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INTRODUCTION Safely increasing organ donation to meet need is a priority. Potential donors may be declined due to perceived blood borne virus (BBV) transmission risk. With hepatitis C (HCV) curative therapy, more potential donors may now be suitable. We sought to describe potential deceased donors with increased BBV transmission risk. METHODS We conducted a cohort study of all potential organ donors referred in New South Wales, Australia, 2010-2018. We compared baseline risk potential donors to potential donors with increased BBV transmission risk, due to history of HIV, HCV or hepatitis B and/or behavioural risk factors. RESULTS There were 624/5749 potential donors (10.9%) perceived to have increased BBV transmission risk. This included 298/5749 (5.2%) with HCV (including HBV co-infections) and 239/5749 (4.2%) with increased risk behaviours (no known BBV). Potential donors with HCV and those with increased risk behaviours were younger and had fewer comorbidities than baseline risk potential donors (p

Summary Viruses are postulated as primary candidate triggers of islet autoimmunity (IA) and type 1 diabetes (T1D), based on considerable epidemiological and experimental evidence. Recent studies have investigated the association between all viruses (the ‘virome’) and IA/T1D using metagenomic next‐generation sequencing (mNGS). Current associations between the early life virome and the development of IA/T1D were analysed in a systematic review and meta‐analysis of human observational studies from Medline and EMBASE (published 2000–June 2020), without language restriction. Inclusion criteria were as follows: cohort and case–control studies examining the virome using mNGS in clinical specimens of children ≤18 years who developed IA/T1D. The National Health and Medical Research Council level of evidence scale and Newcastle–Ottawa scale were used for study appraisal. Meta‐analysis for exposure to specific viruses was performed using random‐effects models, and the strength of association was measured using odds ratios (ORs) and 95% confidence intervals (CIs). Eligible studies (one case–control, nine nested case–control) included 1,425 participants (695 cases, 730 controls) and examined IA (n = 1,023) or T1D (n = 402). Meta‐analysis identified small but significant associations between IA and number of stool samples positive for all enteroviruses (OR 1.14, 95% CI 1.00–1.29, p = 0.05; heterogeneity χ 2 = 1.51, p = 0.68, I 2 = 0%), consecutive positivity for enteroviruses (1.55, 1.09–2.20, p = 0.01; χ 2 = 0.19, p = 0.91, I 2 = 0%) and number of stool samples positive specifically for enterovirus B (1.20, 1.01–1.42, p = 0.04; χ 2 = 0.03, p = 0.86, I 2 = 0%). Virome analyses to date have demonstrated associations between enteroviruses and IA that may be clinically significant. However, larger prospective mNGS studies with more frequent sampling and follow‐up from pregnancy are required to further elucidate associations between early virus exposure and IA/T1D.

The current public health emergency surrounding the COVID-19 pandemic, that is the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in thousands of cases in Australia since 25 January 2020 when the first case was diagnosed. This emerging virus presents particular hazards to researchers and laboratory staff in a clinical setting, highlighted by rapid and widespread global transmission. Based on the epidemiological and clinical data that have become available in mid-2020, we propose the interim classification of SARS-CoV-2 as a Risk Group 3 organism is reasonable, and discuss establishing Biosafety Level 3 (BSL-3) regulations accordingly. Despite its global spread, the reported mortality rate of SARS-CoV-2 ranging from 0.13% to 6.22% is considerably less than that of other Risk Group 4 agents including Ebola and Marburg viruses with fatality rates as high as 90%. In addition, studies have demonstrated that approximately 86% of patients presenting with severe courses of the disease are aged 70 years or above, with the presence of comorbid conditions such as cardiovascular and respiratory system diseases in the majority of all fatal cases. In contrary to recent discussions surrounding the protective and administrative measures needed in a laboratory, the emerging evidence surrounding mortality rate, distinct demographics of severe infections, and the presence of underlying diseases does not justify the categorisation of SARS-CoV-2 as a Risk Group 4 organism. This article summarises biosafety precautions, control measures and appropriate physical containment facilities required to minimise the risk of laboratory-acquired infections with SARS-CoV-2.

Background Molecular assays based on reverse transcription-polymerase chain reaction (RT-PCR) provide reliable results for the detection of respiratory pathogens, although diagnostic agreement varies. This study determined the agreement between the RT-PCR assays (Xpert® Flu/RSV vs Allplex™ RP1) in detecting influenza A, influenza B, and respiratory syncytial viruses (RSVs) in clinical practice. Methods We retrospectively identified 914 patient encounters where testing with both Xpert® Flu/RSV and Allplex™ RP1 was undertaken between October 2015 and September 2019 in seven hospitals across New South Wales, Australia. The diagnostic agreement of the two assays was evaluated using positive percent agreement, negative percent agreement, and prevalence and bias-adjusted kappa. Results The positive percent agreement was 95.1% for influenza A, 87.5% for influenza B, and 77.8% for RSV. The negative percent agreement was 99.4% for influenza A, 99.9% for influenza B, and 100% for RSV. The prevalence and bias-adjusted kappa was 0.98 for influenza A, 0.99 for influenza B, and 0.97 for RSV. In a sensitivity analysis, the positive percent agreement values were significantly higher during the non-influenza season than the influenza season for influenza B and RSV. Conclusions The Xpert® Flu/RSV and Allplex™ RP1 demonstrated a high diagnostic agreement for all three viruses assessed. The seasonal variation in the positive percent agreement of the two assays for influenza B and RSV may have been due to lower numbers assessed, variability in the virology of infections outside the peak season, or changes in the physiology of the infected host in different seasons.

Cytomegalovirus (CMV) viraemia continues to be a frequent complication in the post-haemopoietic stem cell transplantation period despite a low incidence of CMV end-organ disease. Several significant advances in the understanding and management of CMV infection have occurred in the last few years including improved diagnostics, monitoring of CMV immunity, availability of novel anti-CMV drugs, and emerging use of immunotherapies including CMV-specific T-cell infusions. In addition to reviewing these advances we also explore some of the more practical prescribing issues of the older and newer CMV drugs including cost, toxicity and drug interactions to help clinicians navigate this new era of CMV management.

Biosecurity is a term broadly applied to the protection, control and accountability of biological agents and toxins to minimise the risk of their introduction through natural, unintentional (accidents) or deliberate processes. Biosecurity protection involves the engagement of all stakeholders including government, public health networks, industry, and scientific community. While the Commonwealth Government primarily manages biosecurity, it is also a shared responsibility with State and Territory governments. Rapid, accurate diagnosis is essential to informing all levels of response to biosecurity threats. External quality assurance (EQA) through proficiency testing (PT) is an indispensable tool to allow assessment of laboratory performance. This ensures laboratory capability and capacity are in a constant state of readiness to effectively detect biological threats and reduce the impact and transmission of disease. Since 2009, the Royal College of Pathologists Australasia Quality Assurance Program (RCPAQAP) has been contracted by the Australian Government Department of Health to establish a proficiency testing program (PTP) for the detection of biological threat agents. Starting out as a PTP for the detection of Bacillus anthracis, RCPAQAP Biosecurity has undergone significant transformation, thereby building and enhancing laboratory preparedness. Alterations in the program have been in line with the changing landscape of biosecurity and other emerging infectious diseases across Australia, and worldwide.

The COVID-19 pandemic has changed people’s lives and has brought society to a sudden standstill, with lockdowns and social distancing as the preferred preventative measures. To lift these measurements and reduce society’s burden, developing an easy-to-use, rapid, and portable system to detect SARS-CoV-2 is mandatory. To this end, we developed a portable and semi-automated device for SARS-CoV-2 detection based on reverse transcription loop-mediated isothermal amplification followed by a CRISPR/Cas12a reaction. The device contains a heater element mounted on a printed circuit board, a cooler fan, a proportional integral derivative controller to control the temperature, and designated areas for 0.2 mL Eppendorf® PCR tubes. Our system has a limit of detection of 35 copies of the virus per microliter, which is significant and has the capability of being used in crisis centers, mobile laboratories, remote locations, or airports to diagnose individuals infected with SARS-CoV-2. We believe the current methodology that we have implemented in this article is beneficial for the early screening of infectious diseases, in which fast screening with high accuracy is necessary.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection hospitalisations in Aboriginal infants specifically those aged

Focus of Presentation Congenital cytomegalovirus (CMV) is a known cause of sensorineural hearing loss, cerebral palsy and other disabilities. International consensus guidelines (2017) and the Australasian Society of Infectious Diseases (2014) recommend all pregnant women be provided with information on CMV and strategies to reduce their risk of infection. Here we describe the multifaceted strategies implemented to date to promote uptake of these guidelines. Findings At policy level, we influenced national clinical practice standards through input into new CMV prevention recommendations by the Royal Australian and New Zealand College of Obstetricians and Gynaecologists and Department of Health, which sparked state public health campaigns. At the intervention level, we presented hospital in-services, podcasts and webinars and developed an e-learning course for midwives. In collaboration with the Department of Health >11,000 pamphlets were disseminated to NSW GPs. At the community level, we developed patient information and media resources. During a recent month-long campaign, our cCMV video had >62,000 views, CMV content on social media had >1.4M total impressions, >77,000 total engagements and >200,000 viewed CMV awareness pieces via television/radio/print. Conclusions/Implications Implementation of congenital CMV practice guidelines provide an important opportunity to prevent neurodevelopmental disability. Collaborations between families, clinicians, researchers, professional bodies and health departments are essential to drive translation. Key messages A multifaceted approach in implementing congenital CMV practice guidelines gives the opportunity to reach numerous stakeholders including policymakers, health professionals and expectant mothers.

The Environmental Determinants of Islet Autoimmunity (ENDIA) Study is an Australia-wide observational pregnancy-birth cohort of children at genetic risk on account of a first-degree relative with type 1 diabetes (1). 1511 participants were recruited from all Australian States and Territories from 2013-2019 with 1473 live-born infants in follow-up. The standard protocol involves 3-monthly face-to-face visits from pregnancy until the child is 2 years of age, then 6-monthly visits. Study staff across nine centres in five States collect biospecimens (blood, urine, stool, swabs) and administer lifestyle and dietary questionnaires. Approximately 10% of the cohort are engaged in a Regional Participant Program (2) that requires self-collection of sample types except for venepuncture performed at local pathology services.

Chronic hepatitis B prevalence is low in most Australian populations, with universal infant HBV vaccination introduced in 2000. Migrants from high prevalence countries are at risk of acquisition before arrival and non-immune adults are potentially at risk through skin penetrating procedures and sexual contact, particularly during international travel. The risk profile of young adult students, many from high prevalence countries, is inadequately understood. A cross-sectional online survey conducted among university students collected data on demographic, vaccination and travel characteristics and blood samples were tested for hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb). Analyses identified factors associated with HBsAb seroprevalence and self-reported vaccination. The serosurvey was completed by 804 students born between 1988 and 1993, with 613/804 (76.2%, 95% CI 73.2-79.1) self-reporting prior HBV vaccination. Overall, 526/804 (65.4%, 95% CI 62.0%-68.6%) students were seropositive to HBsAb, including 438/613 (71.5%, 95% CI 67.8-74.9) students self-reporting a prior HBV vaccine and 88/191 (46.1%, 95% CI 39.2-53.2) students self-reporting no prior HBV vaccine. Overall, 8/804 (1.0%, 95% CI 0.5%-2.0%) students were HBcAb positive, of whom 1/804 (0.1%, 95% CI 0.02%-0.7%) was currently infectious. The prevalence of chronic HBV infection was low. However, more than one in four students were susceptible to HBV and over-estimated their immunity. Future vaccination efforts should focus on domestic students born before the introduction of the infant program and all international students. Screening and vaccination of students, including through campus-based health services, are an opportunity to catch-up young adults prior to undertaking at-risk activities, including international travel.

© 2019 The Author(s). Background: Medical masks are commonly used in health care settings to protect healthcare workers (HCWs) from respiratory and other infections. Airborne respiratory pathogens may settle on the surface of used masks layers, resulting in contamination. The main aim of this study was to study the presence of viruses on the surface of medical masks. Methods: Two pilot studies in laboratory and clinical settings were carried out to determine the areas of masks likely to contain maximum viral particles. A laboratory study using a mannequin and fluorescent spray showed maximum particles concentrated on upper right, middle and left sections of the medical masks. These findings were confirmed through a small clinical study. The main study was then conducted in high-risk wards of three selected hospitals in Beijing China. Participants (n = 148) were asked to wear medical masks for a shift (6-8 h) or as long as they could tolerate. Used samples of medical masks were tested for presence of respiratory viruses in upper sections of the medical masks, in line with the pilot studies. Results: Overall virus positivity rate was 10.1% (15/148). Commonly isolated viruses from masks samples were adenovirus (n = 7), bocavirus (n = 2), respiratory syncytial virus (n = 2) and influenza virus (n = 2). Virus positivity was significantly higher in masks samples worn for > 6 h (14.1%, 14/99 versus 1.2%, 1/49, OR 7.9, 95% CI 1.01-61.99) and in samples used by participants who examined > 25 patients per day (16.9%, 12/71 versus 3.9%, 3/77, OR 5.02, 95% CI 1.35-18.60). Most of the participants (83.8%, 124/148) reported at least one problem associated with mask use. Commonly reported problems were pressure on face (16.9%, 25/148), breathing difficulty (12.2%, 18/148), discomfort (9.5% 14/148), trouble communicating with the patient (7.4%, 11/148) and headache (6.1%, 9/148). Conclusion: Respiratory pathogens on the outer surface of the used medical masks may result in self-contamination. The risk is higher with longer duration of mask use (> 6 h) and with higher rates of clinical contact. Protocols on duration of mask use should specify a maximum time of continuous use, and should consider guidance in high contact settings. Viruses were isolated from the upper sections of around 10% samples, but other sections of masks may also be contaminated. HCWs should be aware of these risks in order to protect themselves and people around them.

Background Cytomegalovirus (CMV) is the most common congenital infection and can cause hearing loss and neurodevelopmental disability in infected infants. International research shows women have limited knowledge about CMV. Aims To assess pregnant women's knowledge and attitudes about CMV before and after provision of information. Materials and methods Cross-sectional survey of pregnant women between November 2017 and February 2018 at two Australian hospitals. Participating women completed an initial survey on maternal characteristics, knowledge of infections, and CMV risk behaviours. Participants were then given an information leaflet and completed a follow-up survey. Results Four hundred and fifty-seven women completed the initial survey, of whom 73/457 (16%) had heard of CMV. Behaviours increasing risk of CMV transmission were common: 58% reported regularly kissing their child on the lips; 57% did not always wash their hands after changing a wet nappy. Knowledge about CMV significantly improved after reading the leaflet in the 145 women completing the follow-up survey. More women correctly identified that CMV could cause deafness in a baby (35% before, 85% after), was spread by saliva (38% vs 94%) or urine (27% vs 86%) and prevented by hand-washing (55% vs 99%; all P Conclusion Knowledge about CMV was low in pregnant women. An educational leaflet was effective in improving knowledge.

Smallpox was declared eradicated in 1980, with known seed stock retained in two high security Biosafety Level 4 laboratories in the United States and Russia. Experts agree the likelihood of theft from these laboratories is low, and that synthetic creation of smallpox is a theoretical possibility. Until 2017 it was believed that synthetic smallpox was technically too complex a task to be a serious threat. However, in 2017, Canadian scientists synthesised a closely related orthopoxvirus, horsepox, using mail order DNA and $100,000. Simultaneously, terrorist groups have declared intent to conduct biological attacks. In this context an exercise was held on August 16th 2018, with international and cross-sectoral stakeholders to review preparedness for a bioterrorism attack in the Asia-Pacific region and globally. The exercise was conducted by The National Health and Medical Research Council (NHMRC) Centre for Research Excellence, Integrated Systems for Epidemic Response, with contextual input from the Ministry of Health and Medical Services Fiji. The scenario involved a deliberate release in Fiji, followed by a larger release in a more populous Asian country. Mathematical modelling was used to underpin epidemic projections under different conditions. The exercise alternated between clinical, public health, emergency and societal responses, with participants making real-time decisions on cross-sectoral response across the region and the world. Key weak points which are influential in determining the final size and impact of the epidemic were identified (based on mathematical modelling of transmission in Fiji and globally). We identified potential gaps in preparedness for smallpox and factors which influence the severity of a smallpox epidemic. This included identifying which determinants of epidemic size are potentially within our control, and which are not. Influential factors within our control include: preventing an attack through intelligence, law enforcement and legislation; speed of diagnosis; speed and completeness of case finding and case isolation; speed and security of vaccination response, including stockpiling; speed and completeness of contact tracing; protecting critical infrastructure and business continuity; non-pharmaceutical interventions (social distancing, PPE, border control); protecting first responders; operational support and logistics; social mobilisation and risk communication. Based on discussion at the workshop between diverse stakeholders, recommendations were made to guide improved prevention, mitigation and rapid response, thus providing a holistic, cross-sectoral framework for prevention of a worst-case scenario smallpox pandemic.

Purpose Neurological complications of influenza cause significant disease in children. Central nervous system inflammation, the presumed mechanism of influenza-associated encephalopathy, is difficult to detect. Characteristics of children presenting with severe neurological complications of influenza, and potential biomarkers of influenza-associated encephalopathy are described. Methods A multi-center, retrospective case-series of children with influenza and neurological complications during 2017 was performed. Enrolled cases met criteria for influenza-associated encephalopathy or had status epilepticus. Functional outcome at discharge was compared between groups using the Modified Rankin Scale (mRS). Results There were 22 children with influenza studied of whom 11/22 had encephalopathy and 11/22 had status epilepticus. Only one child had a documented influenza immunization. The biomarker CSF neopterin was tested in 10/11 children with encephalopathy and was elevated in 8/10. MRI was performed in all children with encephalopathy and was abnormal in 8 (73%). Treatment of children with encephalopathy was with corticosteroids or intravenous immunoglobulin in 9/11 (82%). In all cases oseltamivir use was low (59%) while admission to the intensive care unit was frequent (14/22, 66%). Clinical outcome at discharge was moderate to severe disability (mRS score > 2) in the majority of children with encephalopathy (7/11, 64%), including one child who died. Children with status epilepticus recovered to near-baseline function in all cases. Conclusion Raised CSF neopterin was present in most cases of encephalopathy, and along with diffusion restriction on MRI, is a useful diagnostic biomarker. Lack of seasonal influenza vaccination represents a missed opportunity to prevent illness in children, including severe neurological disease., Highlights • Elevated CSF neopterin was common in cases of IAE. • Short term outcome for IAE was poor, particularly in those with MRI diffusion restriction. • Seasonal influenza vaccination is important for all children.

Background Influenza is a highly contagious respiratory virus with clinical impacts on patient morbidity, mortality and hospital bed management. The effect of rapid nucleic acid testing (RPCR) in comparison to standard multiplex PCR (MPCR) diagnosis in treatment decisions is unclear. This study aimed to determine whether RPCR influenza testing in comparison to standard MPCR testing was associated with differences in antibiotic and antiviral (oseltamivir) utilisation and hospital length of stay in emergency department and inpatient hospital settings. Methods A retrospective cohort study of positive influenza RPCR and MPCR patients was performed utilising data from the 2017 influenza season. Medical records of correlating patient presentations were reviewed for data collection. An analysis of RPCR versus MPCR patient outcomes was performed examining test turnaround time, antibiotic initiation, oseltamivir initiation and hospital length of stay for both emergency department and inpatient hospital stay. Subgroup analysis was performed to assess oseltamivir use in high risk populations for influenza complications. Statistical significance was assessed using Mann-Whitney test for numerical data and Chi-squared test for categorical data. Odds ratio with 95% confidence intervals were calculated where appropriate. Results Overall, 122 RPCR and 362 MPCR positive influenza patients were included in this study. Commencement of antibiotics was less frequent in the RPCR than MPCR cohorts (51% vs 67%; p p = 0.03, OR 1.81; 95% CI 1.07–3.08). Hospital length of stay was not impacted when either test was used in the emergency department and inpatient settings. Conclusions These findings suggest utilisation of RPCR testing in influenza management can improve antibiotic stewardship through reduction in antibiotic use and improvement in oseltamivir initiation in those at higher risk of complications. Further research is required to determine other factors that may have influenced hospital length of stay and a cost-benefit analysis should be undertaken to determine the financial impact of the RPCR test.

Summary Severe acute respiratory syndrome related coronavirus‐2 (SARS‐CoV‐2) is the cause of Covid‐19 which was classified as a global pandemic in March 2020. The increasing global health and economic burden of SARS‐CoV‐2 has necessitated urgent investigations into the pathogenesis of disease and development of therapeutic and vaccination regimens. Human trials of vaccine and antiviral candidates have been undertaken, but basic pathogenetic studies are still required to inform these trials. Gaps in understanding of cellular infection by, and immunity to, SARS‐CoV‐2 mean additional models are required to assist in improved design of these therapeutics. Human organoids are three‐dimensional models that contain multiple cell types and mimic human organs in ex vivo culture conditions. The SARS‐CoV‐2 virus has been implicated in causing not only respiratory injury but also injury to other organs such as the brain, liver and kidneys. Consequently, a variety of different organoid models have been employed to investigate the pathogenic mechanisms of disease due to SARS‐CoV‐2. Data on these models have not been systematically assembled. In this review, we highlight key findings from studies that have utilised different human organoid types to investigate the expression of SARS‐CoV‐2 receptors, permissiveness, immune response, dysregulation of cellular functions, and potential antiviral therapeutics.

Considerable concerns relating to the duration of protective immunity against SARS-CoV-2 exist, with evidence of antibody titres declining rapidly after infection and reports of reinfection. Here we monitor the antibody responses against SARS-CoV-2 receptor binding domain (RBD) for up to six months after infection. While antibody titres are maintained, about 13% of the cohort’s neutralising responses return to background. However, encouragingly in a selected subset of 13 participants, 12 have detectable RBD-specific memory B cells and these generally are increasing out to 6 months. Furthermore, we are able to generate monoclonal antibodies with SARS-CoV-2 neutralising capacity from these memory B cells. Overall our study suggests that the loss of neutralising antibodies in plasma may be countered by the maintenance of neutralising capacity in the memory B cell repertoire., Graphical Abstract, Abayasingam et al. report that despite the declining anti-RBD antibody titres and neutralising capacity of antibodies in the serum at six months, the memory B cells still contain RBD-specific reactivity that have the capacity to generate antibodies that can neutralise SARS-CoV-2 in vitro.

Serological testing for SARS-CoV-2-specific antibodies provides important research and diagnostic information relating to COVID-19 prevalence, incidence and host immune response. A greater understanding of the relationship between functionally neutralising antibodies detected using microneutralisation assays and binding antibodies detected using scalable enzyme immunoassays (EIA) is needed in order to address protective immunity post-infection or vaccination, and assess EIA suitability as a surrogate test for screening of convalescent plasma donors. We assessed whether neutralising antibody titres correlated with signal cut-off ratios in five commercially available EIAs, and one in-house assay based on expressed spike protein targets. Sera from recovered patients or convalescent plasma donors who reported laboratory-confirmed SARS-CoV-2 infection (n = 200), and negative control sera collected prior to the COVID-19 pandemic (n = 100), were assessed in parallel. Performance was assessed by calculating EIA sensitivity and specificity with reference to microneutralisation. Neutralising antibodies were detected in 166 (83%) samples. Compared with this, the most sensitive EIAs were the Cobas Elecsys Anti-SARS-CoV-2 (98%) and Vitros Immunodiagnostic Anti-SARS-CoV-2 (100%), which detect total antibody targeting the N and S1 antigens, respectively. The assay with the best quantitative relationship with microneutralisation was the Euroimmun IgG. These results suggest the marker used (total Ab vs. IgG vs. IgA) and the target antigen are important determinants of assay performance. The strong correlation between microneutralisation and some commercially available assays demonstrates their potential for clinical and research use in assessing protection following infection or vaccination, and use as a surrogate test to assess donor suitability for convalescent plasma donation.

Understanding the long-term maintenance of SARS-CoV-2 immunity is critical for prediction of protection against reinfection. In a cohort of 24 participants, the association of disease severity and early immunological measurements on the maintenance of humoral immune responses 12 months post-infection were examined. All severely affected participants maintained a stable subset of SARS-CoV-2 receptor-binding domain (RBD) specific memory B cells (MBCs) and good neutralising antibody breadth against the majority of the variants of concern, including the Delta variant. Modelling these immune responses on vaccine efficacy data indicated a level equivalent to a vaccine efficacy of approximately 45-76% against symptomatic reinfection (variant dependent). Overall, these findings indicate durable humoral responses in most participants, provide an estimate of the level of protection and identifies the magnitude and phenotype of baseline antigen-specific CD4+ T cell response as a predictor of maintenance of both antibody neutralisation breadth and RBD-specific MBC levels at 12 months post-infection. Funding: The Kirby Institute is funded by the Australian Government Department of Health and Ageing. The views expressed in this publication do not necessarily represent the position of the Australian Government. Research reported in this publication was supported by Snow Medical Foundation as an investigator-initiated study. The content is solely the responsibility of the authors. RAB, MM, CR and ARL are fellows funded by National Health and Medical Research Council (NHMRC). MWAC is in part funded by the Research Infrastructure Programme of UNSW. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The protocol was approved by the Human Research Ethics Committees of the Northern Sydney Local Health District and the University of New South Wales, NSW Australia (ETH00520) and was conducted according to the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice (ICH/GCP) guidelines and local regulatory requirements. Written informed consent was obtained from all participants before study procedures.

For 27 years, national prospective data on selected rare childhood diseases have been collected monthly by the Australian Paediatric Surveillance Unit (APSU) from paediatricians and other clinical specialists who report cases in children aged up to 16 years. We report here the annual results of APSU surveillance in 2020 for ten rare communicable diseases and complications of communicable diseases, namely: acute flaccid paralysis (AFP); congenital cytomegalovirus (CMV) infection; neonatal herpes simplex virus (HSV) infection; perinatal exposure to human immunodeficiency virus (HIV); paediatric HIV infection; severe complications of seasonal influenza; juvenile onset recurrent respiratory papillomatosis (JoRRP); congenital rubella syndrome; congenital varicella syndrome; and neonatal varicella infection. We describe the results for each disease in the context of the total period of study, including demographics, clinical characteristics, treatment and short-term outcomes. Despite challenges presented by the coronavirus disease 2019 (COVID-19) pandemic in 2020, more than 1,400 paediatricians reported regularly to the APSU and an overall monthly reporting rate of > 90% was achieved. The minimum AFP target of 1 case per 100,000 children aged less than 15 years was achieved and there were few cases of vaccine-preventable diseases (JoRRP, rubella, varicella). However, high cases of congenital CMV, neonatal HSV and perinatal exposure to HIV persist. There were no severe complications of seasonal influenza reported for the first time in 13 years. This is consistent with other surveillance data reporting a decline of influenza and other communicable diseases in 2020, and likely reflects the wider effects of public health measures to reduce transmission of SARS-CoV-2 in the Australian community.

BackgroundSerological testing for SARS-CoV-2 specific antibodies provides important research and diagnostic information relating to COVID-19 prevalence, incidence, and host immune response. A greater understanding of the relationship between functionally neutralising antibodies detected using microneutralisation assays and binding antibodies detected using scalable enzyme immunoassays (EIA) is needed in order to address protective immunity post-infection or vaccination, and assess EIA suitability as a surrogate test for screening of convalescent plasma donors. We assessed whether neutralising antibody titres correlated with signal cut-off ratios in five commercially available EIAs, and one in-house assay based on expressed spike protein targets.MethodsSera from individuals recovered from patients or convalescent plasma donors who reported laboratory-confirmed SARS-CoV-2 infection (n=200), and negative control sera collected prior to the COVID-19 pandemic (n=100) were assessed in parallel. Performance was assessed by calculating EIA sensitivity and specificity with reference to microneutralisation.ResultsNeutralising antibodies were detected in 166 (83%) samples. Compared with this, the most sensitive EIAs were the Cobas Elecsys Anti-SARS-CoV-2 (98%) and Vitros Immunodiagnostic Anti-SARS-CoV-2 (100%), which detect total antibody targeting the N and S1 antigens, respectively. The assay with the best quantitative relationship with microneutralisation was the Euroimmun IgG.ConclusionsThese results suggest the marker used (total Ab vs IgG vs IgA), and the target antigen are important determinants of assay performance. The strong correlation between microneutralisation and some commercially available assays demonstrate their potential for clinical and research use in assessing protection following infection or vaccination, and use as a surrogate test to assess donor suitability for convalescent plasma donation.

IntroductionSolid organ transplant recipients are at risk of infections, which may be either derived through transplantation or acquired later. Blood-borne viruses (BBV) are a particular concern for donor-derived transmissions. There is an increasing emphasis on biovigilance – monitoring the safety of donated organs. However, systematic surveillance to distinguish donor-transmitted infection from de novo post-transplant infection is challenging. Additional information can be obtained through linkage of administrative health data. Objectives and ApproachWe aimed to identify donor-transmitted and de novo BBV infections among organ transplant recipients. We conducted a cohort study of all solid organ donor-recipient pairs in New South Wales, Australia, 2000-2015. Donor and recipient BBV infections were identified by linking transplant registries with administrative health data. Proven/probable donor-transmissions were identified among new recipient infections within 12 months of transplant, classified according to an international algorithm. All other new BBV infections were classified as de novo infections. ResultsAmong 2,120 organ donors, 73 had a BBV infection (11/73 active, 62/73 past). Donors with BBV donated to 176 recipients, of whom 24/176 had the same BBV as their donor, and 152/176 did not; these 152 recipients were at risk of donor-transmission. Among those at risk, there were 3/152 proven/probable BBV transmissions (1 hepatitis C, 2 hepatitis B [HBV]) and 149/152 recipients with non-transmissions. All donor-transmissions were previously recognised by donation services, and were from donors with known BBV. There were no deaths from transmissions. There were 70 recipients with de novo BBV; 2/70 died from new HBV. Conclusion / ImplicationsThis work confirms the safety of Australian organ donation, with no unrecognised BBV transmissions and many non-transmissions from donors with BBV. This may support increasing targeted donation from donors with BBV. However, de novo BBV infections were substantial and preventable. Data-linkage may be a useful adjunct to current biovigilance systems.

The first laboratory confirmed case of Coronavirus disease 2019 (COVID-19) in Australia was in Victoria on 25 January 2020 in a man returning from Wuhan city, Hubei province, the People's Republic of China. This was followed by three cases in New South Wales the following day. The Australian Government activated the Australian Health Sector Emergency Response Plan for Novel Coronavirus on 27 February 2020 in anticipation of a pandemic. Subsequently, the World Health Organization declared COVID-19 to be a Public Health Emergency of International Concern followed by a pandemic on 30 January 2020 and 11 March 2020, respectively. Laboratory testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, is key in identifying infected persons to guide timely public health actions of contact tracing and patient isolation to limit transmission of infection. This article aims to provide a comprehensive overview of current laboratory diagnostic methods for SARS-CoV-2, including nucleic acid testing, serology, rapid antigen detection and antibody tests, virus isolation and whole genome sequencing. The relative advantages and disadvantages of the different diagnostic tests are presented, as well as their value in different clinical, infection control and public health contexts. We also describe the challenges in the provision of SARS-CoV-2 diagnostics in Australia, a country with a relatively low COVID-19 incidence in the first pandemic wave but in which prevalence could rapidly change.

Accumulating evidence supports the high prevalence of co-infections among Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) patients, and their potential to worsen the clinical outcome of COVID-19. However, there are few data on Southern Hemisphere populations, and most studies to date have investigated a narrow spectrum of viruses using targeted qRT-PCR. Here we assessed respiratory viral co-infections among SARS-CoV-2 patients in Australia, through respiratory virome characterization. Nasopharyngeal swabs of 92 SARS-CoV-2-positive cases were sequenced using pan-viral hybrid-capture and the Twist Respiratory Virus Panel. In total, 8% of cases were co-infected, with rhinovirus (6%) or influenzavirus (2%). Twist capture also achieved near-complete sequencing (>90% coverage, >10-fold depth) of the SARS-CoV-2 genome in 95% of specimens with Ct

The adoption of whole genome sequencing (WGS) data over the past decade for pathogen surveillance, and decision-making for infectious diseases has rapidly transformed the landscape of clinical microbiology and public health. However, for successful transition to routine use of these techniques, it is crucial to ensure the WGS data generated meet defined quality standards for pathogen identification, typing, antimicrobial resistance detection and surveillance. Further, the ongoing development of these standards will ensure that the bioinformatic processes are capable of accurately identifying and characterising organisms of interest, and thereby facilitate the integration of WGS into routine clinical and public health laboratory setting. A pilot proficiency testing (PT) program for WGS of infectious agents was developed to facilitate widely applicable standardisation and benchmarking standards for WGS across a range of laboratories. The PT participating laboratories were required to generate WGS data from two bacterial isolates, and submit the raw data for independent bioinformatics analysis, as well as analyse the data with their own processes and answer relevant questions about the data. Overall, laboratories used a diverse range of bioinformatics tools and could generate and analyse high-quality data, either meeting or exceeding the minimum requirements. This pilot has provided valuable insight into the current state of genomics in clinical microbiology and public health laboratories across Australia. It will provide a baseline guide for the standardisation of WGS and enable the development of a PT program that allows an ongoing performance benchmark for accreditation of WGS-based test processes.

Routine biochemical and hematological tests have been reported to be useful in the stratification and prognostication of pediatric and adult patients with diagnosed coronavirus disease (COVID-19), correlating with poor outcomes such as the need for mechanical ventilation or intensive care, progression to multisystem organ failure, and/or death. While these tests are already well established in most clinical laboratories, there is still debate regarding their clinical value in the management of COVID-19, particularly in pediatrics, as well as the value of composite clinical risk scores in COVID-19 prognostication. This document by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on COVID-19 provides interim guidance on: (A) clinical indications for testing, (B) recommendations for test selection and interpretation, (C) considerations in test interpretation, and (D) current limitations of biochemical/hematological monitoring of COVID-19 patients. These evidence-based recommendations will provide practical guidance to clinical laboratories worldwide, underscoring the contribution of biochemical and hematological testing to our collective pandemic response.

Isolation of the new pandemic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for diagnostic and research purposes including assessment of novel therapeutics. Several primary and continuous cell lines are currently used, and new organoid and engineered cell lines are being developed for improved investigation and understanding of the human immune response to this virus. Here we review the growth of SARS-CoV-2 in reference standard cell lines, engineered cell lines and new developments in this field.

The Australian Paediatric Surveillance Unit (APSU) has been prospectively collecting national data on rare childhood conditions since 1993, with monthly reporting of cases by paediatricians. In this report we describe annual results from studies for ten communicable diseases and complications of communicable diseases that were conducted using APSU surveillance in 2019 and place these in an historic context. Results are reported on acute flaccid paralysis, congenital cytomegalovirus infection, neonatal herpes simplex virus infection, perinatal exposure to HIV, paediatric HIV infection, severe complications of seasonal influenza, juvenile onset recurrent respiratory papillomatosis (JoRRP), congenital rubella syndrome, congenital varicella syndrome and neonatal varicella infection. APSU provides rich clinical data to complement data collected from other surveillance systems and to improve understanding and response to rare childhood infections.

Aim: As the COVID-19 pandemic evolves, human milk banks world-wide continue to provide donor human milk to vulnerable infants who lack access to mother's own milk. Under these circumstances, ensuring the safety of donor human milk is paramount, as the risk of vertical transmission of SARS-CoV-2 is not fully understood. Here, we investigate the inactivation of SARS-CoV-2 in human milk by pasteurisation and the stability of SARS-CoV-2 in human milk under cold storage. Methods: SARS-CoV-2 was experimentally inoculated into human milk samples from healthy donors or into a control medium. Triplicates of each sample were layered onto uninfected cells after Holder pasteurisation (63°C for 30 min), heating to 56°C for 30 min, or after 48 h of storage at 4°C or −30°C. Infectious titres of virus were determined at 72 h post-infection by endpoint titration. Results: Following heating to 63°C or 56°C for 30 min, replication competent (i.e. live) SARS-CoV-2 was undetected in both human milk and the control medium. Cold storage of SARS-CoV-2 in human milk (either at 4°C or −30°C) did not significantly impact infectious viral load over a 48 h period. Conclusion: SARS-CoV-2 is effectively inactivated by Holder pasteurisation, suggesting that existing milk bank processes will effectively mitigate the risk of transmission of SARS-COV-2 to vulnerable infants through pasteurised donor human milk. The demonstrated stability of SARS-CoV-2 in refrigerated or frozen human milk may assist in the development of guidelines around safe expressing and storing of milk from COVID-19 infected mothers.

Congenital cytomegalovirus (HCMV) infection may cause significant fetal malformation, lifelong disease, and, in severe cases, fetal or neonatal death. Placental infection with HCMV is the major mechanism of mother-to-child transmission (MTCT) and fetal injury. Thus, any pharmaceutical antiviral interference to reduce viral load may reduce placental damage, MTCT, and fetal disease. However, there is currently no licensed HCMV antiviral for use during pregnancy. In this study, aciclovir and the HCMV-specific antivirals letermovir, maribavir, and cidofovir were compared with ganciclovir for antiviral effects in model systems of pregnancy, including first-trimester TEV-1 trophoblast cell cultures and third-trimester ex vivo placental explant histocultures. HCMV-infected trophoblasts at 7 days postinfection (dpi) showed an EC(50) of 21 μM for aciclovir, 0.0007 μM for letermovir, 0.11 μM for maribavir, and 0.29 μM for cidofovir, relative to 0.42 μM for ganciclovir. Antivirals added at 10 μM showed no cytotoxic effects and did not affect trophoblast cell proliferation (P > 0.9999). Multiple-round HCMV replication measured at 7 dpi showed letermovir, maribavir, and cidofovir treatment inhibited immediate early, early, and true late viral protein expression as assayed on Western blots. Antiviral treatment of HCMV-infected placental explants showed significant inhibition (P 0.9999). In ex vivo model systems, recently trialed HCMV antivirals letermovir and maribavir were effective at inhibiting HCMV replication. They partly fulfil requirements for use as safe and effective therapeutics during pregnancy to control congenital HCMV. Clinical trials of these newer agents would assist assessment of their utility in pregnancy.

Background Blood-borne viral infections can complicate organ transplantation. Systematic monitoring to distinguish donor-transmitted infections from other new infections post transplant is challenging. Administrative health data can be informative. We aimed to quantify post-transplant viral infections, specifically those transmitted by donors and those reactivating or arising new in recipients. Methods We linked transplant registries with administrative health data for all solid organ donor-recipient pairs in New South Wales, Australia, 2000-2015. All new recipient notifications of hepatitis B (HBV), C (HCV), or human immunodeficiency virus (HIV) after transplant were identified. Proven/probable donor transmissions within 12 months of transplant were classified using an international algorithm. Results Of 2120 organ donors, there were 72 with a viral infection (9/72 active, 63/72 past). These 72 donors donated to 173 recipients, of whom 24/173 already had the same infection as their donor, and 149/173 did not, so were at risk of donor transmission. Among those at risk, 3/149 recipients had proven/probable viral transmissions (1 HCV, 2 HBV); none were unrecognized by donation services. There were no deaths from transmissions. There were no donor transmissions from donors without known blood-borne viruses. An additional 68 recipients had new virus notifications, of whom 2/68 died, due to HBV infection. Conclusion This work confirms the safety of organ donation in an Australian cohort, with no unrecognized viral transmissions and most donors with viral infections not transmitting the virus. This may support targeted increases in donation from donors with viral infections. However, other new virus notifications post transplant were substantial and are preventable. Data linkage can enhance current biovigilance systems.

Backgrounds: We aimed to monitor pancreatic exocrine function longitudinally in relation to the development of islet autoimmunity (IA) and type 1 diabetes (T1D) in at-risk children with a first-degree relative with T1D, who were followed prospectively in the Environmental Determinants of Islet Autoimmunity (ENDIA) study. Methods: Fecal elastase-1 (FE-1) concentration was measured longitudinally in 85 ENDIA children from median age 1.0 (IQR 0.7,1.3) year. Twenty-eight of 85 children (progressors) developed persistent islet autoantibodies at median age of 1.5 (IQR 1.1,2.5) years, of whom 11 went on to develop clinical diabetes. The other 57 islet autoantibody-negative children (non-progressors) followed similarly were age and gender-matched with the progressors. An adjusted linear mixed model compared FE-1 concentrations in progressors and non-progressors. Results: Baseline FE-1 did not differ between progressors and non-progressors, or by HLA DR type or proband status. FE-1 decreased over time in progressors in comparison to non-progressors (Wald statistic 5.46, P =.02); in some progressors the fall in FE-1 preceded the onset of IA. Conclusions: Pancreatic exocrine function decreases in the majority of young at-risk children who progress to IA and T1D.

Objectives Infection control policies and guidelines recommend using facemasks and respirators to protect healthcare workers (HCWs) from respiratory infections. Common types of respirators used in healthcare settings are filtering facepiece respirators (FFRs) and powered air-purifying respirators (PAPRs). Aims of this study were to examine the current attitudes and practices of HCWs regarding the selection and use of respiratory protection and determine the acceptability of a novel PAPR. Methods In-depth interviews were undertaken with 20 HCWs from a large tertiary hospital in Sydney, Australia. Participants were fit tested with a lightweight tight-fitting half-facepiece PAPR (CleanSpace2™ Power Unit, PAF-0034, by CleanSpace Technology®) using the TSI™ Portacount quantitative fit test method. Results Interview results showed that HCWs had a limited role in the selection and use of facemasks and respirators and had been using the devices provided by the hospital. The majority of subjects had no knowledge of hospital policy for the use of facemasks and respirators, had not been trained on the use of respirators, and had not been fit tested previously. Compliance with the use of facemasks and respirators was perceived as being low and facemasks and respirators were typically used only for short periods of time. All 20 participants were successfully fit tested to the CleanSpace2™ PAPR (overall geometric mean fit factor—6768). According to the exit surveys, CleanSpace2™ PAPRs were easy to don (14/20) and doff (15/20) and comfortable to wear (14/20). Most participants believed that PAPRs provide higher protection, comfort and reusability over N95 FFR and can be used during pandemics and other high-risk situations. Conclusions HCWs should be aware of infection control policies and training should be provided on the correct use of respiratory protective devices. PAPRs can be used in hospital settings to protect HCWs from certain highly infectious and emerging pathogens, however, HCWs require adequate training on storage, use, and cleaning of PAPRs.

BACKGROUND: Human parechovirus (HPeV) typically infects young children, and although infection is often asymptomatic, some types (eg, HPeV3) are associated with severe clinical manifestations, including central nervous system infection or sepsis-like syndrome, particularly affecting young infants. The third documented national epidemic of HPeV occurred in Australia in 2017-2018. METHODS: Four public laboratories that perform almost all of the HPeV PCR testing in New South Wales provided data regarding HPeV tests performed from July 1, 2017 to June 30, 2018. Limited demographic and clinical data were obtained from electronic medical records for laboratory test-positive cases that presented to each of the 3 pediatric hospitals in New South Wales. RESULTS: Five hundred eighty-one HPeV-positive samples obtained from 395 cases were included in the analysis. The peak of the outbreak occurred in late November 2017 (approximately 35 new cases each week), with the main HPeV epidemic occurring between the spring and summer months of September 2017 to January 2018; although this seasonality was observed primarily in infants less than 12 months of age. Among the 388 pediatric cases, almost half were younger than 2 months (188; 47%) and only 10 were children older than 2 years. The annualized estimated incidence of laboratory confirmed HPeV infection in children was approximately 142.4 cases per 100,000 children younger than 5 years in New South Wales during the epidemic season. CONCLUSIONS: The large burden of HPeV infection and disease identified in young infants in this and previous Australian studies highlight the need for more comprehensive national surveillance of HPeV infections and improved prevention strategies.

Purpose To develop and measure the uptake of a local guideline for herpes simplex keratitis (HSK) and to standardize initial antiviral therapy in Australia. Methods The Registered Nurses' Association of Ontario Toolkit: "Implementation of Best Practice Guidelines" was used to develop, implement, and evaluate the guideline at Sydney Eye Hospital. An implementation team was established to reach consensus on antiviral therapy guidelines through review of available evidence, identifying stakeholders, facilitators and barriers, creating strategies for implementation, and developing a sustainability plan. An audit of all adult HSK cases during a 6-month postguideline implementation period was conducted, and the results were compared with a preimplementation audit. A web-based survey was created to assess clinician awareness, usage, and level of knowledge of the guideline. Results Clinicians, pharmacists, and administrative staff were identified as stakeholders. Changing clinician's behavior was the major barrier to implementation. Implementation strategies included printed and online materials and lectures to clinicians. A postimplementation audit included 85 patients, and 95 clinicians received a web-based survey. The dose of the prescribed antiviral medication was in alignment with the local guideline in 80% (51/64) of the patients compared with 73% (163/223) before implementation (P = 0.331). Stromal HSK with ulceration and keratouveitis were excluded because there were no recommendations before implementation. Over 70% of clinicians (30/41) were aware of the guideline and accessed them through educational resources. Conclusions Guidelines for the management of HSK may improve standardization of initial antiviral therapy in HSK. In practice, most clinicians were aware of and adhered to the local guideline.

Considerable concerns relating to the duration of protective immunity against SARS-CoV-2 have been raised, with evidence of antibody titres declining rapidly after infection and reports of reinfection. Here we monitored antibody responses against SARS-CoV-2 receptor binding domain (RBD) for up to six months after infection. While antibody titres were maintained, half of the cohort’s neutralising responses had returned to background. However, encouragingly in a selected subset of 13 participants, 12 had detectable RBD-specific memory B cells and these generally increased out to 6 months. Furthermore, we were able to generate monoclonal antibodies with SARS-CoV-2 neutralising capacity from these memory B cells. Overall our study suggests that the loss of neutralising antibodies in plasma may be countered by the maintenance of neutralising capacity in the memory B cell repertoire. Funding: The Kirby Institute is funded by the Australian Government Department of Health and Ageing. The views expressed in this publication do not necessarily represent the position of the Australian Government. Research reported in this publication was supported by Snow Medical Foundation as an investigator-initiated study. The content is solely the responsibility of the authors. RAB, MM, CR and ARL are fellows funded by National Health and Medical Research Council (NHMRC). Conflict of Interest: The authors declare no competing interests. Ethical Approval: The protocol was approved by the Human Research Ethics Committees of the Northern Sydney Local Health District and the University of New South Wales, NSW Australia (ETH00520) and was conducted according to the Declaration of Helsinki and International Conference on H armonization Good Clinical Practice (ICH/GCP) guidelines and local regulatory requirements. Written informed consent was obtained from all participants before study procedures.

In 2011, the International Health Regulations Review Committee of the WHO suggested ‘The world is ill-prepared to respond to a severe influenza pandemic or to any similarly global, sustained and threatening public-health emergency’. This was presumably partly in response to known threats that had occurred over the previous decade – Severe Acute Respiratory Syndrome (SARS) in 2003,H1N1 pandemic influenza in 2009, avian influenza H5N1 in 2004, and predated outbreaks with Zikavirus (2015–2016), Ebolavirus (2014), and most recently SARS CoV2, the causative agent of COVID-19 (2020).

Australian national surveillance data was used to assess recognition, sequelae, and antiviral therapy for congenital cytomegalovirus (CMV) cases.Data from congenital CMV cases reported through the Australian Paediatric Surveillance Unit born January 1999 to December 2016 were described and Chi-square tests used to characterise trends and associations in case reporting, maternal CMV serology testing, and antiviral therapy. Descriptive analyses for hearing loss and developmental delay were reported for cases born ≥2004, following introduction of universal neonatal hearing screening.There were 302 congenital CMV cases (214 symptomatic, 88 asymptomatic). Congenital CMV was suspected in 70.6% by 30 days of age, with no differences across birth cohorts. Maternal CMV serology testing was associated with maternal illness during pregnancy but not birth cohort. There was increasing antiviral use for symptomatic cases, being used in 14% born 1999-2004, 19.6% born 2005-2010, and 44.4% born 2011-2016 (p 0.001). For those born ≥2004, hearing loss was reported in 42.1% of symptomatic and 26.6% of asymptomatic cases; while developmental delay was reported in 16.9% of symptomatic and 1.3% of asymptomatic cases.There appears to be under-reporting and under-recognition of congenital CMV despite increasing use of antiviral therapy. Universal newborn CMV screening should be considered to facilitate follow-up of affected children and targeted linkage into hearing and developmental services, and to provide population-level infant CMV epidemiology to support research and evaluation of antiviral and adjunctive therapies.

Along with the reduction in human papillomavirus (HPV) infection and cervical abnormalities as a result of the successful HPV vaccination program, Australia is adopting a new screening strategy. This involves a new paradigm moving from cervical cytological screening to molecular nucleic acid technology (NAT), using HPV DNA assays as primary screening methodology for cervical cancer prevention. These assays must strike a balance between sufficient clinical sensitivity to detect or predict high-grade cervical intraepithelial lesions, the precursor to cervical cancer, without being too sensitive and detecting transient infection not destined for disease. Ensuring the highest quality HPV NAT is thus a priority in order to reduce the possibility of falsely negative screens and manage the risk associated with false positive HPV NAT test results. How to do this needs informed discussion and on-going refinement of the screening algorithm. This is of relevance as more countries move to more sensitive HPV NAT tests for secondary prevention of cervical cancer and as more HPV assays become available.

The first reported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection was identified in Saudi Arabia in September 2012, since which time there have been over 2000 laboratory-confirmed cases, including 750 deaths in 27 countries. Nucleic acid testing (NAT) is the preferred method for the detection of MERS-CoV. A single round of a Proficiency Testing Program (PTP) was used to assess the capability of laboratories globally to accurately detect the presence of MERS-CoV using NAT. A panel of eleven lyophilized specimens containing different viral loads of MERS-CoV, common coronaviruses, and in vitro RNA transcripts was distributed to laboratories in all six World Health Organization regions. A total of 96 laboratories from 79 countries participating in the PTP, with 76 of 96 (79.2%) reporting correct MERS-CoV results for all nine scored specimens. A further 10 laboratories (10.4%) scored correctly in eight of nine specimens of the PTP. The majority of laboratories demonstrated satisfactory performance in detecting the presence of MERS-CoV using NAT. However, some laboratories require improved assay sensitivity, reduced cross contamination of samples, and improved speciation of coronavirus subtypes for potentially complex clinical specimens. Further PTP and enhanced links with expert laboratories globally may improve the laboratory performance.

Preterm birth is a common cause of adverse neonatal and childhood outcomes. It is commonly associated with infection of the maternal-fetal interface. The relationship between periodontitis and preterm labour is controversial.Control placental tissues from uncomplicated term births were compared with those from spontaneous preterm births for incidence of common periodontal bacteria. A chi-square analysis was used to compare the populations, with significance determined at p=0.05.The study group comprised 29 control women who had an uncomplicated term birth, 25 delivered by caesarean section and 4 vaginal deliveries, and 36 women with a spontaneous preterm labour and subsequent delivery at less than 34 weeks gestation. There were significant (p=0.05) differences between the preterm and term groups maternal age with 28.7 compared to 32.0 years old respectively. There was no significant (p=0.05) differences between the groups fetal risk factors or co-morbidities, except the preterm group had a significantly higher (p=0.05) rate of premature rupture of membrane (PROM). There were significantly (p=0.01) more Fusobacterium spp. in the placentas from term births than preterm births.This study found that the common periodontal pathogen, Fusobacterium spp., is not detected more in placentas from preterm birth and may potentially be lower, possibly resulting from bacterial ecological factors in term placentas.

Background Congenital cytomegalovirus (CMV) is the most common non-genetic cause of sensorineural hearing loss. Currently, there are no universal CMV screening programs for newborns or routine CMV testing of neonates with hearing loss in Australia, or elsewhere. Objectives This study was undertaken to determine the prevalence of congenital CMV infection in infants with hearing loss identified using routine resources via the Australian universal neonatal hearing screening (UNHS) program. Study design Infants who failed UNHS, referred for audiological testing and found to have permanent hearing loss were screened for CMV via PCR of urine and saliva. Congenital CMV was diagnosed if CMV was detected in infants ≤30 days of age, or using retrospective testing on stored new born screening cards, retrospective testing, or using clinical criteria if >30 days of age. The cohort was analyzed for time of testing and prevalence of congenital CMV determined. Results The Audiology Department reviewed 1669 infants who failed UNHS between 2009 and 2016. Thirty percent (502/1669) had permanent hearing loss confirmed, of whom 336/502 were offered CMV testing. A definite (n = 11) or probable (n = 8) diagnosis of congenital CMV occurred in 19/323 (5.9%), of whom definite diagnoses were made in 4/19 on tests positive prior to 21 days of life, in 5/19 who were positive on neonatal blood screening card (NBSC) testing, in 2/19 who were positive on placental testing. In 8/19 probable diagnoses were made based on positive testing between ages 23–42 days and a consistent clinical syndrome in the absence of another cause for hearing loss after genetic and other testing. CMV testing mirrored the timing of audiological testing, with ∼40% completing audiology and CMV testing by 21 days, and 64% by 30 days. Conclusion This program, utilizing existing clinical services identified probable congenital CMV in ∼6% of a large cohort failing UNHS with permanent hearing loss, of whom more than half were definite diagnoses. No additional assets were required to those already existing in this tertiary referral pediatric centre, whilst providing useful and timely data for clinical and audiological management.

For over a century, viruses have left a long trail of evidence implicating them as frequent suspects in the development of type 1 diabetes. Through vigorous interrogation of viral infections in individuals with islet autoimmunity and type 1 diabetes using serological and molecular virus detection methods, and mechanistic studies of virus infected human pancreatic β-cells, the prime suspects have been narrowed down to predominantly human enteroviruses. Here we provide a comprehensive overview of evidence supporting the hypothesised role of enteroviruses in the development of islet autoimmunity and type 1 diabetes. We also discuss concerns over the historical focus and investigation bias toward enteroviruses, and summarise current unbiased efforts aimed at characterising the complete population of viruses (the “virome”) contributing early in life to the development of islet autoimmunity and type 1 diabetes. Finally, we review the range of vaccine and antiviral drug candidates currently being evaluated in clinical trials for the prevention and potential treatment of type 1 diabetes.

To assess the knowledge, practice and attitudes of maternity clinicians regarding congenital cytomegalovirus (CMV). It is the most common congenital infection, and well-recognized cause of neurodevelopmental disability and hearing loss. New consensus recommendations state all pregnant women and health-care providers should be educated about congenital CMV infection and preventive measures.An email questionnaire was distributed in October 2015 to specialists, diplomates (general practitioners), and trainees of the Royal Australian New Zealand College of Obstetricians and Gynaecologists (RANZCOG), and Victorian and New South Wales midwives.774 responded: (37.3% specialists, 17.3% diplomates, 16.8% trainees, 28.6% midwives). Clinicians had variable knowledge of fetal sequelae, transmission routes and prevention. Overall, 30.2% felt confident about discussing CMV in pregnancy: less than 10% of midwives (7.4%) and less than half of specialists (47.1%, p .0001). Only 8.8% of respondents routinely discussed CMV prevention with pregnant women. The majority (69.3%) responded that professional societies should make practice recommendations, and 88% thought more patient information was needed, preferably leaflets.Australasian maternity clinicians lack confidence and knowledge about congenital CMV. Few (10%) routinely provide advice on prevention. There is urgent need for clinical guidance and patient information to reduce the burden of disease.

Repeat chlamydia detection after treatment is common, and there is concern that treatment failure may be a cause.Within a randomized trial, we established a prospective cohort of 600 participants with anogenital chlamydia diagnoses (200 each of women, heterosexual men, and men who have sex with men [MSM]). Participants were invited for repeat testing at 3 months and to complete a behavioral survey at 4 months. Positive samples were analyzed for organism DNA load and genovar. We estimated repeat chlamydia positivity, reinfection and treatment failure rates, and investigated the biological and behavioral factors associated with a repeat positive test.A total of 290 participants (100 women, 89 heterosexual men, 101 MSM) were retested at 1 to 4 months, with 43 repeat positives, including 26 classed as reinfection and 9 as treatment failures. Comparing MSM with heterosexual men and women combined, repeat positivity was higher (20.8% vs 11.6%, P = 0.04), and treatment failure was higher (6.9% vs 1.1%, P = 0.01), but there was no difference in reinfection rates (11.9% vs 7.4%, P = 0.21). Among MSM, the odds of repeat positivity increased by 90% with each additional log organism load in the original specimen (baseline) (adjusted odds ratio, 1.9; 95% confidence interval, 1.1-3.2). Among heterosexuals, the odds of repeat positivity decreased by 10% with each additional week delay in being retested for chlamydia (adjusted odds ratio, 0.9; 95% confidence interval, 0.8-0.9).Positive retests were more common among MSM than heterosexuals. Treatment failure was more common in MSM with rectal chlamydia, reinforcing concerns about azithromycin treatment failure.