REACTOGENICITY AND IMMUNOGENICITY OF BOOSTER AGAINST DIPHTHERIA AND TETANUS

M. Ciofi degli Atti, B. Cotter, S. Salmaso, G. Alfarone, G. Gallo, C. von Hunolstein

Istituto Superiore di Sanita', Laboratory of Epidemiology and Biostatistics, Italy., European Program for Intervention Epidemioloy Training., Istituto Superiore di Sanità, Laboratory of Bacteriology and Medical Micology, Italy., Assessorato alla Sanita Regione Veneto, Italy

Introduction: An important issue in immunising older children and adults against diphtheria and tetanus is the reactogenicity of the diphtheria toxoid, which may be overcome with low-dose vaccine preparations. We evaluated whether substituting the paediatric dose (DT, 25 Lf diphtheria/dose) with the adult dose (dT, 2 Lf diphtheria/dose) for a booster administered to pre-school children reduces reactogenicity without loss of immunogenicity.

Methods: The study population consisted of 6-year-olds vaccinated with 3 doses of DT in the first year of life. Children were randomly assigned to the DT or dT group; the study was double-blinded. Side reactions were actively surveyed in the 3 days following vaccination. A sub-population underwent immunogenicity testing: capillary samples were taken before vaccination and 30 days afterwards to measure diphtheria antibody titres.  Geometric mean titres (GMT) and percentage of children with titres => 1 IU/ml (long-term protection) were calculated.

Results: The study included 754 children (372 DT, 382 dT); 143 underwent immunogenicity testing (76 DT, 67 dT). The two vaccine groups were balanced in terms of age, gender and site of injection. Frequency of side reactions was similar, except for local redness (31% DT, 16% dT, p< 0.001) and swelling (35% DT, 24% dT, p<0.001). Of the children undergoing immunogenicity testing, 95% in the dT group and 97% in the DT group had antibody titres => 1 IU/ml.  The GMTs were 7.7 (dT) and 14.1 (DT) (p<0.001).

Conclusions: The use of the DT vaccine is associated with a greater frequency of local side effects, though these are clinically minor. Nonetheless, since the DT vaccine induced higher GMTs, it should be used for the booster dose at 6 years of age, particularly if further boosters will not be administered.