Impact of the COVID-19 pandemic on the Italian national viral hepatitis surveillance: an interrupted time series analysis, 2006-2022.

OBJECTIVES: This study aimed to assess the impact of the COVID-19 pandemic on national surveillance of viral hepatitis in Italy. STUDY DESIGN: Interrupted time series analysis. METHODS: Using an interrupted time series analysis with a customised AutoRegressive Integrated Moving Average model on hepatitis cases reported to the Integrated Epidemiological System of Acute Viral Hepatitis from 2006 to 2022, we examined trends in incidence, time to diagnosis and time to epidemiological investigations for hepatitis A, hepatitis B and hepatitis C. RESULTS: The quarterly incidence of hepatitis B (-0.251, P = 0.05) and hepatitis C (-0.243, P = 0.003) significantly decreased with the onset of the pandemic. Surveillance times for hepatitis B (5.496, P < 0.001) and hepatitis C (35.723, P < 0.001), measured as days lost per quarter, significantly increased 12 and 24 months after the pandemic's start. This aligns with a notable rise in quarterly incidence at 36 months for both (0.032, P = 0.030 for hepatitis B; 0.040, P < 0.001 for hepatitis C). CONCLUSIONS: The decrease in reported cases could be due to an increase in infection prevention control and containment measures put in place in a pandemic context. However, a delay in the initiation of epidemiological investigations was observed, which could lead to a further increase in incidence in the future.

The Erice 58 Charter on 'The health of migrants. An equity challenge for the public health system'.

Abstract: The Erice 58 Charter titled "The Health of Migrants: a Challenge of Equity for the Public Health System", was unanimously approved at the conclusion of the 58th Residential Course of the School of Epidemiology and Preventive Medicine 'Giuseppe D'Alessandro' entitled "The Health of Migrants: a Challenge of Equity for the Public Health System. Epidemiological, clinical-relational, regulatory, organisational, training and public communication aspects at international, national and local level', which took place from 28 March to 2 April 2022 in Erice (Sicily, Italy), at the 'Ettore Majorana' Foundation and Centre for Scientific Culture. The Course was promoted by the Italian Society of Migration Medicine (S.I.M.M.) and the Italian Society of Hygiene, Preventive Medicine and Public Health (SItI), with the collaboration and patronage of the Istituto Superiore di Sanità (ISS). 72 learners participated (mainly resident doctors in 'Hygiene and Preventive Medicine' but also other health service professionals), whose average age was 37 years; on the basis of territorial origin, 13 of the 20 Italian regions were represented. During the intense learning experience, which consisted of 18 frontal lessons (with 20 lecturers from the bio-medical, socio-anthropological and journalistic fields) and 7 working group sessions (supported by 4 classroom tutors in addition to the lecturers) in 'blended learning' mode, the various dimensions and critical issues related to the possibility of guaranteeing truly inclusive health policies for foreigners/migrants, throughout the country, were identified and discussed from an 'Health Equity' perspective. This enabled a small editorial group to draw up the basic document that, in the last session of the Course, was discussed and modified by all participants into the version of the 'Erice 58 Charter' presented here.

Renal Volume in ADPKD Patient Evaluation.

The clinical manifestations of ADPKD are related to the growth of renal cysts. Renal volume has been recognised as the biomarker that is able to identify those patients at risk of complications (hypertension and haematuria) and at risk of progression to End Stage Renal Disease (ESRD). Recently, several scores have been introduced to predict the evolution of ADPKD. The Mayo Clinic Group developed a classification based on renal volume as measured by CT or MRI and corrected for age and height (Ht-TKV); this allowed predicting the evolution of the disease, but it has not been fully validated so far. In addition, it is used to identify patients labelled as "fast progressors" and eligible for Tolvaptan therapy according to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) recommendations. We studied 80 patients who underwent MRI and had been classified as ADPKD typical form (class 1A-1E). A significant correlation between renal volume, hypertension, and low GFR was found (p < 0.005). A progressive increase in disease severity has been found across the different Mayo classes; 41.2% were eligible for Tolvaptan therapy. The results demonstrate that the Mayo method is easy to perform and provides valid information in order to identify with rapidly progressing disease.

Large and prolonged food-borne multistate hepatitis A outbreak in Europe associated with consumption of frozen berries, 2013 to 2014.

In May 2013, Italy declared a national outbreak of hepatitis A, which also affected several foreign tourists who had recently visited the country. Molecular investigations identified some cases as infected with an identical strain of hepatitis A virus subgenotype IA. After additional European Union/European Economic Area (EU/EEA) countries reported locally acquired and travel-related cases associated with the same outbreak, an international outbreak investigation team was convened, a European outbreak case definition was issued and harmonisation of the national epidemiological and microbiological investigations was encouraged. From January 2013 to August 2014, 1,589 hepatitis A cases were reported associated with the multistate outbreak; 1,102 (70%) of the cases were hospitalised for a median time of six days; two related deaths were reported. Epidemiological and microbiological investigations implicated mixed frozen berries as the vehicle of infection of the outbreak. In order to control the spread of the outbreak, suspected or contaminated food batches were recalled, the public was recommended to heat-treat berries, and post-exposure prophylaxis of contacts was performed. The outbreak highlighted how large food-borne hepatitis A outbreaks may affect the increasingly susceptible EU/EEA general population and how, with the growing international food trade, frozen berries are a potential high-risk food.

Assessment of timeliness, representativeness and quality of data reported to Italy's national integrated surveillance system for acute viral hepatitis (SEIEVA).

OBJECTIVES: Periodic assessment of surveillance systems is recommended to verify whether they are appropriately monitoring the public health problem under surveillance. The aim of this study was to evaluate timeliness, data quality and representativeness of data reported to the Italian Integrated Epidemiological System for Acute Viral Hepatitis (SEIEVA). STUDY DESIGN: Cross-sectional analysis of surveillance data. METHODS: Quantitative indicators were used to evaluate representativeness of reported cases, data quality, and timeliness between surveillance steps, for reports of acute viral hepatitis cases with date of onset of symptoms from 2009 to 2012 (N = 4516). RESULTS: Representativeness was 75%. Over 95% of records reported information on age, sex, city of residence, risk factors for hepatitis A and vaccination status. Information on risk factors for hepatitis B and C were reported less consistently (83%), as was information on early outcome (60%). Wide delays were found between surveillance steps. CONCLUSIONS: The system collects high quality data on acute viral hepatitis cases in Italy. Timeliness was found to be the main limit and needs to be improved by optimizing web-based reporting procedures, increasing communication with participating centres, improving feedback and increasing dissemination of surveillance results. The study highlights the importance of reporting timeliness to detect outbreaks of acute viral hepatitis.

HBV whole-genome mutation profile in HIV-1/HBV coinfected patients in a long-term follow-up study.

PURPOSE: Human immunodeficiency virus (HIV-1)-infected patients frequently harbour hepatitis B and C viruses (HBV and HCV, respectively). Possible modifications of the natural history of hepatitis B may occur. The aim of this study was to characterise HBV diversity and evolutionary and mutational viral genome profiles in HIV-1/HBV coinfections. METHODS: HIV-1 and HBV markers determinations (Roche, FRG; Abbott, USA) and HBV genome-length retrospective analysis were performed in follow-up isolates from patients who were either stably HBsAg-negative with a low level of HBV DNA (occult hepatitis B infection, OBI) or HBsAg-positive with a high level of HBV DNA. Phylogenetic analysis (maximum likelihood method, MEGA5), statistical analysis and evolutionary rates calculation (d S/d N) were applied. RESULTS: Positive selection pressures in the PreS/S region and a significantly higher number of mutations in this region including the major hydrophilic region (MHR) and the "a" determinant were shown in HBsAg-negative (possibly OBI) compared to stably HBsAg-positive HIV-1/HBV subgenotypes D3/A2 coinfected patients. Mutants previously described in HIV-1/HBV coinfected patients were found. Known mutants Y100C, P127T and P120A associated to Y134H and S143T and new S mutants, which may potentially affect HBsAg expression and secretion and anti-HBs binding, were detected in baseline sera persisting up to the end of 9 years follow-up. Known mutations of BCP, Pre-C, C and X regions were also characterised. Natural mutants strictly known as being involved in diagnostic failure were not detected; however, numerous corresponding sites showed amino acid variations. CONCLUSIONS: Evolutionary and genotypic differences observed, particularly in the PreS/S region, between HBsAg-negative (OBI) and HBsAg-positive HIV-1/HBV coinfected patients, may contribute, in association with mutations of other genomic regions, to the HBsAg-negative phenotype.

Hepatitis B immunity in teenagers vaccinated as infants: an Italian 17-year follow-up study.

We assessed the persistence of hepatitis B surface antigen antibody (anti-HBs) and immune memory in a cohort of 571 teenagers vaccinated against hepatitis B as infants, 17 years earlier. Vaccinees were followed-up in 2003 and in 2010 (i.e. 10 years and 17 years after primary vaccination, respectively). When tested in 2003, 199 vaccinees (group A) had anti-HBs <10 mIU/mL and were boosted, 372 (group B) were not boosted because they had anti-HBs ≥10 mIU/mL (n = 344) or refused booster (n = 28) despite anti-HBs <10 mIU/mL. In 2010, 72.9% (416/571) of participants had anti-HBs ≥10 mIU/mL (67.3% in group A vs. 75.8% in group B; p 0.03). The geometric mean concentrations (GMCs) were similar in both groups. Between 2003 and 2010, anti-HBs concentrations in previously boosted individuals markedly declined with GMC dropping from 486 to 27.7 mIU/mL (p <0.001). Fifteen vaccinees showed a marked increase of antibody, possibly due to natural booster. In 2010, 96 individuals (37 of group A and 59 of group B) with anti-HBs <10 mIU/mL were boosted; all vaccinees of the former group and all but two of the latter had an anamnestic response. Post-booster GMC was higher in group B (895.6 vs. 492.2 mIU/mL; p 0.039). This finding shows that the immune memory for HBsAg persists beyond the time at which anti-HBs disappears, conferring long-term protection.

Plaque-infiltrating T lymphocytes in patients with carotid atherosclerosis: an insight into the cellular mechanisms associated to plaque destabilization.

AIM: Inflammation plays a crucial role in the progression of atherosclerotic plaques. The aim of the present study was to investigate phenotypic and functional characteristics of plaque-infiltrating T lymphocytes associated with a complicated phenotype of carotid atherosclerotic lesions. METHODS: Atherosclerotic plaques were obtained from 17 patients undergoing carotid endarterectomy and cultured to isolate infiltrating T lymphocytes. Blood samples were obtained from patients and from 20 sex- and age-matched healthy subjects. The presence of lymphocytes (CD3+ cells) within atherosclerotic plaques was determined by immunohistochemistry. Phenotypic characteristics and intracellular cytokine expression of plaque-infiltrating and circulating T lymphocytes were determined by flow cytometry. Cytokine levels in supernatants from infiltrating T cell cultures were evaluated by enzyme-linked immunosorbent assay. RESULTS: A higher number of CD3+ cells was detected in complicated than in uncomplicated plaques. Complicated plaques had higher percentages of tumor necrosis factor (TNF)-α- and interferon (IFN)-γ- positive cells than uncomplicated ones, especially in CD4+ subpopulation. In patients the percentages of TNF-α-positive cells were higher in infiltrating than in circulating lymphocyte samples. Intracellular TNF-α, IFN-γ, interleukin (IL)-4 and IL-10 expression resulted higher in circulating lymphocyte samples from patients than in those from healthy subjects. Supernatants of infiltrating T cell cultures from complicated plaques showed higher levels of TNF-α and lower levels of IL-4 than those from uncomplicated plaques. CONCLUSION: Our data provide new information on the presence of increased percentages of pro-inflammatory T lymphocytes in complicated plaques with respect to uncomplicated ones and support the concept of the key role played by activated T cells in the progression of atherosclerotic lesions.

Identification of IP-10 and IL-5 as proteins differentially expressed in human complicated and uncomplicated carotid atherosclerotic plaques.

Inflammation plays a crucial role in the development and progression of atherosclerotic plaques. The aim of this study is to compare culture supernatants from uncomplicated and complicated carotid atherosclerotic plaques by a multiplex approach, to assess the molecular mediators associated with a plaque complicated phenotype. Atherosclerotic plaques were obtained from 17 patients undergoing carotid endarterectomy. Supernatants from plaque cultures were evaluated by Bio-Plex cytokine assay to determine 27 pro- and anti-inflammatory cytokines, chemokines and growth factors. Complicated plaques secreted higher levels of IP-10 (p = 0.027) and lower levels of IL-5 (p = 0.045) than did uncomplicated ones. Distinctive secretory patterns of cytokines, chemokines and growth factors were present in the two types of plaque. Our study identifies IP-10 and IL-5 as proteins differentiating complicated and uncomplicated plaques from human carotid arteries and provides new insights into the interplay of molecular mediators with atherosclerotic plaque progression.

Caspofungin for the treatment of candidaemia in patients with haematological malignancies.

This study was prospectively conducted in 11 haematology divisions over a 2-year period to evaluate the efficacy of caspofungin in 24 neutropenic patients with haematological malignancies (HM) and candidaemia. These patients had received chemotherapy for HM and were neutropenic (PNN < 0.5 x 10(9)/L) for a median of 12 days (2-41) before candidaemia. The patients received caspofungin for a median duration of 12 days (range 6-26), obtaining a favourable overall response of 58%. At 30 days, 11 patients had died (46%); candidaemia was responsible for mortality in six patients (25%). These results suggest that treatment of candidaemia with caspofungin in neutropenic HM was efficacious, as it is in non-haematological subgroups.

Acute hepatitis A in Italy: incidence, risk factors and preventive measures.

The incidence of, and risk factors for, acute hepatitis A (AHA) were assessed by using data collected from the Italian surveillance system of acute viral hepatitis (SEIEVA). To this end, a case-control study within a population-based surveillance for acute viral hepatitis was performed. AHA incidence has been estimated since 1991; the association with considered risk factors was analysed from 2001 to 2006 employing cases of acute hepatitis B (AHB) as controls. The incidence of AHA declined from 4 / 100 000 in 1991 to 1.4/100 000 in 2006, with a peak during 1996-1998 due to an outbreak in southern Italy. The incidence of AHA was highest among persons aged 15-24 years. The case-fatality rate was 2.9 / 10 000. Contact with individuals with AHA [adjusted OR (OR(adj)) = 3.8, 95% CI 2.7-5.5; population-attributable risk (PAR) = 7.5%], travelling to endemic areas (OR(adj) = 3.1, 95% CI = 2.6-3.8; PAR = 19.5%), ingestion of raw shellfish (OR(adj) = 1.8, 95% CI = 1.6-2.1; PAR = 26.6%), and cohabitation with day care children (OR(adj) = 1.3, 95% CI = 1.01-1.7; PAR = 2.3%) were the main important risk factors. In 2003, an outbreak, with high case-fatality rate occurred among intravenous drug users, in a central Italian town. A weak association was found for male homosexuality when acute hepatitis C cases were employed as controls (OR(adj) = 1.4 CI, 95% CI = 1.1-1.9). Hepatitis A virus infections are currently occurring more frequently in adults, in whom the disease is most severe. In conclusion, looking at the attributable risks, at present most of the AHA infections are due to shellfish consumption, travel to endemic areas and contact with patients with AHA. Vaccination of individuals at increased risk of infection, as well as persons with underling liver disease and those at increased risk of complications, combined with surveillance of shellfish retail outlets are efficient control measures.

Association of intracellular pro- and anti-inflammatory cytokines in peripheral blood with the clinical or ultrasound indications for carotid endarterectomy in patients with carotid atherosclerosis.

Early non-invasive diagnostic information would be useful in identifying patients at risk of progressive carotid atherosclerosis, despite an apparently harmless plaque on ultrasound imaging. In this study, we assessed the possible association of intracellular cytokines in peripheral blood with the ultrasound (stenosis > or = 70%) and clinical indications (transient ischaemic attack, amaurosis fugax or stroke) for carotid endarterectomy (CEA) in patients. Intracellular cytokine expression was determined in 106 patients (67 undergoing and 39 not undergoing CEA). Cells primed for the proinflammatory cytokines tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1beta, IL-6, IL-8 and the anti-inflammatory cytokines IL-4 and IL-10 were found in significantly higher percentages in patients undergoing CEA than in patients who were not (P < 0.05). Intracellular cytokine expression was significantly higher in patients undergoing CEA who had stenosis > or = 70% (TNF-alpha, IFN-gamma, IL-1beta, IL-6, IL-4 and IL-10), with previous stroke (IFN-gamma, IL-1beta, IL-6, IL-8, IL-4 and IL-10) and with amaurosis fugax (IFN-gamma, IL-6, IL-4 and IL-10) than in patients not undergoing CEA. Increased intracellular cytokines in patients' peripheral blood might be a warning signal indicating progressive atherosclerosis. If so, intracellular cytokine monitoring could help in selecting patients at high risk of future clinical cardiovascular events and therefore most likely to benefit from CEA or adjustment of pharmacological therapy.

Chronic and acute alcohol exposure prevents monocyte-derived dendritic cells from differentiating and maturing.

Increasing evidence suggests that alcohol abuse may be linked to adverse immunomodulatory effects on immune responses. Our study was undertaken to clarify the immunological consequences of chronic and acute alcohol exposure on differentiation and maturation of human dendritic cells (DCs). Using immunochemical and cytofluorimetric analysis we determined the phenotype and functions of monocyte-derived DCs from alcoholics and healthy subjects and analyzed their ability to respond to lipopolysaccharide (LPS) in the presence or absence of ethanol (EtOH) exposure. Our results showed that alcoholics inverted exclamation mark| monocytes differentiated to immature DCs with altered phenotype and functions (alc-iDCs). Alc-iDCs showed fewer CD1a+ cells, weaker CD86 expression and higher HLA-DR expression associated with lower endocytosis and allostimulatory functions than iDCs from healthy subjects (control-iDCs). Despite these impairments, alc-iDCs produced TNF-alpha and IL-6 in large amounts. LPS stimulation failed to induce full phenotypical and functional alc-iDC maturation. In vitro acute EtOH exposure also prevented alc-iDCs and control-iDCs from maturing in response to LPS. T-cell priming experiments showed that EtOH treatment prevented LPS-stimulated control-iDCs from priming and polarizing naïve allogeneic T cells into Th1 cells, thus favouring a predominant Th2 environment. Collectively, our results provide evidence that chronic and acute alcohol exposure prevents DCs from differentiating and maturing in response to a microbial stimulus.

NK/T-cell lymphomas 'nasal type': an Italian multicentric retrospective survey.

OBJECTIVE: To evaluate the clinical characteristics and outcome of NK/T-cell lymphoma 'nasal type' developed in Italian patients. PATIENTS: Between 1997 and 2004, 26 new cases of NK/T-cell lymphoma 'nasal type' were diagnosed in 10 Italian Hematology institutions. RESULTS: All patients were Caucasian, male/female ratio was 19/7, with a median age of 50 years (range 20-80). In 23 cases presentation at the onset was in the nasal cavity or adjacent structures, in two cases the lymphoma onset with skin lesions was followed successively by rhynopharyngeal dissemination, while the remaining case had bone marrow and lymph node involvement followed by oro-pharyngeal involvement. Regarding the stage of disease: 12 patients were in stage I; six in stage II; eight in stage IV. Diagnosis was based on the finding of a NK/T-cell phenotype at the histological and immunophenotypic examination of oropharyngeal or cutaneous lesions. All patients but one were treated with chemotherapy, alone in nine cases or associated to radiotherapy in 14 cases; two patients had chemotherapy, radiotherapy and surgery, while one patient underwent only surgery. Chemotherapy was anthracycline-based in 17 out of 25 cases. In those patients in whom radiotherapy was performed, radiation dosages ranged between 36 Gy and 47.5 Gy, with a median dosage of 40 Gy. Nine patients (34%) were responsive to the treatments: six patients obtained a complete remission and other three a partial remission. The remaining 17 patients resulted refractory or presented a limited response to therapy. The median disease-free survival was 14 months and the median overall survival time was 9 months. CONCLUSION: The results of this retrospective survey confirmed that NK/T-cell lymphoma 'nasal type' is a very rare lymphoma in the Italian population, and it is characterized by a very bad prognosis. Due to the rarity of this disease, a standardized therapeutic approach is lacking. More data are needed to know the epidemiology of this kind of lymphoma in Europe.

Screening for hepatocellular carcinoma.

BACKGROUND AND AIM: The incidence of hepatocellular carcinoma is high among cirrhotic patients, ranging from 2 to 3% in western cohorts and 6-11% in eastern cohorts. Although only one randomised trial has been performed, clinical practice generally uses periodic screening to detect hepatocellular carcinoma in cirrhotic patients. We reviewed the scientific literature on hepatocellular carcinoma screening. MATERIALS AND METHODS: Evaluation of studies identified through MEDLINE and EMBASE (1990-May 2003). RESULTS: The available screening tests to detect hepatocellular carcinoma are alpha-fetoprotein (cut-off: 20 ng/ml) and ultrasound, which are generally combined. The reported sensitivity and specificity are 50-85% and 70-90%, respectively. An estimated doubling time of about 6 months has led to the use of an interval of 6 months between screenings. Based on the risk of hepatocellular carcinoma, cirrhotic patients are considered as the target population. Screening seems to detect smaller and more frequently unifocal hepatocellular carcinoma; the residual liver function is important for determining the eligibility for effective treatment (resection); hence the prevention is more effective for patients with well-compensated cirrhosis. The survival estimated by non-randomised studies is slightly longer for patients with screening-detected hepatocellular carcinoma, compared to those with clinically detected hepatocellular carcinoma, although few studies have accounted for 'lead time bias'. CONCLUSIONS: Although screening for the early detection of hepatocellular carcinoma has become quite common in clinical practice, its effectiveness remains controversial. Observational studies that have taken into account lead time bias suggest that survival is greater for patients with screening-detected hepatocellular carcinoma, yet the eligibility for effective treatments is low. Considering that only one randomised controlled trial has been conducted, it is crucial to standardise the screening schedule and to evaluate prevention programmes.

Secondary acute myeloid leukaemia: results of conventional treatments. Experience of GIMEMA trials.

BACKGROUND: The aim of the study was to evaluate the outcome of acute myeloid leukaemia (AML) in patients with a previous malignancy (sAML) treated with chemo- and/or radiotherapy, enrolled in conventional trials. PATIENTS AND METHODS: In a multicentre setting, a prospective non-concurrent analysis was performed on 2513 new AML patients, aged 12-78 years, consecutively enrolled in EORTC-GIMEMA trials between 1987 and 2001. Thirty-eight patients with sAML were identified and compared with a group of 114 de novo AML patients matched according to age, French-American-British criteria, white blood cell count at diagnosis, trial and time of diagnosis of AML. Induction treatment response, disease-free survival (DFS), duration and overall survival (OS) were evaluated in the two groups. RESULTS: Comparing the complete remission (CR) rate between 38 sAML patients and 114 de novo AML patients, selected according to the previously reported criteria, we observed no difference in the CR rates [25/38 (66%) versus 66/114 (58%); Pearson chi(2) 0.7393, P=0.390] as well as no differences while comparing the DFS and the OS between the two groups. CONCLUSION: The results of this study suggest that sAML patients are characterised by a good performance status permitting their recruitment in conventional trials without a previous myelodysplastic phase. Similar to de novo AML patients, sAML patients show good response to treatment and the possibility of cure.

Feasibility of vaccination in preventing secondary cases of hepatitis A virus infection.

Although the secondary transmission of hepatitis A virus (HAV) infection is preventable through vaccination, it is not known whether the vaccination of household contacts is feasible. To this end, we conducted a prospective cohort study among the household contacts, 40 years of age or less, of all persons infected with primary HAV infection (index cases) and admitted to eight hospitals in southern Italy within 7 days of onset. Household contacts were vaccinated, and serum samples were taken at vaccination and after 14 and 45 days. Secondary cases were defined as those with IgM seroconversion occurring at least two weeks after enrollment. Coprimary cases were those assumed to have had the same exposure as the index case. Susceptible cases were those who were negative for both IgG and IgM. A total of 495 household contacts participated (acceptance rate of 65%); 65% were vaccinated within 4 days of admission of the index case and 95% within 7 days. At enrollment, 196 (39.6%) household contacts were immune (IgG-positive serum). During follow-up, 19 (3.8%) were IgM-positive: 13 (2.6%) were coprimary cases and 6 (1.2%; 95% CI: 0.2-3.2) secondary cases (5 identified at 14 days from vaccination and 1 at 45 days). Of the 241 susceptible cases, 192 (79.7%) had developed IgG antibodies at 14 days and only 3 (1.2%) did not develop IgG antibodies at 45 days. The 65% acceptance rate and the finding that 95% of the participating household contacts were vaccinated within 7 days of the index case's hospitalization indicate that timely vaccination is indeed feasible. The necessity of returning for the collection of blood samples probably decreased the acceptance rate.

Risk of hepatitis A infection following travel.

Travel to endemic areas is one of the most frequently reported risk factors for infection with the hepatitis A virus (HAV). We evaluated the association between HAV infection and travel, by area of destination. We conducted a case-control study on all cases of HAV infection reported to the Italian National Surveillance System for Acute Viral Hepatitis in the period 1996-2000. The study population consisted of 9695 persons with HAV infection (cases) and 2590 with HBV infection (controls). The risk of acquiring HAV was highest for travel to Asia, Africa and Latin America [Odds Ratio = 9.30 (95%CI = 6.71-12.9)]; a three-fold statistically significant excess of risk was found for travel to southern Italy (OR = 3.03) and to the Mediterranean Area and Eastern Europe (OR = 3.15). Travel was implicated in 28% of the cases of HAV infection. When stratifying the analysis by area of residence (northern and central Italy vs southern Italy and the Islands), the above-mentioned risks were confirmed only for those residing in northern and central Italy, with no significant risk for those residing in southern Italy and the Islands. Travel to areas endemic for HAV infection constitutes a considerable risk. Our results highlight the importance of developing health policies for improving environmental and hygienic conditions, as well as the prevention of certain eating habits. Vaccination before travelling to a medium or high endemic area could be a safe and effective means of preventing travel-related HAV infection.

Effect of folic acid and vitamin C supplementation on folate status and homocysteine level: a randomised controlled trial in Italian smoker-blood donors.

BACKGROUND: This trial sought to examine the effects of high dosage of folic acid and vitamin C supplementation on red blood cell folate (RCF), serum folate (SF) and homocysteine (Hcy) levels in subjects who smoke more than 15 cigarettes per day. METHODS: A prospective study of 100 Italian repeat blood donors was undertaken to measure RCF, SF and Hcy levels before and after 45 days of vitamin supplementation. All subjects were randomised into four groups: [A] folic acid (FA) 5 mg/day, [B] vitamin C 500 mg/day, [C] FA 5 mg/day plus vitamin C 500 mg/day [D] no supplementation. RESULTS: Before supplementation the median RCF, SF and Hcy levels were similar in the four groups; 32 (40%) subjects had an RCF level below 340 nmol/l, 15 (18.8%) had an SF level below 6.8 nmol/l and 21 (26.3%) had an Hcy level above 16 micromol/l. After 45 days the median RCF and SF levels were significantly (P<0.01) increased in all supplemented subjects. The median Hcy level was significantly (P=0.008) reduced in subjects supplemented with FA and significantly (P=0.01) increased in those supplemented with vitamin C alone. CONCLUSION: The supplementation with 5 FA mg/day is able to increase significantly both RCF and SF levels and reduce Hcy level in Italian smoker-blood donors.