Subcutaneous versus intramuscular injection for booster DT vaccination of adolescents

Abstract

The importance of the injection technique in booster vaccination was investigated in an open randomized study with 252 10-year-old Swedish school-children receiving routine DT vaccination either by subcutaneous or by intramuscular route in the upper arm. The adolescents had previously been primed with DT vaccine at 3, 5 and 12 months of age. Adverse reactions, monitored for 2 weeks, showed the same low rates for systemic reactions in both groups, while the intramuscular administration gave significantly less redness (p<0.001), swelling (p<0.001), itching (p<0.01) and pain (p<0.05). These reactions were also of shorter duration (p<0.01 to p<0.001). Girls were found to have more pain and itching than boys (p<0.001). No significant differences in antibody responses between the two administration routes were found in the 99 samples drawn 2 weeks after the booster. However, girls were found to have a lower response to diphtheria toxoid than boys (p=0.009). Local reactions to a booster can thus be significantly reduced by choice of injection technique, which may be necessary if increased dosages and/or further valences are to be given to adolescents and adults.

Introduction

Booster doses of diphtheria and tetanus toxoid vaccines to adolescents and adults is recommended in most countries1, 2. The need for booster vaccination(s) against pertussis, made possible by the development of acellular pertussis vaccines, is also being discussed[2]. In addition, the antigen content of the booster dose given to adolescents and adults might have to be increased, e.g. the diphtheria toxoid content was raised in Sweden after a diphtheria outbreak in the mid 1980s3, 4, 5, 6. Although a need for some of these changes in immunization policies might be recognized by the scientific society, a limiting factor to public acceptance could be the rate of local side effects. As a disease becomes rare, thanks to a vaccination program, public attention easily shifts to the adverse reactions associated with the vaccination. Thus, adverse effects which can lead to a loss of confidence are important to avoid, especially at times of strong anti-vaccination movements.

We have previously reported a higher rate of local reactions to a booster dose of an adsorbed DT vaccine in 10-year-old Swedish school-children who had received the same vaccine for priming, in contrast to children who had received a fluid DTPw vaccine as infants[7]. An attempt to decrease the rate of local reactions by administration of a non-adsorbed DT vaccine as booster was not successful with regards to reactogenicity although the immunogenicity was equal or higher than to the regular, adsorbed DT vaccine[8]. Another possibility to achieve our goal to decrease local side effects to booster vaccination was indicated by recent studies comparing injection techniques, subcutaneous versus intramuscular, for the priming doses to infants where the i.m. injection route was found to induce less local reactions9, 10, 11.

Recommendations as to the injection technique to be used for vaccines vary between countries. Many European countries and Japan[10]recommend subcutaneous administration, while WHO[12]and the American Academy of Pediatrics[13]recommend intramuscular injections. The choice of injection technique seems to be governed more by tradition than facts since an extensive search of the literature revealed little published data concerning the merits of either technique for booster vaccinations. We therefore undertook to compare the two administrative routes, i.m. versus s.c. in 10-year-old adolescents who received a DT booster vaccination within the frame of the national immunization program and who had been primed in infancy with three doses of DT vaccine.