Scott A Halperin

IWK Health Centre, Halifax, Nova Scotia, Canada

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Publications (320)1249.75 Total impact

  • Canadian Medical Association Journal 08/2015; DOI:10.1503/cmaj.150391 · 5.81 Impact Factor
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    ABSTRACT: This systematic review assessed the effectiveness and safety of pharmacotherapy and combined interventions for reducing vaccine injection pain in individuals across the lifespan. Electronic databases were searched for relevant randomized and quasi-randomized controlled trials. Self-reported pain and fear as well as observer-rated distress were critically important outcomes. Data were combined using standardized mean difference (SMD) or relative risk (RR) with 95% confidence intervals (CI). Fifty-Five studies that examined breastfeeding (which combines sweet-tasting solution, holding and sucking), topical anesthetics, sweet-tasting solutions (sucrose, glucose), vapocoolants, oral analgesics, and combination of two versus one intervention were included. The following results report findings of analyses of critical outcomes with the largest number of participants. Compared to control, acute distress was lower for infants breastfed during vaccination (n=792): SMD -1.78 (CI: -2.35, -1.22) and before vaccination (n=100): SMD -1.43 (CI: -2.14, -0.72). Compared to control/placebo, topical anesthetics showed benefit on acute distress in children (n=1424): SMD -0.91, (CI: -1.36, -0.47) and self-reported pain in adults (n=60): SMD -0.85 (CI: -1.38, -0.32). Acute and recovery distress was lower for children who received sucrose (n=2071): SMD -0.76, (CI: -1.19, -0.34) or glucose (n=818): [SMD: -0.69, (CI: -1.03, -0.35)] compared to placebo/no treatment. Vapocoolants reduced acute pain in adults [(n=185) SMD -0.78, (CI: -1.08, -0.48)] but not children. Evidence from other needle procedures showed no benefit of acetaminophen or ibuprofen. The administration of topical anesthetics before and breastfeeding during vaccine injections showed mixed results when compared to topical anesthetics alone. There were no additive benefits of combining glucose and non-nutritive sucking (pacifier) compared to glucose or non-nutritive sucking (pacifier) alone or breastfeeding and sucrose compared to breastfeeding or sucrose alone. Breastfeeding, topical anesthetics, sweet-tasting solutions and the combination of topical anesthetics and breastfeeding are effective in reducing vaccine injection pain in infants and children and its use should become the standard of care. In adults, limited data demonstrate some benefit of topical anesthetics and vapocoolants.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
    The Clinical journal of pain 07/2015; DOI:10.1097/AJP.0000000000000281 · 2.70 Impact Factor
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    ABSTRACT: The tetanus, diphtheria and acellular pertussis vaccine (Tdap) is recommended for all adults in both Canada and the United States. There are few data on the proportion of Canadian adults vaccinated with Tdap; however, anecdotal reports indicate that uptake is low. This study aimed to explore the knowledge, attitudes, beliefs, and behaviors of Canadian health care providers (HCPs) in an attempt to identify potential barriers and facilitators to Tdap uptake. HCPs were surveyed and a geographic and practice representative sample was obtained (n=1167). In addition 8 focus groups and 4 interviews were conducted nationwide. Results from the survey indicate that less than half (47.5%) of all respondents reported being immunized with Tdap themselves, while 58.5% routinely offer Tdap to their adult patients. Knowledge scores were relatively low (63.2% correct answers). The best predictor of following the adult Tdap immunization guidelines was an awareness of, and agreement with those recommendations. Respondents who were aware of the recommendations were more likely to think that Tdap is safe and effective, that their patients were at significant risk of getting pertussis, and to feel that they had sufficient information (p<0.0001 for each statement). Focus group data supported the survey results and indicated that there are substantial gaps in knowledge of pertussis and Tdap amongst Canadian HCPs. Lack of public knowledge around adult immunization, lack of immunization registries, costing differential between Td and Tdap, workload required to deliver the vaccine, and vaccine hesitancy were identified as barriers to compliance with the national recommendations for universal adult immunization and suggestions provided to better translate recommendations to front line practitioners.
    Human Vaccines & Immunotherapeutics 06/2015; DOI:10.1080/21645515.2015.1046662 · 3.64 Impact Factor
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    ABSTRACT: Pertussis has reemerged as a problem across the world. To better understand the nature of the resurgence, we reviewed recent epidemiologic data and we report disease trends from across the world. Published epidemiologic data from January 2000 to July 2013 were obtained via PubMed searches and open-access websites. Data on vaccine coverage and reported pertussis cases from 2000 through 2012 from the 6 World Health Organization (WHO) regions were also reviewed. Findings are confounded by the lack of systematic and comparable observations in many areas of the world, but also by the cyclic nature of pertussis with peaks occurring every 3 to 5 years. It appears that pertussis incidence has increased in school-age children in North America and western Europe, where acellular pertussis vaccines are used, but an increase has also occurred in some countries that use whole-cell vaccines. Worldwide, pertussis remains a serious health concern, especially for infants, who bear the greatest disease burden. Factors that may contribute to the resurgence include lack of booster immunizations, low vaccine coverage, improved diagnostic methods, and genetic changes in the organism. To better understand the epidemiology of pertussis and optimize disease control, it is important to improve surveillance worldwide, irrespective of pertussis vaccine types and schedules used in each country.
    The Pediatric Infectious Disease Journal 06/2015; DOI:10.1097/INF.0000000000000795 · 3.14 Impact Factor
  • Lauren Davey · Scott A Halperin · Song F Lee
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    ABSTRACT: Streptococci secrete small peptides with important biological functions. These peptides are not amenable to standard immunoblotting, and are often detected indirectly using activity assays, or by alternative approaches that may be expensive and laborious. Here we describe an immunoblotting method that enables reproducible detection of these small streptococcal peptides. Copyright © 2015. Published by Elsevier B.V.
    Journal of microbiological methods 04/2015; 114. DOI:10.1016/j.mimet.2015.04.015 · 2.10 Impact Factor
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    ABSTRACT: Rotavirus is the most common cause of diarrhea leading to hospitalization in young children. Rotavirus vaccines are available in Canada but have not been introduced in all provinces. In a controlled trial, two study sites (Prince Edward Island and the Capital District Health Authority (District 9, Nova Scotia) introduced universal rotavirus vaccine programs for infants at two and four months of age beginning 1 December 2010, using public health nurse or general practitioner-delivery models, respectively. A third site (Saint John, NB) served as the non-intervention control setting. Vaccine coverage, rotavirus hospitalizations, intussusception and all-cause diarrhea were monitored. A universal rotavirus vaccine program with >90% coverage was associated with reductions in rotavirus-associated hospitalizations (from a peak of 52.8 hospitalizations/100,000 population to 0 hospitalizations) in infants < 12 months and 1 to < 2 years of age 12 months after program implementation. No apparent reduction occurred in the site with vaccine coverage of < 40%, or in the non-intervention control site. No cases of intussusception were associated with vaccine receipt, and no increase in all-cause diarrhea was observed. A universal infant rotavirus vaccine program with high coverage was associated with reductions in rotavirus and no safety signals; no reduction was observed in settings with low vaccine coverage.
    Human Vaccines and Immunotherapeutics 03/2015; 11(4). DOI:10.1080/21645515.2015.1012028 · 3.64 Impact Factor
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    ABSTRACT: Increasing the transparency of the evidence base behind health interventions such as pharmaceuticals, biologics, and medical devices, has become a major point of critique, conflict, and policy focus in recent years. Yet the lack of publicly available information regarding the immunogenicity assays upon which many important, widely used vaccines are based has received no attention to date. In this paper we draw attention to this critical public health problem by reporting on our efforts to secure vaccine assay information in respect of 10 vaccines through Canada's access to information law. We argue, under Canadian law, that the public health interest in having access to the methods for these laboratory procedures should override claims by vaccine manufacturers and regulators that this information is proprietary; and, we call upon several actors to take steps to ensure greater transparency with respect to vaccine assays, including regulators, private firms, researchers, research institutions, research funders, and journal editors.
    Human Vaccines & Immunotherapeutics 02/2015; 11(2):498-503. DOI:10.4161/21645515.2014.980194 · 3.64 Impact Factor
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    ABSTRACT: 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.
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    ABSTRACT: Objectives: Examine pertussis cycles between 1990 and 2013 and determinants by age group, immunization cohort and province/territory. Methods: National pertussis case reports were used. 2013 data are preliminary. Peak years were those in which incidence rates were above the preceding and proceeding years. Immunization cohorts were defined by year of birth and dates of program implementation by province/territory. Results: Introduction of acellular vaccine and adolescent booster programs occurred in all provinces/territories between 1997 and 2004. From 1990-1998, pertussis peaks occurred every 4 years with a mean increase of 82% from the preceding year and occurred uniformly across all age groups. The largest case contribution shifted from the 1-4 age group (1990-93) to the 5-9 age group (1994-98). From 1999-2007, no national peaks occurred, peaks within age groups were asynchronous, and the largest case contribution shifted from the 5-9 age group (1999), to the 10-14 age group (2000-05), to the 1-4 age group (2006-07). From 2008-2013, peaks occurred every 4 years and across all age groups with a 30% incidence increase in 2008 and 546% increase in 2012. The largest case contribution alternated between the 1-4 and 20+ age groups. Age groups in the adsorbed whole cell cohort contributed the most cases annually until 2006. National peak years were not dependent on the number of peaking provinces/territories but were typically in years with over 80% case contribution from peaking provinces/territories. Conclusions: Canadian pertussis cycles appear to have been altered by acellular vaccine and adolescent booster programs. Booster programs may have interrupted a marching cohort of children primed with adsorbed whole cell vaccine. With 4 year cycles resuming in 2008 and the 2012 peak, a new pattern of pertussis cycles may have begun. Given differences in cyclic patterns and immunization programs by province/territory, data should be examined by region.
    Canadian Immunization Conference, Ottawa, Ontario, Canada; 12/2014
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    ABSTRACT: This survey study compared pre- and post-pandemic knowledge, attitudes, beliefs, and intended behaviors of pregnant women regarding influenza vaccination (seasonal and/or pandemic) during pregnancy in order to determine key factors influencing their decision to adhere to influenza vaccine recommendations. Only 36% of 662 pre-pandemic respondents knew that influenza was more severe in pregnant women, compared to 62% of the 159 post-pandemic respondents. Of the pre-pandemic respondents, 41% agreed or strongly agreed that that it was safer to wait until after the first 3 months to receive the seasonal influenza vaccine, whereas 23% of the post-pandemic cohort agreed or strongly agreed; 32% of pre-pandemic participants compared to 11% of post-pandemic respondents felt it was best to avoid all vaccines while pregnant. Despite 61% of the pre-pandemic cohort stating that they would have the vaccine while pregnant if their doctor recommended it and 54% citing their doctor/nurse as their primary source of vaccine information, only 20% said their doctor discussed influenza vaccination during their pregnancy, compared to 77% of the post-pandemic respondents who reported having this conversation. Women whose doctors discussed influenza vaccine during pregnancy had higher overall knowledge scores (P < 0.0001; P = 0.005) and were more likely to believe the vaccine is safe in all stages of pregnancy (P < 0.0001; P = 0.001) than those whose doctors did not discuss influenza vaccination. The 2009 H1N1 pandemic experience appeared to change attitudes and behaviours of health care providers and their pregnant patients toward influenza vaccination.
    Human Vaccines and Immunotherapeutics 12/2014; 10(12):3629-3641. DOI:10.4161/21645515.2014.980684 · 3.64 Impact Factor
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    ABSTRACT: Highly pathogenic avian influenza A/H5N1 viruses continue to circulate in birds and infect humans causing serious illness and death.Methods In this randomized, observer-blinded study, adults ≥18 years of age (n = 841) received 3.75 or 7.5 μg hemagglutinin antigen (HA) of an AS03-adjuvanted (AS03A or AS03B) A/Indonesia/5/2005 H5N1 (subclade 2.1) vaccine (priming), followed by the same HA dose of AS03-adjuvanted A/turkey/Turkey/1/05 H5N1 (clade 2.2) influenza vaccine as a booster 6 or 18 months after priming; an unprimed group received placebo at Day 0, and 3.75 μg HA of AS03A-adjuvanted booster vaccine at 6 and 18 months. Antibody responses were assessed by hemagglutination-inhibition assay (HI). Microneutralization (MN) antibody and cellular immunoassays were assessed in a subset of participants.ResultsGeometric mean titers (GMTs) and seroconversion rates (SCRs) were higher in primed vs. unprimed subjects against the booster strain 10 days following booster vaccination at month 6 and month 18. After the booster at 18 months, the lower limit of the 97.5% confidence interval for the difference in SCR and GMT ratios between primed and unprimed subjects was >15% and >2.0, respectively, fulfilling the primary endpoint criteria for superiority against the booster strain. MN and cellular immune responses corresponded with the immunogenicity seen in HI measures.Conclusions Adults primed with a dose-sparing oil-in-water adjuvanted H5N1 subclade vaccine had rapid and durable antibody responses to a heterologous subclade boosting vaccine given 6 or 18 months later.
    Vaccine 11/2014; 33(4). DOI:10.1016/j.vaccine.2014.11.018 · 3.49 Impact Factor
  • Medicine 2.0 Scientific Meeting, Maui, Hawaii; 11/2014
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    ABSTRACT: sec> Background Influenza attack rates are high in 6- to 35-month-old children; vaccines containing both lineages of influenza B (Yamagata and Victoria), in addition to the H3N2 and H1N1 antigens, may improve protection rates. Methods In a randomized double-blind controlled trial, the immunogenicity and reactogenicity of an inactivated quadrivalent influenza vaccine (QIV) and a trivalent control vaccine (TIV) were assessed. Results Six hundred one children (QIV, n = 299; TIV, n = 302) were enrolled at 8 sites in 3 countries. The primary immunogenicity objective was met: the lower limit (LL) of the 2-sided 95% confidence interval (CI) for the seroconversion rate in QIV recipients ranged from 66.6% to 81.3%, which was ≥40% against all 4 strains. The immunogenic superiority of the additional B/Victoria strain in the QIV compared to that in the TIV was confirmed: the LL of the 2-sided 95% CI of the geometric mean titer ratio (QIV/TIV) (6.28 [95% CI, 5.32–7.41]) was greater than 1.5, and the LL of the 2-sided 95% CI for the difference in the seroconversion rate (QIV – TIV) (64.19% [95% CI, 57.65%–69.95%]) was greater than 10%. Injection-site pain and irritability/fussiness were the most commonly reported solicited injection-site and general adverse events, respectively, from days 0 to 6 and were similar in frequency between the groups. Conclusions In children aged 6 to 35 months, a QIV has superior immunogenicity for the added B strain and acceptable immunogenicity for shared strains, with no notable difference in reactogenicity and safety when compared to a TIV. </sec
    10/2014; DOI:10.1093/jpids/piu098
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    ABSTRACT: Background: Group B Streptococcus (GBS) is a serious cause of meningitis and sepsis in young infants. We assessed maternal immunization with an investigational trivalent GBS polysaccharide-CRM conjugate vaccine, with follow-up of both mothers and infants ( NCT01446289). Methods: In a phase II, observer-blind, placebo-controlled study, 86 pregnant women were enrolled at 24–35 weeks gestation and randomized 3:2 to receive intramuscular placebo (saline) or trivalent GBS vaccine containing 5 µg of glycoconjugates of each of GBS serotypes Ia, Ib and III. GBS serotype-specific antibodies were measured in mothers pre- and Day 31 post-immunization, and in mothers and infants at delivery and Day 91 post-partum. Safety was assessed up to at least 5 months postpartum. Results: Of 86 pregnant women enrolled (age 29.8 ± 5.1 years, mean ± SD), 51 received vaccine and 35 placebo at 30.0 ± 3.3 weeks gestation. Low pre-immunization antibodies against serotypes Ia, Ib and III increased 16-, 23- and 20-fold, respectively, at delivery. Among maternal-infant pairs with detectable antibodies, placental transfer was 81% (n=38), 70% (n=35) and 65% (n=33), against serotypes Ia, Ib and III. Infants of vaccinated mothers had increased antibody levels at birth which persisted above placebo group levels through day 91 of age. ELISA GMCs (µg/mL) [95% CI] GBS Serotype Ia Ib III Study Group GBS Placebo GBS Placebo GBS Placebo Mothers N 51 35 51 35 51 35 GMC - Delivery [95% CI] 5.22 [3.37, 8.1] 0.37 [0.22, 0.63] 2.41 [1.48, 3.94] 0.13 [0.07, 0.23] 1.90 [1.15, 3.12] 0.11 [0.06, 0.19] Infants N 35 25 31 20 30 22 GMC - Birth [95% CI] 5.14 [2.64, 10] 0.33 [0.15, 0.71] 2.93 [1.14, 7.57] 0.1 [0.03, 0.32] 1.93 [0.82, 4.59] 0.07 [0.02, 0.18] Infants N 35 25 35 25 35 25 GMC - 91 days [95% CI] 1.28 [0.76, 2.16] 0.25 [0.13, 0.46] 0.54 [0.25, 1.19] 0.06 [0.03, 0.16] 0.43 [0.21, 0.86] 0.07 [0.03, 0.15] Mild or moderate solicited reactions were reported in 54% and 53% of vaccine and placebo groups, respectively, with no vaccine-related SAEs reported. Conclusion: One dose of trivalent GBS vaccine was well-tolerated with no concerning safety signals in pregnant women, and induced increased antibody concentrations in mothers and their infants.
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
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    ABSTRACT: Combination diphtheria-tetanus-5 component acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine (DTaP5-IPV-Hib-HepB) administered either concurrently with 7-valent pneumococcal conjugate vaccine (PCV7) or 1 month apart was generally safe and immunogenic at 2, 4 and 6 months of age. This study examined the effects of a booster dose at age 15 months. Participants were randomized to DTaP5-IPV-Hib-HepB plus PCV7, DTaP5-IPV-Hib-HepB with PCV7 administered 1 month later or a pentavalent DTaP5-IPV/Hib plus HepB plus PCV7 at 15 months of age in a randomized, open-label, phase IIb clinical trial. Immunogenicity endpoints were rates of seroresponse to pertussis toxoid, filamentous hemagglutinin, pertactin and fimbriae types 2 and 3; rates of seroprotection against (Hib) polyribosylribitol phosphate capsular polysaccharide, hepatitis B surface antigen, diphtheria toxoid, tetanus toxoid and poliovirus types 1, 2 and 3; and geometric mean titers to all vaccine antigens. Safety endpoints included solicited injection-site reactions and systemic and serious adverse events. Seroresponse/seroprotection rates for all antigens exceeded prespecified criteria in both groups that received the hexavalent DTaP5-IPV-Hib-HepB; in the group that received the currently licensed pentavalent vaccine, seroresponse/seroprotection rates exceeded the criteria for all antigens except filamentous hemagglutinin. Seroresponse rates were ≥88.9% for pertussis antigens and seroprotection rates against polyribosylribitol phosphate capsular polysaccharide, hepatitis B surface antigen, diphtheria toxoid, tetanus toxoid and poliovirus antigens were ≥95.1% in recipients of DTaP5-IPV-Hib-HepB. DTaP5-IPV-Hib-HepB administered concomitantly with PCV7 or 1 month apart at 15 months of age following the infant series was well-tolerated and elicited antibody responses to all vaccine antigens, with no significant interference from concomitant PCV7 administration ( registration number NCT00362427).
    The Pediatric Infectious Disease Journal 10/2014; 33(1):73-80. DOI:10.1097/01.inf.0000437806.76221.20 · 3.14 Impact Factor
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    ABSTRACT: Infants under 6 months of age are at greatest risk of mortality and severe morbidity from pertussis disease. Interventions that increase pertussis protection in newborns are therefore a clear public health imperative. The objective of this study was to assess maternal pertussis toxin antibody (anti-PT) level as a potential source of mother-to-child transfer of pertussis-associated antibodies that may reduce neonatal risk of pertussis disease. Anti-PT level was assessed in a 2013 cohort of pregnant women from two regions in two Canadian provinces, British Columbia and Nova Scotia. Basic demographics, health, and pertussis immunization history were collected, along with blood specimens. Anti-PT levels were compared for self-reported vaccination status and prior pertussis disease. To assess secular trend, a parallel analysis was also undertaken, using anonymized residual sera from a 1996-1997 cohort of pregnant women in British Columbia. A total of 169 pregnant women participated in the prospective study - 50 from Nova Scotia and 119 from British Columbia. The mean and median age of participants from both sites was 31 years of age (range 16-42 years). The lower limit of quantification of the anti-PT assay was 10 ELISA units per milliliter (EU/ml). Overall, 59% of women had anti-PT levels less than 10EU/ml and anti-PT level did not differ with time since last self-reported pertussis vaccination (χ(2)(2)=3.166, p=0.205). Among a 1996-1997 cohort of pregnant women in British Columbia, 51% had anti-PT levels less than 10EU/ml. Our study found that most pregnant women in two geographically disparate health regions in Canada have low residual anti-PT levels, may be vulnerable to pertussis infection themselves, and would unlikely be a source of passive ante- or postnatal transfer of anti-PT to their newborn.
    Vaccine 09/2014; 32(48). DOI:10.1016/j.vaccine.2014.09.028 · 3.49 Impact Factor
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    ABSTRACT: Rotavirus vaccine is recommended for all infants in Canada. To evaluate the logistics of implementing a universal rotavirus vaccination program, we compared the effectiveness of program implementation in jurisdictions with either a physician-administered or public health nurse-administered program. All infants born between October 1, 2010 and September 30, 2012 in Prince Edward Island and Nova Scotia’s Capital District Health Authority were eligible for the vaccination program. A universal rotavirus vaccination program was implemented and delivered in public health clinics in Prince Edward Island and in physicians’ offices in Nova Scotia. Engagement of vaccinators in delivery of the universal vaccination program was more successful in Prince Edward Island than in Nova Scotia. Vaccine coverage rates rose rapidly in Prince Edward Island, exceeding 90% for both doses within 3 months and remaining at those levels over the two-year program. In contrast, coverage rates in Nova Scotia rose more slowly and never exceeded 40% during the two years. Access to coverage data was more timely and accurate in Prince Edward Island than Nova Scotia. A universal rotavirus vaccination program delivered through public health clinics achieved more rapid and higher levels of coverage than a program administered through physicians’ offices. Trial registration NCT01273077.
    BMC Public Health 09/2014; 14(1):908. DOI:10.1186/1471-2458-14-908 · 2.32 Impact Factor
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    ABSTRACT: 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=0.0014). 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=0.0100) who were not vaccinated in all provinces. There was no impact on the incidence of non-serogroup C disease over the same period (p=0.9811). 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.
    Clinical Infectious Diseases 07/2014; 59(9). DOI:10.1093/cid/ciu597 · 9.42 Impact Factor
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    ABSTRACT: Background: Studies have identified certain neurologic and neurodevelopmental conditions (NNC) as risk factors for severe influenza infection. The Canadian National Advisory Committee on Immunization does not currently recognize children with NNC as having a high risk of complicated influenza infection unless their condition compromises handling of respiratory secretions. We describe the burden of influenza in hospitalized children with NNC, focusing on those without potential airway compromise. Methods: Using multi-year surveillance data obtained by the Canadian Immunization Monitoring Program, Active (IMPACT), we examined presenting signs and symptoms, risk factors and outcomes of children hospitalized with seasonal influenza at 12 Canadian pediatric referral centers. Comparisons were made between children with various NNC and other medical conditions, with and without influenza vaccine indications. The analysis is descriptive with selected comparisons made among groups for important indicators of disease severity. Results: We identified 1991 children hospitalized with influenza over 5 seasons: 293 had NNC, 115 of whom did not have airway compromise or another vaccine indication. The latter group presented with seizures more frequently than those with NNC and a vaccine indication (41.7% vs. 26.4%; P = 0.006) and required intensive care unit admission (20.9% vs. 11.8%; P = 0.02) and mechanical ventilation (14.8% vs. 4.5%; P < 0.001) more often than children without NNC but with a vaccine indication. Conclusions: The burden of influenza infection in children with NNC, even those whose conditions do not obviously compromise respiratory function, is significant. All children with NNC should be recognized as having a high risk of complicated influenza infection and be targeted to receive influenza immunization.
    The Pediatric Infectious Disease Journal 07/2014; 33(7):710-714. DOI:10.1097/INF.0000000000000272 · 3.14 Impact Factor
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    ABSTRACT: Regulatory B (Breg) cells are known to modulate immune responses through predominantly interleukin-10 (IL-10)-dependent mechanisms and can be hypothetically divided into innate and adaptive subsets based on the nature of their activating signals. However, the specific role of different Breg subsets in modulating immune responses remains ambiguous. Here we have shown that Chlamydia induces IL-10-producing splenic B-cell populations consisting of CD43(+) and CD43(-) subsets of IgM(hi)IgD(lo) innate-like B (ILB) cells in vitro. While CD43(+)IL-10-producing B cells displayed innate type features and were readily induced by Chlamydia via Toll-like-receptor (TLR) signaling, CD43(-)IL-10-producing B cells required additional B-cell activating factor (BAFF)-mediated signals from dendritic cells (DCs) for their differentiation and activation, thereby classifying them as adaptive type Bregs. Importantly, CD43(-), but not CD43(+), IL-10-producing ILB cells displayed bona fide Breg activity by potently suppressing interferon-γ (IFN-γ) production in vitro in an IL-10-dependent manner. Furthermore, a novel CD43(-)CD1d(hi)CD5(+) IL-10-producing Breg population was predominantly induced by Chlamydia genital infection in vivo. Correspondingly, mixed bone marrow chimeric mice with B-cell-specific IL-10 deficiency exhibited significantly increased type 1 immune responses, decreased bacterial burden, and reduced oviduct pathology upon infection. Our data demonstrate for the first time a distinct role for CD43(-)CD1d(hi)CD5(+)-adaptive Bregs over CD43(+) innate counterparts in controlling mucosal responses against intracellular bacterial infection.Mucosal Immunology advance online publication, 18 June 2014; doi:10.1038/mi.2014.45.
    Mucosal Immunology 06/2014; 8(1). DOI:10.1038/mi.2014.45 · 7.54 Impact Factor

Publication Stats

6k Citations
1,249.75 Total Impact Points


  • 1997–2015
    • IWK Health Centre
      Halifax, Nova Scotia, Canada
  • 1989–2015
    • Dalhousie University
      • • Canadian Center for Vaccinology
      • • Department of Pediatrics
      Halifax, Nova Scotia, Canada
  • 2009–2013
    • BC Children's Hospital
      Vancouver, British Columbia, Canada
    • University of Toronto
      Toronto, Ontario, Canada
    • The Ottawa Hospital
      Ottawa, Ontario, Canada
    • Stollery Children's Hospital
      Edmonton, Alberta, Canada
  • 2011
    • Crucell
      Leyden, South Holland, Netherlands
  • 2008
    • University of Oxford
      • Department of Paediatrics
      Oxford, ENG, United Kingdom
  • 2004
    • University of Ottawa
      • Department of Pediatrics
      Ottawa, Ontario, Canada
  • 2003
    • SickKids
      Toronto, Ontario, Canada
    • St. Paul's Hospital
      Saskatoon, Saskatchewan, Canada
  • 2000
    • Laval University
      Quebec City, Quebec, Canada
    • University of British Columbia - Vancouver
      Vancouver, British Columbia, Canada
    • University of Manitoba
      Winnipeg, Manitoba, Canada
    • Children's Hospital of Eastern Ontario
      Ottawa, Ontario, Canada
  • 1996
    • Health Canada
      Ottawa, Ontario, Canada
  • 1992
    • Nova Scotia Museum
      Halifax, Nova Scotia, Canada