Genomic surveillance uncovers regional variation in HCV transmission networks in rural United States

Hepatitis C virus (HCV) remains a public health concern in the United States, particularly in rural communities where the opioid epidemic accelerates transmission among people who use drugs (PWUD). Despite this growing burden, the genetic features and transmission dynamics of HCV in these settings are poorly understood. We analyze 692 HCV antibody-positive specimens collected from rural communities in ten U.S. states using amplicon-based deep sequencing and the Global Hepatitis Outbreak and Surveillance Technology (GHOST) platform to reconstruct transmission networks. Among sequenced individuals, 29.5% are linked within clusters. Cluster structure varies by region from sparse networks in Ohio to dense clusters in New England and phylogenetic analyses show that some networks persist for over a decade, indicating sustained transmission. Nearly half of all clusters involve individuals connected through social recruitment, suggesting peer-referral strategies effectively identify transmission chains. Penalized regression retains only a few individual factors including younger age, peer or partner recruitment, illegal income, methamphetamine use, each with modest effects. These findings suggest that clustering is shaped primarily by social and structural contexts rather than individual characteristics and underscore the importance of integrating genomic surveillance with social-network insights to detect emerging HCV clusters and guide targeted interventions in underserved rural communities.

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Publication Details

Journal
Nature Communications
Published
2025-12-02
DOI
https://doi.org/10.1038/s41467-025-66934-y
Primary Topic
Hepatitis C virus research
Type
article
Field-Weighted Citation Impact
0.00

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article

Genomic surveillance uncovers regional variation in HCV transmission networks in rural United States

Jennifer R. Havens, Thomas J. Stopka, Daniel Brook, David J. Bean et al.
Nature Communications
Hepatitis C virus research
article

Genomic surveillance uncovers regional variation in HCV transmission networks in rural United States

Jennifer R. Havens, Thomas J. Stopka, Daniel Brook, David J. Bean, Christopher B. Hurt, Damien C. Tully, Gordon S. Smith, Judith Feinberg, Todd M. Allen, Wiley D. Jenkins, Shanna L. Babalonis, P. Todd Korthuis, Hannah L. F. Cooper, Peter D. Friedmann, L. Sarah Mixson, Thang Long Ngo, Ryan P. Westergaard, William C. Miller, Judith I. Tsui, April M. Young, Karli R. Hochstatter, Karen A. Power, Jacklyn Sarette, Mai T. Pho
article en

Abstract

Hepatitis C virus (HCV) remains a public health concern in the United States, particularly in rural communities where the opioid epidemic accelerates transmission among people who use drugs (PWUD). Despite this growing burden, the genetic features and transmission dynamics of HCV in these settings are poorly understood. We analyze 692 HCV antibody-positive specimens collected from rural communities in ten U.S. states using amplicon-based deep sequencing and the Global Hepatitis Outbreak and Surveillance Technology (GHOST) platform to reconstruct transmission networks. Among sequenced individuals, 29.5% are linked within clusters. Cluster structure varies by region from sparse networks in Ohio to dense clusters in New England and phylogenetic analyses show that some networks persist for over a decade, indicating sustained transmission. Nearly half of all clusters involve individuals connected through social recruitment, suggesting peer-referral strategies effectively identify transmission chains. Penalized regression retains only a few individual factors including younger age, peer or partner recruitment, illegal income, methamphetamine use, each with modest effects. These findings suggest that clustering is shaped primarily by social and structural contexts rather than individual characteristics and underscore the importance of integrating genomic surveillance with social-network insights to detect emerging HCV clusters and guide targeted interventions in underserved rural communities.

Nature CommunicationsVol. 17(1)
University of North Carolina at Chapel Hill (US), West Virginia University (US), Tufts University (US), University of Wisconsin–Madison (US), University of Kentucky (US), Emory University (US), Oregon Health & Science University (US), University of Washington (US), Ragon Institute of MGH, MIT and Harvard (US), West Virginia University Hospitals (US), University of Chicago (US), London School of Hygiene & Tropical Medicine (GB), Baystate Health (US), Friends Research Institute (US), The Ohio State University (US), Clemson University (US), Uganda Virus Research Institute (UG)
National Institute on Drug Abuse
Openalex Percentile: Top 51%
Hepatitis C virus research
DOIOpen Access PDFOpenAlex
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