Valeria Alfonsi

Cross-reactive antibody responses to the 2009 A/H1N1v influenza virus in the Italian population in the pre-pandemic period

To assess in Italy the pre-pandemic susceptibility of the general population to the 2009 A/H1N1v influenza virus, 587 serum samples collected in 2004 were analyzed using haemagglutination-inhibition (HI), single-radial-haemolysis (SRH) and microneutralisation (MN) assays. Serum samples were stratified by age group, gender, and geographic area. Overall, using HI assay, the proportion of subjects showing antibodies cross-reacting with 2009 A/H1N1v virus at seroprotection level (>or=1:40) was estimated to be 6.7%, 12.4%, and 22.4% in individuals born between 2004 and 1949, 1948 and 1939, 1938 and 1909, respectively. With a HI antibody titre of >or=1:10, in the same birth cohort, the seroprotection levels were 13.5%, 19.2%, and 58.2%, respectively. The results suggest that the Italian population was not fully naïf to the current pandemic virus and that the possible previous exposure and immune response increases with age.

Ongoing outbreak of hepatitis A in Italy: preliminary report as of 31 May 2013

Since January 2013, an unusual increase in hepatitis A cases has been detected in northern Italy. A total number of 352 cases were reported to the integrated surveillance system between January and the end of May 2013 and this represents a 70% increase compared to the same period of the previous year. The outbreak is ongoing and the public health authorities are continuing their investigations to establish the transmission vehicle and to control the outbreak.

Surveillance of hepatitis A virus in urban sewages and comparison with cases notified in the course of an outbreak, Italy 2013

BackgroundOver 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.MethodsThe 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.ResultsA 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.ConclusionsThe 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.

Migrant's access to immunization in Mediterranean Countries

Countries bordering the Mediterranean are part of a major migration system. The aim of this study is to assess the main access barriers to immunization of mobile populations in the region and propose an action based framework to decrease health access inequalities. A survey on formal and informal barriers to immunization among mobile communities was conducted among public health officials formally appointed as focal points of the EpiSouth Network by 26 Mediterranean countries. Twenty-two completed the questionnaire. Thirteen countries reported at least one vaccine preventable disease (VPD) outbreak occurring among mobile populations since 2006 even though their legal entitlement to immunization is mostly equivalent to the general populations. Informal barriers, particularly lack of information and lack of trust in authorities, and disaggregation of data collection are the major issues still to be addressed. Mediterranean countries need to fill the gap in immunization coverage among pockets of susceptible individuals in order to prevent VPD outbreaks. Having for the most part ensured free entitlement, introducing more migrant friendly approaches, increasing information availability among mobile communities, building trust in public health services and disaggregating data collection to monitor and evaluate service performance among mobile groups are key aspects to address in the region.

Key Role of Sequencing to Trace Hepatitis A Viruses Circulating in Italy During a Large Multi-Country European Foodborne Outbreak in 2013

Background 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. Methods Molecular characterization was carried out by PCR/sequencing (VP1/2A region), comparison with reference strains and phylogenetic analysis. Results 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. Conclusions 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.

Hepatitis A outbreak in Italy, 2013: a matched case–control study

Between January and May 2013 a hepatitis A (HA) incidence increase was detected in Italy, signalling an outbreak. A retrospective matched case-control study was conducted to identify the source of infection. A case was defined as a resident of any of five regions (Apulia, autonomous province of Bolzano, Emilia-Romagna, Friuli-Venezia-Giulia and autonomous province of Trento), who had symptom onset between 1 January and 31 May2013 as well a positive test for anti-HA virus IgM. We compared each case with four age-and neighbourhood-matched controls. Overall 119 cases and 419 controls were enrolled. Berries were found as the main risk factor for HA (adjusted odds ratio (ORadj): 4.2; 95% confidence interval (CI): 2.5-7.0) followed by raw seafood (ORadj: 3.8; 95% CI: 2.2-6.8; PAF: 26%). Sequencing the virion protein (VP)1-2a region from 24 cases yielded a common sequence (GenBank number: KF182323). The same sequence was amplified from frozen mixed berries consumed by some cases as well as from isolates from Dutch and German HA patients, who had visited some of the affected Italian provinces during the outbreak. These findings suggested berries as the main source of the Italian outbreak. Control measures included voluntary recall of the confirmed frozen mixed berry batches and a trace-back investigation was initiated. The Ministry of Health website recommends frozen berries to be cooked for two minutes before eating. .

Seroprevalence and susceptibility to hepatitis A in the European Union and European Economic Area: a systematic review

Most of the European Union (EU) and European Economic Area (EEA) is considered a region of very low hepatitis A virus (HAV) endemicity; however, geographical differences exist. We did a systematic review with the aim of describing seroprevalence and susceptibility in the general population or special groups in the EU and EEA. We searched databases and public health national institutes websites for HAV seroprevalence records published between Jan 1, 1975, and June 30, 2014, with no language restrictions. An updated search was done on Aug 10, 2016. We defined seroprevalence profiles (very low, low, and intermediate) as the proportion of the population with age-specific anti-HAV antibodies at age 15 and 30 years, and susceptibility profiles (low, moderate, high, and very high) as the proportion of susceptible individuals at age 30 and 50 years. We included 228 studies from 28 of 31 EU and EEA countries. For the period 2000-14, 24 countries had a very low seroprevalence profile, compared with five in 1975-89. The susceptibility among adults ranged between low and very high and had a geographical gradient, with three countries in the low susceptibility category. Since 1975, EU and EEA countries have shown decreasing seropositivity; however, considerable regional variability exists. The main limitations of this study are that the studies retrieved for analysis might not be representative of all EU and EEA publications about HAV and might have poor national representativeness. A large proportion of EU and EEA residents are now susceptible to HAV infection. Our Review supports the need to reconsider specific prevention and control measures, to further decrease HAV circulation while providing protection against the infection in the EU and EEA, and could be used to inform susceptible travellers visiting EU and EEA countries with different HAV endemicity levels.

A large prolonged outbreak of hepatitis A associated with consumption of frozen berries, Italy, 2013-14.

Purpose. In 2013/2014, Italy experienced one of the largest community‐wide prolonged outbreaks of hepatitis A virus (HAV) throughout the country. The article provides a comprehensive description of the outbreak and the investigation carried out by a multidisciplinary National Task Force, in collaboration with regional and local public health authorities. Control strategies of food‐borne HAV infection in both the human and food sectors are also described. Methodology. Enhanced human epidemiological and microbiological surveillance together with microbiological monitoring of HAV in food and trace‐back investigation were conducted. Results. A total of 1803 HAV cases were identified from 1 January 2013 to 31 August 2014, in Italy. Sequencing was possible for 368 cases (20.4%), mostly collected between 1 January 2013 and 28 February 2014, and 246 cases (66.8%) harboured an HAV outbreak strain. Imported frozen berries contaminated with HAV were identified as the vehicle of the outbreak which also involved many other European countries in 2013 and 2014. Epidemiological evidence obtained through a case‐control study was supported by the finding of a 100% nucleotide similarity of the VP1/2A sequences of HAVs detected in human and food samples. Trace‐back investigation revealed an extremely complex supplying network with no possibility for a point source potentially explaining the vast contamination of berries found in Italy. Conclusion. The investigation benefited from an excellent collaboration among different sectors who shared proactively the available information. Our findings highlight the importance of considering frozen berries among the highest risk factors for HAV.

Acute Hepatitis B After the Implementation of Universal Vaccination in Italy: Results From 22 Years of Surveillance (1993–2014)

BACKGROUND Hepatitis B vaccination has proven to be very safe and highly effective. This study assessed the proportion of successfully vaccinated individuals among cases with acute hepatitis B, the proportion of preventable cases if individuals were vaccinated as recommended, and the reasons for failures. METHODS We analyzed data reported to the Italian Surveillance System for Acute Viral Hepatitis from 1993 to 2014. RESULTS A total of 362 of 11 311 (3.2%) cases with acute hepatitis B were vaccinated. Of the 277 cases for whom immunization data were available, 50 (18%) received a complete vaccination course according to the correct schedule and before exposure to hepatitis B virus. Molecular characterization of 17 of these cases showed that 6 were infected with S-gene mutants. Among the 10 949 unvaccinated cases, 213 (1.9%) escaped mandatory vaccination and 2821 (25.8%) were not vaccinated despite being at increased risk of infection. Among the latter, the most common risk factors were cohabitation with hepatitis B surface antigen (HBsAg) carriers, intravenous drug use, and homosexual/bisexual practices. Thirty-seven percent of the unvaccinated households with HBsAg carriers were aware of their risk. Lack of trust in the vaccination, negative attitude, and inaccurate beliefs followed by lack of or poor communication and low perceived severity of the disease were the most frequent reasons for vaccine hesitancy. CONCLUSIONS Development of acute disease in successfully vaccinated individuals is a rare event. Further efforts are needed to enhance the vaccine coverage rate in individuals at increased risk of infection.

Influenza vaccine effectiveness in Italy: Age, subtype-specific and vaccine type estimates 2014/15 season

The 2014/15 influenza season in Europe was characterised by the circulation of influenza A(H3N2) viruses with an antigenic and genetic mismatch from the vaccine strain A/Texas/50/2012(H3N2) recommended for the Northern hemisphere for the 2014/15 season. Italy, differently from other EU countries where most of the subtyped influenza A viruses were H3N2, experienced a 2014/15 season characterized by an extended circulation of two influenza viruses: A(H1N1)pdm09 and A(H3N2), that both contributed substantially to morbidity. Within the context of the existing National sentinel influenza surveillance system (InfluNet) a test-negative case-control study was established in order to produce vaccine effectiveness (VE) estimates. The point estimates VE were adjusted by age group (<5; 5-15; 15-64; 65+ years), the presence of at least one chronic condition, target group for vaccination and need help for walking or bathing. In Italy, adjusted estimates of the 2014/15 seasonal influenza VE against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza for all age groups were 6.0% (95%CI: -36.5 to 35.2%), 43.6% (95%CI: -3.7 to 69.3%), -84.5% (95%CI: (-190.4 to -17.2%) and 50.7% (95% CI: -2.5 to 76.3%) against any influenza virus, A(H1N1)pdm09, A(H3N2) and B, respectively. These results suggest evidence of good VE against A(H1N1)pdm09 and B viruses in Italy and evidence of lack of VE against A(H3N2) virus due to antigenic and genetic mismatch between circulating A(H3N2) and the respective 2014/15 vaccine strain.