Genomic characterization of respiratory syncytial virus genotypes circulating in the paediatric population of Sydney, NSW, Australia.

Respiratory syncytial virus (RSV), or human orthopneumovirus, is a major cause of acute lower respiratory infection (ALRI), particularly in young children, causing significant morbidity and mortality. We used pathogen genomics to characterize the population structure and genetic signatures of RSV isolates circulating in children in New South Wales between 2016 and 2018 and to understand the evolutionary dynamics of these strains in the context of publicly available RSV genomes from the region and globally. Whole-genome phylogenetic analysis demonstrated the co-circulation of a few major RSV clades in the paediatric population from Sydney. The whole-genome-based genotypes A23 (RSV-A ON1-like genotype) and B6 (RSV-B BA9-like genotype) were the predominant RSV-A and RSV-B genotypes circulating during the study period, respectively. These genotypes were characterized with high levels of diversity of predicted N- and O-linked glycosylation patterns in both the G and F glycoproteins. Interestingly, a novel 72-nucleotide triplication in the sequence that corresponds to the C-terminal region of the G gene was identified in four of the A23 genotype sequenced in this study. Consistently, the population dynamics analysis demonstrated a continuous increase in the effective population size of A23 and B6 genotypes globally. Further investigations including functional mapping of mutations and identifying the impact of sequence changes on virus fitness are highly required. This study highlights the potential impact of an integrated approach that uses WG-based phylogeny and studying selective pressure events in understanding the emergence and dissemination of RSV genotypes.

Emerging Genotype IV Japanese Encephalitis Virus Outbreak in New South Wales, Australia.

The detection of a new and unexpected Japanese encephalitis virus (JEV) outbreak in March 2022 in Australia, where JEV is not endemic, demanded the rapid development of a robust diagnostic framework to facilitate the testing of suspected patients across the state of New South Wales (NSW). This nascent but comprehensive JEV diagnostic service encompassed serological, molecular and metagenomics testing within a centralised reference laboratory. Over the first three months of the outbreak (4 March 2022 to 31 May 2022), 1,061 prospective samples were received from 878 NSW residents for JEV testing. Twelve confirmed cases of Japanese encephalitis (JE) were identified, including ten cases diagnosed by serology alone, one case by metagenomic next generation sequencing and real-time polymerase chain reaction (RT-PCR) of brain tissue and serology, and one case by RT-PCR of cerebrospinal fluid, providing an incidence of JE over this period of 0.15/100,000 persons in NSW. As encephalitis manifests in <1% of cases of JEV infection, the population-wide prevalence of JEV infection is likely to be substantially higher. Close collaboration with referring laboratories and clinicians was pivotal to establishing successful JEV case ascertainment for this new outbreak. Sustained and coordinated animal, human and environmental surveillance within a OneHealth framework is critical to monitor the evolution of the current outbreak, understand its origins and optimise preparedness for future JEV and arbovirus outbreaks.

Respiratory syncytial virus in the Western Pacific Region: a systematic review and meta-analysis.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of viral pneumonia and bronchiolitis, especially in younger children. The burden of RSV infection in adults, particularly in the older age group, is increasingly recognised. However, RSV disease burden and molecular epidemiology in the World Health Organization (WHO) Western Pacific Region (WPR) has not been reviewed systematically. The aim of this systematic review is to investigate the epidemiological aspects of RSV (incidence, prevalence, seasonality and hospitalisation status) and the associated molecular data in the WPRO countries. METHODS: A systematic search was conducted in international literature databases (MEDLINE, EMBASE, Scopus and Web of Science) to identify RSV-related publications from January 2000 to October 2017 in the WPR countries. RESULTS: A total of 196 studies from 15 WPR countries were included. The positivity rate for RSV among respiratory tract infection patients was 16.73% (95% confidence interval (CI) = 15.12%-18.4%). The RSV-positive cases were mostly found in hospitalised compared with outpatients (18.28% vs 11.54%, P < 0.001), and children compared with adults (20.72% vs 1.87%, P < 0.001). The seasonality of RSV in the WPR countries follows the latitude, with the peak of RSV season occurring in the winter in temperate countries, and during the rainy season in tropical countries. The molecular epidemiology pattern of RSV in WPR countries was similar to the global pattern, with NA1 (RSV A) and BA (RSV B) being the predominant genotypes. CONCLUSIONS: The available data on RSV are limited in several countries within the WPR, with most data focusing on children and hospitalised patients. Further studies and surveillance, incorporating laboratory testing, are needed to determine the burden of RSV infection in the WPR countries.

Opportunities and challenges to improving antibiotic prescribing practices through a One Health approach: results of a comparative survey of doctors, dentists and veterinarians in Australia.

OBJECTIVES: To explore and compare the knowledge, attitudes and experiences of doctors, dentists and veterinarians (as prescribers) in relation to antibiotic use and antibiotic resistance (AbR), and to consider the implications of these for policy-making that support a One Health approach. DESIGN: A cross-sectional survey conducted online. SETTING: Doctors, dentists and veterinarians practising in primary, secondary or tertiary care in Australia. PARTICIPANTS: 547 doctors, 380 dentists and 403 veterinarians completed the survey. MAIN OUTCOME MEASURES: Prescribers' knowledge, attitudes and perceptions of AbR, the extent to which a range of factors are perceived as barriers to appropriate prescribing practices, and perceived helpfulness of potential strategies to improve antibiotic prescribing in practice. RESULTS: There was substantial agreement across prescriber groups that action on AbR is required by multiple sectors and stakeholders. However, prescribers externalised responsibility to some extent by seeing the roles of others as more important than their own in relation to AbR. There were common and context-specific barriers to optimal prescribing across the prescriber groups. Prescriber groups generally perceived restrictive policies as unhelpful to supporting appropriate prescribing in their practice. CONCLUSIONS: The results have implications for implementing a One Health approach that involves doctors, dentists and veterinarians as key players to tackling the crisis of AbR. The findings are that (1) prescribers understand and are likely receptive to a One Health policy approach to AbR, (2) policy development should be sensitive to barriers that are specific to individual prescriber groups and (3) the development and introduction of interventions that might be perceived as reducing prescriber autonomy will need to be carefully designed and implemented.

Molecular epidemiology of respiratory syncytial virus.

Respiratory syncytial virus (RSV) is a major cause of viral acute respiratory tract infections in young children. The virus is characterised by distinct seasonality that is dependent upon the latitude and its ability to cause reinfection. Respiratory syncytial virus demonstrates a complex molecular epidemiology pattern as multiple strains and/or genotypes cocirculate during a single epidemic. Previous studies have investigated the relationship between RSV genetic diversity, reinfection, and clinical features. Here, we review the evidence behind this relationship together with the impact that the advancement of whole genome sequencing will have upon our understanding and the need for reconsidering the classification of RSV genotypes.

A model of auto immune response.

BACKGROUND: In this work, we develop a theoretical model of an auto immune response. This is based on modifications of standard second messenger trigger models using both signalling pathways and diffusion and a macro level dynamic systems approximation to the response of a triggering agent such as a virus, bacteria or environmental toxin. RESULTS: We show that there, in general, will be self damage effects whenever the triggering agent's effect on the host can be separated into two distinct classes of cell populations. In each population, the trigger acts differently and this behavior is mediated by the nonlinear interactions between two signalling agents. CONCLUSION: If these interactions satisfy certain critical assumptions this will lead to collateral damage. If the initial triggering agent's action involves any critical host cell population whose loss can lead to serious host health issues, then there is a much increased probability of host death. Our model also shows that if the nonlinear interaction assumptions are satisfied, there is a reasonable expectation of oscillatory behavior in host health; i.e. periods of remission.

A theoretical model of the West Nile Virus survival data.

BACKGROUND: In this work, we develop a theoretical model that explains the survival data in West Nile Virus infection. RESULTS: We build a model based on three cell populations in an infected host; the collateral damage cells, the infected dividing cell, and the infected non-dividing cells. T cell-mediated lysis of each of these populations is dependent on the level of MHC-1 upregulation, which is different in the two infected cell populations, interferon-gamma and free virus levels. CONCLUSIONS: The model allows us to plot a measure of host health versus time for a range of initial viral doses and from that infer the dependence of minimal health versus viral dose. This inferred functional relationship between the minimal host health and viral dose is very similar to the data that has been collected for WNV survival curves under experimental conditions.

Nosocomial Transmission from an Adolescent with Sputum Smear-Negative Pulmonary Tuberculosis.

We describe a case of sputum smear-negative pulmonary tuberculosis in an adolescent boy, where a delay in diagnosis and institution of appropriate infection control measures resulted in transmission of infection to at least 3 and possibly as many as 6 healthcare workers. Lapses in the use of standard precautions for infection control were also identified.

Low prevalence of Kingella kingae carriage in children aged 6-48 months in Sydney, Australia.

AIM: A prospective observational study was conducted to estimate the prevalence of oropharyngeal carriage of Kingella kingae in healthy Australian pre-school children. METHODS: Screening for carriage of K. kingae as well as Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus agalactiae, Staphylococcus aureus, Haemophilus influenzae, and K. kingae was undertaken using a single bacterial throat swab taken from well children aged 6 months to 4 years. Standard laboratory procedures were used for culture and identification of organisms. RESULTS: One hundred children were enrolled between October and December 2014 at the Children's Hospital at Westmead. Median age was 24.0 months (range 6.1-48.8 months); 52 children were male and 36 attended day-care facilities. Forty-one children had siblings aged less than 5 years and 67 children had siblings of any age. K. kingae oropharyngeal carriage was not detected in any of the children. Rates of carriage of other organisms were: 30% S. aureus, 21% H. influenzae, 2% S. pneumoniae and 2% S. pyogenes. Thirty-eight children were colonised with Kingella denitrificans. CONCLUSIONS: Our results suggest that prevalence of K. kingae carriage in pre-school children in Sydney is very low and support local and national guidelines that recommend flucloxacillin as empiric first-line therapy for children with osteoarticular infections. Studies conducted over the winter months and in other Australian centres could help answer outstanding questions regarding differences in carriage rates of K. kingae in children.

Sepsis-like disease in infants due to human parechovirus type 3 during an outbreak in Australia.

BACKGROUND: Infections with human parechoviruses (HPeVs) are associated with a wide range of clinical presentations in children, ranging from mild or asymptomatic infections to severe sepsis-like presentations or meningoencephalitis. METHODS: We reviewed medical records of infants admitted to 5 hospitals in New South Wales, Australia, during an outbreak of HPeV-3 infection. Data were collected on clinical presentation, laboratory markers, and outcome of infants with HPeV infection confirmed by reverse transcription polymerase chain reaction. RESULTS: We identified 118 infected infants. Most presented with an acute sepsis-like syndrome with high fever, tachycardia, poor perfusion, and severe irritability. Other common features were erythrodermic rash, abdominal distension, edema, and hepatitis. The age range of infants was 4 days to 9.5 months; 75% were <2 months old, including all but 1 of the 30 infants (25%) admitted to intensive care units (ICUs), who as a group, were significantly younger than infants not admitted to ICUs. Only 4% of evaluable cerebrospinal fluid samples had pleocytosis, but HPeV was detected in 95%. Brain magnetic resonance imaging on a small number of children demonstrated white matter changes and diffusion restriction. Sequencing of the VP1 gene confirmed HPeV-3 in all samples tested. All children recovered without ongoing complications at last follow-up. CONCLUSIONS: We report the largest series of HPeV-3 infection in infants, and the first outbreak in Australia. Infants presented with a severe sepsis-like syndrome with a high rate of ICU admissions, but all recovered from the acute infection without complications. Long-term sequelae are unknown.

Echovirus 19 associated with a case of acute flaccid paralysis.

Acute flaccid paralysis can be caused by many members of the enterovirus genus, most notably the three poliviruses types 1 to 3. We report the case of acute flaccid paralysis caused by echovirus 19. The Western Pacific region has been declared polio free by the WHO since 2000. Australia is now using inactivated polio vaccine in the National Immunization Schedule. This vaccine does not carry the extremely rare risk of vaccine associated acute flaccid paralysis but it does leave our newly vaccinated population open gastrointestinal infection with polioviruses and the risk of circulation of the wild-type virus. Continued surveillance of cases of acute flaccid paralysis is to detect polioviruses is essential until poliovirus is completely eradicated.

The impact of bacterial and viral co-infection in severe influenza.

BACKGROUND: Many questions remain concerning the burden, risk factors and impact of bacterial and viral co-infection in patients with pandemic influenza admitted to the intensive care unit (ICU). OBJECTIVES: To examine the burden, risk factors and impact of bacterial and viral co-infection in Australian patients with severe influenza. PATIENTS/METHODS: A cohort study conducted in 14 ICUs was performed. Patients with proven influenza A during the 2009 influenza season were eligible for inclusion. Demographics, risk factors, clinical data, microbiological data, complications and outcomes were collected. Polymerase chain reaction for additional bacterial and viral respiratory pathogens was performed on stored respiratory samples. RESULTS: Co-infection was identified in 23·3-26·9% of patients with severe influenza A infection: viral co-infection, 3·2-3·4% and bacterial co-infection, 20·5-24·7%. Staphylococcus aureus was the most frequent bacterial co-infection followed by Streptococcus pneumoniae and Haemophilus influenzae. Patients with co-infection were younger [mean difference in age = 8·46 years (95% CI: 0·18-16·74 years)], less likely to have significant co-morbidities (32·0% versus 66·2%, P = 0·004) and less frequently obese [mean difference in body mass index = 6·86 (95% CI: 1·77-11·96)] compared to those without co-infection. CONCLUSIONS: Bacterial or viral co-infection complicated one in four patients admitted to ICU with severe influenza A infection. Despite the co-infected patients being younger and with fewer co-morbidities, no significant difference in outcomes was observed. It is likely that co-infection contributed to a need for ICU admission in those without other risk factors for severe influenza disease. Empiric antibiotics with staphylococcal activity should be strongly considered in all patients with severe influenza A infection.