title: Migration pattern of hepatitis A virus genotype IA in North-Central Tunisia.
abstract: BACKGROUND
  Hepatitis A virus (HAV) epidemiology in Tunisia has changed from high to intermediate endemicity in the last decades. However, several outbreaks continue to occur. The last reported sequences from Tunisian HAV strains date back to 2006. In order to provide an updated overview of the strains currently circulating in Tunisia, a large-scale molecular analysis of samples from hepatitis A cases was performed, the first in Tunisia.
  
  
  RESULTS
  Biological samples were collected from patients with laboratory confirmed hepatitis A: 145 sera samples in Tunis, Monastir, Sousse and Kairouan from 2008 to 2013 and 45 stool samples in Mahdia in 2009. HAV isolates were characterised by nested RT-PCR (VP1/2A region) and sequencing. The sequences finally obtained from 81 samples showed 78 genotype IA and 3 genotype IB isolates. A Tunisian genotype IA sequence dataset, including both the 78 newly obtained IA sequences and 51 sequences retrieved from GenBank, was used for phylogenetic investigation, including analysis of migration pattern among six towns. Virus gene flow from Sfax and Monastir was directed to all other towns; in contrast, the gene flows from Sousse, Tunis, Mahdia and Kairouan were directed to three, two, one and no towns, respectively.
  
  
  CONCLUSIONS
  Several different HAV strains co-circulate in Tunisia, but the predominant genotype still continues to be IA (78/81, 96% isolates). A complex gene flow (migration) of HAV genotype IA was observed, with Sfax and Monastir showing gene flows to all other investigated towns. This approach coupled to a wider sampling can prove useful to investigate the factors underlying the spread of HAV in Tunisia and, thus, to implement appropriate preventing measures.
authors.affiliation: Laboratory of Infectious Diseases and Biological Agents, Faculty of Pharmacy, University of Monastir, 5000, Monastir, Tunisia. amzabir@yahoo.fr.
authors.forename: Abir
authors.initials: A
authors.lastname: Beji-Hamza
authors.affiliation: Viral Hepatitis Unit, Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, V.le Regina Elena, 299, 00161, Rome, Italy. stefania.taffon@iss.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Taffon
authors.affiliation: Laboratory of Microbiology, CHU Fattouma Bourguiba, Monastir, Tunisia. smhalla@gmail.com.
authors.forename: Salma
authors.initials: S
authors.lastname: Mhalla
authors.affiliation: Epidemiology Unit, Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy. alessandra.lopresti@guest.iss.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lo Presti
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy. michele.equestre@iss.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Equestre
authors.affiliation: Viral Hepatitis Unit, Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, V.le Regina Elena, 299, 00161, Rome, Italy. paola.chionne@iss.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Chionne
authors.affiliation: Viral Hepatitis Unit, Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, V.le Regina Elena, 299, 00161, Rome, Italy. elisabetta.madonna@iss.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Madonna
authors.affiliation: Epidemiology Unit, Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy. eleonora.cella@yahoo.it.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Cella
authors.affiliation: Viral Hepatitis Unit, Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, V.le Regina Elena, 299, 00161, Rome, Italy. roberto.bruni@iss.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bruni
authors.affiliation: Epidemiology Unit, Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy. massimo.ciccozzi@iss.it.|University Biomedical Campus, Rome, Italy. massimo.ciccozzi@iss.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Ciccozzi
authors.affiliation: Laboratory of Infectious Diseases and Biological Agents, Faculty of Pharmacy, University of Monastir, 5000, Monastir, Tunisia. aouni_mahjoub2005@yahoo.fr.
authors.forename: Mahjoub
authors.initials: M
authors.lastname: Aouni
authors.affiliation: Viral Hepatitis Unit, Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, V.le Regina Elena, 299, 00161, Rome, Italy. annarita.ciccaglione@iss.it.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Ciccaglione
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D005243:Feces / Q000821:virology; D005260:Female; D051456:Gene Flow; D005838:Genotype; D006506:Hepatitis A / Q000453:epidemiology* / Q000821:virology*; D017957:Hepatitis A Virus, Human / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D044967:Serum / Q000821:virology; D014416:Tunisia / Q000453:epidemiology; D055815:Young Adult
chemical_list: D012367:RNA, Viral