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.

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.

[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.

Prior Antibiotic Therapy and the Onset of Healthcare-Associated Infections Sustained by Multidrug-Resistant Klebsiella pneumoniae in Intensive Care Unit Patients: A Nested Case-Control Study.

Epidemiological research has demonstrated direct relationships between antibiotic consumption and the emergence of multidrug-resistant (MDR) bacteria. In this nested case-control study, we assessed whether prior exposure to antibiotic therapy and its duration affect the onset of healthcare-associated infections (HAIs) sustained by MDR Klebsiella pneumoniae (MDR-Kp) in intensive care unit patients. Cases were defined as patients who developed an MDR-Kp HAI. Controls matched on sex and the length of intensive care unit (ICU) stay were randomly selected from the at-risk population. Any antibiotic agent received in systemic administration before the onset of infection was considered as antibiotic exposure. Multivariable conditional logistic regression analyses were performed to estimate the effect of prior exposure to each antibiotic class (Model 1) or its duration (Model 2) on the onset of HAIs sustained by MDR-Kp. Overall, 87 cases and 261 gender-matched controls were compared. In Model 1, aminoglycosides and linezolid independently increased the likelihood of developing an MDR-Kp HAI, whereas exposure to both linezolid and penicillins reduced the effect of linezolid alone. In Model 2, cumulative exposure to aminoglycosides increased the likelihood of the outcome, as well as cumulative exposures to penicillins and colistin, while a previous exposure to both penicillins and colistin reduced the influence of the two antibiotic classes alone. Our study confirms that aminoglycosides, penicillins, linezolid, and colistin may play a role in favoring the infections sustained by MDR-Kp. However, several double exposures in the time window before HAI onset seemed to hinder the selective pressure exerted by individual agents.

Towards elimination of measles and rubella in Italy: Progress and challenges.

INTRODUCTION: In the WHO European Region, endemic transmission of measles and rubella had been interrupted by 37 and 42 of the 53 member states (MSs), respectively, by 2018. Sixteen MSs are still endemic for measles, 11 for rubella and nine for both diseases, the latter including Italy. Elimination is documented by each country's National Verification Committee (NVC) through an annual status update (ASU). OBJECTIVE: By analysing data used to produce the ASUs, we aimed to describe the advances made by Italy towards elimination of measles and rubella. Moreover, we propose a set of major interventions that could facilitate the elimination process. METHODS: A total of 28 indicators were identified within the six core sections of the ASU form and these were evaluated for the period 2013-2018. These indicators relate to the incidence of measles/rubella; epidemiological investigation of cases; investigation of outbreaks; performance of the surveillance system; population immunity levels; and implementation of supplemental immunization activities (SIAs). RESULTS: From 2013 to 2018, epidemiological and laboratory analyses of measles cases in Italy improved substantially, allowing timely investigation in 2017 and 2018 of most outbreak and sporadic cases and identification of the majority of genotypic variants. Moreover, since 2017, vaccination coverage has increased significantly. Despite these improvements, several areas of concern emerged, prompting the following recommendations: i) improve outbreak monitoring; ii) strengthen the MoRoNet network; iii) increase the number of SIAs; iv) reinforce vaccination services; v) maintain regional monitoring; vi) design effective communication strategies; vii) foster the role of general practitioners and family paediatricians. CONCLUSIONS: The review of national ASUs is a crucial step to provide the NVC with useful insights into the elimination process and to guide the development of targeted interventions. Against this background, the seven recommendations proposed by the NVC have been shared with the Italian Ministry of Health and the Technical Advisory Group on measles and rubella elimination and have been incorporated into the new Italian Elimination Plan 2019-2023 as a technical aid to facilitate the achievement of disease elimination goals.

Polyomaviruses shedding in stool of patients with hematological disorders: detection analysis and study of the non-coding control region's genetic variability.

Fragmented data are available on the human polyomaviruses (HPyVs) prevalence in the gastrointestinal tract. Rearrangements in the non-coding control region (NCCR) of JCPyV and BKPyV have been extensively studied and correlated to clinical outcome; instead, little information is available for KIPyV, WUPyV and MCPyV NCCRs. To get insights into the role of HPyVs in the gastrointestinal tract, we investigated JCPyV, BKPyV, KIPyV, WUPyV and MCPyV distribution among hematological patients in concomitance with gastrointestinal symptoms. In addition, NCCRs and VP1 sequences were examined to characterize the strains circulating among the enrolled patients. DNA was extracted from 62 stool samples and qPCR was carried out to detect and quantify JCPyV, BKPyV, KIPyV, WUPyV and MCPyV genomes. Positive samples were subsequently amplified and sequenced for NCCR and VP1 regions. A phylogenetic tree was constructed aligning the obtained VP1 sequences to a set of reference sequences. qPCR revealed low viral loads for all HPyVs searched. Mono and co-infections were detected. A significant correlation was found between gastrointestinal complications and KIPyV infection. Archetype-like NCCRs were found for JCPyV and BKPyV, and a high degree of NCCRs stability was observed for KIPyV, WUPyV and MCPyV. Analysis of the VP1 sequences revealed a 99% identity with the VP1 reference sequences. The study adds important information on HPyVs prevalence and persistence in the gastrointestinal tract. Gastrointestinal signs were correlated with the presence of KIPyV, although definitive conclusions cannot be drawn. HPyVs NCCRs showed a high degree of sequence stability, suggesting that sequence rearrangements are rare in this anatomical site.

Merkel Cell Polyomavirus DNA Detection in Respiratory Samples: Study of a Cohort of Patients Affected by Cystic Fibrosis.

BACKGROUND: The role of Merkel cell polyomavirus (MCPyV) as a respiratory pathogen is controversial, and it is still unclear in patients with cystic fibrosis (CF). The aim of this study was to define the MCPyV prevalence and epidemiology in CF patients in order to gain new insights into the association between MCPyV infection and respiratory diseases. METHODS: A one-year study was conducted testing oropharyngeal aspirate samples from 249 and 124 CF and non-CF patients, respectively. Detection of MCPyV was carried out by nested polymerase chain reaction (PCR). Moreover, a sequence alignment to examine viral capsid protein 1 (VP1) and a phylogenetic analysis were performed. RESULTS: MCPyV DNA was detected in 65 out of 249 samples analyzed CF (26%), a percentage that was higher than that recorded in non-CF patients (0.8%). There were no statistically significant differences in MCPyV prevalence according to gender, while there was a correlation between MCPyV detection and age. Interestingly, an association between the presence of MCPyV and the concurrent isolation of Staphylococcus aureus was found. Sequence analysis of MCPyV VP1 and phylogenetic analysis revealed a 99% homology with the published sequences of these viruses in GenBank. CONCLUSIONS: Detection of MCPyV in CF patient specimens pointed out a possible interaction between the virus and CF. Further studies are necessary to fully understand the involvement of MCPyV in the pathogenesis of respiratory disorders.