Serosurvey for Japanese encephalitis virus antibodies following an outbreak in an immunologically naïve population, Victoria, 2022: a cross-sectional study.

OBJECTIVES: To investigate the distribution and prevalence of Japanese encephalitis virus (JEV) antibody (as evidence of past infection) in northern Victoria following the 2022 Japanese encephalitis outbreak, seeking to identify groups of people at particular risk of infection; to investigate the distribution and prevalence of antibodies to two related flaviviruses, Murray Valley encephalitis virus (MVEV) and West Nile virus Kunjin subtype (KUNV). STUDY DESIGN: Cross-sectional serosurvey (part of a national JEV serosurveillance program). SETTING: Three northern Victorian local public health units (Ovens Murray, Goulburn Valley, Loddon Mallee), 8 August - 1 December 2022. PARTICIPANTS: People opportunistically recruited at pathology collection centres and by targeted recruitment through community outreach and advertisements. People vaccinated against or who had been diagnosed with Japanese encephalitis were ineligible for participation, as were those born in countries where JEV is endemic. MAIN OUTCOME MEASURES: Seroprevalence of JEV IgG antibody, overall and by selected factors of interest (occupations, water body exposure, recreational activities and locations, exposure to animals, protective measures). RESULTS: 813 participants were recruited (median age, 59 years [interquartile range, 42-69 years]; 496 female [61%]); 27 were JEV IgG-seropositive (3.3%; 95% confidence interval [CI], 2.2-4.8%) (median age, 73 years [interquartile range, 63-78 years]; 13 female [48%]); none were IgM-seropositive. JEV IgG-seropositive participants were identified at all recruitment locations, including those without identified cases of Japanese encephalitis. The only risk factors associated with JEV IgG-seropositivity were age (per year: prevalence odds ratio [POR], 1.07; 95% CI, 1.03-1.10) and exposure to feral pigs (POR, 21; 95% CI, 1.7-190). The seroprevalence of antibody to MVEV was 3.0% (95% CI, 1.9-4.5%; 23 of 760 participants), and of KUNV antibody 3.3% (95% CI, 2.1-4.8%; 25 of 761). CONCLUSIONS: People living in northern Victoria are vulnerable to future JEV infection, but few risk factors are consistently associated with infection. Additional prevention strategies, including expanding vaccine eligibility, may be required to protect people in this region from Japanese encephalitis.

The seroprevalence of antibodies to Japanese encephalitis virus in five New South Wales towns at high risk of infection, 2022: a cross-sectional serosurvey.

OBJECTIVES: To determine the proportion of people in New South Wales towns at high risk of Japanese encephalitis virus (JEV) infections during the 2022 outbreak; to identify risk factors for JEV infection. STUDY DESIGN: Cross-sectional serosurvey study of the seroprevalence of JEV-specific antibodies in NSW. SETTING, PARTICIPANTS: Convenience sample of people (all ages) from five regional NSW towns deemed to be at high risk of JEV infections after first outbreak of Japanese encephalitis in southeastern Australia in early 2022 (Balranald, Corowa, Dubbo, Griffith, Temora), 21 June - 22 July 2022. MAIN OUTCOME MEASURES: Proportion of people seropositive for JEV total antibody, assayed by defined epitope-blocking enzyme-linked immunosorbent assay; prevalence odds ratios for exposure risk factors and protective behaviours. RESULTS: Eighty of 917 eligible participants (559 girls or women, 61%; 42 Aboriginal and Torres Strait Islander people, 4.6%; median age, 52 years [IQR, 37-62 years]) were seropositive for JEV-specific total antibody (8.7%); the median age of seropositive people was 61 years (IQR, 48-70 years). The seropositivity proportion was largest for people aged 65 years or more (30 of 192; weighted proportion, 13.7%) and larger for male than female participants (30 of 358, 10.6% v 50 of 559, 7.5%). Five of 42 samples from Aboriginal and Torres Strait Islander participants were seropositive (12%). We found mixed associations with a range of potential risk factors. CONCLUSION: We found evidence for a substantial number of JEV infections in five regional NSW towns during a single arbovirus season in 2022. Public health responses, including effective surveillance, vaccination against JEV, and mosquito management, are critical for controlling outbreaks. Promoting behaviours that reduce exposure to mosquitoes is a core component of prevention, particularly when the vaccine supply is limited.

The development and evaluation of a vaccination pathway for children with intellectual and developmental disability and needle fear.

This qualitative study describes the development and evaluation of a clinical pathway to facilitate the implementation of catch-up vaccinations for children with significant needle fear, particularly in children with developmental disabilities. The Specialist Immunization Team, based at a tertiary level teaching children's hospital, participated in process mapping activities using Motivational Interviewing (MI) techniques and reflective discussions. Team members developed a clinical pathway by incorporating parental feedback from semistructured interviews and clinical expertise from within the team, facilitated by colleagues from the Child Development Unit. A process map was developed that included process strengths and touch points with an action plan that was discussed and agreed upon. A repeat process mapping activity was conducted 16 months later. Reports from parental feedback included: positive, efficient, and successful experiences of having their child undergo catch-up vaccinations. The experience empowered families for further procedures. Team members reported improvements in triaging appropriate children for the pathway, and an increase in confidence to interact and manage behaviors of children with significant anxiety and challenging behaviors. They also reported an increase in successful vaccinations with improved clinical judgment of facilitating the sedation pathway. This study demonstrates that using group facilitation using motivational interviewing in reflective discussions and process mapping utilizing parent and staff feedback in service improvement activities results in efficient and successful service delivery with improved patient outcomes.

Adverse events following immunisation: Prospective cohort study evaluating Australian children presenting to specialist immunisation clinics.

OBJECTIVE: Prior experience of an adverse event following immunisation is a known barrier to vaccination. Limited Australian data evaluating adverse event recurrence among children exists to inform clinical decisions. We aimed to assess adverse event following immunisation recurrence among children with prior adverse events and to evaluate if family history increased adverse event risk. METHODS: A prospective cohort study was conducted from March 3rd until August 18th, 2023. Children ≤ 16 years with prior adverse events following immunisation in themselves or family were recruited from specialist immunisation clinics at two quaternary paediatric hospitals. Adverse event outcomes were collected via surveys administered at presentation, three, and eight days post vaccination, and analysed by key characteristics and potential risk factors. RESULTS: Forty three of forty nine (43/49, 87.8 %) children enrolled received further vaccines. Of those who completed the follow up surveys, 50.0 % (16/32) reported an adverse event. Recurrence of prior adverse events occurred for 23.3 % (10/43, 95 % CI: 11.8 % - 38.6 %) of the cohort. Two of twelve (2/12, 16.7 %) participants with prior serious adverse events who received further vaccines reported a serious adverse event recurrence. No post review serious adverse events were observed in children with prior non serious adverse events. Neurological conditions were a risk factor for prior (neurological condition 3/3 versus no neurological condition 2/40, p < 0.001) and post review (neurological condition 2/3 versus no neurological condition 0/28, p = 0.006) post vaccination seizures. Family history had no relationship to post review adverse events (family history 5/8 versus no family history 11/23, p = 0.685). CONCLUSION: Revaccination is safe for the majority of children with a personal or family history of adverse event following immunisation.

Seroprevalence of Japanese encephalitis virus-specific antibodies in Australia following novel epidemic spread: protocol for a national cross-sectional study.

INTRODUCTION: Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes encephalitis and other morbidity in Southeast Asia. Since February 2022, geographically dispersed JEV human, animal and vector detections occurred on the Australian mainland for the first time. This study will determine the prevalence of JEV-specific antibodies in human blood with a focus on populations at high risk of JEV exposure and determine risk factors associated with JEV seropositivity by location, age, occupation and other factors. METHOD: Samples are collected using two approaches: from routine blood donors (4153 samples), and active collections targeting high-risk populations (convenience sampling). Consent-based sampling for the latter includes a participant questionnaire on demographic, vaccination and exposure data. Samples are tested for JEV-specific total antibody using a defined epitope-blocking ELISA, and total antibody to Australian endemic flaviviruses Murray Valley encephalitis and Kunjin viruses. ANALYSIS: Two analytic approaches will occur: descriptive estimates of seroprevalence and multivariable logistic regression using Bayesian hierarchical models. Descriptive analyses will include unadjusted analysis of raw data with exclusions for JEV-endemic country of birth, travel to JEV-endemic countries, prior JEV-vaccination, and sex-standardised and age-standardised analyses. Multivariable logistic regression will determine which risk factors are associated with JEV seropositivity likely due to recent transmission within Australia and the relative contribution of each factor when accounting for effects within the model. ETHICS: National Mutual Acceptance ethical approval was obtained from the Sydney Children's Hospitals Network Human Research Ethics Committee (HREC). Local approvals were sought in each jurisdiction. Ethical approval was also obtained from the Australian Red Cross Lifeblood HREC. DISSEMINATION: Findings will be communicated to participants and their communities, and human and animal health stakeholders and policy-makers iteratively and after final analyses. Understanding human infection rates will inform procurement and targeted allocation of limited JEV vaccine, and public health strategies and communication campaigns, to at-risk populations.

Superior immunogenicity of mRNA over adenoviral vectored COVID-19 vaccines reflects B cell dynamics independent of anti-vector immunity: Implications for future pandemic vaccines.

Both vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. The aim of this study was to validate whether immunogenicity differs for adenoviral vectored (AdV) versus mRNA vaccines against SARS-CoV-2, and to investigate how anti-vector immunity and B cell dynamics modulate immunogenicity. We enrolled SARS-CoV-2 infection-naïve health care workers who had received two doses of either AdV AZD1222 (n = 184) or mRNA BNT162b2 vaccine (n = 274) between April and October 2021. Blood was collected at least once, 10-48 days after vaccine dose 2 for antibody and B cell analyses. Median ages were 42 and 39 years, for AdV and mRNA vaccinees, respectively. Surrogate virus neutralization test (sVNT) and spike binding antibody titres were a median of 4.2 and 2.2 times lower, respectively, for AdV compared to mRNA vaccinees (p < 0.001). Median percentages of memory B cells that recognized fluorescent-tagged spike and RBD were 2.9 and 8.3 times lower, respectively for AdV compared to mRNA vaccinees. Titres of IgG reactive with human adenovirus type 5 hexon protein rose a median of 2.2-fold after AdV vaccination but were not correlated with anti-spike antibody titres. Together the results show that mRNA induced substantially more sVNT antibody than AdV vaccine, which reflected greater B cell expansion and targeting of the RBD rather than an attenuating effect of anti-vector antibodies. ClinicalTrials.gov Identifier: NCT05110911.

A case report of disseminated Streptococcus pneumoniae infection complicated by infective endocarditis, septic arthritis and epidural abscess in an immunocompetent patient.

Streptococcus pneumoniae is a highly virulent, vaccine-preventable pathogen which can cause disease on a spectrum from benign to fatal. Apart from pneumonia, it commonly causes septicaemia and meningitis. This case report describes an unusual range of complications in a 53-year-old Caucasian female presenting to a regional hospital, without any risk known factors for severe disease (such as extremes of age, immunodeficiency or co-morbidities). Progressing from an episode of otitis media, her condition rapidly progressed to mastoid sinusitis, septic arthritis, infective endocarditis, epidural abscesses and multiple subcutaneous abscesses. Following quick identification of S. pneumoniae from a positive blood culture, the patient was treated with high-dose benzylpenicillin and ceftriaxone and aggressive source control by surgery, enabling a good clinical recovery.

Successful Use of Cefiderocol to Treat a Multidrug-resistant Stenotrophomonas maltophilia Ventilator-associated Pneumonia in an Extremely Preterm Neonate.

BACKGROUND: Ventilator-associated pneumonia (VAP) caries a morbidity and mortality risk in the preterm neonate, particularly in the context of rising global antimicrobial resistance driving infections due to multidrug-resistant Gram-negative bacteria. Cefiderocol, a siderophilic cephalosporin, has broad Gram-negative antimicrobial activity and central nervous system penetration and is used for the treatment of hospital-acquired pneumonia or VAP in adults. Scarce data exists on its use in neonates. CASE: A female neonate born at 26 + 6 weeks developed VAP at 21 days of life. She was commenced on corticosteroids, vancomycin and ceftazidime but continued to deteriorate. Sputum cultures yielded Stenotrophomonas maltophilia resistant to trimethoprim/sulfamethoxazole, ciprofloxacin and ceftazidime, with potential susceptibility to cefiderocol. Cerebrospinal fluid showed an elevated white cell count. In view of worsening respiratory and hemodynamic status, antibiotic treatment was changed to cefiderocol monotherapy at 30 mg/kg/dose every 8 hours. Within 72 hours of commencing cefiderocol, the neonate was successfully extubated to variable-flow continuous positive airway pressure and showed ongoing clinical improvement. CONCLUSIONS: Cefiderocol was integral for the care of our neonate without any immediate adverse safety consequences. We relied on dosing data from a conference abstract, due to the paucity of evidence on the use of novel antimicrobials. This lack of evidence is particularly concerning given preterm neonates are particularly vulnerable to infections with multidrug-resistant Gram-negative organisms due to their immature immune systems, prolonged hospital stay, repeated interventions and antimicrobial exposure.

Comparative B cell and antibody responses induced by adenoviral vectored and mRNA vaccines against COVID-19.

Both vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. However, adenoviral vectored (AdV) vaccines may be less immunogenic than mRNA vaccines against SARS-CoV-2. We assessed anti-spike and anti-vector immunity among infection-naïve Health Care Workers (HCW) following two doses of AdV (AZD1222) versus mRNA (BNT162b2) vaccine. 183 AdV and 274 mRNA vaccinees enrolled between April and October 2021. Median ages were 42 and 39 years, respectively. Blood was collected at least once, 10-48 days after vaccine dose 2. Surrogate virus neutralization test (sVNT) and spike binding antibody titres were a median of 4.2 and 2.2 times lower, respectively, for AdV compared to mRNA vaccinees (p<0.001). Median percentages of memory B cells that recognized fluorescent-tagged spike and RBD were 2.9 and 8.3 times lower, respectively for AdV compared to mRNA vaccinees. Titres of IgG reactive with human Adenovirus type 5 hexon protein rose a median of 2.2-fold after AdV vaccination but were not correlated with anti-spike antibody titres. Together the results show that mRNA induced substantially more sVNT antibody than AdV vaccine due to greater B cell expansion and targeting of the RBD. Pre-existing AdV vector cross-reactive antibodies were boosted following AdV vaccination but had no detectable effect on immunogenicity.

Clinical and Epidemiologic Profile of Invasive Pneumococcal Disease in Australian Children Following the Relaxation of Nonpharmaceutical Interventions Against SARS-COV-2.

A global resurgence of invasive pneumococcal disease (IPD) has been noted in children. We provide a detailed clinical and epidemiological analysis of IPD in Australian children following relaxation of nonpharmaceutical interventions against coronavirus disease 2019, revealing significant morbidity and mortality-even in vaccinated children without known predisposing risk factors. Almost half of the IPD cases were caused by serotypes not covered by the 13-valent pneumococcal conjugate vaccine.

Tracking the clonal dynamics of SARS-CoV-2-specific T cells in children and adults with mild/asymptomatic COVID-19.

Children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop less severe coronavirus disease 2019 (COVID-19) than adults. The mechanisms for the age-specific differences and the implications for infection-induced immunity are beginning to be uncovered. We show by longitudinal multimodal analysis that SARS-CoV-2 leaves a small footprint in the circulating T cell compartment in children with mild/asymptomatic COVID-19 compared to adult household contacts with the same disease severity who had more evidence of systemic T cell interferon activation, cytotoxicity and exhaustion. Children harbored diverse polyclonal SARS-CoV-2-specific naïve T cells whereas adults harbored clonally expanded SARS-CoV-2-specific memory T cells. A novel population of naïve interferon-activated T cells is expanded in acute COVID-19 and is recruited into the memory compartment during convalescence in adults but not children. This was associated with the development of robust CD4+ memory T cell responses in adults but not children. These data suggest that rapid clearance of SARS-CoV-2 in children may compromise their cellular immunity and ability to resist reinfection.

COVID-19 in New South Wales children during 2021: severity and clinical spectrum.

OBJECTIVES: To describe the severity and clinical spectrum of coronavirus disease 2019 (COVID-19) in children during the 2021 New South Wales outbreak of the Delta variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). DESIGN, SETTING: Prospective cohort study in three metropolitan Sydney local health districts, 1 June - 31 October 2021. PARTICIPANTS: Children under 16 years of age with positive SARS-CoV-2 nucleic acid test results admitted to hospital or managed by the Sydney Children's Hospital Network (SCHN) virtual care team. MAIN OUTCOME MEASURES: Age-specific SARS-CoV-2 infection frequency, overall and separately for SCHN virtual and hospital patients; rates of medical and social reason admissions, intensive care admissions, and paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 per 100 SARS-CoV-2 infections; demographic and clinical factors that influenced likelihood of hospital admission. RESULTS: A total of 17 474 SARS-CoV-2 infections in children under 16 were recorded in NSW, of whom 11 985 (68.6%) received SCHN-coordinated care, including 459 admitted to SCHN hospitals: 165 for medical reasons (1.38 [95% CI, 1.17-1.59] per 100 infections), including 15 admitted to intensive care, and 294 (under 18 years of age) for social reasons (2.45 [95% CI, 2.18-2.73] per 100 infections). In an analysis that included all children admitted to hospital and a random sample of those managed by the virtual team, having another medical condition (adjusted odds ratio [aOR], 7.42; 95% CI, 3.08-19.3) was associated with increased likelihood of medical admission; in univariate analyses, non-asthmatic chronic respiratory disease was associated with greater (OR, 9.21; 95% CI, 1.61-174) and asthma/viral induced wheeze with lower likelihood of admission (OR, 0.38; 95% CI, 0.18-0.78). The likelihood of admission for medical reasons declined from infancy to 5-11 years, but rose again for those aged 12-15 years. Sex and Indigenous status did not influence the likelihood of admission. CONCLUSION: Most SARS-CoV-2 infections (Delta variant) in children were asymptomatic or associated with mild disease. Hospitalisation was relatively infrequent, and most common for infants, adolescents, and children with other medical conditions. More children were hospitalised for social than for medical reasons.

COVID-19 in children. II: Pathogenesis, disease spectrum and management.

The global disruption of the COVID-19 pandemic has impacted the life of every child either directly or indirectly. This review explores the pathophysiology, immune response, clinical presentation and treatment of COVID-19 in children, summarising the most up-to-date data including recent developments regarding variants of concern. The acute infection with SARS-CoV-2 is generally mild in children, whilst the post-infectious manifestations, including paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) and 'long COVID' in children, are more complex. Given that most research on COVID-19 has focused on adult cohorts and that clinical manifestations, treatment availability and impacts differ markedly in children, research that specifically examines COVID-19 in children needs to be prioritised.

COVID-19 in children: I. Epidemiology, prevention and indirect impacts.

Children globally have been profoundly impacted by the coronavirus disease 2019 (COVID-19) pandemic. This review explores the direct and indirect public health impacts of COVID-19 on children. We discuss in detail the transmission dynamics, vaccination strategies and, importantly, the 'shadow pandemic', encompassing underappreciated indirect impacts of the pandemic on children. The indirect effects of COVID-19 will have a long-term impact beyond the immediate pandemic period. These include the mental health and wellbeing risks, disruption to family income and attendant stressors including increased family violence, delayed medical attention and the critical issue of prolonged loss of face-to-face learning in a normal school environment. Amplification of existing inequities and creation of new disadvantage are likely additional sequelae, with children from vulnerable families disproportionately affected. We emphasise the responsibility of paediatricians to advocate on behalf of this vulnerable group to ensure the longer-term effects of COVID-19 public health responses on the health and wellbeing of children are fully considered.

Vaccines for COVID-19: Where do we stand in 2021?

As of July 2021, over 3 billion doses of a COVID-19 vaccines have been administered globally, and there are now 19 COVID-19 vaccines approved for use in at least one country. Several of these have been shown to be highly effective both in clinical trials and real-world observational studies, some of which have included special populations of interest. A small number of countries have approved a COVID-19 vaccine for use in adolescents or children. These are laudable achievements, but the global vaccination effort has been challenged by inequitable distribution of vaccines predominantly to high income countries, with only 0.9% of people in low-income countries having received at least one dose of a COVID-19 vaccine. Addressing this inequity is of critical importance and will result in better control of SARS-CoV-2 globally. Other challenges include: the reduced protection from COVID-19 vaccines against some strains of SARS-CoV-2, necessitating the development of variant specific vaccines; and uncertainties around the duration of protection from vaccine-induced immunity.

Lessons learnt during the COVID-19 pandemic: Why Australian schools should be prioritised to stay open.

In 2020, school and early childhood educational centre (ECEC) closures affected over 1.5 billion school-aged children globally as part of the COVID-19 pandemic response. Attendance at school and access to ECEC is critical to a child's learning, well-being and health. School closures increase inequities by disproportionately affecting vulnerable children. Here, we summarise the role of children and adolescents in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission and that of schools and ECECs in community transmission and describe the Australian experience. In Australia, most SARS-CoV-2 cases in schools were solitary (77% in NSW and 67% in Victoria); of those that did progress to an outbreak, >90% involved fewer than 10 cases. Australian and global experience has demonstrated that SARS-CoV-2 is predominantly introduced into schools and ECECs during periods of heightened community transmission. Implementation of public health mitigation strategies, including effective testing, tracing and isolation of contacts, means schools and ECECs can be safe, not drivers of transmission. Schools and ECEC are essential services and so they should be prioritised to stay open for face-to-face learning. This is particularly critical as we continue to manage the next phase of the COVID-19 pandemic.