ORCID Profile
0000-0002-5683-996X
Current Organisations
Royal Children’s Hospital
,
Murdoch Children's Research Institute
,
University of Melbourne
,
Melbourne Children's Trials Centre
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Publisher: American Medical Association (AMA)
Date: 03-2023
DOI: 10.1001/JAMAPEDIATRICS.2022.5258
Abstract: Obstructive sleep-disordered breathing (SDB) in children is characterized by snoring and difficulty breathing during sleep. SDB affects at least 12% of otherwise healthy children and is associated with significant morbidity. Evidence from small clinical trials suggests that intranasal corticosteroids improve SDB as measured by polysomnography however, the effect on symptoms and quality of life is unclear. To determine whether intranasal mometasone furoate is more effective than intranasal saline for improving symptoms and quality of life in children with SDB. The MIST trial was a multicenter, randomized, double-blind, placebo-controlled trial, recruiting participants from June 8, 2018, to February 13, 2020. Children aged 3 to 12 years who were referred to a specialist for significant SDB symptoms were included exclusions were previous adenotonsillectomy, body mass index greater than the 97th percentile, and severe SDB. Randomization was stratified by site, and data were analyzed on an intention-to-treat basis from October 28, 2020, to September 25, 2022. Participants were randomly assigned to receive mometasone furoate, 50 μg, or sodium chloride (saline), 0.9%, 1 spray per nostril daily, dispensed in identical bottles. The primary outcome was resolution of significant SDB symptoms (ie, reduction to a level no longer requiring referral to a specialist as per the American Academy of Pediatrics guidelines) at 6 weeks, measured by parental report of symptoms using the SDB Score. A total of 276 participants (mean [SD] age, 6.1 [2.3] years 146 male in iduals [53%]) were recruited, 138 in each treatment arm. Resolution of significant SDB symptoms occurred in 56 of 127 participants (44%) in the mometasone group and 50 of 123 participants (41%) in the saline group (risk difference, 4% 95% CI, −8% to 16% P = .51) with 26 participants lost to follow-up and missing values managed by multiple imputation. The main adverse effects were epistaxis, affecting 12 of 124 participants (9.7%) in the mometasone group and 18 of 120 participants (15%) in the saline group, and nasal itch/irritation, affecting 12 of 124 participants (9.7%) in the mometasone group and 22 of 120 participants (18%) in the saline group. Results of this randomized clinical trial suggest that there was no difference in treatment effect between intranasal mometasone and saline for the management of SDB symptoms. The results suggest that almost one-half of children with SDB could be initially managed in the primary care setting and may not require referral to specialist services, as is currently recommended. Australian New Zealand Clinical Trials Registry: ANZCTRN12618000448246
Publisher: Wiley
Date: 11-2022
DOI: 10.1111/PAI.13890
Abstract: IgE‐mediated food allergies have been linked to suboptimal naïve CD4 T (nCD4T) cell activation in infancy, underlined by epigenetic and transcriptomic variation. Similar attenuated nCD4T cell activation in adolescents with food allergy have also been reported, but these are yet to be linked to specific epigenetic or transcriptional changes. We generated genome‐wide DNA methylation data in purified nCD4 T cells at quiescence and following activation in a cohort of adolescents (aged 10–15 years old) with peanut allergy (peanut only or peanut + ≥1 additional food allergy) (FA, n = 29), and age‐matched non‐food allergic controls (NA, n = 18). Additionally, we assessed transcriptome‐wide gene expression and cytokine production in these cells following activation. We found widespread changes in DNA methylation in both NA and FA nCD4T cells in response to activation, associated with the T cell receptor signaling pathway. Adolescents with FA exhibit unique DNA methylation signatures at quiescence and post‐activation at key genes involved in Th1/Th2 differentiation ( RUNX3 , RXRA , NFKB1A , IL4R) , including a differentially methylated region (DMR) at the TNFRSF6B promoter, linked to Th1 proliferation. Combined analysis of DNA methylation, transcriptomic data and cytokine output in the same s les identified an attenuated interferon response in nCD4T cells from FA in iduals following activation, with decreased expression of several interferon genes, including IFN‐γ and a DMR at a key downstream gene, BST2 . We find that attenuated nCD4T cell responses from adolescents with food allergy are associated with specific epigenetic variation, including disruption of interferon responses, indicating dysregulation of key immune pathways that may contribute to a persistent FA phenotype. However, we recognize the small s le size, and the consequent restraint on reporting adjusted p ‐value statistics as limitations of the study. Further study is required to validate these findings.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.VACCINE.2017.08.003
Abstract: Maternal and childhood vaccine decision-making begins prenatally. Amongst pregnant Australian women we aimed to ascertain vaccine information received, maternal immunisation uptake and attitudes and concerns regarding childhood vaccination. We also aimed to determine any correlation between a) intentions and concerns regarding childhood vaccination, (b) concerns about pregnancy vaccination, (c) socioeconomic status (SES) and (d) uptake of influenza and pertussis vaccines during pregnancy and routine vaccines during childhood. Women attending public antenatal clinics were recruited in three Australian states. Surveys were completed on iPads. Follow-up phone surveys were done three to six months post delivery, and infant vaccination status obtained via the Australian Childhood Immunisation Register (ACIR). Between October 2015 and March 2016, 975 (82%) of 1184 mothers consented and 406 (42%) agreed to a follow up survey, post delivery. First-time mothers (445 49%) had significantly more vaccine concerns in pregnancy and only 73% had made a decision about childhood vaccination compared to 89% of mothers with existing children (p-value<0.001). 66% of mothers reported receiving enough information during pregnancy on childhood vaccination. In the post delivery survey, 46% and 82% of mothers reported receiving pregnancy influenza and pertussis vaccines respectively. The mother's degree of vaccine hesitancy and two attitudinal factors were correlated with vaccine uptake post delivery. There was no association between reported maternal vaccine uptake or SES and childhood vaccine uptake. First time mothers are more vaccine hesitant and undecided about childhood vaccination, and only two thirds of all mothers believed they received enough information during pregnancy. New interventions to improve both education and communication on childhood and maternal vaccines, delivered by midwives and obstetricians in the Australian public hospital system, may reduce vaccine hesitancy for all mothers in pregnancy and post delivery, particularly first-time mothers.
Publisher: Wiley
Date: 03-2023
DOI: 10.1111/PAI.13930
Abstract: Children with peanut allergy are at increased risk of developing tree nut allergies, which can be severe and for most lifelong. Introduction of peanut in the first year of life can reduce the risk of peanut allergy however, prevention strategies for tree nut allergies have not been established. We aimed to test the efficacy and safety of a novel strategy, a supervised multi‐nut oral food challenge (OFC) compared with standard care for tree nut allergy prevention in infants at high risk of developing tree nut allergy, TreEAT. TreEAT is a 2‐armed, open‐label, randomized, controlled trial (RCT). Infants ( n = 212) aged 4–11 months with peanut allergy will be randomized 1:1 at peanut allergy diagnosis to either a hospital‐based multi‐tree nut (almond, cashew, hazelnut, and walnut) OFC using multi‐nut butter or standard care (home introduction of in idual tree nuts). All infants will be assessed at age 18 months, with questionnaires and SPT to peanut and tree nuts. Peanut and tree nut OFCs will be performed as required to determine the allergy status for each nut. The primary outcome is tree nut allergy at age 18 months. Secondary outcomes include peanut allergy resolution, proportion, and severity of adverse events related to tree nut ingestion, number and frequency of tree nuts ingested, quality of life and parental anxiety, and allergy‐related healthcare visits from randomization to 18 months of age. Analyses will be performed on an intention‐to‐treat basis. TreEAT was approved by the Royal Children's Hospital Human Research Ethics Committee (#70489). Outcomes will be presented at scientific conferences and disseminated through publication. ClinicalTrials.gov ID: NCT04801823.
Publisher: Informa UK Limited
Date: 15-06-2015
Publisher: Elsevier BV
Date: 03-2020
Publisher: Wiley
Date: 2017
DOI: 10.1111/JSPN.12167
Abstract: Attaining high immunisation coverage rates for children with medical conditions is vital. The Royal Children's Hospital (RCH) Immunisation Service has the opportunity to check each inpatient's immunisation status and provide opportunistic vaccines and/or bring the Australian Childhood Immunisation Register (ACIR) up-to-date. This paper highlights that during admission, one quarter of children were not up-to-date with routine scheduled immunisations and 42% of those inpatients due or overdue for immunisation were vaccinated. The model of establishing routine checking of immunisation records and reminding hospital staff about immunisation can result in improvements in vaccination coverage. Healthcare providers have a responsibility to check immunisation status and offer vaccines when necessary however, often there are missed opportunities to immunise. This paper demonstrates that having a dedicated Immunisation Service, a partnership with a relevant government agency, and effective collaboration with inpatient clinical teams, opportunistic immunisation can be achieved for inpatients.
Publisher: Springer Science and Business Media LLC
Date: 16-05-2017
DOI: 10.1007/S40272-017-0231-7
Abstract: Maternal immunization has undergone a paradigm shift in recent years, as women and healthcare providers accept and recognize the benefits of this strategy not only for the pregnant woman but also for the developing fetus and young infant. This article reviews the evidence for active immunization during pregnancy, with an emphasis on perinatal and infant outcomes. Current recommendations for immunization during pregnancy are presented, with particular focus on the routinely recommended vaccines during pregnancy: influenza and Tdap (tetanus, diphtheria, and pertussis). We discuss future research directions, maternal vaccines in development, and considerations for optimizing and advancing this underutilized strategy.
Publisher: American Society for Microbiology
Date: 28-12-2011
DOI: 10.1128/CVI.05379-11
Abstract: The rate of decay of antibody concentration following serogroup C meningococcal (MenC) polysaccharide-protein conjugate vaccination varies between in iduals. This depends partly on vaccination age but may be influenced by human genetics. We studied 721 single nucleotide polymorphisms (SNPs) across 131 candidate genes in a first cohort of 905 Caucasians (11 to 21 years old mean time after vaccination, 4.9 years) and 30 SNPs across 17 genes in a replication study using 155 children, aged 6 to 12 years (mean time after vaccination, 6.7 years), and 196 infants (1 year old mean time after vaccination, 8 months). In iduals were classified as responders or nonresponders for total MenC IgG concentration and MenC serum bactericidal antibody (SBA) measurements. Associated genes were examined further for quantitative outcome measures. Fifty-nine SNPs in 37 genes were associated with IgG persistence (adjusted for age at measurement), and 56 SNPs in 36 genes were associated with SBA persistence (adjusted for age at measurement and vaccine used). Three SNPs each within the Toll-like receptor 3 (TLR3) (rs3775291, rs3775292, and rs5743312) and CD44 (rs11033013, rs353644, and rs996076) genes were associated with IgG (adjusted for age at measurement) or SBA (adjusted for age at measurement and vaccine used) persistence in the initial genetic study ( P , 0.02 to 0.04). Single SNPs within the TLR3 (rs7657186) ( P = 0.004 [unadjusted]) and CD44 (rs12419062) ( P = 0.01 [unadjusted]) genes were associated with IgG persistence in the replication study. These results suggest that genetic polymorphisms in the TLR3 and CD44 genes are associated with the persistence of the immune response to MenC vaccines 1 to 6 years after vaccination.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2009
Publisher: Elsevier BV
Date: 05-2021
Publisher: Massachusetts Medical Society
Date: 30-07-2020
Publisher: Informa UK Limited
Date: 26-06-2018
Publisher: Authorea, Inc.
Date: 23-10-2022
DOI: 10.22541/AU.166651176.60803175/V1
Abstract: Introduction: Children with peanut allergy are at increased risk of developing tree nut allergies, which can be severe and for most lifelong. Introduction of peanut in the first year of life can reduce the risk of peanut allergy, however, prevention strategies for tree nut allergies have not been established. We aimed to test the efficacy and safety of a novel strategy, a supervised multi-nut oral food challenge (OFC) compared to standard care for tree nut allergy prevention in infants at high risk of developing tree nut allergy, TreEAT. Methods and analysis: TreEAT is a 2-armed, open-label, randomised, controlled trial (RCT). Infants (n=212) aged 4-11months with peanut allergy will be randomised 1:1 at peanut allergy diagnosis to either a hospital-based multi-tree nut (almond, cashew, hazelnut and walnut) OFC using multi-nut butter or standard care (home introduction of in idual tree nuts). All infants will be assessed at age 18months, with questionnaires and SPT to peanut and tree nuts. Peanut and tree nut OFCs will be performed as required to determine allergy status for each nut. The primary outcome is tree nut allergy at age 18 months. Secondary outcomes include peanut allergy resolution, proportion and severity of adverse events related to tree nut ingestion, number and frequency of tree nuts ingested, quality of life and parental anxiety and allergy related healthcare visits from randomisation to 18 months of age. Analyses will be performed on an intention-to-treat basis. Ethics and dissemination TreEAT was approved by the Royal Children’s Hospital Human Research Ethics Committee (#70489). Outcomes will be presented at scientific conferences and disseminated through publication. Trial registration number : ClinicalTrials.gov ID: NCT04801823
Publisher: Elsevier BV
Date: 06-2020
Publisher: American Academy of Pediatrics (AAP)
Date: 09-2021
Abstract: Infant influenza and pertussis disease causes considerable morbidity and mortality worldwide. We examined the effectiveness of maternal influenza and pertussis vaccines in preventing these diseases in infants. This inception cohort study comprised women whose pregnancies ended between September 1, 2015, and December 31, 2017, in Victoria, Australia. Maternal vaccination status was sourced from the Victorian Perinatal Data Collection and linked to 5 data sets to ascertain infant outcomes and vaccination. The primary outcome of interest was laboratory-confirmed influenza or pertussis disease in infants aged & months, 2 to & months, and & months combined. Secondary outcomes included infant hospitalization (emergency presentation or admission) and death. Risk ratios and 95% confidence intervals (CIs) were estimated by Poisson regression. Vaccine effectiveness (VE) was estimated as (1 minus the risk ratio) x 100%. Among 186 962 pregnant women, 85 830 (45.9%) and 128 060 (68.5%) were vaccinated against influenza and pertussis, respectively. There were 175 and 51 infants with laboratory-confirmed influenza and pertussis disease, respectively. Influenza VE was 56.1% (95% CI, 23.3% to 74.9%) for infants aged & months and 35.7% (2.2% to 57.7%) for infants aged 2 to & months. Pertussis VE was 80.1% (95% CI, 37.1% to 93.7%) for infants aged & months and 31.8% (95% CI, −39.1% to 66.6%) for infants aged 2 to & months. Our study provides evidence of the direct effectiveness of maternal influenza and pertussis vaccination in preventing these diseases in infants aged & months. The findings strengthen the importance of maternal vaccination to prevent these diseases in infants.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 05-2020
Publisher: Frontiers Media SA
Date: 02-04-2021
DOI: 10.3389/FIMMU.2021.646677
Abstract: The humoral response to vaccinations varies widely between in iduals. There is no data available on the correlation between responses to different vaccines. In this study, we investigated the correlation of antibody responses between routine vaccine antigens in infants. One and seven months after the 6-month vaccinations and one month after the 12-month vaccinations, antibody concentrations to diphtheria, tetanus, pertussis, polio (serotypes 1-3), Haemophilus influenzae type b (Hib), pneumococcus (13 serotypes), meningococcus C, measles, mumps and rubella were measured using fluorescent bead-based multiplex immune-assays. For the correlation of antibody responses, Spearman’s rank correlation coefficients (ρ) with 95% confidence intervals (CI) were calculated between responses to each vaccine antigen. The correlation between concentrations of antibodies to the vaccinations ending at 6 months of age was higher one month compared to seven months after vaccination. The strongest correlations at both time points were observed between antibody responses to different polio serotypes, certain pneumococcal serotypes and between responses to diphtheria and pneumococcal (conjugated to a diphtheria toxoid) vaccine antigens. Correlation between responses to tetanus, Hib, pertussis, polio and other vaccine antigens were weak. The correlation between antibody responses to the 12-month vaccine antigens was weaker than to the 6-month vaccine antigens and there was a negative correlation between responses to measles, mumps, rubella vaccine and non-live vaccine antigens (meningococcus C, tetanus and Hib). There was only weak correlation between antibody responses to vaccines of the same type (e.g. conjugated polysaccharide or toxoid vaccines). Correlation between antibody responses to similar antigens in the same vaccine (such as different serotypes of a bacteria or virus), as well as responses to antigens conjugated to similar carrier proteins, are strong. In contrast, correlation between responses to other vaccines are weak. Measuring antibody responses to one or a few vaccine antigens therefore does not offer a reliable surrogate marker of responses to unrelated vaccines.
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.VACCINE.2019.03.016
Abstract: Bacillus Calmette-Guérin vaccine (BCG), one of the most widely used vaccines, does not only provide protection against tuberculosis and other mycobacterial infections, but also has non-specific (heterologous) immunomodulatory effects. In participants in a randomised trial, we investigated the effect of neonatal BCG immunisation on antibody responses to routine infant vaccines given in the first year of life. Antibodies against antigens in the diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b (Hib), and the 13-valent pneumococcal conjugate vaccines were measured in 91 (45 BCG-vaccinated, 46 BCG-naïve) infants one month after, and in 310 (169 BCG-vaccinated, 141 BCG-naïve) infants seven months after immunisation at 6 weeks, 4 and 6 months of age. In addition, antibodies against meningococcus C, Hib, measles, mumps, and rubella were measured in 147 (78 BCG-vaccinated, 69 BCG-naïve) infants one month after immunisation at 12 months of age. The seroprotection rates for each vaccine and the geometric mean concentrations (GMC) of antibodies were compared in BCG-vaccinated and BCG-naïve infants. At 7 months of age, seroprotection rates were high in both BCG-vaccinated and BCG-naïve infants. At 13 months of age, seroprotection rates were lower than at 7 months of age, particularly for pertussis and a number of pneumococcal antigens, with generally higher rates for the latter in BCG-vaccinated infants. Although not statistically significant, antibody responses in BCG-vaccinated infants were consistently higher against diphtheria, tetanus, and pneumococcal antigens at both 7 and 13 months of age, and against measles and mumps at 13 months of age, but were lower against Hib one month after immunisation at both 7 and 13 months of age. The immunomodulatory effect of BCG on antibody responses to heterologous vaccines adds to the evidence that BCG immunisation at birth has broad heterologous effects on the infant immune system.
Publisher: Wiley
Date: 21-04-2019
DOI: 10.5694/MJA2.50125
Abstract: To assess variations by time of year and hospital in the uptake of influenza and pertussis vaccinations by pregnant women in Victoria to identify factors associated with vaccination uptake. Retrospective analysis of data in the Victorian Perinatal Data Collection (VPDC), a population surveillance system for obstetric conditions, procedures, and pregnancy and birth outcomes. Women whose pregnancies ended in a live or stillbirth during July 2015 - June 2017. Influenza and pertussis vaccinations during pregnancy. 153 980 pregnancies in 67 hospitals ended during July 2015 - June 2017 59 968 pregnant women (39.0%) were vaccinated against influenza and 98 583 (64.0%) against pertussis. Coverage varied by pregnancy end date, rising for influenza during winter and spring, but for pertussis rising continuously across the two years from 37.5% to 82.2%. Differences between hospitals in coverage were marked. Factors associated with vaccination included greater maternal age, primigravidity, early antenatal care, and GP-led care. The odds of vaccination were statistically significantly lower for women born overseas and those who smoked during pregnancy the odds of vaccination were also lower for Aboriginal and Torres Strait Islander women. Pertussis vaccination of pregnant women in Victoria has increased, but influenza vaccination rates remain moderate and variable. Structural changes at the system level may improve maternal vaccination rates. Embedding the delivery of maternal vaccination programs in antenatal care pathways should be a priority.
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.VACCINE.2018.12.059
Abstract: Data on duration of protection against invasive meningococcal disease post-vaccination with the recombinant, 4-component, meningococcal serogroup B vaccine (4CMenB) are limited. We evaluated bactericidal activity persistence in adolescents/young adults up to 7.5 years post-primary vaccination with 4CMenB, and response to a booster dose compared with vaccine-naïve controls. This open-label, multicenter study (NCT02446743) enrolled 15-24 year-old-previously vaccinated participants from Canada, Australia (group Primed_4y) 4 years post-priming with 4CMenB (2 doses 0,1-month schedule), and Chile (Primed_7.5y) 7.5 years after priming with 4CMenB (2 doses 0,1/0,2/0,6-month schedule) and vaccine-naïve participants of similar age (Naïve_4y and Naïve_7.5y groups). Primed participants received a booster dose vaccine-naïve participants received 2 catch-up doses of 4CMenB, 1 month apart. We evaluated antibody persistence and immune responses using hSBA in terms of geometric mean titers and percentages of participants with hSBA titers ≥4, the kinetics of bactericidal activity post-booster (previously vaccinated) or post-2 doses (vaccine-naïve), and safety. Antibody levels declined at 4 (Primed_4y) and 7.5 (Primed_7.5y) years post-primary vaccination, but remained higher than in vaccine-naïve participants at baseline (≤44% vs ≤ 13% [fHbp] ≤84% vs ≤ 24% [NadA] ≤29% vs ≤ 14% [PorA]) for all vaccine antigens except NHBA (≤81% vs ≤ 79%). One month post-booster and post-second dose, 93-100% of primed and 79-100% of vaccine-naïve participants had hSBA titers ≥4 for all antigens. Kinetics of the antibody response were similar across groups with an early robust response observed 7 days post-booster/second dose. No vaccine-related serious adverse event was reported. For all antigens except NHBA, a higher proportion of primed participants had hSBA titers ≥4, at 4 and 7.5 years post-vaccination, compared with vaccine-naïve participants. A more robust immune response after booster compared to a first dose in vaccine-naïve in iduals, showed effective priming in an adolescent/young adult population. No safety or new reactogenicity issues were identified.
Publisher: Wiley
Date: 28-03-2019
DOI: 10.1111/IMCB.12246
Abstract: It is proposed that measles-containing vaccines have immunomodulatory effects which include a reduction in all-cause childhood mortality. The antibody response to heterologous vaccines provides a means to explore these immunomodulatory effects. This is the first study to investigate the influence of measles-mumps-rubella (MMR) vaccine on the persistence of antibodies to a broad range of heterologous infant vaccinations given in the first year of life. In total, 319 children were included in the study. All infants received routine vaccinations at 6 weeks, 4 and 6 months of age. At 12 months of age, 212 children were vaccinated with MMR and Haemophilus influenzae type b-meningococcus C (Hib-MenC) vaccines while the remaining 99 children had not yet received these vaccines. In the MMR/Hib-MenC-vaccinated group, blood was taken 28 ± 14 days after receiving these vaccines. Antibodies against diphtheria, tetanus, pertussis [pertussis toxin (PT), filamentous hemagglutinin, pertactin], poliomyelitis (type 1, 2, 3) and 13 pneumococcal serotypes were measured. Seroprotection rates and geometric mean antibody concentrations were compared between MMR/MenC-Hib-vaccinated and MMR/MenC-Hib-naïve participants. In the final analysis, 311 children were included. Seroprotection rates were lower in MMR/Hib-MenC-vaccinated children against PT and pneumococcal serotype 19A. After adjustment for prespecified factors, MMR/Hib-MenC-vaccinated infants had significantly higher antibody concentrations against tetanus (likely explained by a boosting effect of the carrier protein, a tetanus toxoid), while for the other vaccine antigens there was no difference in antibody concentrations between the two groups. MMR vaccination given at 12 months of age in a developed country does not significantly influence antibody concentrations to heterologous vaccines received in the first year of life.
Publisher: Massachusetts Medical Society
Date: 11-05-2023
Publisher: BMJ
Date: 22-02-2019
DOI: 10.1136/ARCHDISCHILD-2018-316254
Abstract: Despite immunisation, antibiotics and intensive care management, infection with Streptococcus pneumoniae remains a major cause of morbidity and mortality in children. The WHO currently recommends vaccinating infants with either a 3+0 schedule (6 weeks, 3–4 and 4–6 months of age) or 2+1 schedule (2 doses before 6 months of age, plus a booster dose at 9–15 months of age). This study investigated pneumococcal antibody responses, including persistence of antibodies, after immunisation of healthy infants with a 3+0 schedule. We measured pneumococcal antibody concentrations to all 13 antigens included in the 13-valent pneumococcal conjugate vaccine (PCV13) after immunisation with a 3+0 schedule in 91 infants at 7 months and in 311 infants at 13 months of age. The geometric mean concentrations (GMCs) and the proportion of infants with an antibody concentration above the standard threshold correlate of protection (seroprotection rate) were calculated at both time points. At 7 months of age, GMCs varied between 0.52 µg/mLand 11.52 µg/mL, and seroprotection rates varied between 69% and 100%. At 13 months of age, GMCs had decreased to between 0.22 µg/mLand 3.09 µg/mL, with the lowest responses against serotype 4, followed by 19A, 3, 6B and 23F. Seroprotection rates at 13 months of age were below 90% for most serotypes, with the lowest rates for serotype 4 (23%) followed by 19A (50%), 23F (61%) and 6B (64%). Our study shows that at 13 months of age, many infants vaccinated with a 3+0 schedule have pneumococcal antibody concentrations below the standard threshold correlate of protection. To optimise protection against pneumococcal disease through early childhood and to improve antibody persistence and indirect protective effects, immunisation schedules with booster doses might be necessary.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.JAIP.2019.05.057
Abstract: Cashew is a common cause of tree nut allergy in children. To date there have been few studies of diagnostic tests for cashew allergy, and positive predictive values (PPVs) for cashew as well as other tree nuts are largely extrapolated from studies of peanut allergy. How relevant these cutoffs are for cashew has not been formally explored. We aimed to establish skin prick test (SPT) wheal sizes that correlated to 95% PPV for a positive food challenge for cashew. We included all cashew oral food challenges (OFCs) conducted as part of the HealthNuts (n = 108 age, 4-6 years) and SchoolNuts (n = 37 age, 10-14 years) studies, both recruited from the community (population cohort). A second cohort of all cashew OFCs conducted at the Royal Children's Hospital (RCH) allergy center (n = 343) (2011-2016) and a private allergy clinic based at RCH (n = 43) was included via electronic medical record review (clinic cohort). The 95% PPV for cashew SPT was calculated for both cohorts. Among the population cohort (n = 145), 62% of cashew OFCs were positive compared with 20% of the clinic cohort (n = 386). The SPT cutoff for 95% PPV derived from the population cohort was 10 mm (95% confidence interval [CI], 7.5-12.0). For the clinic cohort, the 95% PPV was 14 mm (95% CI, 9.5-unknown). An SPT wheal size of 8 mm had a PPV of 89% (95% CI, 79-95) in the population cohort and 62% (95% CI, 45-78) in the clinic cohort. A higher SPT wheal size may be more appropriate than the commonly used 8 mm cutoff to guide clinical decisions around when to perform OFC for cashew.
Publisher: Research Square Platform LLC
Date: 08-12-2020
DOI: 10.21203/RS.3.RS-116911/V1
Abstract: Background: Patients with Inflammatory Bowel Disease (IBD) are at increased risk of serious infections, including vaccine preventable diseases. Current evidence suggests uptake of additional recommended special risk vaccinations is low. Identification of IBD patients prior to commencing immunosuppressive therapy allows for optimisation of vaccination, including timely administration of live-attenuated and additional recommended vaccines, such as influenza and pneumococcal vaccines. Methods: Paediatric patients (0-18 years) seen at the tertiary Royal Children’s Hospital, Melbourne, Australia, with a recent diagnosis of IBD were referred by the Gastroenterology Unit to our Specialist Immunisation Clinic (SIC) for assessment and provision of routine and special risk vaccines. Data was collected via a standardised REDCap questionnaire completed in or post attendance at the SIC and included serology results where available. Results: Sixty-nine paediatric patients were recruited to the study between 2014 and 2017. Median age at IBD diagnosis was 11.25 years (IQR 4.64 years), with median time between diagnosis and SIC review of 0.88 years (IQR 2.84 years). At initial review 84.1% (58/69) of patients were up to date with vaccines on the Australian National Immunisation Program (NIP) schedule. Of those who were tested, serological evidence of immunity was demonstrated in 38.3% (23/60) of patients for Hepatitis B, 66.7% (36/54) for measles, 51.9% (28/54) for rubella and 41.9% (26/62) for Varicella Zoster Virus. Prior to SIC review 47.8% (33/69) had additional vaccinations and 92.8% (64/69) had vaccinations administered in the 12 months following SIC assessment. The Pneumococcal conjugate vaccine (76.8%, 53/69) was the most commonly administered vaccine after SIC review, followed by influenza vaccine (69.6%, 48/69). Within 12 months of SIC review 43.5% (30/69) of patients had completed the schedule and were up-to-date as recommended by the SIC. Conclusions: Children with IBD and other special risk groups can benefit from early referral to a SIC team to ensure optimal administration of routine and additionally recommended vaccines, especially live and additional special risk vaccines. The value of optimising immunisations could also be applied to other special risk groups, including adult IBD cohorts, particularly those commencing newer biologic immunosuppressive medications.
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.FOODCHEM.2021.131028
Abstract: Macadamia nut is an increasingly popular food item of a healthy diet. However, macadamia nut is also a potent allergenic food. To date, there is little information about the allergenic proteins involved. In this study, using sera from macadamia nut allergic in iduals, four IgE-binding proteins were detected. Their identities were determined by tandem mass spectrometry with de novo sequencing. Three IgE-reactive proteins, the vicilin Mac i 1, the legumin Mac i 2 and the antimicrobial peptide 2a/Mac i 1 (28-76) were purified from the nut while the non-specific lipid transfer protein was produced as a recombinant in Pichia pastoris. IgE-binding assays using sera from well-characterized groups of tree nut and/or peanut allergic patients revealed that the allergens were mainly recognized by sera from macadamia nut allergic in iduals. Hence, these newly discovered allergens will enable molecular diagnostics to identify patients at high risk of macadamia nut allergy.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2021
Publisher: Elsevier BV
Date: 11-2020
Publisher: Frontiers Media SA
Date: 25-08-2023
Publisher: Elsevier BV
Date: 10-2018
Publisher: Wiley
Date: 24-10-2020
DOI: 10.1111/JPC.15229
Publisher: Elsevier BV
Date: 2021
DOI: 10.1016/J.JAIP.2021.10.070
Abstract: Treatment of food allergy is a rapidly changing landscape, with arguably, the most significant advancement in recent years, the transition of oral immunotherapy (OIT) to clinical practice. As an innovation, OIT is a phase of rapidly increasing demand, particularly for some allergens such as peanut, egg, and milk, which have substantial evidence of efficacy. However, significant questions remain about how to best treat multiple food allergies and less common food allergies and how to optimize long-term safety and efficacy. This review summarizes the currently available resources for integrating food allergy OIT into clinical practice and focuses on the multiple remaining unmet needs such as providing an approach for OIT to food allergens for which there is no or limited evidence practical issues related to food allergy treatment particularly when it is not going well long-term outcomes and follow-up after OIT and strategies to help meet the impending increase in demand.
Publisher: Australian Nursing and Midwifery Federation
Date: 26-05-2021
Publisher: Oxford University Press (OUP)
Date: 11-2022
Abstract: 4CMenB has been shown to be immunogenic with an acceptable safety profile in infants and young adolescents. However, no data on long-term persistence after primary vaccination in adolescents are available. This is the first study to assess antibody persistence, booster response, and safety of 4CMenB in adolescents and young adults up to 7.5 years following the primary vaccination in adolescence. This phase 3b, open-label, extension study (NCT02446743) assessed the antibody persistence and booster response at 4 years (Canada and Australia, NCT01423084) or 7.5 years (Chile, NCT00661713) after primary vaccination with 4CMenB (following 0 + 1-, 0 + 2-, or 0 + 6-month schedules), compared with vaccine-naïve (VN), healthy controls. Chilean follow-on (FO) and VN participants aged 18–24 years received either a booster dose of 4CMenB 7.5 years postprimary series (Group FO, N = 131) or 2 primary doses, 1 month apart (Group VN, N = 150). Immunogenicity was measured using human serum bactericidal antibody assay (hSBA) against antigen-specific strains. Immune response was evaluated 1 month post-booster vaccination and compared with VN controls at 1 month post-first dose. Kinetics of antibody responses were measured at 3, 7, and 30 days post-vaccination. Safety was assessed. Antibody levels waned at 7.5 years postprimary vaccination in Group FO, but were higher than in Group VN at baseline, for all antigens except NHBA (table). At 1 month post-booster ost-first dose, 93–100% (Group FO) and 62–93% (Group VN) of participants had hSBA titres ≥4 GMTs ranged between 41 and 1,951 (Group FO) and 9.43–46 (Group VN) (table). The percentages of FO participants with hSBA titres ≥4 remained similar to prebooster for all 4 antigens at 3 days, increased at 7 days, and remained unchanged or increased further 30 days post-booster. The reactogenicity of 4CMenB was consistent with previous observations in this age group no safety concerns were identified during the study. Antibody levels in adolescents and young adults declined at 7.5 years after a 2-dose primary series of 4CMenB, but were higher than baseline levels in VN controls. An additional dose of 4CMenB elicited strong anamnestic responses—substantially higher than 1 dose in VN controls. Funding: GlaxoSmithKline Biologicals SA. T. Nolan, GSK: Research Contractor and Scientific Advisor, Research grant. Pfizer: Research Contractor, Research grant. M. O’Ryan, GSK: Investigator, Research support. F. De Looze, GSK: Investigator and Research Contractor, Research grant and Research support. H. Marshall, Pfizer: Grant Investigator and Investigator, Research grant. GSK: Grant Investigator and Investigator, Research grant. P. Richmond, GSK: Grant Investigator and Scientific Advisor, Grant recipient. S. Henein, SKDS Research Inc.: Investigator, Research payment. K. Heaton, Devonshire Clinical Research Inc.: Investigator, Research payment. M. Ferguson, GSK: Investigator, Salary from independent research clinic,CRG. D. D’Agostino, GSK: Employee, Salary. D. Toneatto, GSK: Employee and Shareholder, Salary.
Publisher: BMJ
Date: 06-2022
DOI: 10.1136/BMJOPEN-2021-056925
Abstract: Clinical studies supported by immunological data indicate early life intervention strategies to be promising in reducing the growing global burden of food allergies. The events that predispose to food allergy, including the induction of allergen-specific immune responses, appear to be initiated early in development. Early exposure to food allergens in utero and via breast milk is likely to be important in initiating oral tolerance. We aim to determine the effectiveness of higher maternal food allergen consumption during pregnancy and lactation on infant food allergy outcomes. This is a multisite, parallel, two-arm (1:1 allocation), single-blinded (outcome assessors, statistical analyst and investigators), randomised controlled trial. Pregnant women ( weeks’ gestation) whose (unborn) infants have at least two biological family members (mother, father or siblings) with medically diagnosed allergic disease are eligible to participate. After obtaining written informed consent, pregnant women are randomised to either a high egg and peanut diet (at least 6 eggs and 60 peanuts per week) or standard (low) egg and peanut diet (no more than 3 eggs and 30 peanuts per week). The women are asked to follow their allocated diet from weeks’ gestation to 4 months’ lactation. The primary outcome is food challenge proven IgE-mediated egg and/or peanut allergy in the infants at 12 months of age. Key secondary outcomes include infant sensitisation to egg and/or peanut and infant eczema. Our target s le size is 2136 women. Analyses will be performed on an intention-to-treat basis according to a pre-specified statistical analysis plan. Ethical approval has been granted from the Women’s and Children’s Health Network Human Research Ethics Committee (approval number HREC/18/WCHN/42). Trial results will be presented at scientific conferences and published in peer-reviewed journals. Australian New Zealand Clinical Trials Registry ACTRN12618000937213.
Publisher: American Medical Association (AMA)
Date: 09-01-2008
Abstract: Immunization with a meningococcal tetravalent (serogroup ACWY) glycoconjugate vaccine is recommended for all US adolescents. However, the currently licensed vaccine is poorly immunogenic in infancy, when the highest rates of disease are observed. To determine the immunogenicity of a novel tetravalent CRM(197)-conjugated meningococcal vaccine (MenACWY) in infants. Randomized, open-label, controlled study of 225 UK and 196 Canadian 2-month-olds from August 2004 to September 2006. UK infants received a primary course of MenACWY (at 2, 3, and 4 months or 2 and 4 months) or Neisseria meningitidis serogroup C monovalent meningococcal glycoconjugate vaccine (MenC) (at 2 and 4 months). All received MenACWY at 12 months. Canadian infants received MenACWY at 2, 4, and 6 months or 2 and 4 months at 12 months they received MenACWY, a plain tetravalent polysaccharide vaccine, or no vaccine. Percentage of infants with a human complement serum bactericidal activity (hSBA) titer >or=1:4 after a primary course of MenACWY and after a 12-month booster. Safety and reactogenicity of MenACWY were also assessed. According to the prespecified per-protocol analysis, the percentages (95% CIs) of MenACWY 2-, 3-, and 4-month recipients with hSBA titers >or=1:4 after primary immunization were serogroup A, 93% (84%-98%) C, 96% (89%-99%) W-135, 97% (90%-100%) and Y, 94% (86%-98%). With a post hoc intention-to-treat analysis with imputed values for missing data, these values were unchanged for serogroups C and Y for serogroup A, values were 92% (84%-97%), and for W-135, 97% (91%-99%). For the per-protocol analysis of MenACWY 2-, 4-, and 6-month recipients, the percentages (95% CIs) of responders were A, 81% (71%-89%) C, 98% (92%-100%) W-135, 99% (93%-100%) and Y, 98% (92%-100%). With the imputed value analysis, these values were A, 83% (74%-89%) C, 98% (93%-99%) W-135, 99% (94%-100%) and Y, 98% (92%-99%). At least 84% of MenACWY 2- and 4-month recipients achieved hSBA titers >or=1:4 for serogroups C, W-135, and Y after primary immunization, as did at least 60% for serogroup A (per-protocol and imputation analysis). At least 95% of primary and booster MenACWY recipients achieved hSBA titers >or=1:4 for serogroups C, W-135, and Y at 13 months, as did at least 84% for serogroup A (per-protocol and imputation analysis). During the primary immunization course, postimmunization pain on leg movement was observed in 2% of UK MenACWY 2- and 4-month recipients and 4% of MenC 2- and 4-month recipients a temperature of 38 degrees C or greater was observed in 4% and 2% in these groups, respectively. MenACWY is well tolerated and immunogenic in infancy. Trial Registration clinicaltrials.gov Identifier: NCT00262002.
Publisher: Wiley
Date: 04-12-2021
DOI: 10.1111/PAI.13705
Abstract: Measurement of cashew‐specific IgE (sIgE) is often used to confirm sensitization but does not reliably diagnose clinical allergy. Ana o 3 is the dominant cashew allergen detected in 75–100% of patients with cashew allergy but not currently used in clinical practice. To determine if component‐resolved diagnostics using specific IgE to the 2 S albumin from cashew, Ana o 3, improves the accuracy of diagnosing cashew allergy, thereby circumventing the need for an oral food challenge (OFC) in some patients. A population‐based s le of 5276 children was recruited at age 1 year and followed up at age 6 years. Children with positive cashew skin prick test at age 6 underwent an OFC to clarify allergy status. Forty‐seven children (mean age 5.02 ± 0.2) (33 cashew‐allergic and 14 cashew‐tolerant) had cashew sIgE and Ana o 3 sIgE quantified by ImmunoCAP System FEIA. A cutoff of .32 kUA/L for Ana o 3 sIgE provided 95% specificity and 90% sensitivity and correctly identified 90% of clinical cashew allergy. At the same specificity, the sensitivity for cashew sIgE ( .5 kUA/L) was only 26%. Sequential measurement of cashew sIgE followed by Ana o 3 sIgE diagnosed 90% of children with cashew allergy without the need for an OFC. Ana o 3 sIgE testing provides higher diagnostic accuracy than cashew sIgE. Sequential measurement of cashew sIgE followed by Ana o 3 removed the need for a food challenge from 66% down to 12.8% (5‐fold) of children compared with cashew sIgE testing alone.
Publisher: Informa Healthcare
Date: 30-11-2005
DOI: 10.1517/14712598.5.12.1611
Abstract: Meningococcal disease, presenting primarily as septicaemia and meningitis, continues to be a devastating problem around the world. Over the last century, vaccine development has been undertaken in earnest for the prevention of this disease. Polysaccharide vaccines have been available for almost 40 years, yet they are poorly immunogenic in young children who are at the highest risk. Since their introduction into some routine immunisation schedules in 1999, polysaccharide-protein conjugate vaccines for the prevention of serogroup C meningococcal infection have proven efficacious. A quadrivalent polysaccharide-protein conjugate vaccine against serogroups A, C, W135 and Y, which is being introduced in the US this year, is hoped to control disease caused by these serogroups. To date, however, the development of a universally safe, immunogenic and effective serogroup B Neisseria meningitidis vaccine has remained a challenge. This review details the many conventional vaccine strategies and the more recent genome-derived technological approaches being used in serogroup B vaccine development. The future prevention of serogroup B disease will rely on both outer membrane vesicle vaccines being used for serosubtype-specific outbreaks and new vaccines containing multiple other antigens. Investment by the pharmaceutical industry in preclinical research and development provides hope that an efficacious serogroup B meningococcal vaccine can be developed.
Publisher: Elsevier BV
Date: 08-2019
Publisher: Springer Science and Business Media LLC
Date: 24-09-2020
DOI: 10.1186/S12874-020-01111-X
Abstract: Very large cohorts that span an entire population raise new prospects for the conduct of multiple trials that speed up advances in prevention or treatment while reducing participant, financial and regulatory burden. However, a review of literature reveals no blueprint to guide this systematically in practice. This Statement of Intent proposes how erse trials may be integrated within or alongside Generation Victoria (GenV), a whole-of-state Australian birth cohort in planning, and delineates potential processes and opportunities. Parents of all newborns (estimated 160,000) in the state of Victoria, Australia, will be approached for two full years from 2021. The cohort design comprises four elements: (1) consent soon after birth to follow the child and parent/s until study end or withdrawal retrospective and prospective (2) linkage to clinical and administrative datasets and (3) banking of universal and clinical bios les and (4) GenV-collected bios les and data. GenV-collected data will focus on overarching outcome and phenotypic measures using low-burden, universal-capable electronic interfaces, with funding-dependent face-to-face assessments tailored to universal settings during the early childhood, school and/or adult years. For population or registry-type trials within GenV, GenV will provide all outcomes data and consent via traditional, waiver, or Trials Within Cohorts models. Trials alongside GenV consent their own participants born within the GenV window GenV may help identify potential participants via opt-in or opt-out expression of interest. Data sharing enriches trials with outcomes, prior data, and/or access to linked data contingent on custodian’s agreements, and supports modeling of causal effects to the population and between-trials comparisons of costs, benefits and utility. Data access will operate under the Findability, Accessibility, Interoperability, and Reusability (FAIR) and Care and Five Safes Principles. We consider governance, ethical and shared trial oversight, and expectations that trials will adhere to the best practice of the day. Children and younger adults can access fewer trials than older adults. Integrating trials into mega-cohorts should improve health and well-being by generating faster, larger-scale evidence on a longer and/or broader horizon than previously possible. GenV will explore the limits and details of this approach over the coming years.
Publisher: Oxford University Press (OUP)
Date: 07-01-2014
DOI: 10.1093/CID/CIU001
Abstract: Protection against Haemophilus influenzae type b (Hib), a rapidly invading encapsulated bacteria, is dependent on maintenance of an adequate level of serum antibody through early childhood. In many countries, Hib vaccine booster doses have been implemented after infant immunization to sustain immunity. We investigated the long-term persistence of antibody and immunological memory in primary-school children following infant (with or without booster) Hib vaccination. Anti-polyribosylribitol phosphate (PRP) immunoglobulin G (IgG) concentration and the frequency of circulating Hib-specific memory B cells were measured before a booster of a Hib-serogroup C meningococcal (MenC) conjugate vaccine and again 1 week, 1 month, and 1 year after the booster in 250 healthy children aged 6-12 years in an open-label phase 4 clinical study. Six to 12 years following infant priming with 3 doses of Hib conjugate vaccine, anti-PRP IgG geometric mean concentrations were 3.11 µg/mL and 0.71 µg/mL and proportions with anti-PRP IgG ≥1.0 µg/mL were 79% and 43% in children who had or had not, respectively, received a fourth Hib conjugate vaccine dose (mean age, 3.9 years). Higher baseline and post-Hib-MenC booster responses (anti-PRP IgG and memory B cells) were found in younger children and in those who had received a fourth Hib dose. Sustained Hib conjugate vaccine-induced immunity in children is dependent on time since infant priming and receipt of a booster. Understanding the relationship between humoral and cellular immunity following immunization with conjugate vaccines may direct vaccine design and boosting strategies to sustain in idual and population immunity against encapsulated bacteria in early childhood. Clinical Trials Registration ISRCTN728588998.
Publisher: American Medical Association (AMA)
Date: 11-2018
Publisher: Elsevier BV
Date: 08-2011
DOI: 10.1016/J.VACCINE.2011.06.005
Abstract: Preterm infants should receive immunisations according to their chronological, rather than gestational, age however concern about possible adverse events following immunisation (AEFI) in this group often means routine immunisations are delayed. A small number of infants may have apnoea with or without bradycardia temporally associated with immunisation. The risk factors for, and recurrence rate of apnoea with subsequent immunisations are unknown, which makes planning for subsequent immunisations for these highly vulnerable infants difficult. To determine recurrence rates for apnoea temporally associated with immunisation in preterm and term infants and to explore potential risk factors associated with recurrent apnoea in preterm infants. A retrospective analysis of all apnoea +/-bradycardia AEFIs in preterm and term infants, reported to the Surveillance of Adverse Events Following Vaccination In the Community (SAEFVIC), Victoria, Australia over a 3-year period from May 2007 to April 2010. Apnoea +/-bradycardia was defined as temporally associated with immunisation if it occurred up to 48h after immunisation. 7 out of 38 [18%, 95% confidence interval 6-31%] preterm infants with apnoea +/-bradycardia post initial immunisation had recurrent apnoea with subsequent immunisations. Possible risk factors for recurrence included: lower birth weight (p=0.04) and ongoing hospitalisation for complications relating to prematurity (p=0.01). No preterm infant with recurrent apnoea had a third episode of apnoea with subsequent immunisation. None of the 8 term infants with a reported apnoea AEFI had recurrence of apnoea with subsequent immunisation. There is a risk of recurrence of apnoea associated with immunisation in preterm infants. We recommend that preterm infants with apnoea post immunisation should receive reliable cardio-respiratory monitoring for a minimum of 24h following the next scheduled immunisation.
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.JAIP.2022.03.031
Abstract: The association between mode of delivery and the risk of food allergy remains unclear due to the absence of studies with both challenge-proven food allergy outcomes and detailed information on the type of caesarean delivery. We assessed whether emergency or elective caesarean, or caesarean delivery in the presence or absence of labor initiation, is associated with the risk of food allergy. The HealthNuts study recruited 5276 12-month-old infants who underwent skin prick testing and oral food challenge to ascertain food allergy status, and linked the child's study data to additional birth data from the Victorian Perinatal Data Collection. Parents of 3006 children consented to data linkage, and birth data were obtained on 2045. In this subgroup, 30% were born by caesarean and 13% had food allergy. Caesarean delivery, compared with vaginal birth, was not associated with the risk of food allergy (adjusted odds ratio [aOR]: 0.95, 95% confidence interval [CI]: 0.70, 1.30). Neither caesarean delivery before the onset of labor, nor after the onset of labor, was associated with the risk of food allergy (aOR: 0.83, 95% CI: 0.55-1.23 and aOR: 1.13, 95% CI: 0.75-1.72, respectively). Delivery by elective or emergency caesarean, compared with vaginal delivery, was not associated with risk of food allergy (aOR: 1.05, 95% CI: 0.71-1.55 and aOR: 0.86, 95% CI: 0.56-1.31). There was no evidence of effect modification by breastfeeding, older siblings, pet dog ownership, or maternal allergy. Caesarean delivery, either with or without labor, or elective or emergency, was not associated with the risk of food allergy in a population-based cohort of 12-month-old infants.
Publisher: Informa UK Limited
Date: 10-05-2018
Publisher: Figshare
Date: 2018
Publisher: Wiley
Date: 31-03-2009
Publisher: BMJ
Date: 06-2022
DOI: 10.1136/BMJPO-2022-001472
Abstract: COVID-19 mRNA vaccine-associated myocarditis has previously been described however specific features in the adolescent population are currently not well understood. To describe myocarditis adverse events following immunisation reported following any COVID-19 mRNA vaccines in the adolescent population in Victoria, Australia. Statewide, population-based study. Surveillance of Adverse Events Following Vaccination in the Community (SAEFVIC) is the vaccine-safety service for Victoria, Australia. All SAEFVIC reports of myocarditis and myopericarditis in 12–17-year-old COVID-19 mRNA vaccinees submitted between 22 February 2021 and 22 February 2022, as well as accompanying diagnostic investigation results where available, were assessed using Brighton Collaboration criteria for diagnostic certainty. Any mRNA COVID-19 vaccine. Confirmed myocarditis as per Brighton Collaboration criteria (levels 1–3). Clinical review demonstrated definitive (Brighton level 1) or probable (level 2) diagnoses in 75 cases. Confirmed myocarditis reporting rates were 8.3 per 100 000 doses in this age group. Cases were predominantly male (n=62, 82.7%) and post dose 2 (n=61, 81.3%). Rates peaked in the 16–17-year-old age group and were higher in males than females (17.7 vs 3.9 per 100 000, p= .001). The most common presenting symptoms were chest pain, dyspnoea and palpitations. A large majority of cases who had a cardiac MRI had abnormalities (n=33, 91.7%). Females were more likely to have ongoing clinical symptoms at 1-month follow-up (p=0.02). Accurate evaluation and confirmation of episodes of COVID-19 mRNA vaccine-associated myocarditis enabled understanding of clinical phenotypes in the adolescent age group. Any potential vaccination and safety surveillance policies needs to consider age and gender differences.
Publisher: The Royal Australian College of General Practitioners
Date: 10-2020
Publisher: Wiley
Date: 10-10-2019
DOI: 10.1111/APA.14932
Abstract: We investigated the effect of early-life factors, namely sex, delivery mode, feeding method and antibiotic exposure, on antibody responses to routine vaccinations administered during the first year of life. One and seven months after the primary course of routine vaccines and 1 month after routine vaccines at 12 months of age, antibodies against 26 vaccine antigens were measured in 398 healthy infants. The geometric mean concentration (GMC) of antibodies (adjusted for effect modifiers with multiple linear regression) and the seroprotection rate for each vaccine were compared for each early-life factor. Sex had an influence on GMCs. Antibody concentrations were significantly lower at 7 months of age in females for tetanus and filamentous haemagglutinin and at 13 months of age for pertactin. In contrast, at 13 months of age, antibody concentrations were significantly higher in females for polio type 3, pneumococcal serotype 6A and measles. Sex did not have an influence on seroprotection rates. Delivery mode, feeding method and antibiotic exposure did not exert a substantial influence on vaccine antibody concentrations. There is a difference between males and females in the humoral response to routine vaccinations in the first year of life.
Publisher: Wiley
Date: 06-11-2021
DOI: 10.1111/PAI.13684
Abstract: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of updating the guidelines on the diagnosis and management of food allergy. The existing guidelines are based on a systematic review of the literature until 30 September 2012. Therefore, a new systematic review must be undertaken to inform the new guidelines. This systematic review aims to assess the accuracy of index tests to support the diagnosis of IgE‐mediated food allergy. The databases Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID) will be searched for diagnostic test accuracy studies from 1 October 2012 to 30 June 2021. Inclusion and exclusion criteria will be used to select appropriate studies. Data from these studies will be extracted and tabulated, and then reviewed for risk of bias and applicability using the QUADAS‐2 tool. All evaluations will be done in duplicate. Studies with a high risk of bias and low applicability will be excluded. Meta‐analysis will be performed if there are three or more studies of the same index test and food. A protocol for the systematic review and meta‐analyses is presented and was registered using Prospero prior to commencing the literature search. Oral food challenges are the reference standard for diagnosis but involve considerable risks and resources. This protocol for systematic review aims to assess the accuracy of various tests to diagnose food allergy, which can be useful in both clinical and research settings.
Publisher: Wiley
Date: 08-2022
DOI: 10.1111/PAI.13839
Abstract: In the absence of a clear clinical history of reaction, diagnosis of cashew allergy using skin prick tests (SPT) or cashew‐specific IgE requires a high number of oral food challenges (OFC). By using Ana o 3 sIgE alone, or a two‐step diagnostic algorithm using cashew sIgE followed by Ana o 3 sIgE, there is a reduced need for OFC. We aimed to perform a cost comparison for both of these approaches compared with cashew SPT alone. Pooled in idual‐level data from 6 studies were used to determine diagnostic accuracy and OFC rate. Two studies used cashew SPT ( n = 567, 198 allergic), with 95% positive and negative predictive values of ≥12 mm and mm. Four studies were included in the pathways for Ana o 3 sIgE alone or a 2‐step algorithm incorporating cashew and Ana o 3 sIgE ( n = 271, 156 allergic). Cut‐offs used were ≥8.5kUA/L and ≤0.1kUA/L for cashew sIgE and ≥0.35kUA/L and ≤0.1kUA/L for Ana o 3 sIgE. Costs were constructed based on unit prices from hospital inpatient admissions, expenses incurred by families, in idual patient data on allergic reaction types and rates, and adrenaline autoinjector carriage, applying a health system perspective. Modeled data through the Ana o 3 pathway resulted in a 46.43% cost reduction (€307,406/1000 patients) compared with using cashew SPT alone (€573,854/1000 patients). The 2‐step algorithm resulted in a 44.94% cost reduction compared with SPT alone (€315,952.82/1000 patients). Both the Ana o 3 pathway and 2‐step algorithm resulted in a 79%–80% reduction in OFCs compared with SPT. Using Ana o 3 as a standalone test for cashew allergy diagnosis or a 2‐step algorithm incorporating cashew sIgE and Ana o 3 sIgE is accurate and results in a large reduction in both OFCs and health system costs compared with cashew SPT alone.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.VACCINE.2018.02.013
Abstract: 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. 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. 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. 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.
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.JAIP.2018.11.010
Abstract: Diagnosis of peanut allergy presents a significant clinical challenge. Accurate diagnosis is critical for patient management and prevention of allergic reactions, whereas overdiagnosis or failure to diagnose tolerance in a previously allergic patient can lead to unnecessary dietary restrictions and impaired quality of life. Oral food challenges, the criterion standard for diagnosis, pose a risk of potentially severe allergic reactions, and are time- and resource- intensive. In this article, we review other currently available tests for peanut allergy and present the strengths and weaknesses of each to assist the clinician in determining which test might be appropriate for their patients, as well as highlighting emerging tests currently in development. Traditional tests for peanut-specific IgE (skin prick testing and specific IgE) remain useful as first-line tests-a negative test result is useful for excluding peanut allergy and a high positive result has a high specificity for peanut allergy. For those with an intermediate positive test result, Ara h 2 testing might be useful as a second step. Basophil activation tests and peanut protein epitope-specific IgE analyses appear promising in recent studies however, further research is required into standardization, validation, and cost-effectiveness. Given the limitations of existing tests for peanut allergy, there remains a clear need for improvement. Finding a safe and affordable method for peanut allergy diagnosis that is both sensitive and specific remains an active area of research.
Publisher: Wiley
Date: 13-01-2020
DOI: 10.1111/PAI.13439
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.JACI.2022.04.008
Abstract: Prospectively collected data on the natural history of food allergy are lacking. We examined the natural history of egg and peanut allergy in children from age 1 to 6 years and assessed whether a skin prick test (SPT) result or other clinical factors at diagnosis are associated with the persistence or resolution of food allergy in early childhood. The HealthNuts cohort consists of 5276 children who were recruited at age 1 year and have been followed prospectively. Children with food allergy at age 1 year (peanut [n = 156] or raw egg [n = 471] allergy ) and children who developed new sensitizations or food reactions after age 1 year were assessed for food sensitization and allergy (confirmed by oral food challenge when indicated) at the 6-year follow-up. New-onset food allergy developed by age 6 years was more common for peanut (0.7% [95% CI = 0.5%-1.1%]) than egg (0.09% [95% CI = 0.03%-0.3%]). Egg allergy resolved more commonly (89% [95% CI = 85%-92%]) than peanut allergy (29% [95% CI = 22%-38%]) by age 6 years. The overall weighted prevalence of peanut allergy at age 6 years was 3.1% (95% CI = 2.6-3.7%) and that of egg allergy was 1.2% (95% = CI 0.9%-1.6%). The factors at age 1 year associated with persistence of peanut allergy were peanut SPT result of 8 mm or larger (odds ratio [OR] = 2.35 [95% CI 1.08-5.12]), sensitization to tree nuts (adjusted OR [aOR] = 2.51 [95% CI = 1.00-6.35]), and early-onset severe eczema (aOR = 3.23, [95% CI 1.17-8.88]). Factors at age 1 associated with persistence of egg allergy at age 6 were egg SPT result of 4 mm or larger (OR = 2.98 [95% CI 1.35-6.36]), other (peanut and/or sesame) food sensitizations (aOR = 2.80 [95% CI = 1.11-7.03]), baked egg allergy (aOR = 7.41 [95% CI = 2.16-25.3]), and early-onset severe eczema (aOR = 3.77 [95% CI = 1.35-10.52]). Most egg allergy and nearly one-third of peanut allergy resolves naturally by age 6 years. The prevalence of peanut allergy at age 6 years was similar to that observed at age 1 year, largely owing to new-onset food peanut allergy after age 1 year. Infants with early-onset eczema, larger SPT wheals, or multiple food sensitizations and/or allergies were less likely to acquire tolerance to either peanut or egg.
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.JACI.2019.07.032
Abstract: Randomized controlled trials demonstrate that timely introduction of peanut to infants reduces the risk of peanut allergy. However, much debate remains regarding how to best achieve earlier peanut introduction at the population level. Our previous study in 2007-2011 (HealthNuts, n = 5300) indicated that few infants were consuming peanut in the first year. Australian infant feeding guidelines were updated in 2016 to recommend introducing peanut before 12 months for all infants. There were no data available on the subsequent effect on peanut introduction or peanut reactions. We sought to assess the consequences of a nonscreening approach to allergenic food introduction in a population-based s le of infants in their first year of life. EarlyNuts is a population-based, cross-sectional study of 12-month-old infants in Melbourne, Australia, recruited by using an identical s ling frame and methods to HealthNuts (72% response rate vs 73% response rate in HealthNuts). We report here on the first 860 participants recruited between November 2016 and October 2018. Most infants (88.6% 95% CI, 86.1% to 90.7%) had introduced peanut by 12 months (median age, 6 months), an increase from 28.4% (95% CI, 27.2% to 29.7%) in the HealthNuts study. By 12 months, the majority of these (76.4%) had consumed peanut more than 4 times, and 28% were eating peanut more than once per week. Preliminary results on parent-reported reactions show that 4.0% of those consuming peanut by 12 months had possible IgE-mediated reactions. There has been a striking shift toward earlier peanut introduction, with a 3-fold increase in peanut introduction by age 1 year in 2018 compared with 2007-2011.
Publisher: Elsevier BV
Date: 06-2022
Publisher: Wiley
Date: 2022
DOI: 10.1002/CTI2.1387
Abstract: Because of its beneficial off‐target effects against non‐mycobacterial infectious diseases, bacillus Calmette–Guérin (BCG) vaccination might be an accessible early intervention to boost protection against novel pathogens. Multiple epidemiological studies and randomised controlled trials (RCTs) are investigating the protective effect of BCG against coronavirus disease 2019 (COVID‐19). Using s les from participants in a placebo‐controlled RCT aiming to determine whether BCG vaccination reduces the incidence and severity of COVID‐19, we investigated the immunomodulatory effects of BCG on in vitro immune responses to SARS‐CoV‐2. This study used peripheral blood taken from participants in the multicentre RCT and BCG vaccination to reduce the impact of COVID‐19 on healthcare workers (BRACE trial). The whole blood taken from BRACE trial participants was stimulated with γ‐irradiated SARS‐CoV‐2‐infected or mock‐infected Vero cell supernatant. Cytokine responses were measured by multiplex cytokine analysis, and single‐cell immunophenotyping was made by flow cytometry. BCG vaccination, but not placebo vaccination, reduced SARS‐CoV‐2‐induced secretion of cytokines known to be associated with severe COVID‐19, including IL‐6, TNF‐α and IL‐10. In addition, BCG vaccination promoted an effector memory phenotype in both CD4 + and CD8 + T cells, and an activation of eosinophils in response to SARS‐CoV‐2. The immunomodulatory signature of BCG’s off‐target effects on SARS‐CoV‐2 is consistent with a protective immune response against severe COVID‐19.
Publisher: Oxford University Press (OUP)
Date: 10-05-2022
DOI: 10.1093/IJE/DYAC086
Publisher: Elsevier BV
Date: 10-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2015
Publisher: The American Association of Immunologists
Date: 09-2012
Abstract: The maintenance of adequate serum Ab levels following immunization has been identified as the most important mechanism for in idual long-term protection against rapidly invading encapsulated bacteria. The mechanisms for maintaining adequate serum Ab levels and the relationship between Ag-specific memory B cells and Ab at steady state are poorly understood. We measured the frequency of circulating serogroup C meningococcal (MenC)-specific memory B cells in 250 healthy 6- to 12-y-old children 6 y following MenC conjugate vaccine priming, before a booster of a combined Haemophilus influenzae type b–MenC conjugate vaccine and then 1 wk, 1 mo, and 1 y after the booster. We investigated the relationship between circulating MenC-specific memory B cell frequencies and Ab at baseline and following the booster vaccine. We found very low frequencies of circulating MenC-specific memory B cells at steady state in primary school-aged children and little association with MenC IgG Ab levels. Following vaccination, there were robust memory B cell booster responses that, unlike Ab levels, were not dependent on age at priming with MenC. Measurement of B cell memory in peripheral blood does not predict steady state Ab levels nor the capacity to respond to a booster dose of MenC Ag.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-04-2022
Publisher: Wiley
Date: 09-2022
DOI: 10.1111/PAI.13849
Abstract: Early introduction of allergenic foods into an infant's diet is currently the most promising strategy to prevent food allergy, with infant guidelines around the world shifting from promoting avoidance to actively encourage the introduction of allergenic foods in the infant diet. Infant feeding guidelines vary according to regional public health priorities, and knowledge gaps remain, resulting in ongoing challenges for clinicians and families to translate guidelines into practical strategies for the introduction of complementary foods for food allergy prevention. Evidence from Australia demonstrates high community support and uptake of revised guidelines with most parents introducing allergenic foods in the first year of life, although this has not had the expected impact on substantially reducing food allergy prevalence. To uptake of guidelines from other countries is less clear, and several barriers have been noted in infant feeding RCTs, which may warrant intervention strategies. Further research is needed to understand additional strategies for food allergy prevention, particularly in infants who develop food allergy prior to when they are developmentally ready to commence solids. Several RCTs are underway investigating preventative strategies that target the window before allergen ingestion, such as vitamin D supplementation, emollient use, and immunizations that prime the immune response away from a Th2‐driven allergic phenotype. Further research is also needed to understand the role of the environment and the host environment in the development of tolerance to foods.
Publisher: American Academy of Sleep Medicine (AASM)
Date: 15-03-2018
DOI: 10.5664/JCSM.7014
Publisher: American Medical Association (AMA)
Date: 09-2019
Publisher: Elsevier BV
Date: 07-2020
Publisher: Frontiers Media SA
Date: 24-09-2020
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.JAIP.2022.03.018
Abstract: Food-allergic consumers encounter inadequate, confusing, and ambiguous allergen information for packaged and unpackaged foods. Key Australian and New Zealand allergy organizations convened multiple forums to facilitate discussions among consumers, food manufacturers, food retailers, regulatory bodies, researchers, and health professionals to develop a unified approach to improving food allergen management. The following stakeholder consensus statement provides a foundation for advocacy for improved food allergen management and safety. It is the responsibility of consumers to: 1. declare their food allergies and read food labels (including ingredient lists and allergen declaration statements), and 2. ultimately make their own judgment about the foods they choose to consume. We consider that to enable consumers to make informed decisions about their safety, It is the responsibility of packaged food manufacturers to: 1. follow robust allergen management practices including quantitative risk assessment, and 2. use clear, consistent labeling to inform consumers about that food's allergen content, including the possible presence of unintended allergens. It is the responsibility of food service establishments and providers to: 1. follow robust allergen management practices, and 2. ensure that staff understand and can inform consumers about the allergen content of the food they provide, including the possible presence of unintended allergens.
Publisher: BMJ
Date: 10-2021
DOI: 10.1136/BMJOPEN-2021-052101
Abstract: BCG vaccination modulates immune responses to unrelated pathogens. This off-target effect could reduce the impact of emerging pathogens. As a readily available, inexpensive intervention that has a well-established safety profile, BCG is a good candidate for protecting healthcare workers (HCWs) and other vulnerable groups against COVID-19. This international multicentre phase III randomised controlled trial aims to determine if BCG vaccination reduces the incidence of symptomatic and severe COVID-19 at 6 months (co-primary outcomes) compared with no BCG vaccination. We plan to randomise 10 078 HCWs from Australia, The Netherlands, Spain, the UK and Brazil in a 1:1 ratio to BCG vaccination or no BCG (control group). The participants will be followed for 1 year with questionnaires and collection of blood s les. For any episode of illness, clinical details will be collected daily, and the participant will be tested for SARS-CoV-2 infection. The secondary objectives are to determine if BCG vaccination reduces the rate, incidence, and severity of any febrile or respiratory illness (including SARS-CoV-2), as well as work absenteeism. The safety of BCG vaccination in HCWs will also be evaluated. Immunological analyses will assess changes in the immune system following vaccination, and identify factors associated with susceptibility to or protection against SARS-CoV-2 and other infections. Ethical and governance approval will be obtained from participating sites. Results will be published in peer-reviewed open-access journals. The final cleaned and locked database will be deposited in a data sharing repository archiving system. ClinicalTrials.gov NCT04327206
Publisher: Elsevier BV
Date: 03-2020
Publisher: Springer Science and Business Media LLC
Date: 27-02-2020
DOI: 10.1038/S41467-020-14919-4
Abstract: IgE-mediated peanut allergic is common, often serious, and usually lifelong. Not all in iduals who produce peanut-specific IgE will react upon consumption of peanut and can eat the food without adverse reactions, known as sensitized tolerance. Here, we employ high-dimensional mass cytometry to define the circulating immune cell signatures associated with sensitized tolerance and clinical allergy to peanut in the first year of life. Key features of clinical peanut allergic are increased frequency of activated B cells (CD19 hi HLADR hi ), overproduction of TNFα and increased frequency of peanut-specific memory CD4 T cells. Infants with sensitized tolerance display reduced frequency but hyper-responsive naive CD4 T cells and an increased frequency of plasmacytoid dendritic cells. This work demonstrates the utility and power of high-dimensional mass cytometry analysis to interrogate the cellular interactions that are associated with allergic sensitization and clinical food allergy in the first year of life.
Publisher: Elsevier BV
Date: 09-2023
Publisher: American Medical Association (AMA)
Date: 09-2019
Publisher: Informa UK Limited
Date: 11-03-2019
DOI: 10.1080/14760584.2019.1586540
Abstract: Subcutaneous nodules are a rare adverse event following immunization (AEFI). Reported cases have frequently been associated with aluminum-containing vaccines. Despite the development of a consensus definition of a subcutaneous nodule from the Brighton Collaboration in 2004, there continues to be variation in definitions used in published literature. Areas covered: We reviewed the literature regarding subcutaneous nodule etiology, definition, clinical features, management, and approach to future immunizations. Embase and MEDLINE databases were searched with relevant MeSH terms initially on 8 November 2016, the same searches were repeated on 9 September 2018 prior to finalizing this review. We reviewed published case reports and larger studies reporting subcutaneous nodules and also reviewed articles discussing broader use of aluminum in immunizations and AEFIs. Expert commentary: Consensus from clinicians regarding the approach to management of subcutaneous nodules is vital. We believe that the safety concerns regarding aluminum causing subcutaneous nodules are far outweighed by the benefits of vaccines containing aluminum. Ultimately, supporting subsequent immunizations in in iduals that develop nodules needs to be a priority.
Publisher: Springer Science and Business Media LLC
Date: 03-2009
DOI: 10.1038/NRI2494
Abstract: Polysaccharide-encapsulated organisms are the leading cause of bacterial meningitis and pneumonia in children. The use of protein-polysaccharide conjugate vaccines in developed countries over the past two decades has markedly decreased the burden of disease and mortality from these organisms through direct protection of the immunized and through herd immunity. In the next decade, the widespread use of conjugate vaccines in the developing world should prevent millions of deaths. In this Science and Society article, we describe how vaccine-induced immunity wanes rapidly after vaccination in early childhood and argue that strategies that sustain protection in the population must be considered.
Publisher: Wiley
Date: 07-09-2021
DOI: 10.1111/JPC.15731
Publisher: Informa UK Limited
Date: 25-05-2019
Publisher: Wiley
Date: 10-2022
DOI: 10.1111/PAI.13862
Abstract: While the relationship between pollen and respiratory allergies is well‐documented, the role of short‐term pollen exposure in food allergy and eczema flares has not previously been explored. We aimed to investigate these associations in a population‐based s le of children. We investigated 1‐ ( n = 1108) and 6‐year‐old ( n = 675) children in the grass pollen season from the HealthNuts cohort. Grass pollen concentrations were considered on the day of testing (lag 0), up to three days before (lag 1‐lag 3) and cumulatively (lag 0–3). Associations between grass pollen and food skin‐prick test reactivity (SPT ≥ 2 mm at age 1 year and ≥ 3 mm at age 6 years), eczema flares, challenge‐confirmed food allergy, reaction threshold to oral food challenges (OFC), and serum food‐specific IgE levels were analyzed using either logistic or quantile regression models. Atopy and family history of allergic disease were considered as potent effect modifiers. Grass pollen at lag 0–3 (every 20 grains/m 3 increase) was associated with an up to 1.2‐fold increased odds of food SPT reactivity and eczema flares in 6‐year‐olds. In 1‐year‐olds, the associations were only observed for peanut in those with a family history of food allergy. Increasing grass pollen concentrations were associated with a lower reaction threshold to OFC and higher serum IgE levels in peanut‐allergic 1‐year‐olds only. Increasing grass pollen concentration was associated with increased risk of food SPT reactivity and eczema flares in children. The associations in peanut‐allergic infants may be related to immune activation and/or peanut and grass pollen cross‐reactivity leading to a lower reaction threshold.
Publisher: Elsevier BV
Date: 2020
Publisher: Wiley
Date: 2021
DOI: 10.1002/CTI2.1324
Abstract: Rates of IgE‐mediated food allergy (FA) have increased over the last few decades, and mounting evidence implicates disruption of epigenetic profiles in various immune cell types in FA development. Recent data implicate B‐cell dysfunction in FA however, few studies have examined epigenetic changes within these cells. We assessed epigenetic and transcriptomic profiles in purified B cells from adolescents with FA, comparing single‐food‐allergic (peanut only), multi‐food‐allergic (peanut and ≥1 other food) and non‐allergic (control) in iduals. Adolescents represent a phenotype of persistent and severe FA indicative of a common immune deviation. We identified 144 differentially methylated probes (DMPs) and 116 differentially expressed genes (DEGs) that distinguish B cells of in iduals with FA from controls, including differential methylation of the PM20D1 promoter previously associated with allergic disorders. Subgroup comparisons found 729 DMPs specific to either single‐food‐ or multi‐food‐allergic in iduals, suggesting epigenetic distinctions between allergy groups. This included two regions with increased methylation near three S100 genes in multi‐food‐allergic in iduals. Ontology results of DEGs specific to multi‐food‐allergic in iduals revealed enrichment of terms associated with myeloid cell activation. Motif enrichment analysis of promoters associated with DMPs and DEGs showed differential enrichment for motifs recognised by transcription factors regulating B‐ and T‐cell development, B‐cell lineage determination and TGF‐β signalling pathway between the multi‐food‐allergic and single‐food‐allergic groups. Our data highlight epigenetic changes in B cells associated with peanut allergy, distinguishing features of the epigenome between single‐food‐ and multi‐food‐allergic in iduals and revealing differential developmental pathways potentially underpinning these distinct phenotypes.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Wiley
Date: 10-10-2023
DOI: 10.1111/ALL.15902
Publisher: Massachusetts Medical Society
Date: 27-04-2023
Publisher: Wiley
Date: 08-02-2022
DOI: 10.1111/ALL.15229
Abstract: There is increasing understanding, globally, that climate change and increased pollution will have a profound and mostly harmful effect on human health. This review brings together international experts to describe both the direct (such as heat waves) and indirect (such as vector‐borne disease incidence) health impacts of climate change. These impacts vary depending on vulnerability (i.e., existing diseases) and the international, economic, political, and environmental context. This unique review also expands on these issues to address a third category of potential longer‐term impacts on global health: famine, population dislocation, and environmental justice and education. This scholarly resource explores these issues fully, linking them to global health in urban and rural settings in developed and developing countries. The review finishes with a practical discussion of action that health professionals around the world in our field can yet take.
Publisher: Springer Science and Business Media LLC
Date: 03-2022
DOI: 10.1007/S10875-022-01230-8
Abstract: Measurement of pre- and post-pneumococcal antibody levels after immunization with the 23-valent capsular polysaccharide pneumococcal vaccine (23vPPV) is indicative of a T-independent antibody response. The World Health Organisation ELISA is considered gold standard yet is labor-intensive and technically difficult to perform. Interpretation criteria defining an adequate response to 23vPPV remain controversial. The diagnostic Immunology Laboratory at The Royal Children's Hospital, Melbourne (RCH), performs an in-house multi-serotype automated ELISA. The primary objective of this study was to verify RCH interpretation criteria for the laboratory's automated ELISA. Forty pneumococcal conjugate vaccine (PCV)-naïve healthy adults aged 18 to 25 years and 22 PCV-primed healthy children aged 2 to 5 years were immunized with 23vPPV. A serum s le was collected immediately prior and 28 to 42 (± 7) days post immunization. S les were analyzed on the Tecan Freedom Evo 200 ELISA with adequate response defined as post-immunization antibody level of 1.3 µg/mL or fourfold rise from baseline in ≥ 10/15 serotypes in adult participants and ≥ 4/8 serotypes in pediatric participants. Thirty-nine (97.5%) adults and 22 (100%) children achieved an adequate response to 23vPPV. In PCV-naïve adults, serotypes contained within the conjugate vaccines were less immunogenic, with 12 (30%) adults not achieving an adequate antibody response when only PCV serotypes were used for interpretation. Our diagnostic laboratory has verified the interpretation criteria used for an automated multi-serotype pneumococcal ELISA method. Clinical Trial Registration: ANZCTR registration number ACTRN12618000822280.
Publisher: Massachusetts Medical Society
Date: 30-07-2020
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.VACCINE.2017.01.075
Abstract: In Australia, influenza vaccination is recommended for all women who will be pregnant during the influenza season. Vaccine safety and effectiveness are key concerns and influencers of uptake for both vaccine providers and families. We assessed the safety of receiving an influenza vaccination during any trimester of pregnancy with respect to preterm births and infant birthweight. We conducted a nested retrospective cohort study of 'FluMum' participants (2012-2014). Our primary exposure of interest was influenza vaccination during pregnancy. The primary outcomes of interest were infant birthweight and weeks' gestation at birth for live singleton infants. Analyses included comparisons of these birth outcomes by vaccination status and trimester of pregnancy an influenza vaccine was given. We calculated means, proportions, and relative risks and performed multivariable logistic regression for potential confounding factors. In the 7126 mother-infant pairs enrolled in this study, mean maternal age at infant birth was 31.7years. Influenza vaccine uptake in pregnancy was 34%. Most mothers with a known date of vaccination received a vaccine in the second trimester (51%). Those mothers with a co-morbidity or risk factor were 13% more likely to have influenza vaccine during pregnancy compared to other mothers (RR 1.13, 95% CI 1.04-1.24, p=0.007). Mean weeks' gestation at birth was 38.7 for the vaccinated and 38.8 for the unvaccinated group (p=0.051). Infants in the vaccinated group weighed 15g less in birthweight compared to the unvaccinated infants (95% CI -12.8 to 42.2, p=0.29). Results arising from this large Australian cohort study are reassuring with respect to two critical safety outcomes preterm births and low infant birthweights. Studies examining a broader range of birth outcomes following influenza vaccination during pregnancy are required, particularly now that maternal vaccination in pregnancy has expanded to include pertussis as well as influenza.
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.JACI.2018.07.038
Abstract: Longitudinal population-based data regarding tree nut allergy are limited. We sought to determine the population prevalence of tree nut allergy at age 6 years and explore the relationship between egg and peanut allergy at age 1 year and development of tree nut allergy at age 6 years. A population-based s le of 5276 children was recruited at age 1 year and followed up at age 6 years. At age 1 year, allergies to egg and peanut were determined by means of oral food challenge, and parents reported their child's history of reaction to tree nuts. Challenge-confirmed tree nut allergy was assessed at age 6 years. At age 1 year, the prevalence of parent-reported tree nut allergy was 0.1% (95% CI, 0.04% to 0.2%). Only 18.5% of infants had consumed tree nuts in the first year of life. At age 6 years, challenge-confirmed tree nut allergy prevalence was 3.3% (95% CI, 2.8% to 4.0%), with cashew the most common (2.7% 95% CI, 2.2% to 3.3%). Of children with peanut allergy only at age 1 year, 27% (95% CI, 16.1% to 39.7%) had tree nut allergy at age 6 years compared with 14% (95% CI, 10.4% to 17.9%) of those with egg allergy only and 37% (95% CI, 27.2% to 47.4%) of those with both peanut and egg allergy. Tree nut allergy is uncommon in the first year of life, likely because of limited tree nut consumption. At age 6 years, tree nut allergy prevalence is similar to peanut allergy prevalence. More than a third of children with both peanut and egg allergy in infancy have tree nut allergy at age 6 years. Understanding how to prevent tree nut allergy should be an urgent priority for future research.
Publisher: Authorea, Inc.
Date: 13-06-2022
DOI: 10.22541/AU.165509953.37222599/V1
Abstract: Background: In the absence of a clear clinical history of reaction, diagnosis of cashew allergy using skin prick tests (SPT) or cashew-specific IgE requires a high number of oral food challenges (OFC). By using Ana o 3 sIgE alone, or a two-step diagnostic algorithm using cashew sIgE followed by Ana o 3 sIgE, there is a reduced need for OFC. We aimed to perform a cost comparison for both of these approaches compared to cashew SPT alone. Methods: Pooled in idual level data from 6 studies was used to determine diagnostic accuracy and OFC rate. Two studies used cashew SPT (n=567, 198 allergic), with 95% positive and negative predictive values of ≥12mm and mm. Four studies were included in the pathways for Ana o 3 sIgE alone or a 2-step algorithm incorporating cashew and Ana o 3 sIgE (n=271, 156 allergic). Cut-offs used were ≥8.5kUA/L and ≤0.1kUA/L for cashew sIgE and ≥0.35kUA/L and ≤0.1kUA/L for Ana o 3 sIgE. Costs were constructed based on unit prices from hospital inpatient admissions, expenses incurred by families, in idual patient data on allergic reaction types and rates and adrenaline autoinjector carriage, applying a health system perspective. Results: Modelled data through the Ana o 3 pathway resulted in a 46.43% cost reduction (\\euro307,406/1000 patients) compared to using cashew SPT alone (\\euro573,854/1000 patients). The 2-step algorithm resulted in a 44.94% cost reduction compared to SPT alone (\\euro315,952.82/1000 patients). Both the Ana o 3 pathway and 2-step algorithm resulted in a 79-80% reduction in OFCs compared to SPT. Conclusions: Using Ana o 3 as a standalone test for cashew allergy diagnosis or a 2-step algorithm incorporating cashew sIgE and Ana o 3 sIgE is accurate and results in a large reduction in both OFCs and health system costs compared to cashew SPT alone.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Cold Spring Harbor Laboratory
Date: 24-05-2023
DOI: 10.1101/2023.05.22.541509
Abstract: Metagenome-assembled genomes have greatly expanded the reference genomes for skin microbiome. However, the current reference genomes are largely based on s les from adults in North America and lack representation from infants and in iduals from other continents. Here we used ultra-deep shotgun metagenomic sequencing to profile the skin microbiota of 215 infants at age 2-3 months and 12 months who were part of the VITALITY trial in Australia as well as 67 maternally-matched s les. Based on the infant s les, we present the Early-Life Skin Genomes (ELSG) catalog, comprising 9,194 bacterial genomes from 1,029 species, 206 fungal genomes from 13 species, and 39 eukaryotic viral sequences. This genome catalog substantially expands the ersity of species previously known to comprise human skin microbiome and improves the classification rate of sequenced data by 25%. The protein catalog derived from these genomes provides insights into the functional elements such as defense mechanisms that distinguish early-life skin microbiome. We also found evidence for vertical transmission at the microbial community, in idual skin bacterial species and strain levels between mothers and infants. Overall, the ELSG catalog uncovers the skin microbiome of a previously underrepresented age group and population and provides a comprehensive view of human skin microbiome ersity, function, and transmission in early life.
Publisher: Oxford University Press (OUP)
Date: 15-06-2010
DOI: 10.1086/652765
Abstract: After immunization with serogroup C meningococcal (MenC) conjugate vaccine, antibody responses and vaccine effectiveness are sustained in adolescents, in contrast to rapid waning in young children. We investigated the persistence of serum bactericidal antibody (SBA) titers in children 6 years after immunization with MenC vaccine (primed between 2 months and 6 years of age). The response to a Haemophilus influenzae type b-MenC conjugate (Hib-MenC) booster was also measured. A phase 4 clinical trial was conducted among 250 healthy 6-12-year-old children. SBA titers were measured before, 1 month after, and 1 year after Hib-MenC administration. The correlate of protection was an SBA titer of 8. An SBA titer of 8 was observed in 61 (25% [95% confidence interval {CI}, 20%-30%]) of 244 participants (mean age, 9.1 years mean interval since MenC immunization, 6.75 years). The proportion with an SBA titer of 8 and the SBA geometric mean titer increased with age, from 12% (95% CI, 4%-23%) to 48% (95% CI, 29%-67%) and from 2.90 (95% CI, 2.11-3.99) to 17.20 (95% CI, 6.80-43.5), respectively, from a mean age of 7.0 to 12.1 years. One month after the Hib-MenC booster, all participants had an SBA titer of 8, which was sustained in 99.6% at 1 year. As a result of waning antibody, the majority of 6-12-year-old children in the United Kingdom have inadequate serological protection against MenC. The persistence of MenC immunity and the response to a Hib-MenC booster is dependent on age at priming. A booster was highly effective in this cohort and could sustain population immunity against MenC disease. Trial registration. Current Controlled Trials ( www.controlled-trials.com ) identifier: ISRCTN72858898 .
Publisher: American Medical Association (AMA)
Date: 03-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2020
Publisher: Informa Healthcare
Date: 30-11-2005
DOI: 10.1517/14712598.5.12.1611
Abstract: Meningococcal disease, presenting primarily as septicaemia and meningitis, continues to be a devastating problem around the world. Over the last century, vaccine development has been undertaken in earnest for the prevention of this disease. Polysaccharide vaccines have been available for almost 40 years, yet they are poorly immunogenic in young children who are at the highest risk. Since their introduction into some routine immunisation schedules in 1999, polysaccharide-protein conjugate vaccines for the prevention of serogroup C meningococcal infection have proven efficacious. A quadrivalent polysaccharide-protein conjugate vaccine against serogroups A, C, W135 and Y, which is being introduced in the US this year, is hoped to control disease caused by these serogroups. To date, however, the development of a universally safe, immunogenic and effective serogroup B Neisseria meningitidis vaccine has remained a challenge. This review details the many conventional vaccine strategies and the more recent genome-derived technological approaches being used in serogroup B vaccine development. The future prevention of serogroup B disease will rely on both outer membrane vesicle vaccines being used for serosubtype-specific outbreaks and new vaccines containing multiple other antigens. Investment by the pharmaceutical industry in preclinical research and development provides hope that an efficacious serogroup B meningococcal vaccine can be developed.
Publisher: Wiley
Date: 02-2022
DOI: 10.1111/PAI.13749
Abstract: While exposure to environmental greenness in childhood has shown mixed associations with the development of allergic disease, the relationship with food allergy has not been explored. We investigated the association between exposure to environmental greenness and challenge‐confirmed food allergy in a large population‐based cohort. The HealthNuts study recruited 5276 12‐month‐old infants in Melbourne, Australia, who underwent skin prick testing to peanut, egg, and sesame infants with a detectable wheal underwent food challenges to determine food allergy status. Environmental greenness was estimated using the normalized difference vegetation index (NDVI) for five buffer zones around the infant's home address: at the home, 100 m, 500 m, 800 m, and 1600 m radial distances. Environmental greenness was categorized into 3 tertiles and mixed effects logistic regression models quantified the association between greenness and the risk of food allergy, adjusting for confounding and accounting for clustering at the neighborhood level. NDVI data were available for n = 5097. For most buffer zones, medium and high greenness, compared to low greenness, was associated with an increased risk of peanut allergy (eg, 100 m tertile 2 aOR 1.89 95% CI 1.22–2.95, tertile 3 aOR 1.78 95% CI 1.13–2.82). For egg allergy, the effect sizes were smaller (100 m tertile 2 aOR 1.52 95% CI 1.16–1.97, tertile 3 aOR 1.38 95% CI 1.05–1.82). Socioeconomic status (SES) modified the association between greenness and peanut allergy, but not egg allergy associations were apparent in the low SES group but not in the high SES group ( p for interaction 0.08 at 100 m). Air pollution (PM2.5) also modified the associations between environmental greenness and food allergy, with associations present in high air pollution areas but not low ( p for interaction at 100 m 0.05 for peanut and 0.06 for egg allergy.) Increased exposure to environmental greenness in the first year of life was associated with an increased risk of food allergy. Increased greenness may correlate with higher pollen levels which may trigger innate immune responses skewing the immune system to the Th2‐dependent allergic phenotype additionally, some pollen and food allergens are cross‐reactive. Given the mixed data on greenness and other allergies, the relationship appears complex and may also be influenced by confounding variables outside those that were measured in this study.
Publisher: Oxford University Press (OUP)
Date: 23-11-2019
DOI: 10.1093/CID/CIY517
Abstract: Inactivated influenza vaccine (IIV) and pertussis vaccination are recommended in pregnancy. Limited safety data exist for women who received IIV vaccine during the first trimester of pregnancy or received both vaccines in pregnancy. We assessed adverse birth outcomes between vaccinated and unvaccinated pregnancies. Among prospectively enrolled Australian "FluMum" participants (2012-2015), primary exposure was receipt and timing of IIV during pregnancy. Primary outcomes included preterm birth, low birthweight at term (LBWT), and small for gestational age (SGA). We compared birth outcomes for IIV in pregnancy with women unvaccinated in pregnancy using Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs). Adjusted HRs (aHRs) controlled for potential confounding variables. Sensitivity analyses were conducted in a subgroup of women who received pertussis vaccination during pregnancy to assess whether associations between IIV and adverse outcomes were maintained after adjusting for pertussis vaccination. Among 8827 participants in our study, women who received IIV in pregnancy did not have an elevated risk of an adverse birth outcome compared with unvaccinated pregnant women: preterm births (HR, 1.10 [95% CI, .92-1.31] P = .28) LBWT (HR, 1.05 [95% CI, .76-1.44] P = .77) or SGA (HR, 0.99 [95% CI, .86-1.15] P = .94). Adjustment for pertussis vaccination during pregnancy yielded similar results: preterm births (aHR, 1.05 [95% CI, .82-1.34] P = .69) LBWT (aHR, 0.81 [95% CI, .50-1.29] P = .37) SGA (aHR, 0.92 [95% CI, .74-1.14] P = .43). There was no evidence of elevated risk by trimester of IIV. No significant associations were found between maternal IIV or pertussis vaccination in pregnancy and adverse birth outcomes, regardless of the trimester of pregnancy a vaccination was given compared to unvaccinated pregnancies.
Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.VACCINE.2018.05.018
Abstract: Sedation for immunizations is of particular importance in a subset of paediatric patients with anxiety disorders, needle phobia, developmental or behavioural disorders. The Royal Children's Hospital (RCH) Melbourne offers a unique immunization under sedation service for these patients. We aimed to evaluate the number and types of patients using inpatient sedation for immunizations, distraction and sedation techniques used, and outcomes of these procedures. A medical record review was conducted on all patients who had immunization under sedation between January 2012 to December 2016 in the RCH Day Medical Unit (DMU). A total of 139 children and adolescents had 213 vaccination encounters. More than half of the vaccination encounters involved multiple vaccines. A total of 400 vaccines were administered. One third of patients (32.3%) had multiple DMU admissions for vaccinations. The median age of patients was 13 years. There were only 10 (4.7%) failed attempts at vaccination all due to patient non-compliance with prescribed sedation. The majority of patients (58.9%) had a diagnosis of needle phobia. Sedation was most commonly adequately achieved with inhaled nitrous oxide (54.7% sole agent). Midazolam was often used as an adjunct therapy (42.8%). Local anaesthetic cream or play therapy, were used in only 5.9% and 3.9% of patients respectively, although this may reflect poor documentation rather than actual practice. For a subset of paediatric patients for which standard immunization procedures have failed, distraction techniques and conscious sedation enable immunizations to be given safely and effectively. Future research will develop protocols to streamline immunization procedures under sedation.
Publisher: Wiley
Date: 17-01-2023
DOI: 10.1111/CEA.14281
Abstract: To summarise the associations between antenatal or early‐life blood vitamin D and the development of eczema/food allergy in childhood. A systematic review and meta‐analyses were conducted to synthesize the published literature. Two reviewers independently performed the study selection and data extraction on Covidence. We assessed the risk of bias for observational studies by using the Newcastle‐Ottawa Scale and the Cochrane Risk of Bias tool for clinical trials. The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). We systematically searched PubMed and Embase from inception and April 2022. Human studies that investigated prospective associations between antenatal or early‐life blood vitamin D levels, dietary intake or supplementation and childhood eczema/food allergy. Forty‐three articles including six randomised controlled trials (RCTs) were included. Four RCTs of vitamin D supplementation during pregnancy showed no evidence of an effect on the incidence of eczema (pooled odds ratio [OR] = 0.85 0.67–1.08, I 2 = 6.7%, n = 2074). Three RCTs reported null associations between supplementation in pregnancy/infancy and food allergy. From six cohort studies, increasing cord blood vitamin D levels were associated with reduced prevalence of eczema at/close to age one (OR per 10 nmol/L increase = 0.89 0.84–0.94, I 2 = 0%, 2025 participants). We found no evidence of an association between maternal antenatal or infant vitamin D level or dietary intake and the development of food allergy or eczema in offspring. We found an association between higher vitamin D levels in cord blood and reduced risk of eczema in cohort studies. Further trials with maternal and infant supplementation are needed to confirm if vitamin D supplementation can effectively prevent eczema or food allergy in childhood. PROSPERO, No. CRD42013005559.
Publisher: Elsevier BV
Date: 09-2021
Publisher: Elsevier BV
Date: 09-2021
DOI: 10.1016/J.JVAL.2021.02.010
Abstract: To identify published economic evaluations of interventions aimed at preventing, diagnosing, or treating food allergies in children. We examined economic evaluations published from 2000 to 2019. Data analyzed included: food allergy type, study population/setting, intervention/comparator, and economic evaluation details. Quality assessment used reporting and economic modeling checklists. Two reviewers simultaneously undertook article screening, data extraction, and quality assessment. 17 studies were included: 8 peanut allergy (PA) studies, 8 cow's milk allergy (CMA) studies, and 1 egg allergy (EA) study. All PA studies reported incremental costs per quality-adjusted life-year gained for diagnostic strategies, management pathways for peanut exposure, and immunotherapies. Immunotherapies rendered inconsistent cost-effectiveness results. CMA studies reported costs per symptom-free day or probability of developing CMA tolerance. Cost-effectiveness of extensively hydrolyzed casein formula for CMA treatment was consistently demonstrated. Early introduction of cooked egg in first year of life dominated all EA prevention strategies. Quality assessment showed average noncompliance for 3.5 items/study (range 0-11) for modeling methods and 3.4 items/study (range 0-8) for reporting quality. Key quality concerns included limited justification for model choice, evidence base for model parameters, source of utility values, and representation of uncertainty. Recent cost-effectiveness literature of interventions in PA, CMA, and EA is limited and erse. Interventions for diagnosis and treatment of CMA and prevention of EA were generally cost-effective however, results for PA were variable and dependent on effectiveness and utility values used. There is a need to expand economic evaluation of interventions for childhood food allergy and to improve methods and reporting.
Publisher: Public Library of Science (PLoS)
Date: 10-10-2019
Publisher: Elsevier BV
Date: 07-2023
Publisher: American Medical Association (AMA)
Date: 05-07-2022
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.VACCINE.2015.02.008
Abstract: Anaphylaxis is a rare life-threatening adverse event following immunization (AEFI). Variability in presentation can make differentiation between anaphylaxis and other AEFI difficult. This study summarizes pediatric anaphylaxis AEFI reported to an Australian state-based passive surveillance system. All suspected and reported pediatric (<18 years) anaphylaxis AEFI notified to SAEFVIC (Surveillance of Adverse Events Following Vaccination In the Community) Melbourne, Australia, between May 2007 to May 2013 were analyzed. Clinical descriptions of the AEFI, using the internationally recognized Brighton Collaboration case definition (BCCD) and final outcome were documented. 93% (25/27) of AEFI classified as anaphylaxis met BCCD criteria, with 36% (9/25), assessed as the highest level of diagnostic certainty (Level 1). Median age was 4.7 years (range 0.3-16.2) 48% of cases were male. The vaccine antigens administered included: diphtheria, tetanus, acellular pertussis (DTaP) alone or in combination vaccines containing other antigens in 11 of 25 cases (44%) and live attenuated measles mumps rubella (MMR) vaccine for six (five also had other vaccines concomitantly administered). The estimated incidence rate of anaphylaxis for DTaP vaccines was 0.36 cases per 100,000 doses, and 1.25 per 100,000 doses for MMR vaccines. The majority of cases had rapid onset, but in 24% (6/25) of cases, first symptoms of anaphylaxis developed ≥30 min after immunization. In 60% (15/25) of cases, symptoms resolved ≤60 min of presentation. Intramuscular adrenaline was administered in 90% (18/25) of cases. All cases made a full recovery with no sequelae identified. This comprehensive case series of pediatric anaphylaxis as an AEFI identified that diagnostic criteria are useful when applied to a passive vaccine surveillance system when adequate clinical information is available. Anaphylaxis as an AEFI is rare and usually begins within 30 min of vaccination. However, healthcare professionals and vaccinees arents should be aware that onset of anaphylaxis can be delayed beyond 30 min following immunization and that medical attention should be sought promptly if anaphylaxis is suspected.
Publisher: Elsevier BV
Date: 08-2023
Publisher: Wiley
Date: 08-03-2021
DOI: 10.1111/CEA.13857
Abstract: Approximately 5% of adolescents have a food allergy, with peanut and tree nut allergies the most common. Having two or more food allergies in adolescence also doubles the risk of any adverse food reaction, and is associated with increased dietary and social burden. Investigations of immune function in persistently food allergic children are rare. In the present study, we aimed to investigate the immune mechanisms that underlie food allergy in adolescence. We used high-dimensional flow cytometry, unsupervised computational analysis and functional studies to comprehensively phenotype a range of non-antigen-specific immune parameters in a group of well-characterized adolescents with clinically defined single peanut allergy, multi-food allergy and aged-matched non-food allergic controls. We show that food allergic adolescents have higher circulating proportions of dendritic cells (p = .0084, FDR-adjusted p = .087, median in no FA: 0.63% live cells, in FA: 0.93%), and higher frequency of activated, memory-like Tregs relative to non-food allergic adolescents (p = .011, FDR-adjusted p = .087, median in no FA: 0.49% live cells, in FA: 0.65%). Cytokine profiling revealed that CD3/CD28 stimulated naïve CD4 T cells from food allergic adolescents produced less IL-6 (p = .0020, FDR-adjusted p = .018, median log2 fold change [stimulated/unstimulated] in no FA: 3.03, in FA: 1.92) and TNFα (p = .0044, FDR-adjusted p = .020, median in no FA: 9.16, in FA: 8.64) and may secrete less IFNγ (p = .035, FDR-adjusted p = .11, median in no FA: 6.29, in FA: 5.67) than naïve CD4 T cells from non-food allergic controls. No differences between clinical groups were observed for LPS-stimulated monocyte secretion of cytokines. These results have important implications for understanding the evolution of the immune response in food allergy throughout childhood, revealing that dendritic cell and T-cell signatures previously identified in early life may persist through to adolescence.
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.JAIP.2019.01.025
Abstract: The rate of true vaccine allergy is unknown. Children with potential IgE-mediated adverse events following immunization (AEFI) should undergo allergy investigation that may include skin testing or challenge. Previous protocols tend to be highly conservative and often suggest invasive testing for all, a practice not evidence based, technically difficult, and unpleasant in children. It has more recently been suggested that skin testing may be restricted to those with allergic-like events within the first hour and those with a history of anaphylaxis. We aimed to describe the outcome of vaccine skin testing and challenge in children referred to a tertiary pediatric hospital with a potential IgE-mediated AEFI. The secondary aim was to identify any significant risk factors for vaccine allergy. A retrospective review of all children (<18 years) who underwent vaccine skin testing (skin prick testing or intradermal testing [IDT]) or challenge over a 5-year period (May 1, 2011, to April 30, 2016) at the Royal Children's Hospital Melbourne is presented. There were 95 admissions in 73 children. Eight percent (6 of 73) of children had confirmed vaccine allergy (positive skin testing or challenge to the index vaccination). Two had positive IDT to a suspect vaccine but challenge negative to an alternative brand vaccine. Two had negative IDT but subsequent positive challenge and two had immediate urticaria on challenge without prior skin testing. All children in the positive group either had index reaction within 15 minutes of vaccination or had history consistent with anaphylaxis. The vast majority of children (92%) presenting with a potential IgE-mediated AEFI are able to tolerate challenge to a suspect vaccine without reaction. We present our investigation protocol recommending skin testing in all children with anaphylaxis and challenge with a suspect vaccine if negative testing or previous nonanaphylactic potential IgE-mediated AEFI.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.VACCINE.2015.06.103
Abstract: For decades, a broadly effective vaccine against serogroup B Neisseria meningitidis (MenB) has remained elusive. Recently, a four-component recombinant vaccine (4CMenB) has been developed and is now approved in Europe, Canada, Australia and some Latin American countries. This phase III, randomized study evaluated the lot consistency, early immune responses and the safety profile of 4CMenB in 11 to 17-year-old adolescents in Australia and Canada (NCT01423084). In total, 344 adolescents received two doses of one of 2 lots of 4CMenB, 1-month apart. Immunogenicity was assessed before, 2-weeks and 1-month following the second vaccination. Serum bactericidal activity using human complement (hSBA) was measured against three reference strains 44/76-SL, 5/99 and NZ98/254, selected to express one of the vaccine antigens Neisseria adhesin A (NadA), factor H binding protein (fHbp) and porin A (PorA) containing outer membrane vesicle (OMV), respectively. Responses to the Neisseria heparin binding antigen (NHBA) were assessed with enzyme linked immunosorbent assay (ELISA). Local and systemic reactions were recorded for 7 days following each vaccination unsolicited adverse events were monitored throughout the study. Immunological equivalence of the two lots of 4CMenB was established at 1-month. At baseline, ≤7% of participants had hSBA titers ≥5 to all three reference strains. Two weeks following the second dose of 4CMenB, all participants had hSBA titers ≥5 against fHbp and NadA compared with 84-96% against the PorA reference strains. At 1-month, corresponding proportions were 99%, 100% and 70-79%, respectively. Both lots were generally well tolerated and had similar adverse event profiles. Two doses of 4CMenB had an acceptable safety profile and induced a robust immune response in adolescents. Peak antibody responses were observed at 14 days following vaccination. While a substantial non-uniform antigen-dependent early decline in antibody titers was seen thereafter, a significant percentage of participants continued to maintain protective hSBA titers at 1-month.
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.VACCINE.2019.10.104
Abstract: Pertussis immunization during pregnancy results in high pertussis antibody concentrations in young infants but may interfere with infant immune responses to post-natal immunization. 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 (27 601 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. 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. ClinicalTrials.gov: NCT02422264.
Publisher: Wiley
Date: 03-2023
DOI: 10.1111/IMCB.12628
Abstract: Childhood is a critical period of immune development. During this time, naïve CD4 (nCD4) T cells undergo programmed cell differentiation, mediated by epigenetic changes, in response to external stimuli leading to a baseline homeostatic state that may determine lifelong disease risk. However, the ontogeny of epigenetic signatures associated with CD4 T cell activation during key developmental periods are yet to be described. We investigated genome‐wide DNA methylation (DNAm) changes associated with nCD4 T activation following 72 h culture in media+anti‐CD3/CD28 beads in healthy infants (aged 12 months, n = 18) and adolescents (aged 10–15 years, n = 15). We integrated these data with transcriptomic and cytokine profiling from the same s les. nCD4 T cells from both age groups show similar extensive epigenetic reprogramming following activation, with the majority of genes involved in the T cell receptor signaling pathway associated with differential methylation. Additionally, we identified differentially methylated probes showing age‐specific responses, that is, responses in only infants or adolescents, including within a cluster of T cell receptor (TCR) genes. These encoded several TCR alpha joining (TRAJ), and TCR alpha variable (TRAV) genes. Cytokine data analysis following stimulation revealed enhanced release of IFN‐γ, IL‐2 and IL‐10, in nCD4 T cells from adolescents compared with infants. Overlapping differential methylation and cytokine responses identified four probes potentially underpinning these age‐specific responses. We show that DNAm in nCD4T cells in response to activation is dynamic in infancy and adolescence, with additional evidence for age‐specific effects potentially driving variation in cytokine responses between these ages.
Publisher: Elsevier BV
Date: 05-2020
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.VACCINE.2019.10.105
Abstract: 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. 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. 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. 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. ClinicalTrials.gov: NCT02377349.
Publisher: Wiley
Date: 11-2022
DOI: 10.1111/PAI.13883
Abstract: Australia has one of the highest prevalence of childhood food allergy in the world, but there are no data on its economic burden in Australia. We used data from the HealthNuts study, a population‐based longitudinal study undertaken in Melbourne, Australia. Infants were recruited at age 12 months between Sept 2007 and Aug 2011 with food allergy diagnosed using oral food challenges. Health care costs of out‐of‐hospital services were collected through data linkage to Australia's universal health insurance scheme Medicare. Two‐part model was used to compare costs after controlling for potential confounders. 2919 children were included, and 390 (13.4%) had challenge‐confirmed food allergy at age 1 year. Compared with children without food allergy, children with food allergy had significantly higher costs for GP visits, specialist visits, tests, and prescriptions in the first four years of life. The total Medicare cost associated with food allergy from age 1 to 4 years was estimated to be AUD$889.7 (95% CI $566.1–$1188.3) or €411.0 (95% CI €261.5–€549.0) per child. This was projected into an annual Medicare cost of AUD$26.1 million (95% CI $20.1–$32.3 million) or €12.1 (95% CI €9.3–€14.9 million) based on population size in 2020. Childhood food allergy causes considerable Medicare costs for out‐of‐hospital services in the first four years after birth in Australia. These findings can help anticipate the financial impact on the health care system associated with childhood food allergy, act as a useful costing resource for future evaluations, and inform management of childhood food allergy internationally.
Publisher: Springer Science and Business Media LLC
Date: 04-01-2022
DOI: 10.1186/S12879-021-06976-X
Abstract: Patients with Inflammatory Bowel Disease (IBD) are at increased risk of serious infections, including vaccine preventable diseases. Current evidence suggests uptake of additional recommended special risk vaccinations is low. Identification of IBD patients prior to commencing immunosuppressive therapy allows for optimisation of vaccination, including timely administration of live-attenuated and additional recommended vaccines, such as influenza and pneumococcal vaccines. Paediatric patients (0–18 years) seen at the tertiary Royal Children’s Hospital, Melbourne, Australia, with a recent diagnosis of IBD were referred by the Gastroenterology Unit to our Specialist Immunisation Clinic (SIC) for assessment and provision of routine and special risk vaccines. Data was collected via a standardised REDCap questionnaire completed in or post attendance at the SIC and included serology results where available. Sixty-nine paediatric patients were recruited to the study between 2014 and 2017. Median age at IBD diagnosis was 11.25 years (IQR 4.64 years), with median time between diagnosis and SIC review of 0.88 years (IQR 2.84 years). At initial review 84.1% (58/69) of patients were up to date with vaccines on the Australian National Immunisation Program (NIP) schedule. Of those who were tested, serological evidence of immunity was demonstrated in 38.3% (23/60) of patients for Hepatitis B, 66.7% (36/54) for measles, 51.9% (28/54) for rubella and 41.9% (26/62) for Varicella Zoster Virus. Prior to SIC review 47.8% (33/69) had additional vaccinations and 92.8% (64/69) had vaccinations administered in the 12 months following SIC assessment. The Pneumococcal conjugate vaccine (76.8%, 53/69) was the most commonly administered vaccine after SIC review, followed by influenza vaccine (69.6%, 48/69). Within 12 months of SIC review 43.5% (30/69) of patients had completed the schedule and were up-to-date as recommended by the SIC. Children with IBD and other special risk groups can benefit from early referral to a SIC team to ensure optimal administration of routine and additionally recommended vaccines, especially live and additional special risk vaccines. The value of optimising immunisations could also be applied to other special risk groups, including adult IBD cohorts, particularly those commencing newer biologic immunosuppressive medications.
Publisher: AMPCo
Date: 04-2020
DOI: 10.5694/MJA2.50535
Publisher: Elsevier BV
Date: 10-2023
Publisher: Elsevier BV
Date: 02-2022
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.JACI.2021.10.018
Abstract: The prevalence of food allergy (FA) is increasing in some areas of the globe, highlighting the need for better strategies for prevention, diagnosis, and therapy. In the last few decades, we have made great strides in understanding the causes and mechanisms underlying FAs, prompting guideline updates. Earlier guidelines recommended avoidance of common food allergens during pregnancy and lactation and delaying the introduction of allergenic foods in children aged between 1 and 3 years. Recent guidelines for allergy prevention recommend consumption of a healthy and erse diet without eliminating or increasing the consumption of allergenic foods during pregnancy or breast-feeding. Early introduction of allergenic foods is recommended by most guidelines for allergy prevention after a period of exclusive breast-feedng (6 months [World Health Organization] or 4 months [European Academy of Allergy and Clinical Immunology]). New diagnostics for FA have been developed with varied availability of these tests in different countries. Finally, the first oral immunotherapy drug for FA was approved by the US Food and Drug Administration and European Medicines Agency in 2020. In this review, we will address the global prevalence of FA, our current understanding of the causes of FA, and the latest guidelines for preventing, diagnosing, and treating FA. We will also discuss similarities and differences between FA guidelines.
Publisher: Springer Science and Business Media LLC
Date: 06-2013
Location: United Kingdom of Great Britain and Northern Ireland
Location: Australia
Location: United States of America
Start Date: 2016
End Date: 2019
Funder: GlaxoSmithKline Australia
View Funded ActivityStart Date: 2017
End Date: 2018
Funder: MedImmune
View Funded ActivityStart Date: 2014
End Date: 2017
Funder: Pfizer Australia
View Funded ActivityStart Date: 2020
End Date: 2021
Funder: Bill and Melinda Gates Foundation
View Funded ActivityStart Date: 2016
End Date: 2019
Funder: Novavax
View Funded ActivityStart Date: 2013
End Date: 2017
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2017
End Date: 2018
Funder: Murdoch Children's Research Institute
View Funded ActivityStart Date: 2019
End Date: 2023
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2018
End Date: 2022
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2018
End Date: 2022
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2020
End Date: 2020
Funder: Canadian Institutes of Health Research
View Funded ActivityStart Date: 2020
End Date: 2023
Funder: Thrasher Research Fund
View Funded ActivityStart Date: 2017
End Date: 2018
Funder: Murdoch Children's Research Institute
View Funded ActivityStart Date: 2021
End Date: 2026
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2015
End Date: 2015
Funder: Murdoch Children's Research Institute
View Funded Activity