Sexual transmission of the hepatitis C virus and efficacy of prophylaxis with intramuscular immune serum globulin. A randomized controlled trial.

OBJECTIVE: To estimate the risk of sexual transmission of hepatitis C and to assess the value of prophylaxis with periodic intramuscular immune serum globulin administration. METHODS: Of 1102 steady heterosexual partners of patients with antibodies to the hepatitis C virus (HCV), 899 were enrolled in a single-blind, randomized, controlled trial. All the partners tested negative for antibodies to HCV and had normal baseline serum aminotransferase concentrations. The partners were assigned to receive 4 mL of 16% polyvalent immune serum globulin prepared from unscreened donors every 2 months (n = 450) or a placebo (n = 449). Tests for HCV infection were performed every 4 months. RESULTS: Eight hundred eighty-four partners completed the study. Seven partners became infected with HCV: 6 in the control group (incidence density, 12.00 per 1000 person-years; 95% confidence interval, 3.0 21.61) and 1 in the immune serum globulin group (incidence density, 1.98 per 1000 person-years; 95% confidence interval, 0-5.86). The risk of infection was significantly higher for partners in the control group (P = .03): for each year approximately 1% of the partners became infected. Sequence homology studies strongly suggest the sexual transmission of HCV. All immune serum globulin lots used had high enzyme-linked immunosorbent assay titers of neutralizing antibodies to HCV envelope glycoproteins and high neutralization titers in the neutralization of binding assay. CONCLUSIONS: Hepatitis C can be sexually transmitted. Immune serum globulin prepared from unscreened donors significantly reduced the risk. The treatment was safe and well tolerated. Because only immune serum globulin from unscreened donors (and not from those screened for HCV) contain anti-HCV neutralizing antibodies, hyperimmune anti-HCV immune serum globulin should be prepared from blood testing positive for antibodies to HCV, which is currently discarded.

Understanding the dynamics of the HIV epidemic among Italian intravenous drug users: a cross-sectional versus a longitudinal approach.

We studied annual human immunodeficiency virus (HIV) seroprevalence and incidence in a large number of intravenous drug users attending drug treatment centers in three Italian urban areas. We also evaluated risk factors for HIV seropositivity and for HIV seroconversion. The results showed that HIV prevalence and incidence are declining. HIV prevalence declined dramatically in study participants that were < 25 years old. Prevalent HIV cases were associated with older age and longer duration of intravenous drug use; however, short duration of drug use increased the risk of seroconversion. The findings of our study suggest that comparing cross-sectional and longitudinal data contributes to a better understanding of the dynamics of the HIV epidemic among intravenous drug users.

Hepatitis B vaccination coverage among healthcare workers in Italy.

In 1996, the vaccination coverage against hepatitis B virus among 3,157 healthcare workers in Italy was inversely related to the level of hepatitis B virus endemicity in the area of residence. Youngest age and lowest years of employment were independent predictors of the likelihood of vaccine acceptance.

Prophylaxis of hepatitis C with intramuscular immunoglobulin: clinical and economic appraisal.

Hepatitis C virus (HCV) affects millions of individuals worldwide. In most cases, HCV infection progresses to chronic liver disease and, subsequently, to liver cirrhosis and hepatocellular carcinoma. HCV is transmitted by the parenteral route, for example by transfusion of blood or blood products, injection during drug abuse, etc., and by the inapparent parenteral route (penetration of the virus through difficult-to-identify microlesions present on the skin or mucosae), for example, sexual exposure or household exposure to infected contacts, etc. The cost of chronic hepatitis C and its sequelae is high in both financial and human terms. At present, only anti-HCV screening of blood/organ/tissue donors and universal precautions for the prevention of blood-borne infections are recommended for HCV prevention. Before the discovery of the main aetiological agent of non-A, non-B hepatitis (HCV), several randomised controlled clinical trials demonstrated that standard intramuscular immunoglobulin exerted a preventive effect on post-transfusional and sexual and /or horizontal transmission of non-A, non-B hepatitis. When serological tests for HCV infection became available, bimonthly inoculation of standard unscreened intramuscular immunoglobulin (prepared from plasma pools containing about 2% of anti-HCV-positive units) was demonstrated to significantly prevent sexually transmitted HCV infection. The immunoglobulin used contained high titres of anti-HCV neutralising antibodies (anti-E2 neutralisation of binding assay), whereas currently available commercial screened immunoglobulin (prepared from anti-HCV-negative blood units) did not. This finding suggested that anti-HCV neutralising antibodies are concentrated only in anti-HCV-positive units (which are currently discarded). Thus, anti-HCV hyperimmune globulin (HCIg) can be produced only from anti-HCV-positive units. The neutralising titre can be increased by the exclusive use of units with higher titres of neutralising antibodies. Unlike other hyperimmune globulins, which are produced from a limited number of selected donors, HCIg should be produced from a large number of units so as to contain neutralising antibodies to the different HCV strains. HCIg will have a number of advantages: (i) it is easy to produce and inexpensive; (ii) it has a long half-life, allowing infrequent administration; (iii) new additional viral inactivation procedures have been introduced to eradicate transmission of infection, and (iv) it may be possible to neutralise all the emerging HCV strains. HCIg could be used in all individuals at risk of HCV infection (sexual partners, haemodialysis patients, etc), in preventing reinfection of transplanted livers, and perhaps also in the treatment of chronic hepatitis C, alone or associated with other drugs.

Risk management of HBsAg or anti-HCV positive healthcare workers in hospital.

Recommendations are made for controlling the transmission of the hepatitis B and hepatitis C viruses from healthcare workers to patients. These recommendations were based both on the literature and on experts' opinions, obtained during a Consensus Conference. The quality of the published information and of the experts' opinions was classified into 6 levels, based on the source of the information. The recommendations can be summarised as follows: all healthcare workers must undergo hepatitis B virus vaccination and adopt the standard measures for infection control in hospitals; healthcare workers who directly perform invasive procedures must undergo serological testing and the evaluation of markers of viral infection. Those found to be positive for: 1) HBsAg and HBeAg, 2) HBsAg and hepatitis B virus DNA, or 3) anti-hepatitis C virus and hepatitis C virus RNA must abstain from directly performing invasive procedures; no other limitations in their activities are necessary. Infected healthcare workers are urged to inform their patients of their infectious status, although this is left to the discretion of the healthcare worker; whose privacy is guaranteed by law. If exposure to hepatitis B virus occurs, the healthcare worker must undergo prophylaxis with specific immunoglobulins, in addition to vaccination.

Sexual transmission of hepatitis C virus and prevention with intramuscular immunoglobulin.

The sexual transmission of hepatitis C virus (HCV) has long been debated. The prevalence of infected at-risk partners varies from 0% to 30%. In a prospective study, the risk of infection was quantified in steady heterosexual partners and the prophylactic effect of normal human polyvalent immune serum globulin (ISG) was evaluated. A total of 899 at-risk partners of HCV-infected patients were enrolled in a single-blind randomized controlled trial and assigned to receive every 2 month 4 mL of intramuscular ISG from unscreened donors (450 partners) or placebo (499 partners). Seven partners developed acute HCV infection (increased aminotransferase levels and appearance of HCV-RNA): six of the placebo group (incidence density [ID] 12.00/1,000 person year; 95% confidence interval [CI] 3.0 to 21.61), and only one of the ISG-treated group (ID 1.98/1,000 person year; 95% CI 0 to 5.86). The risk of infection was significantly higher in controls versus treated individuals (p = 0.03). Six couples had genotype 1b (85%), and one couple had genotype 1a; HCV sequence homology strongly supported sexual transmission. Our trial demonstrates that HCV infection can be sexually transmitted and quantifies the risk of sexual transmission: for every year of at-risk sexual relationship, almost 1% of the partners became infected. Intramuscular ISG is safe and well tolerated. Unlike ISG from screened donors, ISG from donors unscreened for anti-HCV contains high titers of anti-gpE1/gpE2 neutralizing antibodies and high neutralizing activity. Anti-HCV hyperimmune globulin could be prepared from anti-HCV-positive blood units and could be used to protect sexual partners and in other at-risk situations of exposure to HCV infection.

[Epidemiology and prevention of HCV infection in dialysis centers]. / Epidemiologia e prevenzione dell'infezione da HCV nei centri di dialisi.

From many epidemiological studies comes out that haemodialysis patients are at high risk of hepatitis C virus (HCV) infection. This review shows the results of several prevalence and incidence studies carried out in dialysis centres. The prevalence of anti-HCV antibodies in haemodialysis patients varies from 20% to 38%. From these surveys comes out that serodiagnostic tests, usually employed in laboratory diagnosis (ELISA and RIBA), may underestimate the true prevalence of HCV infection. The very important risk factors in the haemodialysis units are blood transfusion and the length of time on haemodialysis. Nevertheless, these are not sufficient to explain completely the high prevalence of subjects HCV positive among the dialysis patients. Contamination of environmental surfaces, caused by a non correct application of the asepsis and disinfection techniques, could be, according to several authors, the more important cause of this infection among the dialysis patients.

[The evaluation of the risk factors for congenital hypothyroidism: the outlook of a case-control study]. / Valutazione dei fattori di rischio dell'ipotiroidismo congenito: prospettive di uno studio caso-controllo.

The availability of a National Register of congenital hypothyroid infants allowed to perform descriptive studies on characteristics of the cases and the efficiency of the neonatal screening. Continuous and exhaustive recording of data concerning congenital hypothyroidism cases provided valuable epidemiological informations about congenital hypothyroidism in Italy. Moreover, the National Register allowed to develop a network of collaboration which can promote a population based case-control study. As the etiopathogenesis of congenital hypothyroidism has not been completely elucidated, performing of a case-control study can contribute to evidence the most important risk factors of congenital hypothyroidism and to improve the prevention also by prenatal diagnosis of this disease. Screening centers will be involved in the study and questionnaires of the National Register for congenital hypothyroidism will be used to record case and control informations. A biological bank concerning cases, controls and their parents, will be organized.

[The knowledge, attitudes and practice in regard to the risk for occupational HIV infection in a group of gynecologists from 3 Italian regions]. / Conoscenze, atteggiamenti e pratica sul rischio di infezione professionale da HIV in un gruppo di ginecologi di tre regioni italiane.

The risk of occupational infection by blood-borne pathogens has been well evaluated. However, a low perception of this risk among health care workers (HCWs) and a low compliance to infection control measures has been documented by several studies. During a meeting of gynecologists of Southern Italy, a survey of knowledge, attitudes and practices (K.A.P.) on HIV and other blood-borne viral infections was conducted among 143 obstetricians-gynecologists. 133 (93%) HCWs answered the questionnaire. 81% of them recalled almost one occupational exposure during their career and 54% almost two in the past year. Our data suggest a low knowledge about HIV and the other blood-borne viral infections and Universal Precautions (UP): only 16% of HCWs knew the rate of vertical transmission of HIV, less than 15% knew the rate of seroconversion after occupational exposure to HBV and HCV, and finally only 33% knew to which body fluids apply UP. Moreover, 93.7% of HCWs believed that HIV antibody screening of all patients is an effective strategy to reduce the risk of occupation HIV infection. More than 90% of gynecologists used to request HIV-antibodies to pregnant women, 21% after the first trimester. Although HCWs interviewed can not be considered representative of Italian gynecologists, our data suggest the need of an intensive training to increase gynecologists' knowledge about HIV, other blood-borne pathogens and the risk of occupational infections also in order to modify attitudes and practices.

Consensus recommendations for managing asymptomatic persistent non-virus non-alcohol related elevation of aminotransferase levels: suggestions for diagnostic procedures and monitoring.

A persistent increase in non-virus non-alcohol related aminotransferase levels can have multiple causes, which differ in terms of prevalence and clinical importance. In the general population, the most frequent cause is non-alcoholic hepatic steatosis, which can evolve into steato-hepatitis and cirrhosis. The treatment for steatosis and non-alcoholic steato-hepatitis consists of modifying lifestyles, whereas the effectiveness of drug treatment remains to be determined. Other much less frequent (yet not rare) causes of persistent non-virus non-alcohol related elevations in aminotransferase levels are celiac disease and hemochromatosis, whereas autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, and alpha-1-anti-trypsin deficit are rare. Given that some of these conditions are susceptible to treatment, early diagnosis is important. No epidemiological data are available for evaluating the prevalence of elevated aminotransferase levels correlated with the toxicity of drugs or other xenobiotics, including herbal products. The present document, created by a panel of experts based on a systematic review of scientific evidence, is mainly geared towards physicians working in General Medicine and Transfusion Centres, who generally represent the first contact of persons with elevated aminotransferase levels. The document includes suggestions for diagnosing causes of persistent non-virus non-alcohol related increases in aminotransferase levels, considering the frequency and response to treatment. The conditions requiring specialized visits are also indicated.

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.

Vaccination policy against hepatitis A in Italy.

In Italy, improved sanitation and living conditions have led to a decline in the rate of hepatitis A infection among children generating an increasing proportion of adults susceptible to this virus. Shellfish consumption is a major source of infection while person to person transmission is important in the spread of infection and in the maintenance of outbreaks. Thus prevention of secondary HAV infection is a crucial point. A randomised controlled trial of hepatitis A vaccine in household contacts of people with sporadic HAV infection in Italy has shown a protective efficacy of 82% (CI 20-96%). The two secondary infections in the vaccine group were symptomless, suggesting that the disease expression may be weaker in vaccinated subjects.

A village outbreak of hepatitis A: acquaintance network and inapparent pre-school transmission compared.

A village outbreak of 38 cases of serologically confirmed hepatitis A is described. The epidemic curve was a propagative one and all of the cases occurred in primary school-age or pre-school children. In 1984 the incidence in this age group was 5,000 per 100,000, about 50 times the corresponding national rate. Although 21 of the cases attended the single primary school, these cases were not clustered within school years or classes and examination of onset dates showed only four cases could have resulted from case transmission within classes. A matched triplet case-control study was undertaken to measure the risk associated with prior contact with a case within the acquaintance network and the risk of household contact with either of the two pre-school nurseries where inapparent transmission may have been occurring. Whereas a similar proportion of cases and controls had direct or indirect contact with the nurseries, 48% of cases, compared with 9% of controls, reported a previous case of jaundice within 6 weeks amongst their acquaintance network (matched triplet analysis P less than .0001).

Incidence rate and risk factors for HCV seroconversion among injecting drug users in an area with low HIV seroprevalence.

We conducted a study on injecting drug users attending one of 3 drug treatment centres in Naples, to estimate HIV and hepatitis C virus (HCV) incidence rates and to identify risk factors for seroconversion. Incidence rates were estimated using as denominator the person-time of follow-up of participants who were negative for both HIV and HCV at enrollment and who were retested within 6-12 months. Information on risk factors was collected using a standardized questionnaire. A nested case-control analysis was performed comparing seroconverters with persistently HCV-negative individuals. None of the initially non-infected participants seroconverted for HIV, while the incidence rate for HCV infection was approximately 29 per 100 person-years. Analysis of risk factors showed that age > 28 years and injecting use of cocaine were associated with HCV seroconversion. The protective role of methadone treatment was also marginally significant. Our findings suggest that HCV infection may represent an important public health problem in areas with low HIV circulation. The identification of specific risk factors for HCV infection is needed to plan effective prevention strategies.

Niflumic acid and cutaneous reactions in children.

In a case control study of adverse drug reactions in children, the odds ratio of developing a serious mucocutaneous event among users of niflumic acid, adjusted for concomitant use of all other drugs, was 4.9 (95% CI 1.9 to 12.8). Given the availability of safer analgesics and antipyretics, there is no indication, in our opinion, that requires the prescription of substances which bear an increased risk.

Risk factors for acute hepatitis B: a case-control study.

Over the period 1989-1991 a case-control study was carried out in the area of Naples comparing 162 subjects with acute hepatitis B and 788 hospitalized control subjects. The results of multivariate analysis showed that surgical intervention (odds ratio 3.8; 95% CI 1.2-11.7), household contact with an hepatitis B surface antigen (HBsAg) positive carrier (odds ratio 2.7; 95% CI 1.1-6.7) and intravenous drug use (odds ratio 13.0; 95% CI 3.2-52.7) were risk factors independently associated with hepatitis B. No association was found with the other risk factors considered, such as blood transfusion, hospitalization, other percutaneous exposures, dental therapy, contact with an icteric case, barber shop shaving and two or more sexual partners. As a significant proportion of the general population undergoes surgical intervention, efficient procedures for sterilization of instruments should be implemented, together with the use of disposable materials, to control the spread of HBV infection in surgical settings.

Case control study of risk factors for hepatitis A: Naples 1990-1991. Hepatitis Collaborating Group.

An increased incidence of hepatitis A was observed in Naples from 1990-1991. A hospital-based case-control study was carried out to evaluate the relative importance of various risk factors. A hundred and ninety-eight cases and 238 hospital controls were recruited during the study period. The strongest association was contact with a jaundiced person among children. A correlation was also shown for children and adults with raw shellfish consumption and pre-school nursery attendance or presence in the household of children attending pre-school nurseries. History of travel and intravenous drug use were risk factors for adult subjects. Considering the relative importance of the specific risk factors we found that 38% of the acute hepatitis A cases were attributable to contact with a jaundiced person, 15% to presence in the household of children attending pre-school nurseries and 28% to raw shellfish consumption.

Ad hoc survey of hepatitis B vaccination campaign in newborns of HBsAg positive mothers and in 12-year-old subjects in southern Italy.

The ongoing vaccination campaign against hepatitis B (HB) for newborns of hepatitis B surface antigen (HBsAg) positive mothers and for 12-year-old subjects was evaluated in Naples, Italy, an area of relatively high HB endemicity. Subjects were recruited by a random sampling procedure. Among 2060 pregnant women studied, 1887 (91.6%) were screened for HBsAg. HBsAg prevalence was 2.5% (47/1887). Immunoprophylaxis according to the protocol (immunoglobulins within 24 h plus vaccine within 7 days after birth) was administered in 26 (55.3%) out of the 47 newborns of HBsAg positive mothers; vaccination was delayed (later than 7 days after birth) for 14 (29.8%) infants; in the remaining seven newborns (14.9%) were not given immunoglobulins at birth. All infants were vaccinated. Out of the 1000 adolescents sampled 130 (13%) were not found due to an inaccurate census list; 727 (83.3%) of the 870 investigated had received a three-dose HB vaccine series. Overall, the HB vaccination program in Italy is working well. However, further efforts should be made to improve the efficacy and effectiveness of the campaign.