Rose-Marie Carlsson

Subcutaneous versus intramuscular injection for booster DT vaccination of adolescents

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.

Safety and immunogenicity of a combined diphtheria-tetanus-acellular pertussis-inactivated polio vaccine-Haemophilus influenzae type b vaccine administered at 2-4-6-13 or 3-5-12 months of age.

METHODS In an open randomized study we compared the safety and immunogenicity of two schedules for priming and booster vaccinations of infants. A pentavalent combination vaccine, including a lyophilized Haemophilus influenzae type b-tetanus toxoid conjugate vaccine reconstituted with a liquid diphtheria, tetanus, acellular pertussis (pertussis toxoid and filamentous hemagglutinin) and inactivated polio vaccine (DTaP-IPV/Act-HIB; Pasteur Mérieux Connaught, Lyon, France) was administered to 236 Swedish infants either at 2, 4 and 6 months or at 3 and 5 months, and a booster dose was administered 7 months after the last primary dose. Adverse events were monitored by diaries for 3 days after each vaccination and by questions at the ensuing visits. Antibodies against the different vaccine components were analyzed after the primary series of vaccinations, before and after the booster injections. RESULTS There were no serious adverse reactions, and the rates of febrile events and local reactions were low in both groups. The three dose primary schedule induced higher geometricmean concentrations for all antigens than did the two dose schedule, but there were no differences between the groups in proportions with protective antibody titers against diphtheria, tetanus, Hib and polio or in proportions with certain defined levels of pertussis antibodies. Prebooster results showed a similar pattern, with the exception that the group primed with three injections showed higher proportions of infants with detectable antibodies against polio-virus types 1 and 3. After booster vaccinations there were no differences between the two schedules in geometric mean or in proportions with antibodies above defined antibody concentrations, indicating effective priming from both primary series of vaccinations. Conclusion. The combined vaccine DTaP-IPV/ Act-HIB vaccine was equally safe and immunogenic when administered according to both time schedules studied.

Control of pertussis--lessons learnt from a 10-year surveillance programme in Sweden.

Sweden was the only country in the world without any general pertussis vaccination when acellular pertussis (aP) vaccines were introduced. Since 1996 aP vaccines are given at the ages of 3, 5 and 12 months, with a 99% coverage, and until 2007 without a later booster. The long-term effects of aP vaccines, monitored within an enhanced surveillance project, were discussed at an international workshop in Stockholm in November 2008. The unique Swedish experience demonstrates that aP vaccines are capable of achieving the primary goal of a national vaccination programme, i.e., to significantly reduce the burden of pertussis in pre-school children. Throughout the 10-year surveillance period the highest age-specific incidence was reported in unvaccinated infants or those who had received only one dose, with most hospitalisations in this age group and eight deaths among unvaccinated infants. Complementary strategies are needed to achieve further reduction in morbidity from circulation of Bordetella pertussis.

Antibody persistence in five-year-old children who received a pentavalent combination vaccine in infancy

Background. Antibody persistence was studied in 5.5-year-old Swedish children who in infancy completed a vaccine trial of a combined diphtheria toxoid, tetanus toxoid, acellular pertussis, inactivated polio and Haemophilus influenzae type b conjugate vaccine. Three priming doses at ages 2-4-6 months induced higher geometric mean concentrations of antibodies for all antigens than did two doses at 3-5 months, but there were no differences in proportions with protective antibody concentrations. After the booster dose administered at 13 or 12 months of age, respectively, there were no differences in concentrations or proportions between the groups. Methods. In the present follow-up serum samples from 180 of the 228 vaccinees, 88 from the 4-dose and 92 from the 3-dose group, were 4.5 years later again tested for antibodies. Results. The two groups did not differ significantly in antibody concentrations or proportions with antibodies above protective or other defined levels, with the exception of poliovirus type 3 (P ≤ 0.01). In all 89% had ≥0.01 IU/ml antibodies against diphtheria by enzyme-linked immunosorbent assay and 76% by the Vero cell neutralization test, 93% had ≥0.01 IU/ml antibodies against tetanus, 96 to 99% had detectable antibodies against the polioviruses and 97% had ≥0.15 &mgr;g/ml H. influenzae type b antibodies. As for pertussis only 44% had detectable antibodies against pertussis toxoid by enzyme-linked immunosorbent assay but 99% by Chinese hamster ovary cell neutralization test, and 94% had detectable antibodies against filamentous hemagglutinin. Conclusion. We found the persistence of antibodies satisfactory, with no clinically relevant differences in antibody concentrations demonstrated between children vaccinated according to a three dose or a four dose schedule in infancy.

Studies on a Hib-tetanus toxoid conjugate vaccine: effects of co-administered tetanus toxoid vaccine, of administration route and of combined administration with an inactivated polio vaccine.

A freeze-dried tetanus toxoid (T) conjugated Haemophilus influenzae type b (Hib) vaccine, was reconstituted in either diphtheria toxoid (D), DT or a combined DT and inactivated polio vaccine (IPV), and administered in an open randomized trial either intramuscularly (i.m. ) or subcutaneously (s.c.) to 287 Swedish infants at three, five and 12 months of age. When not included in the mixture, IPV was administered s.c. at a separate site. The geometric mean concentrations of Hib antibodies after primary and booster vaccinations were 1.0 and 11.6 microg/ml, respectively, with no differences related to co-administration of the carrier protein T. Antibodies against T were induced by the T conjugated Hib vaccine (Hib-T) alone in 69/95 infants aged six months, and in 87/93 children aged 13 months, although infants receiving both Hib-T and T had significantly higher concentrations. Antibody responses to Hib, D, T or polio were not negatively influenced by administration route or by mixing with IPV, except that the mixed vaccine DT-IPV induced lower anti-polio GM titers after primary vaccination than did separate IPV. More local reactions were induced by the s.c. than by the i.m. route (P-values from 0.001 to 0.01). Slight increases in rates of local reactions and febrile events (>/=38 degrees C) occurred by order of dose. The low Hib antibody concentrations after the first two doses in this and other Swedish studies are unlikely to be of clinical relevance. The tetanus antibody response from T as a carrier protein alone was not sufficient for basic tetanus immunization, but should be considered in future use of additional T conjugated vaccines.

Surveillance of infant pertussis in Sweden 1998-2012; severity of disease in relation to the national vaccination programme.

In Sweden, pertussis was excluded from the national vaccination programme in 1979 until acellular vaccination was introduced in a highly endemic setting in 1996. The general incidence dropped 10-fold within a decade, less in infants. Infant pertussis reached 40-45 cases per 100,000 in 2008 to 2012; few of these cases were older than five months. We present an observational 15-year study on the severity of infant pertussis based on 1,443 laboratory-confirmed cases prospectively identified from 1998 to 2012 in the national mandatory reporting system and followed up by telephone contact. Analyses were made in relation to age at onset of symptoms and vaccination history. Pertussis decreased in non-vaccinated infants (2003 to 2012, p<0.001), indicating herd immunity, both in those too young to be vaccinated and those older than three months. The hospitalisation rates also decreased (last five-year period vs the previous five-year periods, p <0.001), but 70% of all cases in under three month-old infants and 99% of cases with apnoea due to pertussis were admitted to hospital in 1998 to 2012. Median duration of hospitalisation was seven days for unvaccinated vs four days for vaccinated infants aged 3-5 months. Nine unvaccinated infants died during the study period.

Vaccination of children – summary and conclusions from a systematic review.

Vaccination of children – summary and conclusions from a systematic review The full review can be found in Acta Pædiatrica 2010; 99: s461 Sven-Arne Silfverdal, Lennart Nilsson, Margareta Blennow, Rose-Marie Carlsson, Lars Å Hanson, Anders Lindberg, Lars Lindquist, Margaretha Magnusson, Anders Norlund, Olof Nyrén, Per Olcén, Patrick Olin, Juliette Säwe, Ann Söderström, Birger Trollfors, Åke Örtqvist (ake.ortqvist@sll.se)1.Department of Pediatrics, Bnai Zion Medical Center, The B. and R. Rappaport Faculty of Medicine, Technion, Haifa, Israel 2.Pediatric Infectious Disease Unit, Meyer Children’s Hospital, Rambam Medical Center, The B. and R. Rappaport Faculty of Medicine, Technion, Haifa, Israel 3.Pediatric Intensive Care Unit, Meyer Children’s Hospital, Rambam Medical Center, The B. and R. Rappaport Faculty of Medicine, Technion, Haifa, Israel 4.Metabolic Unit, Meyer Children’s Hospital, Rambam Medical Center, The B. and R. Rappaport Faculty of Medicine, Technion, Haifa, Israel

Vaccination of children – summary and conclusions from a systematic reviewThe full review can be found in Acta Pædiatrica 2010; 99: s461

Vaccination of children - summary and conclusions from a systematic reviewThe full review can be found in Acta Paediatrica 2010; 99: s461