Epigenetic scars of CD8+ T cell exhaustion persist after cure of chronic infection in humans.

T cell exhaustion is an induced state of dysfunction that arises in response to chronic infection and cancer. Exhausted CD8+ T cells acquire a distinct epigenetic state, but it is not known whether that chromatin landscape is fixed or plastic following the resolution of a chronic infection. Here we show that the epigenetic state of exhaustion is largely irreversible, even after curative therapy. Analysis of chromatin accessibility in HCV- and HIV-specific responses identifies a core epigenetic program of exhaustion in CD8+ T cells, which undergoes only limited remodeling before and after resolution of infection. Moreover, canonical features of exhaustion, including super-enhancers near the genes TOX and HIF1A, remain 'epigenetically scarred.' T cell exhaustion is therefore a conserved epigenetic state that becomes fixed and persists independent of chronic antigen stimulation and inflammation. Therapeutic efforts to reverse T cell exhaustion may require new approaches that increase the epigenetic plasticity of exhausted T cells.

Real-time analysis of hospital length of stay in a mixed SARS-CoV-2 Omicron and Delta epidemic in New South Wales, Australia.

BACKGROUND: The distribution of the duration that clinical cases of COVID-19 occupy hospital beds (the 'length of stay') is a key factor in determining how incident caseloads translate into health system burden. Robust estimation of length of stay in real-time requires the use of survival methods that can account for right-censoring induced by yet unobserved events in patient progression (e.g. discharge, death). In this study, we estimate in real-time the length of stay distributions of hospitalised COVID-19 cases in New South Wales, Australia, comparing estimates between a period where Delta was the dominant variant and a subsequent period where Omicron was dominant. METHODS: Using data on the hospital stays of 19,574 individuals who tested positive to COVID-19 prior to admission, we performed a competing-risk survival analysis of COVID-19 clinical progression. RESULTS: During the mixed Omicron-Delta epidemic, we found that the mean length of stay for individuals who were discharged directly from ward without an ICU stay was, for age groups 0-39, 40-69 and 70 +, respectively, 2.16 (95% CI: 2.12-2.21), 3.93 (95% CI: 3.78-4.07) and 7.61 days (95% CI: 7.31-8.01), compared to 3.60 (95% CI: 3.48-3.81), 5.78 (95% CI: 5.59-5.99) and 12.31 days (95% CI: 11.75-12.95) across the preceding Delta epidemic (1 July 2021-15 December 2021). We also considered data on the stays of individuals within the Hunter New England Local Health District, where it was reported that Omicron was the only circulating variant, and found mean ward-to-discharge length of stays of 2.05 (95% CI: 1.80-2.30), 2.92 (95% CI: 2.50-3.67) and 6.02 days (95% CI: 4.91-7.01) for the same age groups. CONCLUSIONS: Hospital length of stay was substantially reduced across all clinical pathways during a mixed Omicron-Delta epidemic compared to a prior Delta epidemic, contributing to a lessened health system burden despite a greatly increased infection burden. Our results demonstrate the utility of survival analysis in producing real-time estimates of hospital length of stay for assisting in situational assessment and planning of the COVID-19 response.

Sentinel cluster of locally acquired Japanese encephalitis in southern Australia.

Prior to January 2022, only a single case of infection with Japanese encephalitis virus (JEV) had been reported on the Australian mainland, acquired in the northern extremity on Cape York. We report the clinical characteristics of the sentinel cluster of cases that confirmed the local acquisition of JEV in southern Australia along the Murray River bordering New South Wales and Victoria.

Sexual Misconduct: What Does a 20-Year Review of Cases in Quebec Reveal about the Characteristics of Professionals, Victims, and the Disciplinary Process?

While there is a considerable body of literature on sexual aggression, we know much less about the violation of sexual boundaries within professional relationships. To address this knowledge gap, the characteristics of cases of sexual misconduct in the province of Quebec were extracted, based on a search of published disciplinary decisions between 1998 and 2020, using the legal databases CANLII and SOQUIJ. The search yielded 296 decisions including 249 male and 47 female members from 22 professional orders, and involving 470 victims. Results indicate that male professionals approaching mid-career accounted for a greater proportion of cases of sexual misconduct. Moreover, physical and mental health professionals were overrepresented in cases, as were female adult victims. Acts of sexual misconduct concerned mostly sexual touching and intercourse and occurred during consultations. Female professionals were more inclined to establish romantic and sexual relationships with clients than their male counterparts. Of the 92.0% of professionals found guilty of at least one count of sexual misconduct, two thirds eventually returned to practice. Following the guilty verdict, few faced rehabilitative measures. Recommendations are provided for the prevention of sexual recidivism and the accompaniment of victims of sexual misconduct throughout the disciplinary process.

Sexual self-concept, functioning, and practices of women with binge eating episodes.

PURPOSE: Positive sexuality has received little empirical attention in relation to eating disorders. Two tendencies related to sexuality have been identified among women with anorexia nervosa (avoidance) and bulimia nervosa (disinhibition), but it is unclear if they also apply to women with binge eating episodes without compensatory behaviors. This study aimed at (1) exploring the sexual self-concept, functioning, and practices of women with binge eating episodes with or without comorbid restrictive and/or compensatory behaviors, considering past experiences of violence, and (2) verifying the presence of distinct profiles of sexual dispositions among this population. METHODS: In total, 253 women reporting recurrent episodes of loss of control related to food intake in the past 5 years, completed a web-based questionnaire. Descriptive and correlational analyses were conducted to outline participants' sexual self-concept, functioning, and practices and to examine the relationship between these factors. A two-step cluster analysis was also performed to determine whether participants presented distinct profiles of sexual dispositions. RESULTS: Participants were generally characterized by a negative sexual self-concept and poor sexual functioning. While a first subgroup of participants displayed a pattern of sexual difficulties and avoidance, a second subgroup had a positive sexual self-concept, better sexual functioning and a wider range of sexual practices. Subgroups did not differ relative to binge eating. CONCLUSIONS: Sexuality offers a platform for positive embodiment, which can lead to the improvement of body image and mind-body connection and may thus constitute an essential clinical target to improve treatment related to binge eating episodes. LEVEL OF EVIDENCE: Level II: The experimental study is a non-randomized controlled trial.

Towards healthier and more sustainable diets in the Australian context: comparison of current diets with the Australian Dietary Guidelines and the EAT-Lancet Planetary Health Diet.

BACKGROUND: There is increasing focus on moving populations towards healthier and more environmentally sustainable dietary patterns. The Australian Dietary Guidelines provide dietary patterns that promote health and wellbeing. It is unclear how these guidelines align with the more recently published global recommendations of the EAT-Lancet Planetary Health Reference Diet, and how Australian diets compare to both sets of recommendations. METHODS: Data from one 24-h recall collected for the 2011-13 National Nutrition and Physical Activity Survey were analysed for 5,920 adults aged 19-50 years. Subgroups of this population were identified by diet quality and lower or higher consumption of foods often considered to be environmentally intensive (higher animal meat and dairy foods) or associated with healthiness (higher vegetables and lower discretionary choices). Food group and nutrient composition of Australian diets were compared to diets modelled on the Australian Dietary Guidelines and Planetary Health Reference Diet. The environmental impacts of diets were estimated using an index of combined metrics. RESULTS: Compared with the Planetary Health Reference Diet, the Australian Dietary Guidelines contained more servings of the vegetable, dairy and alternatives, fruit, and discretionary choices. The amount of meat and alternatives was higher in the Planetary Health Reference Diet than Australian Dietary Guidelines due to the inclusion of more plant-based meat alternatives. The average Australian diet contained two to almost four times the Australian Dietary Guidelines and Planetary Health Reference Diet maximum recommended intake of discretionary choices, and provided inadequate amounts of the vegetables, cereals, unsaturated fats and meats and alternatives food groups, primarily due to lower intakes of plant-based alternatives. The average Australian diet also contained less dairy and alternatives than the Australian Dietary Guidelines. In the average Australian diet, red meat and poultry contributed 73% to the total servings of meat and alternatives compared to 33% and 10% for the Australian Dietary Guidelines and Planetary Health Reference Diet respectively. The modelled Australian Dietary Guidelines diet met the relevant nutrient reference value for all 22 nutrients examined, whereas the Planetary Health Reference Diet contained an inadequate amount of calcium. The environmental impact scores of the Planetary Health Reference Diet and Australian Dietary Guidelines were 31% and 46% lower than the average Australian diet. CONCLUSIONS: Significant changes are required for Australians' dietary intake to align more closely with national and global dietary recommendations for health and environmental sustainability.

Adolescents' Perception of Their Sexual Self, Relational Capacities, Attitudes Towards Sexual Pleasure and Sexual Practices: a Descriptive Analysis.

Positive psychosexual development in adolescence is crucial to sexual health. Evidence suggests that adolescent's psychosexual development is influenced by the sexual self-concept, relational skills, attitudes toward sexual pleasure, and sexual practices. To date, however, understanding of normative dispositions and experiences that positively shape adolescents' psychosexual development remains limited. The goal of the study was to provide a descriptive analysis of adolescents' perceptions of their sexual self, relational skills, and attitudes towards sexual pleasure as well as their sexual practices while considering age and gender differences. A Canadian sample of 1584 adolescents (49.7% girls, 49.4% boys and 0.9% gender diverse) aged 14 to 18 years old (M = 15.53, SD = 0.93) completed a self-reported questionnaire evaluating various aspects of sexuality and sexual practices. Results indicated that most youth are sexually active through autoerotic or partnered sexual practices, and that positive perceptions towards the sexual self, relational capacities and pleasure increase with age. Moreover, compared to girls, boys presented a more positive sexual self-concept, less positive perceptions of their relational skills and they were more likely to report autoerotic sexual practices. Cluster analysis supported classifying adolescents into the following profiles: positive, mildly positive, mildly negative and negative perception of the sexual self and sexuality. These profiles varied according to sexual practices, gender and age. This study provides further insight into general patterns and heterogeneity of adolescents' sexuality that are relevant for adapting sexuality education and sexual health intervention.

Treatment of invasive IMP-4 Enterobacter cloacae infection in transplant recipients using ceftazidime/avibactam with aztreonam: A case series and literature review.

Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) are an emerging threat in both solid organ and stem cell transplant recipients. Invasive CPE infections in transplant recipients are associated with a high mortality, often due to limited therapeutic options and antibacterial toxicities. One of the most therapeutically challenging group of CPE are the metallo-ß-lactamase (MBL)-producing Gram-negative bacteria, which are now found worldwide, and often need treatment with older, highly toxic antimicrobial regimens. Newer ß-lactamase inhibitors such as avibactam have well-established activity against certain carbapenemases such as Klebsiella pneumoniae carbapenemases (KPC), but have no activity against MBL-producing organisms. Conversely, aztreonam has activity against MBL-producing organisms but is often inactivated by other co-existing ß-lactamases. Here, we report four cases of invasive MBL-CPE infections in transplant recipients caused by IMP-4-producing Enterobacter cloacae who were successfully treated with a new, mechanism-driven antimicrobial combination of ceftazidime/avibactam with aztreonam. This novel antimicrobial combination offers a useful treatment option for high-risk patients with CPE infection, with reduced drug interactions and toxicity.

Parental food choices for children when eating out: attitudes and impact of healthy choice menu labelling based on a hypothetical scenario.

OBJECTIVE: To understand how healthy menu labelling information is used by parents/caregivers and where it fits within predictors of healthy meal choices when eating out. DESIGN: Parents were recruited to complete a 15-min observational, online survey regarding their experiences and hypothetical choices when eating out with their child/ren. SETTING: Australia. PARTICIPANTS: Eligible participants had one or more child/ren aged between 2 and 12 years and attended cafes, restaurants, hotels and clubs (CRHC) for lunch or dinner at least four times a year. Of initial respondents (n 1802), 92·5 % provided complete and valid data. Participants were 84·7 % female, ranging from 18 to 68 years old. RESULTS: 98·3 % believed that healthier alternatives should be available for children in CRHC. For general food choices, health was a strong motivator (45·7 %); however, parents reported eating at CRHC mainly for pleasure or a treat (61·2 %) and being driven by children's taste preferences (85·9 %) when selecting menu items. 59·0 % of orders included a combination of healthy and traditional items. 42·0 % of the sample were influenced by the healthy choice (HC) labelling. Multiple regression revealed that, in addition to some demographic variables, the percent of HC ordered was positively associated with self-reported parent vegetable consumption, making food choices for the children for health reasons, familiarity with HC items and making order choices due to dietary needs and good nutrition. CONCLUSIONS: Despite a preference for availability of healthier children's menu choices in CRHC, menu labelling highlighting healthy options may have limited impact relative to child preferences.

Levels of Human Immunodeficiency Virus DNA Are Determined Before ART Initiation and Linked to CD8 T-Cell Activation and Memory Expansion.

Initiation of antiretroviral therapy (ART) in early compared with chronic human immunodeficiency virus (HIV) infection is associated with a smaller HIV reservoir. This longitudinal analysis of 60 individuals who began ART during primary HIV infection (PHI) investigates which pre- and posttherapy factors best predict HIV DNA levels (a correlate of reservoir size) after treatment initiation during PHI. The best predictor of HIV DNA at 1 year was pre-ART HIV DNA, which was in turn significantly associated with CD8 memory T-cell differentiation (effector memory, naive, and T-bet-Eomes- subsets), CD8 T-cell activation (CD38 expression) and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) expression on memory T cells. No associations were found for any immunological variables after 1 year of ART. Levels of HIV DNA are determined around the time of ART initiation in individuals treated during PHI. CD8 T-cell activation and memory expansion are linked to HIV DNA levels, suggesting the importance of the initial host-viral interplay in eventual reservoir size.

Compassionate drug (mis)use during pandemics: lessons for COVID-19 from 2009.

BACKGROUND: New emerging infections have no known treatment. Assessing potential drugs for safety and efficacy enables clinicians to make evidence-based treatment decisions and contributes to overall outbreak control. However, it is difficult to launch clinical trials in the unpredictable environment of an outbreak. We conducted a bibliometric systematic review for the 2009 influenza pandemic to determine the speed and quality of evidence generation for treatments. This informs approaches to high-quality evidence generation in this and future pandemics. METHODS: We searched PubMed for all clinical data (including clinical trial, observational and case series) describing treatment for patients with influenza A(H1N1)pdm09 and ClinicalTrials.gov for research that aimed to enrol patients with the disease. RESULTS: Thirty-three thousand eight hundred sixty-nine treatment courses for patients hospitalised with A(H1N1)pdm09 were detailed in 160 publications. Most were retrospective observational studies or case series. Five hundred ninety-two patients received treatment (or placebo) as participants in a registered interventional clinical trial with results publicly available. None of these registered trial results was available during the timeframe of the pandemic, and the median date of publication was 213 days after the Public Health Emergency of International Concern ended. CONCLUSION: Patients were frequently treated for pandemic influenza with drugs not registered for this indication, but rarely under circumstances of high-quality data capture. The result was a reliance on use under compassionate circumstances, resulting in continued uncertainty regarding the potential benefits and harms of anti-viral treatment. Rapid scaling of clinical trials is critical for generating a quality evidence base during pandemics.

Food group intake at self-reported eating occasions across the day: secondary analysis of the Australian National Nutrition Survey 2011-2012.

OBJECTIVE: To examine core and discretionary food and beverage intake at eating occasions, and to explore the variation in consumption by age and gender in Australian adults and children. DESIGN: The study utilised one 24-h dietary recall with self-reported eating occasions from a nationally representative sample of Australians. Average servings of each food group for age and gender subpopulations were compared with the Australian Dietary Guidelines. The percentage contribution of each eating occasion to total daily food group intake and typical composition of eating occasions were described. Frequently consumed discretionary foods were reported for eating occasions by age and gender. SETTING: 2011-2012 Australian National Nutrition and Physical Activity Survey. PARTICIPANTS: 12 153 Australian people aged 2 years and above. RESULTS: Grains were consumed in equal proportions throughout the day across all age and gender subgroups, while remaining core food groups were unequally distributed, featuring more prominently at specific eating occasions. Children consumed two-thirds of their fruit intake as snacks, and up to three quarters of adults' vegetable and meat intake was consumed at dinner. Children consumed more of their discretionary intake at mid-meals, while adults consumed a greater proportion as part of a main meal. CONCLUSIONS: The present study provides a detailed understanding about when food groups are consumed, the 'typical' meal composition across the day, and how consumption patterns and compliance with dietary guidelines differ by age group and gender. These findings can assist in developing more specific nutrition messages which may help to achieve greater improvements in population dietary intake.

Exhaustion of Activated CD8 T Cells Predicts Disease Progression in Primary HIV-1 Infection.

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n = 122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression. Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/µl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed. Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants. Expression of 'exhaustion' or 'immune checkpoint' markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches.

Inflammatory co-morbidities in HIV+ individuals: learning lessons from healthy ageing.

Increased life expectancy due to improved efficacy of cART has uncovered an increased risk of age-related morbidities in HIV+ individuals and catalyzed significant research into mechanisms driving these diseases. HIV infection increases the risk of non-communicable diseases common in the aged, including cardiovascular disease, neurocognitive decline, non-AIDS malignancies, osteoporosis, and frailty. These observations suggest that HIV accelerates immunological ageing, and there are many immunological similarities with the aged, including shortened telomeres, accumulation of senescent T cells and altered monocyte phenotype/function. However, the most critical similarity between HIV+ individuals and the elderly, which most likely underpins the heightened risk of non-communicable diseases, is chronic inflammation and associated immune activation. Here, we review the similarities between HIV+ individuals and the aged regarding the pathogenesis of inflammatory diseases, the current evidence for mechanisms driving these processes and discuss current and potential therapeutic strategies for addressing inflammatory co-morbidity in HIV+ infection.

Estimation of the UV susceptibility of aerosolized SARS-CoV-2 to 254 nm irradiation using CFD-based room disinfection simulations.

The recent COVID-19 pandemic has raised interest in efficient air disinfection solutions. The application of germicidal ultraviolet (GUV) irradiation is an excellent contender to prevent airborne transmission of COVID-19, as well as other existing and future infectious airborne diseases. While GUV has already been proven effective in inactivating SARS-CoV-2, quantitative data on UV susceptibility and dose requirements, needed to predict and optimize the performance of GUV solutions, is still limited. In this study, the UV susceptibility of aerosolized SARS-CoV-2 to 254 nm ultraviolet (UV) irradiation is investigated. This is done by employing 3D computational fluid dynamics based simulations of SARS-CoV-2 inactivation in a test chamber equipped with an upper-room UV-C luminaire and comparing the results to previously published measurements performed in the same test chamber. The UV susceptibility found in this study is (0.6 ± 0.2) m2/J, which is equivalent to a D90 dose between 3 and 6 J/m2. These values are in the same range as previous estimations based on other corona viruses and inactivation data reported in literature.

ß-Glucan content and in vitro bile-acid binding capacity of Agaricus bisporus and Pleurotus spp.

The cholesterol lowering properties of oats and barley, attributed to their high ß-glucan content, are well established, but it remains unclear whether mushrooms, also rich in ß-glucan, exhibit a similar functionality. We aimed to quantify the ß-glucan content of commonly consumed Australian mushrooms and evaluated their bile acid binding capacity, the primary cholesterol lowering mechanism of ß-glucan. Raw, boiled and fried Australian grown Agaricus bisporus (button, cup, flat and brown mushrooms) and Pleurotus spp. (shimeji and oyster) along with oats were freeze-dried and the ß-glucan content was determined. The bile acid binding capacity of these samples was assessed using an in vitro digestion assay. The ß-glucan content of freeze-dried raw A. bisporus mushrooms (4.5-8.1 g per 100 g) was similar to that of oats (7.6 g per 100 g, all p > 0.05), whereas Pleurotus mushrooms contained ∼5 times more ß-glucan (32.5-37.4 g, p < 0.05). Boiling increased the ß-glucan content of oyster, button, flat and brown mushrooms by 3-7% (p < 0.05), but did not affect the ß-glucan content of shimeji or cup mushrooms. Frying had no effect on any mushroom type. The bile acid binding capacity of A. bisporus mushrooms (29-36%) was equivalent to that of raw oats (36%, p > 0.05), whereas the bile acid binding capacity of oyster mushrooms (22%) was lower than that of oats (p < 0.05). Both boiling and frying increased the bile acid binding capacity. The cholesterol lowering effects of A. bisporus mushrooms and the acceptability of consumption at the required levels need to be confirmed by clinical trials.

Rapid antiretroviral therapy in primary HIV-1 infection enhances immune recovery.

OBJECTIVE: We present findings from a large cohort of individuals treated during primary HIV infection (PHI) and examine the impact of time from HIV-1 acquisition to antiretroviral therapy (ART) initiation on clinical outcomes. We also examine the temporal changes in the demographics of individuals presenting with PHI to inform HIV-1 prevention strategies. METHODS: Individuals who fulfilled the criteria of PHI and started ART within 3 months of confirmed HIV-1 diagnosis were enrolled between 2009 and 2020. Baseline demographics of those diagnosed between 2009 and 2015 (before preexposure prophylaxis (PrEP) and universal ART availability) and 2015-2020 (post-PrEP and universal ART availability) were compared. We examined the factors associated with immune recovery and time to viral suppression. RESULTS: Two hundred four individuals enrolled, 144 from 2009 to 2015 and 90 from 2015 to 2020; median follow-up was 33 months. At PHI, the median age was 33 years; 4% were women, 39% were UK-born, and 84% were MSM. The proportion of UK-born individuals was 47% in 2009-2015, compared with 29% in 2015-2020. There was an association between earlier ART initiation after PHI diagnosis and increased immune recovery; each day that ART was delayed was associated with a lower likelihood of achieving a CD4 + cell count more than 900 cells/µl [hazard ratio 0.99 (95% confidence interval, 95% CI 0.98-0.99), P  = 0.02) and CD4/CD8 more than 1.0 (hazard ratio 0.98 (95% CI 0.97-0.99). CONCLUSION: Early initiation of ART at PHI diagnosis is associated with enhanced immune recovery, providing further evidence to support immediate ART in the context of PHI. Non-UK-born MSM accounts for an increasing proportion of those with primary infection; UK HIV-1 prevention strategies should better target this group.

Non-SARS-CoV-2 respiratory viral detection and whole genome sequencing from COVID-19 rapid antigen test devices: a laboratory evaluation study.

BACKGROUND: There has been high uptake of rapid antigen test device use for point-of-care COVID-19 diagnosis. Individuals who are symptomatic but test negative on COVID-19 rapid antigen test devices might have a different respiratory viral infection. We aimed to detect and sequence non-SARS-CoV-2 respiratory viruses from rapid antigen test devices, which could assist in the characterisation and surveillance of circulating respiratory viruses in the community. METHODS: We applied archival clinical nose and throat swabs collected between Jan 1, 2015, and Dec 31, 2022, that previously tested positive for a common respiratory virus (adenovirus, influenza, metapneumovirus, parainfluenza, rhinovirus, respiratory syncytial virus [RSV], or seasonal coronavirus; 132 swabs and 140 viral targets) on PCR to two commercially available COVID-19 rapid antigen test devices, the Panbio COVID-19 Ag Rapid Test Device and Roche SARS-CoV-2 Antigen Self-Test. In addition, we collected 31 COVID-19 rapid antigen test devices used to test patients who were symptomatic at The Royal Melbourne Hospital emergency department in Melbourne, Australia. We extracted total nucleic acid from the device paper test strips and assessed viral recovery using multiplex real-time PCR (rtPCR) and capture-based whole genome sequencing. Sequence and genome data were analysed through custom computational pipelines, including subtyping. FINDINGS: Of the 140 respiratory viral targets from archival samples, 89 (64%) and 88 (63%) were positive on rtPCR for the relevant taxa following extraction from Panbio or Roche rapid antigen test devices, respectively. Recovery was variable across taxa: we detected influenza A in nine of 18 samples from Panbio and seven of 18 from Roche devices; parainfluenza in 11 of 20 samples from Panbio and 12 of 20 from Roche devices; human metapneumovirus in 11 of 16 from Panbio and 14 of 16 from Roche devices; seasonal coronavirus in eight of 19 from Panbio and two of 19 from Roche devices; rhinovirus in 24 of 28 from Panbio and 27 of 28 from Roche devices; influenza B in four of 15 in both devices; and RSV in 16 of 18 in both devices. Of the 31 COVID-19 devices collected from The Royal Melbourne Hospital emergency department, 11 tested positive for a respiratory virus on rtPCR, including one device positive for influenza A virus, one positive for RSV, four positive for rhinovirus, and five positive for SARS-CoV-2. Sequences of target respiratory viruses from archival samples were detected in 55 (98·2%) of 56 samples from Panbio and 48 (85·7%) of 56 from Roche rapid antigen test devices. 98 (87·5%) of 112 viral genomes were completely assembled from these data, enabling subtyping for RSV and influenza viruses. All 11 samples collected from the emergency department had viral sequences detected, with near-complete genomes assembled for influenza A and RSV. INTERPRETATION: Non-SARS-CoV-2 respiratory viruses can be detected and sequenced from COVID-19 rapid antigen devices. Recovery of near full-length viral sequences from these devices provides a valuable opportunity to expand genomic surveillance programmes for public health monitoring of circulating respiratory viruses. FUNDING: Australian Government Medical Research Future Fund and Australian National Health and Medical Research Council.

Characterising HIV-1 transmission in Victoria, Australia: a molecular epidemiological study.

Background: In Australia the incidence of HIV has declined steadily, yet sustained reduction of HIV transmission in this setting requires improved public health responses. As enhanced public health responses and prioritisation of resources may be guided by molecular epidemiological data, here we aimed to assess the applicability of these approaches in Victoria, Australia. Methods: A comprehensive collection of HIV-1 pol sequences from individuals diagnosed with HIV in Victoria, Australia, between January 1st 2000 and December 31st 2020 were deidentified and used as the basis of our assessment. These sequences were subtyped and surveillance drug resistance mutations (SDRMs) identified, before definition of transmission groups was performed using HIV-TRACE (0.4.4). Phylodynamic methods were applied using BEAST (2.6.6), assessing effective reproductive numbers for large groups, and additional demographic data were integrated to provide a high resolution view of HIV transmission in Victoria on a decadal time scale. Findings: Based on standard settings for HIV-TRACE, 70% (2438/3507) of analysed HIV-1 pol sequences were readily assigned to a transmission group. Individuals in transmission groups were more commonly males (aOR 1.50), those born in Australia (aOR 2.13), those with probable place of acquisition as Victoria (aOR 6.73), and/or those reporting injectable drug use (aOR 2.13). SDRMs were identified in 375 patients (10.7%), with sustained transmission of these limited to a subset of smaller groups. Informative patterns of epidemic growth, stabilisation, and decline were observed; many transmission groups showed effective reproductive numbers (R e ) values reaching greater than 4.0, representing considerable epidemic growth, while others maintained low R e values. Interpretation: This study provides a high resolution view of HIV transmission in Victoria, Australia, and highlights the potential of molecular epidemiology to guide and enhance public health responses in this setting. This informs ongoing discussions with community groups on the acceptability and place of molecular epidemiological approaches in Australia. Funding: National Health and Medical Research Council, Australian Research Council.