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Next-Generation Sequencing Reveals Frequent Opportunities for Exposure to Hepatitis C Virus in Ghana
Joseph C Forbi1, Jennifer E Layden2,3, Richard O Phillips4,5
1Molecular Epidemiology and Bioinformatics Laboratory, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
Insights
Hepatitis C Virus (HCV) infection in Ghana shows high genetic diversity, particularly for genotype 2 (HCV-2), with evidence of rapid strain switching and transmission. This suggests a long epidemic history of HCV-2 in the region.
Area of Science:
- Virology
- Epidemiology
- Genetics
Background:
- Hepatitis C Virus (HCV) causes significant liver disease globally, with high prevalence in sub-Saharan Africa.
- West Africa is a known origin for two HCV genotypes, but regional genetic diversity remains poorly understood.
- Understanding HCV genetic composition is crucial for public health interventions in endemic areas.
Purpose of the Study:
- To genetically characterize Hepatitis C Virus (HCV) strains circulating in blood donors in Kumasi, Ghana.
- To investigate the genetic diversity, population structure, and evolutionary history of HCV in the region.
- To assess the implications of HCV genetic diversity for transmission dynamics.
Main Methods:
- Conventional and next-generation sequencing (NGS) were used to analyze 65 HCV strains.
- Phylogenetic analysis was performed on consensus sequences from the 5'-untranslated region, HVR1, and NS5B gene.
- Bayesian analysis was employed to estimate the evolutionary history of HCV strains.
Main Results:
- HCV genotypes 1 (15%) and 2 (85%) were identified, with HCV-2 being predominant.
- Significant genetic heterogeneity of HCV-2 was observed in Ghana, with intermixed sequences in phylogenetic analysis.
- Intra-host sequencing revealed multiple infections, strain co-infections, and evidence of recent HCV transmission among donors.
- Bayesian analysis indicated HCV-2 strains have been expanding in Ghana since the 16th century.
Conclusions:
- The HCV population in Kumasi, Ghana, is genetically diverse, dominated by HCV-2.
- Evidence of co-infections, transmission, and rapid strain switching suggests frequent HCV exposure and a long epidemic history.
- Findings highlight the need for targeted public health strategies considering the specific HCV genetic landscape in Ghana.
Abstract:
Globally, hepatitis C Virus (HCV) infection is responsible for a large proportion of persons with liver disease, including cancer. The infection is highly prevalent in sub-Saharan Africa. West Africa was identified as a geographic origin of two HCV genotypes. However, little is known about the genetic composition of HCV populations in many countries of the region. Using conventional and next-generation sequencing (NGS), we identified and genetically characterized 65 HCV strains circulating among HCV-positive blood donors in Kumasi, Ghana. Phylogenetic analysis using consensus sequences derived from 3 genomic regions of the HCV genome, 5'-untranslated region, hypervariable region 1 (HVR1) and NS5B gene, consistently classified the HCV variants (n = 65) into genotypes 1 (HCV-1, 15%) and genotype 2 (HCV-2, 85%). The Ghanaian and West African HCV-2 NS5B sequences were found completely intermixed in the phylogenetic tree, indicating a substantial genetic heterogeneity of HCV-2 in Ghana. Analysis of HVR1 sequences from intra-host HCV variants obtained by NGS showed that three donors were infected with >1 HCV strain, including infections with 2 genotypes. Two other donors share an HCV strain, indicating HCV transmission between them. The HCV-2 strain sampled from one donor was replaced with another HCV-2 strain after only 2 months of observation, indicating rapid strain switching. Bayesian analysis estimated that the HCV-2 strains in Ghana were expanding since the 16th century. The blood donors in Kumasi, Ghana, are infected with a very heterogeneous HCV population of HCV-1 and HCV-2, with HCV-2 being prevalent. The detection of three cases of co- or super-infections and transmission linkage between 2 cases suggests frequent opportunities for HCV exposure among the blood donors and is consistent with the reported high HCV prevalence. The conditions for effective HCV-2 transmission existed for ~ 3-4 centuries, indicating a long epidemic history of HCV-2 in Ghana.
