Lives saved by public health restrictions over the Victorian COVID-19 Delta variant epidemic wave, Aug-Nov 2021.

BACKGROUND: Prior to mid-2021, Australia's approach to COVID-19 was to eliminate community transmission. However, between August-November 2021, the state of Victoria, Australia, experienced an outbreak of the Delta variant that continued to grow despite extensive lockdowns and public health measures in place. While these public health restrictions were ultimately unable to stop community transmission, they likely had a major impact reducing transmission and adverse health outcomes relative to voluntary risk-mitigation only (e.g., in response to rising cases and deaths, some people may avoid crowded settings, hospitality, retail, social occasions, or indoor settings). This study aims to estimate the impact of the August-November 2021 enforced public health restrictions in Victoria, compared to voluntary risk-mitigation only. METHODS: An agent-based model was calibrated to Victorian epidemiological, health and behavioural data from 1 August to 30 November 2021, as well as policies that were implemented over that period. Two counter-factual scenarios were run for the same period with (a) no restrictions in place; or (b) voluntary risk-mitigation only, based on behaviour measured over the December-January Omicron BA.1 epidemic wave when restrictions were not in place. RESULTS: Over August-November 2021, the baseline model scenario resulted in 97,000 (91,000-102,000) diagnoses, 9100 (8500-9700) hospital admissions, and 480 (430-530) deaths. Without any restrictions in place, there were 3,228,000 (3,200,000-3,253,000) diagnoses, 375,100 (370,200-380,900) hospital admissions, and 16,700 (16,000-17,500) deaths. With voluntary risk-mitigation equal to those observed during the Omicron BA.1 epidemic wave, there were 1,507,000 (1,469,000-1,549,000) diagnoses, 130,300 (124,500-136,000) hospital admissions, and 5500 (5000-6100) deaths. CONCLUSION: Public health restrictions implemented in Victoria over August-November 2021 are likely to have averted more than 120,000 hospitalizations and 5000 deaths relative to voluntary risk-mitigation only. During a COVID-19 epidemic wave voluntary behaviour change can reduce transmission substantially, but not to the same extent as enforced restrictions.

Response to treatment following recently acquired hepatitis C virus infection in a multicentre collaborative cohort.

Pegylated interferon therapy is highly effective in recently acquired HCV. The optimal timing of treatment, regimen and influence of host factors remains unclear. We aimed to measure sustained virological response (SVR) during recent HCV infection and identify predictors of response. Data were from five prospective cohorts of high-risk individuals in Australia, Canada, Germany and the United States. Individuals with acute or early chronic HCV who commenced pegylated interferon therapy were included. The main outcome was SVR, and predictors were assessed using logistic regression. Among 516 with documented recent HCV infection, 237 were treated (pegylated interferon n = 161; pegylated interferon/ribavirin n = 76) (30% female, median age 35 years, 56% ever injected drugs, median duration of infection 6.2 months). Sixteen per cent (n = 38) were HIV/HCV co-infected. SVR among those with HCV mono-infection was 64% by intention to treat; SVR was 68% among HCV/HIV co-infection. Independent predictors of SVR in HCV mono-infection were duration of HCV infection (the odds of SVR declined by 8% per month of infection, aOR 0.92, 95% CI 0.85-0.99, P = 0.033), IFNL4 genotype (adjusted OR 2.27, 95% CI 1.13-4.56, P = 0.021), baseline HCV RNA <400 000 IU/mL (aOR 2.06, 95% CI 1.03-4.12, P = 0.041) and age ≥40 years (vs <30: aOR 2.92, 95% CI 1.31-6.49, P = 0.009), with no difference by drug regimen, HCV genotype, symptomatic infection or gender. The effect of infection duration on odds of SVR was greater among genotype-1 infection. Interferon-based HCV treatment is highly effective in recent HCV infection. Duration of infection, IFNL4 genotype and baseline HCV RNA levels can predict virological response and may inform clinical decision-making.

Factors associated with hepatitis C virus RNA levels in early chronic infection: the InC3 study.

Improved understanding of natural history of hepatitis C virus (HCV) RNA levels in chronic infection provides enhanced insights into immunopathogenesis of HCV and has implications for the clinical management of chronic HCV infection. This study assessed factors associated with HCV RNA levels during early chronic infection in a population with well-defined early chronic HCV infection. Data were from an international collaboration of nine prospective cohorts studying acute HCV infection (InC(3) study). Individuals with persistent HCV and detectable HCV RNA during early chronic infection (one year [±4 months] postinfection) were included. Distribution of HCV RNA levels during early chronic infection was compared by selected host and virological factors. A total of 308 individuals were included. Median HCV RNA levels were significantly higher among males (vs females; 5.15 vs 4.74 log IU/mL; P < 0.01) and among individuals with HIV co-infection (vs no HIV; 5.89 vs 4.86; P = 0.02). In adjusted logistic regression, male sex (vs female, adjusted odds ratio [AOR]: 1.93; 95%CI: 1.01, 3.69), interferon lambda 4 (IFNL4) rs12979860 CC genotype (vs TT/CT; AOR: 2.48; 95%CI: 1.42, 4.35), HIV co-infection (vs no HIV; AOR: 3.27; 95%CI: 1.35, 7.93) and HCV genotype G2 (vs G3; AOR: 5.40; 95%CI: 1.63, 17.84) were independently associated with high HCV RNA levels (>5.6 log IU/mL = 400 000 IU/mL). In conclusion, this study demonstrated that IFNL4 rs12979860 CC genotype, male sex, HIV co-infection and HCV genotype G2 are associated with high HCV RNA levels in early chronic infection. These factors exert their role as early as one year following infection.

Does informing people who inject drugs of their hepatitis C status influence their injecting behaviour? Analysis of the Networks II study.

BACKGROUND: People who inject drugs (PWID) are at risk of hepatitis C virus (HCV). It is plausible that PWID who receive a diagnosis of HCV will reduce their injecting risk out of concern for their injecting partners, although evidence for this is currently limited. The aim of this study was to investigate whether informing PWID of their HCV diagnosis was associated with a change in injecting behaviour. METHODS: Prospective, longitudinal study of PWID recruited from street drug markets across Melbourne, Australia. Interviews and HCV testing were conducted at 3-monthly intervals. The association between receiving a diagnosis of HCV and (i) injecting frequency and (ii) injecting equipment borrowing, was examined using generalized estimating equations (GEE) analysis. RESULTS: Thirty-five individuals received a diagnosis of HCV during the study period. Receiving a diagnosis of HCV was associated with a decrease of 0.35 injections per month (p=0.046) but there was no change in injecting equipment borrowing (p=0.750). CONCLUSIONS: A small reduction in injecting frequency was observed in PWID who received a diagnosis of HCV. This finding should be investigated further in larger studies examining a wider range of injecting risk behaviours.

Identifying newly acquired cases of hepatitis C using surveillance: a literature review.

Surveillance of newly acquired hepatitis C virus (HCV) infection is crucial for understanding the epidemiology of HCV and informing public health practice. However, monitoring such infections via surveillance systems is challenging because they are commonly asymptomatic. A literature review was conducted to identify methodologies used by HCV surveillance systems to identify newly acquired infections; relevant surveillance systems in 15 countries were identified. Surveillance systems used three main strategies to identify newly acquired infections: (1) asking physicians to classify cases; (2) identifying symptomatic cases or cases with elevated alanine aminotransferases; and (3) identifying cases with documented evidence of anti-HCV antibody seroconversion within a specific time-frame. Case-ascertainment methods varied with greater completeness of data in enhanced compared to passive surveillance systems. Automated systems that extract and link testing data from multiple laboratory and clinic databases may provide an opportunity for collecting testing histories for individuals that is less resource intensive than enhanced surveillance.

Modelling hepatitis C transmission over a social network of injecting drug users.

Hepatitis C virus (HCV) is a blood-borne virus that disproportionately affects people who inject drugs (PWIDs). Based on extensive interview and blood test data from a longitudinal study in Melbourne, Australia, we describe an individual-based transmission model for HCV spread amongst PWID. We use this model to simulate the transmission of HCV on an empirical social network of PWID. A feature of our model is that sources of infection can be both network neighbours and non-neighbours via "importing". Data-driven estimates of sharing frequency and rate of importing are provided. Compared to an appropriately calibrated fully connected network, the empirical network provides some protective effect on the time to primary infection. We also illustrate heterogeneities in incidence rate of infection, both across and within node degrees (i.e., number of network partners). We explore the reduced risk of infection from spontaneously clearing cutpoint nodes whose infection status oscillates, both in theory and in simulation. Further, we show our model-based estimate of per-event transmission probability largely agrees with previous estimates at the lower end of the range 1-3% commonly cited.