Risk of parenterally transmitted hepatitis following exposure to invasive procedures in Italy: SEIEVA surveillance 2000-2021.

BACKGROUND & AIMS: Surgical interventions and invasive diagnostic/therapeutic procedures are known routes of transmission of viral hepatitis. Using data from the Italian surveillance system for acute viral hepatitis (SEIEVA), the aim of this study was to investigate the association between specific types of invasive procedures and the risk of acute HBV and HCV infections. METHODS: Data from SEIEVA (period 2000-2021) were used. The association between acute HBV and HCV infection and potential risk factors, i.e. surgical interventions and diagnostic/therapeutic procedures (given according to the ICD-9-CM classification), was investigated in comparison to age-matched hepatitis A cases, used as controls, by conditional multiple logistic regression analysis. RESULTS: A total of 8,176 cases with acute HBV, 2,179 with acute HCV, and the respective age-matched controls with acute HAV infection were selected for the main analysis. Most of the procedures evaluated were associated with the risk of acquiring HBV or HCV. The strongest associations for HBV infection were: gynaecological surgery (odds ratio [OR] 5.19; 95% CI 1.12-24.05), otorhinolaryngological surgery (OR 3.78; 95% CI 1.76-8.09), and cardiac/thoracic surgery (OR 3.52; 95% CI 1.34-9.23); while for HCV infection, they were: neurosurgery (OR 11.88; 95% CI 2.40-58.85), otorhinolaryngological surgery (OR 11.54; 95% CI 2.55-52.24), and vascular surgery (OR 9.52; 95% CI 3.25-27.87). Hepatitis C was also strongly associated with ophthalmological surgery (OR 8.32; 95% CI 2.24-30.92). Biopsy and/or endoscopic procedures were significantly associated with both HCV (OR 3.84; 95% CI 2.47-5.95) and, to a lesser extent, HBV infection (OR 1.48; 95% CI 1.16-1.90). CONCLUSIONS: Despite the progress made in recent years, invasive procedures still represent a significant risk factor for acquiring parenterally transmitted hepatitis viruses, thus explaining the still numerous and unexpected cases diagnosed among the elderly population in Italy. Our results underline the importance of observing universal precautions to control the iatrogenic transmission of hepatitis viruses. IMPACT AND IMPLICATIONS: Cases of parenterally transmitted acute viral hepatitis in the elderly population, that are difficult to explain based on the most widely recognised risk factors, continue to be diagnosed in Italy. Based on the Italian SEIEVA surveillance of acute viral hepatitis data, this study highlights an increased risk of acquiring hepatitis B and C following exposure to invasive procedures, which might explain the observed cases in elderly individuals. Furthermore, this finding emphasises the need to observe universal precautions strictly, in healthcare settings, including in the case of minor surgical procedures.

[An update on the epidemiology of hepatitis A in Italy 2015-2019. Data from the surveillance of acute viral hepatitis SEIEVA]. / Aggiornamento sull'epidemiologia dell'epatite A in Italia negli ultimi cinque anni. Dati dalla sorveglianza SEIEVA 2015-2019.

BACKGROUND: hepatitis A is an infective disease whose global diffusion appears to be variable and strictly related to socioeconomic status, hygiene conditions, and access to potable water. During last twenty years, Italy registered a constant decrease of new cases with recurrent epidemic outbreaks. OBJECTIVES: to outline the hepatitis A epidemiological situation in Italy in the five-year period 2015-2019. DESIGN: descriptive study based on cases reported to the National Surveillance System for Acute Viral Hepatitis (SEIEVA). SETTING AND PARTICIPANTS: hepatitis A cases reported to SEIEVA from 2015 to 2019. MAIN OUTCOME MEASURES: hepatitis A incidence, percentages of cases exposed to known risk factors, distribution of cases by vaccination status. RESULTS: during the whole observational period, SEIEVA registered 4,929 type A hepatitis cases. The epidemic curve initially showed a trend with a low incidence level interrupted in August 2016 with the onset of a large epidemic, in the period between August 2016 and December 2017, involving 3,428 cases mostly adult men exposed to homosexual intercourses (MSM). Since January 2018, the trend of the cases has been decreasing even though its level is still higher than the pre-epidemic period. Based on the analysis of the epidemic curve, three periods characterized by different trends in the monthly number of notified cases were identified: January 2015-July 2016 (pre-epidemic period), August 2016-December 2017 (epidemic period), January 2018-December 2019 (post-epidemic period). In the last observation period, cases show different characteristics compared to the previous periods. They are mainly males under 18 years (p=0.026), subjects travelling to Morocco (8.9% vs 15.9%; p< 0.001) or being in contact with an infected person (p< 0.001). The multivariate analysis confirmed a significantly higher probability for cases notified in the post-epidemic period, compared to the pre-epidemic, to be secondary cases or to have traveled to Morocco. Compared to the pre-epidemic period and the epidemic period, there was a higher percentage of subjects who received a single dose of anti-hepatitis A vaccine (p=0.001). Taking into account only secondary cases reported in the third period, the percentage of cases with incomplete vaccination rises to 31%; in this group, a single dose of the vaccine was administered at a median of 11.5 days before the onset of symptoms. CONCLUSIONS: vaccination is of paramount importance for the prevention of hepatitis A in all risk groups, including adult males exposed to same-sex sexual intercourse and travelers to areas at high-medium endemic level, especially children, as the timeliness in the vaccination of contacts is fundamental and crucial for interrupting the chains of infection. The observed increase in secondary cases and the delay in the administration of doses lead to a reflection on the need for greater promotion of vaccination, but also highlight the critical issues in the organization of vaccination services, mainly in the areas that have reported the greatest number of cases.

[Epidemiology and surveillance of hepatitis E in Italy: data from the SEIEVA surveillance system 2007-2019]. / Epidemiologia e sorveglianza dell'epatite E in Italia: dati dalla sorveglianza SEIEVA 2007-2019.

BACKGROUND: hepatitis E is a disease spread all over the world, with endemic levels varying according to ecological and socioeconomic factors. In developing countries, large epidemics spread mainly through contaminated water; in developed countries, hepatitis E has always been considered a sporadic disease, closely associated to the travels to endemic areas, especially in Southeastern Asia. In the last years, this perception is significantly changing, because of an increasing number of autochthonous cases reported in many European countries. OBJECTIVES: to describe the epidemiological picture of hepatitis E in Italy from 2007 to 2019. DESIGN: descriptive study based on the cases reported to the special surveillance of acute viral hepatitis (SEIEVA); case-control analytical study for the analysis of risk factors associated with hepatitis E. SETTING AND PARTICIPANTS: hepatitis E cases reported to SEIEVA in the period 2007-2019. MAIN OUTCOME MEASURES: number of cases notified by year, percentages of cases exposed to known risk factors, odds ratios. RESULTS: from January 2007 to June 2019, 385 hepatitis E cases were notified to SEIEVA. The annual number increased from 12 in 2007 to 49 in 2018, the increasing trend continued in 2019, when 39 cases were observed in the first 6 months of the year. Northern and Central Regions reported most of the cases; only a few were diagnosed in Southern Regions. Based on SEIEVA data, the trend of hepatitis E notifications has increased according to the increasing propensity to the differentiated diagnosis, at least until 2018. However, only 46% of suspected cases are tested to detect the presence of anti-HEV IgM antibodies, during the observation period; the percentage of tested cases is significantly lower in the South than in Northern and Central Italy (p<0.001). The reported cases have a median age of 48 years (range: 5-87) and are mostly males (80%); 32% was observed in foreign citizens mainly from endemic areas of South Asia (Bangladesh, India, and Pakistan). In 72.5% of cases, the infection was contracted in Italy. The most frequent risk factor is the consumption of raw or undercooked pork meat, especially sausages (70% of cases), significantly associated with hepatitis E risk (OR 3.0; IC95% 1.4-6.1). Other important risk factors are wild boar sausages consumption (40% of cases, OR 4.6, not statistically significant), and travels to endemic areas during the six weeks before the disease (31% of cases, OR 3.2; IC95% 1.6-6.4). CONCLUSIONS: hepatitis E can now be considered as endemic even in industrialized countries. In Italy, from 2007 an increasing number of cases has been reported. However, the real impact of HEV infection is still underestimated due to the limited number of clinical centres which perform tests for the search of anti-HEV IgM antibodies in cases of acute hepatitis. An ad hoc surveillance has been activated in January 2019 in some Local Health Units/Regions and extended to a national level starting from January 2020. This initiative is necessary in order to better dimension the burden of the disease associated with HEV infection, to study its epidemiology, and to increase awareness of this infection among health professionals.

Active surveillance for safety monitoring of seasonal influenza vaccines in Italy, 2015/2016 season.

BACKGROUND: Surveillance for adverse events following immunization is an important component of any national immunization programme because it is critical to assessing the safety of vaccines and to detecting potentially rare and severe adverse events and responding in a timely manner. We conducted an enhanced active surveillance aimed at assessing the safety of flu vaccines in the 2015-2016 season in Italy. The study was targeted to the population groups for which the seasonal vaccine is recommended in Italy. METHODS: During the study period, a total of 3213 individuals receiving seasonal influenza vaccination were registered on the web-based platform. Any adverse events experienced after 7 days from vaccination by individuals aged six months or more were collected through a telephone interview or by a web-based self-administered questionnaire. All individuals experiencing at least one event during the 7 days of follow-up were contacted for follow-up to 60 days. RESULTS: Overall, 854 events were reported: 845 events (26%) after administration of the first dose and 9 (12%) after the second dose. The majority of adverse events reported after 7 days from the first dose were of little clinical importance, and most involved local symptoms. CONCLUSION: Our data, even though the number of vaccinated individuals was smaller than expected, is consistent with the safety of influenza vaccines in Italy during the 2015-2016 season regarding the most common adverse events. Further efforts are needed to obtain sufficient power to study rarer adverse events. Active monitoring and systematic studies to test generated signals and hypotheses are crucial to intensify awareness among the public and professionals with regard to the safety of vaccines.

Hepatitis E in Italy: 5 years of national epidemiological, virological and environmental surveillance, 2012 to 2016.

Increasing numbers of hepatitis E cases are being reported in several European countries, including Italy, but the burden of hepatitis E virus (HEV) infection is largely unknown in the latter. To gain a better understanding of HEV epidemiology at national level in Italy, we piloted a strengthened and integrated human (epidemiological and virological) and environmental HEV surveillance system between 2012 and 2016. Over the 5-year period, 169 confirmed hepatitis E cases were identified, with a national annual incidence of 0.72 cases per 1,000,000. Of 65 HEV-RNA positive samples of sufficient quality for molecular analysis, 66% were genotype HEV3, 32% HEV1 and 1% HEV4. The most frequent risk factor reported by all HEV3 infected cases, was the consumption of undercooked pork and sausage. For the environmental surveillance, 679 urban sewage samples were collected from 53 wastewater treatment plants and HEV-RNA was detected in 38/679 of the samples. Among these, 25 (66%) were genotype HEV3 and the remaining were HEV1. We demonstrate that autochthonous transmission and environmental circulation of genotype HEV3 is adding to travel-related HEV transmission in Italy. We recommend the 'One Health' approach to integrated surveillance, and to include HEV-related messages within health information campaigns focussing on food security.

Hepatitis A outbreak disproportionately affecting men who have sex with men (MSM) in the European Union and European Economic Area, June 2016 to May 2017.

Between 1 June 2016 and 31 May 2017, 17 European Union (EU) and European Economic Area countries reported 4,096 cases associated with a multi-country hepatitis A (HA) outbreak. Molecular analysis identified three co-circulating hepatitis A virus (HAV) strains of genotype IA: VRD_521_2016, V16-25801 and RIVM-HAV16-090. We categorised cases as confirmed, probable or possible, according to the EU outbreak case definitions. Confirmed cases were infected with one of the three outbreak strains. We investigated case characteristics and strain-specific risk factors for transmission. A total of 1,400 (34%) cases were confirmed; VRD_521_2016 and RIVM-HAV16-090 accounted for 92% of these. Among confirmed cases with available epidemiological data, 92% (361/393) were unvaccinated, 43% (83/195) travelled to Spain during the incubation period and 84% (565/676) identified as men who have sex with men (MSM). Results depict an HA outbreak of multiple HAV strains, within a cross-European population, that was particularly driven by transmission between non-immune MSM engaging in high-risk sexual behaviour. The most effective preventive measure to curb this outbreak is HAV vaccination of MSM, supplemented by primary prevention campaigns that target the MSM population and promote protective sexual behaviour.

Low 2016/17 season vaccine effectiveness against hospitalised influenza A(H3N2) among elderly: awareness warranted for 2017/18 season.

In a multicentre European hospital study we measured influenza vaccine effectiveness (IVE) against A(H3N2) in 2016/17. Adjusted IVE was 17% (95% confidence interval (CI): 1 to 31) overall; 25% (95% CI: 2 to 43) among 65-79-year-olds and 13% (95% CI: -15 to 30) among those ≥ 80 years. As the A(H3N2) vaccine component has not changed for 2017/18, physicians and public health experts should be aware that IVE could be low where A(H3N2) viruses predominate.

2015/16 seasonal vaccine effectiveness against hospitalisation with influenza A(H1N1)pdm09 and B among elderly people in Europe: results from the I-MOVE+ project.

We conducted a multicentre test-negative case-control study in 27 hospitals of 11 European countries to measure 2015/16 influenza vaccine effectiveness (IVE) against hospitalised influenza A(H1N1)pdm09 and B among people aged ≥ 65 years. Patients swabbed within 7 days after onset of symptoms compatible with severe acute respiratory infection were included. Information on demographics, vaccination and underlying conditions was collected. Using logistic regression, we measured IVE adjusted for potential confounders. We included 355 influenza A(H1N1)pdm09 cases, 110 influenza B cases, and 1,274 controls. Adjusted IVE against influenza A(H1N1)pdm09 was 42% (95% confidence interval (CI): 22 to 57). It was 59% (95% CI: 23 to 78), 48% (95% CI: 5 to 71), 43% (95% CI: 8 to 65) and 39% (95% CI: 7 to 60) in patients with diabetes mellitus, cancer, lung and heart disease, respectively. Adjusted IVE against influenza B was 52% (95% CI: 24 to 70). It was 62% (95% CI: 5 to 85), 60% (95% CI: 18 to 80) and 36% (95% CI: -23 to 67) in patients with diabetes mellitus, lung and heart disease, respectively. 2015/16 IVE estimates against hospitalised influenza in elderly people was moderate against influenza A(H1N1)pdm09 and B, including among those with diabetes mellitus, cancer, lung or heart diseases.

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.

Promotion of influenza vaccination among health care workers: findings from a tertiary care children's hospital in Italy.

BACKGROUND: The aims of this study were: a) to evaluate attitudes and practices of health care workers (HCWs) towards influenza vaccination and their opinion regarding a vaccination promotion toolkit; b) to estimate hospital HCWs' influenza vaccination coverage rates (VC). METHODS: The Bambino Gesù Children's Hospital (OPBG) is an academic hospital in Italy. Since 2009, free influenza vaccination is offered to HCWs during working hours. In October-December 2013, a communication campaign based on a standardized toolkit was conducted. In December 2013, we performed a cross-sectional survey in a sample of hospital wards, based on a self-administered questionnaire including participants' characteristics; self-reported influenza vaccination history; reasons for vaccination or missed vaccination; opinion regarding the toolkit. Multivariable logistic analysis was used to assess independent predictors of influenza vaccination status. Annual VC for years 2009-2013 was estimated by using the number of seasonal influenza vaccine doses administered to HCWs as numerator, and the number of hospital HCWs as denominator. RESULTS: Out of 191 HCWs who participated in the survey, 35.6% reported at least one influenza vaccination during their life; 6.8% adhered to annual revaccination. Years of service and professional category were significantly and independently associated with vaccination (adjusted-OR: 2.4 for > 10 years of service, compared to < 5 years of service; adjusted-OR: 2.6 for physicians compared to nurses). Patient protection was the main reported reason for vaccination (34.3%); considering influenza a mild disease was the main reason for non-vaccination (36.9%); poor vaccine effectiveness was the main reason for missed annual revaccination (28.8%). Overall, 75% of respondents saw at least one promotion tool; 65.6% of them found the information useful. Hospital VC decreased from 30% in 2009, to 5% in 2012. In 2013, VC was 14%. CONCLUSIONS: Satisfactory influenza VC in HCWs is hard to achieve. In 2013, along with the toolkit implementation, we observed an increase in HCWs' vaccination coverage, nevertheless, it remained unsatisfactory. Tailored information strategies targeting nurses and recently employed HCWs should be implemented. Institution of declination statements, adding influenza vaccination to financial incentive systems, or vaccination requirements should also be considered to increase influenza VC among HCWs.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Attitude and compliance towards influenza vaccination among health care workersin two Italian hospitals after a vaccination promotion campaign]. / Atteggiamento degli operatori sanitari di due ospedali italiani nell'ambito di una campagna di promozione della vaccinazione antinfluenzale.

In the season 2013-2014, a campaign to promote influenza vaccination among health care workers (HCWs) was conducted in two Italian hospitals, based on an educational toolkit and attitude and compliance towards vaccination were investigated. Overall, 36% of the HCWs get vaccinated almost once, 2.3% in 2013-14 season for the first time, 57% never, 7% do not know or not remember. The main reason for vaccination was reportedly to avoid taking sick-leave (29.7%); while refusal was guided by the low risk-perception associated with influenza (38.5%). Interventions based only on education and communication seem not to be sufficient; an integrated approach with multiple components is needed to achieve higher coverage rates and to ensure a successful vaccination campaign.

Differences in Incidence of Acute Viral Hepatitis between Foreigners and Autochthonous Population in Italy.

BACKGROUND: In European countries, the prevalence of HBV and HCV in refugees and migrants tends to reflect the prevalence in their countries of origin. The aim of this study is to analyse acute viral hepatitis cases diagnosed in Italy among foreign citizens and to compare incidence rates in foreigners and Italians. METHODS: We analysed the cases of each viral hepatitis type among foreigners. Standardised incidence rates were compared between natives and foreigners. RESULTS: Between 2004 and 2019, 15,872 cases of acute viral hepatitis were notified by 10 Italian regions, 14.8% among foreign citizens. Until 2012, the percentage increased gradually, while a fluctuating trend set in from 2013 onwards; in 2019, 23.9% of cases were foreigners. Data from the SEIEVA surveillance show higher standardised incidence rates of hepatitis A and B among foreign citizens; no significant difference emerged between Italians and foreigners in terms of their hepatitis C incidence. CONCLUSIONS: foreign citizens have an increased incidence of hepatitis A and B. Regarding hepatitis A, vaccination is strongly recommended to foreigners travelling to their countries of origin. Screening tests for hepatitis B and C infection should be offered to newly arrived migrants from high prevalence countries, or having specific risk factors.

A large food-borne outbreak of campylobacteriosis in kindergartens and primary schools in Pescara, Italy, May-June 2018.

Introduction. In May-June 2018, an outbreak of campylobacteriosis involved students and school staff from kindergartens and primary schools in Pescara, southern Italy.Aim. We present details of the epidemiological and microbiological investigation, and the findings of the analytical study, as well as the implemented control measures.Methodology. To identify possible risk factors associated with the observed outbreak, a case control study was conducted using a questionnaire to collect information on the date of symptoms onset, type and duration of symptoms, type of healthcare contact, school attendance, and food items consumed at school lunches during the presumed days of exposure. Attack rates were calculated for each date and school. Logistic regression models were used to estimate the odds ratios of being a case and the odds of illness by food items consumed, respectively. Moreover, we carried out a comparative genomic analysis using whole genome multilocus sequence typing (wgMLST) of Campylobacter jejuni strains isolated during the outbreak investigation to identify the source of the outbreak.Results. Overall, 222 probable cases from 21 schools were identified, and C. jejuni was successfully isolated from 60 patients. The meals in the schools involved were provided by two cooking centres managed by a joint venture between two food companies. Environmental and food sampling, epidemiological and microbiological analyses, as well as a case control study with 176 cases and 62 controls from the same schools were performed to identify the source of the outbreak. The highest attack rate was recorded among those having lunch at school on 29 May (7.8 %), and the most likely exposure was 'caciotta' cheese (odds ratio 2.40, 95 % confidence interval 1.10-5.26, P=0.028). C. jejuni was isolated from the cheese, and wgMLST showed that the human and cheese isolates belonged to the same genomic cluster, confirming that the cheese was the vehicle of the infection.Conclusion. It is plausible that a failure of the pasteurization process contributed to the contamination of the cheese batches. Timely suspension of the catering service and summer closure of the schools prevented further spread.

No Evidence of SARS-CoV-2 Circulation in Rome (Italy) during the Pre-Pandemic Period: Results of a Retrospective Surveillance.

In March 2020, the World Health Organization (WHO) declared that the COVID-19 outbreak recorded over the previous months could be characterized as a pandemic. The first known Italian SARS-CoV-2 positive case was reported on 21 February. In some countries, cases of suspected "COVID-19-like pneumonia" had been reported earlier than those officially accepted by health authorities. This has led many investigators to check preserved biological or environmental samples to see whether the virus was detectable on dates prior to those officially stated. With regard to Italy, the results of a microbiological screening in sewage samples collected between the end of February and the beginning of April 2020 from wastewaters in Milan (Northern Italy) and Rome (Central Italy) showed presence of SARS-CoV-2. In the present study, we evaluated, by means of a standardized diagnostic method, the SARS-CoV-2 infection prevalence amongst patients affected by severe acute respiratory syndrome (SARI) in an academic hospital located in Central Italy during the period of 1 November 2019-1 March 2020. Overall, the number of emergency room (ER) visits during the investigated period was 13,843. Of these, 1208 had an influenza-like syndrome, but only 166 matched the definition of SARI as stated in the study protocol. A total of 52 SARI cases were laboratory confirmed as influenza: 26 as a type B virus, 25 as a type A, and 1 as both viruses. Although about 17% of the total sample had laboratory or radiological data compatible with COVID-19, all the nasopharyngeal swabs stored underwent SARS-CoV-2 RT-PCR and tested negative. Based on our result, it is confirmed that the COVID-19 pandemic spread did not start prior to the "official" onset in central Italy. Routine monitoring of SARI causative agents at the local level is critical for reporting epidemiologic and etiologic trends that may differ from one country to another and also among different influenza seasons. This has a practical impact on prevention and control strategies.

The Exponential Phase of the Covid-19 Pandemic in Central Italy: An Integrated Care Pathway.

The Coronavirus Disease (Covid-19) pandemic is rapidly spreading across the world, representing an unparalleled challenge for health care systems. There are differences in the estimated fatality rates, which cannot be explained easily. In Italy, the estimated case fatality rate was 12.7% in mid-April, while Germany remained at 1.8%. Moreover, it is to be noted that different areas of Italy have very different lethality rates. Due to the complexity of Covid-19 patient management, it is of paramount importance to develop a well-defined clinical workflow in order to avoid the inconsistent management of patients. The Integrated Care Pathway (ICP) represents a multidisciplinary outline of anticipated care to support patient management in the Sant'Andrea Hospital, Rome. The main objective of this pilot study was to develop a new ICP evaluated by care indicators, in order to improve the COVID-19 patient management. The suggested ICP was developed by a multi-professional team composed of different specialists and administrators already involved in clinical and management processes. After a review of current internal practices and published evidences, we identified (1) the activities performed during care delivery, (2) the responsibilities for these activities, (3) hospital structural adaptation needs and potential improvements, and (4) ICP indicators. The process map formed the basis of the final ICP document; 160 COVID-19 inpatients were considered, and the effect of the ICP implementation was evaluated over time during the exponential phase of the COVID-19 pandemic. In conclusion, a rapid adoption of ICP and regular audits of quality indicators for the management of COVID-19 patients might be important tools to improve the quality of care and outcomes.

Moderate Vaccine Effectiveness against Severe Acute Respiratory Infection Caused by A(H1N1)pdm09 Influenza Virus and No Effectiveness against A(H3N2) Influenza Virus in the 2018/2019 Season in Italy.

Every season, circulating influenza viruses change; therefore, vaccines must be reformulated each year. We aimed to estimate vaccine effectiveness (VE) against severe influenza infection for the 2018/19 season in Italy. We conducted a test-negative design case-control study at five Italian hospitals. We estimated influenza VE against severe acute respiratory infection (SARI) requiring hospitalisation overall, and by virus subtype, vaccine brand, and age. The 2018/19 season was characterised by A(H1N1)pmd09 and A(H3N2) influenza viruses. Vaccine coverage among <18 years recruited SARI cases was very low (3.2%). Seasonal vaccines were moderately effective against type A influenza overall (adjusted VE = 40.5%; 95% confidence interval (CI) = 18.7-56.4%) and subtype A(H1N1)pmd09 viruses (adjusted VE = 55%; 95% CI = 34.5-69.1%), but ineffective against subtype A(H3N2) viruses (adjusted VE = 2.5%; 95% CI = -50.0-36.7%). Both Fluad and Fluarix Tetra vaccines were effective against type A influenza overall and subtype A(H1N1)pdm09 viruses. VE appeared to be similar across age groups (0-64 years, ≥65 years). Seasonal influenza vaccines in the 2018/19 season were moderately effective in preventing SARI caused by A(H1N1)pdm09 influenza but ineffective against A(H3N2).

Vaccine effectiveness against influenza A(H3N2) and B among laboratory-confirmed, hospitalised older adults, Europe, 2017-18: A season of B lineage mismatched to the trivalent vaccine.

BACKGROUND: Influenza A(H3N2), A(H1N1)pdm09 and B viruses co-circulated in Europe in 2017-18, predominated by influenza B. WHO-recommended, trivalent vaccine components were lineage-mismatched for B. The I-MOVE hospital network measured 2017-18 seasonal influenza vaccine effectiveness (IVE) against influenza A(H3N2) and B among hospitalised patients (≥65 years) in Europe. METHODS: Following the same generic protocol for test-negative design, hospital teams in nine countries swabbed patients ≥65 years with recent onset (≤7 days) severe acute respiratory infection (SARI), collecting information on demographics, vaccination status and underlying conditions. Cases were RT-PCR positive for influenza A(H3N2) or B; controls: negative for any influenza. "Vaccinated" patients had SARI onset >14 days after vaccination. We measured pooled IVE against influenza, adjusted for study site, age, sex, onset date and chronic conditions. RESULTS: We included 3483 patients: 376 influenza A(H3N2) and 928 B cases, and 2028 controls. Most (>99%) vaccinated patients received the B lineage-mismatched trivalent vaccine. IVE against influenza A(H3N2) was 24% (95% CI: 2 to 40); 35% (95% CI: 6 to 55) in 65- to 79-year-olds and 14% (95% CI: -22 to 39) in ≥80-year-olds. Against influenza B, IVE was 30% (95% CI: 16 to 41); 37% (95% CI: 19 to 51) in 65- to 79-year-olds and 19% (95% CI: -7 to 38) in ≥80-year-olds. CONCLUSIONS: IVE against influenza B was similar to A(H3N2) in hospitalised older adults, despite trivalent vaccine and circulating B lineage mismatch, suggesting some cross-protection. IVE was lower in those ≥80 than 65-79 years. We reinforce the importance of influenza vaccination in older adults as, even with a poorly matched vaccine, it still protects one in three to four of this population from severe influenza.

Effectiveness of the trivalent MF59 adjuvated influenza vaccine in preventing hospitalization due to influenza B and A(H1N1)pdm09 viruses in the elderly in Italy, 2017 - 2018 season.

Background: Evidence on influenza vaccine effectiveness (VE) in preventing mortality and morbidity in the elderly is weak. Our aim was to measure the VE against severe outcomes in the elderly. Methods: We conducted a multicentre hospital-based test-negative design (TND) case-control study, during the 2017/18 season, in four Italian hospitals. The study population included individuals aged ≥65 years hospitalized with Severe Acute Respiratory Infections (SARI). Patients were classified as cases and controls based on the results of the PCR influenza testing. We estimated VE by virus subtypes and specific VE for the trivalent adjuvanted vaccine (TIVadj). Results: 502 patients with SARI were enrolled: 118 (23.5%) tested positive (cases) and 384 (76.5%) tested negative (controls) for influenza. The adjusted VE of 48.5% for all vaccines was comparable to the adjusted VE for the TIVadj vaccine (48.3%). Adjusted VE for the TIVadj vaccine was 67.5% for A(H1N1)pdm09 and 44.5% for B viruses. Conclusion: We show a moderate adjusted VE of the TIVadj against all viruses, a good adjusted VE against A(H1N1)pdm09 strains and a moderate adjusted VE against B strains, despite a mismatch between the B circulating lineage and the lineage included in the vaccine. This is likely due to the cross-protection among B strains induced by the TIVadj in elderly patients.

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.