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Background: Early formula supplementation (EFS, formula on birthdate or day after) is associated with maternal obesity and reduced breastfeeding, but the effect of prenatal breastfeeding intention on these relationships is understudied. Objectives: We evaluated how EFS affected breastfeeding outcomes after controlling for obesity, sociodemographic and health factors. Methods: Multivariable regression modeling, stratified by prenatal breastfeeding intention. Conclusions: Our findings suggest that EFS may be less disruptive to breastfeeding in mothers with strong intention to meet breastfeeding recommendations, regardless of maternal BMI.

Summary: As SARS-CoV-2 becomes endemic, it is critical to understand immunity following early-life infection. We evaluated humoral responses to SARS-CoV-2 in 23 infants/young children. Antibody responses to SARS-CoV-2 spike antigens peaked approximately 30 days after infection and were maintained up to 500 days with little apparent decay. While the magnitude of humoral responses was similar to an adult cohort recovered from mild/moderate COVID-19, both binding and neutralization titers to WT SARS-CoV-2 were more durable in infants/young children, with spike and RBD IgG antibody half-life nearly 4X as long as in adults. IgG subtype analysis revealed that while IgG1 formed the majority of the response in both groups, IgG3 was more common in adults and IgG2 in infants/young children. These findings raise important questions regarding differential regulation of humoral immunity in infants/young children and adults and could have broad implications for the timing of vaccination and booster strategies in this age group.

Human parechovirus (HPeV) is a leading cause of Central Nervous System (CNS) infection in infancy. Despite this, little is known regarding the long-term neuropsychological impacts from HPeV infection. The aim of the present study was to explore the long-term neuropsychological impacts eight-year post-HPeV infection contracted during infancy. This study also aimed to investigate the differential impacts of HPeV itself compared to the effects of secondary meningitis ( n  = 23) or encephalitis ( n  = 3) associated with HPeV infection. Thirty-nine HPeV children participated in the study. Children completed performance-based measures of neuropsychological and language functioning (the Wechsler Abbreviated Scale of Intelligence, the Clinical Evaluation of Language Fundamentals - Fourth Edition, and the Test of Everyday Attention for Children). Parents completed questionnaire-based measures of emotional, behavioral, and pragmatic language functioning (the Behaviour Rating Inventory of Executive Functioning, the Child Behavior Checklist, and the Social Communication Questionnaire). Results revealed that, overall, children with HPeV were significantly more impaired on measures of selective, sustained, and divided attention compared to normative test populations. The current study incidentally found at least double the prevalence of Attention-Deficit/Hyperactivity Disorder (ADHD) in the HPeV sample than what is typical in the normal population, suggesting that HPeV infection during infancy may be a risk factor for the later development of ADHD. Additionally, the presence of secondary meningitis or encephalitis did not relate to poorer neuropsychological outcomes in the current sample. The findings of this study have important implications regarding clinical management for children following HPeV infection in infancy.

Background: Pediatric long COVID remains incompletely understood with scant Australian data available. We aimed to assess the impacts of the 2021 Delta variant of SARS-CoV-2 outbreak on symptoms and functioning 12 weeks post-acute infection in a cohort of children and adolescents., Methods: The parents/carers of 11,864 patients with PCR-confirmed SARS-CoV-2 were invited, via email or text message, to complete an online survey assessing symptoms and functional impairment., Findings: 1731 (17.6%) responded to the survey. 203 (11.7%) reported continued symptoms and/or functional impairment which were flagged for clinical review, all others reported recovery. Of the 169 subsequently clinically reviewed, 63 had already recovered (37.3%) and 17 had exacerbation of pre-existing condition(s) (10.1%); 63 (37.3%) were diagnosed with a Post COVID Condition (PCC). Of these, 21 (12.4%) were considered to have features compatible with the United Kingdom consensus cases definition for Long COVID., Interpretation: During an outbreak of SARS-CoV-2 an online questionnaire with subsequent clinical review revealed self-reported non-recovery at 12 weeks in a minority of cases, with a spectrum of features. Long COVID comprised only a subset of cases with self-reported non-recovery, and is infrequent in children and adolescents, but still comprises a likely significant burden that warrants attention., Impact: Our study provides the only comprehensive estimate of the frequency and spectrum of post-COVID conditions in children from Australia. The high frequency of self-reported recovery, and low frequency of Long COVID compatible illness adds to the literature from other settings. Risk factors for post-COVID conditions in children are identified and include: age >11 year, and previous medical co-morbidity., (© 2024. The Author(s).)

Although a more efficient adaptive humoral immune response has been proposed to underlie the usually favorable outcome of pediatric COVID-19, the breadth of viral and vaccine cross-reactivity toward the ever-mutating Spike protein among variants of concern (VOCs) has not yet been compared between children and adults. We assessed antibodies to conformational Spike in COVID-19-naïve children and adults vaccinated by BNT162b2 and ChAdOx1, and naturally infected with SARS-CoV-2 Early Clade, Delta, and Omicron. Sera were analyzed against Spike including naturally occurring VOCs Alpha, Beta, Gamma, Delta, and Omicron BA.1, BA.2, BA.5, BQ.1.1, BA2.75.2, and XBB.1, and variants of interest Epsilon, Kappa, Eta, D.2, and artificial mutant Spikes. There was no notable difference between breadth and longevity of antibody against VOCs in children and adults. Vaccinated individuals displayed similar immunoreactivity profiles across variants compared with naturally infected individuals. Delta-infected patients had an enhanced cross-reactivity toward Delta and earlier VOCs compared to patients infected by Early Clade SARS-CoV-2. Although Omicron BA.1, BA.2, BA.5, BQ.1.1, BA2.75.2, and XBB.1 antibody titers were generated after Omicron infection, cross-reactive binding against Omicron subvariants was reduced across all infection, immunization, and age groups. Some mutations, such as 498R and 501Y, epistatically combined to enhance cross-reactive binding, but could not fully compensate for antibody-evasive mutations within the Omicron subvariants tested. Our results reveal important molecular features central to the generation of high antibody titers and broad immunoreactivity that should be considered in future vaccine design and global serosurveillance in the context of limited vaccine boosters available to the pediatric population., (© 2023. The Author(s).)

The nests of ground-nesting birds rely heavily on camouflage for their survival, and predation risk, often linked to ecological changes from human activity, is a major source of mortality. Numerous ground-nesting bird populations are in decline, so understanding the effects of camouflage on their nesting behavior is relevant to their conservation concerns. Habitat three-dimensional (3D) geometry, together with predator visual abilities, viewing distance, and viewing angle, determine whether a nest is either visible, occluded, or too far away to detect. While this link is intuitive, few studies have investigated how fine-scale geometry is likely to help defend nests from different predator guilds. We quantified nest visibility based on 3D occlusion, camouflage, and predator visual modeling in northern lapwings, Vanellus vanellus , on different land management regimes. Lapwings selected local backgrounds that had a higher 3D complexity at a spatial scale greater than their entire clutches compared to local control sites. Importantly, our findings show that habitat geometry-rather than predator visual acuity-restricts nest visibility for terrestrial predators and that their field habitats, perceived by humans as open, are functionally closed with respect to a terrestrial predator searching for nests on the ground. Taken together with lapwings' careful nest site selection, our findings highlight the importance of considering habitat geometry for understanding the evolutionary ecology and management of conservation sites for ground-nesting birds., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Acute respiratory infections (ARI), especially lower respiratory infections (LRI), are a leading cause of childhood morbidity and mortality globally. Non-pharmaceutical interventions (NPI) employed during the COVID-19 pandemic have impacted on the epidemiology and burden of paediatric ARI, although accurately describing the full nature of the impact is challenging. For most ARI pathogens, a reduction was observed in the early phase of the pandemic, correlating with the most stringent NPI. In later phases of the pandemic resurgence of disease was observed as NPI eased. This pattern was most striking for seasonal viruses, such as influenza and respiratory syncytial virus. The impact on ARI-associated bacterial disease varied; marked reductions in invasive Streptococcus pneumoniae and Streptococcus pyogenes were observed, followed by a resurgence that correlated with increases in respiratory viral infections. For Corynebacterium diphtheriae,Bordetella pertussis, andMycoplasma pneumoniae, a sustained reduction of disease was observed well into 2022 in most regions. Proposedmechanisms for the varied epidemiological disruption amongst ARI pathogens includedifferential effects of NPI on specific pathogens, population-level immunological effects, and ecological and genetic pathogen adaptations. Additionally, important indirect effects of pandemic restrictions on paediatric respiratory infections have been identified. These occurred as a result of disruptions to routine health services, reductions in vaccination coverage, and disruptions to respiratory infection research and surveillance activities. Impacts have been disproportionately borne by those in low resource settings. We discuss opportunities to leverage pandemic learnings to support improved understanding of the epidemiology of paediatric respiratory infections to inform future prevention and health system strengthening. Educational Aims. The reader will gain an improved understanding of., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Emerging infectious disease threats require rapid response tools to inform diagnostics, treatment, and outbreak control. RNA-based metagenomics offers this; however, most approaches are time-consuming and laborious. Here, we present a simple and fast protocol, the RAPID prep assay, with the aim of providing a cause-agnostic laboratory diagnosis of infection within 24 h of sample collection by sequencing ribosomal RNA-depleted total RNA. The method is based on the synthesis and amplification of double-stranded cDNA followed by short-read sequencing, with minimal handling and clean-up steps to improve processing time. The approach was optimized and applied to a range of clinical respiratory samples to demonstrate diagnostic and quantitative performance. Our results showed robust depletion of both human and microbial rRNA, and library amplification across different sample types, qualities, and extraction kits using a single workflow without input nucleic-acid quantification or quality assessment. Furthermore, we demonstrated the genomic yield of both known and undiagnosed pathogens with complete genomes recovered in most cases to inform molecular epidemiological investigations and vaccine design. The RAPID prep assay is a simple and effective tool, and representative of an important shift toward the integration of modern genomic techniques with infectious disease investigations.

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., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Enteroviruses (EV) commonly cause hand, foot and mouth disease (HFMD), and can also cause potentially fatal neurological and systemic complications. In our laboratory, sequencing 5' untranslated region (UTR) of the viral genome has been the routine method of genotyping EVs. During a recent localised outbreak of aseptic meningitis, sequencing the 5'UTR identified the causative virus as EV-A71, which did not fit with the clinical syndrome or illness severity. When genotyped using a different target gene, VP1, the result was different. This led us to evaluate the accuracy of the two different target genome regions and compare them against whole genome sequencing (WGS). We aimed to optimise the algorithm for detection and characterisation of EVs in the diagnostic laboratory. We hypothesised that VP1 and WGS genotyping would provide different results than 5'UTR in a subset of samples. Clinical samples from around New South Wales which were positive for EV by commercial polymerase chain reaction (PCR) assays were genotyped by targeting three different viral genome regions: the 5'UTR, VP1 and WGS. Sequencing was performed by Sanger and next generation sequencing. The subtyping results were compared. Of the 74/118 (63%) samples that were successfully typed using both the 5'UTR and the VP1 method, the EV typing result was identical for 46/74 (62%) samples compared to WGS as the gold standard. The same EV group but different EV types were found in 22/74 (30%) samples, and 6/74 (8%) samples belonged to different EV groups depending on typing method used. Genotyping with WGS and VP1 is more accurate than 5'UTR. Genotyping by the 5'UTR method is very sensitive, but less specific., (Copyright © 2022 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

The incidence of enterovirus D68 (EV-D68) in New South Wales, Australia, is unknown. As part of a state-wide surveillance program, enterovirus positive diagnostic specimens were assessed from patients presenting to hospitals with respiratory and meningitis syndromes from August 2018 to November 2019. Diagnostic enterovirus positive samples were collected from 339 patients and re-extracted followed by targeted PCR across the whole EV-D68 genome (7.4 kb). Obtained amplicons (n=208) were sequenced using Illumina sequencing technology and the phylogenetic relationships analysed relative to EV-D68 Fermon strain. We identified EV-D68 in 31 patients, both children (n=27) and adults (n=4). Phylogenetically, the majority (n=30) were from subclade B3, the same as that causing outbreaks of EV-D68 across the USA and Europe during 2018. These data strengthen the importance of having an active enterovirus surveillance network., (Copyright © 2022 Royal College of Pathologists of Australasia. All rights reserved.)

Encephalitis is most often caused by a variety of infectious agents identified through diagnostic tests utilizing cerebrospinal fluid. We investigated the clinical characteristics and potential aetiological agents of unexplained encephalitis through metagenomic sequencing of residual clinical samples from multiple tissue types and independent clinical review. Forty-three specimens were collected from 18 encephalitis cases with no cause identified by the Australian Childhood Encephalitis study. Samples were subjected to total RNA sequencing ('metatranscriptomics') to determine the presence and abundance of potential pathogens, and to describe the possible aetiologies of unexplained encephalitis. Using this protocol, we identified five RNA and two DNA viruses associated with human infection from both non-sterile and sterile sites, which were confirmed by PCR. These comprised two human rhinoviruses, two human seasonal coronaviruses, two polyomaviruses and one picobirnavirus. Human rhinovirus and seasonal coronaviruses may be responsible for five of the encephalitis cases. Immune-mediated encephalitis was considered likely in six cases and metatranscriptomics did not identify a possible pathogen in these cases. The aetiology remained unknown in nine cases. Our study emphasizes the importance of respiratory viruses in the aetiology of unexplained child encephalitis and suggests that non-central-nervous-system sampling in encephalitis clinical guidelines and protocols could improve the diagnostic yield.

This study aimed to quantify the amount of pharmaceutical waste produced in New Zealand, and determine the composition of pharmaceutical waste from community pharmacies in Auckland, New Zealand. Pharmaceutical waste collected in New Zealand is increasing, peaking at 542 tonne in 2019. Pharmaceutical waste collected from hospitals and pharmacies in Auckland increased by more than fourfold from 2016 to 2020. An audit of the types of pharmaceutical waste collected from community pharmacies revealed that the most common classes of drugs identified in this waste stream belonged to the nervous system, cardiovascular system and alimentary tract, and metabolism. Following examination of the contents of 12 pharmaceutical waste bins, 475 different pharmaceutical products were identified, highlighting the breadth of drugs in this waste stream. A range of dosage forms and hence materials were identified, which could present challenges for future waste treatment approaches. Hazardous drugs were identified including cytotoxic compounds, which should go into a separate waste stream for incineration. There is a need for similar data to be collected from multiple sites to fully appreciate the magnitude and composition of pharmaceutical waste. This will allow for the suitability of current practices for managing this hazardous waste stream to be evaluated., Competing Interests: Conflict of interestNone., (© The Author(s) 2022.)