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, T ; 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, 2024-01-27)
    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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    Keeping kids in school: modelling school-based testing and quarantine strategies during the COVID-19 pandemic in Australia
    Abeysuriya, RG ; Sacks-Davis, R ; Heath, K ; Delport, D ; Russell, FM ; Danchin, M ; Hellard, M ; McVernon, J ; Scott, N (FRONTIERS MEDIA SA, 2023-06-02)
    BACKGROUND: In 2021, the Australian Government Department of Health commissioned a consortium of modelling groups to generate evidence assisting the transition from a goal of no community COVID-19 transmission to 'living with COVID-19', with adverse health and social consequences limited by vaccination and other measures. Due to the extended school closures over 2020-21, maximizing face-to-face teaching was a major objective during this transition. The consortium was tasked with informing school surveillance and contact management strategies to minimize infections and support this goal. METHODS: Outcomes considered were infections and days of face-to-face teaching lost in the 45 days following an outbreak within an otherwise COVID-naïve school setting. A stochastic agent-based model of COVID-19 transmission was used to evaluate a 'test-to-stay' strategy using daily rapid antigen tests (RATs) for close contacts of a case for 7 days compared with home quarantine; and an asymptomatic surveillance strategy involving twice-weekly screening of all students and/or teachers using RATs. FINDINGS: Test-to-stay had similar effectiveness for reducing school infections as extended home quarantine, without the associated days of face-to-face teaching lost. Asymptomatic screening was beneficial in reducing both infections and days of face-to-face teaching lost and was most beneficial when community prevalence was high. INTERPRETATION: Use of RATs in school settings for surveillance and contact management can help to maximize face-to-face teaching and minimize outbreaks. This evidence supported the implementation of surveillance testing in schools in several Australian jurisdictions from January 2022.
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    Working with West African migrant communities on HIV prevention in Australia
    Lemoh, C ; Biggs, B-A ; Hellard, M (CSIRO Publishing, 2008-11-18)
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    Delayed diagnosis of HIV infection in Victoria 1994 to 2006
    Lemoh, C ; Guy, R ; Yohannes, K ; Lewis, J ; Street, A ; Biggs, B ; Hellard, M (CSIRO PUBLISHING, 2009)
    BACKGROUND: The identification of factors associated with delayed diagnosis of HIV infection in Victoria, Australia was the aim of the present study. METHODS: Demographic and epidemiological characteristics of cases notified to the Victorian HIV surveillance database between 1 January 1994 and 31 December 2006 were analysed. Delayed diagnosis was defined as: CD4 count below 200 cells mm(-3) at HIV diagnosis or diagnosis of AIDS earlier than 3 months after HIV diagnosis. RESULTS: Diagnosis of HIV was delayed in 627 (22.6%) of 2779 cases. Of these, 528 (84.2%) had either a high-risk exposure or were born in a high-prevalence country. The most common exposure was male homosexual contact in 64.3% of cases. Independent risk factors for delayed diagnosis were: older age at diagnosis (30-39 years odds ratio [OR] 2.15, > or = 50 years OR 7.50, P < 0.001), exposure via routes other than male homosexual sex or injecting drug use (heterosexual sex OR 2.51, P < 0.001, unknown/other route OR 4.24, P < 0.001); birth in Southern/Eastern Europe (OR 2.54), South-east Asia (OR 2.70) or the Horn of Africa/North Africa (OR 3.71, P < 0.001), and male gender (OR 0.47 for females, P < 0.001). CONCLUSION: Delay in the diagnosis of HIV infection is common in Victoria, but potentially avoidable in the majority of cases. Most people with delayed diagnosis had a history of male homosexual contact, injecting drug use, birth in a high-prevalence country or sexual contact with such individuals. An accurate sexual history, together with knowledge of their country of birth, should identify most individuals who should be offered an HIV test.
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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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    Assessment of the lifetime prevalence and incidence of induced abortion and correlates among female sex workers in Mombasa, Kenya: a secondary cohort analysis
    Simmelink, AM ; Gichuki, CM ; Ampt, FH ; Manguro, G ; Lim, MSC ; Agius, P ; Hellard, M ; Jaoko, W ; Stoove, MA ; L'Engle, K ; Temmerman, M ; Gichangi, P ; Luchters, S (BMJ PUBLISHING GROUP, 2022-10)
    INTRODUCTION: Prevalence of lifetime-induced abortion in female sex workers (FSWs) in Kenya was previously estimated between 43% and 86%. Our analysis aimed at assessing lifetime prevalence and correlates, and incidence and predictors of induced abortions among FSWs in Kenya. METHODS: This is a secondary prospective cohort analysis using data collected as part of the WHISPER or SHOUT cluster-randomised trial in Mombasa, assessing effectiveness of an SMS-intervention to reduce incidence of unintended pregnancy. Eligible participants were current FSWs, 16-34 years and not pregnant or planning pregnancy. Baseline data on self-reported lifetime abortion, correlates and predictors were collected between September 2016 and May 2017. Abortion incidence was measured at 6-month and 12-month follow-up. A multivariable logistic regression model was used to assess correlates of lifetime abortion and discrete-time survival analysis was used to assess predictors of abortions during follow-up. RESULTS: Among 866 eligible participants, lifetime abortion prevalence was 11.9%, while lifetime unintended pregnancy prevalence was 51.2%. Correlates of lifetime abortions were currently not using a highly effective contraceptive (adjusted OR (AOR)=1.76 (95% CI=1.11 to 2.79), p=0.017) and having ever-experienced intimate partner violence (IPV) (AOR=2.61 (95% CI=1.35 to 5.06), p=0.005). Incidence of unintended pregnancy and induced abortion were 15.5 and 3.9 per 100 women-years, respectively. No statistically significant associations were found between hazard of abortion and age, sex work duration, partner status, contraceptive use and IPV experience. CONCLUSION: Although experience of unintended pregnancy remains high, lifetime prevalence of abortion may have decreased among FSW in Kenya. Addressing IPV could further decrease induced abortions in this population. TRIAL REGISTRATION NUMBER: ACTRN12616000852459.
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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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    A multinational Delphi consensus to end the COVID-19 public health threat
    Lazarus, J ; Romero, D ; Kopka, CJ ; Karim, SA ; Abu-Raddad, LJ ; Almeida, G ; Baptista-Leite, R ; Barocas, JA ; Barreto, ML ; Bar-Yam, Y ; Bassat, Q ; Batista, C ; Bazilian, M ; Chiou, S-T ; del Rio, C ; Dore, GJ ; Gao, GF ; Gostin, LO ; Hellard, M ; Jimenez, JL ; Kang, G ; Lee, N ; Maticic, M ; McKee, M ; Nsanzimana, S ; Oliu-Barton, M ; Pradelski, B ; Pyzik, O ; Rabin, K ; Raina, S ; Rashid, SF ; Rathe, M ; Saenz, R ; Singh, S ; Trock-Hempler, M ; Villapol, S ; Yap, P ; Binagwaho, A ; Kamarulzaman, A ; El-Mohandes, A (NATURE PORTFOLIO, 2022-11-10)
    Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic1,2. Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches1, while maintaining proven prevention measures using a vaccines-plus approach2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities3 in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with >5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.