See also separate article Diphtheria.

Introduction

Classical diphtheria is an acute communicable respiratory infection. Vaccination confers protection against disease by production of antibodies to the diphtheria toxin. When treated with formaldehyde and heat, diphtheria toxin loses its ability to bind to cells and its enzymatic activity, but retains its immunogenicity. This treatment converts diphtheria toxin to a toxoid. The vaccine is produced from purified inactivated toxin from a strain of Corynebacterium diphtheriae.

Available vaccines

Diphtheria vaccines are available in 2 strengths according to dose of toxoid:¹

• High-dose - vaccines contain >30 IU of diphtheria toxoid and are used to achieve satisfactory primary immunisation of children - as in DTaP vaccine (capital D = high-dose).²
• Low-dose - vaccines contain only 2 IU of toxoid and are used for primary immunisation of those aged over 10 years and for subsequent boosters (lower case d signifies low-dose as in dTaP).

Monovalent diphtheria vaccine is not available. Vaccination should only given as a component of the following combination products:

• Diphtheria/tetanus/acellular pertussis/inactivated polio/Haemophilus influenzae type b vaccines (DTaP/IPV/ Hib).
• Diphtheria/tetanus/acellular pertussis/inactivated polio vaccines (DTaP/IPV or dTaP/IPV).
• Tetanus/ diphtheria/inactivated polio (Td/IPV).

Administration

• Five doses of a diphtheria-containing vaccine are given intramuscularly.
• Upper arm or anterolateral thigh sites are recommended to minimise risks of local reactions.
• Other vaccinations such as measles, mumps and rubella (MMR), meningitis C or hepatitis B can be given at the same time but should be injected at an alternative site and preferably in a different limb.

Schedule

Primary immunisation

• All infants should receive the primary immunisation course involving 3 doses of diphtheria-containing vaccine.³
• It is recommended that DTaP/IPV/ Hib be given at 2, 3 and 4 months of age as levels of passively acquired maternal antitoxin decline.
• However, if necessary, the same dosing schedule can be used in children up to 10 years of age.
• Older individuals should receive 3 doses of a d-containing preparation (usually Td/IPV) at monthly intervals.

Be aware that recent research has shown that Caucasian infants are less likely to have received the triple vaccine than most ethnic minority groups.⁴

Boosters

• The first booster dose is given to children between the ages of 3½ and 5 years.
• Either DTaP/IPV or dTaP/IPV will elicit an adequate immune response.
• If primary immunisation has been delayed, the first booster dose must be given at least one year after completion of the initial course.⁵
• All individuals aged over 10 years who require a first booster should be given a dose of Td/IPV.

The second booster dose is offered to 13 to 18 year-olds by the school health service:

• The Td/IPV preparation should always be used.
• If previous doses have been delayed, the second booster should be given at least 5 years after the first booster.
• Note that patients may have inadvertently already received a diphtheria booster associated with tetanus toxoid.

Adults with an incomplete primary series may also benefit from a booster dose, if long-term protection is required.⁶ A second booster dose raises immunity to 92%.⁷

Other recipients

Immigrants

Children from developing countries may not be fully immunised against diseases such as diphtheria. If the history is unclear, children are considered unimmunised and should complete the full UK schedule.

Travellers

Travellers to endemic areas should be fully immunised according to the UK schedule before travel.⁸ Travellers to developing countries for over one month's duration, who had their last diphtheria booster dose more than 10 years ago, should be offered a further booster of Td/IPV.

Laboratory and healthcare workers

Individuals who may be exposed to diphtheria at work must be fully immunised and should be offered a booster dose.¹ Further boosters should be given every 10 years if risks persist. Workers who are unimmunised should undergo the complete vaccination schedule with subsequent antibody testing as proof of immunity.

Contacts

Close contacts of a diphtheria case should be offered full immunisation or a booster if their most recent vaccine dose was more than 12 months ago.⁹

Contra-indications

The diphtheria vaccination should not be administered to patients with:²

• Confirmed anaphylactic reaction to diphtheria toxoid-containing vaccine.
• Confirmed anaphylactic reaction to neomycin, streptomycin or polymyxin B.
• Acute illness with systemic upset and fever.
• Evolving or undiagnosed, deteriorating neurological abnormalities.

Situations that do not prohibit diphtheria vaccination

The following situations do not prohibit diphtheria vaccination:

• History of a stable neurological condition, seizures or febrile convulsions (without neurological deterioration).
• Fever, persistent screaming, severe local reactions or hypotonic-hyporesponsive episodes following previous diphtheria vaccinations.
• Immunosuppression including HIV infection (but individuals may not achieve an adequate immunological response)
• Pregnancy or breast-feeding.

Adverse reactions

These should be reported via the Yellow Card Scheme.¹

• Pain, swelling, redness or a transient nodule at the injection site may occur.
• Fever, convulsions, screaming, pallor, cyanosis and hypotonic-hyporesponsive episodes.
• Allergic reactions and very occasional anaphylactic episodes.¹⁰

There is no evidence for any association between the DTaP vaccine and autism.¹¹

Document references

1. Immunisation against infectious disease - 'The Green Book'; Dept of Health (various dates)
2. Summary of Product Characteristics - Revaxis® (Diphtheria, tetanus and poliomyelitis (inactivated) vaccine (adsorbed)); Sanofi Pasteur MSD Limited; Updated May 2008; electronic Medicines Compendium
3. Immunization, surveillance, assessment and monitoring: diphtheria, World Health Organization
4. Baker D, Garrow A, Shiels C; Inequalities in immunisation and breast feeding in an ethnically diverse urban J Epidemiol Community Health. 2010 May 12. [abstract]
5. The Immunological Basis for Immunisation, Module 2: Diphtheria, World Health Organization
6. Hasselhorn HM, Hofmann F, Nubling M; Effect of a diphtheria booster vaccination in adults with a documented history of an incomplete primary series vaccination. Infection. 2004 Oct;32(5):282-6. [abstract]
7. Vellinga A, Van Damme P, Joosens E, et al; Second diphtheria booster in adults raises immunity to 92%. BMJ. 2001 Dec 1;323(7324):1308.
8. 'Yellow Book': Health information for overseas travel, Dept of Health, 2001
9. Bonnet JM & Begg NT. Control of diphtheria: guidance for consultants in communicable disease control. Commun Dis Public Health, 1999; 2: 242-9
10. Bohlke K, Davis RL, Marcy SM, et al; Risk of anaphylaxis after vaccination of children and adolescents. Pediatrics. 2003 Oct;112(4):815-20. [abstract]
11. Andrews N, Miller E, Grant A, et al; Thimerosal exposure in infants and developmental disorders: a retrospective cohort study in the United kingdom does not support a causal association.; Pediatrics. 2004 Sep;114(3):584-91. [abstract]

Internet and further reading

• Immunization, surveillance, assessment and monitoring: diphtheria, World Health Organization
• Diphtheria Information; Dept of Health
• Dimirci CS; Diphtheria, eMedicine, July 2008

Acknowledgements