Hepatitis C and the absence of genomic data in low-income countries: a barrier on the road to elimination?

Niebel, Marc; Singer, Joshua B.; Nickbakhsh, Sema; Gifford, Robert J.; Thomson, Emma C.

doi:10.1016/s2468-1253(17)30257-1

Cited by 18 publications

(19 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At the time of writing, the majority of HCV sequences obtained from SSA represent short regions of the HCV core or NS5B genes, and coverage of whole genes that encode the targets of DAA therapy is extremely sparse. (12) In our population-based study in Uganda, we confirmed 20 cases of active HCV infection from 565 individuals tested with multiple serological assays. We noted a preponderance of older individuals infected with HCV (age 48-90 years).…”

Section: Discussionsupporting

confidence: 52%

“…In SSA, approximately 11 million people are infected, the majority with genotypes that have received little or no attention in clinical treatment or vaccine trials, and it is likely that genotypes remain undiscovered. At the time of writing, the majority of HCV sequences obtained from SSA represent short regions of the HCV core or NS5B genes, and coverage of whole genes that encode the targets of DAA therapy is extremely sparse …”

Section: Discussionmentioning

confidence: 99%

“…g4 HCV is associated with infection in East, Central, and North Africa, where up to 20% of some older populations are infected with the virus through historical iatrogenic transmission . Few clinical trials have been carried out in SSA, where g1, g2, g4, g5, and g7 are present, and very few sequences spanning the NS3, NS5A, and NS5B genes are available for analysis of potential resistance mutations . Many of these genotypes were sequenced in emigrants from Africa who were diagnosed with HCV in other countries, and it is therefore likely that these represent only a small sample of viral strains from a far larger pool of genetic diversity .…”

mentioning

confidence: 99%

“…(10,11) Few clinical trials have been carried out in SSA, where g1, g2, g4, g5, and g7 are present, and very few sequences spanning the NS3, NS5A, and NS5B genes are available for analysis of potential resistance mutations. (12) Many of these genotypes were sequenced in emigrants from Africa who were diagnosed with HCV in other countries, and it is therefore likely that these represent only a small sample of viral strains from a far larger pool of genetic diversity. (13)(14)(15)(16) Accurate classification is clinically important because treatment response rates and treatment recommendations vary by genotype.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Highly Diverse Hepatitis C Strains Detected in Sub‐Saharan Africa Have Unknown Susceptibility to Direct‐Acting Antiviral Treatments

et al. 2019

Self Cite

View full text Add to dashboard Cite

The global plan to eradicate hepatitis C virus (HCV) led by the World Health Organization outlines the use of highly effective direct‐acting antiviral drugs (DAAs) to achieve elimination by 2030. Identifying individuals with active disease and investigation of the breadth of diversity of the virus in sub‐Saharan Africa (SSA) is essential as genotypes in this region (where very few clinical trials have been carried out) are distinct from those found in other parts of the world. We undertook a population‐based, nested case‐control study in Uganda and obtained additional samples from the Democratic Republic of Congo (DRC) to estimate the prevalence of HCV, assess strategies for disease detection using serological and molecular techniques, and characterize genetic diversity of the virus. Using next‐generation and Sanger sequencing, we aimed to identify strains circulating in East and Central Africa. A total of 7,751 Ugandan patients were initially screened for HCV, and 20 PCR‐positive samples were obtained for sequencing. Serological assays were found to vary significantly in specificity for HCV. HCV strains detected in Uganda included genotype (g) 4k, g4p, g4q, and g4s and a newly identified unassigned g7 HCV strain. Two additional unassigned g7 strains were identified in patients originating from DRC (one partial and one full open reading frame sequence). These g4 and g7 strains contain nonstructural (ns) protein 3 and 5A polymorphisms associated with resistance to DAAs in other genotypes. Clinical studies are therefore indicated to investigate treatment response in infected patients. Conclusion : Although HCV prevalence and genotypes have been well characterized in patients in well‐resourced countries, clinical trials are urgently required in SSA, where highly diverse g4 and g7 strains circulate.

show abstract

Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Highly Diverse Hepatitis C Strains Detected in Sub‐Saharan Africa Have Unknown Susceptibility to Direct‐Acting Antiviral Treatments

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Whilst these differences may reflect genuine variation in the contribution of different genotypes to the total global pool of infection - with B and C coming from high-prevalence, densely populated regions - significant under-sampling of HBV sequences from other regions is likely (especially from low-income regions). Similar trends in isolate bias have been reported in the HCV field (32). Consequently, the sequences available in publicly available databases are likely to under-represent the true extent of HBV diversity and, as more sequences are generated reference sets will need to be reviewed.…”

Section: Discussionsupporting

confidence: 83%

Analysis of genomic-length HBV sequences to determine genotype and subgenotype reference sequences

McNaughton

Revill

Matthews

et al. 2019

Preprint

View full text Add to dashboard Cite

Hepatitis B virus (HBV) is a diverse, partially double-stranded DNA virus, with 9 genotypes (A-I), and a putative 10th genotype (J), thus far characterised. Given the broadening interest in HBV sequencing, there is an increasing requirement for a consistent, unified approach to HBV genotype and subgenotype classification. We set out to generate an updated resource of reference sequences using the diversity of all genomic-length HBV sequences available in public databases. We collated and aligned genomic-length HBV sequences from public databases and used maximum-likelihood phylogenetic analysis to identify genotype clusters. Within each genotype, we examined the phylogenetic support for currently defined subgenotypes, as well as identifying well-supported clades and deriving reference sequences for them. An alignment of these reference sequences and maximum-likelihood phylogenetic trees of the sequences are provided to simplify classification. Based on the phylogenies generated, we present a comprehensive set of HBV reference sequences at the genotype and subgenotype level.

show abstract

Hepatitis C virus genotype 4: A poorly characterized endemic genotype

Leumi

Kassas

Zhong

2021

Journal of Medical Virology

View full text Add to dashboard Cite

Globally, 13% of all hepatitis C virus (HCV) infections are caused by genotype 4 (GT4), which consists of 17 subtypes with various levels of susceptibility to anti-HCV therapy.This genotype is endemic in the Middle East and Africa and has considerably spread to Europe lately. The molecular features of HCV-GT4 infection, as well as its appropriate therapeutics, are poorly characterized as it has not been the subject of widespread basic research. As such, in this review, we aim to gather the current state of knowledge of this genotype with a particular emphasis on its heterogeneity, sequence signatures, resistance-associated substitutions, and available in vivo and in vitro models used for its study. We urge developing more cell-culture models based on different GT4 subtypes to better understand the virology and therapeutic response of this particular genotype. This review may raise more awareness about this genotype and trigger more basic research work to develop its research tools. This will be critical to design better therapeutics and help to provide adequate guidelines for physicians working with HCV-GT4 patients.

show abstract

Hepatitis C and the absence of genomic data in low-income countries: a barrier on the road to elimination?

Cited by 18 publications

References 3 publications

Highly Diverse Hepatitis C Strains Detected in Sub‐Saharan Africa Have Unknown Susceptibility to Direct‐Acting Antiviral Treatments

Highly Diverse Hepatitis C Strains Detected in Sub‐Saharan Africa Have Unknown Susceptibility to Direct‐Acting Antiviral Treatments

Analysis of genomic-length HBV sequences to determine genotype and subgenotype reference sequences

Hepatitis C virus genotype 4: A poorly characterized endemic genotype

Contact Info

Product

Resources

About