title: Next-Generation Sequencing Reveals Frequent Opportunities for Exposure to Hepatitis C Virus 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.
authors.affiliation: Molecular Epidemiology and Bioinformatics Laboratory, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Forbi
authors.affiliation: Department of Public Health Sciences, Loyola University Chicago, Maywood, Illinois, United States of America.|Department of Medicine, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, United States of America.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Layden
authors.affiliation: Komfo Anokye Teaching Hospital, Kumasi, Ghana, West Africa.|Kwame Nkrumah University of Science and Technology, Kumasi, Ghana, West Africa.
authors.forename: Richard O
authors.initials: RO
authors.lastname: Phillips
authors.affiliation: Department of Public Health Sciences, Loyola University Chicago, Maywood, Illinois, United States of America.
authors.forename: Nallely
authors.initials: N
authors.lastname: Mora
authors.affiliation: Molecular Epidemiology and Bioinformatics Laboratory, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Xia
authors.affiliation: Molecular Epidemiology and Bioinformatics Laboratory, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: David S
authors.initials: DS
authors.lastname: Campo
authors.affiliation: Molecular Epidemiology and Bioinformatics Laboratory, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Purdy
authors.affiliation: Molecular Epidemiology and Bioinformatics Laboratory, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Zoya E
authors.initials: ZE
authors.lastname: Dimitrova
authors.affiliation: Komfo Anokye Teaching Hospital, Kumasi, Ghana, West Africa.
authors.forename: Dorcas O
authors.initials: DO
authors.lastname: Owusu
authors.affiliation: Molecular Epidemiology and Bioinformatics Laboratory, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Lili T
authors.initials: LT
authors.lastname: Punkova
authors.affiliation: Molecular Epidemiology and Bioinformatics Laboratory, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Pavel
authors.initials: P
authors.lastname: Skums
authors.affiliation: Komfo Anokye Teaching Hospital, Kumasi, Ghana, West Africa.
authors.forename: Shirley
authors.initials: S
authors.lastname: Owusu-Ofori
authors.affiliation: Komfo Anokye Teaching Hospital, Kumasi, Ghana, West Africa.|Kwame Nkrumah University of Science and Technology, Kumasi, Ghana, West Africa.
authors.forename: Fred Stephen
authors.initials: FS
authors.lastname: Sarfo
authors.affiliation: Molecular Epidemiology and Bioinformatics Laboratory, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Vaughan
authors.affiliation: Molecular Epidemiology and Bioinformatics Laboratory, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Hajung
authors.initials: H
authors.lastname: Roh
authors.affiliation: Komfo Anokye Teaching Hospital, Kumasi, Ghana, West Africa.
authors.forename: Ohene K
authors.initials: OK
authors.lastname: Opare-Sem
authors.affiliation: Department of Public Health Sciences, Loyola University Chicago, Maywood, Illinois, United States of America.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Cooper
authors.affiliation: Molecular Epidemiology and Bioinformatics Laboratory, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Yury E
authors.initials: YE
authors.lastname: Khudyakov
mesh_terms: D000328:Adult; D058872:Epidemics; D019143:Evolution, Molecular; D005814:Genes, Viral; D014644:Genetic Variation; D005838:Genotype; D005869:Ghana / Q000453:epidemiology; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000453:epidemiology / Q000635:transmission / Q000821:virology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D058889:Molecular Typing; D010802:Phylogeny; D017422:Sequence Analysis, DNA