ORIGINE, EPIDEMIOLOGIA E FILOGEOGRAFIA DEI GENOTIPI D E A DEL VIRUS DELL'EPATITE B

Hepatitis B virus (HBV) is the leading cause of liver disease and infects an estimated 240 million people worldwide. It is characterized by an high degree of genetic heterogeneity because of the use of a reverse transcriptase during viral replication. The ten genotypes (A-J) that have been described so far further segregate into a number of subgenotypes which have distinct ethno-geographic distribution. Genotypes A and D are ubiquitous and the most prevalent genotypes in Europe (mainly represented by subgenotypes D1-3 and A2); genotypes B and C are restricted to eastern Asia and Oceania; genotype E to central and western Africa; and genotypes H and F (classified into 4 subgenotypes) to Latin America and Alaska. The aim of this study was to determine the HBV genotypes/subgenotypes circulating in Italy and to study their distribution in relation to demographic and risk factors. To this aim, we analyzed the P gene sequences of a total 230 HBsAg-positive Italian patients. Our study showed that the HBV genotype prevalent in Italy was D (72.2%) followed by A (18.7%). In particular in patients infected with HBV-D the subgenotype prevalent was D3 (80.1%); in patients with HBV-A the subgenotype prevalent was A2 (93%). The subgenotype D3 was common among subjects who used injecting drug (69.2%) while the subgenotype A2 was common among subjects having sex with men (66.7%). Furthermore, to reconstruct the spatio-temporal dynamics (origin and geographic dispersion) of the genotypes/subgenotypes widespread in Italy and in Europe, the Italian HBV sequences characterized in this study were aligned with reference sequences obtained in different countries, retrieved from public databases. The study was performed using new methods of phylogenetic analysis based on molecular clocks coalescent theory and the phylogeographic approach. The phylogeographical analysis of HBV-D showed that India had the highest posterior probability of being the location of the tree root, whereas central Asia was the most probable location of the common ancestor of subgenotypes D1-D3. The time of the most recent common ancestor (tMRCA) of the tree root was 128 years ago, which suggests that the common ancestor of the currently circulating subgenotypes existed in the second half of the XIX century. The mean tMRCA of subgenotypes D1-D3 was between the 1940s and the 1950-60s. On the basis of our phylogeographic reconstruction, it seems that HBV-D reached the Mediterranean area in the middle of the XX century by means of at least two routes: the first pathway (mainly due to the spread of subgenotype D1) crossing the Middle East and reaching north Africa and the eastern Mediterranean, and the second pathway (closely associated with D2) that crossed the former Soviet Union and reached eastern Europe and the Mediterranean through Albania. The phylogeographical analysis of HBV-A showed that the common ancestor of the currently circulating A subgenotypes was placed in west-central Africa a mean 1057 years ago. The genotype diverged into two main clades at the beginning of the 13th century: one including all of the west-central African quasi-subgenotypes and the other corresponding to subgenotype A1, originating in east Africa and further segregating into two main subclades: an \u201cAfrican\u201d and a \u201cCosmopolitan\u201d clade. It is likely that the slave trade was the main source the spread of Cosmopolitan HBV-A1, which was exported to Asia in the 17th century as a result of Arab or Portuguese trade, and to Latin America in the 18th centuries through the trans-Atlantic slave trade. The origin of the currently circulating A2 strains dates back to the first decades of the 20th century, and the evolutionary demography analysis suggests an exponential growth of infections, between 1970s and the mid-1990s. This study suggests that the HBV genotypes were dispersed in Europe in different times and through different transmission routes. In particular, some genotypes (such as HBV-D or HBV-A2) spread recently (in the last 100 years), mainly through parenteral or sexual exposure; on the contrary other strains (such as HBV-A1) have been dispersed in more ancient times and are now linked to individuals of particular geographic origin or ethnicity

Attitude towards Intranasal Vaccines and Psychological Determinants: Effects on the General Population in Northern Italy

Little is known about the use of intranasal vaccines, but some studies have shown that this innovative way of administration is preferred over needle injection as it is considered both less painful and intrusive to the body, equally effective, and associated with fewer side effects. This study aimed to investigate specific psychological determinants (intolerance of uncertainty, persecutory ideation, perceived control, vaccine hesitancy) of attitude toward nasal vaccine delivery. A convenience sample including 700 Italian participants took part in this cross-sectional study and completed an online questionnaire. A structural equation model with a latent variable was performed to study the relationship between psychological variables, vaccine hesitancy, and attitude toward nasal vaccine delivery. The results indicate that both a hesitant attitude toward vaccination (beta = 0.20, p = 0.000) and low perceived control (beta = -0.20, p = 0.005) may directly increase preference for nasal administration; furthermore, high levels of persecutory ideation may indirectly influence the propensity for intranasal vaccine. These findings suggest that pharmaceutical companies could implement nasal vaccines and provide detailed information on these vaccines through informational campaigns. Hesitant individuals with low levels of perceived control could more easily comply with these types of vaccines

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

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

Recurrence of another hepatitis B virus escape mutant comes back in a patient infected with HIV and low CD4+ count

The case of an HIV-positive patient who cleared formerly acute HBV infection and experienced HBV exacerbation before starting antiretroviral therapy (ART) followed by a severe elevation of liver enzymes one month after the introduction of ART is reported. Laboratory tests revealed the presence of a subgenotype A2 carrying at least seven different mutations within the S protein and high lopinavir plasma concentrations. Irrespectively of the many possible mechanisms of HBV reactivation in patients infected with HIV (escape mutants selection, host immune deficiency progression, antiretroviral-related immune reconstitution, glucocorticosteroids, chemotherapy), the message is that HIV patients should be monitored strictly not only by serological and virological assays to recognize early HBV reactivation, but also for drug over-exposure

Enigmatic origin of hepatitis B virus : An ancient travelling companion or a recent encounter?

Hepatitis B virus (HBV) is the leading cause of liver disease and infects an estimated 240 million people worldwide. It is characterised by a high degree of genetic heterogeneity because of the use of a reverse transcriptase during viral replication. The ten genotypes (A-J) that have been described so far further segregate into a number of subgenotypes which have distinct ethno-geographic distribution. Genotypes A and D are ubiquitous and the most prevalent genotypes in Europe (mainly represented by subgenotypes D1-3 and A2); genotypes B and C are restricted to eastern Asia and Oceania; genotype E to central and western Africa; and genotypes H and F (classified into 4 subgenotypes) to Latin America and Alaska. This review summarises the data obtained by studying the global phylodynamics and phylogeography of HBV genotypes, particularly those concerning the origin and dispersion histories of genotypes A, D, E and F and their subgenotypes. The lack of any consensus concerning the HBV substitution rate and the conflicting data obtained using different calibration approaches make the time of origin and divergence of the various genotypes and subgenotypes largely uncertain. It is hypothesised that HBV evolutionary rates are time dependent, and that the changes depend on the main transmission routes of the genotypes and the dynamics of the infected populations

Mental health and risk perception among Italian healthcare workers during the second month of the Covid-19 pandemic

A multicentre cross-sectional study was conducted to assess perceived risk and fear of contagion, as well as mental health outcomes among 650 Italian healthcare workers during the COVID-19 outbreak. A relevant proportion of the sample reported symptoms of anxiety, depression, and distress. Female sex, nursing profession, fear of being infected, as well as the time of exposure to the COVID-19 spread and the fact of directly attending infected patients were the main risk factors for developing mental health disturbances. Tailored interventions need to be implemented to reduce psychological burden in healthcare workers, with a particular attention to nurses

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