Population dynamics of HCV subtypes in injecting drug-users on methadone maintenance treatment in China associated with economic and health reform

The extensive genetic heterogeneity of hepatitis C virus (HCV) requires in-depth understanding of the population dynamics of different viral subtypes for more effective control of epidemic outbreaks. We analyzed HCV sequences data from 125 participants in Wuhan, China. These participants were newly infected by subtype 1b (n=13), 3a (n=15), 3b (n=50), and 6a (n=39) while on methadone maintenance treatment (MMT). Bayesian phylogenies and demographic histories were inferred for these subtypes. Participants infected with HCV-1b and 3a were clustered in well-supported monophyletic clades, indicating local sub-epidemics. Subtypes 3b and 6a strains were intermixed with other Chinese isolates, as well as isolates from other Asian countries, reflecting ongoing across geographic boundary transmissions. Subtypes 1b and 3a declined continuously during the past ten years, consistent with the health and economic reform in China, while subtype 3b showed ongoing exponential growth and 6a was characterized by several epidemic waves, possibly related to the recently growing number of travelers between China and other Asian countries. In conclusion, results of this study suggest that HCV subtype 3b and 6a sub-A epidemics in China are currently not under control, and new epidemic waves may emerge given the rapid increase in international traveling following substantial economic growth. By analysis of the recent sequence data among drug users in Wuhan who were under methadone maintenance treatment, several HCV subtypes and transmission clusters were detected. The population dynamics of the detected subtypes were consistent with the economic growth and health care reform in China over the past 30 years, while the detected clusters provided evidence regarding the significance of continued injecting drug use and sexual risk behavior in fueling the epidemic. These findings provided new evidence regarding HCV in Wuhan and suggest urgent need for more effective prevention interventions targeting specific risk behaviors and new domestic and international collaborative prevention strategies for potential new waves of different HCV subtype epidemics. side of a specific topology. In such a likelihood map, three areas can be distinguished: (a) the three corners, representing fully resolved tree topologies, i.e. the presence of tree like phylogenetic signal in the data; (b) the center, representing the star-like phylogeny, and (c) the three side areas, indicating network-like phylogeny, i.e. presence of recombination or conflicting phylogenetic signals. Findings from extensive simulation studies and analysis of real data sets suggest that >30% dots in the central area indicate significant phylogenetic noise (star-like signal), reducing the reliability of phylogeny inference(11-13).

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