Diphtheria vaccine

Combined diphtheria + tetanus immunization

In a prospective cohort study in Italy, 380 children aged 6 years were randomly assigned to receive either the DT or the Td vaccine as a booster dose in order to determine whether a booster dose of Td (diphtheria–tetanus vaccine with a reduced amount of diphtheria toxoid, adult formulation) would produce comparable diphtheria antibody titers but lower reactogenicity than DT (childhood formulation). The frequencies of symptoms within 3 days of vaccine administration were similar in the two groups, except for local redness and swelling, which were significantly more common in the children who received DT vaccine: redness 31% versus 16%, and swelling 36% versus 26%. The mean duration of local symptoms was 3.3 days in the diphtheria–tetanus group and 2.6 days in the Td group. After booster immunization, 97% of children in the DT group and 91% of those in the Td group had antibody concentrations of at least 1 IU/ml (“long-term” protection titer) [ ].

There have been comparisons of the immunogenicity and reactogenicity of different diphtheria vaccines. They have involved single or combined administration of diphtheria and/or tetanus toxoids [ , ], booster immunization using Td vaccines including either aluminium hydroxide or calcium phosphate as adjuvant [ ], or either plain or adsorbed formulations [ ].

Adverse events after diphtheria–tetanus vaccine in the USA in 1982–84 have been reviewed in detail [ ]. The usual types of local intolerance can be seen. For example, some 5% of schoolchildren develop redness and swelling, whilst some older children develop enlargement of the regional lymph nodes. Such reactions are much less common in young children, and much more common in children given combined vaccines.

General reactions (seen in some older children and adults) are usually limited to brief fever; sustained fever and other systemic reactions are uncommon unless the person has been hyperimmunized. After the administration of DT vaccine, local reactions, generally erythema and induration, with or without tenderness, can occur. In hyperimmunized cases, Arthus-type hypersensitivity reactions can occur. These characteristically severe local reactions generally start 2–8 hours after an injection. People who have such reactions usually have very high serum antitoxin concentrations and one should be careful not to administer a booster more than once every 10 years.

The occurrence of epidemic diphtheria in Eastern Europe led to the recommendation in the UK that those aged 15–18 years should receive a combined tetanus and low-dose diphtheria toxoid vaccine instead of a tetanus booster alone. In March 1995, 220 children aged 14–16 years were inadvertently given high-dose diphtheria and tetanus toxoid vaccine, and their parents were sent a questionnaire; 153 replied. A total of 141 (92%) of adolescents reported one or more reactions, most of which were classified as mild or moderate and lasted less than 1 week. However, 47 (31%) reported at least one severe local or systemic reaction [ ].

In a study of adverse events after immunization in New Zealand in 1990–95 [ ], reactions at the injection site after adult tetanus–diphtheria vaccine (68 reports per 100 000 immunizations) were reported five times more often than with tetanus vaccine.

Combined diphtheria + tetanus + pertussis immunization

An overview of clinical trials with a special diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine has been published [ ]. The vaccine contains as pertussis components purified filamentous hemagglutinin, pertactin, and genetically engineered pertussis toxin. The vaccine induces high and long-lasting immunity and is at least as efficacious as most whole-cell pertussis vaccines and similar in efficacy to the most efficacious DTaP vaccines that contain three pertussis antigens. The vaccine is better tolerated than whole-cell vaccines and has a similar reactogenicity profile to other acellular vaccines.

A vaccine containing diphtheria and tetanus toxoids and DTaP with reduced antigen content for diphtheria and pertussis (TdaP) has been compared with a licensed reduced adult-type diphtheria–tetanus vaccine and with an experimental candidate monovalent DTaP vaccine with reduced antigen content [ ]. A total of 299 healthy adults (mean age 30 years) were randomized into three groups to receive one dose of the study vaccines. The antibody responses (antidiphtheria, antitetanus, antipertussis toxin, antipertactin, antifilamentous hemagglutinin) were similar in all groups. The most frequently reported local symptom was pain at the injection site (62–94%), but there were no reports of severe pain; redness and swelling with a diameter of 5 cm or more occurred in up to 13%. The incidence of local symptoms was similar after TdaP and Td immunization. The most frequently reported general symptoms were headache and fatigue (20–50%). The incidence of general symptoms was similar in the TdaP and Td groups. There were no reports of fever over 39 °C. No serious adverse events were reported.

Data from the Third National Health and Nutrition Survey (1988–94) have been used to analyse the possible effects of DTP or tetanus immunization on allergies and allergy-related symptoms among 13 944 infants, children, and adolescents aged 2 months to 16 years in the USA [ ]. The authors concluded that DTP or tetanus immunization increases the risk of allergies and related respiratory symptoms in children and adolescents. However, the small number of non-immunized individuals and the study design limited their ability to make firm causal inferences about the true magnitude of effect.