Introduction
Diphtheria vaccines are biological preparations that provide active immunization against Corynebacterium diphtheriae, the bacterium responsible for diphtheria. These vaccines contain diphtheria toxoid, a formaldehyde-inactivated toxin that retains immunogenic properties while being non-toxic. Diphtheria vaccines are typically administered in combination with other vaccines, most commonly tetanus and pertussis vaccines (DTaP, Tdap, Td), and are fundamental components of childhood immunization programs worldwide.
Mechanism of Action
Diphtheria vaccines work by stimulating the immune system to produce antibodies against diphtheria toxin. The formaldehyde-inactivated toxoid retains the antigenic epitopes of the native toxin but lacks toxic activity. Upon administration, antigen-presenting cells process the toxoid and present it to T lymphocytes, which subsequently activate B lymphocytes to produce specific anti-diphtheria antibodies (primarily IgG). These antibodies provide protection by neutralizing the pathogenic exotoxin produced by C. diphtheriae, preventing its binding to cell receptors and subsequent cellular damage.
Indications
- Primary immunization against diphtheria in children and adults
- Booster vaccinations to maintain immunity
- Post-exposure prophylaxis in unvaccinated or incompletely vaccinated individuals
- Included in routine childhood immunization schedules (as DTaP or DT)
- Adolescent and adult booster vaccinations (as Tdap or Td)
- Special populations: travelers to endemic areas, laboratory workers, military personnel
Dosage and Administration
Primary immunization series in children:- 2, 4, and 6 months (DTaP)
- Booster at 15-18 months and 4-6 years
- Single dose of Tdap followed by Td boosters every 10 years
- Route: Intramuscular injection
- Site: anterolateral thigh (infants) or deltoid muscle (older children and adults)
- Dosage: 0.5 mL per injection
- Pregnancy: Tdap recommended during each pregnancy (27-36 weeks gestation)
- Immunocompromised patients: generally recommended but may have reduced immunogenicity
- Catch-up vaccination: follow CDC ACIP recommended schedules
Pharmacokinetics
As a vaccine, pharmacokinetic parameters are not typically measured in the conventional sense. The immune response develops over weeks following administration:
- Onset of immune response: antibody production begins within days
- Peak antibody levels: reached approximately 4 weeks post-vaccination
- Duration of immunity: protective antibody levels typically persist for approximately 10 years
- No classical absorption, distribution, metabolism, or elimination profile
Contraindications
- Severe allergic reaction (e.g., anaphylaxis) to a previous dose of diphtheria vaccine
- Known severe allergy to any component of the vaccine
- Encephalopathy within 7 days of previous pertussis-containing vaccine (for combination vaccines)
- Guillain-Barré syndrome within 6 weeks of previous tetanus toxoid-containing vaccine
Warnings and Precautions
- Moderate or severe acute illness with or without fever: defer vaccination
- History of Arthus-type hypersensitivity reactions after previous dose: defer vaccination for at least 10 years
- Latex sensitivity: some packaging components may contain natural rubber latex
- Syncope may occur following vaccination
- Apnea in preterm infants: monitor respiratory status for 48-72 hours
- Thrombocytopenia or neurologic disorders: evaluate risks and benefits
Drug Interactions
- Immunosuppressive therapies (chemotherapy, radiation, high-dose corticosteroids) may diminish immune response
- Administration with other vaccines: generally can be given simultaneously at different sites
- Immune globulin administration: may interfere with vaccine immune response if given concurrently
- Anticoagulant therapy: increased risk of bleeding at injection site
Adverse Effects
Common (≥10%):- Local reactions: pain, redness, swelling at injection site
- Systemic: fever, drowsiness, irritability
- Mild systemic symptoms: headache, fatigue, myalgia
- Extensive limb swelling
- Fever >39°C
- Anorexia, vomiting
- High fever (>40.5°C)
- Hypotonic-hyporesponsive episode
- Seizures
- Anaphylaxis
- Brachial neuritis
Monitoring Parameters
- Local reaction at injection site for 48-72 hours post-vaccination
- Temperature for 24-48 hours post-vaccination
- Serologic testing for antibody titers in certain high-risk populations
- Vaccine adverse event reporting
- Documentation of vaccination dates and lot numbers
Patient Education
- Explain expected local reactions and management (cool compress, analgesics)
- Discuss potential systemic symptoms and when to seek medical attention
- Emphasize importance of completing the vaccination series
- Provide information on booster dose requirements
- Discuss rare but serious adverse reactions and when to seek immediate care
- Provide Vaccine Information Statement (VIS) and answer questions
- Encourage reporting of any adverse events to Vaccine Adverse Event Reporting System (VAERS)
References
1. Centers for Disease Control and Prevention. (2021). Diphtheria, Tetanus, and Pertussis Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recommendations and Reports, 70(2), 1-30.
2. World Health Organization. (2017). Diphtheria vaccine: WHO position paper. Weekly Epidemiological Record, 92(31), 417-436.
3. American Academy of Pediatrics. (2021). Diphtheria. In: Red Book: 2021 Report of the Committee on Infectious Diseases, 32nd edition.
4. Plotkin SA, Orenstein WA, Offit PA. (2018). Vaccines, 7th edition. Elsevier Saunders.
5. Hamborsky J, Kroger A, Wolfe S. (2015). Epidemiology and Prevention of Vaccine-Preventable Diseases. Public Health Foundation.
6. FDA prescribing information for various diphtheria-containing vaccines.
7. Immunization Action Coalition. (2022). Diphtheria: Questions and Answers.
Note: This monograph provides general information. Always consult current CDC ACIP guidelines and FDA-approved prescribing information for specific recommendations.