Epidemiologia e filodinamica dei genotipi e sottogenotipi di HBV pi\uf9 diffusi in Italia e in Albania

The molecular epidemiology and phylodynamic history of HBV in Italy and Albania was studied on 230 Italian isolates drawn during the period 1980-2007 and 73 Albanian isolates drawn between 2005-2007 from patients living in a homogenous geographical area. Evolutionary rates were estimated and HBV demographic history was reconstructed by using a statistical approach based on coalescent theory. In Italy, the predominant genotype resulted was D (72%) followed by genotype A (20%), F and G (3%) both; among the subgenotypes, D3 was predominant in intravenous drug users (IVDUs) and A2 in men-having-sex-with-men (MSM). In Albania, the only genotype resulted was D, the predominant subgenotypes were D2 (72%), followed by D1 and D3 (14%) both. The evolutionary rates in Albanian D2 and Italian D3 subgenotype were equal. In Italy, the diffusion of D3 subgenotype was identified between 1950 and 1980 probably by use of non safely blood transfusions. In Albania, the entry and diffusion of D2 subgenotype was identified between 1986 and 1995 probably by parenteral transmission of the HBV. The exponential growth rate of D3 epidemic in Italy was significantly lower than that of D2 in Albania

Bayesian phylogeography of Crimean-Congo hemorrhagic fever virus in Europe

Crimean-Congo hemorrhagic fever (CCHF) is a zoonosis mainly transmitted by ticks that causes severe hemorrhagic fever and has a mortality rate of 5-60%. The first outbreak of CCHF occurred in the Crimean peninsula in 1944-45 and it has recently emerged in the Balkans and eastern Mediterranean. In order to reconstruct the origin and pathway of the worldwide dispersion of the virus at global and regional (eastern European) level, we investigated the phylogeography of the infection by analysing 121 publicly available CCHFV S gene sequences including two recently characterised Albanian isolates. The spatial and temporal phylogeny was reconstructed using a Bayesian Markov chain Monte Carlo approach, which estimated a mean evolutionary rate of 2.96 7 10-4 (95%HPD=1.6 and 4.7 7 10-4) substitutions/site/year for the analysed fragment. All of the isolates segregated into seven highly significant clades that correspond to the known geographical clades: in particular the two new isolates from northern Albania clustered significantly within the Europe 1 clade. Our phylogeographical reconstruction suggests that the global CCHFV clades originated about one thousand years ago from a common ancestor probably located in Africa. The virus then spread to Asia in the XV century and entered Europe on at least two occasions: the first in the early 1800s, when a still circulating but less or non-pathogenic virus emerged in Greece and Turkey, and the second in the early 1900s, when a pathogenic CCHFV strain began to spread in eastern Europe. The most probable location for the origin of this European clade 1 was Russia, but Turkey played a central role in spreading the virus throughout Europe. Given the close proximity of the infected areas, our data suggest that the movement of wild and domestic ungulates from endemic areas was probably the main cause of the dissemination of the virus in eastern Europe

Within-Host Dynamics of the Hepatitis C Virus Quasispecies Population in HIV-1/HCV Coinfected Patients

HIV/HCV coinfected individuals under highly active antiretroviral therapy (HAART) represent an interesting model for the investigation of the role played by the immune system in driving the evolution of the HCV quasispecies. We prospectively studied the intra-host evolution of the HCV heterogeneity in 8 coinfected subjects, selected from a cohort of 32 patients initiating HAART: 5 immunological responders (group A) and 3 immunological non-responders (group B), and in two HCV singly infected controls not assuming drugs (group C). For all these subjects at least two serial samples obtained at the first observation (before HAART) and more than 1 year later, underwent clonal sequence analysis of partial E1/E2 sequences, encompassing the whole HVR1. Evolutionary rates, dated phylogenies and population dynamics were co-estimated by using a Bayesian Markov Chain Monte Carlo approach, and site specific selection pressures were estimated by maximum likelihood-based methods. The intra-host evolutionary rates of HCV quasispecies was 10 times higher in subjects treated with HAART than in controls without immunodeficiency (1.9 and 2.3×10−3 sub/site/month in group A and B and 0.29×10−3 sub/site/month in group C individuals). The within-host Bayesian Skyline plot analysis showed an exponential growth of the quasispecies populations in immunological responders, coinciding with a peak in CD4 cell counts. On the contrary, quasispecies population remained constant in group B and in group C controls. A significant positive selection pressure was detected in a half of the patients under HAART and in none of the group C controls. Several sites under significant positive selection were described, mainly included in the HVR1. Our data indicate that different forces, in addition to the selection pressure, drive an exceptionally fast evolution of HCV during HAART immune restoration. We hypothesize that an important role is played by the enlargement of the viral replicative space

Spatial and Temporal Dynamics of Hepatitis B Virus D Genotype in Europe and the Mediterranean Basin

Hepatitis B virus genotype D can be found in many parts of the world and is the most prevalent strain in south-eastern Europe, the Mediterranean Basin, the Middle East, and the Indian sub-continent. The epidemiological history of the D genotype and its subgenotypes is still obscure because of the scarcity of appropriate studies. We retrieved from public databases a total of 312 gene P sequences of HBV genotype D isolated in various countries throughout the world, and reconstructed the spatio-temporal evolutionary dynamics of the HBV-D epidemic using a Bayesian framework

Reconstruction of the epidemic history of hepatitis B virus genotype D in Albania

Despite a recent decrease in the prevalence of HBsAg in the general population, Albania is still highly endemic for HBV infection. Genotype D is the most prevalent HBV strain in the Mediterranean area. We studied the prevalence and distribution of HBV genotypes and subgenotypes in a total of 73 HBsAg-positive patients living in Albania, and reconstructed the epidemiological history of the most prevalent HBV D subgenotype using a "phylodynamic" framework. A time-scaled genealogy of the Albanian patients' and reference P gene sequences with known sampling dates was reconstructed using an MCMC Bayesian approach that allows population growth to be estimated on the basis of coalescent theory. All of the Albanian subjects were infected with the HBV D genotype, and a percentage varying from 44.4% to 100% (depending on the ethnic or risk group) were infected with subgenotype D2, the most prevalent in the study population (72.4%). The other subgenotypes present in a minority of subjects were D1 (13.8%) and D3 (13.8%). The Bayesian skyline plot population dynamics analysis showed that genotype D2 entered the Albanian population in the late 1960s, and that the effective number of infections grew gradually until the second half of the 1980s and more rapidly until the mid-1990s, when it reached a plateau that still persists today. Our data suggest that political and socio-economic factors played an important role in determining the rapid spread of HBV infection in Albania

Reconstruction of the evolutionary dynamics of hepatitis C virus subtypes in Montenegro and the Balkan region

More than 20million hepatitis C virus (HCV) carriers live in the countries of the Eastern Mediterranean. We determined HCV genotype distribution among chronically infected patients in Montenegro and investigated the phylodynamics and phylogeography of the most represented HCV subtypes. The HCV-NS5b sequences of the Montenegrin patients were compared with sequences isolated in different known localities of the Mediterranean area, Europe and Asia. A Bayesian approach was used in order to allow the simultaneous estimate of the evolutionary rate, time-scaled phylogeny, demography and ancestral spatial status. The most frequent HCV subtypes among the Montenegrin patients, were 1b (34.7%) and 3a (24.7%), but there was also a significant prevalence of 1a and 4d (19.5%). Subtype 3a was significantly more frequent among younger patients and intravenous drug users (IDUs), whereas subtype 1b was more frequently associated with iatrogenic exposure and older ages. The spatio-temporal analysis of the epidemic suggested that HCV-1b penetrated Europe at the beginning of the XX century, probably through Greece and Cyprus and in the 1920s reached Montenegro, where there was an exponential increase in the effective number of infections between the 1950s and 1970s. The phylogeographic and phylodynamic analysis of HCV 3a showed that its most probable origin was in the Indian sub-continent (Pakistan in our reconstruction) about 300years ago. The evolutionary dynamics analysis showed that HCV-3a reached Montenegro more recently in the late 1970s and underwent multi-phasic growth still persisting. Our data suggest multiple introduction of HCV subtypes in the area, supported by different causes of dispersion: adverse social conditions and unsafe medical practices for HCV-1b and i.v. drug use for HCV-3a

The First Meeting of the European Register of Cystic Echinococcosis (Erce)

Cystic echinococcosis (CE) is a zoonotic parasitic disease endemic in southern and eastern European countries. The true prevalence of CE is difficult to estimate due to the high proportion of asymptomatic carriers who never seek medical attention and to the underreporting of diagnosed cases, factors which contribute to its neglected status. In an attempt to improve this situation, the European Register of Cystic Echinococcosis (ERCE), was launched in October 2014 in the context of the HERACLES project. ERCE is a prospective, observational, multicentre register of patients with probable or confirmed CE. The first ERCE meeting was held in November 2015 at the Italian National Institute of Health (Istituto Superiore di Sanita, ISS) in Rome, to bring together CE experts currently involved in the Register activities, to share and discuss experiences, and future developments., Although the Register is still in its infancy, data collected at the time of writing this report, had outnumbered the total of national cases reported by the European endemic countries and published by the European Centre for Disease Prevention and Control in 2015. This confirms the need for an improved reporting system of CE at the European level. The collection of standardized clinical data and samples is expected to support a more rational, stage-specific approach to clinical management, and to help public authorities harmonize reporting of CE. A better understanding of CE burden in Europe will encourage the planning and implementation of public health policies toward its control.PubMedWoSScopu

The first meeting of the European Register of Cystic Echinococcosis (ERCE)

Cystic echinococcosis (CE) is a zoonotic parasitic disease endemic in southern and eastern European countries. The true prevalence of CE is difficult to estimate due to the high proportion of asymptomatic carriers who never seek medical attention and to the underreporting of diagnosed cases, factors which contribute to its neglected status. In an attempt to improve this situation, the European Register of Cystic Echinococcosis (ERCE), was launched in October 2014 in the context of the HERACLES project. ERCE is a prospective, observational, multicentre register of patients with probable or confirmed CE. The first ERCE meeting was held in November 2015 at the Italian National Institute of Health (Istituto Superiore di Sanita, ISS) in Rome, to bring together CE experts currently involved in the Register activities, to share and discuss experiences, and future developments.Although the Register is still in its infancy, data collected at the time of writing this report, had outnumbered the total of national cases reported by the European endemic countries and published by the European Centre for Disease Prevention and Control in 2015. This confirms the need for an improved reporting system of CE at the European level. The collection of standardized clinical data and samples is expected to support a more rational, stage-specific approach to clinical management, and to help public authorities harmonize reporting of CE. A better understanding of CE burden in Europe will encourage the planning and implementation of public health policies toward its control