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Spatiotemporal Reconstruction of the Introduction of Hepatitis C Virus into Scotland and Its Subsequent Regional Transmission.

ABSTRACT: A more comprehensive understanding of hepatitis C virus (HCV) transmission dynamics could facilitate public health initiatives to reduce the prevalence of HCV in people who inject drugs. We aimed to determine how HCV sequences entered and spread throughout Scotland and to identify transmission hot spots. A Scottish data set with embedded demographic data was created by sequencing the NS5B of 125 genotype 1a (Gt1a) samples and 166 Gt3a samples and analyzed alongside sequences from public databases. Applying Bayesian inference methods, we reconstructed the global origin and local spatiotemporal dissemination of HCV in Scotland. Scottish sequences mainly formed discrete clusters interspersed between sequences from the rest of the world; the most recent common ancestors of these clusters dated to 1942 to 1952 (Gt1a) and 1926 to 1942 (Gt3a), coincident with global diversification and distribution. Extant Scottish sequences originated in Edinburgh (Gt1a) and Glasgow (Gt3a) in the 1970s, but both genotypes spread from Glasgow to other regions. The dominant Gt1a strain differed between Edinburgh (cluster 2 [C2]), Glasgow (C3), and Aberdeen (C4), whereas significant Gt3a strain specificity occurred only in Aberdeen. Specific clusters initially formed separate transmission zones in Glasgow that subsequently overlapped, occasioning city-wide cocirculation. Transmission hot spots were detected with 45% of samples from patients residing in just 9 of Glasgow's 57 postcode districts. HCV was introduced into Scotland in the 1940s, concomitant with its worldwide dispersal likely arising from global-scale historical events. Cluster-specific transmission hubs were identified in Glasgow, the key Scottish city implicated in HCV dissemination. This fine-scale spatiotemporal reconstruction improves understanding of HCV transmission dynamics in Scotland.HCV is a major health burden and the leading cause of hepatocellular carcinoma. Public health needle exchange and "treatment as prevention" strategies targeting HCV are designed to reduce prevalence of the virus in people who inject drugs (PWID), potentially mitigating the future burden of HCV-associated liver disease. Understanding HCV transmission dynamics could increase the effectiveness of such public health initiatives by identifying and targeting regions playing a central role in virus dispersal. In this study, we examined HCV transmission in Scotland by analyzing the genetic relatedness of strains from PWID alongside data inferring the year individuals became infected and residential information at a geographically finer-scale resolution than in previous studies. Clusters of Scotland-specific strains were identified with regional specificity, and mapping the spread of HCV allowed the identification of key areas central to HCV transmission in Scotland. This research provides a basis for identifying HCV transmission hot spots.

SUBMITTER: McNaughton AL

PROVIDER: S-EPMC4645645 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Spatiotemporal Reconstruction of the Introduction of Hepatitis C Virus into Scotland and Its Subsequent Regional Transmission.

McNaughton Anna L AL Cameron Iain Dugald ID Wignall-Fleming Elizabeth B EB Biek Roman R McLauchlan John J Gunson Rory N RN Templeton Kate K Tan Harriet Mei-Lin HM Leitch E Carol McWilliam EC

Journal of virology 20150826 22

<h4>Unlabelled</h4>A more comprehensive understanding of hepatitis C virus (HCV) transmission dynamics could facilitate public health initiatives to reduce the prevalence of HCV in people who inject drugs. We aimed to determine how HCV sequences entered and spread throughout Scotland and to identify transmission hot spots. A Scottish data set with embedded demographic data was created by sequencing the NS5B of 125 genotype 1a (Gt1a) samples and 166 Gt3a samples and analyzed alongside sequences f ...[more]

PMID: 26311892

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Project description:Background and aimsTo reduce hepatitis C virus (HCV) transmission among people who inject drugs (PWID), Scottish Government-funded national strategies, launched in 2008, promoted scaling-up opioid substitution therapy (OST) and needle and syringe provision (NSP), with some increases in HCV treatment. We test whether observed decreases in HCV incidence post-2008 can be attributed to this intervention scale-up.DesignA dynamic HCV transmission model among PWID incorporating intervention scale-up and observed decreases in behavioural risk, calibrated to Scottish HCV prevalence and incidence data for 2008/09.SettingScotland, UK.ParticipantsPWID.MeasurementsModel projections from 2008 to 2015 were compared with data to test whether they were consistent with observed decreases in HCV incidence among PWID while incorporating the observed intervention scale-up, and to determine the impact of scaling-up interventions on incidence.FindingsWithout fitting to epidemiological data post-2008/09, the model incorporating observed intervention scale-up agreed with observed decreases in HCV incidence among PWID between 2008 and 2015, suggesting that HCV incidence decreased by 61.3% [95% credibility interval (CrI) = 45.1-75.3%] from 14.2/100 person-years (py) (9.0-20.7) to 5.5/100 py (2.9-9.2). On average, each model fit lay within 84% (10.1/12) of the confidence bounds for the 12 incidence data points against which the model was compared. We estimate that scale-up of interventions (OST + NSP + HCV treatment) and decreases in high-risk behaviour from 2008 to 2015 resulted in a 33.9% (23.8-44.6%) decrease in incidence, with the remainder [27.4% (17.6-37.0%)] explained by historical changes in OST + NSP coverage and risk pre-2008. Projections suggest that scaling-up of all interventions post-2008 averted 1492 (657-2646) infections over 7 years, with 1016 (308-1996), 404 (150-836) and 72 (27-137) due to scale-up of OST + NSP, decreases in high-risk behaviour and HCV treatment, respectively.ConclusionsMost of the decline in hepatitis C virus (HCV) incidence in Scotland between 2008 and 2015 appears to be attributable to intervention scale-up (opioid substitution therapy and needle and syringe provision) due to government strategies on HCV and drugs.

Project description:Background and aimsPeople who inject drugs (PWID) experience high incarceration rates, and previous incarceration is associated with elevated hepatitis C virus (HCV) transmission risk. In Scotland, national survey data indicate lower HCV incidence in prison than the community (4.3 versus 7.3 per 100 person-years), but a 2.3-fold elevated transmission risk among recently released (< 6 months) PWID. We evaluated the contribution of incarceration to HCV transmission among PWID and the impact of prison-related prevention interventions, including scaling-up direct-acting antivirals (DAAs) in prison.DesignDynamic mathematical modelling of incarceration and HCV transmission, using approximate Bayesian computation for model calibration.SettingScotland, UK.ParticipantsA simulated population of PWID.MeasurementsPopulation-attributable fraction (PAF) of incarceration to HCV transmission among PWID. Decrease in HCV incidence and chronic prevalence due to current levels of prison opiate substitution therapy (OST; 57% coverage) and HCV treatment, as well as scaling-up DAAs in prison and/or preventing the elevated risk associated with prison release.FindingsIncarceration contributes 27.7% [PAF; 95% credible interval (CrI) -3.1 to 51.1%] of HCV transmission among PWID in Scotland. During the next 15 years, current HCV treatment rates (10.4/6.8 per 1000 incarcerated/community PWID annually), with existing prison OST, could reduce incidence and chronic prevalence among all PWID by a relative 10.7% (95% CrI = 8.4-13.3%) and 9.7% (95% CrI = 7.7-12.1%), respectively. Conversely, without prison OST, HCV incidence and chronic prevalence would decrease by 3.1% (95% CrI = -28.5 to 18.0%) and 4.7% (95% CrI = -11.3 to 14.5%). Additionally, preventing the heightened risk among recently released PWID could reduce incidence and chronic prevalence by 45.0% (95% CrI = 19.7-57.5%) and 33.3% (95% CrI = 15.6-43.6%) or scaling-up prison HCV treatments to 80% of chronic PWID prison entrants with sufficient sentences (>16 weeks) could reduce incidence and prevalence by 45.6% (95% CrI = 38.0-51.3%) and 45.5% (95% CrI = 39.3-51.0%), respectively.ConclusionsIncarceration and the elevated transmission risk following prison release can contribute significantly to hepatitis C virus transmission among people who inject drugs. Scaling-up hepatitis C virus treatment in prison can provide important prevention benefits.

Dataset Information

Spatiotemporal Reconstruction of the Introduction of Hepatitis C Virus into Scotland and Its Subsequent Regional Transmission.

Publications

Spatiotemporal Reconstruction of the Introduction of Hepatitis C Virus into Scotland and Its Subsequent Regional Transmission.

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