Search

Objective: Post-licensure vaccine safety surveillance of adverse events following immunisation is critical to ensure public safety and confidence in vaccines. This paper aims to describe the governance structure and data linkage methodology behind the establishment of the largest linked vaccine safety surveillance data resource in Australia - The Vaccine Safety Health Link (VSHL)., Methods: The Vaccine Safety Health Link contains linked records from the Australian Immunisation Register with records from hospital, perinatal, mortality, and notifiable disease datasets in near real-time. Linkage is done by the Centre for Victorian Data Linkage who receive the datasets in an identifiable format which then undergo standardisation, enrichment, linkage, quality assurance and de-identification, prior to being supplied for analysis., Results: The VSHL data resource allows sensitive and rapid analysis of a broad spectrum of suspected adverse events to ensure the safety of all vaccines administered. It is also used to refute spurious concerns where no associations are found, upholding trust, and maintaining vaccine confidence., Conclusions: The Vaccine Safety Health Link's surveillance design complements existing vaccine safety surveillance methods. Challenges encountered and lessons learnt using Vaccine Safety Health Link would benefit linkage projects globally., Implications for Public Health: In its first two years, The Vaccine Safety Health Link has been used for 14 vaccine safety investigations. Studies into these conditions would not have otherwise been possible. The Vaccine Safety Health Link also partners with the Global Vaccine Data Network™ for approved collaborative studies with a combined population of over 300 million people., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Cardiovascular disease contributes substantially to global mortality and morbidity. Respiratory tract infections, particularly influenza, may trigger an increase in the short-term risk of acute myocardial infarction (AMI) and stroke. Recent studies have also linked this risk to other respiratory viruses, including respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the pathogen-specific relative contributions, the strength of their associations, and overall public health significance are poorly understood. Assuming causal links, understanding, quantifying, and comparing the effects of different pathogens as triggering factors for acute cardiovascular events is critical to guide future research and prevention. Our aim is to conduct a systematic review to examine the relative effects of laboratory-confirmed respiratory virus infections as triggers for acute myocardial infarction and stroke., Methods: We will conduct a comprehensive search of Ovid MEDLINE, PubMed, Ovid Embase, Cochrane Library Central Register of Controlled Trials, and Web of Science, from inception to the end of March 2024. Studies capturing respiratory viral infection(s) using laboratory-confirmatory methods, incidence of AMI or stroke (ischaemic or haemorrhagic), and those involving human participants in any country, will be assessed for eligibility. We will include the following analytical epidemiological study types: randomised controlled trials, cohort and case-control studies, self-controlled case series, and case-crossover designs. We will not impose restrictions on the date, language, study population, geographical region, or sample size, to minimise the risk of introducing biases. Search results will be screened for eligibility by two independent reviewers, and discrepancies resolved by consensus and/or arbitration by a third reviewer. We will assess the risk of bias among the included studies by adopting the Cochrane Collaboration tools for randomised and non-randomised studies. The overall quality of studies will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We will examine sources of heterogeneity, and if studies are sufficiently homogeneous, a meta-analysis will be conducted to calculate the pooled effect sizes. Reporting will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines., Registration: International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42024494997., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Nguyen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Acute Disseminated Encephalomyelitis (ADEM) and Transverse Myelitis (TM) are within the group of immune mediated disorders of acquired demyelinating syndromes. Both have been described in temporal association following various vaccinations in case reports and case series and have been evaluated in observational studies. A recent analysis conducted by The Global Vaccine Data Network (GVDN) observed an excess of ADEM and TM cases following the adenoviral vectored ChAdOx1 nCoV-19 (AZD1222) and mRNA-1273 vaccines, compared with historically expected background rates from prior to the pandemic. Further epidemiologic studies were recommended to explore these potential associations. We utilized an Australian vaccine datalink, Vaccine Safety Health-Link (VSHL), to perform a self-controlled case series analysis for this purpose. VSHL was selected for this analysis as while VSHL data are utilised for GVDN association studies, they were not included in the GVDN observed expected analyses. The VSHL dataset contains vaccination records sourced from the Australian Immunisation Register, and hospital admission records from the Victorian Admitted Episodes Dataset for 6.7 million people. These datasets were used to determine the relative incidence (RI) of G040 (ADEM) and G373 (TM) ICD-10-AM coded admissions in the 42-day risk window following COVID-19 vaccinations as compared to control periods either side of the risk window. We observed associations between ChAdOx1 adenovirus vector COVID-19 vaccination and ADEM (all dose RI: 3.74 [95 %CI 1.02,13.70]) and TM (dose 1 RI: 2.49 [95 %CI: 1.07,5.79]) incident admissions. No associations were observed between mRNA COVID-19 vaccines and ADEM or TM. These findings translate to an extremely small absolute risk of ADEM (0.78 per million doses) and TM (1.82 per million doses) following vaccination; any potential risk of ADEM or TM should be weighed against the well-established protective benefits of vaccination against COVID-19 disease and its complications. This study demonstrates the value of the GVDN collaboration leveraging large population sizes to examine important vaccine safety questions regarding rare outcomes, as well as the value of linked population level datasets, such as VSHL, to rapidly explore associations that are identified., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Abstract: (No abstract provided)., (© Commonwealth of Australia CC BY-NC-ND.)

Introduction: Evidence regarding audiovestibular adverse events post COVID-19 vaccination to date has been inconclusive regarding a potential association. This study aimed to determine if there was an increase in audiovestibular events following COVID-19 vaccination in South-eastern Australia during January 2021-March 2023., Methods: A multi-data source approach was applied. First, a retrospective observational analysis of spontaneous reports of audiovestibular events to a statewide vaccine safety surveillance service, SAEFVIC. Second, a self-controlled case series analysis using general practice data collected via the POpulation Level Analysis and Reporting (POLAR) tool., Results and Conclusions: This study is the first to demonstrate an increase in general practice presentations of vertigo following mRNA vaccines (RI = 1.40, P <.001), and tinnitus following both the Vaxzevria® adenovirus vector and mRNA vaccines (RI = 2.25, P <.001 and 1.53, P <.001 respectively). There was no increase in hearing loss following any COVID-19 vaccinations. Our study, however, was unable to account for the potential of concurrent COVID-19 infections, which literature has indicated to be associated with audiovestibular events. Healthcare providers and vaccinees should be alert to potential audiovestibular complaints after COVID-19 vaccination. Our analysis highlights the importance of using large real-world datasets to gather reliable evidence for public health decision making., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Aishwarya N Shetty, Hannah J Morgan, Linny K Phuong, John Mallard, Diana Vlasenko, Nigel W Crawford, Jim P Buttery and Hazel J Clothier reports financial support was provided by Department of Health, Victoria. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.]., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Understanding background incident rates of adverse events following immunisation (AEFI) is essential to rapidly detect, evaluate, respond to, and communicate about vaccine safety concerns, especially for new vaccines. Creating estimates based on geographic specific population level data is increasingly important, as new AEFI presentations will be subject to the same local influences of population demography, exposures, health system variations and level of health care sought., Methods: We conducted a retrospective cohort analysis of hospital admissions, emergency department presentations and general practice consultations from 2015 to 2019-before introduction of COVID-19, Mpox or Shingrix vaccination-to estimate background incident rates for 37 conditions considered potential AEFI of special interest (AESI). Background incident rates per 100,000 population were calculated and presented as cases expected to occur coincidentally 1 day, 1 week and 6 weeks post-vaccination, by life-stage age-groups and presenting healthcare setting. We then assessed the proportional contribution of each data source to inform each AESI background rate estimate., Results: 16,437,156 episodes of the 37 AESI were identified. Hospital admissions predominantly informed 19 (51%) of AESI, including exclusively ADEM and CVST; 8 AESI (22%) by primary care, and 10 (27%) a mix. Four AESI (allergic urticaria, Bell's palsy, erythema multiform and sudden death) were better informed by emergency presentations than admissions, but conversely 11 AESI (30%) were not captured in ICD-10 coded emergency presentations at all., Conclusions: Emergent safety concerns are inevitable in population-wide implementation of new vaccines, therefore understanding local background rates aids both safety signal detection as well as maintaining public confidence in vaccination. Hospital and primary care data sources can be interrogated to inform expected background incident rates of adverse events that may occur following vaccination. However, it is necessary to understand which data-source provides best intelligence according to nature of condition and presenting healthcare setting., Competing Interests: Declaration of competing interest Hazel J Clothier, Aishwarya N Shetty, Jim P Buttery reports financial support was provided by Department of Health, Victoria. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Myocarditis and myopericarditis are well described adverse events of special interest (AESI) following COVID-19 vaccinations. Although reports are reassuring regarding initial clinical outcomes, information about longer term outcomes remains limited. We aimed to further this knowledge and report outcomes to 6 months post diagnosis from a single population cohort., Methods: Reports of myocarditis following COVID-19 vaccination were followed up by SAEFVIC (Surveillance of Adverse Events Following Vaccination in the Community), the state-wide vaccine safety service for Victoria, Australia. Confirmed myocarditis cases (Brighton Collaboration Criteria levels 1-3) were followed up via surveys at 1, 3 and 6 months post symptom onset. Responses received between 22 February 2021 and 30 September 2022 were analysed., Results: 87.5 % (N = 182) of eligible participants completed at least 1 survey report. 377 reports were analysed. 76.9 % of completed reports were from male patients. The median age of patients was 21 years [IQR: 16 to 32]. 54.8 % (n = 74) of survey reports at 6 months, reported ongoing symptoms. At all follow-up time points, females were significantly more likely to have ongoing symptoms. At 6 months, 51.9 % of male respondents reported symptom resolution compared to 22.6 % of female patients (p = 0.002). Females were also more likely to continue medication and have ongoing exercise restrictions. However, males were significantly more likely to have higher initial peak troponin results and abnormal initial cardiac imaging investigations., Conclusions: There appears to be a significant proportion of patients who experience ongoing symptoms to 6 months post onset amongst patients that experience these AESI. Male patients were more likely to report earlier and more complete symptom recovery, despite significantly higher average initial peak troponin. This difference in phenotypic presentation in females compared to males warrants further investigation and there is a need for longer term follow up data., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Shoulder Injury Related to Vaccine Administration (SIRVA) is a preventable adverse event following incorrect vaccine administration, which can result in significant long-term morbidity. There has been a notable surge in reported cases of SIRVA as a rapid national population-based COVID-19 immunization program has been rolled out across Australia., Methods: Surveillance of Adverse Events Following Vaccination in the Community (SAEFVIC) in Victoria identified 221 suspected cases of SIRVA following the commencement of the COVID-19 vaccination program, reported between February 2021 and February 2022. This review describes the clinical features and outcomes of SIRVA in this population. Additionally, a suggested diagnostic algorithm is proposed, in order to facilitate early recognition and management of SIRVA., Results: 151 cases were confirmed as SIRVA, with 49.0% having received vaccines at state vaccination centers. 75.5% were suspected incorrect administration site, with most patients experiencing shoulder pain and restricted movement within 24 hours of vaccination, lasting on average 3 months., Conclusion: Improved awareness and education regarding SIRVA is imperative in a pandemic vaccine roll-out. The development of a structured framework for evaluating and managing suspected SIRVA will aid in timely diagnosis and treatment, essential to mitigate potential long-term complications.

Purpose: Shoulder injury directly related to vaccination (SIRVA) occurs when a vaccine is administered too high in the shoulder. The primary aim of this study was to accurately detail the occurrence, symptoms, diagnosis, management and long-term outcomes of SIRVA cases in Victoria, Australia., Principal Results: The study identified 102 SIRVA cases from 2007 to 2020 from the Surveillance of Adverse Events Following Vaccination in the Community (SAEFVIC) database. The majority [73/85; (86 %)] of cases resolved completely with a median time to resolution of 8 weeks and no statistically significant difference in recovery by immunisation provider type or baseline imaging., Major Conclusions: This large case series includes long-term clinical progress in SIRVA, allowing accurate evaluation and analysis. Further evaluation is required to establish if other risk factors contribute to SIRVA, which may help with targeted, tailored education for providers on correct vaccine administration technique, including in large and rapid vaccine rollouts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Guillain-Barré syndrome (GBS) is an adverse event of special interest (AESI) for surveillance systems monitoring adverse events following immunisation (AEFI) with COVID-19 vaccines. Emerging data support a temporal association between GBS and adenovirus-vector COVID-19 vaccines. We present a case series of GBS reports submitted between February and November 2021 to our enhanced spontaneous surveillance system (SAEFVIC) in Victoria, Australia, following vaccination with either the adenovirus-vector vaccine Vaxzevria ChadOx1-S (AstraZeneca) or an mRNA vaccine (Comirnaty BNT162b2 [Pfizer-BioNTech] or Spikevax mRNA-1273 [Moderna]). For each report, Brighton Collaboration case definitions were used to describe diagnostic certainty. Severity was graded using the GBS Disability Score. The observed incidence of GBS following immunisation against COVID-19 was compared to expected background ICD10-AM G61.0 coded hospitalisations. There were 41 total cases of GBS reported to SAEFVIC following Vaxzevria (n = 38), Comirnaty (n = 3), or Spikevax (n = 0) vaccines. The observed GBS incidence rate exceeded the expected background rate for Vaxzevria only, with 1.85 reports per 100,000 doses following dose 1, higher than the expected rate of 0.39 hospital admissions per 100,000 adults within 42 days of vaccination. Of 38 GBS reports following Vaxzevria, the median age at vaccination was 66 years and median onset of symptoms was 14 days following immunisation. There was one death. Four cases initially categorised as GBS were later reclassified as acute-onset chronic inflammatory demyelinating polyneuropathy. Fatigue was the predominant persisting symptom reported at follow up. Additional global studies are required to characterise risk factors, clinical variability, and to provide precision and generalizability regarding AEFI risks such as GBS associated with different vaccine platforms, which will help inform communication of the potential benefits and risks of COVID19 vaccination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The Victorian Specialist Immunization Services (VicSIS) was established in Victoria, Australia, in February 2021, aiming to enhance vaccine safety services for Coronavirus disease (COVID-19) vaccines. VicSIS supports practitioners and patients with complex vaccine safety questions, including those who experience adverse events following immunization (AEFI) after COVID-19 vaccines. VicSIS provides individual vaccination recommendations, allergy testing, vaccine challenges, and vaccination under supervision. VicSIS initially comprised of eight adult COVID-19 specialist vaccination clinics, subsequently, expanding to better support pediatric patients as the Australian vaccine roll-out extended to adolescents and children. Since their establishment to September 2021, the inaugural VicSIS clinics received a total of 26,401 referrals and reviewed 6,079 patients. Consults were initially predominantly for pre-vaccination reviews, later predominantly becoming post-vaccination AEFI reviews as the program progressed. Regardless of the type of consult, the most common consult outcome was a recommendation for routine vaccination (73% and 55% of consult outcomes respectively). VicSIS is an integral component of the COVID-19 vaccination program and supports confidence in COVID-19 vaccine safety by providing consistent advice across the state. VicSIS aims to strengthen the health system through the pandemic, bolstering specialist immunization services beyond COVID-19 vaccines, including training the next generation of vaccinology experts.

Immunization implementation in the community relies upon post-licensure vaccine safety surveillance to maintain safe vaccination programs and to detect rare AEFI not observed in clinical trials. The increasing availability of electronic health-care related data and correspondence from both health-related providers and internet-based media has revolutionized health-care information. Many and varied forms of health information related to adverse event following immunization (AEFI) are potentially suitable for vaccine safety surveillance. The utilization of these media ranges from more efficient use of electronic spontaneous reporting, automated solicited surveillance methods, screening various electronic health record types, and the utilization of natural language processing techniques to scan enormous amounts of internet-based data for AEFI mentions. Each of these surveillance types have advantages and disadvantages and are often complementary to each other. Most are "hypothesis generating," detecting potential safety signals, where some, such as vaccine safety datalinking, may also serve as "hypothesis testing" to help verify and investigate those potential signals.

Importance: COVID-19 mRNA vaccine-associated myocarditis has previously been described; however specific features in the adolescent population are currently not well understood., Objective: To describe myocarditis adverse events following immunisation reported following any COVID-19 mRNA vaccines in the adolescent population in Victoria, Australia., Design: Statewide, population-based study., Setting: Surveillance of Adverse Events Following Vaccination in the Community (SAEFVIC) is the vaccine-safety service for Victoria, Australia., Participants: 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., Exposures: Any mRNA COVID-19 vaccine., Main Outcomes/mmeasure: Confirmed myocarditis as per Brighton Collaboration criteria (levels 1-3)., Results: 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=<0.001).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)., Conclusion: 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Brighton Collaboration Global Alignment of Immunization Safety in Pregnancy (GAIA) project developed case definitions for the assessment of adverse events in mothers and infants following maternal immunization. This study evaluated the applicability of these definitions to data collected in routine clinical care and research trial records across 7 sites in high-resource settings., Methods: Data collection forms were designed and used to retrospectively abstract the key elements of the GAIA definitions from records for 5 neonatal and 5 maternal outcomes, as well as gestational age. Level of diagnostic certainty was assessed by the data abstractor and an independent clinician, and then verified by Automated Brighton Case logic. The ability to assign a level of diagnostic certainty for each outcome and the positive predictive value (PPV) for their respective ICD-10 codes were evaluated., Results: Data from 1248 case records were abstracted: 624 neonatal and 622 maternal. Neonatal outcomes were most likely to be assessable and assigned by the level of diagnostic certainty. PPV for preterm birth, low birth weight, small for gestational age and respiratory distress were all above 75%. Maternal outcomes for preeclampsia and fetal growth restriction showed PPV over 80%. However, microcephaly (neonatal outcome) and dysfunctional labor (maternal outcome) were often nonassessable, with low PPVs., Conclusions: The applicability of GAIA case definitions to retrospectively ascertain and classify maternal and neonatal outcomes was variable among sites in high-resource settings. The implementation of the case definitions is largely dependent on the type and quality of documentation in clinical and research records in both high- and low-resource settings. While designed for use in the prospective evaluation of maternal vaccine safety, the GAIA case definitions would likely need to be specifically adapted for observational studies using alternative sources of data, linking various data sources and allowing flexibility in the ascertainment of the elements and levels of certainty of the case definition., Competing Interests: A.K. has worked as a consultant for GlaxoSmithKline and Pfizer on maternal immunization projects not related to this study. F.M.M. is a member of the DSMB member for various vaccines including for maternal immunization for Pfizer, Moderna and the US National Institutes of Health. She has received funding to her institution to conduct clinical trials related to maternal immunization and epidemiology from Novavax, Janssen, Glaxo Smith Kline, the US National Institutes of Health and the US Centers for Disease Control and Prevention. E.P.S. has worked as a consultant for Sanofi on immunization projects not related to this study. She has received funding to her institution from vaccine manufacturers to conduct clinical research. I.B.Y. has received funding from Center for Childhood Infections and Vaccines at Emory University and Children’s Healthcare of Atlanta. I.B.Y. has received funding to her institution to conduct clinical research from BioFire, MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Novavax, Sanofi-Pasteur and Micron. J.P.B. has received funding to his institution to conduct clinical research from MedImmune, Pfizer, GSK, Merck, Novavax, Sanofi-Pasteur and Seqirius. C.E.J. has worked as a consultant for MSD, Sanofi and Pfizer on maternal immunization projects not related to this study. She has received funding to her institution to conduct clinical trials from vaccine manufacturers. The other authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Emerging evidence suggest a possible association between immune thrombocytopenia (ITP) and some formulations of COVID-19 vaccine. We conducted a retrospective case series of ITP following vaccination with Vaxzevria ChadOx1-S (AstraZeneca) and mRNA Comirnaty BNT162b2 COVID-19 (Pfizer-BioNTech) vaccines and compare the incidence to expected background rates for Victoria during the first six months of the Australian COVID-19 vaccination roll-out in 2021. Cases were identified by reports to the Victorian state vaccine safety service, SAEFVIC, of individuals aged 18 years or older presenting with thrombocytopenia following COVID-19 vaccination without evidence of thrombosis. Twenty-one confirmed or probable cases of ITP were identified following receipt of AstraZeneca (n = 17) or Pfizer-BioNTech (n = 4) vaccines. This translates to an observed incidence of 8 per million doses for AstraZeneca vaccine, twice the expected background rate of 4.1 per million. The observed rate for Pfizer-BioNTech was consistent with the expected background rate. The median time to onset for the cases post AstraZeneca vaccination was 10 days (range 1-78) and median platelet nadir 5 × 10 9 /L (range 0-67 × 10 9 /L). Hospital presentations or admissions for management of symptoms such as bleeding occurred in 18 (86%) of the cases. The majority of cases (n = 11) required intervention with at least 2 therapy modalities. In conclusion, we observed a substantially higher than expected rate of ITP following AstraZeneca vaccination. ITP is the second haematological adverse event, distinct from that of thrombosis with thrombocytopenia syndrome (TTS), observed following AstraZeneca vaccination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Group B Streptococcus (GBS) is a major contributor to neonatal sepsis worldwide. Late-onset group B Streptococcus disease (LOGBS) and its risk factors remain poorly understood. The isolation of GBS from breast milk has been described in cases of LOGBS. This potential association has raised concerns for mothers and clinicians regarding the safety of ongoing breastfeeding. In this study, we aimed to investigate whether exposure to breast milk is associated with increased risk of LOGBS., Methods: A case-control study of LOGBS was conducted across 4 hospital networks in Victoria, Australia, including the 2 major tertiary pediatric centers in the state, to evaluate 11 years of data (2007-2017). Cases were captured initially from microbiology databases and recaptured with International Classification of Diseases discharge coding. Each case patient was matched with 4 controls to assess feeding status. Patients were matched for chronological age, gestation, discharge status, recruitment site, and calendar year., Results: We identified 92 cases of LOGBS: 73 cases on initial capture and 76 cases on the recapture analysis. Case patients were matched with 368 controls: 4 controls to each patient. Seventy-two patients were exposed to breast milk at the time of LOGBS (78.3%), compared with 274 controls (74.5%; odds ratio 1.2 [95% confidence interval 0.7-2.3])., Conclusions: Breastfeeding was not associated with increased risk of LOGBS. Breast milk should not be tested for GBS during a first episode of LOGBS., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Acute disseminated encephalomyelitis (ADEM) is an autoimmune, central nervous system demyelinating disorder that follows antecedent immunologic challenges, such as infection or vaccination. This study aimed to investigate the potential association between routine childhood vaccinations and ADEM. Children under 7 years of age admitted to the two tertiary level pediatric hospitals in Victoria, Australia with ADEM from 2000-2015 had their clinical information linked to vaccination records from the Australian Childhood Immunization Register. Chart review was undertaken utilizing the Brighton Collaboration ADEM criteria. The self-controlled case-series (SCCS) methodology was employed to determine the relative incidences of ADEM post-vaccination in two risk intervals: 5-28 days and 2-42 days. Forty-six cases were eligible for SCCS analysis with a median age of 3.2 years. Of the forty-six cases, three were vaccine proximate cases and received vaccinations 23, 25 and 28 days before ADEM onset. Two vaccine proximate cases received their 4-year-old scheduled vaccinations (MMR and DTPa-IPV) and one vaccine proximate case the 1-year old scheduled vaccinations (MMR and Hib-MenC). The relative incidence of ADEM during the narrow and broad risk intervals were 1.041 (95% CI 0.323-3.356, p = 0.946) and 0.585 (95% CI 0.182-1.886, p = 0.370) respectively. Sensitivity analyses did not yield any substantial deviations. These results do not provide evidence of an association between vaccinations routinely provided to children aged under 7 years in Australia and the incidence of ADEM. However, these results should be interpreted with caution as the number of ADEM cases identified was limited and further research is warranted.

Competing Interests: JPB declares no competing interests. CK reports a patent Rv3 rotavirus vaccine issued (PCT/AU2013/000945).

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Rational medication use for treatment is mandatory, particularly in children as they are vulnerable to possible hazards of drugs. Understanding the medication use pattern is of importance to identify the problems of drug therapy and to improve the appropriate use of medication among this population., Methods: A post-hoc study of the RV3-BB Phase IIb trial to children aged 0-18 months which was conducted in Indonesia during January 2013 to July 2016. Any concomitant medication use and health events among 1621 trial participants during the 18 months of follow-up were documented. Information on medication use included the frequency, formulation, indication, duration of usage, number of regimens, medication types, and therapeutic classes., Results: The majority of participants (N = 1333/1621; 82.2%) used at least one non-antibiotic medication for treatment during the 18-month observation period. A total of 7586 medication uses were recorded, mostly in oral formulation (90.5%). Of all illnesses recorded, 24.7% were treated with a single drug regimen of non-antibiotic medication. The most common therapeutic classes used were analgesics/antipyretics (30.1%), antihistamines for systemic use (17.4%), cough and cold preparations (13.5%), vitamins (8.6%), and antidiarrheals (6.6%). The main medication types used were paracetamol (29.9%), chlorpheniramine (16.8%), guaifenesin (8.9%), zinc (4.6%), and ambroxol (4.1%). Respiratory system disorder was the most common reason for medication use (51.9%), followed by gastrointestinal disorders (19.2%), pyrexia (16.9%), and skin disorders (7.0%)., Conclusion: A large number of children were exposed to at least one medication during their early life, including those where evidence of efficacy and safety in a pediatric population is lacking. This supports the need for further research on pediatric drug therapy to improve the appropriate use of medication in this population., Competing Interests: The authors have the following interests: NSB is a paid employee of PT Biofarma. PT Biofarma is a state-owned company (owned by Indonesia government) that provides all vaccines for Indonesia National Immunization Program. Additionally, PT Biofarma was one of the non-commercial funders for the RV3-BB Phase IIB trial. No consultation was done to the funder relating to the trial. The trial was a phase IIB trial and while the RV3-BB rotavirus vaccine is not yet marketed, this vaccine is being developed with the intention for eventual usage in the national immunization program. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Juvenile idiopathic arthritis (JIA) is a collective term for a group of inflammatory conditions of uncertain origin, which causes chronic arthritis in one or more joints. The clinical course of JIA is characterised by episodes of increased activity, termed flares. Vaccinations have previously been proposed as a "trigger" for some flares, although evidence supporting this is scant., Objective: To explore whether routine childhood vaccinations are associated with an increased risk of flares of arthritis activity in children with JIA., Methods: Patients aged below 6 years with a diagnosis of JIA were recruited from the Rheumatology Clinical Database at the Royal Children's Hospital, Melbourne, Australia, from 1 January 2010 to 30 April 2016. Patient immunisation status was cross-checked with the Australian Childhood Immunisation Register (ACIR). The self-controlled case series methodology (Rowhani-Rahbar et al., 2012) was applied to determine whether the risk of arthritis flares in the three months following immunisation was greater than the baseline risk for each patient., Results: 138 patients were included in the study. 32 arthritis flares occurred in the 90 days following immunisation. The risk of arthritis flares during the 90 days following immunisation was reduced compared with patients' baseline risk (RR 0.59 (95% CI 0.39-0.89, p = 0.012))., Conclusion: Routine childhood immunisations were not associated with arthritis flare onset in patients with JIA. The risk of arthritis flares in the 90 days following vaccination was lower than the baseline risk. In the context of COVID19, vaccination will not increase interaction with the healthcare system beyond the immunisation encounter., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Naba M. Alfayadh et al.)

Background: The increasing availability of electronic healthcare data offers an opportunity to enhance adverse events following immunisation (AEFI) signal monitoring in near real-time., Aim: To evaluate the potential use of telephone helpline data to augment the existing AEFI surveillance system in Victoria, Australia., Methods: Anonymised telephone helpline call data were extracted between 2009 and 2017. For comparison, we included AEFI reports to the Victorian enhanced passive surveillance system, SAEFVIC-"Surveillance of Adverse Events Following Vaccination In the Community". The temporal pattern cross-correlation coefficient at different time lags was estimated as a measure of timeliness evaluation. Historically known AEFI signals in 2010 and 2015 were examined using the Farrington statistical signal detection algorithm., Result: During the study period, overall, the telephone helpline centre received 2,005,226 calls. Of these, 0.68% (13,719) were AEFI-related. In the same period, SAEFVIC received 10,367 AEFI related reports. Cross-correlation analysis, generally, showed that the two datasets were moderately correlated (r = 0.4) at a negative lag of 1 week. For individual years, the cross-correlation coefficient was highest (r = 0.66) in 2010 with the telephone helpline data leading by 2 weeks. Our analysis indicated the 2010 reported incidence of febrile convulsions and the 2015 reported increased allergic-related reactions following seasonal influenza vaccination three weeks and one week earlier respectively., Conclusion: Telephone helpline data was able to detect an increased rate of AEFI earlier than the enhanced passive AEFI surveillance system. This dataset offers a valuable and near real-time component of an integrated AEFI early signal detection system in Australia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: SAEFVIC is the Victorian surveillance system for adverse events following immunisation (AEFI). It enhances passive surveillance by also providing clinical support and education to vaccinees and immunisation providers. This report summarises surveillance, clinical and vaccine pharmacovigilance activities of SAEFVIC in 2018., Methods: A retrospective observational cohort study of AEFI reports received by SAEFVIC in 2018, compared with previous years since 2008. Data were categorised by vaccinee demographics of age, sex, pregnancy and Indigenous status, vaccines administered and AEFI reactions reported. Age cohorts were defined as infant (0-12 months); young child (1-4 years); school-aged (5-17 years); adult (18-64 years); and older person (65+ years). Proportional reporting ratios were calculated for signal investigation of serious adverse neurological events with all vaccines and with influenza vaccines. Clinical support services and educational activities are described., Results: SAEFVIC received 1730 AEFI reports (26.8 per 100,000 population), with 9.3% considered serious. Nineteen percent (n = 329) attended clinical review. Annual AEFI reporting trends increased for infants, children and older persons, but were stable for school-aged and adult cohorts. Females comprised 55% of all reports and over 80% of reports among adults. There were 17 reports of AEFI in pregnant women and 12 (0.7%) in persons identifying as Indigenous Australians. A possible signal regarding serious adverse neurological events (SANE) was detected, but was not supported by signal validation testing. A clinical investigation is ongoing. Two deaths were reported coincident to immunisation with no evidence of causal association., Conclusion: SAEFVIC continues to provide robust AEFI surveillance supporting vaccine safety monitoring in Victoria and Australia, with new signal detection and validation methodologies strengthening capabilities., (© Commonwealth of Australia CC BY-NC-ND.)

Background: New jurisdictionally-based vaccination programs were established providing free quadrivalent influenza vaccine (QIV) for preschool Australian children in 2018. This was in addition to the National Immunisation Program (NIP) funded QIV for Indigenous children and children with comorbid medical conditions. We assessed the impact of this policy change on influenza disease burden and vaccine coverage, as well as report on 2018 vaccine effectiveness in a hospital-based surveillance system., Methods: Subjects were recruited prospectively from twelve PAEDS-FluCAN sentinel hospital sites (April until October 2018). Children aged ≤16 years hospitalised with an acute respiratory illness (ARI) and laboratory-confirmed influenza were considered cases. Hospitalised children with ARI who tested negative for influenza were considered controls. VE estimates were calculated from the adjusted odds ratio of vaccination in cases and controls., Results: A total of 458 children were hospitalised with influenza: 31.7% were <2 years, 5.0% were Indigenous, and 40.6% had medical comorbidities predisposing to severe influenza. Influenza A was detected in 90.6% of children (A/H1N1: 38.0%; A/H3N2: 3.1%; A/unsubtyped 48.6%). The median length of stay was 2 days (IQR: 1,3) and 8.1% were admitted to ICU. Oseltamivir use was infrequent (16.6%). Two in-hospital deaths occurred (0.45%). 12.0% of influenza cases were vaccinated compared with 36.0% of test-negative controls. Vaccine effectiveness of QIV for preventing influenza hospitalisation was estimated at 78.8% (95%CI: 66.9; 86.4)., Conclusions: Compared with 2017 (n = 1268 cases), a significant reduction in severe influenza was observed in Australian children, possibly contributed to by improved vaccine coverage and high vaccine effectiveness. Despite introduction of jurisdictionally-funded preschool programs and NIP-funded vaccine for children with risk factors for severe disease, improved coverage is required to ensure adequate protection against paediatric influenza morbidity and mortality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)