Factors associated with intention for revaccination among patients with adverse events following immunization.

OBJECTIVES: Individuals and healthcare providers may be uncertain about the safety of revaccination after an adverse event following immunization (AEFI). We identified factors associated with physician recommendation for revaccination and participant intention to be revaccinated among patients with adverse events following immunization (AEFIs) assessed in the Canadian Special Immunization Clinic (SIC) Network from 2013 to 2019. METHODS: This prospective observational study included patients assessed in the Canadian Special Immunization Clinic Network from 2013 to 2019 for an AEFI who required additional doses of the vaccine temporally associated with their AEFI. Participants underwent standardized assessment and data collection. Physician recommendations regarding revaccination and participant intent for revaccination were recorded. AEFI impact on daily activities and need for medical attention was captured as low, moderate, high impact and serious (e.g., requiring hospitalization). Multivariable logistic regression analysis identified factors associated with physician recommendation and participant intention for revaccination, controlling for province of assessment. RESULTS: Physician recommendation was significantly associated with the type of AEFI and AEFI impact. Compared to large local reaction, physician recommendation for revaccination was reduced for immediate hypersensitivity (aOR: 0.24 [95% CI: 0.08-0.76]) and new onset autoimmune disease (aOR: 0.16; 95% CI: 0.04-0.69). Compared to low impact AEFIs, physician recommendation was reduced for moderate (aOR: 0.22 [95% CI: 0.07-0.65]), high impact (aOR: 0.08 [95% CI: 0.02-0.30]), and serious AEFIs (aOR: 0.11 [95% CI: 0.03-0.37]). Participant intention for revaccination was significantly associated with AEFI impact, with reduced odds for high versus low impact AEFIs (aOR: 0.12 [95% CI: 0.04-0.42]). CONCLUSION: Physicians appear to use AEFI type and impact to guide recommendations while patients use primarily AEFI impact to form intentions for revaccination. The findings may help inform counselling for patients with AEFIs.

Revaccination and Adverse Event Recurrence in Patients with Adverse Events following Immunization.

OBJECTIVES: To estimate the risk of recurrence of adverse events following immunization (AEFIs) upon revaccination and to determine among patients with suspected vaccine allergy whether allergy skin test positivity was associated with AEFI recurrence. STUDY DESIGN: This prospective observational study included patients assessed in the Canadian Special Immunization Clinic Network from 2013 to 2019 with AEFIs who required revaccination with the vaccine temporally associated with their AEFI. Participants underwent standardized assessment and data collection. Special Immunization Clinic physicians used guidelines to inform their recommendations. Participants were followed up after revaccination to capture AEFI recurrences. Data were transferred to a central database for descriptive analysis. RESULTS: Overall, 588 participants were assessed for 627 AEFIs; 570 (91%) AEFIs occurred in children <18 years of age. AEFIs included immediate hypersensitivity (130/627; 21%), large local reactions (110/627; 18%), nonurticarial rash (51/627; 8%), seizures (26/627; 4%), and thrombocytopenia (11/627; 2%). Revaccination was recommended to 513 of 588 (87%) participants. Among participants recommended and due for revaccination during the study period, 63% (299/477) were revaccinated. AEFI recurrence was 10% (31/299) overall, 31% (15/49) for large local reactions, and 7% (5/66) for immediate hypersensitivity. No recurrence was serious. Among 92 participants with suspected vaccine allergy who underwent skin testing and were revaccinated, the negative predictive value of skin testing for AEFI recurrence was 96% (95% CI 92.5%-99.5%). CONCLUSIONS: Most individuals with AEFIs were safely revaccinated. Among those with suspected vaccine allergy, skin testing may help determine the safety of revaccination.

Antiviral Use in Canadian Children Hospitalized for Influenza.

OBJECTIVES: Antivirals are recommended for children hospitalized with influenza but are underutilized. We describe antiviral prescribing during influenza admissions in Canadian pediatric centers and identify factors associated with antiviral use. METHODS: We performed active surveillance for laboratory-confirmed influenza hospitalizations among children ≤16 years old at the 12 Canadian Immunization Monitoring Program Active hospitals, from 2010-2011 to 2018-2019. Logistic regression analyses were used to identify factors associated with antiviral use. RESULTS: Among 7545 patients, 57.4% were male; median age was 3 years (interquartile range: 1.1-6.3). Overall, 41.3% received antiviral agents; 72.8% received antibiotics. Antiviral use varied across sites (range, 10.2% to 81.1%) and influenza season (range, 19.9% to 59.6%) and was more frequent in children with ≥1 chronic health condition (52.7% vs 36.7%; P < .001). On multivariable analysis, factors associated with antiviral use included older age (adjusted odds ratio [aOR] 1.04 [95% confidence interval (CI), 1.02-1.05]), more recent season (highest aOR 9.18 [95% CI, 6.70-12.57] for 2018-2019), admission during peak influenza period (aOR 1.37 [95% CI, 1.19-1.58]), availability of local treatment guideline (aOR 1.54 [95% CI, 1.17-2.02]), timing of laboratory confirmation (highest aOR 2.67 [95% CI, 1.97-3.61] for result available before admission), presence of chronic health conditions (highest aOR 4.81 [95% CI, 3.61-6.40] for cancer), radiographically confirmed pneumonia (aOR 1.39 [95% CI, 1.20-1.60]), antibiotic treatment (aOR 1.51 [95% CI, 1.30-1.76]), respiratory support (1.57 [95% CI, 1.19-2.08]), and ICU admission (aOR 3.62 [95% CI, 2.88-4.56]). CONCLUSIONS: Influenza antiviral agents were underused in Canadian pediatric hospitals, including among children with high-risk chronic health conditions. Prescribing varied considerably across sites, increased over time, and was associated with patient and hospital-level characteristics. Multifaceted hospital-based interventions are warranted to strengthen adherence to influenza treatment guidelines and antimicrobial stewardship practices.

Pregnancy Among HIV-Serodiscordant Couples: Case Report of Vertical Transmission and Retrospective Case Series.

BACKGROUND: HIV transmission during pregnancy and breastfeeding among serodiscordant heterosexual couples represents an ongoing barrier to the elimination of vertical transmission of HIV-1 infection in Canada. OBJECTIVE: To report a case of vertical HIV transmission during breastfeeding and examine the prevalence of risk factors for HIV transmission in the pregnancy and postpartum periods among serodiscordant couples where the male partner is HIV positive and female partner HIV negative. METHODS: Case report and retrospective chart review of HIV-serodiscordant pregnant couples over an eight-year period in Edmonton, Canada. RESULTS: We report a case of maternal primary HIV infection during the postpartum period and vertical transmission to a nursing infant that went undetected until the infant presented with AIDS. We also report a series of 41 serodiscordant pregnant couples identified by our public health nurse between 2008 and 2016. Among HIV-infected male partners, 20 (49%) had a detectable viral load (VL) during their partner's pregnancy and during breastfeeding, with median peak VL 4,700 copies/mL (range 49-120,000) and 5,100 copies/mL (range 40-120,000) during pregnancy and breastfeeding, respectively. None of the female partners seroconverted during pregnancy, but three seroconverted at 1.8, 2.4, and 6.9 years after delivery. No vertical transmission occurred. CONCLUSION: Despite concerted attempts to minimize HIV transmission during pregnancy and breastfeeding in our well-resourced setting, residual transmission risk remains due to non-suppressed viral load within many HIV-serodiscordant pregnant couples.

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

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.

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

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.

Overview of the respiratory syncytial virus vaccine candidate pipeline in Canada.

A vaccine for respiratory syncytial virus (RSV) has been actively sought for over 60 years due to the health impacts of RSV disease in infants, but currently the only available preventive measure in Canada and elsewhere is limited to passive immunization for high-risk infants and children with a monoclonal antibody. RSV vaccine development has faced many challenges, including vaccine-induced enhancement of RSV disease in infants. Several key developments in the last decade in the fields of cellular immunology and protein structure have led to new products entering late-stage clinical development. As of July 2019, RSV vaccine development is being pursued by 16 organizations in 121 clinical trials. Five technologies dominate the field of RSV vaccine development, four active immunizing agents (live-attenuated, particle-based, subunit-based and vector-based vaccines) and one new passive immunizing agent (monoclonal antibody). Phase 3 clinical trials of vaccine candidates for pregnant women, infants, children and older adults are under way. The next decade will see a dramatic transformation of the RSV prevention landscape.

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

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.

Gap analyses to assess Canadian readiness for respiratory syncytial virus vaccines: Report from an expert retreat.

Respiratory syncytial virus (RSV) can cause severe disease in infants and older adults. Various vaccine candidates are in development and may become authorized for use in Canada within the next 2-5 years. The Public Health Agency of Canada sought to enhance preparedness for RSV vaccine and passive immunization candidates by organizing an expert retreat to identify knowledge gaps in surveillance and research and development in the context of provincial and territorial RSV public health priorities. We determined that RSV candidate vaccines in development directly address four out of five identified public health priorities, and identified remaining data gaps around vaccine efficacy and effectiveness. We determined that limited or sufficient surveillance data is available to support decision-making for four out of five RSV public health priorities and identified data gaps for several key populations: (i) for RSV cases under 17 years of age, gaps remain for denominator data to calculate incidence and data on medically attended outpatient visits; (ii) for RSV cases in Indigenous and remote communities, gaps remain for data on incidence, prevalence, specific risk factors, feasibility and acceptability; and (iii) for RSV cases in older adults, gaps remain for data on incidence. This process demonstrated the feasibility of, and stakeholder support for, gap analyses in surveillance data to support decisions about prospective vaccines and immune products.

Summary of the NACI Statement on the Use of Bivalent Factor H Binding Protein Meningococcal Serogroup B (MenB-fHBP) Vaccine for the Prevention of Meningococcal B Disease.

BACKGROUND: TrumenbaTM, a bivalent, factor-H binding protein meningococcal serogroup B (MenB-fHBP) vaccine was authorized for use in Canada in October 2017 for the prevention of invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup B in individuals 10-25 years of age. The National Advisory Committee on Immunization (NACI) provides recommendations regarding the use of meningococcal vaccines to the Public Health Agency of Canada. OBJECTIVE: To summarize NACI recommendations regarding the use of MenB-fHBP vaccine in Canada. METHODS: The NACI Meningococcal Disease Working Group developed a predefined search strategy to identify all eligible studies, assessed the quality of these studies, and summarized and analyzed the findings. According to the NACI evidence-based process, the working group then proposed recommendations and identified the grade of evidence that supported them. In light of the evidence, the recommendations were then considered and approved by NACI. RESULTS: The two serogroup B meningococcal vaccines currently authorized for use in Canada are not interchangeable as they contain different antigens and there are no published studies on the immunogenicity resulting from a vaccination series combining the two products. Following the review of evidence, NACI recommends that MenB-fHBP vaccine may be considered as an option for use in individuals 10 years of age and older in situations when a serogroup B meningococcal vaccine should be offered: 1) during serogroup B meningococcal disease outbreaks or with the emergence of hyperendemic N. meningitidis strains that are predicted to be susceptible to the vaccine; 2) for individuals who are close contacts with a case of invasive meningococcal disease caused by serogroup B N. meningitidis; 3) for individuals with underlying medical conditions that would put them at higher risk of meningococcal disease than the general population; or 4) for individuals at higher risk of exposure to serogroup B meningococcal isolates than the general population. NACI also recommends that MenB-fHBP vaccine may be considered as an option for individuals 10-25 years of age who are not at higher risk of meningococcal disease than the general population, but who wish to reduce their risk of invasive serogroup B meningococcal disease. CONCLUSION: NACI recommends immunization against serogroup B IMD for all individuals who are at a higher risk of disease due to an underlying medical condition or an increased risk of exposure. In addition to providing guidance to public health decision-makers (i.e. provinces/territories making decisions for publicly-funded immunization programs), these NACI recommendations provide information to individuals, vaccine providers and organizations about vaccines that may not currently be included in publicly funded immunization programs. NACI continues to recommend against the use of the serogroup B vaccines in routine universal immunization programs in Canada at this time.

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

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.

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

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.

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

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.

Challenges to achieving and maintaining viral suppression among children living with HIV.

OBJECTIVES: The objective of this study was to determine the time to, and durability of, viral suppression, among Canadian children living with HIV after initiation of combination antiretroviral therapy (cART). DESIGN: Prospective, multicenter Canadian cohort study (Early Pediatric Initiation Canada Child Cure Cohort), using both prospective and retrospectively collected data. METHODS: Kaplan-Meir survival estimates with Cox regression were used to determine the time to and risk factors for viral suppression, defined as two consecutive undetectable viral loads (<50 copies/ml) at least 30 days apart after initiation of cART. RESULTS: A total of 228 children were enrolled between December 2014 and December 2018. The time to viral suppression was significantly shorter among children initiating cART after 5 ≤ 5 vs. years or less of age [adjusted hazard ratio (aHR) 1.57, 95% confidence interval (CI) 1.13-2.20], among those born after 2010 vs. prior (aHR 1.71, 95% CI 1.04-2.79), and among those without child protection services involvement (aHR 1.44, 95% CI 1.03-2.01). Overall, 27% of children had a viral rebound within 3 years of achieving viral suppression; the risk of viral rebound was significantly lower among children initiating cART after 5 vs. 5 years or less of age [adjusted odds ratio (aOR): 0.32, 95% CI 0.13-0.81], those whose families had not received social assistance (aOR 0.16, 95% CI 0.06-0.46), and females vs. males (aOR 0.51, 95% CI 0.26-0.99). CONCLUSION: Only 73% of the children in the Early Pediatric Initiation Canada Child Cure Cohort had maintained viral suppression 3 years after it was first achieved. Age at cART initiation, and socioeconomic factors were predictors of both time to viral suppression and risk of viral rebound in this cohort.

From mother to baby: antenatal exposure to monoclonal antibody biologics.

INTRODUCTION: More women with autoimmune and inflammatory conditions are being treated with monoclonal antibody biologics (mAbs) during their pregnancy, to maintain clinical remission. The use of anti-tumor necrosis factor alpha agents in pregnancy appears to be safe but less is known regarding other mAbs, such as anti-integrins and anti-cytokine agents. There are currently no comprehensive guidelines on how to manage the exposed infants. Areas covered: We review recent literature to assess the impact of mAbs on birth and early infant outcomes, including what is currently known about maternal and infant drug levels at birth and drug clearance in the infant. We describe the potential risks of infections and reported hematological and immunological effects of antenatal mAbs exposure on the infant and provide guidance on the management of the exposed infant. Expert opinion: Exposed infants should be monitored closely. Certain mAb exposures require specific testing and management. Safety monitoring should be done in a multidisciplinary approach and should include pediatric care providers. The current clinical experience with anti-tumor necrosis factor agents in pregnancy cannot be extrapolated to other mAbs. Long-term observational studies and a multicenter international registry are needed to better appreciate the impact of exposure, especially to newer mAbs.

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

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.

Missed opportunities for prevention of vertical HIV transmission in Canada, 1997-2016: a surveillance study.

BACKGROUND: Vertical HIV transmission has declined in Canada, but missed opportunities for prevention continue to occur. We sought to determine the adequacy, and changes over time in adequacy, of uptake of maternal and neonatal antiretroviral therapy for the prevention of vertical HIV transmission, and to determine the vertical transmission rate over time and according to adequacy of antenatal antiretroviral therapy during the combination antiretroviral therapy era in Canada. METHODS: The Canadian Perinatal HIV Surveillance Program collects data annually through retrospective chart review concerning HIV-infected women and their infants. We determined receipt of adequate antiretroviral treatment (antenatal combination antiretroviral treatment for ≥ 4 wk, intrapartum intravenous zidovudine treatment and 4-6 wk of infant oral zidovudine treatment) and predictors of inadequate antenatal combination antiretroviral therapy (none or < 4 wk) in Canada in 1997-2016. RESULTS: We identified 3785 mother-infant pairs. Uptake of 4 weeks or more of antenatal combination antiretroviral therapy increased over time across all provinces/territories and regardless of maternal race/ethnicity or risk category (p < 0.001). During 2011-2016, 92 women (6.5%) received no or less than 4 weeks of antenatal combination antiretroviral therapy, 146 women (10.7%) received no intrapartum zidovudine treatment, and 43 infants (3.1%) received less than 4 weeks of zidovudine treatment. In multivariate analysis restricted to 2011-2016, higher uptake of adequate antenatal combination antiretroviral therapy was seen among black women than among Indigenous (odds ratio [OR] 2.99, 95% confidence interval [CI] 1.23-7.26) or white (OR 1.87, 95% CI 0.99-1.27) women and in British Columbia/Yukon Territory than in Alberta (OR 3.31, 95% CI 1.06-10.32), Ontario (OR 3.16, 95% CI 1.08-9.26) or Quebec (OR 3.44, 95% CI 1.09-10.84). Among the 14 vertical HIV transmission events during 2011-2016 (vertical transmission rate 1.0%), maternal HIV infection was diagnosed before the onset of labour in 5 cases, and only 2 women received adequate antenatal combination antiretroviral therapy. INTERPRETATION: Efforts to improve timely access to care, HIV screening and treatment for all women, combined with enhanced resources targeting populations at increased risk for HIV infection, will be needed if vertical HIV transmission is to be eliminated in Canada.

Invasive Haemophilus Influenzae Type B Infections in Children with Cancer in the Era of Infant HIB Immunization Programs (1991-2014): A Report From the Canadian Immunization Monitoring Program Active.

We studied the epidemiology of Haemophilus influenzae type b infections among children with cancer admitted to Canadian pediatric hospitals. From 1991 to 2014, 13 cases among children with cancer were identified through active surveillance. Average age was 6.7 years. Six of 7 cases eligible for infant immunization were age-appropriately immunized (vaccine failures). Children with cancer may benefit from booster Hib immunization.

Diagnosis and management of infants with congenital cytomegalovirus infection.

Congenital cytomegalovirus infection (cCMV) is the most common congenital infection, occurring in approximately 0.5% of live births. Most infected newborns are asymptomatic, but up to 20% develop sensorineural hearing loss or other permanent neurologic sequelae. The presentation of newborns with symptomatic cCMV is highly variable, and the infection is usually not diagnosed in the absence of a screening program. Newborn cCMV screening programs are estimated to be beneficial and cost-effective, and are increasingly being implemented. Diagnosis requires direct detection of virus in a sample obtained before 3 weeks of life, and is best performed by polymerase chain reaction (PCR) of saliva or urine, either of which is more sensitive than dried blood spot. Antiviral treatment of selected newborns with cCMV-related disease appears to improve hearing and neurocognitive outcomes. All infected infants should be evaluated promptly to determine appropriate therapy, and receive close audiologic and developmental follow-up.