Migration pattern of hepatitis A virus genotype IA in North-Central Tunisia

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Migration pattern of hepatitis A virus genotype IA in North-Central Tunisia Abir Beji-Hamza1, Stefania Taffon2, Salma Mhalla3, Alessandra Lo Presti4, Michele Equestre5, Paola Chionne2, Elisabetta Madonna2, Eleonora Cella4, Roberto Bruni2*, Massimo Ciccozzi4,6, Mahjoub Aouni1 and Anna Rita Ciccaglione2

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. Keywords: HAV, Sequencing, Phylogenetic analysis, Viral gene flow

Background Hepatitis A virus (HAV), a member of the family Picornaviridae, genus Hepatovirus, is the major cause of acute hepatitis throughout the world and causes substantial morbidity in both developed and developing countries [1]. HAV is mainly transmitted by the faecal-oral route. HAV can survive for long in water and numerous epidemics have been observed following consumption of contaminated drinking water, food produce and shellfish [2-10]. The true incidence of hepatitis A is often * Correspondence: [email protected] 2 Viral Hepatitis Unit, Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, V.le Regina Elena, 299, 00161 Rome, Italy Full list of author information is available at the end of the article

underestimated because of under-reporting as a result of its widely asymptomatic and milder forms of infection; thus, the epidemiologic pattern is indicated primarily by