Hepatitis C virus subtype diversity and transmission clusters characteristics among drug users in Zhuhai, South China

Abstract

Background: Hepatitis C virus (HCV) infection poses a major public health challenge globally, especially among injecting drug users. China has the world's largest burden of HCV infections. However, little is known about the characteristics of transmission networks among drug user populations. This study aims to investigate the molecular epidemiology and transmission characteristics of HCV infections among drug users in Zhuhai, a bustling port city connecting Mainland China and its Special Administrative Regions.

Methods: Participants enrolled in this study were drug users incarcerated at Zhuhai's drug rehabilitation center in 2015. Their sociodemographic and behavioral information, including gender, promiscuity, drug use method, and so forth, was collected using a standardized questionnaire. Plasmas separated from venous blood were analyzed for HCV infection through ELISA and RT-PCR methods to detect anti-HCV antibodies and HCV RNA. The 5'UTR fragment of the HCV genome was amplified and further sequenced for subtype identifications and phylogenetic analysis. The phylogenetic tree was inferred using the Maximum Likelihood method based on the Tamura-Nei model, and the transmission cluster network was constructed using Cytoscape3.8.0 software with a threshold of 0.015. Binary logistic regression models were employed to assess the factors associated with HCV infection.

Results: The overall prevalence of HCV infection among drug users was 44.37%, with approximately 19.69% appearing to clear the HCV virus successfully. Binary logistic regression analysis revealed that those aged over 40, engaging in injecting drug use, and being native residents were at heightened risk for HCV infection among drug user cohorts. The predominant HCV subtypes circulating among those drug users were 6a (60.26%), followed by 3b (16.7%), 3a (12.8%), 1b (6.41%) and 1a (3.85%), respectively. Molecular transmission network analysis unveiled the presence of six transmission clusters, with the largest propagation cluster consisting of 41 individuals infected with HCV subtype 6a. Furthermore, distinct transmission clusters involved eight individuals infected with subtype 3b and seven with subtype 3a were also observed.

Conclusion: The genetic transmission networks revealed a complex transmission pattern among drug users in Zhuhai, emphasizing the imperative for a targeted and effective intervention strategy to mitigate HCV dissemination. These insights are pivotal for shaping future national policies on HCV screening, treatment, and prevention in port cities.

Keywords: Drug user; Hepatitis C virus; High-risk factor; Molecular transmission network; Phylogenetic tree.

Fig. 1

Maximum-likelihood phylogenetic tree of the HCV 5’UTR sequences from 6 reference sequences and 78 drug users in Zhuhai, China. The HCV genotypes were labeled in different colors. The outside circles provide sociodemographic and behavioral information on these individuals

Fig. 2

Hepatitis C virus molecular transmission network of drug users in Zhuhai, China. Six transmission clusters were identified, with the number of sequences per cluster varying from 2 to 41. Each node represents a person, and the line between the two nodes indicates a transmission line. The fill color, shape, borderline type, and size of each node indicate the HCV subtype, residence place, history of injecting drug use, and age details of the individual, respectively. The three diameter levels of the node, starting from the smallest, represent the age range less than 30, 31–40, and over 40, respectively