Rosa Cristina Coppola

Long-term immunogenicity of hepatitis B vaccination and policy for booster: an Italian multicentre study

BACKGROUND Universal anti-hepatitis-B vaccination of infants and adolescents was implemented in Italy in 1991. We undertook a multicentre study in previously vaccinated individuals to assess the duration of immunity and need for booster, over 10 years after vaccination. METHODS In 1212 children and 446 Italian Air Force recruits vaccinated as infants and adolescents, respectively, we measured the concentrations of antibodies to hepatitis-B surface antigen (anti-HBs) and the presence of antibodies to hepatitis-B core antigen (anti-HBc) at enrollment; postimmunisation values were not available. Individuals positive for anti-HBc were tested for hepatitis B surface antigen (HBsAg) and hepatitis B viral DNA. Individuals with anti-HBs concentrations at 10 IU/L or more were regarded as protected; those with antibody less than 10 IU/L were given a booster dose and retested 2 weeks later. Individuals showing postbooster anti-HBs concentrations of less than 10 IU/L were offered two additional vaccine doses and retested 1 month after the third dose. FINDINGS Protective anti-HBs concentrations were retained in 779 (64%, 95% CI 61.6-67) children and 398 (89%, 86.4-92.1) recruits. We recorded antibody amounts of less than 10 IU/L in 433 children (36%, 33-38.4) and 48 (11%, 7.9-13.6) recruits. One child and four recruits were positive for anti-HBc, but negative for HBsAg and hepatitis B viral DNA. Antibody concentrations were higher in recruits than in children (geometric mean titre 234.8 IU/L vs 32.1 IU/L, p=0.0001). 332 (97%) of 342 children and 46 (96%) of 48 recruits who received a booster showed an anamnestic response, whereas ten (3%) children and two (4%) recruits remained negative for anti-HBs or had antibody concentrations of less than 10 IU/L. Prebooster and postbooster antibody titres were strongly correlated with each other in both groups. All individuals given two additional vaccine doses (eight children and two recruits) showed anti-HBs amounts of more than 10 IU/L at 1 month after vaccination. INTERPRETATION Strong immunological memory persists more than 10 years after immunisation of infants and adolescents with a primary course of vaccination. Booster doses of vaccine do not seem necessary to ensure long-term protection.

Risk groups for hepatitis A virus infection

We report the conduct and results of a systematic search for evidence of risk of infection with hepatitis A virus (HAV) among blood transfusion recipients, travellers, the military, healthcare workers, sewage workers, foodhandlers, day care assistants, institutionalised subjects, blood transfusion recipients, drug addicts, homosexuals, prisoners and other risk groups such a liver transplantees. We report our recommendations for the use of the HAV vaccine in these groups.

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.

Burnout and workload among health care workers: the moderating role of job control.

Background As health care workers face a wide range of psychosocial stressors, they are at a high risk of developing burnout syndrome, which in turn may affect hospital outcomes such as the quality and safety of provided care. The purpose of the present study was to investigate the moderating effect of job control on the relationship between workload and burnout. Methods A total of 352 hospital workers from five Italian public hospitals completed a self-administered questionnaire that was used to measure exhaustion, cynicism, job control, and workload. Data were collected in 2013. Results In contrast to previous studies, the results of this study supported the moderation effect of job control on the relationship between workload and exhaustion. Furthermore, the results found support for the sequential link from exhaustion to cynicism. Conclusion This study showed the importance for hospital managers to carry out management practices that promote job control and provide employees with job resources, in order to reduce the burnout risk.

Molecular characterisation of HCV genotype 4 isolates circulating in Italy.

The characteristics of genotype 4 subtype variability of HCV isolates circulating in Italy were studied. The viral isolates were identified from 736 HCV‐RNA positive sera originated from seroepidemiological studies undertaken in 4 different regions of North, South Italy and Sardinia. 24 out of 28 genotype 4 isolates (86%) were classified by phylogenetic analysis of E1 genome region (915–1128) as belonging to subtype 4d (Neighbour Joining Method). Three isolates classified as subtype 4a were detected in haemophilic patients, possibly related to infections from blood products. One isolate classified as a new subtype derived from an Eritrean patient subjected to haemodialysis. Very high genome homogeneity (mean 4.3%) was shown by genetic comparisons (DNA dist programs Phylip Package) for all the 4d isolates relative to the studies performed in Veneto, Calabria and Sardinia and originated from subjects from the general population and outpatients (19 subtype 4d isolates out of 24). In the 3 studies different prevalence rates of HCV genotype 4 (3.1%, 1.3%, 14% respectively) were found. In contrast a considerable degree of heterogeneity, both intragroup and with the other groups (mean 8.2% and 8.7%, respectively) was observed among subtype 4d isolates identified in the patients of a haemodialysis centre in Apulia region. In conclusion the subtype 4d of genotype 4 was highly prevalent and endemic in Italy. An elevated level of viral heterogeneity was observed in one study carried out in a region of Southern Italy. This can be related to a longer period of past endemicity of this genotype and to a high level of exposure to reinfections in particular categories of patients such as haemodialysis patients. J. Med. Virol. 62:84–90, 2000.

Sexual behaviour and risk factors for the acquisition of human papillomavirus infections in young people in Italy: suggestions for future vaccination policies

BackgroundHuman Papillomavirus (HPV) is the most common sexually transmitted infection. The main risk factors correlated with HPV infection are: early sexual debut, the number of partners, frequency and type of sexual contact and partner’s sexual histories.We surveyed sexual habits among young people in order to provide information that might orient decision-makers in adopting HPV multi-cohort vaccination policies.MethodsWe administered a questionnaire to students (14–24 years old) in five Italian cities.Results7298 questionnaires were analyzed (4962 females and 2336 males); 55.3% of females (95% CI 53.9–56.7) and 52.5% of males (95% CI 50.5–54.5) reported regular sexual activity. The mean age at sexual debut was 15.7 ± 1.6 and 15.6 ± 1.6 for females and males, respectively, and the median age was 16 for both sexes.With regard to contraceptive use during the last year, 63.6% of males and 62.8% of females responded affirmatively; 42.6% of males and 42.8% of females used condoms.ConclusionThe results reveal precocious sexual activity among respondents, with the mean age at first intercourse declining as age decreases. Condom use proved to be scant. Considering lifestyle-related risk factors, males appear to have a higher probability of acquiring HPV infection than females.These data support the importance of promoting multi-cohort HPV vaccination strategies for females up to 25 years of age. It is essential to improve vaccination coverage through different broad-spectrum strategies, including campaigns to increase awareness of sexually transmitted diseases and their prevention.

HCV transmission in family members of subjects with HCV related chronic liver disease

To investigate the risk of sexual and intrafamilial transmission of HCV, 220 family members of 76 patients (index cases) with chronic type C viral liver disease were tested for serological markers of HCV Of the family members, 129 were offspring, 64 sexual partners, 15 parents and 12 siblings of the index cases. Anti-HCV was tested in all the household contacts; HCV-RNA was tested in antibody positive samples. The serologic markers of HCV were tested in a control group of 168 family members of 81 patients with chronic hepatitis unrelated to HCV. The overall prevalence of anti-HCV was 8.2% compared to 0.6% in the control group (p < 0.001). Sexual partners were anti-HCV positive more frequently than the other contacts (20% vs 2.2%; p < 0.001), without any difference in males or females. No correlation was observed between the occurrence of HCV infection in contacts and age, severity of liver disease or risk factor for the acquisition of HCV in the index cases. Seven of the 18 (39%) anti-HCV positive family contacts had biochemical evidence of chronic liver disease, histologically confirmed in the 6 patients who underwent a liver biopsy. Liver chemistry was normal in all the HCV-negative contacts. Ten of the 18 anti-HCV positive contacts (55%) were HCV-RNA positive. Genotypes were the same (lb) in 4 of the 7 viremic couples of subjects: in 3 of the 6 couples of sexual partners and in the only mother/son couple. These data suggest the occurrence of intraspousal transmission of HCV, while intrafamiliar acquisition of HCV in non-sexual contacts seems to be rare.

HCV, HIV, HBV and HDV infections in intravenous drug addicts

Hepatitis viruses and the acquired immunodeficiency viruses often infect intravenous drug addicts (IVDAs). Our study includes 255 IVDAs (26 females and 229 males, aged 20–35 years) from Cagliari. Of 255 subjects examined, 207 (81.1%) were positive for anti-HCV and 84 (32.9%) for anti-HIV. Nineteen (7.4%) subjects were HBsAg carriers, and 12 of these (63%) had an HDV super-infection. Markers of previous HBV infections were tested in 223 cases and 137 (61.4%) were found positive; of these 14 (10.2%) also had HDV infection. Of the 223 drug addicts examined for all infection markers, 18 (8%) were negative to all markers, 46 (20.6%) were positive to only one, 89(39.9%) were positive to two, 64 (28.7%) to three and 6 (2.6%) were positive to all. Subjects with a single infection were significantly fewer than those with multiple infections. The correlations studied among the various markers did not point out any statistically significant associations. Even so, a previous HBV infection was more common while active HBV/HDV infections were less common among subjects with anti-HCV; HDV infection was more common among HIV-positive subjects. In HBsAg carriers neither HBV-DNA nor HCV-RNA was detected; HCV-RNA was found more frequently in anti-HIV positive subjects than in subjects with the anti-HCV isolate.

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.

Sexual behaviour and multiple infections in drug abusers

We have studied the prevalence and the serological profile of HBV, HCV, HDV and HIV infections in 137 Italian subjects addicted to the intravenous use of heroine and correlated the virological findings with sexual behaviour. HBV and HCV viremia were also measured in 114 patients. Anti-HCV was detected in 81% of the addicts, and one or more markers of HBV infection were detected in 62.8% (4.4% were carriers of HBsAg, 58.4% had evidence of past HBV infection and 13.1% of the latter also had HDV markers). Anti-HIV was positive in 23.4%; 26% of those positive for anti-HCV and 4.6% of those positive for HBV markers had no other viral marker: none had only anti-HIV. HBV-DNA was negative in the carriers of HBsAg, and HCV-RNA was not detected in any of the HBsAg carriers who also had circulating anti-HCV Overall, 34% of the anti-HCV positive addicts had HCV-RNA in their blood. The prevalence of the virus infection correlated with the duration of drug addiction but not with sexual behaviour, and sexual behaviour did not influence the acquisition of any virus. HCV infection was most frequent and probably the first infection to occur, but exposure to HBV was also common despite a low rate of HBsAg carriage. The prevalence of HDV infection was high (50%) in the HBsAg carriers, while the overall prevalence of HIV was lower (23%) than expected. Lack of HBV-DNA and HCV-RNA in carriers of HBV with anti-HCV in serum may indicate that HBV and HCV mutually inhibit their own replication.