Jan J. Ochnio

A modified vaccine reduces the rate of large injection site reactions to the preschool booster dose of diphtheria-tetanus-acellular pertussis vaccine : Results of a randomized, controlled trial

Background: Large injection site reactions commonly follow booster doses of diphtheria-tetanus-acellular pertussis (DTaP) vaccines at 4–6 years of age. A vaccine with lower diphtheria and pertussis dosage (Tdap) might be better tolerated for this dose. Methods: We conducted a randomized, controlled, evaluator-blinded comparison of local reactions to DTaP.inactivated poliomyelitis vaccine (IPV) or Tdap booster vaccinations, in 4- to 5.5-year-old children. Reactions were assessed daily by parents and after 48 hours by study nurses. Serologic responses were measured before and 4 weeks after vaccination and examined in relation to large local reactions (≥50 mm redness and/or swelling). Results: 288 children were vaccinated, 145 with DTaP.IPV and 143 with Tdap, and after 48 hours examiners noted local redness ≥ 50mm in 17.2 and 6.3%, respectively (P = 0.004). DTaP.IPV vaccinees initially experienced local pain (in 54%) which limited arm motion (in 37%), but symptoms largely resolved by 48 hours. Tdap vaccinees had fewer symptoms (pain in 20%, limited arm motion in 14%). Children with large reactions to DTaP.IPV more often than nonreactors had elevated preimmunization antibody concentrations to 1 or more of diphtheria, pertussis toxin or pertactin and elevated postimmunization antibody concentrations to all antigens except fimbriae. Booster responses to Tdap were reduced with the smaller antigen doses but were generally satisfactory. Conclusions: This preschool DTaP.IPV booster vaccination caused large local reactions in 1 in 5 children, with transient discomfort. With Tdap vaccine, such reactions were significantly fewer but not eliminated. A Tdap.IPV vaccine warrants study for routine use at 4–6 years of age.

Hepatitis A Virus Infections in Urban Children—Are Preventive Opportunities Being Missed?

To determine the prevalence of hepatitis A virus (HAV) infections in children in a large urban center, a point prevalence survey was conducted using a novel, ultrasensitive assay for HAV-specific IgG in saliva. A structured sample of 224 grade-six students (5.8% of grade registrants) was obtained from 23 schools throughout Vancouver. All students provided saliva samples adequate for testing. The anti-HAV prevalence rate was 7.1% (95% confidence interval, 4.1%-11.3%). Among 167 Canadian-born students, only 5 (3%) were positive, whereas among 57 students born elsewhere, 11 (19.3%) were positive (P < .001), with circumstances in the latter group supporting infection prior to emigration. No clustering of positive persons was evident. The cumulative risk of HAV infection in Canadian-born children was low through age 11-12 years even in less affluent parts of the city, speaking against a need for routine use of HAV vaccine in this setting.

Cellular immunity as a potential cause of local reactions to booster vaccination with diphtheria and tetanus toxoids and acellular pertussis antigens.

Background: Booster doses of diphtheria-tetanus-acellular pertussis (DTaP) vaccines restore waning serum antibody values but frequently cause local inflammation. Cell-mediated immunity (CMI) develops after primary DTaP vaccination and might contribute to local reactions to booster doses, a possibility explored in this study. Methods: Healthy 4 to 5-year-old children were bled before DTaP.IPV booster vaccination. Peripheral blood mononuclear cells were tested for proliferative responses to D toxoid (DT), T toxoid, pertussis toxoid, pertactin, filamentous hemagglutinin and fimbriae (FIM) types 2, 3, and cytokine release patterns assessed. Proliferative responses were examined in relation to prebooster serum antibody concentrations and local reaction rates, previously reported. Results: Among 167 subjects tested, proliferative response rates were: filamentous hemagglutinin 95%, pertussis toxoid 90%, T toxoid 84%, pertactin 67%, DT 41%, and FIM 31%. Responses were present to 3 to 6 antigens in 87% of subjects and absent altogether in 2%. Subjects without residual pertussis antibodies often had CMI to pertussis antigens. Subjects with CMI had higher corresponding serum antibody concentrations before the booster, compared with CMI-negative subjects. CMI responses were mixed TH1/TH2 type by cytokine profile for all antigens. Injection site erythema (≥5 mm) was twice as frequent in those with than without CMI to DT (P = 0.009) or FIM (P = 0.042, Fisher exact test), the only antigens evaluable. Conclusion: CMI to vaccine antigens was often detectable in children before preschool booster vaccination and preliminary evidence suggests a role for CMI in local reactions to this dose.

Comparative safety of tetanus-diphtheria toxoids booster immunization in students in Grades 6 and 9

BACKGROUND Tetanus-diphtheria toxoids (Td) booster immunization is generally recommended for Grade 9 students (14- to 16-year-olds) but targeting younger students may enhance vaccine uptake or facilitate simultaneous vaccinations. However, earlier vaccination might cause greater side effects. This study was undertaken to compare the safety of Td vaccinations in students in Grade 6 (11 to 12 years old) and Grade 9. METHODS A controlled, sequential assessment of Td vaccine, adsorbed, was conducted in one urban school district, starting with Grade 9 students. Grade 6 students were given Td concurrently with Dose 3 of hepatitis B vaccine. Adverse effects were assessed during visits 2 days after vaccination. Participation criteria, immunization technique and assessment procedures were standardized. RESULTS Of 410 students vaccinated, 204 in Grade 9 and 206 in Grade 6, 391 (95.4%) were assessed in person. Nineteen missed follow-up visits but telephone interviewers established that none missed school because of vaccine side effects. At follow-up Grade 6 students more often reported deltoid pain with arm movement (35.2% vs. 10.8%, P < 0.001). Injection site redness > or = 50 mm in diameter was present in 12.2% of Grade 6 and 3.6% of Grade 9 students (P < 0.001) whereas swelling > or = 50 mm diameter was present in 22.4 and 10.8%, respectively (P < 0.01). Fewer than 10% of subjects took analgesics for injection site pain. Only 5 students (1.3%) rated Td site morbidity as severe/unacceptable. Hepatitis B site morbidity was minimal in comparison. CONCLUSION Td boosters were moderately reactogenic in adolescents. Younger students more often experienced injection site morbidity but considered it bearable. Booster immunizations can reasonably be offered within the age range of 11 to 16 years.

A nationwide survey of past hepatitis A infections among Canadian adults.

BACKGROUND Hepatitis A virus (HAV) infection rates in Canada are low and declining. A nationwide pediatric serosurvey in 2003 confirmed that HAV infection is uncommon in children. Additional seroepidemiological data for adults would help to guide domestic use of HAV vaccines. METHODS A country-wide survey of HAV antibody positivity and selected risk factors was conducted among 18-69 year olds identified by random digit dialing, in samples proportional to regional populations. Volunteers were sent study materials and returned oral fluid and completed questionnaires by mail. An ultra-sensitive assay was used to detect HAV antibody in oral fluid. Multiple logistic regression was used for risk factor assessment. RESULTS Of 2104 potential study participants, 1552 (74%) returned an adequate oral fluid specimen and questionnaire. Anti-HAV was detected in 509 individuals (33%) and was associated with birth in HAV endemic areas, self-reported hepatitis A vaccination, prior travel to endemic areas, and increasing age. Only 15% reported having been vaccinated. Among Canadian-born, non-vaccinated participants anti-HAV was present in 20%, ranging regionally from 14% to 30%. Age-specific positivity rates in this subset were: 18-29 years 2.6%; 30-39 years 6.1%; 40-49 years 11.4%; 50-59 years 26.4% and 60-69 years 45.9%. Travel to HAV-endemic countries was reported by 55% of participants but only 24% of travelers had been vaccinated. CONCLUSIONS Past HAV infection rates among Canadian-born, non-vaccinated individuals are low in young adults and increase by two-fold per age decade. Travel to endemic areas is a significant risk factor, amenable to prevention by greater use of HAV vaccine.

Immunologic considerations for the timing of the booster dose of 7-valent pneumococcal conjugate vaccine in young children.

Background: The booster (fourth) dose of 7-valent pneumococcal conjugate vaccine (PCV7) is recommended to be given at 12–15 months but in Canada it better fits the national schedule at 18 months, prompting this comparison of the safety and immunogenicity of booster immunization at 15 or 18 months. Methods: Children who had completed a study of primary PCV7 immunization (with final serology at 7–8 months of age) were enrolled at 12 months, bled and randomly assigned to receive a PCV7 booster at age 15 or 18 months, with serologic testing before and 4 weeks afterward. Adverse events were documented for 3 days postbooster. Antibody concentrations were measured for the 7 pneumococcal serotypes and Haemophilus influenzae type b at 7–8, 12, 15 or 18 months and after boosting. Results: Three hundred thirty-one children were boosted, 167 at 15 months and 164 at 18 months. Pneumococcal geometric mean antibody concentrations declined by 15 months to 23.4% of peak geometric mean concentrations at age 7–8 months and to 19.8% by 18 months. Spontaneous increases in 1 or more antibody concentrations were noted in 195 subjects (61.7%), most commonly with types 6B and 19F. Antibody responses to PCV7 were similarly brisk at 15 and 18 months. Mild injection-site redness and swelling were significantly more frequent at 15 than 18 months but no other differences in reactogenicity were observed. Conclusions: Residual antibody concentrations differed minimally between 15 and 18 months. Spontaneous antibody increases often occurred before boosting, possibly from colonization. PCV7 booster vaccination at 18 months appears to be safe and provides comparable immunogenicity to 15 months vaccination.

The Prevalence of Hepatitis A in Children in British Columbia

BACKGROUND The risk of hepatitis A virus (HAV) infection during childhood is difficult to estimate without population serosurveys because HAV-related symptoms are often mild at this age. Few serosurveys have been conducted in Canada. The present study surveyed teenagers in two nonurban regions of British Columbia where the historical rate of reported HAV either exceeded (region A) or was less than (region B) the historical provincial rate. METHODS A point prevalence survey of salivary HAV-specific immunoglobulin G was conducted in high schools among grade 9 students in regions A and B. A questionnaire was used to gather sociodemographic data. The survey was extended to grade 1 and grade 5 students in community 1 of region B. Associations between risk factors and prior infection were evaluated by logistic regression. RESULTS Eight hundred eleven grade 9 students were tested. Antibody to HAV was detected in 4.7% of students in region A (95% CI 2.9% to 7.2%) and 9.6% of students in region B (95% CI 6.9% to 12.9%). The region B figure reflected HAV antibody prevalence rates of 19.5% in community 1 and 2.5% in the remainder of the region. Younger students in community 1 had low HAV antibody to HAV prevalence rates (3.9% for grade 1 and 3.1% for grade 5), and positive tests in this community were associated with a particular school, foreign travel and brief residence. The risk factors for HAV infection in grade 9 students were not determined. CONCLUSIONS Children in nonurban areas of British Columbia are generally at low risk of HAV infection during the first decade of life regardless of the reported population rates, thereby permitting the consideration of school-based HAV immunization programs.