Human Neonatal Rotavirus Vaccine (RV3-BB) to Target Rotavirus from Birth.

BACKGROUND: A strategy of administering a neonatal rotavirus vaccine at birth to target early prevention of rotavirus gastroenteritis may address some of the barriers to global implementation of a rotavirus vaccine. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in Indonesia to evaluate the efficacy of an oral human neonatal rotavirus vaccine (RV3-BB) in preventing rotavirus gastroenteritis. Healthy newborns received three doses of RV3-BB, administered according to a neonatal schedule (0 to 5 days, 8 weeks, and 14 weeks of age) or an infant schedule (8 weeks, 14 weeks, and 18 weeks of age), or placebo. The primary analysis was conducted in the per-protocol population, which included only participants who received all four doses of vaccine or placebo within the visit windows, with secondary analyses performed in the intention-to-treat population, which included all participants who underwent randomization. RESULTS: Among the 1513 participants in the per-protocol population, severe rotavirus gastroenteritis occurred up to the age of 18 months in 5.6% of the participants in the placebo group (28 of 504 babies), in 1.4% in the neonatal-schedule vaccine group (7 of 498), and in 2.7% in the infant-schedule vaccine group (14 of 511). This resulted in a vaccine efficacy of 75% (95% confidence interval [CI], 44 to 91) in the neonatal-schedule group (P<0.001), 51% (95% CI, 7 to 76) in the infant-schedule group (P=0.03), and 63% (95% CI, 34 to 80) in the neonatal-schedule and infant-schedule groups combined (combined vaccine group) (P<0.001). Similar results were observed in the intention-to-treat analysis (1649 participants); the vaccine efficacy was 68% (95% CI, 35 to 86) in the neonatal-schedule group (P=0.001), 52% (95% CI, 11 to 76) in the infant-schedule group (P=0.02), and 60% (95% CI, 31 to 76) in the combined vaccine group (P<0.001). Vaccine response, as evidenced by serum immune response or shedding of RV3-BB in the stool, occurred in 78 of 83 participants (94%) in the neonatal-schedule group and in 83 of 84 participants (99%) in the infant-schedule group. The incidence of adverse events was similar across the groups. No episodes of intussusception occurred within the 21-day risk period after administration of any dose of vaccine or placebo, and one episode of intussusception occurred 114 days after the third dose of vaccine in the infant-schedule group. CONCLUSIONS: RV3-BB was efficacious in preventing severe rotavirus gastroenteritis when administered according to a neonatal or an infant schedule in Indonesia. (Funded by the Bill and Melinda Gates Foundation and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612001282875 .).

Respiratory virus detection and co-infection in children and adults in a large Australian hospital in 2009-2015.

AIM: This hospital network-based retrospective observational study aimed to describe the prevalence and seasonality of paediatric and adult viral respiratory pathogens and their rates of co-infections, following the introduction of a rapid multiplex molecular diagnostic assay. METHODS: All nasopharyngeal samples tested in patients presenting to Monash Health, Melbourne, Australia, from August 2009 to July 2015 by means of multiplex tandem polymerase chain reaction using the Respiratory Pathogen 12Plex kit (AusDiagnostics) were included in the analysis. RESULTS: There were 28 729 patient samples analysed after duplicate samples were excluded. Positive results were twice as likely in paediatrics, 7573/11 491 (65.9%), compared to adults, 5410/17 238 (31.4%). Co-infection was more frequent in paediatrics, 1642/7573 (21.7% of positives), compared to adults 299/5410 (5.5%). Adenovirus had a high prevalence as a co-infection, 639/990 (64.5%), in paediatrics. Testing frequency increased by 179% in the paediatric group and by 949% for adults over the 6 years of observation. CONCLUSIONS: This study demonstrated a significant difference in the positive detection rate of pathogens and co-infections between the population groups. Adenovirus had a surprisingly high prevalence as a co-infection, especially in paediatric patients. Over the study period, rapid uptake of the test was observed, especially in adults. This raises concerns about how we can ensure that testing remains rational and is able to be provided in a cost-effective manner in the future.

Empiric antibiotic regimens for neonatal sepsis in Australian and New Zealand neonatal intensive care units.

AIM: Neonatal sepsis remains an important cause of morbidity and mortality, and requires prompt empiric treatment. However, only a minority of babies who receive antibiotics for suspected sepsis have an infection. Antimicrobial exposure in infancy has important short- and long-term consequences. There is no consensus regarding empirical antimicrobial regimens. METHODS: The study included a survey of empiric antimicrobial regimens in all tertiary neonatal intensive care units in Australia and New Zealand in 2013-2014. RESULTS: All 27 units responded. For early-onset sepsis, all units used a combination of gentamicin with either penicillin or ampicillin. For late-onset sepsis, the frequency of units using empiric vancomycin (41%) versus empiric flucloxacillin (48%) was similar. Gestational age or the presence of a central venous catheter had little influence on using vancomycin instead of flucloxacillin. For late-onset sepsis with meningitis there was marked variation in antimicrobial combinations, with 15 different regimens described. A total of 93% used a cefotaxime-based regimen, either as monotherapy (22%) or combined with a second (22%) or third (48%) agent. For suspected necrotising enterocolitis, 89% used an aminoglycoside, metronidazole and a penicillin. Historical outbreaks of multi-resistant organisms exerted long-term influence over regimen choice. CONCLUSIONS: There was limited use of broad-spectrum agents such as carbapenems or third-generation cephalosporins. In this region with low methicillin-resistant Staphylococcus aureus prevalence, empiric vancomycin use was common, selected for activity against coagulase-negative staphylococci. Empiric vancomycin is rarely necessary because coagulase-negative staphylococci are often contaminants and sepsis is rarely fulminant, occurring almost exclusively in extremely low birthweight infants. Implementation of appropriate, local antimicrobial policies is crucial to minimise antimicrobial exposure in this vulnerable population and halt the development of antimicrobial resistance.

Allergic adverse events following 2015 seasonal influenza vaccine, Victoria, Australia.

Australia was alerted to a possible increase in allergy-related adverse events following immunisation (AEFI) with 2015 seasonal trivalent influenza vaccines (TIV) by the Victorian state vaccine safety service, SAEFVIC. We describe SAEFVIC's initial investigation and upon conclusion of the 2015 influenza vaccination programme, to define the signal event and implications for vaccine programmes. Allergy-related AEFI were defined as anaphylaxis, angioedema, urticaria or generalised allergic reaction. Investigations compared 2015 TIV AEFI reports to previous years as proportions and reporting risk (RR) per 100,000, stratified by influenza vaccine brand. The initial investigation showed an increased proportion of allergy-related AEFI compared with 2014 (25% vs 12%), predominantly in adults, with insufficient clinical severity to alter the programme risk-benefit. While overall TIV AEFI RR in 2015 was similar to previous years (RR: 1.07, 95% confidence interval (CI): 0.88-1.29), we identified a near-doubling RR for allergy-related AEFI in 2015 (RR: 1.78, 95% CI: 1.14-- 2.80) from 2011 to 2014 with no difference by vaccine brand or severity increase identified. This increase in generalised allergy-related AEFI, across all used vaccine brands, supports evidence of variable reactogenicity arising from influenza vaccine strain variations. This investigation underlines the importance of effective seasonal influenza vaccine pharmacovigilance.

The safety of seasonal influenza vaccines in Australian children in 2013.

OBJECTIVE: To examine influenza vaccine safety in Australian children aged under 10 years in 2013. DESIGN, PARTICIPANTS AND SETTING: Active prospective surveillance study conducted with parents or carers of children who received influenza vaccine in outpatient clinics at six tertiary paediatric hospitals or from selected primary health care providers between 18 March and 19 July 2013. MAIN OUTCOME MEASURES: Parental-reported frequency of systemic reactions (fever, headache, nausea, abdominal symptoms, convulsions, rash, rigors and fatigue), injection site reactions (erythema, swelling and/or pain at the injection site), use of antipyretics or analgesics, and medical attendance or advice within 72 hours after vaccination. RESULTS: Of 981 children enrolled in the surveillance, 893 children aged 6 months to < 10 years were eligible for inclusion. These children received 1052 influenza vaccine doses. Fever was reported in 5.5% (95% CI, 4.1%-7.3%) and 6.5% (95% CI, 3.5%-10.9%) of children after Doses 1 and 2, respectively. One febrile convulsion occurred in a child with a known seizure disorder. Injection site reactions occurred in 21.2% (95% CI, 18.5%-24.1%) and 6.0% (95% CI, 3.1%-10.2%) after Doses 1 and 2, respectively; most were mild. Very few parents sought medical follow-up for their child's reaction: 22 (2.6%; 95% CI, 1.6%-3.9%) after Dose 1, and 11 (5.5%; 95% CI, 2.8%-9.6%) after Dose 2. CONCLUSIONS: These results are consistent with clinical trials and other observational studies of influenza vaccines currently registered for use in young children in Australia and can reassure parents and health care providers that influenza vaccination is safe and well tolerated.

Improving preterm infants' immunisation status: a follow-up audit.

AIM: Preterm infants are at increased risk of vaccine preventable diseases. An audit in 2007 identified suboptimal immunisation status of preterm infants. The aim of this study was to complete the 'audit loop', reviewing preterm infants' immunisation status at a single tertiary paediatric hospital. METHODS: A retrospective follow-up immunisation audit was conducted at The Royal Children's Hospital, Melbourne, neonatal unit. The 'audit loop' included a preterm infants' reminder sticker and feedback of the original audit findings to Royal Children's Hospital health-care professionals. Immunisation status was determined using the Australian Childhood Immunisation Register record for all admitted preterm infants born <32 weeks gestation (July 2008-June 2009). RESULTS: Conducted in March 2011, the median age of participants (n = 57) was 2.5 years (range 1.7-3.1 years). Forty-four per cent (25/57) had a history of chronic lung disease, 86% (49/57) were <1500 g and 42% (24/57) <28 weeks gestation. The majority (96% (55/57)) were up to date with routine immunisations at 12 months of age. There was a 2.4-fold increase, compared with the original audit, for receipt of the additional recommended hepatitis B vaccine at 12 months of age, as well as influenza vaccine in infants with chronic lung disease. CONCLUSION: This study showed that a simple reminder combined with education strategies can improve vaccine delivery in special risk groups such as preterm infants.

Letter to the Editor: A comparison of post-COVID vaccine myocarditis classification using the Brighton Collaboration criteria versus (United States) Centers for Disease Control criteria: an update.

Abstract: (No abstract provided).

Acute disseminated encephalomyelitis and transverse myelitis following COVID-19 vaccination - A self-controlled case series analysis.

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.

What would have happened anyway? Population data source considerations when estimating background incident rates of adverse events following immunisation to inform vaccine safety.

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.

Long term follow up and outcomes of Covid-19 vaccine associated myocarditis in Victoria, Australia: A clinical surveillance study.

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.

Audiovestibular adverse events following COVID-19 vaccinations.

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.

Human papillomavirus vaccine in boys: background rates of potential adverse events.

OBJECTIVES: To determine background rates of potential adverse events following immunisation (AEFI) before expansion of the quadrivalent human papillomavirus (4vHPV) vaccination program to adolescent boys. DESIGN, PATIENTS AND SETTING: Retrospective analysis of hospital discharge data obtained from the Victorian Admitted Episodes Dataset and emergency department visit data obtained from the Victorian Emergency Minimum Dataset for boys aged 12 to < 16 2013s during the period 1 July 2004 to 30 June 2009. MAIN OUTCOME MEASURES: Numbers of and incidence rates for Guillain-Barré syndrome, anaphylaxis, seizures, syncope and other potential AEFI from 1 July 2004 to 30 June 2009, and estimated numbers of events after 4vHPV vaccination assuming no association (other than temporal) with the vaccine. RESULTS: We estimated background rates of neurological and allergic events in adolescent boys to be 252.9 and 175.2 per 100 000 person-2013s, respectively. Assuming an 80% vaccination rate with three doses per person - which equates to 1 440 000 doses administered nationally per 2013 in the first 2 2013s of the program - about 2.4 episodes of Guillain-Barré syndrome would be expected to occur in the 6 weeks following vaccination. Within 1 day of vaccination, about 3.9 seizures, 0.3 episodes of anaphylaxis and 6.5 acute allergy presentations would be expected. CONCLUSIONS: Routinely collected health outcome administration data can inform postlicensure safety surveillance of target conditions that might be perceived as AEFI.

Changes in the epidemiology of gastroenteritis in a paediatric short stay unit following the introduction of rotavirus immunisation.

AIM: Acute gastroenteritis (AGE) has been a significant component of the clinical load in the short stay unit (SSU) at the Royal Children's Hospital (RCH) since its establishment in 2004. Since the introduction of routine rotavirus immunisation in Australia in 2007 there has been a clinical impression of a substantial reduction in AGE managed in the SSU. This study aimed to examine changes in the epidemiology of AGE in the SSU, and RCH overall, between 2005 and 2009 and explore whether this reflects a change specifically in AGE due to rotavirus. METHODS: Discharge coding data for AGE from all inpatient wards, the SSU and emergency department (ED) at the RCH were examined. Stool virology results for the same period were analysed. RESULTS: Since 2007 there has been a 58% reduction in AGE admissions to the SSU. The median age of patients admitted to the RCH with rotaviral enteritis has increased from 1.3 years to 3.8 years. Presentations to the ED for AGE have fallen from 53 to 34 cases per 1000 attendances between 2004 and 2009, and admission rates from the ED have fallen from 23 to 13% of AGE presentations. Detection rates of rotavirus fell from 13.1 to 6.7% between 2005 and 2009. CONCLUSION: A marked decrease in AGE-related clinical activity and reduction in rotavirus detection at the RCH has occurred since the introduction of routine rotavirus immunisation in Australia. This has significant resource planning implications for units based on short stay models of care.

Identification of strains of RotaTeq rotavirus vaccine in infants with gastroenteritis following routine vaccination.

BACKGROUND: RotaTeq vaccine was introduced into the Australian National Immunisation Program in 2007. This study identified and characterised rotavirus strains excreted by infants who presented with symptoms of gastroenteritis following recent RotaTeq vaccination. METHODS: Fecal samples (N = 61) from children who developed gastroenteritis following recent RotaTeq vaccination were forwarded to the Australian Rotavirus Surveillance Program (ARSP). RotaTeq-positive samples were genotyped and regions of the VP3, VP4, VP6, and VP7 genes were sequenced. Also, 460 rotavirus-positive ARSP routine surveillance samples were analyzed by dot-blot Northern hybridization to detect RotaTeq vaccine-derived strains circulating in the community. RESULTS: Thirteen of the 61 samples collected from infants developing gastroenteritis after RotaTeq vaccination contained vaccine-derived (vd) rotavirus strains. Of these, 4 contained a vdG1P[8] strain derived by reassortment between the G1P[5] and G6P[8] parental vaccine strains. Northern hybridization analysis of 460 surveillance samples identified 3 samples that contained RotaTeq vaccine-derived strains, including 2 vdG1P[8] reassortant vaccine strains. CONCLUSIONS: During replication and excretion of RotaTeq vaccine, reassortment of parental strains can occur. Shedding of RotaTeq vaccine strains in 7 of 13 infants was associated with underlying medical conditions that may have altered their immune function. The benefits of vaccination outweigh any small risk of vaccine-associated gastroenteritis.

Shoulder injury following COVID-19 vaccine administration: a case series and proposed diagnostic algorithm.

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.

Recurrent 6th nerve palsy in a child following different live attenuated vaccines: case report.

BACKGROUND: Recurrent benign 6th nerve palsy in the paediatric age group is uncommon, but has been described following viral and bacterial infections. It has also been temporally associated with immunization, but has not been previously described following two different live attenuated vaccines. CASE PRESENTATION: A case is presented of a 12 month old Caucasian boy with recurrent benign 6th nerve palsy following measles-mumps-rubella and varicella vaccines, given on separate occasions with complete recovery following each episode. No alternate underlying etiology was identified despite extensive investigations and review. CONCLUSIONS: The majority of benign 6th nerve palsies do not have a sinister cause and have an excellent prognosis, with recovery expected in most cases. The exact pathophysiology is unknown, although hypotheses including autoimmune mechanisms and direct viral invasion could explain the pathophysiology behind immunization related nerve palsies. It is important to rule out other aetiologies with thorough history, physical examination and investigations. There is limited information in the literature regarding the safety of a repeat dose of a live vaccine in this setting. Future immunizations should be considered on a case-by-case basis.