Hepatitis C Virus Transmission Dynamics Research Articles

Historical drivers of HCV Subtypes 1b and 3a in Thailand and 6f in Phetchabun, an HCV endemic area of the country.

The World Health Organization has set a target to eliminate viral hepatitis as a public threat by 2030. In pursuit of this goal, Thailand initiated a hepatitis C virus (HCV) microelimination project targeting Phetchabun province, a well-recognized high-burden HCV endemic area. However, the historical transmission dynamics of HCV in Phetchabun, and in Thailand in general, remain unclear. This study investigates the epidemic histories of HCV in Phetchabun, focusing on Subtypes 1b, 3a, and 6f, and their relationship with HCV in other regions of Thailand, using molecular phylogenetic analyses. Our results reveal nationwide the presence of Subtypes 1b and 3a, while Subtype 6f is mainly confined to Phetchabun. The initial spread of Subtype 1b was inferred to coincide with World War II and the period of suboptimal medical and hygienic standards in Thai blood transfusion services, suggesting a correlation between the two. The early expansion of Subtype 3a was, on the other hand, found to correlate with the epidemic of intravenous drug use in Thailand during the time of Vietnam War. The early expansion of Subtype 6f, in contrast, appears to coincide with the period of severe regional political conflict and social and economic instability. All these findings suggest the complex interplay between social determinants of health and HCV transmission. Post the mid-1990s/early 2000s, all subtypes showed significantly reduced population growth rates, aligning with improvements in blood transfusion safety standards, the nationwide "War on Drugs" policy, and enhanced accessibility to public healthcare and HCV treatments. These combined efforts likely have contributed to curbing the spread of HCV in Thailand. Nevertheless, our analyses reveal that the prevalence of HCV in Thailand remains high overall, emphasizing the need for further research and a nationwide approach to more effectively reduce the HCV burden in Thailand.

Hepatitis C Virus in people with experience of injection drug use following their displacement to Southern Ukraine before 2020

BackgroundDue to practical challenges associated with genetic sequencing in low-resource environments, the burden of hepatitis C virus (HCV) in forcibly displaced people is understudied. We examined the use of field applicable HCV sequencing methods and phylogenetic analysis to determine HCV transmission dynamics in internally displaced people who inject drugs (IDPWID) in Ukraine.MethodsIn this cross-sectional study, we used modified respondent-driven sampling to recruit IDPWID who were displaced to Odesa, Ukraine, before 2020. We generated partial and near full length genome (NFLG) HCV sequences using Oxford Nanopore Technology (ONT) MinION in a simulated field environment. Maximum likelihood and Bayesian methods were used to establish phylodynamic relationships.ResultsBetween June and September 2020, we collected epidemiological data and whole blood samples from 164 IDPWID (PNAS Nexus.2023;2(3):pgad008). Rapid testing (Wondfo® One Step HCV; Wondfo® One Step HIV1/2) identified an anti-HCV seroprevalence of 67.7%, and 31.1% of participants tested positive for both anti-HCV and HIV. We generated 57 partial or NFLG HCV sequences and identified eight transmission clusters, of which at least two originated within a year and a half post-displacement.ConclusionsLocally generated genomic data and phylogenetic analysis in rapidly changing low-resource environments, such as those faced by forcibly displaced people, can help inform effective public health strategies. For example, evidence of HCV transmission clusters originating soon after displacement highlights the importance of implementing urgent preventive interventions in ongoing situations of forced displacement.

Persistent Transmission of HCV among Men Who Have Sex with Men despite Widespread Screening and Treatment with Direct-Acting Antivirals.

Background: In the Netherlands, unrestricted access to direct-acting antivirals (DAAs) halved the incidence of acute hepatitis C virus (HCV) infections among HIV-infected men who have sex with men (MSM). To develop strategies that can further reduce the spread of HCV, it is important to understand the transmission dynamics of HCV. We used phylogenetic analysis of a dense sample of MSM to provide insight into the impact of unrestricted access to DAAs on HCV transmission in the Netherlands and in Belgium. Methods: We included 89 MSM that were recently infected with HCV genotype 1a in ten Dutch and one Belgian HIV treatment centers. Sequences were generated using next gene sequencing and Sanger sequencing. Maximum likelihood phylogenetic analysis (general time reversible model) was performed on concatenated NS5A and NS5B sequences and a reference set of 389 highly similar control sequences selected from GenBank. A cluster was based on a minimum bootstrap support of 90% and a 3% genetic distance threshold. Results: We found that 78 (88%) of individuals were part of seven major clusters. All clusters included individuals from across the study region, however, different cities were part of different clusters. In three clusters, HIV-negative MSM clustered with sequences from HIV-positive MSM. All clusters that were observed before the introduction of DAAs persisted after unrestricted access to DAAs became available. Conclusion: Recently acquired HCV infections among MSM in the Netherlands and Belgium are strongly clustered and therefore highly suitable for targeted prevention strategies, such as contact tracing and partner notification. Importantly, despite an HCV incidence reduction after high DAA uptake and continuously monitoring, HCV transmission persisted in the same clusters.

Can hepatitis C elimination targets be sustained among people who inject drugs post-2030?

In high-income countries, people who inject drugs (PWID) are a priority population for eliminating hepatitis C virus (HCV) by 2030. Despite evidence informing micro-elimination strategies, little is known regarding efforts needed to maintain elimination targets in populations with ongoing acquisition risks. This model-based study investigates post-elimination transmission dynamics of HCV and HIV among PWID under different scenarios where harm reduction interventions and HCV testing and treatment are scaled-down.We calibrated a dynamic compartmental model of concurrent HCV and HIV transmission among PWID in Montréal (Canada) to epidemiological data (2003-2018). We then simulated achieving the World Health Organization elimination targets by 2030. Finally, we assessed the impact of four post-elimination scenarios (2030-2050): 1) scaling-down testing, treatment, opioid agonist therapy (OAT), and needle and syringe programs (NSP) to pre-2020 levels; 2) only scaling-down testing and treatment; 3) suspending testing and treatment, while scaling down OAT and NSP to pre-2020 levels; 4) suspending testing and treatment and maintaining OAT and NSP coverage required for elimination.Scaling down interventions to pre-2020 levels (scenario 1) leads to a modest rebound in chronic HCV incidence from 2.4 to 3.6 per 100 person-years by 2050 (95% credible interval - CrI: 0.8-7.2). When only scaling down testing and treatment (scenario 2), chronic HCV incidence continues to decrease. In scenario 3 (suspending treatment and scaling down OAT and NSP), HCV incidence and mortality rapidly increase to 11.4 per 100 person-years (95%CrI: 7.4-15.5) and 3.2 per 1000 person-years (95%CrI: 2.4-4.0), respectively. HCV resurgence was mitigated in scenario 4 (maintaining OAT and NSP) as compared to scenario 3. All scenarios lead to decreases in the proportion of reinfections among incident cases and have little impact on HIV incidence and HIV-HCV coinfection prevalence.Despite ongoing transmission risks, HCV incidence rebounds slowly after 2030 under pre-2020 testing and treatment levels. This is heightened by maintaining high-coverage harm reduction interventions. Overall, sustaining elimination would require considerably less effort than achieving it.

Sensitivity analysis of chronic hepatitis C virus infection with immune response and cell proliferation

A new mathematical model of chronic hepatitis C virus (HCV) infection incorporating humoral and cell-mediated immune responses, distinct cell proliferation rates for both uninfected and infected hepatocytes, and antiviral treatment all at once, is formulated and analyzed meticulously. Analysis of the model elucidates the existence of multiple equilibrium states. Moreover, the model has a locally asymptotically stable disease-free equilibrium (DFE) whenever the basic reproduction number is less than unity. Local sensitivity analysis (LSA) result exhibits that the most influential (negatively sensitive) parameters on the epidemic threshold are the drug efficacy of blocking virus production and the drug efficacy of removing infection. However, LSA does not accurately assess uncertainty and sensitivity in the system and may mislead us since by default this technique holds all other parameters fixed at baseline values. To overcome this pitfall, one of the most robust and efficient global sensitivity analysis (GSA) methods, which is Latin hypercube sampling-partial rank correlation coefficient technique, elucidates that the proliferation rate of infected hepatocytes and the drug efficacy of killing infected hepatocytes are highly sensitive parameters that affect the transmission dynamics of HCV in any population. Our study suggests that cell proliferation of the infected hepatocytes can be very crucial in controlling disease outbreak. Thus, a future HCV drug that boosts cell-mediated immune response is expected to be quite effective in controlling disease outbreak.

Shared HCV Transmission Networks Among HIV-1-Positive and HIV-1-Negative Men Having Sex With Men by Ultradeep Sequencing.

Several studies reported hepatitis C virus (HCV) transmission networks among men having sex with men (MSM) in Europe and the spread of HCV strains from HIV-HCV coinfected toward HCV monoinfected MSM. We aimed to investigate HCV transmission dynamics among HIV-positive and HIV-negative MSM by ultradeep sequencing (UDS). NS5B fragment (388 bp) was sequenced from virus of 50 HIV-positive and 18 HIV-negative patients diagnosed with recent HCV infection. UDS data were analyzed by Geneious (version 10.3.2). Phylogenetic trees were constructed by FastTree (version 2.1) and submitted to ClusterPicker (version 1.2.3) for transmission chain detection at different thresholds of maximum genetic distance (MGD) (3% for Sanger, 3% and 4.5% for UDS). Ten, 17, and 18 HCV transmission chains were identified by Sanger at 3%, UDS at 3% and at 4.5% of MGD, respectively. Of 68 subjects enrolled, 38 (55.9%), 38 (55.9%), and 43 (65.3%) individuals were involved in transmission networks found by Sanger at 3%, UDS at 3%, and at 4.5% of MGD, respectively. Mixed transmission chains including HIV-positive and HIV-negative subjects were detected for 8/10 chains by Sanger at 3%, for 9/17 by UDS at 3%, and for 10/18 by UDS at 4.5% of MGD. Overall, the number of HIV-negative individuals clustering with HIV-positive ones was 9/18 by Sanger, 9/18 by UDS at 3%, and 10/18 by UDS at 4.5% of MGD. HIV-positive and HIV-negative MSM shared HCV transmission networks, which emphasizes the need for HCV surveillance and prevention measures in these communities regardless of the HIV status.

A21 Retrospectively describing hepatitis C virus transmission dynamics and tracking HCV transmission networks in real-time for strategic elimination interventions

Despite impressive uptake of direct acting antivirals for hepatitis C virus (HCV) in the Netherlands among HIV/HCV co-infected men who have sex with men (MSM), HCV transmission continues, especially among patients previously successfully treated for HCV. The incidence of reinfection occurs at the extremely high rate of 15 per 100 person-years. Clearly, more sophisticated methods are necessary to identify the sources and timing of new HCV infections among MSM. The aim of this research is to phylogenetically characterize HCV transmission dynamics within MSM-specific networks in order to provide a solid base for targeted interventions to monitor, control, and eventually stop the ongoing transmission of HCV among HIV-infected MSM and to prevent further spread of HCV to the community at large. The methodology that will be used is two-fold. Firstly, it concerns setting up a real-time monitoring system to track the HCV epidemic using phylogenetic tools and open-source software from http://nextstrain.org. Secondly, several phylogenetic methods will be used to retrospectively identify transmission clusters in Amsterdam and define epidemiological characteristics, including the directionality of transmission and the size and introduction dates of the clusters. This means that cluster cut-off points will have to be calculated. This research will result in a web-based molecular surveillance tool to monitor the persistence of endemic clades, emergence of new clades, and transmission clusters in ‘real time’, which, combined with clinical and epidemiological data, will be used for targeted interventions. The surveillance tool will be based on the open-source software from nextstrain.org. Secondly, by retrospectively describing the HCV transmission clusters in terms of introduction dates and subsequent dynamics, we may be able to better predict the future dynamics of the different clusters. High-resolution viral sequencing will allow us to identify the source and timing of (new) HCV infections and follow the trajectory of these MSM-specific lineages through the MSM population. Real-time insight in transmission networks using a web-based molecular surveillance tool will identify key targets for rapid interventions, awareness campaigns, and testing strategies. This can be used to prevent further spread to HIV-negative MSM and to control and eventually eliminate HCV from the MSM population.

Deep sequencing increases hepatitis C virus phylogenetic cluster detection compared to Sanger sequencing

Effective surveillance and treatment strategies are required to control the hepatitis C virus (HCV) epidemic. Phylogenetic analyses are powerful tools for reconstructing the evolutionary history of viral outbreaks and identifying transmission clusters. These studies often rely on Sanger sequencing which typically generates a single consensus sequence for each infected individual. For rapidly mutating viruses such as HCV, consensus sequencing underestimates the complexity of the viral quasispecies population and could therefore generate different phylogenetic tree topologies. Although deep sequencing provides a more detailed quasispecies characterization, in-depth phylogenetic analyses are challenging due to dataset complexity and computational limitations. Here, we apply deep sequencing to a characterized population to assess its ability to identify phylogenetic clusters compared with consensus Sanger sequencing. For deep sequencing, a sample specific threshold determined by the 50th percentile of the patristic distance distribution for all variants within each individual was used to identify clusters. Among seven patristic distance thresholds tested for the Sanger sequence phylogeny ranging from 0.005–0.06, a threshold of 0.03 was found to provide the maximum balance between positive agreement (samples in a cluster) and negative agreement (samples not in a cluster) relative to the deep sequencing dataset. From 77 HCV seroconverters, 10 individuals were identified in phylogenetic clusters using both methods. Deep sequencing analysis identified an additional 4 individuals and excluded 8 other individuals relative to Sanger sequencing. The application of this deep sequencing approach could be a more effective tool to understand onward HCV transmission dynamics compared with Sanger sequencing, since the incorporation of minority sequence variants improves the discrimination of phylogenetically linked clusters.

Dynamics of HCV in the Presence of Optimal Bleaching

In an effort to slow transmission of blood-borne pathogens among intravenous drug misusers, clinicians through harm reduction programs have tried to educate intravenous drug misusers about the dangers of sharing needles and other injecting equipment. These programs encourage the use of new needles for every injection or, when new equipment is not available, too clean needles by bleaching them before they are reused. In this paper, a mathematical model for the transmission dynamics of hepatitis C virus (HCV) has been proposed and investigated. The impacts of bleaching and individual withdrawal on the transmission dynamics of HCV are discussed through the basic reproductive number and numerical simulations. For the time dependent control, we formulate the appropriate optimal control problem and investigate the necessary conditions for HCV control in order to determine the impact of bleaching on HCV prevalence. Although, bleaching is not 100 % effective, results in this paper suggests that if bleaching is 70 % effective in the absence of time dependent control then cumulative cases of new HCV infections may have a significant decline. However, in the presence of time dependent control we have established that if bleaching is 55 % effective HCV may die out.

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

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.

Transmission of Hepatitis C Virus among Prisoners, Australia, 2005–2012

Hepatitis C virus (HCV) is predominantly transmitted between persons who inject drugs. For this population, global prevalence of HCV infection is high and incarceration is common and an independent risk factor for HCV acquisition. To explore HCV transmission dynamics in incarcerated populations, we integrated virus sequences with risk behavior and spatiotemporal data and analyzed transmission clusters among prisoners in Australia. We detected 3 clusters of recent HCV transmission consisting of 4 likely in-custody transmission events involving source/recipient pairs located in the same prison at the same time. Of these 4 events, 3 were associated with drug injecting and equipment sharing. Despite a large population of prisoners with chronic HCV, recent transmission events were identified in the prison setting. This ongoing HCV transmission among high-risk prisoners argues for expansion of prevention programs to reduce HCV transmission in prisons.

A molecular phylogenetics-based approach for identifying recent hepatitis C virus transmission events

Improved surveillance methods are needed to better understand the current hepatitis C virus (HCV) disease burden and to monitor the impact of prevention and treatment interventions on HCV transmission dynamics. Sanger sequencing (HCV NS5B, HVR1 and Core-E1-HVR1) and phylogenetics were applied to samples from individuals diagnosed with HCV in British Columbia, Canada in 2011. This included individuals with two or three sequential samples collected <1year apart. Patristic distances between sequential samples were used to set cutoffs to identify recent transmission clusters. Factors associated with transmission clustering were analyzed using logistic regression. From 618 individuals, 646 sequences were obtained. Depending on the cutoff used, 63 (10%) to 92 (15%) unique individuals were identified within transmission clusters of predicted recent origin. Clustered individuals were more likely to be <40years old (Adjusted Odds Ratio (AOR) 2.12, 95% CI 1.21–3.73), infected with genotype 1a (AOR 6.60, 95% CI 1.98–41.0), and to be seroconverters with estimated infection duration of <1year (AOR 3.13, 95% CI 1.29–7.36) or >1year (AOR 2.19, 95% CI 1.22–3.97).Conclusion: Systematic application of molecular phylogenetics may be used to enhance traditional surveillance methods through identification of recent transmission clusters.

Differential characteristics of primary infection and re-infection can cause backward bifurcation in HCV transmission dynamics

Backward bifurcation, a phenomenon typically characterized by the co-existence of multiple stable equilibria when the associated reproduction number of the model is less than unity, has been observed in numerous disease transmission models. This study establishes, for the first time, the presence of this phenomenon in the transmission dynamics of hepatitis C virus (HCV) within an IDU population. It is shown that the phenomenon does not exist under four scenarios, namely (i) in the absence of re-infection, (ii) in the absence of differential characteristics of HCV infection (with respect to infectivity, progression, treatment and recovery) between re-infected individuals and primary-infected individuals, (iii) when re-infected and treated individuals do not transmit HCV infection and (iv) when the average infectivity-adjusted duration of re-infection is less than that of primary infection. This study identifies, using sensitivity analysis, five parameters of the model that have the most influence on the disease transmission dynamics, namely: effective contact rate, progression rate from acute to chronic infection, recovery rate from acute infection, natural death rate and the relative infectiousness of chronically-infected individuals. Numerical simulations of the model show that the re-infection of recovered individuals has marginal effect on the HCV burden (as measured in terms of the cumulative incidence and the prevalence of the disease) in the IDU community. Furthermore, treatment of infected IDUs, even for small rate (such as 4%), offers significant impact on curtailing HCV spread in the community.

On the Role of Optimal Counseling and Antiviral Therapy on Controlling HCV among Intravenous Drug Misusers

Hepatitis C virus (HCV) remains a major health challenge despite the availability of highly effective antiviral drugs. Prior studies suggest that many physicians are reluctant to treat intravenous drug misusers due to low levels of treatment adherence associated with intravenous drug misusers. HCV treatment guidelines and recommendations stipulate that HCV patients in treatment should abstain from intravenous drug misuse activities in order to reduce the likelihood of treatment failure, drug resistance, reinfection, superinfection, or mixed infection. In this paper, a mathematical model for exploring the transmission dynamics of HCV among intravenous drug misusers is proposed. The model incorporates essential characteristics of intravenous drug misusers such as relapse and nonadherence to treatment guidelines. With the aid of optimal control theory we assess the effects of time dependent HCV screening and treatment. Results from this study provide a framework for designing the appropriate strategies on controlling the long-term dynamics of HCV among intravenous drug users.

Mathematical analysis of hepatitis C model for intravenous drug misusers: Impact of antiviral therapy, abstinence and relapse

Despite advances in hepatitis C therapy and better knowledge of viral/host factors related to disease progression, hepatitis C virus (HCV) remains the leading cause of chronic liver disease, causing progression to end-stage liver disease (ESLD) as well as the development of hepatocellular carcinoma. In this paper a mathematical model for assessing the impact of antiviral therapy, abstinence and relapse on the transmission dynamics of HCV is formulated and analyzed. A threshold quantity known as the reproductive number has been computed, and the stability of the steady states has been investigated. The dynamical analysis reveals that the model has globally asymptotically stable steady states. The impacts of antiviral therapy, abstinence and relapse on the transmission dynamics of HCV are discussed through the basic reproductive number and numerical simulations.

HEPATITIS C VIRUS AND INTRAVENOUS DRUG MISUSE: A MODELING APPROACH

Hepatitis C virus (HCV) is a blood-borne infection that can lead to progressive liver failure, cirrhosis, hepatocellular carcinoma and death. A deterministic mathematical model for assessing the impact of daily intravenous drug misuse on the transmission dynamics of HCV is presented and analyzed. A threshold quantity known as the reproductive number has been computed. Stability of the steady states has been investigated. The dynamical analysis reveals that the model has globally asymptotically stable steady states. The impact of daily intravenous drug misuse on the transmission dynamics of HCV has been discussed through the basic reproductive number and numerical simulations.

Social Networks Shape the Transmission Dynamics of Hepatitis C Virus

Hepatitis C virus (HCV) infects 170 million people worldwide, and is a major public health problem in Brazil, where over 1% of the population may be infected and where multiple viral genotypes co-circulate. Chronically infected individuals are both the source of transmission to others and are at risk for HCV-related diseases, such as liver cancer and cirrhosis. Before the adoption of anti-HCV control measures in blood banks, this virus was mainly transmitted via blood transfusion. Today, needle sharing among injecting drug users is the most common form of HCV transmission. Of particular importance is that HCV prevalence is growing in non-risk groups. Since there is no vaccine against HCV, it is important to determine the factors that control viral transmission in order to develop more efficient control measures. However, despite the health costs associated with HCV, the factors that determine the spread of virus at the epidemiological scale are often poorly understood. Here, we sequenced partial NS5b gene sequences sampled from blood samples collected from 591 patients in São Paulo state, Brazil. We show that different viral genotypes entered São Paulo at different times, grew at different rates, and are associated with different age groups and risk behaviors. In particular, subtype 1b is older and grew more slowly than subtypes 1a and 3a, and is associated with multiple age classes. In contrast, subtypes 1a and 3b are associated with younger people infected more recently, possibly with higher rates of sexual transmission. The transmission dynamics of HCV in São Paulo therefore vary by subtype and are determined by a combination of age, risk exposure and underlying social network. We conclude that social factors may play a key role in determining the rate and pattern of HCV spread, and should influence future intervention policies.

Preventing hepatitis C virus infection in injection drug users: risk reduction is not enough

Preventing hepatitis C virus infection in injection drug users: risk reduction is not enough

The epidemiology and iatrogenic transmission of hepatitis C virus in Egypt: a Bayesian coalescent approach.

Hepatitis C virus (HCV) is a leading cause of liver cancer and cirrhosis, and Egypt has possibly the highest HCV prevalence worldwide. In this article we use a newly developed Bayesian inference framework to estimate the transmission dynamics of HCV in Egypt from sampled viral gene sequences, and to predict the public health impact of the virus. Our results indicate that the effective number of HCV infections in Egypt underwent rapid exponential growth between 1930 and 1955. The timing and speed of this spread provides quantitative genetic evidence that the Egyptian HCV epidemic was initiated and propagated by extensive antischistosomiasis injection campaigns. Although our results show that HCV transmission has since decreased, we conclude that HCV is likely to remain prevalent in Egypt for several decades. Our combined population genetic and epidemiological analysis provides detailed estimates of historical changes in Egyptian HCV prevalence. Because our results are consistent with a demographic scenario specified a priori, they also provide an objective test of inference methods based on the coalescent process.