Medicine (RMH) - Research Publications

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    Literature Highlights.
    Trauer, JM ; Tiberi, S ; Graham, SM ; Blackbourn, HD (International Union Against Tuberculosis and Lung Disease, 2023-10-01)
    Literature Highlights is a digest of notable papers recently published in the leading respiratory journals, allowing our readers to stay up-to-date with research advances. Coverage in this issue includes time to smear and culture conversion during TB treatment; probability of diagnosing ventilator-associated pneumonia in intensive care and use of antimicrobials; optimising computer-aided chest X-ray to diagnose intra-thoracic TB in children; and clinical standards for asthma in low- and middle-income countries.
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    Transmission of SARS-CoV-2 in a primary school setting with and without public health measures using real-world contact data: A modelling study.
    Yan, L ; Talic, S ; Wild, H ; Gasevic, D ; Gasević, D ; Ilic, D ; Deppeler, J ; Corrigan, D ; Martinez-Maldonado, R ; Trauer, J (Edinburgh University Global Health Society, 2022-10-01)
    BACKGROUND: Stringent public health measures have been shown to influence the transmission of SARS-CoV-2 within school environments. We investigated the potential transmission of SARS-CoV-2 in a primary school setting with and without public health measures, using fine-grained physical positioning traces captured before the COVID-19 pandemic. METHODS: Approximately 172.63 million position data from 98 students and six teachers from an open-plan primary school were used to predict a potential transmission of SARS-CoV-2 in primary school settings. We first estimated the daily average number of contacts of students and teachers with an infected individual during the incubation period. We then used the Reed-Frost model to estimate the probability of transmission per contact for the SARS-CoV-2 Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron variant (B.1.1.529). Finally, we built a binomial distribution model to estimate the probability of onward transmission in schools with and without public health measures, including face masks and physical distancing. RESULTS: An infectious student would have 49.1 (95% confidence interval (CI) = 46.1-52.1) contacts with their peers and 2.00 (95% CI = 1.82-2.18) contacts with teachers per day. An infectious teacher would have 47.6 (95% CI = 45.1-50.0) contacts with students and 1.70 (95% CI = 1.48-1.92) contacts with their colleague teachers per day. While the probability of onward SARS-CoV-2 transmission was relatively low for the Alpha and Delta variants, the risk increased for the Omicron variant, especially in the absence of public health measures. Onward teacher-to-student transmission (88.9%, 95% CI = 88.6%-89.1%) and teacher-to-teacher SARS-CoV-2 transmission (98.4%, 95% CI = 98.5%-98.6%) were significantly higher for the Omicron variant without public health measures in place. CONCLUSIONS: Our findings illustrate that, despite a lower frequency of close contacts, teacher-to-teacher close contacts demonstrated a higher risk of transmission per contact of SARS-CoV-2 compared to student-to-student close contacts. This was especially significant with the Omicron variant, with onward transmission more likely occurring from teacher index cases than student index cases. Public health measures (eg, face masks and physical distance) seem essential in reducing the risk of onward transmission within school environments.
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    COVID-19 collaborative modelling for policy response in the Philippines, Malaysia and Vietnam.
    Hughes, A ; Ragonnet, R ; Jayasundara, P ; Ngo, H-A ; de Lara-Tuprio, E ; Estuar, MRJ ; Teng, TR ; Boon, LK ; Peariasamy, KM ; Chong, Z-L ; Ghazali, IMM ; Fox, GJ ; Nguyen, T-A ; Le, L-V ; Abayawardana, M ; Shipman, D ; McBryde, ES ; Meehan, MT ; Caldwell, JM ; Trauer, JM (Elsevier, 2022-12)
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    Estimating the long-term effects of mass screening for latent and active tuberculosis in the Marshall Islands
    Ragonnet, R ; Williams, BM ; Largen, A ; Nasa, J ; Jack, T ; Langinlur, MK ; Ko, E ; Rahevar, K ; Islam, T ; Denholm, JT ; Marais, BJ ; Marks, GB ; McBryde, ES ; Trauer, JM (OXFORD UNIV PRESS, 2022-10-13)
    BACKGROUND: Ambitious population-based screening programmes for latent and active tuberculosis (TB) were implemented in the Republic of the Marshall Islands in 2017 and 2018. METHODS: We used a transmission dynamic model of TB informed by local data to capture the Marshall Islands epidemic's historical dynamics. We then used the model to project the future epidemic trajectory following the active screening interventions, as well as considering a counterfactual scenario with no intervention. We also simulated future scenarios including periodic interventions similar to those previously implemented, to assess their ability to reach the End TB Strategy targets and TB pre-elimination in the Marshall Islands. RESULTS: The screening activities conducted in 2017 and 2018 were estimated to have reduced TB incidence and mortality by around one-third in 2020, and are predicted to achieve the End TB Strategy milestone of 50% incidence reduction by 2025 compared with 2015. Screening interventions had a considerably greater impact when latent TB screening and treatment were included, compared with active case finding alone. Such combined programmes implemented at the national level could achieve TB pre-elimination around 2040 if repeated every 2 years. CONCLUSIONS: Our model suggests that it would be possible to achieve TB pre-elimination by 2040 in the Marshall Islands through frequent repetition of the same interventions as those already implemented in the country. It also highlights the importance of including latent infection testing in active screening activities.
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    Detecting Mycobacterium tuberculosis Infection in Children Migrating to Australia.
    Laemmle-Ruff, I ; Graham, SM ; Williams, B ; Horyniak, D ; Majumdar, SS ; Paxton, GA ; Soares Caplice, LV ; Hellard, ME ; Trauer, JM (Centers for Disease Control and Prevention (CDC), 2022-09)
    In 2015, Australia updated premigration screening for tuberculosis (TB) disease in children 2-10 years of age to include testing for infection with Mycobacterium tuberculosis and enable detection of latent TB infection (LTBI). We analyzed TB screening results in children <15 years of age during November 2015-June 2017. We found 45,060 child applicants were tested with interferon-gamma release assay (IGRA) (57.7% of tests) or tuberculin skin test (TST) (42.3% of tests). A total of 21 cases of TB were diagnosed: 4 without IGRA or TST, 10 with positive IGRA or TST, and 7 with negative results. LTBI was detected in 3.3% (1,473/44,709) of children, for 30 applicants screened per LTBI case detected. LTBI-associated factors included increasing age, TB contact, origin from a higher TB prevalence region, and testing by TST. Detection of TB and LTBI benefit children, but the updated screening program's effect on TB in Australia is likely to be limited.
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    Sustaining effective COVID-19 control in Malaysia through large-scale vaccination
    Jayasundara, P ; Peariasamy, KM ; Law, KB ; Abd Rahim, KNK ; Lee, SW ; Ghazali, IMM ; Abayawardana, M ; Linh-Vi, L ; Khalaf, RKS ; Razali, K ; Le, X ; Chong, ZL ; McBryde, ES ; Meehan, MT ; Caldwell, JM ; Ragonnet, R ; Trauer, JM (ELSEVIER, 2021-12)
    INTRODUCTION: As of 3rd June 2021, Malaysia is experiencing a resurgence of COVID-19 cases. In response, the federal government has implemented various non-pharmaceutical interventions (NPIs) under a series of Movement Control Orders and, more recently, a vaccination campaign to regain epidemic control. In this study, we assessed the potential for the vaccination campaign to control the epidemic in Malaysia and four high-burden regions of interest, under various public health response scenarios. METHODS: A modified susceptible-exposed-infectious-recovered compartmental model was developed that included two sequential incubation and infectious periods, with stratification by clinical state. The model was further stratified by age and incorporated population mobility to capture NPIs and micro-distancing (behaviour changes not captured through population mobility). Emerging variants of concern (VoC) were included as an additional strain competing with the existing wild-type strain. Several scenarios that included different vaccination strategies (i.e. vaccines that reduce disease severity and/or prevent infection, vaccination coverage) and mobility restrictions were implemented. RESULTS: The national model and the regional models all fit well to notification data but underestimated ICU occupancy and deaths in recent weeks, which may be attributable to increased severity of VoC or saturation of case detection. However, the true case detection proportion showed wide credible intervals, highlighting incomplete understanding of the true epidemic size. The scenario projections suggested that under current vaccination rates complete relaxation of all NPIs would trigger a major epidemic. The results emphasise the importance of micro-distancing, maintaining mobility restrictions during vaccination roll-out and accelerating the pace of vaccination for future control. Malaysia is particularly susceptible to a major COVID-19 resurgence resulting from its limited population immunity due to the country's historical success in maintaining control throughout much of 2020.
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    Mental Health Outcomes in Australian Healthcare and Aged-Care Workers during the Second Year of the COVID-19 Pandemic
    McGuinness, SL ; Johnson, J ; Eades, O ; Cameron, PA ; Forbes, A ; Fisher, J ; Grantham, K ; Hodgson, C ; Hunter, P ; Kasza, J ; Kelsall, HL ; Kirkman, M ; Russell, G ; Russo, PL ; Sim, MR ; Singh, KP ; Skouteris, H ; Smith, KL ; Stuart, RL ; Teede, HJ ; Trauer, JM ; Udy, A ; Zoungas, S ; Leder, K (MDPI, 2022-05)
    OBJECTIVE: the COVID-19 pandemic has incurred psychological risks for healthcare workers (HCWs). We established a Victorian HCW cohort (the Coronavirus in Victorian Healthcare and Aged-Care Workers (COVIC-HA) cohort study) to examine COVID-19 impacts on HCWs and assess organisational responses over time. METHODS: mixed-methods cohort study, with baseline data collected via an online survey (7 May-18 July 2021) across four healthcare settings: ambulance, hospitals, primary care, and residential aged-care. Outcomes included self-reported symptoms of depression, anxiety, post-traumatic stress (PTS), wellbeing, burnout, and resilience, measured using validated tools. Work and home-related COVID-19 impacts and perceptions of workplace responses were also captured. RESULTS: among 984 HCWs, symptoms of clinically significant depression, anxiety, and PTS were reported by 22.5%, 14.0%, and 20.4%, respectively, highest among paramedics and nurses. Emotional exhaustion reflecting moderate-severe burnout was reported by 65.1%. Concerns about contracting COVID-19 at work and transmitting COVID-19 were common, but 91.2% felt well-informed on workplace changes and 78.3% reported that support services were available. CONCLUSIONS: Australian HCWs employed during 2021 experienced adverse mental health outcomes, with prevalence differences observed according to occupation. Longitudinal evidence is needed to inform workplace strategies that support the physical and mental wellbeing of HCWs at organisational and state policy levels.
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    Population-wide active case finding and prevention for tuberculosis and leprosy elimination in Kiribati: the PEARL study protocol
    Coleman, M ; Hill, J ; Timeon, E ; Tonganibeia, A ; Eromanga, B ; Islam, T ; Trauer, JM ; Chambers, ST ; Christensen, A ; Fox, GJ ; Marks, GB ; Britton, WJ ; Marais, BJ (BMJ PUBLISHING GROUP, 2022-04)
    INTRODUCTION: Population-wide interventions offer a pathway to tuberculosis (TB) and leprosy elimination, but 'real-world' implementation in a high-burden setting using a combined approach has not been demonstrated. This implementation study aims to demonstrate the feasibility and evaluate the effect of population-wide screening, treatment and prevention on TB and leprosy incidence rates, as well as TB transmission. METHODS AND ANALYSIS: A non-randomised 'screen-and-treat' intervention conducted in the Pacific atoll of South Tarawa, Kiribati. Households are enumerated and all residents ≥3 years, as well as children <3 years with recent household exposure to TB or leprosy, invited for screening. Participants are screened using tuberculin skin testing, signs and symptoms of TB or leprosy, digital chest X-ray with computer-aided detection and sputum testing (Xpert MTB/RIF Ultra). Those diagnosed with disease are referred to the National TB and Leprosy Programme for management. Participants with TB infection are offered TB preventive treatment and those without TB disease or infection, or leprosy, are offered leprosy prophylaxis. The primary study outcome is the difference in the annual TB case notification rate before and after the intervention; a similar outcome is included for leprosy. The effect on TB transmission will be measured by comparing the estimated annual risk of TB infection in primary school children before and after the intervention, as a co-primary outcome used for power calculations. Comparison of TB and leprosy case notification rates in South Tarawa (the intervention group) and the rest of Kiribati (the control group) before, during and after the intervention is a secondary outcome. ETHICS AND DISSEMINATION: Approval was obtained from the University of Sydney Human Research Ethics Committee (project no. 2021/127) and the Kiribati Ministry of Health and Medical Services (MHMS). Findings will be shared with the MHMS and local communities, published in peer-reviewed journals and presented at international conferences.
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    An approach for improving the quality of country-level TB modelling
    McQuaid, CF ; Clarkson, MC ; Bellerose, M ; Floyd, K ; White, RG ; Menzies, NA (INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D), 2021-08-01)
    Mathematical modelling is increasingly used to inform budgeting and strategic decision-making by national TB programmes. Despite the importance of these decisions, there is currently no mechanism to review and confirm the appropriateness of modelling analyses. We have developed a benchmarking, reporting, and review (BRR) approach and accompanying tools to allow constructive review of country-level TB modelling applications. This approach has been piloted in five modelling applications and the results of this study have been used to revise and finalise the approach. The BRR approach consists of 1) quantitative benchmarks against which model assumptions and results can be compared, 2) standardised reporting templates and review criteria, and 3) a multi-stage review process providing feedback to modellers during the application, as well as a summary evaluation after completion. During the pilot, use of the tools prompted important changes in the approaches taken to modelling. The pilot also identified issues beyond the scope of a review mechanism, such as a lack of empirical evidence and capacity constraints. This approach provides independent evaluation of the appropriateness of modelling decisions during the course of an application, allowing meaningful changes to be made before results are used to inform decision-making. The use of these tools can improve the quality and transparency of country-level TB modelling applications.
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    Ethics of selective restriction of liberty in a pandemic
    Cameron, J ; Williams, B ; Ragonnet, R ; Marais, B ; Trauer, J ; Savulescu, J (BMJ PUBLISHING GROUP, 2021-08)
    Liberty-restricting measures have been implemented for centuries to limit the spread of infectious diseases. This article considers if and when it may be ethically acceptable to impose selective liberty-restricting measures in order to reduce the negative impacts of a pandemic by preventing particularly vulnerable groups of the community from contracting the disease. We argue that the commonly accepted explanation-that liberty restrictions may be justified to prevent harm to others when this is the least restrictive option-fails to adequately accommodate the complexity of the issue or the difficult choices that must be made, as illustrated by the COVID-19 pandemic. We introduce a dualist consequentialist approach, weighing utility at both a population and individual level, which may provide a better framework for considering the justification for liberty restrictions. While liberty-restricting measures may be justified on the basis of significant benefits to the population and small costs for overall utility to individuals, the question of whether it is acceptable to discriminate should be considered separately. This is because the consequentialist approach does not adequately account for the value of equality. This value may be protected through the application of an additional proportionality test. An algorithm for making decisions is proposed. Ultimately whether selective liberty-restricting measures are imposed will depend on a range of factors, including how widespread infection is in the community, the level of risk and harm a society is willing to accept, and the efficacy and cost of other mitigation options.