Pneumococcal and influenza immunization in asplenic persons: a retrospective population-based cohort study 1990-2002

<p>Abstract</p> <p>Background</p> <p>Splenectomy is associated with increased risk for bacteremia, due to impaired clearance of bloodborne agents and to altered phagocytosis and humoral immunity. We conducted a retrospective cohort study of patients at risk for splenectomy for a 13-year period to determine immunization coverage, and outcomes of those with and without splenectomy, and with or without receipt of influenza or pneumococcal vaccine.</p> <p>Methods</p> <p>Data were extracted from the provincial Medical Services Insurance database for insured services rendered by a physician for 1990-2002, and from the Vital Statistics Death database. The eligible cohort was selected based on diagnostic codes for hematologic conditions for which splenectomy might be considered, such as immune thrombocytopenia. Each patient was followed longitudinally from the date of first diagnosis until 31Dec2002, or death, or relocation out-of province. In addition, persons with splenectomy and no hematologic condition were identified and followed for 6 months post-surgery. Infectious illness rates per 100 person-years of observation and death rates were calculated with and without splenectomy. Death rates were determined using splenectomy status as a time-dependent covariate. The relationship between splenectomy and death according to immunization status was examined using Cox proportional hazard ratios.</p> <p>Results</p> <p>Of 38,812 persons in the cohort 427 subjects with a hematologic diagnosis had splenectomy and another 452 subjects without a hematologic diagnosis had this surgery. 72% were > 18 years of age. Pneumococcal immunization was recorded in 16.5% of asplenic patients overall, and was not associated with reduced risk of death in these persons (adjusted Hazard Ratio [HR] = 1.07, 95% CI 0.70 - 1.65). Influenza immunization was recorded in 53.1% of asplenic patients overall, and was associated with reduced risk of death (adjusted HR = 0.46, 0.33-0.62). No pneumococcal or influenza immunization was recorded in patients with a hematologic diagnosis without splenectomy. Infectious illness visits were higher among all patients who had a splenectomy than among those without a splenectomy (151 visits/100 person-years of observation in the post-splenectomy period vs. 120 visits/100 person-years; p < 0.0001).</p> <p>Conclusions</p> <p>In asplenic patients, influenza immunization is associated with a 54% reduced risk of death compared to unimmunized asplenic persons; no reduction in risk was demonstrated with (polysaccharide) pneumococcal vaccine. Vaccine coverage in the entire cohort was less than routinely recommended. Improved delivery of infection prevention programs to this population is warranted. Conjugate pneumococcal vaccines should be urgently studied in this immunocompromised population.</p

Does influenza vaccination improve pregnancy outcome? Methodological issues and research needs

AbstractEvidence that influenza vaccination during pregnancy is safe and effective at preventing influenza disease in women and their children through the first months of life is increasing. Several reports of reduced risk of adverse outcomes associated with influenza vaccination have generated interest in its potential for improving pregnancy outcome. Gavi, the Vaccine Alliance, estimates maternal influenza immunization programs in low-income countries would have a relatively modest impact on mortality compared to other new or under-utilized vaccines, however the impact would be substantially greater if reported vaccine effects on improved pregnancy outcomes were accurate. Here, we examine the available evidence and methodological issues bearing on the relationship between influenza vaccination and pregnancy outcome, particularly preterm birth and fetal growth restriction, and summarize research needs. Evidence for absence of harm associated with vaccination at a point in time is not symmetric with evidence of benefit, given the scenario in which vaccination reduces risk of influenza disease and, in turn, risk of adverse pregnancy outcome. The empirical evidence for vaccination preventing influenza in pregnant women is strong, but the evidence that influenza itself causes adverse pregnancy outcomes is inconsistent and limited in quality. Studies of vaccination and pregnancy outcome have produced mixed evidence of potential benefit but are limited in terms of influenza disease assessment and control of confounding, and their analytic methods often fail to fully address the longitudinal nature of pregnancy and influenza prevalence. We recommend making full use of results of randomized trials, re-analysis of existing observational studies to account for confounding and time-related factors, and quantitative assessment of the potential benefits of vaccination in improving pregnancy outcome, all of which should be informed by the collective engagement of experts in influenza, vaccines, and perinatal health

Risk of asthma in children diagnosed with bronchiolitis during infancy: Protocol of a longitudinal cohort study linking emergency department-based clinical data to provincial health administrative databases

Introduction The Canadian Bronchiolitis Epinephrine Steroid Trial (CanBEST) and the Bronchiolitis Severity Cohort (BSC) study enrolled infants with bronchiolitis during the first year of life. The CanBEST trial suggested that treatment of infants with a combined therapy of high-dose corticosteroids and nebulised epinephrine reduced the risk of admission to hospital. Our study aims to - (1) quantify the risk of developing asthma by age 5 and 10 years in children treated with high-dose corticosteroid and epinephrine for bronchiolitis during infancy, (2) identify risk factors associated with development of asthma in children with bronchiolitis during infancy, (3) develop asthma prediction models for children diagnosed with bronchiolitis during infancy. Methods and analysis We propose a longitudinal cohort study in which we will link data from the CanBEST and BSC study with routinely collected data from provincial health administrative databases. Our outcome is asthma incidence measured using a validated health administrative data algorithm. Primary exposure will be treatment with a combined therapy of high-dose corticosteroids and nebulised epinephrine for bronchiolitis. Covariates will include type of viral pathogen, disease severity, medication use, maternal, prenatal, postnatal and demographic factors and variables related to health service utilisation for acute lower respiratory tract infection. The risk associated with development of asthma in children treated with high-dose corticosteroid and epinephrine for bronchiolitis will be assessed using multivariable Cox proportional hazards regression models. Prediction models will be developed using multivariable logistic regression analysis and internally validated using a bootstrap approach. Ethics and dissemination Our study has been approved by the ethics board of all four participating sites of the CanBEST and BSC study. Finding of the study will be disseminated to the academic community and relevant stakeholders through conferences and peer-reviewed publications. Trial registration number ISRCTN56745572; Post-results

Prenatal exposure to the 2009 pandemic H1N1 influenza vaccine on health outcomes in children

Introduction During the 2009 H1N1 pandemic, less than half of pregnant women in Ontario received the recommended influenza vaccine. Commonly-cited reasons for low vaccine uptake include misconceptions about the possible impact of maternal influenza infection and vaccine safety. Providing data on previously understudied pediatric health outcomes may help increase vaccine uptake. Objectives and Approach We conducted a retrospective cohort study of all live births from November 2nd, 2009 to October 31st, 2010 using the BORN Ontario province-wide birth registry containing information on H1N1 vaccination. These data were deterministically/probabilistically linked with several health administrative databases held at the Institute for Clinical Evaluative Sciences to ascertain specific immune-related pediatric health outcomes and health services utilization over 5 years of follow-up. Negative binomial regression models were used to evaluate the association between prenatal H1N1 vaccination and outcomes. Stabilized inverse probability of treatment weights (sIPTW) derived from the propensity scores were used to adjust for potential confounding. Results The study cohort included 104,310 eligible infants, 31,310 (30%) of whom were born to H1N1-vaccinated women. Median follow-up time was 5 years. Using sIPTWs we were able to achieve good balance of baseline measured covariates across exposure groups, with no absolute standardized differences larger than 7%. The sIPTW-adjusted analyses indicated no significant associations between prenatal exposure to H1N1 vaccination and upper respiratory infections (adjusted rate ratio [aRR] 1.01; 95% confidence interval [CI] 0.98-1.03), lower respiratory infections (aRR 1.00; 95%CI 0.96-1.04), otitis media (aRR 1.04; 95%CI 1.00-1.07), all infections (aRR 1.00; 95%CI 0.98-1.03), and rates of urgent and in-patient health services utilization (aRR 1.00; 95%CI 0.98-1.02). Conclusion/Implications Our primary findings suggest there are no associations between prenatal exposure to H1N1 vaccination and (1) the development of several immune-related health outcomes in children; (2) rates of health services utilization. Furthermore, our study provides new evidence on the long-term safety of influenza vaccination during pregnancy, which is currently lacking

Parental characteristics and perspectives pertaining to neonatal visits to the emergency department: a multicentre survey

BACKGROUND: Parents take neonates to the emergency department for many reasons, often nonurgent, pressuring an already burdened system. We aimed to characterize these visits and families to identify potential strategies to decrease neonatal emergency department visits. METHODS: We developed and implemented a survey that explored characteristics of neonates and parents/guardians evaluated in the emergency department, perspectives of parents and use of health care services. Parents presenting with a neonate to the emergency department in 5 large academic hospitals in Ontario were surveyed between December 2013 and June 2015. We used descriptive statistics to report survey data and explored correlations between factors. RESULTS: A total of 1533 surveys were completed. The most common reasons for presenting were jaundice (441 [28.8%]) and feeding issues (251 [16.4%]). The majority of respondents (73.9% [1104/1494]) had received advice before going to the emergency department. In most cases (86.4% [954/1104]), this was from a health care provider, who frequently advised going to the emergency department. Although most parents (86.8% [1280/1475]) reported high confidence in caring for a sick or injured child, 42.3% (643/1519) were unsure of the severity, and most (90.4% [578/639]) of these parents felt that the infant required assessment immediately or the same day. Of parents who felt the condition was not serious, 83.2% (198/238) thought that same-day evaluation was required. Nearly half of respondents (44.4% [621/1400]) said they would have gone to their health care provider with a same-day appointment, and 28.1% (344/1225) would have gone to their care provider with a next-day appointment. INTERPRETATION: Parents\u27 reported confidence in caring for sick or injured infants does not match the perceived urgency of neonatal conditions, which likely contributes to emergency department overuse. Any system to decrease nonurgent emergency department use by neonates would need to be immediately responsive, providing same-day help

Influenza epidemiology and immunization during pregnancy: Final report of a world health organization working group

From 2014 to 2017, the World Health Organization convened a working group to evaluate influenza disease burden and vaccine efficacy to inform estimates of maternal influenza immunization program impact. The group evaluated existing systematic reviews and relevant primary studies, and conducted four new systematic reviews. There was strong evidence that maternal influenza immunization prevented influenza illness in pregnant women and their infants, although data on severe illness prevention were lacking. The limited number of studies reporting influenza incidence in pregnant women and infants under six months had highly variable estimates and underrepresented low- and middle-income countries. The evidence that maternal influenza immunization reduces the risk of adverse birth outcomes was conflicting, and many observational studies were subject to substantial bias. The lack of scientific clarity regarding disease burden or magnitude of vaccine efficacy against severe illness poses challenges for robust estimation of the potential impact of maternal influenza immunization programs

Association of COVID-19 Vaccination During Pregnancy With Incidence of SARS-CoV-2 Infection in Infants

IMPORTANCE: Pregnant women are recommended to receive COVID-19 vaccination to reduce risk of severe COVID-19. Whether vaccination during pregnancy also provides passive protection to infants after birth remains unclear. OBJECTIVE: To determine whether COVID-19 vaccination in pregnancy was associated with reduced risk of COVID-19 in infants up to age 4 months during COVID-19 pandemic periods dominated by Delta and Omicron variants. DESIGN, SETTING, AND PARTICIPANTS: This nationwide, register-based cohort study included all live-born infants born in Norway between September 1, 2021, and February 28, 2022. EXPOSURES: Maternal messenger RNA COVID-19 vaccination during second or third trimester compared with no vaccination before or during pregnancy. MAIN OUTCOMES AND MEASURES: The risk of a positive polymerase chain reaction test result for SARS-CoV-2 during an infant's first 4 months of life by maternal vaccination status during pregnancy with either dose 2 or 3 was estimated, as stratified by periods dominated by the Delta variant (between September 1 and December 31, 2021) or Omicron variant (after January 1, 2022, to the end of follow-up on April 4, 2022). A Cox proportional hazard regression was used, adjusting for maternal age, parity, education, maternal country of birth, and county of residence. RESULTS: Of 21 643 live-born infants, 9739 (45.0%) were born to women who received a second or third dose of a COVID-19 vaccine during pregnancy. The first 4 months of life incidence rate of a positive test for SARS-CoV-2 was 5.8 per 10 000 follow-up days. Infants of mothers vaccinated during pregnancy had a lower risk of a positive test compared with infants of unvaccinated mothers and lower risk during the Delta variant-dominated period (incidence rate, 1.2 vs 3.0 per 10 000 follow-up days; adjusted hazard ratio, 0.29; 95% CI, 0.19-0.46) compared with the Omicron period (incidence rate, 7.0 vs 10.9 per 10 000 follow-up days; adjusted hazard ratio, 0.67; 95% CI, 0.57-0.79). CONCLUSIONS AND RELEVANCE: The results of this Norwegian population-based cohort study suggested a lower risk of a positive test for SARS-CoV-2 during the first 4 months of life among infants born to mothers who were vaccinated during pregnancy. Maternal COVID-19 vaccination may provide passive protection to young infants, for whom COVID-19 vaccines are currently not available

Developing Product Label Information to Support Evidence-Informed Use of Vaccines in Pregnancy

Background: Product labelling information describing the use of vaccines in pregnancy continues to contain cautionary language even after clinical and epidemiological evidence of safety becomes available. This language raises safety concerns among healthcare providers who may hesitate to recommend vaccines during pregnancy. Purpose: To develop clear evidence-based language about vaccine safety and effectiveness in pregnancy for inclusion in vaccine product labels. Methods: We conducted a three-stage consensus-methods project with stakeholders, including: healthcare providers, vaccine regulators, industry representatives, and experts in public health, communication, law, ethics, and social sciences. Using qualitative and quantitative methods, we held a nominal group technique (NGT) meeting, followed by a Delphi survey, and then a consensus workshop with a subset of Delphi participants. We developed a methodological tool to analyse data for consensus. Principal results: Stakeholders (N = 14) at the NGT meeting drafted product label statements for evaluation in the Delphi survey. Survey participants (N = 41) provided feedback on statements for five hypothetical vaccines. Workshop participants (N = 27) initiated discussions that demonstrated a lack of awareness that the regulatory purpose of product labels is to provide a scientific summary of product-specific preclinical and clinical trial data. Each stage of this project built on earlier stages until we achieved strong consensus on the language, structure, and types of data that stakeholders wanted to include in inactivated influenza vaccine (IIV) and tetanus-diphtheria-acellular pertussis (Tdap) vaccine product labels in Canada. Conclusions: The revised statements for IIV and Tdap aligned with workshop participants’ goals that the product label be evidence-based, with a consistent structure and language that is easily understood by healthcare providers. Emergent methods uncovered stakeholder concerns about the regulatory purpose, content, and evidence used in product labels. Involving healthcare providers in the development and regular updating of product information could prevent interpretations of that information that contribute to vaccine hesitancy

Childhood seizures after prenatal exposure to maternal influenza infection: a population-based cohort study from Norway, Australia and Canada.

OBJECTIVE: To assess whether clinical and/or laboratory-confirmed diagnosis of maternal influenza during pregnancy increases the risk of seizures in early childhood. DESIGN: Analysis of prospectively collected registry data for children born between 2009 and 2013 in three high-income countries. We used Cox regression to estimate country-level adjusted HRs (aHRs); fixed-effects meta-analyses were used to pool adjusted estimates. SETTING: Population-based. PARTICIPANTS: 1 360 629 children born between 1 January 2009 and 31 December 2013 in Norway, Australia (New South Wales) and Canada (Ontario). EXPOSURE: Clinical and/or laboratory-confirmed diagnosis of maternal influenza infection during pregnancy. MAIN OUTCOME MEASURES: We extracted data on recorded seizure diagnosis in secondary/specialist healthcare between birth and up to 7 years of age; additional analyses were performed for the specific seizure outcomes 'epilepsy' and 'febrile seizures'. RESULTS: Among 1 360 629 children in the study population, 14 280 (1.0%) were exposed to maternal influenza in utero. Exposed children were at increased risk of seizures (aHR 1.17, 95% CI 1.07 to 1.28), and also febrile seizures (aHR 1.20, 95% CI 1.07 to 1.34). There was no strong evidence of an increased risk of epilepsy (aHR 1.07, 95% CI 0.81 to 1.41). Risk estimates for seizures were higher after influenza infection during the second and third trimester than for first trimester. CONCLUSIONS: In this large international study, prenatal exposure to influenza infection was associated with increased risk of childhood seizures