Pietro Ragni

Prevalence of Infected Patients and Understaffing Have a Role in Hepatitis C Virus Transmission in Dialysis

To assess hepatitis C virus (HCV) incidence rates and identify determinants of infection among hemodialysis patients, a multicenter study was conducted in 58 units in ITALY: An initial seroprevalence survey was conducted among 3,492 patients already on hemodialysis therapy as of January 1997 and among an additional 434 patients who began dialysis up to January 1998. HCV antibodies were assessed by third-generation enzyme immunoassays. Patients testing seronegative at baseline were enrolled into a 1-year incidence study with serological follow-up at 6 and 12 months. For patients who seroconverted, an HCV RNA assay was performed on stored baseline samples to confirm new infection. A nested case-control study was subsequently performed to investigate potential risk factors. For each incident case, three controls negative for both HCV antibodies and HCV RNA were randomly selected. At enrollment, HCV seroprevalence was 30.0%. During follow-up, 23 new HCV cases were documented, with a cumulative incidence of 9.5 cases/1,000 patient-years. By logistic regression analysis, an increased risk for HCV infection emerged for patients attending the dialysis units with a high prevalence of HCV-infected patients at baseline (odds ratio [OR], 4.6) and for those attending units with a low personnel-patient ratio (OR, 5.4). Among extradialysis factors, a history of surgical intervention in the previous 6 months (OR, 16.7) significantly increased HCV risk. These findings suggest that the combination of understaffing and a high level of infected patients in the dialysis setting increases the risk for HCV nosocomial transmission. This is likely related to an increased likelihood for breaks in infection control measures.

Risk of parenterally transmitted hepatitis following exposure to surgery or other invasive procedures: results from the hepatitis surveillance system in Italy

BACKGROUND/AIMS To evaluate the strength of association between parenterally transmitted viral hepatitis and specific types of invasive procedures. METHODS Data from the surveillance system for type-specific acute viral hepatitis (SEIEVA) during the period 1994-1999 were used. The association of acute hepatitis B virus (HBV) and hepatitis C virus (HCV) infection with the potential risk factors (odds ratios (OR)) was estimated comparing 3120 hepatitis B and 1023 hepatitis C cases with 7158 hepatitis A cases, used as controls, by multiple logistic regression analysis. RESULTS Most procedures resulted in being associated with the risk of acquiring acute HBV or HCV. The strongest associations were: for HBV infection, abdominal surgery (adjusted OR = 3.9; 95% confidence intervals (CI) = 2.0-7.5), oral surgery (OR = 2.7; 95% CI = 1.6-4.5) and gynaecological surgery (OR = 2.6; 95% CI = 1.2-5.5); for HCV infection, obstetric/gynaecological interventions (OR = 12.1; 95% CI = 5.6-26.3), abdominal surgery (OR = 7.0; 95% CI = 3.2-14.9) and ophthalmological surgery (OR = 5.2; 95% CI = 1.1-23.2). Biopsy and/or endoscopy were associated with HCV, but not with HBV infection. CONCLUSIONS Invasive procedures represent an important mode of HBV and HCV transmission. Since a large proportion of the adult general population is exposed to these procedures and an effective HCV vaccine is not yet available, non-immunological means of controlling iatrogenic modes of transmission are extremely important.

The impact of the hepatitis B mass immunisation campaign on the incidence and risk factors of acute hepatitis B in Italy

BACKGROUND/AIMS This study aimed to evaluate the impact of the campaign for hepatitis B mass immunisation of children and teenagers, introduced in 1991, on the incidence of and risk factors for hepatitis B in Italy. METHODS Hepatitis B cases reported to the surveillance system for type-specific acute viral hepatitis (SEIEVA) during the period 1987-1997 were used to estimate incidence. To assess the association between potential risk factors and hepatitis B cases, hepatitis A cases generated by the same surveillance system were used as controls. RESULTS During the period 1987-1997, 8275 acute hepatitis B cases were reported to SEIEVA. Hepatitis B incidence declined from 10.4/100,000 in 1987 to 2.9/100,000 in 1997. The fall was more evident before than after the introduction of compulsory vaccination against hepatitis B. The results of multivariate analysis showed that during the years 1995-1997, blood transfusion, intravenous drug use, surgical intervention, dental therapy, other parenteral exposures, multiple sexual partners, and being in the household of a chronic HBsAg carrier were all exposures independently associated with hepatitis B. CONCLUSIONS The strong association linking acute hepatitis B with iatrogenic exposures, which are more common in adults, suggests that the present immunisation strategy should be combined with the implementation of non-immunologic preventive measures.

Incidence of and risk factors for hepatitis A in Italy: public health indications from a 10-year surveillance

Abstract Background/Aims: This study aimed to evaluate the incidence of and risk factors for acute viral hepatitis A (HAV) in Italy. Methods: Data were from a surveillance system for type-specific acute viral hepatitis (SEIEVA). To estimate the association of hepatitis A cases with the potential risk factors (Odds Ratios) and the proportion of all hepatitis A cases attributable to a given risk factor (population attributable risk), hepatitis B cases were used as controls. Independent predictors of HAV were estimated by conditional multiple logistic regression. Results: During the period 1985–1994, 25 553 viral hepatitis cases were reported. Of these, 6408 (25%) were due to hepatitis A (HAV). HAV incidence declined from 10/100 000 in 1985 to 2/100 000 in 1987. Since 1991, however, an increase in HAV has been observed. The majority of cases were 15–24 years old; the incidence was higher in males and in subjects residing in southern Italy. Only one death (0.02%) was observed. Shellfish consumption was the most frequently reported risk factor (62%). The proportion of cases reporting personal contact with an icteric case, travel to a high-medium endemic areas, and family contact with a child attending a day-care centre (household of day-care child) was 17%, 19% and 15%, respectively. The results of multivariate analysis showed that shellfish consumption (OR=2.6; 95% CI=2.4–2.9), travel to endemic areas for people residing in northern and central Italy (OR=5.4; 95% CI=4.6–6.2) and household of day-care child (OR=1.2; 95% CI=1.03–1.4), were all types of exposure independently associated with HAV. The estimates of population-attributable risk show that shellfish consumption explained as many as 42.2%, travel to high-medium endemic areas for people residing in northern and central Italy 24.2%, and household of day-care child only 1.4% of all acute hepatitis A cases in Italy. Conclusions: These findings indicate that HAV in Italy is mainly a food-borne disease. Vaccination against hepatitis A is strongly recommended for travellers to endemic areas.

Changing epidemiology of parenterally transmitted viral hepatitis: results from the hepatitis surveillance system in Italy

BACKGROUND In 1991, compulsory hepatitis B virus vaccination and screening for anti-hepatitis C virus of blood banks were introduced in Italy. AIM To evaluate the impact of preventive measures on the incidence and risk factors for parenterally transmitted viral hepatitis. METHODS Data from the surveillance system for acute viral hepatitis for the period 1985-99 were used. Temporal trends in distribution of reported risk factors were analysed by comparing three-year periods: 1987-89 and 1997-99. RESULTS The incidence (no. cases per 100,000 population) of hepatitis B was 12 in 1985 and 3 in 1999; the incidence of hepatitis non-A, non-B decreased from 5 to 1 in the same period. These decreases were more evident among young adults and before rather than after 1991. Multiple sexual partners, other parenteral exposures and dental treatment remain the most common risk factors for parenterally transmitted viral hepatitis. An increase in frequency over time was observed for other parenteral exposures, whereas a marked decrease was evident for blood transfusion and household contact with an HB-sAg carrier. Invasive medical procedures continue to represent an important source of infection. Intravenous drug use was reported particularly by young adults with non-A, non-B hepatitis, with increased frequency over time. CONCLUSIONS Non-immunologic measures for preventing hepatitis B and non-A, non B due to iatrogenic and other parenteral exposures, combined with hepatitis B virus vaccination, could further reduce parenteral transmission.

Factors affecting the compliance of the antenatal hepatitis B screening programme in Italy

The effectiveness in the prevention of perinatally transmitted HBV infection was assessed in 11858 pregnant women consecutively recruited in public and private hospitals in six Italian regions during a 2 months period in 2001. Of them 10881 (91.8%) attended HBsAg antenatal screening. The overall HBsAg prevalence was 1.7% (CI 95%: 1.4-1.9); it was 1.4% (CI 95%: 1.2-1.7) in pregnant women born in Italy but 5.9% (CI 95%: 4.1-8.1) in those born in Asia, Africa, central and south America, and eastern Europe. Results of multiple logistic regression analysis indicate that birth in foreign countries (OR 2.0; CI 95%: 1.3-3.0), family size with more than 4 members in the household (OR 3.5; CI 95%:2.7-4.6), and birth in a private hospital (OR 1.9; CI 95%: 1.3-2.8) were all independent predictors of lack of adherence to HBsAg screening. Out of the 182 new-borns of HBsAg positive mothers 172 (95.0%) were given active plus passive immunisation; this figure was 100% in new-borns of foreign mothers. These findings evidence a good effectiveness in the prevention of perinatally transmitted HBV in Italy. More efforts should be addressed to improve the effectiveness of the programme among foreign pregnant women who have high rate of HBsAg and more likely escape HBsAg screening than Italian pregnant women.

Acute Hepatitis Delta Virus Infection in Italy: Incidence and Risk Factors after the Introduction of the Universal Anti-Hepatitis B Vaccination Campaign

BACKGROUND Updates on the incidence of and risk factors for acute hepatitis delta virus infection in Italy, as well as in other countries, are lacking, and the impact of the mandatory anti-hepatitis B vaccination has not been evaluated. METHODS We performed a case-control study within a population-based surveillance for acute viral hepatitis. RESULTS During 1993-2004, 344 cases of acute hepatitis delta virus infection were reported. After a peak in 1993 (2.8 cases per 1 million population), the incidence decreased from 1.7 to 0.5 cases per 1 million population. Coinfections were prevalent. The decrease in incidence particularly affected young adults, and it paralleled the decrease in incidence of acute hepatitis B. In 1993, being an injection drug user (adjusted odds ratio [OR(adj)], 67.9; 95% confidence interval [CI], 18.1-254.5) or being a member of a household with a carrier of hepatitis B surface antigen (OR(adj,) 14.8; 95% CI, 3.0-72.9) were the only independent predictors of infection. During 1994-2004, being an injection drug user (OR(adj), 36.8; 95% CI, 20.7-65.4), cohabitation with an injection drug user (OR(adj), 4.2, 95% CI, 1.7-12.3), hospitalization (OR(adj), 3.5; 95% CI, 1.9-6.6), receipt of dental therapy (OR(adj), 2.3; 95% CI, 1.4-3.6), promiscuous sexual activity (OR(adj), 2.2; 95% CI, 1.4-3.6), and receipt of beauty treatment (OR(adj), 2.0; 95% CI, 1.3-3.2) were independently associated with infection. CONCLUSIONS Incidence of acute hepatitis delta infection is markedly decreasing in Italy. Undergoing invasive medical procedures, engaging in promiscuous sexual activity, and receiving beauty treatments are emerging, in addition to injection drug use, as important risk factors for infection. Further efforts are needed to increase vaccine coverage in high-risk groups and to implement the safety of invasive procedures performed both inside and outside health care facilities.

Case fatality rate of acute viral hepatitis in Italy: 1995-2000. An update.

BACKGROUND Fulminant hepatic failure is the most serious complication of viral hepatitis. Although this event occurs rarely, it may be fatal. AIMS To evaluate the case fatality rate (several deaths divided by number of cases x 100) for each viral hepatitis type in Italy from 1995 to 2000. PATIENTS Acute hepatitis cases identified by the surveillance system for acute viral hepatitis, which covers approximately 58% of the Italian population. RESULTS Twenty-five deaths (0.1%) occurred among the 18 460 acute viral hepatitis cases observed from 1995 to 2000, a rate threefold lower than the 0.3% reported during the period 1985-1994. The highest case fatality rate (0.4%) was seen for acute hepatitis B (18 deaths among 4257 cases). Only one death (0.01%) occurred among the 11 063 acute hepatitis A cases and two deaths (0.1%) among the 1536 acute hepatitis C cases. No deaths were observed among the 309 acute hepatitis A cases superimposed on chronic HBsAg carriers and the 166 superimposed on chronic HCV carriers. Intravenous drug use (22.2% of cases) and other parenteral exposures (22.2% of cases) were the most frequent non-mutually exclusive sources of infection reported by subjects who died of acute hepatitis B. CONCLUSIONS Analysis of surveillance system data from 1995 to 2000 indicates that, in Italy, deaths due to acute viral hepatitis are rare, but most commonly observed with acute hepatitis B. There is no evidence that acute hepatitis A may be fatal in chronic HBsAg or HCV carriers. The overall better survival rate may probably reflect improvements in the treatment of fulminant hepatitis in the last few years in Italy.

Heterosexual transmission of hepatitis C in Italy

Data from a surveillance system for type‐specific acute viral hepatitis in Italy has been used to evaluate the risk of heterosexual transmission of hepatitis C virus (HCV) associated with sexual activity with multiple partners in subjects ⩾15 years of age. Hepatitis A cases were used as controls. During the period 1991–1996, 1,359 acute hepatitis C and 4,365 hepatitis A cases were recorded among subjects ⩾15 years of age. Intravenous drug use was the most frequent source of infection (35.9%) reported by HCV cases; two or more sexual partners during the 6 months before disease onset accounted for 34.9% of hepatitis C cases. Adjusting by multiple logistic regression analysis for the confounding effect of all risk factors considered (blood transfusion, intravenous drug use, surgical intervention, dental therapy, other parenteral exposure), and for age, sex, area of residence, and educational level of subjects, showed that having two or more sexual partners is an independent predictor of the likelihood of hepatitis C (OR = 2.2; 95% CI = 1.7–2.7). After excluding intravenous drug users and patients transfused with blood from analysis, the increase in the adjusted OR for the association between HCV and the number of sexual partners correlated with the increase in the number of sexual partners. The risk of hepatitis C was 2.0 times higher (95% CI = 1.4–2.9) for subjects with two sexual partners and 2.8 times higher (95% CI = 2.1–3.8) for subjects with three or more sexual partners, as compared to subjects with less than two sexual partners. These findings suggest that heterosexual transmission may play an important role in the spread of hepatitis C in Italy. J. Med. Virol. 57:111–113, 1999.

An early (3-6 weeks) active surveillance study to assess the safety of pandemic influenza vaccine Focetria in a province of Emilia-Romagna region, Italy - part one.

INTRODUCTION An observational, non-comparative, prospective, surveillance study of individuals vaccinated with the MF59-adjuvanted A/H1N1 influenza vaccine, Focetria, (Novartis Vaccines & Diagnostics, Siena, Italy), was performed in Italy during the 2009 A/H1N1 influenza pandemic. METHOD This study assessed the short-term (six-week) safety profile of the investigational vaccine in real time. After vaccination (N=7943), adverse events (AE) were assessed using both active (telephone) and passive (healthcare database) follow-up in enrolled vaccinated subjects, including infants (6-23 months), pregnant women, and the immunosuppressed. The treating physicians of all subjects experiencing AEs post-vaccination were consulted for clinical information on the conditions reported. All AEs were coded according to ICD-10. RESULTS A total of 1583 AEs occurred during the study, 67 (4.2%) of which were serious adverse events (SAEs). One SAE was considered to be possibly related to vaccination (transitory and ill-defined neurologic disorder experienced by a 16-year-old asthmatic male). Three adverse events of special interest (AESI) were identified (convulsions experienced by two epileptic subjects), none of which were considered to be vaccine-related. Six individuals died during the study period, in each case the cause of death was not related to vaccination (four cases of severe underlying co-morbidity, one case of psychoactive drug misuse, and one case of acute myocardial infarction). CONCLUSIONS No cases of clinically relevant AEs, SAEs, or AESI were observed within a six-week period of vaccine administration. In accordance with existing clinical and post-marketing safety data, the results of this active surveillance study demonstrate a good safety profile for the MF59-adjuvanted A/H1N1 vaccine, Focetria, within the general population.