Circulation of enterovirus D68 (EV-D68) causing respiratory illness in New South Wales, Australia, between August 2018 and November 2019.

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.

Clinical characteristics and outcomes of COVID-19 in a low-prevalence, well resourced setting, Sydney, Australia.

BACKGROUND: The Northern Sydney Local Health District was one of the first health regions to be affected by COVID-19 in Australia. AIMS: To describe the clinical characteristics, risk factors and outcomes in our low-prevalence Australian population. METHODS: This is a retrospective analysis of 517 laboratory-confirmed COVID-19 cases between January and June 2020. Patient information was collected as part of routine care within the COVID-19 Virtual Hospital system. Outcomes examined were death, recovery at 30 days and intensive care unit (ICU) admission. RESULTS: The case fatality rate was 1.8%. Multivariate analysis showed factors independently associated with death, composite outcome of death/ICU admission or incomplete recovery at 30 days were age >80 years and presence of two or more comorbidities. Most cases acquired COVID-19 through international (50.9%) or cruise ship travel (9.1%). Healthcare workers comprised 12.8% of the cohort and represented a disproportionately high percentage of the 'unknown' source group (27.6%). The median incubation period was 5 days (interquartile range 3-8); one patient had an incubation period of 15 days. Hospitalisation was required in 11.8%, ICU admission in 2.1% and ventilation in 1.4%. A Radiographic Assessment of Lung Oedema score on chest X-ray of >10 was independently associated with death. CONCLUSIONS: In this low prevalence, well resourced Australian setting, we report an overall low mortality. Factors associated with adverse patient outcomes on multivariate analysis were age greater than 80 and the presence of two or more comorbidities. These data can assist in early risk stratification of COVID-19 patients, and in surge capacity planning for hospitals.

An evaluation of 4 commercial assays for the detection of SARS-CoV-2 antibodies in a predominantly mildly symptomatic low prevalence Australian population.

A total of 1080 individual patient samples (158 positive serology samples from confirmed, predominantly mildly symptomatic COVID-19 patients and 922 serology negative including 496 collected pre-COVID) from four states in Australia were analysed on four commercial SARS-CoV-2 serological assays targeting antibodies to different antigens (Roche Elecsys and Abbott Architect: nucleocapsid; Diasorin Liaison and Euroimmun: spike). A subset was compared to immunofluorescent antibody (IFA) and micro-neutralisation. Sensitivity and specificity of the Roche (n = 1033), Abbott (n = 806), Diasorin (n = 1034) and Euroimmun (n = 175) were 93.7 %/99.5 %, 90.2 %/99.4 %, 88.6 %/98.6 % and 91.3 %/98.8 %, respectively. ROC analysis with specificity held at 99 % increased the sensitivity for the Roche and Abbott assays from 93.7% to 98.7% (cut-off 0.21) and 90.2 % to 94.0 % (cut-off 0.91), respectively. Overall seropositivity of samples increased from a maximum of 23 % for samples 0-7 days-post-onset of symptoms (dpos), to 61 % from samples 8-14dpos and 93 % from those >14dpos. IFA and microneutralisation values correlated best with assays targeting antibodies to spike protein with values >80 AU/mL on the Diasorin assay associated with neutralising antibody. Detectable antibody was present in 22/23 (96 %), 20/23 (87 %), 15/23 (65 %) and 9/22 (41 %) patients with samples >180dpos on the Roche, Diasorin, Abbott and microneutralisation assays respectively. Given the low prevalence in this community, two-step algorithms on initial positive results saw an increase in the positive predictive value (PPV) of positive samples (39 %-65 % to ≥98 %) for all combinations. Similarly accuracy increased from a range of 98.5 %-99.4 % to ≥99.8 % assuming a 1 % seroprevalence. Negative predictive value (NPV) was high (≥99.8 %) regardless of which assay was used initially.

Self-collection: An appropriate alternative during the SARS-CoV-2 pandemic.

OBJECTIVES: To evaluate the reliability of self-collection for SARS-CoV-2 and other respiratory viruses because swab collections for SARS-CoV-2 put health workers at risk of infection and require use of personal protective equipment (PPE). METHODS: In a prospective study, patients from two states in Australia attending dedicated COVID-19 collection clinics were offered the option to first self-collect (SC) nasal and throat swabs (SCNT) prior to health worker collect (HC) using throat and nasal swabs (Site 1) or throat and nasopharyngeal swabs (Site 2). Samples were analysed for SARS-CoV-2 as well as common respiratory viruses. Concordance of results between methods was assessed using Cohen's kappa (κ) and Cycle threshold (Ct) values were recorded for all positive results as a surrogate measure for viral load. RESULTS: Of 236 patients sampled by HC and SC, 25 had SARS-CoV-2 (24 by HC and 25 by SC) and 63 had other respiratory viruses (56 by HC and 58 by SC). SC was highly concordant with HC (κ = 0.890) for all viruses including SARS-CoV-2 and more concordant than HC to positive results by any method (κ = 0.959 vs 0.933). Mean SARS-CoV-2 E-gene and N-gene, rhinovirus and parainfluenza Ct values did not differ between HC and SCNT. CONCLUSIONS: Self-collection of nasal and throat swabs offers a reliable alternative to health worker collection for the diagnosis of SARS-CoV-2 and other respiratory viruses and provides patients with easier access to testing, reduces exposure of the community and health workers to those being tested and reduces requirement for PPE.

Next generation sequencing of human enterovirus strains from an outbreak of enterovirus A71 shows applicability to outbreak investigations.

BACKGROUND: The most recent documented Australian outbreak of enterovirus A71 (EV-A71) occurred in Sydney from 2012 to 2013. Over a four-month period more than 100 children presented to four paediatric hospitals with encephalitic presentations including fever and myoclonic jerks. The heterogeneous presentations included typical encephalomyelitis, and cardiopulmonary complications. OBJECTIVES: To characterise the genomes of enterovirus strains circulating during the 2013 Sydney EV-A71 outbreak and determine their phylogeny, phylogeography and association between genome and clinical phenotype. STUDY DESIGN: We performed an analysis of enterovirus (EV) positive specimens from children presenting to hospitals in the greater Sydney region of Australia during the 2013 outbreak. We amplified near full-length genomes of EV, and used next generation sequencing technology to sequence the virus. We used phylogenetic/phylogeographic analysis to characterize the outbreak viruses. RESULTS: We amplified and sequenced 23/63 (37 %) genomes, and identified the majority (61 %) as EV-A71. The EV-A71 sequences showed high level sequence homology to C4a genogroups of EV-A71 circulating in China and Vietnam during 2012-13. Phylogenetic analysis showed EV-A71 strains associated with more severe symptoms, including encephalitis or cardiopulmonary failure, grouped together more closely than those from patients with hand, foot and mouth disease. Amongst the non-EV-A71 sequences were five other EV subtypes (representing enterovirus subtypes A and B), reflecting the diversity of EV co-circulation within the community. CONCLUSIONS: This is the first Australian study investigating the near full-length genome of EV strains identified during a known outbreak of EV-A71. EV-A71 sequences were very similar to strains circulating in Asia during the same time period. Whole genome sequencing offers additional information over routine diagnostic testing such as characterisation of emerging recombinant strains and inform vaccine design.

Utility of selection methods for specialist medical training: A BEME (best evidence medical education) systematic review: BEME guide no. 45.

BACKGROUND: Selection into specialty training is a high-stakes and resource-intensive process. While substantial literature exists on selection into medical schools, and there are individual studies in postgraduate settings, there seems to be paucity of evidence concerning selection systems and the utility of selection tools in postgraduate training environments. AIM: To explore, analyze and synthesize the evidence related to selection into postgraduate medical specialty training. METHOD: Core bibliographic databases including PubMed; Ovid Medline; Embase, CINAHL; ERIC and PsycINFO were searched, and a total of 2640 abstracts were retrieved. After removing duplicates and screening against the inclusion criteria, 202 full papers were coded, of which 116 were included. RESULTS: Gaps in underlying selection frameworks were illuminated. Frameworks defined by locally derived selection criteria, and heavily weighed on academic parameters seem to be giving way to the evidencing of competency-based selection approaches in some settings. Regarding selection tools, we found favorable psychometric evidence for multiple mini-interviews, situational judgment tests and clinical problem-solving tests, although the bulk of evidence was mostly limited to the United Kingdom. The evidence around the robustness of curriculum vitae, letters of recommendation and personal statements was equivocal. The findings on the predictors of past performance were limited to academic criteria with paucity of long-term evaluations. The evidence around nonacademic criteria was inadequate to make an informed judgment. CONCLUSIONS: While much has been gained in understanding the utility of individual selection methods, though the evidence around many of them is equivocal, the underlying theoretical and conceptual frameworks for designing holistic and equitable selection systems are yet to be developed.

Paediatrician beliefs and practices around influenza vaccination.

AIM: The uptake of influenza vaccination in children with high-risk medical conditions continues to be low in Australia and internationally. We aimed to determine Australian paediatricians' beliefs and practices around the influenza vaccination of children. METHODS: This was conducted as a cross sectional survey of paediatricians from two tertiary paediatric hospitals in Sydney. RESULTS: There were 101 participants. Influenza vaccination was not prioritised compared with other vaccines and clinical issues, with fewer than half of respondents strongly agreeing that influenza vaccination was useful. Paediatricians' knowledge of guidelines and recommendations in this area was suboptimal. Interventions thought most likely to improve vaccine coverage included better education of doctors, greater vaccine availability in outpatient clinics and automated reminder systems. CONCLUSION: The inclusion of influenza vaccine on the standard Australian immunisation schedule may be required to improve vaccine coverage in high-risk children.

Antibiotic duration and timing of the switch from intravenous to oral route for bacterial infections in children: systematic review and guidelines.

Few studies are available to inform duration of intravenous antibiotics for children and when it is safe and appropriate to switch to oral antibiotics. We have systematically reviewed antibiotic duration and timing of intravenous to oral switch for 36 paediatric infectious diseases and developed evidence-graded recommendations on the basis of the review, guidelines, and expert consensus. We searched databases and obtained information from references identified and relevant guidelines. All eligible studies were assessed for quality. 4090 articles were identified and 170 studies were included. Evidence relating antibiotic duration to outcomes in children for some infections was supported by meta-analyses or randomised controlled trials; in other infections data were from retrospective series only. Criteria for intravenous to oral switch commonly included defervescence and clinical improvement with or without improvement in laboratory markers. Evidence suggests that intravenous to oral switch can occur earlier than previously recommended for some infections. We have synthesised recommendations for antibiotic duration and intravenous to oral switch to support clinical decision making and prospective research.

Prevalence and determinants of influenza vaccine coverage at tertiary pediatric hospitals.

Despite long-standing recommendations, the uptake of influenza vaccination in children with high risk medical conditions is low. This study aimed to examine the uptake of influenza vaccination amongst a cohort of Australian children and factors associated with vaccine acceptance. Three hundred and sixteen parents of children attending outpatient clinics at the two pediatric hospitals in Sydney were recruited. The reported vaccination coverage rate was 41% among children with high risk conditions and 14% among standard risk children. There was a median of three clinic visits per high risk child at which an opportunity to vaccinate was apparently missed. Healthcare worker recommendation, having a high risk condition and parental beliefs about influenza and influenza vaccination were the most important determinants of vaccine uptake. Further studies on the beliefs and practices of doctors in this area will help guide interventions to improve vaccination rates in high risk children.

Q Fever with transient antiphospholipid antibodies associated with cholecystitis and splenic infarction.

We describe a case of Q fever associated with the transient presence of antiphospholipid antibodies in a 9-year-old boy presenting with acalculous cholecystitis and splenic infarction. Antiphospholipid antibodies are commonly associated with acute Q fever in adults but have previously been thought to be of little clinical significance. Recent data suggest that antiphospholipid antibodies may be responsible for certain clinical manifestations of acute Q fever.