Immunogenicity of 2 and 3 Doses of the Quadrivalent Human Papillomavirus Vaccine up to 120 Months Postvaccination: Follow-up of a Randomized Clinical Trial.

BACKGROUND: Several countries have implemented a 2-dose (2D) human papillomavirus (HPV) vaccination schedule for adolescents based on immunobridging studies. We compared immunogenicity of 2D vs 3-dose (3D) schedules of the quadrivalent vaccine (4vHPV) up to 10 years after the first dose. METHODS: Girls aged 9-13 years were randomized to receive 2D or 3D and were compared with women aged 16-26 receiving 3D at day 1 and months 7, 24, and 120 after the first dose. Antibody levels for HPV6/11/16/18 were evaluated using the competitive Luminex immunoassay (cLIA) and total immunoglobulin G assay. Geometric mean titers (GMTs) and seropositivity rates were compared between the different groups at different time points. Noninferiority of GMT ratios was defined as the lower bound of the 2-sided 95% confidence interval (CI) being greater than 0.5. Kinetics of antibody titers over time among study groups were examined. RESULTS: At 120 months, data from 35 2D girls, 38 3D girls, and 30 3D women were used for analyses. cLIA seropositivity rates were above 95% for all HPV vaccine types and all schedules, except HPV18, with the lowest seropositivity observed among 3D women (60.0%; 95% CI, 40.6%-77.3%). GMT ratios (cLIA) for both 2D and 3D girls were noninferior to 3 doses in women for HPV6/11/16/18. Trends were comparable between assays. CONCLUSIONS: GMTs for HPV6/11/16/18 after 2D or 3D of 4vHPV in girls were noninferior to 3D in adult women up to 120 months postvaccination. This study demonstrates long-term immunogenicity of the 2D HPV vaccine schedule.

Outcomes of invasive meningococcal disease in adults and children in Canada between 2002 and 2011: a prospective cohort study.

BACKGROUND: Neisseria meningitidis causes 500 000 cases of septicemia and meningitis worldwide annually, with approximately 200 cases in Canada each year. Previous studies describe a case-fatality rate of 5%-15% and up to 20% of survivors suffering from long-term disability. METHODS: This study was performed in Canada between 2002 and 2011; the study area included >50% of the country's population. We identified risk factors associated with death and the development of complications in children and adults admitted to hospital with confirmed invasive meningococcal disease (IMD). Clinical information was obtained from hospital records. Risk factors for death and complications were analyzed by univariate and multivariable analyses. RESULTS: Of 868 individuals hospitalized with IMD, there were 73 deaths (8.4%) and 157 (18%) developed complications. The most common complications were hearing loss (5.4%), skin scarring (5.4%), amputation (3.4%), renal dysfunction (2.6%), and seizures (2.5%). Mortality was independently associated with shock (adjusted odds ratio [aOR], 23.30; P<.0001), age (aOR, 1.02 per 1-year increased age; P<.0001), symptom onset within 24 hours of admission (aOR, 1.80; P=.0471), and admission to the intensive care unit (aOR, 0.41; P=.0196). Development of complications was independently associated with seizures (aOR, 4.55; P<.0001), shock (aOR, 3.10; P<.0001), abnormal platelet count (aOR, 2.14; P=.0002), bruising (aOR, 3.17; P=.0059), abnormal white blood cell count (aOR, 0.52; P=.0100), and prior antibiotic exposure (aOR, 0.27; P=.0273). CONCLUSIONS: Outcomes following IMD remain poor in this resource-rich setting in the 21st century. These data identify priorities for clinical management of adults and children with IMD, and provide prognostic information for affected patients and their families and cost-effectiveness analyses for meningococcal vaccine programs.

The impact of the meningococcal serogroup C conjugate vaccine in Canada between 2002 and 2012.

BACKGROUND: Before 2001, the incidence of invasive meningococcal disease (IMD) in Canada was 1.0 per 100 000 per year, with 40% of cases caused by serogroup C organisms. During 2001-2005 all provinces introduced the meningococcal serogroup C conjugate vaccine (MCCV) into their routine infant immunization schedule. METHODS: Active, prospective, population-based surveillance of IMD in children and adults was conducted by the Canadian Immunization Monitoring Program, ACTive (IMPACT) during 2002-2012. Inclusion criteria were admission to hospital and identification of Neisseria meningitidis from a sterile site. Incidence was estimated using population census data from Statistics Canada. RESULTS: Prior to MCCV introduction, serogroup C disease incidence was 0.07-0.25 per 100 000 per year depending on the province. Following vaccine introduction, serogroup C disease decreased to <0.05 per 100 000 per year, with a reduction of 14% per year (P = .0014). A decrease occurred in all provinces, despite differing schedules being implemented. The largest decrease of 83% (from 0.27 to 0.05 per 100 000 per year) occurred in the 15-24 year age group (P = .0100) who were not vaccinated in all provinces. There was no impact on the incidence of nonserogroup C disease over the same period (P = .9811). CONCLUSIONS: MCCV dramatically reduced the incidence of serogroup C IMD in Canada through both direct and indirect effects. The observation that disease incidence decreased with different schedules suggests that the doses at 12 months (common to all provinces) and adolescence (7 of 8 provinces studied) were critical in achieving disease control.

Knowledge, attitudes, beliefs and behaviours of older adults about pneumococcal immunization, a Public Health Agency of Canada/Canadian Institutes of Health Research Influenza Research Network (PCIRN) investigation.

BACKGROUND: Fewer Canadian seniors are vaccinated against pneumococcal disease than receive the influenza vaccine annually. Improved understanding of factors influencing pneumococcal vaccination among older adults is needed to improve vaccine uptake. METHODS: A self-administered survey measuring knowledge, attitudes, beliefs and behaviours about pneumococcal vaccination was administered to a cohort of seniors participating in a clinical trial of seasonal influenza vaccines at eight centers across Canada. Eligible participants were ambulatory adults 65 years of age or older, in good health or with stable health conditions, previously given influenza vaccine. The primary outcome was self-reported receipt of pneumococcal vaccination. Multi-variable logistic regression was used to determine factors significantly associated with pneumococcal vaccine receipt. RESULTS: A total of 863 participants completed questionnaires (response rate 92%); 58% indicated they had received the pneumococcal vaccine. Being offered the vaccine by a health care provider had the strongest relationship with vaccine receipt (AOR 23.4 (95% CI 13.4-40.7)). Other variables that remained significantly associated with vaccine receipt in the multivariable model included having heard of the vaccine (AOR 10.1(95% CI 4.7-21.7)), and strongly agreeing that it is important for adults > 65 to be vaccinated against pneumococcus (AOR 3.3 (95% CI 1.2-9.2)). Participants who were < 70 years of age were less likely to be vaccinated. CONCLUSIONS: These results indicate healthcare recommendation significantly influenced vaccine uptake in this population of older adults. Measures to encourage healthcare providers to offer the vaccine may help increase coverage.

Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial.

IMPORTANCE: Global use of human papillomavirus (HPV) vaccines to prevent cervical cancer is impeded by cost. A 2-dose schedule for girls may be possible. OBJECTIVE: To determine whether mean antibody levels to HPV-16 and HPV-18 among girls receiving 2 doses was noninferior to women receiving 3 doses. DESIGN, SETTING, AND PATIENTS: Randomized, phase 3, postlicensure, multicenter, age-stratified, noninferiority immunogenicity study of 830 Canadian females from August 2007 through February 2011. Follow-up blood samples were provided by 675 participants (81%). INTERVENTION: Girls (9-13 years) were randomized 1:1 to receive 3 doses of quadrivalent HPV vaccine at 0, 2, and 6 months (n = 261) or 2 doses at 0 and 6 months (n = 259). Young women (16-26 years) received 3 doses at 0, 2, and 6 months (n = 310). Antibody levels were measured at 0, 7, 18, 24, and 36 months. MAIN OUTCOMES AND MEASURES: Primary outcome was noninferiority (95% CI, lower bound >0.5) of geometric mean titer (GMT) ratios for HPV-16 and HPV-18 for girls (2 doses) compared with young women (3 doses) 1 month after last dose. Secondary outcomes were noninferiority of GMT ratios of girls receiving 2 vs 3 doses of vaccine; and durability of noninferiority to 36 months. RESULTS: The GMT ratios were noninferior for girls (2 doses) to women (3 doses): 2.07 (95% CI, 1.62-2.65) for HPV-16 and 1.76 (95% CI, 1.41-2.19) for HPV-18. Girls (3 doses) had GMT responses 1 month after last vaccination for HPV-16 of 7736 milli-Merck units per mL (mMU/mL) (95% CI, 6651-8999) and HPV-18 of 1730 mMU/mL (95% CI, 1512-1980). The GMT ratios were noninferior for girls (2 doses) to girls (3 doses): 0.95 (95% CI, 0.73-1.23) for HPV-16 and 0.68 (95% CI, 0.54-0.85) for HPV-18. The GMT ratios for girls (2 doses) to women (3 doses) remained noninferior for all genotypes to 36 months. Antibody responses in girls were noninferior after 2 doses vs 3 doses for all 4 vaccine genotypes at month 7, but not for HPV-18 by month 24 or HPV-6 by month 36. CONCLUSIONS AND RELEVANCE: Among girls who received 2 doses of HPV vaccine 6 months apart, responses to HPV-16 and HPV-18 one month after the last dose were noninferior to those among young women who received 3 doses of the vaccine within 6 months. Because of the loss of noninferiority to some genotypes at 24 to 36 months in girls given 2 doses vs 3 doses, more data on the duration of protection are needed before reduced-dose schedules can be recommended. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00501137.

Cross-reactive and vaccine-induced antibody to an emerging swine-origin variant of influenza A virus subtype H3N2 (H3N2v).

BACKGROUND: Cases of infection due to a novel swine-origin variant of influenza A virus subtype H3N2 (H3N2v) have recently been identified in the United States, primarily among children. We estimate levels of cross-reactive antibody to H3N2v by age and assess whether seasonal trivalent inactivated influenza vaccine (TIV), with or without adjuvant, may increase seroprotection. METHODS: Antibody to H3N2v was assessed by hemagglutination inhibition (HI) assay and, for a subset, also by microneutralization assay. Seroprevalence and seroprotection were defined as an HI titer of ≥40, and levels were compared with those for ancestral and contemporary human strains. The analysis included 1116 sera collected during fall 2010, corresponding to approximately 100 sera per decade of life. Vaccine-induced antibody levels were also assessed in sera from 136 children aged <10 years and 65 adults aged 20-59 years before and after receipt of 2010-2011 split TIV and in sera from 182 elderly individuals aged ≥65 years before and after receipt of 2011-2012 split TIV (for 31 individuals), MF59-adjuvanted TIV (for 72), or unadjuvanted subunit TIV (for 79). RESULTS: The overall prevalence of HI titers of ≥40 against A(H3N2)v was 25%. No children aged <5 years and <20% of individuals aged ≤14 years or ≥40 years had an HI titer of ≥40. Conversely, among individuals aged 15-39 years, half of teens and adults showed H3N2v seroprotection. Following TIV receipt, <15% of individuals in any vaccine group developed a 4-fold increase in antibody level. CONCLUSIONS: A substantial proportion of adolescents and young adults have cross-reactive antibody against emerging H3N2v, whereas children and older adults show broad susceptibility. Recent formulations of TIV do not substantially increase seroprotection. A specific vaccine would be needed if H3N2v establishes epidemic spread. CLINICAL TRIALS REGISTRATION: NCT01140009 and NCT01368796.

Cost effectiveness of infant vaccination for rotavirus in Canada.

INTRODUCTION: Rotavirus is the main cause of gastroenteritis in Canadian children younger than five years of age, resulting in significant morbidity and cost. The present study provides evidence on the cost effectiveness of two alternative rotavirus vaccinations (RotaTeq [Merck Frosst Canada Ltd, Canada] and Rotarix [GlaxoSmithKline, Canada]) available in Canada. METHODS: Analysis was conducted through a Markov model that followed a cohort of children from birth to five years of age. Analysis used pertinent data on the natural history of rotavirus and the effects of vaccination. Estimates of heath care costs for children requiring hospitalizations and emergency department visits were derived from the Canadian Immunization Monitoring Program, Active (IMPACT) surveillance, emergency department studies, as well as other Canadian studies. The model estimated the effect of vaccination on costs and quality-adjusted life years (QALYs). RESULTS: The incremental cost per QALY gained from the health care system perspective was $122,000 for RotaTeq and $108,000 for Rotarix. From the societal perspective, both vaccination strategies were dominant - both cost saving and more effective. The cost-effectiveness of vaccination is dependent on the mode of administration, the perspective adopted and the cost of the vaccine. CONCLUSIONS: From a societal perspective, a universal vaccination program against rotavirus will be both cost saving and more effective than no vaccination. Becasue the majority of rotavirus infections do not require emergency department visits or hospital admission, from a health care system perspective, a program would not be considered cost effective.

INTRODUCTION: Le rotavirus est la principale cause de gastroentérite chez les enfants canadiens de moins de cinq ans, ce qui s'associe à une morbidité et à des coûts considérables. La présente étude expose des données probantes sur le rapport coût-efficacité de deux vaccins contre le rotavirus (RotaTeq [Merck Frosst Canada Ltée, Canada] et Rotarix [GlaxoSmithKline, Canada]) offerts au Canada. MÉTHODOLOGIE: Les chercheurs ont effectué l'analyse au moyen d'un modèle de Markov qui consistait à suivre une cohorte d'enfants entre la naissance et cinq ans. L'analyse faisait appel à des données pertinentes sur l'évolution naturelle du rotavirus et sur les effets de la vaccination. Les évaluations des coûts de santé à l'égard des enfants devant être hospitalisés et consulter à l'urgence étaient tirées de la surveillance du Programme canadien de surveillance active de l'immunisation (IMPACT), d'études des départements d'urgence et d'autres études canadiennes. Le modèle a permis d'évaluer l'effet de la vaccination sur les coûts et les années de vie ajustées en fonction de la qualité (AVAQ). RÉSULTATS: Le coût incrémentiel par AVAQ épargné par le système de santé s'élevait à 122 000 $ à l'aide du vaccin RotaTeq et à 108 000 $ à l'aide du vaccin Rotarix. Sur le plan sociétal, les deux stratégies vaccinales étaient dominantes, c'est-à-dire qu'elles étaient à la fois rentables et plus efficaces. Le rapport coût-efficacité de la vaccination dépend du mode d'administration, de la perspective adoptée et du coût du vaccin. CONCLUSIONS: Sur le plan sociétal, un programme de vaccination universel contre le rotavirus sera à la fois rentable et plus efficace que l'absence de vaccination. Puisque la majorité des infections à rotavirus n'exigent pas de consultation à l'urgence ou d'hospitalisation, le programme ne serait pas rentable pour le système de santé.

Strategies for successful rapid trials of influenza vaccine.

BACKGROUND: In contrast to the gradual pace of conventional vaccine trials, evaluation of influenza vaccines often must be accelerated for use in a pandemic or for annual re-licensure. Descriptions of how best to design studies for rapid completion are few. PURPOSE: In August, 2010, we conducted a rapid trial with a seasonal influenza vaccine for 2010-2011 given to persons vaccinated with an adjuvanted H1N1 vaccine in 2009, to determine whether re-exposure to the H1N1(2009) component of the seasonal vaccine would cause increased reactions. We describe the strategies that we believe were responsible for success in meeting the desired timeline. METHODS: The key means for expediting the study were: use of a few experienced, well-staffed centers; efficient completion of administrative approvals; advance recruitment of volunteers; synchronized start among centers with rapid completion (≤1 week) of first visits; rapid data assembly via the Internet; and a well-prepared data analysis plan. We chose to use a randomized, blinded, cross-over design to allow estimation of vaccine-attributable adverse event rates, with sufficient power (320 participants) to detect events occurring at true rates ≥1% with ≥90% probability. RESULTS: Planned enrollment numbers, center synchronization, and timelines, including review by a safety board prior to the cross-over step (second doses), were achieved. A detailed safety report was delivered to federal health officials just 32 days after study initiation and was used to fine-tune public messaging prior to the mass vaccination programs across Canada. LIMITATIONS: This aggressive timeline could not have been met without opportunities for careful planning and the prior existence of a network of experienced, collaborating trial centers. CONCLUSIONS: The means used to accelerate this study timeline were successful and could be used in other urgent situations but the mechanics of collaborative trials must be well rehearsed as a precondition.

Optimizing Canadian public immunization programs: a prescription for action.

Recent expansion of public vaccination programs for children and youth offers new health benefits but at substantially increased cost. As with other large public investments, immunization programs ought to be systematically evaluated for safety, effectiveness and economic value. At present, program evaluations are suboptimal in most provinces and territories. Experts in public health and vaccinology who attended a workshop in 2009 reviewed the shortcomings and produced "prescriptions for action" to improve matters. Six key recommendations were made: 1) a formal requirement should exist to evaluate all public vaccination programs appropriately; 2) greater voluntary harmonization of programs will facilitate evaluations; 3) a mechanism is needed to prioritize and coordinate program-specific evaluations; 4) new funding mechanisms are needed for basic jurisdictional studies and joint studies of broad relevance; 5) strong emphasis is needed on capacity development and training; and 6) administrative barriers to accessing health information systems and publishing evaluation studies need to be overcome. The expert group considered the need to improve program evaluations as urgent and compelling, with success achievable with dedicated funding and effective leadership. Demonstrating that Canadian immunization programs are among the world's best and safest is a sound strategy for maintaining public participation in those programs.

Changing epidemiology of invasive pneumococcal disease in Canada, 1998-2007: update from the Calgary-area Streptococcus pneumoniae research (CASPER) study.

BACKGROUND: Routine infant vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) began in the Calgary Health Region (Alberta, Canada) in 2002. We measured the impact of this vaccine program on invasive pneumococcal disease (IPD). METHODS: Prospective, population-based surveillance of all cases of IPD (with culture specimens obtained from sterile sites) was conducted from January 1998 through December 2007. Demographic and clinical data were collected. All viable isolates were saved and serotyped. RESULTS: There were 1182 IPD cases over the 10-year period. Comparison of the vaccine period (2003-2007) with the prevaccine period (1998-2001) revealed that the incidence of IPD due to PCV7 serotypes decreased significantly by 86%, 59%, 38%, and 78% in the 6-23-month, 2-4-year, 16-64-year, and 65-84-year age groups, respectively. The total number of IPD cases decreased by 77%, 45%, and 34% in the 6-23-month, 2-4-year, and 65-84-year age groups, respectively. The incidence of IPD due to non-PCV7 serotypes increased by 183%, and the total incidence of IPD increased by 73% among adults aged 16-64 years; however, this increase was primarily attributed to a large outbreak of serotype 5 IPD among homeless adults during the period 2005-2007. There were 5 cases of IPD due to PCV7 serotypes among vaccinated children in the vaccine period. CONCLUSIONS: Since the introduction of PCV7 vaccine, there has been a profound decrease in the total number of cases of IPD among children and in cases due to PCV7 serotypes among subjects of all ages in Calgary, indicating a strong direct effect and herd effect of the vaccine. The serotypes that now cause IPD have changed significantly. The magnitude and impact of replacement IPD caused by non-PCV7 serotypes is not yet known.

The impact of childhood meningococcal serogroup C conjugate vaccine programs in Canada.

BACKGROUND: Conjugate meningococcal vaccines may decrease the incidence of disease. The staggered implementation of universal childhood meningococcal C conjugate (MenC) immunization programs across Canada offers an opportunity to evaluate the influence of these programs. METHODS: From 2002 to 2006, we conducted active, population-based surveillance for adult and pediatric hospital admissions related to meningococcal infections at the 12 centers of the Canadian Immunization Monitoring Program, Active (IMPACT), in collaboration with local public health officials. RESULTS: A total of 376 cases were reported during the 5 years of surveillance. Yearly totals were as follows: 96 in 2002, 73 in 2003, 81 in 2004, 58 in 2005, and 68 in 2006. Case fatality was 9.3% and adults had a significantly higher case fatality rate than children.Average incidence per 100,000 was 0.62 (95% confidence interval [CI]: 0.50-0.76) in 2002 and 0.42 (95% CI: 0.32-0.53) in 2006. The highest rates were in children age 0 to 4 years, followed by adolescents age 15 to 19 years. Incidence of group C disease decreased significantly during the 5 years from 0.23 (95% CI: 0.16-0.32) in 2002 to 0.08 (95% CI: 0.04-0.14) in 2006, whereas incidence remained stable for groups B, Y, and W135. The decrease in group C disease was seen in provinces that first implemented MenC immunization programs. CONCLUSIONS: A substantial decrease in group C incidence occurred in provinces with early MenC immunization programs. Serogroup C incidence remained stable in provinces without MenC programs. We found no evidence of serogroup replacement.

Epidemiology of pertussis and Haemophilus influenzae type b disease in Canada with exclusive use of a diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b pediatric combination vaccine and an adolescent-adult tetanus-diphtheria-acellular pertussis vaccine: implications for disease prevention in the United States.

BACKGROUND: During the decade 1998-2007, a combination DTaP(5)-IPV/Hib vaccine was used exclusively in Canada to immunize infants and young children against diphtheria, tetanus, pertussis, polio, and invasive Haemophilus influenzae type b (Hib) disease. METHODS: Medline was used to search for publications during 1996-2008 related to the epidemiology and vaccine prevention of pertussis and invasive Hib disease in Canada. Related abstracts and presentations were reviewed, when available, and epidemiologic data since 1985 were obtained from the Public Health Agency of Canada public Web site. RESULTS: Reports of pertussis have declined substantially in preschool and school-aged children during the past decade, and cyclical peaks in disease incidence have been blunted or eliminated. In provinces and territories where Tdap(5) vaccine has been administered to 14- to 16-year-olds, marked reductions of pertussis have been documented in adolescents as well as younger age groups, possibly due to herd immunity. Incidence rates of invasive Hib disease among Canadian children <5 years declined markedly after introduction of Hib conjugate vaccines, and the disease has remained under control with exclusive use of DTaP(5)-IPV/Hib vaccine. Most cases of invasive Hib disease occur among unimmunized or only partially vaccinated children. The reduction of Hib case reports has been documented throughout Canada, including among Aboriginal children who are at high risk for this disease. CONCLUSIONS: The Canadian experience with DTaP(5)-IPV/Hib and Tdap(5) vaccines is relevant to the United States because immunization schedules, vaccination coverage rates, and epidemiologic patterns of pertussis and Hib diseases are similar in the 2 countries, and because both vaccines are licensed for use in the United States.

Will Infant Hepatitis B Immunization Protect Adults?

Globally, infant hepatitis B virus (HBV) immunization programs are markedly reducing the rate of chronic HBV infections among children <5 years of age. Desirable improvements include increased birth dose coverage and better prevention of perinatal HBV transmission. Follow-up studies show that by the teenage years most of those immunized as infants have lost circulating anti-HBs antibody and some fail to respond to challenge HBV vaccination, implying loss of protection from infection. With high exposure to HBV, such individuals can develop breakthrough HBV infection but this rarely leads to chronic infection, the main goal of prevention programs. While longer-term follow-up studies into adulthood are needed, current evidence does not support a need for booster immunization of otherwise healthy teens or young adults.

Ongoing control of Haemophilus influenzae type B infections in Canadian children, 2004-2007.

The uniform use in Canada of a single Haemophilus influenzae type b conjugate vaccine in combination with diphtheria, tetanus, acellular pertussis, and inactivated poliovirus vaccines (DTaP.IPV/Hib) facilitates ongoing assessment of vaccine effectiveness, including any effects of recently added concurrent vaccinations and increasing time since vaccination. Surveillance at 12 pediatric centers in 2004-2007 indicates that vaccine failures remain rare and case totals approach an irreducible minimum, with no age shift.

The epidemiology of children hospitalized with herpes zoster in Canada: Immunization Monitoring Program, Active (IMPACT), 1991-2005.

BACKGROUND: Varicella zoster virus causes varicella (chickenpox) and can reactivate to cause herpes zoster (HZ). In Canada, live attenuated varicella vaccine was recommended for routine use among healthy susceptible children age 1 year and older, in 1999. Varicella vaccine has had a profound impact on the incidence of varicella; however the impact on HZ remains uncertain. METHODS: Surveillance for HZ admissions was conducted by the Immunization Monitoring Program, Active (IMPACT) surveillance network comprising 12 centers representing over 90% of pediatric tertiary care beds in Canada. Active surveillance for HZ was undertaken in 1991-1996 and reintroduced in 1999. A clinical diagnosis was accepted, with or without laboratory confirmation. For each case, a detailed case report form was completed. RESULTS: In total, 648 children were admitted with HZ; 342 (52.8%) were boys and the mean age was 9.9 +/- 4.4 years. Five hundred seventy-seven (89.0%) were immunocompromised and 71 immunocompetent (10.8%). Five hundred seventy-one (88.1%) had a history of varicella zoster virus infection. Varicella vaccination was documented in 4 children before admission. Most (85.5%) presented with localized disease. Immunocompetent children were more likely than immunocompromised children to be hospitalized with ophthalmic disease (odds ratio 5.1, P < 0.001) or with at least 1 complication (odds ratio 3.0, P < 0.001). Only 1 death was attributable to HZ. CONCLUSIONS: Immunocompromised children represented the overwhelming majority of IMPACT hospitalized cases. Complications directly resulting from HZ were common in immunocompetent children. As varicella vaccine use becomes more widespread, the IMPACT network will continue to play an important role in monitoring the changing epidemiology of HZ in children.

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 effect of changing from whole-cell to acellular pertussis vaccine on the epidemiology of hospitalized children with pertussis in Canada.

BACKGROUND: Between July 1997 and April 1998, universal childhood immunization programs in Canada changed from using a whole-cell pertussis to a 5-component acellular pertussis-containing vaccine. To assess effects on pertussis epidemiology of this nationwide change, we analyzed hospitalizations during 1991-2004 using the Canadian Immunization Monitoring Program, Active (IMPACT) pertussis database. METHODS: IMPACT is an active surveillance network based in 12 pediatric tertiary-care hospitals across Canada. Characteristics of hospitalized cases of pertussis were compared by type of vaccine received or by birth date (if immunization records were unavailable or the child was unvaccinated). Age-stratified incidence rates were calculated by year and vaccine type. RESULTS: Two thousand ninety-six cases of pertussis were admitted to IMPACT centers, 1174 during the whole-cell vaccine program (WCV-P) and 842 during the acellular vaccine program (ACV-P). Pertussis incidence among children <5 years old decreased significantly during the ACV-P, causing an increase in the residual proportion of cases either too young to be immunized (<2 months old: ACV-P 39% versus WCV-P 26.1%; P < 0.0001) or too young for a second dose (2-3 months old: 42.9% versus 34.2%, respectively; P < 0.0001). A significantly smaller proportion of cases (ACV-P 15.1% versus WCV-P 27.3%) occurred in infants who were old enough (4-11 months of age) to have received 2 or 3 doses of vaccine. CONCLUSIONS: With ACV-P, pertussis hospitalizations in children 4-59 months old decreased in frequency, consistent with improved vaccine effectiveness, but remained prominent among very young infants. Improved control strategies are needed to reduce infections among infants too young for pertussis vaccination.

Effectiveness of pneumococcal conjugate vaccine in Greater Vancouver, Canada: 2004-2005.

Active, population-based surveillance for invasive pneumococcal infections in Greater Vancouver (population 473,000 children) demonstrated a rapid, substantial decrease in incidence rates for children 6-23 months old with routine infant vaccination. In the subpopulation with best case ascertainment disease rates for 6-23 month olds decreased 84.6% (92.5% for vaccine serotypes).