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Chronic hepatitis B virus (CHB) infection remains a leading cause of hepatic inflammation and damage. Several studies have suggested the significant role of CX3C chemokine receptor 1 (CX3CR1) in inflammatory damages. The polymorphisms V249I and T280M affect receptor expression and function. In the current study, we investigated the association of V249I and T280M variants of the CX3CR1 fractalkine receptor with susceptibility to CHB disease. In total, 280 patients with chronic hepatitis B and 260 controls from different cities of Tunisia recruited in the Pasteur Institute of Tunisia between January 2017 and December 2022 were genotyped for the V249I and T280M CX3CR1 gene. The allele and genotype frequencies of these variants did not show significant associations with susceptibility to CHB infection (p > 0.05). Analysis of allele and genotype frequencies showed that there was no differences in age and sex distribution between patients and the control group, but when CHB patients were stratified according to age, a clear significant difference was obtained for the T280M polymorphism (p < 10−3, OR = 88.91; p < 10−3, OR = 37.42, for genotype and allelic distribution, respectively) with the MM genotype being more frequent in patients aged ≥ 50 years. The most frequently combined genotypes in the Tunisian population were VVTT, VITT and VITM both in patients (48.9%, 22.5% and 22.1%, respectively) and in controls (52%, 23.8%, 13.5%, respectively) compared to the extremely rare IITT, IITM or IIMM genotypes. In conclusion, this study suggests a noteworthy genotype–age association, particularly involving the T280M variant

Background The intra-host diversity of SARS-CoV-2 in pediatric populations remains insufficiently studied. To address this significant knowledge gap, the present study investigates the intra-host variability of SARS-CoV-2 in both immunocompetent and immunodeficient children, including those with severe cases. The research encompasses both short-term and long-term infections, aiming to provide a comprehensive understanding of viral dynamics in these vulnerable groups. Materials and methods This study analyzed 47 pediatric COVID-19 patients: 37 with short-term infections and 10 with long-term infections including 3 immunodeficient cases. Viral RNA was extracted and detected using RT-qPCR, followed by whole-genome sequencing (WGS) using the Illumina COVIDSeq assay. Bioinformatics analysis was performed with the nextflow/viralrecon pipeline. The number of single nucleotide polymorphisms (SNPs) and the frequency of Major (M-SNPs) and minor (m-SNPs) missense SNPs were analyzed using the ggplot2 R package and GraphPad Prism software, respectively. Results A total of 96 SARS-CoV-2 sequences from 45 patients (35 short-term and 10 long-term shedders), were classified into four variants: Alpha, B.1.160, Delta, and Omicron. SNPs were common across SARS-CoV-2 variants (88.21%-100%), with frequent cytosine-to-thymidine (C > T) substitutions (44.05%-52.85%). Missense mutations were also prominent (57.52% to 80.32%). Variability in SNPs numbers was observed over time in Delta and Omicron variants, particularly in severe and immunodeficient cases. Missense m-SNPs exhibited variation in long-term shedders, especially among severe immunocompetent and immunodeficient patients. Conclusion Our findings revealed significant intra-host variability in SARS-CoV-2 among severe and immunodeficient pediatric patients. These results underscore the critical importance of continuous surveillance of viral variants within pediatric populations to enhance our understanding of their impact on disease progression and clinical outcomes.

The SARS-CoV-2 Omicron variant has exhibited a rapid progression around the world, but its molecular insights in North Africa remain understudied. This study characterizes the genetic diversity, dynamics, and evolutionary trends of the Omicron variant in Tunisia over a 33-month period (December 2021–August 2024). In total, 928 high-quality whole-genome sequences were considered in this study, of which 559 were retrieved from the GISAID database and 369 were generated in our laboratory. Phylogenetic analysis of the dominant subvariants (BA.1, BA.2, and BA.5) was performed using IQ-TREE. BA.2 was the predominant subvariant (38%), followed by BA.1 (24.0%), Omicron recombinants (19%), and BA.5 (18%). BA.2 diversified into JN, KP, and BN sub-lineages. Recombinants were dominated by XBB (98.8%), primarily including EG.4, XBB.1.5, and XBB.2.3.11, with rare detection of XDK and XDQ. Phylogenetic analysis revealed local clusters in BA.1, BA.2, and BA.5 alongside imported strains. Tunisia’s Omicron wave was mainly driven by BA.2 and its recombinants, with evidence of localized viral evolution and sporadic introductions. The detection of rare recombinants underlines the importance of integrating regional genomic surveillance with epidemiological data in order to help guide future public health strategies.

Introduction RT-PCR testing on nasopharyngeal swabs is a key component in the COVID-19 fighting, provided to use sensitive and specific SARS-CoV2 genome targets. In this study, we aimed to evaluate and to compare 4 widely used WHO approved RT-PCR protocols on real clinical specimens, to decrypt the reasons of the diverging results and to propose recommendations for the choice of the genome targets. Methods 260 nasopharyngeal samples were randomly selected among the samples tested between Week-16, 2020 and week-16 2021, in the Institut Pasteur de Tunis, Tunisia, one of the referent laboratories of COVID-19 in Tunisia. All samples were tested by Charité, Berlin protocol (singleplex envelop (E) and singleplex RNA-dependent RNA polymerase (RdRp)), Hong Kong Universiy, China protocol (singleplex nucleoprotein (N) and singleplex Open reading frame Orf1b), commercial test DAAN Gene® (using the CDC China protocol), (triplex N, Orf1ab with internal control) and Institut Pasteur Paris protocol (IPP) (triplex IP2(nsp9) and IP4 (nsp12) with internal control). For IPP, a selection from samples positive by IP2 but negative with IP4 was re-tested by exactly the same protocol but this time in singleplex. New results were described and analyzed. Results In vitro analysis showed discordant results in 29.2% of cases (76 out of 260). The most discordant protocol is DAAN Gene® due to the false positive late signals with N target. Discordant results between the two protocol’s targets are more frequent when viral load are low (high Ct values). Our results demonstrated that the multiplexing has worsened the sensitivity of the IP4 target. Conclusion We provide concise recommendations for the choice of the genome targets, the interpretation of the results and the alarm signals which makes suspect a gene mutation.

With the introduction of direct-acting antiviral treatment (DAA), Tunisia has committed to achieving the international goal of eliminating viral hepatitis. Because the specific DAA prescribed depends on viral genotype, viral genotyping remains of great importance. The aim of the present study was to outline the trends in the distribution of HCV genotypes from 2002 to 2017 in the Tunisian general population in order to guide authorities towards the most appropriate therapeutic strategies for preventing HCV infection. A total of 2532 blood samples were collected over a 16-year period and from all regions of Tunisia. Genotyping showed that genotype 1 (subtype 1b) was the most prevalent genotype in the country (n = 2012; 79.5%), followed by genotype 2 (n = 339; 13.3%). Genotypes 3, 4 and 5 were detected in 4.8%, 2.2% and 0.1% of the country’s population, respectively. Mixed infections with different HCV genotypes were detected in 0.1% of the population (one case each of genotypes 1b + 4, 1b + 2 and 2 + 4). Interestingly, a significant increase in genotypes 2, 3 and 4 was observed over time (p = 0.03). Sixteen different subtypes were detected over the study period, most of which were subtypes of genotype 2, and some of these subtypes appeared to be new. Patients infected with genotypes 1a, 3 and 4 were significantly younger than those infected with genotypes 1b and 2 (p < 0.01). Furthermore, genotypes 1b and 2 were detected more often in women than men, while genotypes 1a and 3 were detected mostly in men (P < 0.01). Our study confirms a large predominance of genotype1/subtype1b in Tunisia and shows a significant increase in the prevalence of other genotypes over time. These findings reinforce the need for an additional HCV genotype survey to improve the design of treatment strategies in Tunisia.

Hepatitis 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. Tunisian 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. Phylogenetic 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. The 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.

Background Primary Immunodeficiency disorders (PID) can increase the risk of severe COVID-19 and prolonged infection. This study investigates the duration of SARS-CoV-2 excretion and the genetic evolution of the virus in pediatric PID patients as compared to immunocompetent (IC) patients. Materials and methods A total of 40 nasopharyngeal and 24 stool samples were obtained from five PID and ten IC children. RNA detection was performed using RT-qPCR, and whole-genome sequencing was conducted with the NexSeq 1000 platform. Data analysis used the nextflow/viralrecon pipeline. Hotspot amino acid frequencies were investigated using GraphPad Prism v10. Phylodynamic analysis was conducted with BEAST software. Results In IC children, the viral excretion period lasted up to 14 days in nasopharyngeal swabs, with an average duration of 7 days, and ranged from 7 to 14 days in stool samples. In PID patients, the viral RNA was detected in nasopharyngeal for periods between 7 and 28 days, with an average duration of 15 days, and up to 28 days in stool samples. Two SARS-CoV-2 variants were detected in PID patients: Delta (AY.122) and Omicron (BA.1.1). Patients with antibody and combined deficiencies, exhibited the most prolonged shedding periods in both nasopharyngeal and stool samples and one patient presented complications and fatal outcome. Specific Hotspot amino acid changes were detected in PID: A2821V and R550H (ORF1ab). Conclusion Our findings underscore the prolonged excretion of SARS-CoV-2 RNA in patients with antibody and combined deficiencies. Thus, specialized care is essential for effectively managing PID patients.

Background In Tunisia a first SARS-CoV-2 confirmed case was reported in March 03, 2020. Since then, an increase of cases number was observed from either imported or local cases. The aim of this preliminary study was to better understand the molecular epidemiology and genetic variability of SARS-CoV-2 viruses circulating in Tunisia and worldwide. Methods Whole genome sequencing was performed using NGS approach on six SARS. CoV-2 highly positive samples detected during the early phase of the outbreak. Results Full genomes sequences of six Tunisian SARS-CoV-2 strains were obtained from imported and locally transmission cases during the COVID-19 outbreak. Reported sequences were non-identical with 0.1% nucleotide divergence rate and clustered into 6 different clades with worldwide sequences. SNPs results favor the distribution of the reported Tunisian sequences into 3 major genotypes. These SNP mutations are critical for diagnosis and vaccine development. Conclusions These results indicate multiple introductions of the virus in Tunisia and add new genomic data on SARS-CoV-2 at the international level.

Hepatocellular 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.

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.