Reactogenicity and safety of DTPa vaccine and Haemophilus influenzae type b conjugate vaccine (Hib) in a single injection vs DTPw and Hib as separate injections as a booster vaccination in 18-month-old children

Objective: To compare the reactogenicity and safety of the administration of diphtheria-tetanus-acellular pertussis (DTPa) and Haemophilus influenzae type b conjugate (Hib) vaccines in one injection with those of the simultaneous administration of diphtheria-tetanus-whole cell pertussis (DTPw) and Hib vaccines in opposite limbs as booster doses to 18-month-old children previously primed with three doses of DTPw and Hib vaccines as a primary vaccination course. Design and Setting: Nonblind, prospective, randomised, multicentre comparative study set in Spain. Patients and Participants: 216 children (17.2 ± 0.99 months old). Methods: Children were randomised to receive DTPa/Hib (group 1; n = 111) or DTPw + Hib (group 2; n = 105) and were followed for up to 30 days post-vaccination. All children received oral polio vaccine concomitantly. Local and general symptoms were recorded by parents on diary cards. Results: The incidences of any solicited local reaction and any solicited general symptom 'probably related' or 'suspected to be related' to vaccination were statistically significantly higher (p < 0.0001) in group 2 than in group 1. Pain at the injection site was the most commonly reported local reaction, both in terms of any pain (40% in group 1; 89% at the DTPw site in group 2; p < 0.0001) and in pain that caused the child to cry when the limb was moved (1% and 42%; p < 0.0001). Any redness or swelling were significantly more common (p < 0.0001) at the DTPw injection site (71% and 60%, respectively) than at the DTPa/Hib site (34% and 27%). Fever (rectal temperature ≥38°C) was recorded for 10% and 56% of participants in groups 1 and 2, respectively (p < 0.0001). Only one case in group 1 and three cases in group 2 had fever >39.5°C. Fussiness (group 1: 28%; group 2: 71%), loss of appetite (15% and 37%, respectively), and restlessness (16% and 34%, respectively) were also statistically significantly more frequent (at least p < 0.003) in DTPw + Hib recipients. Analgesics/antipyretics were prescribed as prophylactic treatment in only <8% of cases; however, antipyretics were significantly more often prescribed (p < 0.0001) after vaccination in group 2 children (46%) than in group 1 children (6%). Unsolicited symptoms were recorded for 33 participants, including 22 cases [group 1: one case; group 2 (DTPw limb): 21 cases] of lameness that resolved within 1 to 5 days (median 1 day). Conclusions: Administration of DTPa/Hib in one injection leads to better reactogenicity and safety profiles than the administration of DTPw + Hib as two injections as booster doses to 18-month-old children primed with DTPw and Hib vaccines.