Genotype Distribution and Prevalence of Human Pegivirus among High-Risk Populations in Tunisia

International audienceObjective: A recently discovered non-A-E hepatitis virus has been designated as human Pegivirus (HPgV). HPgV is prevalent in high-risk groups such as patients with hepatitis C virus (HCV), and it is of interest for patients who are at risk for transmitted infections. The aim of this study was to evaluate the prevalence of HPgV as well as the genotype distribution among patients in the Tunisian population who are infected with HCV and also in multitransfused patients. Methods: A total of 144 patients were screened using RTPCR/nested PCR of the 5′-untranslated region (UTR); 14 cases were sequenced and phylogenetically analyzed. Results: Seven (14.9%) subjects from the multitransfused group and 7 (7.2%) patients infected with HCV, respectively, were found positive for HPgV RNA. Sequencing and phylogenetic analysis of the 14 cases revealed that genotype 2a was the main genotype circulating in Tunisian patients. Genotype 2b was found in the amplified samples of 2 HCV-infected patients. Conclusion: This study enriches the limited data on HPgV prevalence in Tunisia, and shows, for the first time, the molecular epidemiology of the circulating strains in this country

Identification of two novel hepatitis C virus subtype 2 from Tunisia (2v and 2w).

BackgroundHepatitis C virus (HCV) has a high genetic diversity. Eight genotypes and 90 subtypes are currently described. Genotypes are clinically significant for therapeutic management and their determination is necessary for epidemiological studies.MethodsTunisian patients plasma samples (n = 6) with unassigned HCV-2 subtype using partial sequencing in the NS5B and Core/E1 regions were analyzed by realizing whole-genome sequencing analysis. Phylogenetic analyses were performed to assign subtypes.ResultsPhylogenetic analysis of the full genome sequences of Tunisian strains shows two subtypes within HCV-2. These later were genetically distinct from all previously established HCV-2 subtypes with nucleotide divergence greater than 15% (20% -31%). These two subtypes are proposed as new subtypes 2v and 2w.ConclusionsThe discovery of two new HCV-2 subtypes circulating in the Tunisian population confirms the great diversity of HCV-2 viruses and increases the total number of HCV-2 subtypes from 21 to 23

Les virus de l'hépatite profitent des pratiques traditionnelles pour augmenter la charge du carcinome hépatocellulaire en Tunisie

International audienceHepatocellular carcinoma (HCC) is a major public health issue in Africa. In Tunisia, hepatitis B virus (HBV) is known to be an important risk factor for HCC in the south of the country, but the role played by hepatitis C virus (HCV) still remains unclear. The aim of the current case-control study was to identify risk factors for HCC development in the northern part of the country. Clinical and biological data including viral hepatitis status (serological and molecular) and non-infectious risk factors from 73 patients with HCC and 70 control subjects without hepatic diseases were collected. The mean age of the patients was 63 ± 10 years, and the ratio of males to females was 1.1. HCC occurred in cirrhotic liver in 72.0% of the cases. HCV infection was the dominant risk factor (64.3% of cases); the presence of HBV was observed in 53.4% of the cases. Occult hepatitis B and C were implicated, respectively, in 30.1% and 9.6% of the cases. HCV genotype 1b was predominant. Patients originating from western Tunisia formed a homogeneous group, characterized by significantly higher rates of tattoos or scarifications (83%) and HCV infection (80%) than those from other parts of the country. Chronic HCV infection is currently the primary risk factor for HCC in Tunisia; HBV infection remains frequent in its overt or occult infection forms. Traditional esthetic practices apparently contribute to increasing the burden of terminal liver diseases in western Tunisia

Phylogenetic Analysis and Epidemic History of Hepatitis C Virus Genotype 2 in Tunisia, North Africa.

HCV genotype 2 (HCV-2) has a worldwide distribution with prevalence rates that vary from country to country. High genetic diversity and long-term endemicity were suggested in West African countries. A global dispersal of HCV-2 would have occurred during the 20th century, especially in European countries. In Tunisia, genotype 2 was the second prevalent genotype after genotype 1 and most isolates belong to subtypes 2c and 2k. In this study, phylogenetic analyses based on the NS5B genomic sequences of 113 Tunisian HCV isolates from subtypes 2c and 2k were carried out. A Bayesian coalescent-based framework was used to estimate the origin and the spread of these subtypes circulating in Tunisia. Phylogenetic analyses of HCV-2c sequences suggest the absence of country-specific or time-specific variants. In contrast, the phylogenetic grouping of HCV-2k sequences shows the existence of two major genetic clusters that may represent two distinct circulating variants. Coalescent analysis indicated a most recent common ancestor (tMRCA) of Tunisian HCV-2c around 1886 (1869-1902) before the introduction of HCV-2k in 1901 (1867-1931). Our findings suggest that the introduction of HCV-2c in Tunisia is possibly a result of population movements between Tunisia and European population following the French colonization

Molecular epidemiology of hepatitis B and Delta virus strains that spread in the Mediterranean North East Coast of Tunisia

International audienceBackground: Tunisia is classified as an area of middle endemic for hepatitis B virus (HBV) infection, however little is known about hepatitis Delta virus (HDV) infection. Objectives: This study aimed to address the prevalence of HDV infection, to identify possible risks factors, and to analyze the genetic diversity of HDV strains that are spreading in Tunisia. Study design: A retrospective large-scale study including 1615 HBsAg positive patients, native of the North East coast of Tunisia, recruited from Gastroenterology departments, was conducted. Demographic, epidemiological, ethnical, clinical and biological data were recorded. HBV and HDV serological analyses and DNA and RNA viral load quantification were performed. Genotyping of HBV and HDV strains was performed using nucleotide sequencing followed by phylogenetic analyses. Results: The study population included 819(50.7%) men and 796(49.3%) women; aged 12-90 years (mean age 41 + 13 years). A very low prevalence of HDV infection, 2% was observed. No risk factor, except a history of hospitalization for surgery was found. All HDV strains belonged to genotype 1, with a wide distribution within the HDV-1 group. They all share the African amino acid marker, a serine at position 202 of the large Delta protein. HBV genotypes were distributed as follows: HBV/D1 (56.8%), HBV/D7 (40.9%), and HBV/A2 (2.3%). Conclusion: Tunisia is a low endemic region for HDV infection, due to an efficient policy of HBV infection control. HDV-1 is the sole genotype found, with a high diversity within this group. Further studies are ongoing in order to better characterize and manage the HBV/HDV-infected patients according to the genetic variability of the viral strains. (C) 2015 Elsevier B.V. All rights reserved

Phylogenetic analysis of isolates from subtype 2c.

<p>Phylogenetic analyses were performed using the Maximum Composite Likelihood method included in the MEGA package (version 5.1). The reliability of the phylogenetic constructions was estimated by bootstrap analysis with 1000 pseudo replicate data sets. The tree is based on the analysis of a 222-nucleotide-long fragment in the NS5B region (nucleotides 8316 to 8537 according to the H77-1a prototype strain, AF009606). It includes the 102 studied Tunisian sequences (in red) and 53 HCV-2c field sequences from other countries (in black). All the sequences were indicated by their Accession Numbers followed by the country code and the collection date. The country codes according to the standard abbreviation are: France (FRA), Martinique (MTQ), Canada (CAN), Italy (ITA), Venezuela (VEN), Ghana (GHA), Russia (RUS), Netherlands (NLD), Spain (ESP), Japan (JPN), Germany (DEU), Argentina (ARG) and United Kingdom (GBR).</p

Bayesian Skyline Plots for Demographic Reconstruction using NS5B sequences.

<p>A) subtype 2c, B) subtype 2k; X-axis: Date in Years; Y-axis: Estimated effective number of infections; Bold Line: Mean Effective Number of viral population. Upper and lower Lines: Upper and Lower HPD95% (High Population Density) of Effective Number of viral population.</p