Infectious Diseases - Research Publications

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    Point-of-care HCV RNA testing improves hepatitis C testing rates and allows rapid treatment initiation among people who inject drugs attending a medically supervised injecting facility.
    MacIsaac, MB ; Whitton, B ; Anderson, J ; Cogger, S ; Vella-Horne, D ; Penn, M ; Weeks, A ; Elmore, K ; Pemberton, D ; Winter, RJ ; Papaluca, T ; Howell, J ; Hellard, M ; Stoové, M ; Wilson, D ; Pedrana, A ; Doyle, JS ; Clark, N ; Holmes, JA ; Thompson, AJ (Elsevier BV, 2024-03)
    BACKGROUND: To achieve hepatitis C virus (HCV) elimination targets, simplified care engaging people who inject drugs is required. We evaluated whether fingerstick HCV RNA point-of-care testing (PoCT) increased the proportion of clients attending a supervised injecting facility who were tested for hepatitis C. METHODS: Prospective single-arm study with recruitment between 9 November 2020 and 28 January 2021 and follow-up to 31 July 2021. Clients attending the supervised injecting facility were offered HCV RNA testing using the Xpert® HCV Viral Load Fingerstick (Cepheid, Sunnyvale, CA) PoCT. Participants with a positive HCV RNA test were prescribed direct acting antiviral (DAA) therapy. The primary endpoint was the proportion of clients who engaged in HCV RNA PoCT, compared to a historical comparator group when venepuncture-based hepatitis C testing was standard of care. RESULTS: Among 1618 clients who attended the supervised injecting facility during the study period, 228 (14%) engaged in PoCT. This was significantly higher than that observed in the historical comparator group (61/1,775, 3%; p < 0.001). Sixty-five (28%) participants were HCV RNA positive, with 40/65 (62%) receiving their result on the same day as testing. Sixty-one (94%) HCV RNA positive participants were commenced on DAA therapy; 14/61 (23%) started treatment on the same day as diagnosis. There was no difference in the proportion of HCV RNA positive participants commenced on treatment with DAA therapy when compared to the historical comparator group (61/65, 94% vs 22/26, 85%; p = 0.153). However, the median time to treatment initiation was significantly shorter in the PoCT cohort (2 days (IQR 1-20) vs 41 days (IQR 22-76), p < 0.001). Among participants who commenced treatment and had complete follow-up data available, 27/36 (75%) achieved hepatitis C cure. CONCLUSIONS: HCV RNA PoCT led to a significantly higher proportion of clients attending a supervised injecting facility engaging in hepatitis C testing, whilst also reducing the time to treatment initiation.
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    The impact of point-of-care hepatitis C testing in needle and syringe exchange programs on linkage to care and treatment uptake among people who inject drugs: An Australian pilot study
    Howell, J ; Traeger, MW ; Williams, B ; Layton, C ; Doyle, JS ; Latham, N ; Draper, B ; Bramwell, F ; Membrey, D ; McPherson, M ; Roney, J ; Stoove, M ; Thompson, AJ ; Hellard, ME ; Pedrana, A (WILEY, 2022-05)
    Point-of-care (POC) diagnostics overcome barriers to conventional hepatitis C (HCV) testing in people who inject drugs. This study assessed impact on hepatitis C treatment uptake of POC HCV testing in needle and syringe exchange programs (NSPs). Rapid EC was a single-arm interventional pilot study of HCV POC testing conducted in three inner-city community clinics with NSPs. Twelve months after the POC testing, a retrospective medical record and Pharmaceutical Benefits Scheme audit was performed to determine the number of HCV RNA-positive participants who were prescribed HCV treatment. 70 HCV RNA-positive Rapid EC study participants were included. 44 (63%) were prescribed DAAs; 26 (59%) completed treatment and 15 (34%) had SVR testing, all of whom were cured. Age ≥ 40 years (aOR 3.45, 95% CI 1.10-11.05, p = .03) and secondary school education (aOR 5.8, 95% CI 1.54-21.80, p = .009) had higher likelihood of being prescribed DAAs, whereas homelessness was inversely associated with prescription of DAAs (aOR 0.30, 95% CI 0.09-1.04, p = .057). Median time to receive a DAA script from date of diagnosis was seven days (IQR 0 to 14 days), and time to filling the DAA prescription was 2 days (IQR 0-12 days). In conclusion, provision of POC testing through NSPs was effective for linking new clients to HCV treatment and reduced the time to treatment. Further studies are needed to define the most cost-effective use of POC testing in models of care for people who inject drugs to increase HCV treatment uptake.
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    Evaluating the potential cost-effectiveness of microarray patches to expand access to hepatitis B birth dose vaccination in low-and middle-income countries: A modelling study.
    Seaman, CP ; Mvundura, M ; Frivold, C ; Morgan, C ; Jarrahian, C ; Howell, J ; Hellard, M ; Scott, N ; Jean, K (Public Library of Science (PLoS), 2022)
    Timely birth dose vaccination is key for achieving elimination of hepatitis B, however, programmatic requirements for delivering current vaccine presentations to births outside of health facilities inhibits coverage within many low-and middle-income countries (LMICs). Vaccine technologies in development such as microarray patches (MAPs) could assist in overcoming these barriers, but procurement could incur higher per-dose commodity costs than current ten-dose (US$0.34) and single-dose (US$0.62) vial presentations, necessitating an evaluation of the economic value proposition for MAPs. Within 80 LMICs offering universal hepatitis B birth dose vaccination, the cost-effectiveness of using MAPs to expand coverage was evaluated using a mathematical model. We considered three potential per dose MAP prices (US$1.65, US$3.30, and US$5.00), and two potential MAP use-cases: (1) MAPs are used by lay-health workers to expand birth dose coverage outside of health facility settings, and (2) MAPs are also preferred by qualified health workers, replacing a proportion of existing coverage from vaccine vials. Analysis took the health system perspective, was costed in 2020 US$, and discounted at 3% annually. Across minimal (1% additional coverage) and maximal (10% additional and 10% replacement coverage) MAP usage scenarios, between 2.5 (interquartile range [IQR]: 1.9, 3.1) and 38 (IQR: 28,44) thousand DALYs were averted over the estimated 2020 birth cohort lifetime in 80 LMICs. Efficiency of MAPs was greatest when used to provide additional coverage (scenario 1), on average saving US$88.65 ($15.44, $171.22) per DALY averted at a price of US$5.00 per MAP. Efficiency was reduced when used to replace existing coverage (scenario 2); however, at prices up to US$5.00 per MAP, we estimate this use-case could remain cost-effective in at least 73 (91%) modelled LMICs. Our findings suggest even at higher procurement costs, MAPs are likely to represent a highly cost-effective or cost-saving mechanism to expand reach of birth dose vaccination in LMICs.
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    Real-world monitoring progress towards the elimination of hepatitis C virus in Australia using sentinel surveillance of primary care clinics; an ecological study of hepatitis C virus antibody tests from 2009 to 2019 (vol 150, E7, 2022)
    Lee Wilkinson, A ; Pedrana, A ; Traeger, MW ; Asselin, J ; El-Hayek, C ; Nguyen, L ; Polkinghorne, V ; Doyle, JS ; Thompson, AJ ; Howell, J ; Scott, N ; Dimech, W ; Guy, R ; Hellard, M ; Stoove, M (CAMBRIDGE UNIV PRESS, 2022-03-04)
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    Exploring the Public Health and Social Implications of Future Curative Hepatitis B Interventions
    Wallace, J ; Richmond, J ; Howell, J ; Hajarizadeh, B ; Power, J ; Treloar, C ; Revill, PA ; Cowie, B ; Wang, S ; Stoove, M ; Pedrana, A ; Hellard, M (MDPI, 2022-11)
    Hepatitis B is a significant global health issue where the 296 million people estimated to live with the infection risk liver disease or cancer without clinical intervention. The World Health Organization has committed to eliminating viral hepatitis as a public health threat by 2030, with future curative hepatitis B interventions potentially revolutionizing public health responses to hepatitis B, and being essential for viral hepatitis elimination. Understanding the social and public health implications of any cure is imperative for its successful implementation. This exploratory research, using semi-structured qualitative interviews with a broad range of professional stakeholders identifies the public health elements needed to ensure that a hepatitis B cure can be accessed by all people with hepatitis B. Issues highlighted by the experience of hepatitis C cure access include preparatory work to reorientate policy settings, develop resourcing options, and the appropriateness of health service delivery models. While the form and complexity of curative hepatitis B interventions are to be determined, addressing current disparities in cascade of care figures is imperative with implementation models needing to respond to the cultural contexts, social implications, and health needs of people with hepatitis B, with cure endpoints and discourse being contested.
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    Comparative Analysis of Mammal Genomes Unveils Key Genomic Variability for Human Life Span (vol 38, pg 4948, 2021)
    Wallace, J ; Richmond, J ; Howell, J ; Hajarizadeh, B ; Power, J ; Treloar, C ; Revill, P ; Cowie, B ; Wang, S ; Stoove, M ; Pedrana, A ; Hellard, M (OXFORD UNIV PRESS, 2022-12-05)
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    The cost-effectiveness of universal hepatitis B screening for reaching WHO diagnosis targets in Australia by 2030
    Xiao, Y ; Hellard, ME ; Thompson, AJ ; Seaman, C ; Howell, J ; Scott, N (WILEY, 2023-03-06)
    OBJECTIVES: To assess the impact on diagnosis targets, cost, and cost-effectiveness of universal hepatitis B screening in Australia. DESIGN: Markov model simulation of disease and care cascade progression for people with chronic hepatitis B in Australia. SETTING: Three scenarios were compared: 1. no change to current hepatitis B virus (HBV) testing practice; 2. universal screening strategy, with the aim of achieving the WHO diagnosis target by 2030 (90% of people with chronic hepatitis B diagnosed), based on opportunistic (general practitioner-initiated) screening for HBsAg; 3. universal screening strategy, and also ensuring that 50% of people with chronic hepatitis B are receiving appropriate clinical management by 2030. MAIN OUTCOME MEASURES: Projected care cascade for people with chronic hepatitis B, cumulative number of HBV-related deaths, intervention costs, and health utility (quality-adjusted life-years [QALYs] gained during 2020-2030). An incremental cost-effectiveness ratio (ICER) threshold (v scenario 1) of $50 000 per QALY gained was applied. RESULTS: Compared with scenario 1, 80 HBV-related deaths (interquartile range [IQR], 41-127 deaths) were averted during 2020-2030 in scenario 2, 315 HBV-related deaths (IQR, 211-454 deaths) in scenario 3. Scenario 2 cost $84 million (IQR, $41-106 million) more than scenario 1 during 2020-2030 (+8%), yielding an ICER of $104 921 (IQR, $49 587-107 952) per QALY gained. Scenario 3 cost $263 million (IQR, $214-316 million) more than scenario 1 during 2020-2030 (+24%), yielding an ICER of $47 341 (IQR, $32 643-58 200) per QALY gained. Scenario 3 remained cost-effective if the test positivity rate was higher than 0.35% or the additional costs per person tested did not exceed $4.02. CONCLUSIONS: Universal screening for hepatitis B will be cost-effective only if the cost of testing is kept low and people receive appropriate clinical management.
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    Impact of COVID-19 lockdown restrictions on hepatitis C testing in Australian primary care services providing care for people who inject drugs
    Traeger, MW ; van Santen, DK ; Sacks-Davis, R ; Asselin, J ; Carter, A ; Doyle, JS ; Pedrana, A ; Wilkinson, AL ; Howell, J ; Thatcher, R ; Didlick, J ; Donovan, B ; Guy, R ; Hellard, ME ; Stoove, MA (WILEY, 2022-10)
    In 2020, the Australian state of Victoria experienced the longest COVID-19 lockdowns of any jurisdiction, with two lockdowns starting in March and July, respectively. Lockdowns may impact progress towards eliminating hepatitis C through reductions in hepatitis C testing. To examine the impact of lockdowns on hepatitis C testing in Victoria, de-identified data were extracted from a network of 11 services that specialize in the care of people who inject drugs (PWID). Interrupted time-series analyses estimated weekly changes in hepatitis C antibody and RNA testing from 1 January 2019 to 14 May 2021 and described temporal changes in testing associated with lockdowns. Interruptions were defined at the weeks corresponding to the start of the first lockdown (week 14) and the start (week 80) and end (week 95) of the second lockdown. Pre-COVID, an average of 80.6 antibody and 25.7 RNA tests were performed each week. Following the first lockdown in Victoria, there was an immediate drop of 23.2 antibody tests and 8.6 RNA tests per week (equivalent to a 31% and 46% drop, respectively). Following the second lockdown, there was an immediate drop of 17.2 antibody tests and 4.6 RNA tests per week (equivalent to a 26% and 33% drop, respectively). With testing and case finding identified as a key challenge to Australia achieving hepatitis C elimination targets, the cumulative number of testing opportunities missed during lockdowns may prolong efforts to find, diagnose and engage or reengage in care of the remaining population of PWID living with hepatitis C.
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    A survey of knowledge, attitudes, barriers and support needs in providing hepatitis B care among GPs practising in Australia
    Xiao, Y ; van Gemert, C ; Howell, J ; Wallace, J ; Richmond, J ; Adamson, E ; Thompson, A ; Hellard, M (BMC, 2022-06-02)
    BACKGROUND: In Australia, only 22% of people with chronic hepatitis B (CHB) are clinically managed; and a national effort is engaging primary care workforce in providing CHB-related care. This study explored CHB-related knowledge, attitudes, barriers and support needs of general practitioners (GPs). METHODS: A survey was sent to a random sample of 1,000 Australian GPs in April- October 2018; 134 of 978 eligible GPs completed the questionnaire (14%). RESULTS: Respondents had high knowledge of at-risk populations (> 79%) and hepatitis B serology (82%), and most saw hepatitis B testing and monitoring as part of their work (95% and 86%, respectively). However, the survey revealed low knowledge, awareness and intention with respect to hepatitis B treatment: 23% correctly understood treatment initiation; 40% were aware that treatment for CHB could be dispensed in the community; 23% agreed that prescribing was part of their work. Lack of time was considered the greatest barrier (38%) and clear guidelines was the most important facilitator to providing care (72%). CONCLUSION: Interventions are needed to generate interest and skills to provide CHB-related care by GPs.
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    Feasibility of decentralised, task-shifted hepatitis C testing and treatment services in urban Myanmar: implications for scale-up.
    Draper, BL ; Yee, WL ; Shilton, S ; Bowring, A ; Htay, H ; Nwe, N ; Markby, J ; Kyi, KP ; Easterbrook, P ; Naing, W ; Win, TM ; Aung, KS ; Howell, J ; Pedrana, A ; Hellard, M (BMJ, 2022-05-03)
    OBJECTIVES: To assess the feasibility considerations for a decentralised, one-stop-shop model of care implemented in Yangon, Myanmar. SETTING: Two primary care level clinics in urban Yangon, Myanmar. DESIGN: This is a feasibility study of a highly effective care model. Using Intervention Complexity Framework by Gericke et al, we collated and analysed programmatic data and evaluation data to outline key project implementation requirements and experiences. PARTICIPANTS: Programmatic data were collected from clinical records, GeneXpert device test and maintenance reports, national guidelines, product and device instructions and site monitoring visit reports. Healthcare providers involved in delivering care model contributed interview data. RESULTS: The main feasibility considerations are appropriate storage for test kits and treatments (in response to temperature and humidity requirements), installation of a continuous stable electricity supply for the GeneXpert device, air-conditioning for the laboratory room hosting GeneXpert, access to a laboratory for pretreatment assessments and clear referral pathways for specialist consultation when required. Lessons from our project implementation experiences included the extensive time requirements for patient education, the importance of regular error monitoring and stock storage reviews and that flexible appointment scheduling and robust reminder system likely contributed to high retention in care. CONCLUSIONS: Detailed documentation and dissemination of feasibility requirements and implementation considerations is vital to assist others to successfully implement a similar model of care elsewhere. We provide 10 recommendations for successful implementation. TRIAL REGISTRATION NUMBER: The trial was registered at ClinicalTrials.gov NCT03939013 on May 6, 2019. This manuscript presents post-results data on feasibility.