptoms can include malaise, sore throat, and low-grade fever. A classic feature of respiratory diphtheria is a gray-colored pseudo-membrane that firmly adheres to the mucosal lining of the nasopharynx, tonsils, or larynx. This pseudo-membrane can extend further into the nasal cavity or larynx, obstructing the airways. Cardiac and neurological complications can occur once the toxin reaches the bloodstream. Respiratory droplets or close contact can transmit diphtheria.[1][3]

Pertussis is a respiratory disease, also known colloquially as whooping cough, caused by the gram-negative bacillus, Bordetella pertussis. The disease characteristically has three stages: catarrhal, paroxysmal, and convalescent. The catarrhal stage includes symptoms of coryza, mild cough, and low-grade fever. Around one to two weeks, the infected person enters the paroxysmal stage with symptoms of spasmodic coughing, posttussive vomiting, and inspiratory whoop. Symptoms slowly improve in the convalescent stage but can last for weeks to months. B. pertussis is transmittable through aerosolized droplets generated by coughing or sneezing. People are most infectious at the catarrhal stage or the beginning of the paroxysmal stage.[1][4]

Mechanism of Action

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Mechanism of Action

The DTaP vaccine is a combination vaccine against diphtheria, tetanus, and pertussis. It consists of diphtheria and tetanus toxoids (inactivated toxins) and acellular pertussis antigens. The tetanus component of the vaccine is about 5 to 10 levels of flocculation (Lf) units of manufactured tetanus toxoid. The diphtheria component is a manufactured diphtheria toxoid of about 15 to 25 Lf units. The acellular pertussis component of a DTaP vaccine consists of manufactured pertussis antigens called pertussis toxin, filamentous haemagglutinin, pertactin, and fimbriae type 2 and 3.[1]

The vaccine produces an active immune response of the body by developing antibodies and antitoxins against the toxoids and acellular pertussis antigens. There are two single DTaP vaccines available in the United States and approved by the FDA.

Administration

The CDC’s Advisory Committee on Immunization Practices (ACIP) recommends administering the DTaP five-dose vaccine series for children six weeks continuing through to six years of age.[5] Routine dose recommendations are for the following ages:

  • Two months: minimum age of six weeks
  • Four months: the second dose should be given at least four weeks after the first
  • Six months: the third dose should be given at least four weeks after the second
  • Fifteen through eighteen months: the minimum age for the fourth dose is 12 months, and should be given at a minimum of six months after the third dose. It may be counted as valid if given at least four months after the third dose, and the child was at least 12 months old.
  • Four through six years: the minimum age for the fifth dose is four years old. The dose should be given at least six months after the fourth dose.  

The DTaP dose is 0.5 mL and given intramuscularly. The preferred intramuscular injection site for infants to two years of age is the anterolateral aspect of the thigh. For children three years of age and older, the preferred site is the deltoid muscle.[1] DTaP vaccines can also be available in combination with other childhood vaccines.

Children unimmunized or incompletely immunized should receive catch-up immunizations. This process is possible with minimal intervals between doses. 

  • Dose 1 to dose 2 - four weeks
  • Dose 2 to dose 3 - four weeks
  • Dose 3 to dose 4 - six months; the minimum age for dose 4 is 12 months.
  • Dose 4 to dose 5 - six months

DTaP is approved during the last 3 months of pregnancy to prevent pertussis in infants under 2 months old.

Adverse Effects

Whole-cell pertussis vaccines, known as DTP vaccines, were commonly associated with local adverse events, including swelling, redness, and pain at the injection site. DTaP vaccines replaced DTP vaccines in the 1990s to reduce the number of these common adverse events. Less common adverse events for pertussis vaccines are seizures, hypotonic-hyporesponsive episodes, and prolonged crying.[1][4]

Vaccines with tetanus toxoids can cause brachial neuritis based on case reports and studies reviewed by the World Health Organization and ACIP. The cases can be severe but are rare, and brachial neuritis is usually self-limited.[1][2]

ACIP has reviewed several studies regarding the simultaneous administration of DTaP with other vaccines. There may be an increased risk of febrile seizures within 24 hours when administering the inactivated influenza vaccine along with the pneumococcal 13-valent conjugate vaccine or the DTaP vaccine. The overall risk for febrile seizures is small with any combination of vaccines. Therefore, the ACIP recommends a simultaneous administration of these vaccines.[1]

Contraindications

Severe allergic reactions or anaphylaxis after administration of the DTaP vaccine or vaccine component is considered a contraindication. Encephalopathy (coma, a decreased level of consciousness, or prolonged seizures) that occurs within seven days of DTaP administration and with no identifiable cause is also a contraindication. Pregnancy should not be considered a contraindication to DTaP vaccination.[6][7][8]

Monitoring

ACIP reviewed studies that showed children developed a significant antibody response and antitoxin levels of the diseases after three to four doses of either Infanrix or Daptacel. The Vaccine Adverse Event Reporting System (VAERS) and Vaccine Safety Datalink (VSD) surveyed any adverse events with the acellular pertussis vaccine in the United States. Overall, the studies support the safety of DTaP.[1]

Clinicians should defer any vaccines with pertussis components in infants or children with suspected or evolving neurological disease, including seizures. Vaccination with pertussis components can begin or resume upon establishing a treatment regimen or the condition has stabilized.[1]

An Arthus reaction (type III hypersensitivity reaction) can occur after administering vaccines with diphtheria toxoids or tetanus toxoids.[9] Symptoms of the reaction include severe pain, swelling, induration, edema, hemorrhage, and occasionally necrosis. The reaction is rare after vaccine administration and resolves over time. An Arthus reaction is not a contraindication to the DTaP vaccine, but any vaccines with tetanus toxoids should be administered every ten years.[1]

Toxicity

There is no known antidote or treatment for the DTaP vaccine. Anaphylaxis can occur but is extremely rare. The reaction is treatable with an intramuscular injection of epinephrine.[10]

Enhancing Healthcare Team Outcomes

Vaccine coverage is considered high among infants, children, and adolescents, but clinical data shows that adults have reduced immunity. Vaccine coverage declines with increasing age, resulting from waning immunity or non-vaccination. Vaccines with acellular pertussis do not protect for as long as the prior whole-cell pertussis vaccines. In 2005, the ACIP recommended that adolescents and adults over ten years of age receive a single dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (TdaP) vaccine. After receiving Tdap, the recommendation for adolescents and adults is to receive a booster dose of tetanus and diphtheria toxoids (Td) vaccine every ten years or when indicated for wound management. [Level 1]

In 2012, to reduce the burden of pertussis in infants, ACIP recommended a dose of Tdap for women during each pregnancy. Clinical studies indicated that newborn infants of mothers vaccinated during pregnancy had higher concentrations of pertussis antibodies at birth compared to newborns of unvaccinated mothers during pregnancy. [Level 1]

In various healthcare settings, exposure to pertussis can occur to healthcare providers, patients, or hospital visitors. The management of exposure or pertussis outbreak can be complicated and costly depending on the approach. [Level 3] Postexposure prophylaxis (PEP) is recommended for healthcare personnel in contact with persons at risk for pertussis. This prophylaxis includes antibiotic treatment with a macrolide such as azithromycin and immediate evaluation of persons with an illness that presents with a cough.

Vaccination programs, in general, require the efforts of an interprofessional team approach. The treating physician (MD, DO, NP, or PA) will order these, and they are often administered by nursing staff. Pharmacists will assist in dose preparation and must know the vaccination schedules or have access to them; many states permit pharmacists to administer vaccines subject to age limitations. This scope of practice for pharmacists continues to expand, depending on the state.[11] To be sure, all members of the healthcare team should familiarize themselves thoroughly with the various vaccination schedules. Nursing will also be in the best position to monitor for adverse events or allergic reactions, which, while rare, can occur. These events should be reported to the physician immediately. Only through this type of collaborative interprofessional care can tetanus/diphtheria/pertussis vaccines be administered most effectively for optimal results. [Level 5]

References


[1]

Liang JL, Tiwari T, Moro P, Messonnier NE, Reingold A, Sawyer M, Clark TA. Prevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports. 2018 Apr 27:67(2):1-44. doi: 10.15585/mmwr.rr6702a1. Epub 2018 Apr 27     [PubMed PMID: 29702631]


[2]

. Tetanus vaccines: WHO position paper – February 2017. Releve epidemiologique hebdomadaire. 2017 Feb 10:92(6):53-76     [PubMed PMID: 28185446]


[3]

. Diphtheria vaccine: WHO position paper – August 2017. Releve epidemiologique hebdomadaire. 2017 Aug 4:92(31):417-35     [PubMed PMID: 28776357]


[4]

. Pertussis vaccines: WHO position paper - September 2015. Releve epidemiologique hebdomadaire. 2015 Aug 28:90(35):433-58     [PubMed PMID: 26320265]


[5]

Robinson CL, Bernstein H, Romero JR, Szilagyi P. Advisory Committee on Immunization Practices Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger - United States, 2019. MMWR. Morbidity and mortality weekly report. 2019 Feb 8:68(5):112-114. doi: 10.15585/mmwr.mm6805a4. Epub 2019 Feb 8     [PubMed PMID: 30730870]


[6]

Sur DKC, Chande ND. Immunizations in Pregnancy: Updated Recommendations. American family physician. 2020 Aug 15:102(4):205-206     [PubMed PMID: 32803926]


[7]

Cappozzo F, Dal Zotto A, Scollo M, Bernardini D, Maria Dal Zotto A, Bonvecchio L, Tognetto G, Marinangeli S, Negrello C, Lanza P, Cocco A, Falivene P, Vianello L, Di Caprio A, Gabutti G, Saugo M. dTap vaccination uptake during pregnancy: Pregnant women-focused and health professionals-focused predictors in the Veneto Region (Italy). Vaccine. 2021 Nov 16:39(47):6913-6919. doi: 10.1016/j.vaccine.2021.10.012. Epub 2021 Oct 25     [PubMed PMID: 34711438]


[8]

Layton JB, Butler AM, Li D, Boggess KA, Weber DJ, McGrath LJ, Becker-Dreps S. Prenatal Tdap immunization and risk of maternal and newborn adverse events. Vaccine. 2017 Jul 24:35(33):4072-4078. doi: 10.1016/j.vaccine.2017.06.071. Epub 2017 Jun 29     [PubMed PMID: 28669620]


[9]

Wang MH, Hu A, Lee YS, Lai CC. Arthus Reaction. The Journal of emergency medicine. 2019 Apr:56(4):450-451. doi: 10.1016/j.jemermed.2018.12.047. Epub 2019 Feb 27     [PubMed PMID: 30826085]


[10]

Moro PL, Perez-Vilar S, Lewis P, Bryant-Genevier M, Kamiya H, Cano M. Safety Surveillance of Diphtheria and Tetanus Toxoids and Acellular Pertussis (DTaP) Vaccines. Pediatrics. 2018 Jul:142(1):. doi: 10.1542/peds.2017-4171. Epub 2018 Jun 4     [PubMed PMID: 29866795]


[11]

Echtenkamp CA, Lampkin SJ, Hassan AK. Pharmacists' Attitudes and Practices Regarding Tetanus, Diphtheria and Pertussis (Tdap) Vaccination in Pregnancy and Surrounding Newborns. Pharmacy (Basel, Switzerland). 2018 Apr 25:6(2):. doi: 10.3390/pharmacy6020036. Epub 2018 Apr 25     [PubMed PMID: 29693570]