Abstract Hepatitis B virus (HBV) infection is a world wide public health problem of major concern. HBV infection may lead to chronic liver disease, including cirrhosis and hepatocellular carcinoma ...(HCC). Vaccination is the most effective measure to control and prevent hepatitis B and its long-term serious sequelae on global scale, both in terms of cost-effectiveness and benefit-cost ratios. According to the WHO recommendations, universal vaccination has been currently implemented in 168 countries world wide with an outstanding record of safety and efficacy. The effective implementation of such programmes of vaccination has resulted in a substantial decrease in disease burden, in the carrier rate and in hepatitis B-related morbidity and mortality. A future challenge is to overcome the social and economic hurdles which still hamper the introduction of hepatitis B vaccination on a global scale.
Vaccination is the most effective way to control and prevent acute and chronic hepatitis B, including cirrhosis and HCC, on a global scale. According to WHO recommendations, 190 countries in the ...world have introduced hepatitis B vaccination into their national childhood immunization programs with an excellent profile of safety, immunogenicity, and effectiveness. Following vaccination, seroprotection rates are close to 100% in healthy children and over 95% in healthy adults. Persistence of anti-HBs is related to the antibody peak achieved after vaccination. The peak is higher the longer the antibody duration is. Loss of anti-HBs does not necessarily mean loss of immunity since most vaccinated individuals retain immune memory for HBsAg and rapidly develop strong anamnestic responses when boosted. Evidence indicates that the duration of protection can persist for at least 35 years after priming. Hence, booster doses of vaccines are currently not recommended to sustain long-term immunity in healthy vaccinated individuals. In Italy, vaccination against hepatitis B is met with success. In 2020, Italy became one of the first countries in Europe to be validated for achieving the WHO regional hepatitis B control targets.
...for immunocompetent children and adults, the administration of booster dose(s) is not routinely given in Italy to sustain long-term immunity in the general population, while is recommended in ...immunocompromised patients when level of antibody falls below the protective threshold (10 mIU/ml) 3. ...due to the biological association between HBV and hepatitis delta virus (HDV, a defective hepatotropic RNA virus which requires the concomitant presence of HBV to replicate), an added benefit we have achieved is that, according to the SEIEVA data, the incidence of hepatitis delta has also declined significantly in Italy (from 3.89 per 1,000,000 in 1990 to zero per 1,000,000 in 2020) following the implementation of hepatitis B vaccination 9. ...vaccination has clearly proven to be very successful in Italy, resulting in remarkable progress towards the control and prevention of hepatitis B. Our findings compare well with data coming from previously highly endemic countries (e.g. Taiwan, the Gambia, and Alaska) where the impact of vaccination in term of reduction in incidence of the disease, in carrier rate, and in HBV-related mortality has been highly impressive.
Recent molecular diagnostic methods have significantly improved the diagnosis of viral pneumonia in intensive care units (ICUs). It has been observed that 222G/N changes in the HA gene of H1N1pdm09 ...are associated with increased lower respiratory tract (LRT) replication and worse clinical outcome. In the present study, the frequency of respiratory viruses was assessed in respiratory samples from 88 patients admitted to 16 ICUs during the 2014-2015 winter-spring season in Lombardy. Sixty-nine out of 88 (78.4%) patients were positive for a respiratory viral infection at admission. Of these, 57/69 (82.6%) were positive for influenza A (41 A/H1N1pdm09 and 15 A/H3N2), 8/69 (11.6%) for HRV, 2/69 (2.9%) for RSV and 2/69 (2.9%) for influenza B. Phylogenetic analysis of influenza A/H1N1pdm09 strains from 28/41 ICU-patients and 21 patients with mild respiratory syndrome not requiring hospitalization, showed the clear predominance of subgroup 6B strains. The median influenza A load in LRT samples of ICU patients was higher than that observed in the upper respiratory tract (URT) (p<0.05). Overall, a greater number of H1N1pdm09 virus variants were observed using next generation sequencing on partial HA sequences (codons 180-286) in clinical samples from the LRT as compared to URT. In addition, 222G/N/A mutations were observed in 30% of LRT samples from ICU patients. Finally, intra-host evolution analysis showed the presence of different dynamics of viral population in LRT of patients hospitalized in ICU with a severe influenza infection.
Over the past 20 years, Hepatitis A notifications in Italy have been in decline. Since the beginning of 2013 however, Italy has been experiencing a foodborne hepatitis A outbreak caused by genotype ...IA, involving hundreds of cases. Consumption of frozen mixed berries was deemed the potential vehicle of infection.We aimed to investigate the spread of hepatitis A virus (HAV) in Italy through the monitoring of urban sewages collected at Wastewater Treatment Plants (WTPs) and a subsequent comparison of environmental surveillance data with data from the clinical surveillance performed during the epidemic.
The study covered 15 months, from July 2012 to September 2013, comprising the outbreak and the preceding six months. Environmental surveillance consisted of the analysis of urban sewage samples collected at 19 WTPs in seven of the Italian regions most affected by the epidemic. HAV isolates were detected and typed using a nested RT-PCR targeting the VP1/2A junction. Parallel clinical surveillance was performed by the sentinel surveillance system for acute viral hepatitis (SEIEVA) and by the ministerial Central Task Force on Hepatitis A, established with the purpose of determining the source of the outbreak and adopting appropriate outbreak control strategies.
A total of 38/157 wastewater samples (24.2%) were positive for HAV, 16 collected in 2012 and 22 in 2013. Several HAV strains were detected, including the IA variant implicated in the outbreak and isolated from clinical cases over the same period. The vast majority of sequences belonged to genotype IB. Interestingly however, although these included variants related to strains that had been involved in past Italian epidemics, none were detected in recent clinical samples, probably due to underreporting or asymptomatic circulation. Conversely, a number of sequences were identified in clinical samples that were not found in wastewaters.
The percentage of sewage samples detected as HAV-positive in this study are consistent with the classification of Italy as a country with low/intermediate endemicity. A combined environmental/clinical surveillance is able to provide a more complete picture of the spread of HAV and of the genotypes circulating in the population, allowing a better understanding of changes in disease trends.
Hepatitis B virus is a worldwide leading cause of acute and chronic liver disease including cirrhosis and hepatocellular carcinoma. Effective vaccines have been available since the early '80s and ...vaccination has proved highly successful in reducing the disease burden, the development of the carrier state and the HB-related morbidity and mortality in the countries where vaccination has been implemented.
Neutralizing (protective) antibodies (anti-HBs) induced by vaccination are targeted largely towards the amino acid hydrophilic region, referred to as the common a determinant which is present on the outer protein coat or surface antigen (HBsAg), spanning amino acids 124-149. This provides protection against all HBV genotypes (from A to H) and is responsible for the broad immunity afforded by hepatitis B vaccination. Thus, alterations of residues within this region of the surface antigen may determine conformational changes that can allow replication of the mutated HBV in vaccinated people.
An important mutation in the surface antigen region was identified in Italy some 25 years ago in infants born to HBsAg carrier mothers who developed breakthrough infections despite having received HBIG and vaccine at birth. This virus had a point mutation from guanosine to adenosine at nucleotide position 587, resulting in aa substitution from glycine (G) to arginine (R) at position 145 in the a determinant. Since the G145R substitution alters the projecting loop (aa 139-147) of the a determinant, the neutralizing antibodies induced by vaccination are no longer able to recognize the mutated epitope. Beside G145R, other S-gene mutations potentially able to evade neutralizing anti-HBs and infect vaccinated people have been described worldwide.
In addition, the emergence of Pol mutants associated with resistance to treatment with nucleos(t)ide analogues can select viruses with crucial changes in the overlapping S-gene, potentially able to alter the S protein immunoreactivity. Thus such mutants have the potential to infect both naïve and immunized people, negatively affecting the efficacy of both the antiviral treatment and the vaccination programs.
Despite concern, at present the overall impact of vaccine escapes mutants seems to be low and they do not pose a public health threat or a need to modify the established hepatitis B vaccination programs. The development of novel NAs with a high barrier to resistance is warranted.
Background & Aims In developed countries, hepatitis E is usually associated with travelling to endemic areas, but a growing number of sporadic cases are also seen in patients with no travel history. ...The aim of this study was to assess the impact and the molecular epidemiology of hepatitis E in Italy. Methods Between January 1994 and October 2009, we analyzed 651 patients with acute non-A–C hepatitis. Diagnosis of hepatitis E was based on the presence of IgM anti-HEV and/or the detection of HEV RNA by RT-PCR. Viral isolates were sequenced and phylogenetically characterized. Results A total of 134 out of 651 (20.6%) patients tested had acute hepatitis E. All were anti-HEV IgM and IgG positive and 96 (71.6%) were also positive for HEV RNA. Moreover, 39 (6%) patients were anti-HEV IgG positive but negative for both IgM anti-HEV and HEV RNA. A total of 109 (81.3%) patients developed hepatitis E travelling to endemic areas, 3 (2.3%) acquired intra-familial infection from relatives who developed travel-related disease, while 22 (16.4%) patients denied having travelled abroad. In all patients, acute disease had a self-limited course with ALT normalization within 3–6 weeks. Phylogenetic analysis of 39 isolates from patients with a travel-related disease showed that they belonged to genotype 1, while sequences from five patients with autochthonous hepatitis E belonged to genotype 3. Conclusions In Italy, most cases of hepatitis E are travel related, caused by viral genotype 1, while autochthonous cases are caused by genotype 3. The prevalence of genotype 3 among pigs and boars suggests that HEV infection may have zoonotic origins in non-endemic countries.
Abstract Viral hepatitis B is a leading cause of acute and chronic liver disease worldwide, including cirrhosis and hepatocellular carcinoma. Vaccination is the most effective measure for controlling ...and preventing hepatitis B and its severe long-term sequelae. According to the World Health Organization (WHO), by the end of 2008 177 countries had introduced hepatitis B vaccination into their national routine neonatal, infant and/or adolescent immunisation programmes, and Italy was one of the first countries to implement a universal strategy of hepatitis B vaccination. The implementation of such vaccination programmes has globally resulted in a marked decrease in disease burden, in the carrier rate and in hepatitis B-related morbidity and mortality. Despite this success, work remains to be done to fully achieve the WHO goal of control of hepatitis B and HBV-related diseases on a global scale.
Foodborne Hepatitis A Virus (HAV) outbreaks are being recognized as an emerging public health problem in industrialized countries. In 2013 three foodborne HAV outbreaks occurred in Europe and one in ...USA. During the largest of the three European outbreaks, most cases occurred in Italy (>1,200 cases as of March 31, 2014). A national Task Force was established at the beginning of the outbreak by the Ministry of Health. Mixed frozen berries were early demonstrated to be the source of infection by the identity of viral sequences in patients and in food. In the present study the molecular characterization of HAV isolates from 355 Italian cases is reported.
Molecular characterization was carried out by PCR/sequencing (VP1/2A region), comparison with reference strains and phylogenetic analysis.
A unique strain was responsible for most characterized cases (235/355, 66.1%). Molecular data had a key role in tracing this outbreak, allowing 110 out of the 235 outbreak cases (46.8%) to be recognized in absence of any other link. The data also showed background circulation of further unrelated strains, both autochthonous and travel related, whose sequence comparison highlighted minor outbreaks and small clusters, most of them unrecognized on the basis of epidemiological data. Phylogenetic analysis showed most isolates from travel related cases clustering with reference strains originating from the same geographical area of travel.
In conclusion, the study documents, in a real outbreak context, the crucial role of molecular analysis in investigating an old but re-emerging pathogen. Improving the molecular knowledge of HAV strains, both autochthonous and circulating in countries from which potentially contaminated foods are imported, will become increasingly important to control outbreaks by supporting trace back activities, aiming to identify the geographical source(s) of contaminated food, as well as public health interventions.
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