Infectious Diseases - Research Publications

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    Anti-PEG Antibodies Boosted in Humans by SARS-CoV-2 Lipid Nanoparticle mRNA Vaccine
    Ju, Y ; Lee, WS ; Pilkington, EH ; Kelly, HG ; Li, S ; Selva, KJ ; Wragg, KM ; Subbarao, K ; Nguyen, THO ; Rowntree, LC ; Allen, LF ; Bond, K ; Williamson, DA ; Truong, NP ; Plebanski, M ; Kedzierska, K ; Mahanty, S ; Chung, AW ; Caruso, F ; Wheatley, AK ; Juno, JA ; Kent, SJ (AMER CHEMICAL SOC, 2022-06-27)
    Humans commonly have low level antibodies to poly(ethylene) glycol (PEG) due to environmental exposure. Lipid nanoparticle (LNP) mRNA vaccines for SARS-CoV-2 contain small amounts of PEG, but it is not known whether PEG antibodies are enhanced by vaccination and what their impact is on particle-immune cell interactions in human blood. We studied plasma from 130 adults receiving either the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) mRNA vaccines or no SARS-CoV-2 vaccine for PEG-specific antibodies. Anti-PEG IgG was commonly detected prior to vaccination and was significantly boosted a mean of 13.1-fold (range 1.0-70.9) following mRNA-1273 vaccination and a mean of 1.78-fold (range 0.68-16.6) following BNT162b2 vaccination. Anti-PEG IgM increased 68.5-fold (range 0.9-377.1) and 2.64-fold (0.76-12.84) following mRNA-1273 and BNT162b2 vaccination, respectively. The rise in PEG-specific antibodies following mRNA-1273 vaccination was associated with a significant increase in the association of clinically relevant PEGylated LNPs with blood phagocytes ex vivo. PEG antibodies did not impact the SARS-CoV-2 specific neutralizing antibody response to vaccination. However, the elevated levels of vaccine-induced anti-PEG antibodies correlated with increased systemic reactogenicity following two doses of vaccination. We conclude that PEG-specific antibodies can be boosted by LNP mRNA vaccination and that the rise in PEG-specific antibodies is associated with systemic reactogenicity and an increase of PEG particle-leukocyte association in human blood. The longer-term clinical impact of the increase in PEG-specific antibodies induced by lipid nanoparticle mRNA vaccines should be monitored. It may be useful to identify suitable alternatives to PEG for developing next-generation LNP vaccines to overcome PEG immunogenicity in the future.
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    Estimating the number of new hepatitis C infections in Australia in 2015, prior to the scale-up of direct-acting antiviral treatment
    Palmer, AY ; Wilkinson, A ; Aitken, C ; Dietze, P ; Dore, GJ ; Maher, L ; Sacks-Davis, R ; Stoove, M ; Wilson, D ; Hellard, M ; Scott, N (WILEY, 2021-03-20)
    BACKGROUND AND AIM: The recent downward revision of the estimated number of people living with chronic hepatitis C in Australia means that the annual number of new hepatitis C infections should also be revised. We aimed to estimate the annual number of new hepatitis C infections among people who inject drugs (PWID) in Australia in 2015, prior to the introduction of direct-acting antiviral (DAA) treatment for hepatitis C, as an updated baseline measure for assessing the impact of DAAs on hepatitis C incidence over the next 10 years. METHODS: A systematic review identified articles estimating hepatitis C incidence rates among PWID between 2002 and 2015. Reported incidence rates were adjusted to account for unrepresentative needle and syringe program (NSP) coverage among study participants compared with PWID overall. The total number of PWID in Australia and the hepatitis C RNA prevalence among PWID were taken from published estimates. The annual number of new infections was estimated by multiplying the pooled NSP coverage-adjusted incidence rate by the number of susceptible PWID in 2015. RESULTS: Five studies were included, with unadjusted incidence rates ranging from 7.6 to 12.8 per 100 person-years. The overall pooled incidence rate (after adjusting for NSP coverage) was 9.9 per 100 person-years (95% confidence interval: 8.3-11.8). This led to an estimate of 4126 (range 2499-6405) new hepatitis C infections in 2015. CONCLUSIONS: Our updated estimate provides an important baseline for evaluating the impact of hepatitis C elimination efforts and can be used to validate outcomes of future modeling studies.
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    Hepatitis C treatment in a co-located mental health and alcohol and drug service using a nurse-led model of care
    Harney, BL ; Brereton, R ; Whitton, B ; Pietrzak, D ; Paige, E ; Roberts, SK ; Birks, S ; Saraf, S ; Hellard, ME ; Doyle, JS (WILEY, 2021-03-03)
    Hepatitis C virus (HCV) is more prevalent among people with experience of severe mental illness compared to the general population, due in part to higher levels of injecting drug use. Delivering HCV care through mental health services may reduce barriers to care and improve outcomes. A nurse-led HCV program was established in a co-located mental health and addiction service in Melbourne, Australia. People with a history of injecting drug use, including current use, were referred for HCV testing by nurses, with support provided on-site from a general practitioner and remotely from infectious disease and hepatology specialists. A nurse practitioner, general practitioner or specialists were able to prescribe HCV treatment. One-hundred and thirty people were referred to the nurse-led service, among whom 112 (86%) were engaged in care. Of those 112, 84 (75%) were found to have detectable HCV RNA, 70 (83%) commenced treatment; 28 (40%) prescriptions were nurse initiated, 19 (27%) were general practitioner initiated and 20 (29%) were prescribed from hospital clinics or elsewhere. All people with an SVR result (48/70) achieved HCV cure (intention to treat SVR 69%, per-protocol SVR 100%). Treatment commencement was highest among people prescribed opioid agonist therapy (28/29, 96%) compared to those who were not (18/26, 69%). In conclusion, a nurse-led, HCV service for people with severe mental illness including pathways to specialist support when needed can achieve high treatment uptake and cure. Further implementation work is required to improve treatment uptake, particularly among people not prescribed opioid agonist therapy, and to improve follow-up for SVR testing.
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    Aberration on excitation focal spot caused by oblique interface with refractive indices discontinuous and its correction with pure-phase compensation for laser scanning microscopy.
    Zhu, Y ; Zhang, C ; Zhao, W ; Wang, J ; Wang, K ; Bai, J (Wiley, 2021-06)
    The interface of mediums with refractive indices discontinuous, for example air-glass and glass-water, are inevitable in microscopic imaging. In this work, the aberration of oblique interface with refractive index discontinuous on the laser scanning microscope was investigated theoretically with numerical simulations. It was found that the position, shape and FWHM of focal spots, were all significantly affected by the aberration due to oblique interface. The aberration can cause serious shifting of focal spots in the axial direction of beam during z -scanning and lead to an inaccurate reconstruction of three-dimensional (3D) targets. The aberration can also lead to a decreasing spatial resolution. To correct the influence of the aberration, a pure-phase modulation method has been proposed. By applying a phase compensation map into a spatial light modulator (SLM), the oblique interface aberration had been corrected experimentally in a laser scanning microscope. We hope this research can attract the attention of researchers when using scanning microscope, especially for reconstructing 3D biological and material structures.
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    Transition from periodic to chaotic AC electroosmotic flows near electric double layer
    Hu, Z ; Zhao, T ; Zhao, W ; Yang, F ; Wang, H ; Wang, K ; Bai, J ; Wang, G (Wiley, 2021-04-01)
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    Risk factors for TB in Australia and their association with delayed treatment completion.
    Coorey, NJ ; Kensitt, L ; Davies, J ; Keller, E ; Sheel, M ; Chani, K ; Barry, S ; Boyd, R ; Denholm, J ; Watts, K ; Fox, G ; Lowbridge, C ; Perera, R ; Waring, J ; Marais, B ; Viney, K (International Union Against Tuberculosis and Lung Disease, 2022-05-01)
    BACKGROUND: Australia has a low incidence of TB and has committed to eliminating the disease. Identification of risk factors associated with TB is critical to achieving this goal.METHODS: We undertook a prospective cohort study involving persons receiving TB treatment in four Australian jurisdictions. Risk factors and their association with delayed treatment completion (treatment delayed by at least 1 month) were analysed using univariate analyses and multivariate logistic regression.RESULTS: Baseline surveys were completed for 402 persons with TB. Most (86.1%) were born overseas. Exposure to a person with TB was reported by 19.4%. Diabetes mellitus (10.2%), homelessness (9.2%), cigarette smoking (8.7%), excess alcohol consumption (6.0%) and mental illness (6.2%) were other common risk factors. At follow-up, 24.8% of patients had delayed treatment completion, which was associated with adverse events (34.1%, aOR 6.67, 95% CI 3.36-13.27), excess alcohol consumption (6.0%, aOR 21.94, 95% CI 6.03-79.85) and HIV co-infection (2.7%, aOR 8.10, 95% CI 1.16-56.60).CONCLUSIONS: We identified risk factors for TB and their association with delayed treatment completion, not all of which are routinely collected for surveillance purposes. Recognition of these risk factors should facilitate patient-centred care and assist Australia in reaching TB elimination.
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    Simultaneous detection of multiple pathogens with the TaqMan Array Card.
    Lappan, R ; Jirapanjawat, T ; Williamson, DA ; Lange, S ; Chown, SL ; Greening, C (Elsevier BV, 2022)
    Quantitative polymerase chain reaction (qPCR) is a gold standard method for the detection and quantification of pathogenic organisms. Standard qPCR is inexpensive, sensitive and highly specific to the pathogen of interest. While qPCR assays can be multiplexed to allow the detection of multiple organisms in one reaction, it is prohibitively labour intensive to screen large numbers of samples for several pathogens at the same time. The TaqMan Array Card (TAC) is a cost-effective and accurate technique that expands the number of assays that can be simultaneously performed on a sample, with no increase in set-up time and only small reductions in sensitivity. This approach is highly beneficial in settings where there is a need to monitor a large panel of pathogens. We illustrate the application of TAC to the monitoring of gastrointestinal pathogens, which span viral, bacterial, protist and helminth taxa. This protocol outlines the laboratory set-up of a TaqMan Array Card, and some recommended data processing steps to aid in accurate interpretation of the results. A video protocol is additionally provided to assist in the use of the technique.•The TAC is designed primarily for gene expression assays, but has recently been utilised in several studies for pathogen detection in human clinical samples.•We expand the use of TAC for pathogen detection across human, animal and environmental sample types, and have developed a protocol and guidelines for the processing and interpretation of results that circumvents issues with the automated outputs.•This technique is applicable to pathogen or organism detection in any context, if quality nucleic acid extracts can be obtained from the sample type of interest.
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    Feasibility of a refurbished shipping container as a transportable laboratory for rapid SARS-CoV-2 diagnostics.
    Muhi, S ; Tayler, N ; Hoang, T ; Prestedge, J ; Lee, JYH ; Ballard, SA ; Isles, N ; Wlodek, A ; Greenhalgh, A ; Williamson, DA ; Howden, BP ; Stinear, TP (Microbiology Society, 2022)
    Background: Australia's response to the coronavirus disease 2019 (COVID-19) pandemic relies on widespread availability of rapid, accurate testing and reporting of results to facilitate contact tracing. The extensive geographical area of Australia presents a logistical challenge, with many of the population located distant from a laboratory capable of robust severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection. A strategy to address this is the deployment of a mobile facility utilizing novel diagnostic platforms. This study aimed to evaluate the feasibility of a fully contained transportable SARS-CoV-2 testing laboratory using a range of rapid point-of-care tests. Method: A 20 ft (6.1 m) shipping container was refurbished (GeneWorks, Adelaide, South Australia) with climate controls, laboratory benches, hand-wash station and a class II biosafety cabinet. Portable marquees situated adjacent to the container served as stations for registration, sample acquisition and personal protective equipment for staff. Specimens were collected and tested on-site utilizing either the Abbott ID NOW or Abbott Panbio rapid tests. SARS-CoV-2 positive results from the rapid platforms or any participants reporting symptoms consistent with COVID-19 were tested on-site by GeneXpert Xpress RT-PCR. All samples were tested in parallel with a standard-of-care RT-PCR test (Panther Fusion SARS-CoV-2 assay) performed at the public health reference laboratory. In-laboratory environmental conditions and data management-related factors were also recorded. Results: Over a 3 week period, 415 participants were recruited for point-of-care SARS-CoV-2 testing. From time of enrolment, the median result turnaround time was 26 min for the Abbott ID NOW, 32 min for the Abbott Panbio and 75 min for the Xpert Xpress. The environmental conditions of the refurbished shipping container were found to be suitable for all platforms tested, although humidity may have produced condensation within the container. Available software enabled turnaround times to be recorded, although technical malfunction resulted in incomplete data capture. Conclusion: Transportable container laboratories can enable rapid COVID-19 results at the point of care and may be useful during outbreak settings, particularly in environments that are physically distant from centralized laboratories. They may also be appropriate in resource-limited settings. The results of this pilot study confirm feasibility, although larger trials to validate individual rapid point-of-care testing platforms in this environment are required.
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    Analysis of fat mass value, clinical and metabolic data and interleukin-6 in HIV-positive males using regression analyses and artificial neural network
    Shamsuddin, NF ; Mohktar, MS ; Rajasuriar, R ; Zaman, WSWK ; Ibrahim, F ; Kamarulzaman, A (Universidade Estadual de Maringa, 2022-01-12)
    The purpose of this study is to analyses the relationship between fat mass and inflammation marker, interleukin-6, clinical and metabolic data in 71 human immunodeficiency virus (HIV)-positive male patients using bivariate linear regression analyses and artificial neural network. The data used consisted of measurements collected from HIV male subjects aged 26 to 69 years, with body mass index (BMI) values between 15.47 and 36.98 kg m-2 and the fat mass values between 1.00 kg and 16.70 kg. The bivariate linear regression analyses showed that weight, waist-hip ratio, BMI, triglycerides, high-density lipoprotein and HIV viral load value were significant risk factors associated with the body fat mass in male HIV patients. Furthermore, an in-depth non-linear analysis has been performed using artificial neural network (ANN) to predict fat mass by using the significant predictors as input. ANN model with four hidden neurons obtained the highest mean predictive accuracy percentage of 85.26%. The finding of this study is able to help with the evaluation of the fat mass in the male HIV patients that consequently reflects the patients metabolic-related irregularity and immune response. It is also believed that the outcome from the analysis can help future HIV-related study on the prediction of body fat mass in male HIV patients especially in settings where dual energy X-ray absorptiometry assessments, the standard measurement method for fat mass are not available or affordable
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    Tuberculosis mortality: quantifying agreement in clinical cause of death assessments.
    Denholm, JT ; Marais, BJ ; Donnan, EJ ; Waring, J ; Stapledon, R ; Taylor, JW ; Mahanty, S (Wiley, 2022-04-18)
    OBJECTIVES: Mortality is a key statistic for public health globally, and mortality reduction is a key target of 'End TB' strategy. However, cause of death in relation to tuberculosis (TB) may be controversial, and we aimed to evaluate classification in Australia. METHODS: We surveyed Australian clinicians and public health officers, presenting a variety of scenarios. Respondents were asked to classify each scenario with regards to whether TB was considered causative, contributory or not related to death. RESULTS: Fifty-nine individuals completed the survey. Respondents were experienced TB clinicians and public health officers (median 14 years of TB care experience), with a majority having recently been involved in death certification/classification. In most scenarios, there was substantial variation, particularly where death was related to TB medications, or if an alternative contributing process was recognised, such as cardiovascular complications. Variation in classification was not evidently associated with classification experience. CONCLUSION: We found significant variation in cause of death classification among experienced TB clinicians and public health officers, using representative TB death scenarios. IMPLICATIONS FOR PUBLIC HEALTH: Consensus and transparency with regards to classification would assist in more uniform cause of death classification across jurisdictions and allow for better tracking of this critical performance measure.