No abstract

Summary Subsidized direct‐acting antiviral (DAA) treatment recently became available to all adults living with chronic hepatitis C virus (HCV) in Australia. Based on rapid uptake (32 600 people initiated DAA in 2016), we estimated the impact on HCV epidemiology and mortality in Australia and determined if Australia can meet the WHO HCV elimination targets by 2030. Using a mathematical model, we simulated pessimistic, intermediate and optimistic DAA treatment scenarios in Australia over 2016‐2030. We assumed treatment and testing rates were initially higher for advanced fibrosis and the same across HCV transmission risk level sub‐populations. We also assumed constant testing rates after 2016. We compared the results to the 2015 level and a counterfactual (IFN‐based) scenario. During 2016‐2030, we estimated an intermediate DAA treatment scenario (2016, 32 600 treated; 2017, 21 370 treated; 2018 17 100 treated; 2019 and beyond, 13 680 treated each year) would avert 40 420 new HCV infections, 13 260 liver‐related deaths (15 320 in viraemic; −2060 in cured) and 10 730 HCC cases, equating to a 53%, 63% and 75% reduction, respectively, compared to the IFN‐based scenario. The model also estimated that Australia will meet the WHO targets of incidence and treatment by 2028. Time to a 65% reduction in liver‐related mortality varied considerably between HCV viraemic only cases (2026) and all cases (2047). Based on a feasible DAA treatment scenario incorporating declining uptake, Australia should meet key WHO HCV elimination targets in 10 to15 years. The pre‐DAA escalation in those with advanced liver disease makes the achievement of the liver‐related mortality target difficult.

Australia's early introduction and high coverage of NSPs has significantly reduced the prevalence of HIV and HCV among IDUs. NSPs are a cost-effective public health strategy and will result in substantial net cost savings in the future.

This research highlights the large benefits of NSPs, puts forward a quantitative relationship between incidence and syringe distribution, and indicates that increased coverage could result in significant reductions in viral transmissions among IDUs.

This study describes Chromobacterium violaceum's use of extracellular membrane vesicles (MVs) to both solubilize and transport violacein to other microorganisms. Violacein is a hydrophobic bisindole with known antibiotic activities against other microorganisms. Characterization of the MVs found they carried more violacein than protein (1.37 AE 0.19-fold), suggesting they may act as a reservoir for this compound. However, MVs are not produced in response to violaceina ΔvioA isogenic mutant, which is incapable of making violacein, actually produced significantly more MVs (3.2-fold) than the wild-type strain. Although violacein is insoluble in water (Log P octanol: water = 3.34), 79.5% remained in the aqueous phase when it was present within the C. violaceum MVs, an increase in solubility of 1740-fold. Moreover, tests with a strain of Staphylococcus aureus showed MVassociated violacein is bactericidal, with 3.

No abstract

IMPORTANCEAchievement of the World Health Organization (WHO) target of eliminating hepatitis C virus (HCV) by 2030 will require an increase in key services, including harm reduction, HCV screening, and HCV treatment initiatives in member countries. These data are not available for Canada but are important for informing a national HCV elimination strategy. OBJECTIVE To use a decision analytical model to explore the association of different treatment strategies with HCV epidemiology and HCV-associated mortality in Canada and to assess the levels of service increase needed to meet the WHO elimination targets by 2030. DESIGN, SETTING, AND PARTICIPANTS Study participants in this decision analytical model included individuals with hepatitis C virus infection in Canada. Five HCV treatment scenarios (optimistic, very aggressive, aggressive, gradual decrease, and rapid decrease) were applied using a previously validated Markov-type mathematical model. The optimistic and very aggressive treatment scenarios modeled a sustained annual treatment of 10 200 persons and 14 000 persons, respectively, from 2018 to 2030. The aggressive, gradual decrease, and rapid decrease scenarios assessed decreases in treatment uptake from 14 000 persons to 10 000 persons per year, 12 000 persons to 8500 persons per year, and 12 000 persons to 4500 persons per year, respectively, between 2018 and 2030. MAIN OUTCOMES AND MEASURES Hepatitis C virus prevalence and HCV-associated health outcomes were assessed for each of the 5 treatment scenarios with the goal of identifying strategies to achieve HCV elimination by 2030. RESULTS An estimated mean 180 142 persons (95% CI, 122 786-196 862 persons) in Canada had chronic HCV infection at the end of 2017. The optimistic and gradual decrease scenarios estimated a decrease in HCV prevalence from 180 142 persons to 37 246 persons and 37 721 persons, respectively, by 2030. Relative to 2015, this decrease in HCV prevalence was associated with 74%, 69%, and 69% reductions in the prevalence of decompensated cirrhosis, hepatocellular carcinoma, and liver-associated mortality, respectively, leading to HCV elimination by 2030. More aggressive treatment uptake (very aggressive scenario) could result in goal achievement up to 3 years earlier than 2030, although a rapid decrease in the initiation of treatment (rapid decrease scenario) would preclude Canada from reaching the HCV elimination goal by 2030. CONCLUSIONS AND RELEVANCEThe study findings suggest that Canada could meet the WHO goals for HCV elimination by 2030 by sustaining the current national HCV treatment rate during the next decade. This target will not be achieved if treatment uptake is allowed to decrease rapidly.

No abstract