Publications by authors named "Scott A Halperin"

225 Publications

Health Outcomes in Young Children Following Pertussis Vaccination During Pregnancy.

Pediatrics 2021 May 19;147(5). Epub 2021 Apr 19.

University of Ottawa, Ottawa, Ontario, Canada;

Background And Objectives: Maternal immunization with tetanus, diphtheria, and acellular pertussis vaccine (Tdap) is routinely recommended in many countries as a strategy to protect young infants against severe pertussis infection; few studies have assessed whether prenatal exposure to the vaccine is associated with any longer-term adverse health effects in children. We evaluated the long-term safety of exposure to Tdap vaccination during pregnancy.

Methods: Population-based retrospective cohort study conducted in Ontario, Canada using multiple linked province-wide health administrative databases. All live births between April 2012 and March 2017 were included, and children were followed for up to 6 years to ascertain study outcomes. Children exposed to prenatal Tdap were propensity score matched to unexposed children at a 1:5 ratio. Tdap vaccination during pregnancy was ascertained by using vaccine-specific fee codes. Immune-related (infectious diseases, asthma) and nonimmune-related (neoplasm, sensory disorders) outcomes and a nonspecific morbidity outcome (urgent or inpatient health service use) were evaluated from birth to end of follow-up.

Results: Of 625 643 live births, 12 045 (1.9%) were exposed to Tdap in utero. There were no significant increased risks of adverse childhood outcomes and prenatal Tdap exposure; however, we observed inverse associations (adjusted incidence rate ratio [95% confidence interval]) with upper respiratory infections (0.94 [0.90-0.99]), gastrointestinal infections (0.85 [0.79-0.91]), and urgent and inpatient health service use (0.93 [0.91-0.96]).

Conclusions: Exposure to Tdap vaccination in pregnancy was not associated with any increased risk of adverse health outcomes in early childhood, supporting the long-term safety of Tdap administration in pregnancy.
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http://dx.doi.org/10.1542/peds.2020-042507DOI Listing
May 2021

Obstetric and perinatal health outcomes after pertussis vaccination during pregnancy in Ontario, Canada: a retrospective cohort study.

CMAJ Open 2021 Apr-Jun;9(2):E349. Epub 2021 Apr 13.

Children's Hospital of Eastern Ontario Research Institute (Fakhraei, Sucha, Fell); Ottawa Hospital Research Institute (Fakhraei, Hawken, Wilson, Walker), Ottawa, Ont.; ICES Central (Crowcroft, Hawken, Kwong, Fell); University of Toronto (Crowcroft, Bolotin, Biringer, Dubey, Jamieson, Kwong); Public Health Ontario (Bolotin, Jamieson, Kwong), Toronto, Ont.; ICES uOttawa (Sucha); University of Ottawa (Hawken, Cook, Walker, Laverty, Fell); Bruyère Research Institute (Wilson), Ottawa, Ont.; Kingston Health Sciences Centre (Gaudet); Queen's University (Gaudet), Kingston, Ont.; Public Health England (Amirthalingam), London, UK; Mount Sinai Hospital (Biringer), Toronto, Ont.; Society of Obstetricians and Gynaecologists of Canada (Cook), Ottawa, Ont.; Toronto Public Health (Dubey), Toronto, Ont.; Canadian Centre for Vaccinology (Halperin), Dalhousie University and IWK Health Centre, Halifax, NS; Vaccine Evaluation Center (Sadarangani), BC Children's Hospital Research Institute; Department of Pediatrics (Sadarangani), University of British Columbia, Vancouver, BC

Background: In February 2018, Canada's National Advisory Committee on Immunization recommended maternal vaccination with tetanus-diphtheria-acellular pertussis (Tdap) vaccine during pregnancy to prevent severe pertussis infection in young infants. This study assessed the relation between maternal Tdap vaccination and obstetric and perinatal outcomes in Ontario.

Methods: We performed a population-based cohort study of all births from April 2012 to March 2017 using multiple linked health administrative databases. We used Cox regression with a time-dependent exposure variable to estimate adjusted hazard ratios (HRs) for preterm birth (< 37 wk), very preterm birth (< 32 wk) and stillbirth. We assessed remaining outcomes (gestational hypertension, chorioamnionitis, postpartum hemorrhage, severe postpartum hemorrhage, being small for gestational age, neonatal intensive care unit stay > 24 h, composite neonatal morbidity) using log-binomial regression to generate adjusted risk ratios (RRs). We adjusted estimates for potential confounding using propensity score weighting.

Results: Of 615 213 infants (live births and stillbirths), 11 519 were exposed to Tdap vaccination in utero. There was no increased risk for preterm birth (adjusted HR 0.98, 95% confidence interval [CI] 0.91-1.06), very preterm birth (adjusted HR 1.10, 95% CI 0.86-1.41), stillbirth (adjusted HR 1.15, 95% CI 0.82-1.60) or being small for gestational age (adjusted RR 0.96, 95% CI 0.90-1.02). The risks of a neonatal intensive care unit stay exceeding 24 hours (adjusted RR 0.82, 95% CI 0.76-0.88) and neonatal morbidity (adjusted RR 0.81, 95% CI 0.75-0.87) were decreased. There was no association with chorioamnionitis (adjusted RR 1.17, 95% CI 0.99-1.39), postpartum hemorrhage (adjusted RR 1.01, 95% CI 0.91-1.13) or severe postpartum hemorrhage (adjusted RR 0.79, 95% CI 0.55-1.13), but we observed a reduced risk of gestational hypertension (adjusted RR 0.87, 95% CI 0.78-0.96).

Interpretation: Our results complement evidence that maternal Tdap vaccination is not associated with adverse outcomes in mothers or infants. Ongoing evaluation in Canada is needed as maternal Tdap vaccination coverage increases in coming years.
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http://dx.doi.org/10.9778/cmajo.20200239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084546PMC
April 2021

Impact of maternal diphtheria-tetanus-acellular pertussis vaccination on pertussis booster immune responses in toddlers: Follow-up of a randomized trial.

Vaccine 2021 03 19;39(11):1598-1608. Epub 2021 Feb 19.

GSK, Vaccines, 1300 Wavre, Belgium.

Background: Transplacentally transferred antibodies induced by maternal pertussis vaccination interfere with infant immune responses to pertussis primary vaccination. We evaluated whether this interference remains in toddlers after booster vaccination.

Methods: In a prior phase IV, observer-blind, placebo-controlled, randomized study (NCT02377349), pregnant women in Australia, Canada and Europe received intramuscular tetanus-reduced-antigen-content diphtheria-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) at 27-36 weeks' gestation, with crossover immunization postpartum. Their infants were primed (study NCT02422264) and boosted (at 11-18 months; current study NCT02853929) with diphtheria-tetanus-three-component acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenzae type b vaccine (DTaP-HepB-IPV/Hib) and 13-valent pneumococcal conjugate vaccine. Immunogenicity before and after booster vaccination, and reactogenicity and safety of the booster were evaluated descriptively.

Results: 263 (Tdap group) and 277 (control group) toddlers received a DTaP-HepB-IPV/Hib booster. Pre-booster vaccination, observed geometric mean concentrations (GMCs) for the three pertussis antigens and diphtheria were 1.4-1.5-fold higher in controls than in the Tdap group. No differences were observed for the other DTaP-HepB-IPV/Hib antigens. One month post-booster vaccination, booster response rates for pertussis antigens were ≥ 92.1% and seroprotection rates for the other DTaP-HepB-IPV/Hib antigens were ≥ 99.2% in both groups (primary objective). Higher post-booster GMCs were observed in controls versus the Tdap group for anti-filamentous hemagglutinin (1.2-fold), anti-pertussis toxoid (1.5-fold) and anti-diphtheria (1.4-fold). GMCs for the other DTaP-HepB-IPV/Hib antigens were similar between groups. Serious adverse events were reported for three toddlers (controls, not vaccination-related). One death occurred pre-booster (Tdap group, not vaccination-related).

Conclusions: As a consequence of interference of maternal pertussis antibodies with infant immune responses to pertussis primary vaccination, pertussis antibody concentrations were still lower in toddlers from Tdap-vaccinated mothers before DTaP-HepB-IPV/Hib booster vaccination. After the booster, antibody concentrations were lower for filamentous hemagglutinin and pertussis toxoid but not for pertactin. The clinical significance of this interference requires further evaluation.

Clinical Trial Registration: ClinicalTrials.gov: NCT02853929.
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http://dx.doi.org/10.1016/j.vaccine.2021.02.001DOI Listing
March 2021

Pertussis vaccination in pregnancy in Canada: a cost-utility analysis.

CMAJ Open 2020 Oct-Dec;8(4):E651-E658. Epub 2020 Oct 19.

Vaccine Evaluation Center (Abu-Raya, Bettinger, Sadarangani), BC Children's Hospital Research Institute; Division of Infectious Diseases (Abu-Raya, Bettinger, Sadarangani), Department of Pediatrics, University of British Columbia, Vancouver, BC; School of Epidemiology and Public Health (Coyle), University of Ottawa, Ottawa, Ont.; Stollery Children's Hospital (Vaudry), Women and Children's Health Research Institute, University of Alberta, Edmonton, Alta.; Canadian Center for Vaccinology (Halperin), IWK Health Centre and Dalhousie University, Halifax, NS

Background: The Canadian National Advisory Committee on Immunization recommends universal vaccination against pertussis in pregnancy. We assessed the cost-effectiveness of vaccination with tetanus-diphtheria-acellular pertussis (Tdap) vaccine in pregnancy in Canada.

Methods: We conducted a cost-utility analysis comparing a vaccination program to no program corresponding with the 2017 Canadian guideline for economic evaluation from the Canadian Agency for Drugs and Technologies in Health. We developed 2 models - part decision tree, part Markov model - to estimate the long-term cost and quality-adjusted life-years (QALYs) for pregnant women and their infants. We obtained epidemiologic data from 2006 to 2015, and derived costs and utility values from relevant sources. Results were reported in 2019 Canadian dollars. We obtained expected values through probabilistic analysis, with methodologic and structural uncertainty assessed through scenario analyses. The analysis adopted an acquisition price of Tdap vaccine of $12.50, with scenario analysis conducted to identify the threshold price for vaccination to be cost-effective.

Results: In the base-case scenario, for every 1000 pregnant women vaccinated, the program would lead to a gain of 0.3 QALYs, occurring solely in infants, at an increased total cost of $12 987, or $44 301 per QALY gained. Based on a threshold of $50 000 per QALY gained, vaccination would have been cost-effective in 6 of the 10 years included in the model (range of incremental costs $20 463-$100 348 per QALY gained). The threshold cost for Tdap vaccine to be cost-effective over the 10-year horizon was $14.03.

Interpretation: Based on a threshold of $50 000 per QALY gained, vaccination against pertussis in pregnancy would be cost-effective if the acquisition cost per vaccine were $14.03 or less. Province- and territory-specific analyses should be done to inform local decision-making.
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http://dx.doi.org/10.9778/cmajo.20200060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588263PMC
May 2021

Active surveillance of acute paediatric hospitalisations demonstrates the impact of vaccination programmes and informs vaccine policy in Canada and Australia.

Euro Surveill 2020 06;25(25)

The IMPACT and PAEDS investigators are acknowledged at the end of this article.

Sentinel surveillance of acute hospitalisations in response to infectious disease emergencies such as the 2009 influenza A(H1N1)pdm09 pandemic is well described, but recognition of its potential to supplement routine public health surveillance and provide scalability for emergency responses has been limited. We summarise the achievements of two national paediatric hospital surveillance networks relevant to vaccine programmes and emerging infectious diseases in Canada (Canadian Immunization Monitoring Program Active; IMPACT from 1991) and Australia (Paediatric Active Enhanced Disease Surveillance; PAEDS from 2007) and discuss opportunities and challenges in applying their model to other contexts. Both networks were established to enhance capacity to measure vaccine preventable disease burden, vaccine programme impact, and safety, with their scope occasionally being increased with emerging infectious diseases' surveillance. Their active surveillance has increased data accuracy and utility for syndromic conditions (e.g. encephalitis), pathogen-specific diseases (e.g. pertussis, rotavirus, influenza), and adverse events following immunisation (e.g. febrile seizure), enabled correlation of biological specimens with clinical context and supported responses to emerging infections (e.g. pandemic influenza, parechovirus, COVID-19). The demonstrated long-term value of continuous, rather than incident-related, operation of these networks in strengthening routine surveillance, bridging research gaps, and providing scalable public health response, supports their applicability to other countries.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.25.1900562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331140PMC
June 2020

Assessing the completeness of infant and childhood immunizations within a provincial registry populated by parental reporting: A study using linked databases in Ontario, Canada.

Vaccine 2020 07 20;38(33):5223-5230. Epub 2020 Jun 20.

Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada; Toronto Western Family Health Team, University Health Network, Toronto, Ontario, Canada; North York General Hospital, Toronto, Ontario, Canada.

Introduction: In Ontario, Canada, parents have the responsibility to report their child's routine infant and childhood vaccines to the provincial immunization registry (the Digital Health Immunization Repository; DHIR) without healthcare provider validation. Despite its use in routine immunization coverage monitoring, no study has previously examined the completeness of immunization data within the DHIR.

Methods: We assessed the completeness of DHIR immunizations, as compared to immunizations within the Electronic Medical Records-Primary Care (EMRPC) database, also known as EMRALD, a network of family physician electronic medical records (EMRs). We linked client records from the DHIR and EMRPC to a centralized population file. To create the study cohort, we examined children born during 2005-2008 and further defined the cohort based on those rostered to an EMRPC physician, visit criteria to ensure ongoing care by an EMRPC provider, and school attendance in Ontario at age 7. We calculated up-to-date (UTD) immunization coverage at age 7 for individual vaccines and overall using data from the DHIR and EMRPC separately, and compared the estimates.

Results: The analytic cohort to assess DHIR data completeness included 2,657 children. Overall UTD coverage (all vaccines assessed) was 82.0% in the DHIR and 67.6% in EMRPC. UTD coverage was higher in the DHIR for all vaccines assessed individually, with the exception of meningococcal C conjugate vaccine (difference = 0.3%). After excluding two EMRPC sites with irregularities in immunization data, the difference in overall UTD coverage between systems decreased from 14.4% to 6.6% INTERPRETATION: These results validate the use of DHIR for coverage assessment but also suggest that bidirectional exchange of immunization information has the potential to increase immunization data completeness in both systems.
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http://dx.doi.org/10.1016/j.vaccine.2020.06.003DOI Listing
July 2020

Review of pediatric encephalitis and encephalopathy cases following immunization reported to the Canadian Immunization Monitoring Program Active (IMPACT) from 1992 to 2012.

Vaccine 2020 06 12;38(28):4457-4463. Epub 2020 May 12.

Department of Pediatrics, Dalhousie University and Canadian Center for Vaccinology, IWK Health Centre, Halifax, NS, Canada. Electronic address:

Background: Neurological adverse events following immunization (AEFI) remain poorly characterized. Our objective was to describe pediatric acute and chronic encephalopathy and encephalitis cases following immunization reported via active sentinel surveillance from 1992 to 2012.

Methods: This case series provides a descriptive analysis of encephalopathy/encephalitis admissions reported to the Canadian Immunization Monitoring Program ACTive (IMPACT). Acute cases were reported if symptom onset (seizures, decreased level of consciousness, change in mental status) occurred 0-7 days after tetanus or pertussis-containing vaccines, 0-15 days after other inactivated vaccines, or 5-30 days after live vaccines. Chronic cases of subacute sclerosing panencephalitis or subacute progressive rubella encephalitis were reported at any interval after vaccination. Clinical data were examined to identify possible causes for encephalopathy/encephalitis other than vaccination.

Results: Sixty-one cases of encephalopathy/encephalitis following immunization were reported to IMPACT over 21 years; 57 (93.4%) were classified as acute and 4 (6.6%) were chronic cases of subacute sclerosing panencephalitis. Most patients (73.8%) were previously healthy and immunocompetent. The vaccines most frequently administered prior to presentation were diphtheria-tetanus-pertussis, measles-mumps-rubella, and influenza. At discharge, 38 patients (62.3%) had normal neurological status or were expected to recover. Forty patients (70.2%) with acute encephalopathy/encephalitis had a more likely alternate etiology besides vaccination based on neuroimaging, symptoms suggestive of infection, laboratory-confirmed non-vaccine-related infection, or clinical diagnosis. No cases of encephalitis were causally associated with pertussis or influenza vaccines. Two patients (50%) with subacute sclerosing panencephalitis had known wild-type measles infection prior to immunization. Three deaths were reported during hospitalization (4.9%); all were acute encephalitis/encephalopathy cases and none were confirmed to be vaccine-related.

Conclusions: Encephalopathy/encephalitis following immunization remains a rare but serious adverse event. Most cases had another more likely etiology than vaccination. Continued monitoring and analysis of AEFI is paramount to ensure the safety of immunization programs.
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http://dx.doi.org/10.1016/j.vaccine.2020.04.035DOI Listing
June 2020

Vaccination during pregnancy: Canadian maternity care providers' opinions and practices.

Hum Vaccin Immunother 2020 11 9;16(11):2789-2799. Epub 2020 Apr 9.

Society of Obstetricians and Gynaecologists of Canada , Ottawa, Canada.

A number of countries have implemented vaccination in pregnancy as a strategy to reduce the burden of influenza and pertussis. The aim of this study was to assess the involvement of Canadian maternity care providers in administration of vaccines to their pregnant patients. A cross-sectional web-based survey was sent to family physicians, obstetricians-gynecologists, midwives, pharmacists, and nurses. A multivariable logistic regression model was used to determine variables independently associated with offering vaccination services in pregnancy in providers' practice. A total of 1,135 participants participated. Overall, 64% (n = 724) of the participants reported offering vaccines in their practice and 56% (n = 632) reported offering vaccines to pregnant patients. The main reasons reported for not offering vaccination services in pregnancy were the belief that vaccination was outside of the scope of practice; logistical issues around access to vaccines; or lack of staff to administer vaccines. In multivariable analysis, the main factors associated with vaccination of pregnant patients in practices where vaccination services were offered were: providers' confidence in counseling pregnant patients about vaccines, seeing fewer than 11 pregnant patients on average each week, and being a nurse or a family physician. Although the majority of participants expressed strong support for vaccination during pregnancy, half were not offering vaccination services in their practice. Many were not equipped to offer vaccines in their practice or felt that it was not their role to do so. To enhance vaccine acceptance and uptake in pregnancy, it will be important to address the logistical barriers identified in this study.
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http://dx.doi.org/10.1080/21645515.2020.1735225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733901PMC
November 2020

Implementation Effectiveness of a Parent-Directed YouTube Video ("It Doesn't Have To Hurt") on Evidence-Based Strategies to Manage Needle Pain: Descriptive Survey Study.

JMIR Pediatr Parent 2020 Mar 4;3(1):e13552. Epub 2020 Mar 4.

Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.

Background: Despite the availability of high-quality evidence and clinical practice guidelines for the effective management of pediatric pain, this evidence is rarely used in practice for managing children's pain from needle procedures such as vaccinations. Parents are generally unaware of pain management strategies they can use with their children.

Objective: This study aimed to develop, implement, and evaluate the implementation effectiveness of a parent-directed YouTube video on evidence-based strategies to manage needle pain in children.

Methods: This was a descriptive study. Analytics were extracted from YouTube to describe video reach. A Web-based survey was used to seek parent and health care professional (HCP) feedback about the video. The 2-minute 18-second video was launched on YouTube on November 4, 2013. In the video, a 4-year-old girl tells parents what they should and should not do to help needles hurt less. The key evidence-based messages shared in the video were distraction, deep breathing, and topical anesthetic creams. A group of parents (n=163) and HCPs (n=278) completed the Web-based survey. Measures of reach included number of unique views, country where the video was viewed, sex of the viewer, and length of watch time. The Web-based survey assessed implementation outcomes of the video, such as acceptability, appropriateness, penetration, and adoption.

Results: As of November 4, 2018 (5 years after launch), the video had 237,132 unique views from 182 countries, with most viewers watching an average of 55.1% (76/138 seconds) of the video. Overall, both parents and HCPs reported strong acceptance of the video (ie, they liked the video, found it helpful, and felt more confident) and reported significant improvements in plans to use distraction, deep breathing, and topical anesthetic creams.

Conclusions: This parent-directed YouTube video was an acceptable and appropriate way to disseminate evidence about the procedure of pain management to a large number of parents.
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http://dx.doi.org/10.2196/13552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081136PMC
March 2020

Randomized Trial of 2 Schedules of Meningococcal B Vaccine in Adolescents and Young Adults, Canada.

Emerg Infect Dis 2020 03;26(3):454-462

Emergency vaccination programs often are needed to control outbreaks of meningococcal disease caused by Neisseria meningitidis serogroup B (MenB) on college campuses. Such campaigns expend multiple campus and public health resources. We conducted a randomized, controlled, multicenter, observer-blinded trial comparing immunogenicity and tolerability of an accelerated vaccine schedule of 0 and 21 days to a longer interval of 0 and 60 days for 4-component MenB vaccine (MenB-4C) in students 17-25 years of age. At day 21 after the first MenB-4C dose, we observed protective human serum bactericidal titers >4 to MenB strains 5/99, H44/76, and NZ 98/254 in 98%-100% of participants. Geometric mean titers increased >22-fold over baseline. At day 180, >95% of participants sustained protective titers regardless of their vaccine schedule. The most common adverse event was injection site pain. An accelerated MenB-4C immunization schedule could be considered for rapid control of campus outbreaks.
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http://dx.doi.org/10.3201/eid2603.190160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045834PMC
March 2020

Waning Vaccine Immunity and Vaccination Responses in Children Treated for Acute Lymphoblastic Leukemia: A Canadian Immunization Research Network Study.

Clin Infect Dis 2020 12;71(9):e439-e448

Departments of Pediatrics and Microbiology & Immunology and the Canadian Center for Vaccinology, Dalhousie University, and the IWK Health Centre, Halifax, Nova Scotia, Canada.

Background: There is no uniform guideline for postchemotherapy vaccination of children with acute lymphoblastic leukemia (ALL). We evaluated waning immunity to 14 pneumococcal serotypes, pertussis toxin (PT), tetanus toxoid (TT) and varicella, and immunogenicity of postchemotherapy diphtheria, tetanus, pertussis, hepatitis B, polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) and pneumococcal vaccination among previously vaccinated children treated for ALL.

Methods: This was a multicenter trial of children with ALL enrolled 4-12 months postchemotherapy completion. Exclusion criteria included: infant ALL, relapsed ALL, and stem cell transplant recipients. Immunocompetent children were recruited as controls. Postchemotherapy participants received DTaP-IPV-Hib and 13-valent pneumococcal conjugate vaccine (PCV13) concurrently, followed by 23-valent pneumococcal polysaccharide vaccine (PPV23) 2 months later. Serology was measured at baseline, 2 and 12 months postvaccination. Adverse events were captured via surveys.

Results: At enrollment, postchemotherapy participants (n = 74) were less likely than controls (n = 78) to be age-appropriately immunized with DTaP (41% vs 89%, P < .001) and PCV (59% vs 79%, P = .008). Geometric mean concentrations (GMCs) to TT, PT, PCV serotypes, and varicella were lower in postchemotherapy participants than controls after adjusting for previous vaccine doses (P < .001). Two months postvaccination, GMCs to TT, PT, and PCV serotypes increased from baseline (P < .001 for all antigens) and remained elevated at 12 months postvaccination. Antibody levels to PPV23 serotypes also increased postvaccination (P < .001). No serious adverse events were reported.

Conclusions: Children treated for ALL had lower antibody levels than controls against pneumococcal serotypes, tetanus, pertussis, and varicella despite previous vaccination. Postchemotherapy vaccination with DTaP-IPV-Hib, PCV13, and PPV23 was immunogenic and well tolerated. Children with ALL would benefit from systematic revaccination postchemotherapy.

Clinical Trials Registration: NCT02447718.
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http://dx.doi.org/10.1093/cid/ciaa163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713683PMC
December 2020

Estimated susceptibility of Canadian meningococcal B isolates to a meningococcal serogroup B vaccine (MenB-FHbp).

Vaccine 2020 02 23;38(8):2026-2033. Epub 2020 Jan 23.

National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg R3E3R2, Canada.

Background: Invasive meningococcal disease caused by Neisseria meningitidis serogroup B (MenB) remains a health risk in Canada and globally. Two MenB vaccines are now approved for use. An understanding of the genotype of Canadian strains and the potential strain coverage conferred by the MenB-FHbp vaccine is needed to inform immunization policies.

Methods: Serogroup B Neisseria meningitidis strains responsible for meningococcal disease in Canada from 2006 to 2012 were collected as part of the Canadian Immunization Monitoring Program Active surveillance network. Genotypic analysis was done on MenB isolates from 2006 to 2012 with determination of fHbp surface expression for a subset of isolates: those occurring from 2010 to 2012.

Results: Two clonal complexes (cc269 and cc41/44) were observed in 68.8% of the 276 isolates. A total of 50 different fHbp peptides were identified among isolates from 2006 to 2012. Surface expression of fHbp was detected on 95% of MenB isolates from 2010 to 2012 and 91% of isolates expressed fHbp at levels that are predicted to be susceptible to the bactericidal immune response elicited by the MenB-FHbp vaccine. Some regional differences were observed, particularly in isolates from British Columbia and Quebec.

Conclusion: The majority of MenB isolates responsible for meningococcal disease in Canada expressed fHbp at levels predicted to be sufficient for complement mediated bactericidal activity in the presence of MenB-FHbp induced serum antibodies.
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http://dx.doi.org/10.1016/j.vaccine.2019.12.051DOI Listing
February 2020

Immunogenicity, transplacental transfer of pertussis antibodies and safety following pertussis immunization during pregnancy: Evidence from a randomized, placebo-controlled trial.

Vaccine 2020 02 24;38(8):2095-2104. Epub 2019 Nov 24.

GSK, Wavre, Belgium. Electronic address:

Background: Pertussis immunization during pregnancy is recommended in many countries. Data from large randomized controlled trials are needed to assess the immunogenicity, reactogenicity and safety of this approach.

Methods: This phase IV, observer-blind, randomized, placebo-controlled, multicenter trial assessed immunogenicity, transplacental transfer of maternal pertussis antibodies, reactogenicity and safety of a reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap) during pregnancy. Women received Tdap or placebo at 27-36 weeks' gestation with crossover ≤ 72-hour-postpartum immunization. Immune responses were assessed before the pregnancy dose and 1 month after, and from the umbilical cord at delivery. Superiority (primary objective) was reached if the lower limits of the 95% confidence intervals (CIs) of the pertussis geometric mean concentration (GMC) ratios (Tdap/control) in cord blood were ≥ 1.5. Solicited and unsolicited adverse events (AEs) and pregnancy-/neonate-related AEs of interest were recorded.

Results: 687 pregnant women were vaccinated (Tdap: N = 341 control: N = 346). Superiority of the pertussis immune response (maternally transferred pertussis antibodies in cord blood) was demonstrated by the GMC ratios (Tdap/control): 16.1 (95% CI: 13.5-19.2) for anti-filamentous hemagglutinin, 20.7 (15.9-26.9) for anti-pertactin and 8.5 (7.0-10.2) for anti-pertussis toxoid. Rates of pregnancy-/neonate-related AEs of interest, solicited general and unsolicited AEs were similar between groups. None of the serious AEs reported throughout the study were considered related to maternal Tdap vaccination.

Conclusions: Tdap vaccination during pregnancy resulted in high levels of pertussis antibodies in cord blood, was well tolerated and had an acceptable safety profile. This supports the recommendation of Tdap vaccination during pregnancy to prevent early-infant pertussis disease.

Clinical Trial Registration: ClinicalTrials.gov: NCT02377349.
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http://dx.doi.org/10.1016/j.vaccine.2019.10.105DOI Listing
February 2020

Impact of tetanus-diphtheria-acellular pertussis immunization during pregnancy on subsequent infant immunization seroresponses: follow-up from a large randomized placebo-controlled trial.

Vaccine 2020 02 24;38(8):2105-2114. Epub 2019 Nov 24.

GSK, Wavre, Belgium. Electronic address:

Background: Pertussis immunization during pregnancy results in high pertussis antibody concentrations in young infants but may interfere with infant immune responses to post-natal immunization.

Methods: This phase IV, multi-country, open-label study assessed the immunogenicity and safety of infant primary vaccination with DTaP-HepB-IPV/Hib and 13-valent pneumococcal conjugate vaccine (PCV13). Enrolled infants (6-14 weeks old) were born to mothers who were randomized to receive reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) during pregnancy (27-36 weeks' gestation) with crossover immunization postpartum. All infants received 2 or 3 DTaP-HepB-IPV/Hib and PCV13 doses according to national schedules. Immunogenicity was assessed in infants pre- and 1 month post-primary vaccination. The primary objective was to assess seroprotection/vaccine response rates for DTaP-HepB-IPV/Hib antigens 1 month post-primary vaccination.

Results: 601 infants (Tdap group: 296; control group: 305) were vaccinated. One month post-priming, seroprotection rates were 100% (diphtheria; tetanus), ≥98.5% (hepatitis B), ≥95.9% (polio) and ≥94.5% (Hib) in both groups. Vaccine response rates for pertussis antigens were significantly lower in infants whose mothers received pregnancy Tdap (37.5-77.1%) versus placebo (90.0-99.2%). Solicited and unsolicited adverse event rates were similar between groups. Serious adverse events occurred in 2.4% (Tdap group) and 5.6% (control group) of infants, none were vaccination-related.

Conclusions: Pertussis antibodies transferred during pregnancy may decrease the risk of pertussis infection in the first months of life but interfere with the infant's ability to produce pertussis antibodies, the clinical significance of which remains unknown. Safety and reactogenicity results were consistent with previous experience.

Clinical Trial Registration: ClinicalTrials.gov: NCT02422264.
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http://dx.doi.org/10.1016/j.vaccine.2019.10.104DOI Listing
February 2020

Immunogenicity, Lot Consistency, and Extended Safety of rVSVΔG-ZEBOV-GP Vaccine: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study in Healthy Adults.

J Infect Dis 2019 08;220(7):1127-1135

Merck & Co., Inc., Kenilworth, New Jersey.

Background: This double-blind study assessed immunogenicity, lot consistency, and safety of recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSVΔG-ZEBOV-GP).

Methods: Healthy adults (N = 1197) were randomized 2:2:2:2:1 to receive 1 of 3 consistency lots of rVSVΔG-ZEBOV-GP (2 × 107 plaque-forming units [pfu]), high-dose 1 × 108 pfu, or placebo. Antibody responses pre-/postvaccination (28 days, 6 months; in a subset [n = 566], months 12, 18, and 24) were measured. post hoc analysis of risk factors associated with arthritis following vaccination was performed.

Results: ZEBOV-GP enzyme-linked immunosorbent assay (ELISA) geometric mean titers (GMTs) increased postvaccination in all rVSVΔG-ZEBOV-GP groups by 28 days (>58-fold) and persisted through 24 months. The 3 manufacturing lots demonstrated equivalent immunogenicity at 28 days. Neutralizing antibody GMTs increased by 28 days in all rVSVΔG-ZEBOV-GP groups, peaking at 18 months with no decrease through 24 months. At 28 days, ≥94% of vaccine recipients seroresponded (ZEBOV-GP ELISA, ≥2-fold increase, titer ≥200 EU/mL), with responses persisting at 24 months in ≥91%. Female sex and a history of arthritis were identified as potential risk factors for the development of arthritis postvaccination.

Conclusions: Immune responses to rVSVΔG-ZEBOV-GP persisted to 24 months. Immunogenicity and safety results support continued rVSVΔG-ZEBOV-GP development.

Clinical Trials Registration: NCT02503202.
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http://dx.doi.org/10.1093/infdis/jiz241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812306PMC
August 2019

Assessment of population immunity to measles in Ontario, Canada: a Canadian Immunization Research Network (CIRN) study.

Hum Vaccin Immunother 2019 16;15(12):2856-2864. Epub 2019 Jul 16.

Public Health Ontario, Toronto, ON, Canada.

Canada eliminated measles in 1998. We conducted a sero-epidemiology study to estimate population immunity to measles in the province of Ontario, Canada and to identify groups at higher risk of outbreaks. We used a previously developed modified enzyme immunoassay to test 1,199 residual sera from patients aged 1-39 years. We re-tested negative and equivocal sera using a plaque reduction neutralization assay. We interpreted our results in the context of Ontario's immunization program and vaccine coverage data. Of 1,199 sera, 1035 (86.3%, 95% confidence interval (CI) 84.4, 88.2) were above the measles threshold for protection, 70 (5.8%, 95% CI 4.5, 7.2) were equivocal and 94 (7.8%, 95% CI 6.3, 9.4) were negative. The proportion of positive sera was highest for those 1-5 years, with 180/199 (90.5%, 95% CI 86.4, 94.5) positive sera, and lowest for those age 12-19 years, at 158/199 (79.4%, 95% CI 73.8, 85.0). Adjusted for age, females were more likely than males to have antibody titers above the threshold of protection (odds ratio = 1.60, 95% CI 1.14, 2.24). Most of the study cohort were eligible for two measles vaccine doses, and vaccine uptake in Ontario is >90% for school-aged cohorts. We observed a higher than expected proportion of sera with antibody levels below the threshold of protection, suggesting that immunity in some Ontario age-groups may be waning, despite high vaccine coverage. Alternatively, the traditional measles correlates of protection may not be an appropriate measure of population protection in measles-eliminated settings.
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http://dx.doi.org/10.1080/21645515.2019.1619402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930091PMC
May 2020

Identification of Redox Partners of the Thiol-Disulfide Oxidoreductase SdbA in Streptococcus gordonii.

J Bacteriol 2019 05 24;201(10). Epub 2019 Apr 24.

Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada

We previously identified a novel thiol-disulfide oxidoreductase, SdbA, in that formed disulfide bonds in substrate proteins and played a role in multiple phenotypes. In this study, we used mutational, phenotypic, and biochemical approaches to identify and characterize the redox partners of SdbA. Unexpectedly, the results showed that SdbA has multiple redox partners, forming a complex oxidative protein-folding pathway. The primary redox partners of SdbA that maintain its active site in an oxidized state are a surface-exposed thioredoxin family lipoprotein called SdbB (Sgo_1171) and an integral membrane protein annotated as CcdA2. Inactivation of and simultaneously, but not individually, recapitulated the mutant phenotype. The mutant had defects in a range of cellular processes, including autolysis, bacteriocin production, genetic competence, and extracellular DNA (eDNA) release. AtlS, the natural substrate of SdbA produced by the mutant lacked activity and an intramolecular disulfide bond. The redox state of SdbA in the mutant was found to be in a reduced form and was restored when and were knocked back into the mutant. In addition, we showed that SdbB formed a disulfide-linked complex with SdbA in the cell. Recombinant SdbB and CcdA2 exhibited oxidase activity and reoxidized reduced SdbA Collectively, our results demonstrate that uses multiple redox partners for oxidative protein folding. is a commensal bacterium of the human dental plaque. Previously, we identified an enzyme, SdbA, that forms disulfide bonds in substrate proteins and plays a role in a number of cellular processes in Here, we identified the redox partners of SdbA. We showed that SdbA has multiple redox partners, SdbB and CcdA2, forming a complex oxidative protein-folding pathway. This pathway is essential for autolysis, bacteriocin production, genetic competence, and extracellular DNA (eDNA) release in These cellular processes are considered to be important for the success of as a dental plaque organism. This is the first example of an oxidative protein-folding pathway in Gram-positive bacteria that consists of an enzyme that uses multiple redox partners to function.
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http://dx.doi.org/10.1128/JB.00030-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482928PMC
May 2019

Effectiveness of Influenza Vaccination on Hospitalizations and Risk Factors for Severe Outcomes in Hospitalized Patients With COPD.

Chest 2019 01;155(1):69-78

Centre Hospitalier Universitaire de Québec, Quebec, QC, Canada.

Background: The effectiveness of influenza vaccination in reducing influenza-related hospitalizations among patients with COPD is not well described, and influenza vaccination uptake remains suboptimal.

Methods: Data were analyzed from a national, prospective, multicenter cohort study including patients with COPD, hospitalized with any acute respiratory illness or exacerbation between 2011 and 2015. All patients underwent nasopharyngeal swab screening with polymerase chain reaction (PCR) testing for influenza. The primary outcome was an influenza-related hospitalization. We identified influenza-positive cases and negative control subjects and used multivariable logistic regression with a standard test-negative design to estimate the vaccine effectiveness for preventing influenza-related hospitalizations.

Results: Among 4,755 hospitalized patients with COPD, 4,198 (88.3%) patients with known vaccination status were analyzed. The adjusted analysis showed a 38% reduction in influenza-related hospitalizations in vaccinated vs unvaccinated individuals. Influenza-positive patients (n = 1,833 [38.5%]) experienced higher crude mortality (9.7% vs 7.9%; P = .047) and critical illness (17.2% vs 12.1%; P < .001) compared with influenza-negative patients. Risk factors for mortality in influenza-positive patients included age > 75 years (OR, 3.7 [95% CI, 0.4-30.3]), cardiac comorbidity (OR, 2.0 [95% CI, 1.3-3.2]), residence in long-term care (OR, 2.6 [95% CI, 1.5-4.5]), and home oxygen use (OR, 2.9 [95% CI, 1.6-5.1]).

Conclusions: Influenza vaccination significantly reduced influenza-related hospitalization among patients with COPD. Initiatives to increase vaccination uptake and early use of antiviral agents among patients with COPD could reduce influenza-related hospitalization and critical illness and improve health-care costs in this vulnerable population.

Trial Registry: ClinicalTrials.govNo.:NCT01517191; URL www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2018.10.044DOI Listing
January 2019

Burden of Children Hospitalized With Pertussis in Canada in the Acellular Pertussis Vaccine Era, 1999-2015.

J Pediatric Infect Dis Soc 2020 Apr;9(2):118-127

Vaccine Evaluation Center, BC Children's Hospital, University of British Columbia, Vancouver, Canada.

Background: Recent increases in pertussis morbidity and mortality rates among young infants have led to a recommendation in some countries for vaccination against pertussis during pregnancy. Having data on the burden of pediatric pertussis in a large population over time is important for establishing the true burden of disease in the acellular pertussis (aP) vaccine era. Here, we describe age-specific epidemiology and morbidity and mortality rates in children hospitalized with pertussis over 17 years across Canada in the aP vaccine era.

Methods: Patients aged ≤16 years who were admitted to 1 of 12 pediatric tertiary-care hospitals across Canada between 1999 and 2015 with confirmed (laboratory-confirmed or epidemiologically linked) or probable (clinically diagnosed) pertussis were included.

Results: Overall, 1402 patients with pertussis were included. Infants aged <2 months had the highest mean annual incidences of pertussis hospitalization and intensive care unit (ICU) admission (116.40 [95% confidence interval (CI), 85.32-147.49] and 33.48 [95% CI, 26.35-40.62] per 100 000 population, respectively). The overall proportion of children who required ICU admission was 25.46%, and the proportion was highest in infants aged <2 months (37.90%). Over the span of this study, 21 deaths occurred. Age of <16 weeks, prematurity, encephalopathy, and a confirmed pertussis diagnosis were independent risk factors for ICU admission. Age of <4 weeks, prematurity, and female sex were independent risk factors for death.

Conclusions: In the aP vaccine era, endemic pertussis still contributes considerably to childhood morbidity and death, particularly in infants aged <2 months. Vaccination against pertussis during pregnancy has the potential to reduce this disease burden.
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http://dx.doi.org/10.1093/jpids/piy128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192396PMC
April 2020

Effect of alcohol skin cleansing on vaccination-associated infections and local skin reactions: a randomized controlled trial.

Hum Vaccin Immunother 2019 16;15(4):995-1002. Epub 2019 Jan 16.

a Leslie Dan Faculty of Pharmacy , University of Toronto , Toronto , Ontario , Canada.

Objectives: Recommendations regarding the need to use alcohol prior to vaccine injections are inconsistent and based on low-level evidence. The objective was to assess the effectiveness of alcohol in reducing local skin reactions and infection post-vaccination.

Methods: Randomized controlled trial in a pediatric clinic. A research assistant cleansed the skin with alcohol at (swab group) or adjacent to (control group) the pre-defined injection site(s). Clinicians, parents and children were blinded to group allocation. Parents reported local skin reactions using paper diaries for 15 days post-vaccination (Day 0-14). Telephone interviews were conducted Day 1, 5, and 14. The Brighton Collaboration criteria were used to diagnose cellulitis and infectious abscess Day 5 and afterward.

Results: 170 children participated (May-November 2017). Baseline characteristics did not differ (p > 0.05) between groups. Children received 1-4 separate injections. There were no differences between swab and control groups in the incidence of any local skin reactions (58% vs. 54%), and specifically, pain (45% vs. 40%), redness (26% vs. 21%), swelling (20% vs. 13%), warmth (19% vs. 27%), and spontaneous drainage of pus (0% in both groups) over the post-vaccination follow-up period. Day 5 data was available for 99% of participants from diaries and telephone surveys; there were no cases of cellulitis or infectious abscess.

Conclusion: These findings are the first direct evidence for vaccine injections demonstrating that cleansing the skin with alcohol may not be needed. Our study is underpowered; however, to detect a difference in incidence of skin infection, future research is recommended.
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http://dx.doi.org/10.1080/21645515.2018.1553474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6605859PMC
February 2020

Vaccination Against Influenza in Pregnancy: A Survey of Canadian Maternity Care Providers.

J Obstet Gynaecol Can 2019 Apr 6;41(4):479-488. Epub 2018 Nov 6.

Society of Obstetricians and Gynaecologists of Canada, Ottawa, ON.

Objective: Influenza vaccine uptake among Canadian pregnant individuals is suboptimal. Failure to incorporate vaccination into routine prenatal care and a lack of recommendations from healthcare providers are recognized as barriers to vaccination. The aim of this study was to assess Canadian maternity care providers' knowledge, attitudes, and practices regarding influenza vaccination in pregnancy.

Methods: A cross-sectional Web-based questionnaire was sent during July and August 2017 to family physicians, obstetricians-gynaecologists, midwives, pharmacists, and nurses who care for pregnant individuals. A multivariable logistic regression model was used to determine variables independently associated with providers' recommendation of the influenza vaccine in pregnancy.

Results: The analysis included 1061 providers. Most participants (85%) reported being vaccinated against influenza themselves, and 72% reported recommending the influenza vaccine to all of their pregnant patients during the previous influenza season. Participants' attitudes regarding influenza vaccination during pregnancy were generally positive: 64% strongly agreed that pregnant individuals are at an increased risk of complications from influenza, and 69% strongly agreed that it is safe to vaccinate pregnant individuals against influenza. The main determinants of participants' recommendations for influenza vaccination to all pregnant patients were following official recommendations on influenza vaccination, discussing vaccines with most or all pregnant individuals seen in their practice, and being vaccinated themselves during the previous influenza season.

Conclusion: Enhancing influenza vaccine uptake in pregnancy is largely dependent on maternity care providers' recommendations. This study provides valuable insight on providers' knowledge, attitudes, and practices.
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http://dx.doi.org/10.1016/j.jogc.2018.09.007DOI Listing
April 2019

Knowledge, attitudes, behaviours, and beliefs of healthcare provider students regarding mandatory influenza vaccination.

Hum Vaccin Immunother 2019 4;15(3):700-709. Epub 2019 Jan 4.

a Department of Pediatrics , Dalhousie University , Halifax , Nova Scotia , Canada.

Influenza infection poses the same risk to healthcare students as to practising clinicians. While there is substantial dialog about the benefits, risks, and ethics of mandatory influenza immunization policies in Canada, there has been little engagement of healthcare students. To explore the knowledge, attitudes, beliefs, and behaviours of healthcare students, we administered a web-based survey to students at Dalhousie University. Influenza vaccination status varied by program type, with 86.3% of medical students (n = 124) and 52.4% of nursing students (n = 96) self-reporting receipt of the influenza vaccine both in the previous and current seasons; pharmacy students' coverage fell between the two. Pharmacy students had higher mean knowledge scores (10.0 out of 13 questions) than medical (9.26) and nursing (8.88) students. Between 56.1% and 64.5% of students across disciplines were in support of a mandatory masking or vaccination policy, and between 72.6% and 82.3% of students would comply if such a policy were in place. A sense of duty to be immunized, desire to be taught more about influenza and influenza vaccine, belief that the hospital has a right to know vaccination status, support for declination policy, and willingness to accept consequences of noncompliance were all predictors of student support of mandatory policies. Medical and pharmacy students tended to hold more pro-influenza vaccination attitudes, had higher knowledge scores, and better vaccine coverage than nursing students. Based on the overall vaccination behaviour, knowledge, beliefs, and attitudes of students surveyed, this study demonstrates that mandatory influenza immunization policies are generally supported by the next generation of practitioners.
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http://dx.doi.org/10.1080/21645515.2018.1543523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6605728PMC
February 2020

A Randomized Controlled Trial of the Safety and Immunogenicity of Tetanus, Diphtheria, and Acellular Pertussis Vaccine Immunization During Pregnancy and Subsequent Infant Immune Response.

Clin Infect Dis 2018 09;67(7):1063-1071

Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, Canada.

Background: Immunization of pregnant women with tetanus-diphtheria-acellular pertussis vaccine (Tdap) provides protection against pertussis to the newborn infant.

Methods: In a randomized, controlled, observer-blind, multicenter clinical trial, we measured the safety and immunogenicity of Tdap during pregnancy and the effect on the infant's immune response to primary vaccination at 2, 4, and 6 months and booster vaccination at 12 months of age. A total of 273 women received either Tdap or tetanus-diphtheria (Td) vaccine in the third trimester and provided information for the safety analysis and samples for the immunogenicity analyses; 261 infants provided serum for the immunogenicity analyses.

Results: Rates of adverse events were similar in both groups. Infants of Tdap recipients had cord blood levels that were 21% higher than maternal levels for pertussis toxoid (PT), 13% higher for filamentous hemagglutinin (FHA), 4% higher for pertactin (PRN), and 7% higher for fimbriae (FIM). These infants had significantly higher PT antibody levels at birth and at 2 months and significantly higher FHA, PRN, and FIM antibodies at birth and 2 and 4 months, but significantly lower PT and FHA antibody levels at 6 and 7 months and significantly lower PRN and FIM antibody levels at 7 months than infants whose mothers received Td. Differences persisted prebooster at 12 months for all antigens and postbooster 1 month later for PT, FHA, and FIM.

Conclusions: This study demonstrated that Tdap during pregnancy results in higher levels of antibodies early in infancy but lower levels after the primary vaccine series.

Clinical Trials Registration: NCT00553228.
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http://dx.doi.org/10.1093/cid/ciy244DOI Listing
September 2018

Contact among healthcare workers in the hospital setting: developing the evidence base for innovative approaches to infection control.

BMC Infect Dis 2018 04 17;18(1):184. Epub 2018 Apr 17.

Institute for Resources, Environment and Sustainability, University of British Columbia, 2202 Main Mall, Vancouver, BC, V6T 1Z4, Canada.

Background: Nosocomial, or healthcare-associated infections (HAI), exact a high medical and financial toll on patients, healthcare workers, caretakers, and the health system. Interpersonal contact patterns play a large role in infectious disease spread, but little is known about the relationship between health care workers' (HCW) movements and contact patterns within a heath care facility and HAI. Quantitatively capturing these patterns will aid in understanding the dynamics of HAI and may lead to more targeted and effective control strategies in the hospital setting.

Methods: Staff at 3 urban university-based tertiary care hospitals in Canada completed a detailed questionnaire on demographics, interpersonal contacts, in-hospital movement, and infection prevention and control practices. Staff were divided into categories of administrative/support, nurses, physicians, and "Other HCWs" - a fourth distinct category, which excludes physicians and nurses. Using quantitative network modeling tools, we constructed the resulting HCW "co-location network" to illustrate contacts among different occupations and with locations in hospital settings.

Results: Among 3048 respondents (response rate 38%) an average of 3.79, 3.69 and 3.88 floors were visited by each HCW each week in the 3 hospitals, with a standard deviation of 2.63, 1.74 and 2.08, respectively. Physicians reported the highest rate of direct patient contacts (> 20 patients/day) but the lowest rate of contacts with other HCWs; nurses had the most extended (> 20 min) periods of direct patient contact. "Other HCWs" had the most direct daily contact with all other HCWs. Physicians also reported significantly more locations visited per week than nurses, other HCW, or administrators; nurses visited the fewest. Public spaces such as the cafeteria had the most staff visits per week, but the least mean hours spent per visit. Inpatient settings had significantly more HCW interactions per week than outpatient settings.

Conclusions: HCW contact patterns and spatial movement demonstrate significant heterogeneity by occupation. Control strategies that address this diversity among health care workers may be more effective than "one-strategy-fits-all" HAI prevention and control programs.
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http://dx.doi.org/10.1186/s12879-018-3093-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5905140PMC
April 2018

A Respiratory Syncytial Virus Vaccine Based on the Small Hydrophobic Protein Ectodomain Presented With a Novel Lipid-Based Formulation Is Highly Immunogenic and Safe in Adults: A First-in-Humans Study.

J Infect Dis 2018 07;218(3):378-387

Canadian Center for Vaccinology (Dalhousie University, IWK Health Centre, and the Nova Scotia Health Authority).

Background: Respiratory syncytial virus infection can cause lower respiratory tract infection in older adults comparable to influenza, but no vaccines are available.

Methods: This was a randomized, observer-blinded, first-in-humans study of a novel synthetic RSV antigen based on the ectodomain of the small hydrophobic glycoprotein (SHe) of RSV subgroup A, formulated with either the lipid and oil-based vaccine platform DepoVax (DPX-RSV[A]) or alum (RSV[A]-Alum), in healthy, 50-64-year-old individuals. Two dose levels (10 or 25 µg) of SHe with each formulation were compared to placebo. A booster dose was administered on day 56.

Results: There was no indication that the vaccine was unsafe. Mild pain, drowsiness, and muscles aches were the most common solicited adverse events (AEs), and the frequencies of the AEs did not increase after dose 2. Robust anti-SHe-specific immune responses were demonstrated in the DPX-RSV(A) 10-μg and 25-μg groups (geometric mean titer, approximately 10-fold and 100-fold greater than that of placebo at days 56 and 236, respectively), and responses were sustained in the DPX-RSV(A) 25-μg group at day 421. Responses to the RSV(A)-Alum vaccines were very low.

Conclusions: A novel antigen from the SH protein of RSV, formulated in a lipid and oil-based vaccine platform, was highly immunogenic, with sustained antigen-specific antibody responses, and had an acceptable safety profile.
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http://dx.doi.org/10.1093/infdis/jiy177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6049039PMC
July 2018

Influenza vaccine effectiveness to prevent influenza-related hospitalizations and serious outcomes in Canadian adults over the 2011/12 through 2013/14 influenza seasons: A pooled analysis from the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS Network).

Vaccine 2018 04 13;36(16):2166-2175. Epub 2018 Mar 13.

University of Alberta Hospital, Edmonton, Alberta, Canada.

Background: Ongoing assessment of influenza vaccine effectiveness (VE) is critical to inform public health policy. This study aimed to determine the VE of trivalent influenza vaccine (TIV) for preventing influenza-related hospitalizations and other serious outcomes over three consecutive influenza seasons.

Methods: The Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN) conducted active surveillance for influenza in adults ≥16 years (y) of age during the 2011/2012, 2012/2013 and 2013/2014 seasons in hospitals across Canada. A test-negative design was employed: cases were polymerase chain reaction (PCR)-positive for influenza; controls were PCR-negative for influenza and were matched to cases by date, admission site, and age (≥65 y or <65 y). All cases and controls had demographic and clinical characteristics (including influenza immunization status) obtained from the medical record. VE was estimated as 1-OR (odds ratio) in vaccinated vs. unvaccinated patients × 100%. The primary outcome was VE of TIV for preventing laboratory-confirmed influenza-related hospitalization; secondary outcomes included VE of TIV for preventing influenza-related intensive care unit (ICU) admission/mechanical ventilation, and influenza-related death.

Results: Overall, 3394 cases and 4560 controls were enrolled; 2078 (61.2%) cases and 2939 (64.5%) controls were ≥65 y. Overall matched, adjusted VE was 41.7% (95% Confidence Interval (CI): 34.4-48.3%); corresponding VE in adults ≥65 y was 39.3% (95% CI: 29.4-47.8%) and 48.0% (95% CI: 37.5-56.7%) in adults <65 y, respectively. VE for preventing influenza-related ICU admission/mechanical ventilation in all ages was 54.1% (95% CI: 39.8-65.0%); in adults ≥65 y, VE for preventing influenza-related death was 74.5% (95% CI: 44.0-88.4%).

Conclusions: While effectiveness of TIV to prevent serious outcomes varies year to year, we demonstrate a statistically significant and clinically important TIV VE for preventing hospitalization and other serious outcomes over three seasons. Public health messaging should highlight the overall benefit of influenza vaccines over time while acknowledging year to year variability. ClinicalTrials.gov Identifier: NCT01517191.
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http://dx.doi.org/10.1016/j.vaccine.2018.02.093DOI Listing
April 2018

Immunogenicity and safety of one or two doses of the quadrivalent meningococcal vaccine MenACWY-TT given alone or with the 13-valent pneumococcal conjugate vaccine in toddlers: A phase III, open-label, randomised study.

Vaccine 2018 03 2;36(14):1908-1916. Epub 2018 Mar 2.

GSK, Avenue Fleming 20 (W23), 1300 Wavre, Belgium. Electronic address:

Background: We evaluated the immunogenicity and safety of 1 and 2 doses of quadrivalent meningococcal serogroup A, C, W and Y tetanus toxoid-conjugate vaccine (MenACWY-TT) given alone or co-administered with 13-valent pneumococcal conjugate vaccine (PCV13) in toddlers.

Methods: In this phase III, open-label, controlled, multicentre study (NCT01939158), healthy toddlers aged 12-14 months were randomised into 4 groups to receive 1 dose of MenACWY-TT at month (M) 0 (ACWY_1), 2 doses of MenACWY-TT at M0 and M2 (ACWY_2), MenACWY-TT and PCV13 at M0 (Co-ad), or PCV13 at M0 and MenACWY-TT at M2 (PCV13/ACWY). Immune responses were assessed 1 month post-each vaccination. Solicited and unsolicited symptoms were recorded for 4 and 31 days post-each vaccination, respectively; serious adverse events (SAEs) and new onset of chronic illnesses (NOCIs) up to M9 from first vaccination.

Results: 802 toddlers were vaccinated. Post-dose 1 of MenACWY-TT, ≥92.8% of toddlers had rSBA titres ≥1:8, and ≥62.5% had hSBA titres ≥1:4 for each meningococcal serogroup. Post-dose 2 of MenACWY-TT, rSBA titres ≥1:8 were observed in ≥98.0% and hSBA titres ≥1:4 in ≥95.3% of toddlers. Percentages of toddlers with hSBA titres ≥1:4 were higher after 2 doses versus 1 dose of MenACWY-TT for MenW (97.1% versus 62.5-68.9%) and MenY (95.3% versus 64.3-67.6%). Non-inferiority of immune responses to co-administered MenACWY-TT and PCV13 over their separate administration was demonstrated. AEs incidence was comparable among groups. SAEs were reported for 4.9%, 5.1%, 5.5% and 7.5%, and NOCIs for 2.0%, 3.0%, 0.5% and 3.5% of toddlers in the ACWY_1, ACWY_2, Co-ad and PCV13/ACWY groups, respectively; 4 SAEs reported in 3 toddlers were vaccine-related. Two fatal vaccine-unrelated SAEs were reported.

Conclusion: MenACWY-TT was immunogenic when administered as a single dose at 12-14 months of age. A second dose in toddlers increased hSBA responses against MenW and MenY. MenACWY-TT and PCV13 can be co-administered without impairing the immunogenicity or safety profile of either vaccine.
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http://dx.doi.org/10.1016/j.vaccine.2018.02.013DOI Listing
March 2018

Randomized Controlled Trial of the Safety and Immunogenicity of Revaccination With Tetanus-Diphtheria-Acellular Pertussis Vaccine (Tdap) in Adults 10 Years After a Previous Dose.

J Pediatric Infect Dis Soc 2019 May;8(2):105-114

Sanofi Pasteur, Swiftwater, Pennsylvania.

Background: Reduced-antigen-content tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended in many countries for boosting immunity in adolescents and adults. Although immunity to these antigens wanes with time, currently available Tdap products are not labeled for repeat administration in the United States.

Methods: We performed an observer-blinded, randomized controlled trial in 1330 adults aged 18 to <65 years who received either the Tdap (n = 1002) or tetanus-diphtheria (Td) (n = 328) vaccine 8 to 12 years after a dose of Tdap vaccine administered previously. Solicited adverse events following immunization were documented for 7 days after vaccination, and serious adverse events and adverse events of medical significance were documented for 6 months after vaccination. Levels of antibodies against component vaccine antigens were measured before and 1 month after vaccination.

Results: A solicited adverse event was reported by 87.7% of Tdap and 88.0% of Td vaccine recipients. We found no significant differences in the rates of injection-site reactions, systemic reactions, or serious adverse events between the vaccine groups. A robust antibody response to each pertussis antigen in the Tdap-vaccinated group was found; postvaccination-to-prevaccination geometric mean antibody concentration ratios were 8:1 (pertussis toxoid), 5.9 (filamentous hemagglutinin), 6.4 (pertactin), and 5.2 (fimbriae 2 and 3). Postvaccination geometric mean concentrations of tetanus antibody (4.20 and 4.74 IU/mL, respectively) and diphtheria antibody (10.1 and 12.6 IU/mL, respectively) were similar in the Tdap and Td groups, and the rates of seroprotection against tetanus and diphtheria were >99% in both groups.

Conclusions: A second dose of Tdap vaccine in adults approximately 10 years after a previous dose was well tolerated and immunogenic. These data might facilitate consideration of providing Tdap booster doses to adults.
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http://dx.doi.org/10.1093/jpids/pix113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510947PMC
May 2019

Waning of measles maternal antibody in infants in measles elimination settings - A systematic literature review.

Vaccine 2018 02 2;36(10):1248-1255. Epub 2018 Feb 2.

Public Health Ontario, 480 University Avenue, Suite 300, Toronto, ON M5G 1V2, Canada; Dalla Lana School of Public Health, University of Toronto, 155 College St, Toronto, ON M5T 3M7, Canada. Electronic address:

Introduction: Most infants are born with immunity to measles through maternal antibodies transferred in pregnancy, which decay over time. However, in measles elimination settings, where measles does not circulate endemically and most immunity is from immunization rather than infection, maternal antibody levels are lower. This results in infant immunity that wanes earlier, and a wider susceptibility gap between maternal antibody decay and infant immunization than in non-eliminated settings. We aimed to systematically quantify the extent and duration of protection from measles in infants in settings that have sustained measles elimination.

Methods: We conducted a systematic review of studies of measles maternal antibody waning in infants in measles elimination settings. We searched MEDLINE, Embase, CINAHL, Scopus, BIOSIS Previews, and Global Health databases for relevant studies. Studies were included if they were set in countries that had eliminated measles for ≥3 years, and if the study cohort included healthy, full-term, unvaccinated infants ≤12 months, born to healthy mothers, and reported a relevant measure of measles maternal antibody in infants. We assessed study quality using the MetaQAT tool.

Results: We identified 4692 unique citations, eight of which met inclusion criteria. One study reported anti-measles antibody in cord blood, six reported antibody in infant sera, and one reported both. Two studies reported that 80 and 100% of infants were protected from measles at birth. One study reported no protection amongst 3-7 month old infants, and another reported limited protection in infants >4 months. The remaining studies reported the proportion of infants with detected antibody, but not the proportion immune.

Conclusion: Although limited, these data suggest that in settings that have sustained measles elimination, some infants are susceptible to measles well before the age of routine measles immunization. Setting-specific seroprevalence and vaccine effectiveness studies are required to evaluate this in different jurisdictions.
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http://dx.doi.org/10.1016/j.vaccine.2018.01.002DOI Listing
February 2018