Decitabine (5-Aza-2'-deoxycytidine; DAC) plus daunorubicin as a first line treatment in patients with acute myeloid leukemia: preliminary observations.

The authors report on the preliminary results of an ongoing phase II trial whereby the combination of the new DNA hypomethylating agent, 5-Aza-deoxycytidine (DAC), plus daunorubicin was given as first-line induction therapy to non-pretreated patients with acute myeloid leukemia (except FAB M3). DAC was given as a 4-h intravenous infusion at the dose of 90 mg/m2 daily from days 1-5, while daunorubicin was administered at the dose of 50 mg/m2 on days 1-3. A maximum of two courses were given to the patients with an interval of 4-6 weeks. Up to now, eight patients were accrued, of those six were evaluable for toxicity and response. The main toxic effects were bone marrow suppression, mucositis, nausea and vomiting, and alopecia. All six patients achieved a complete remission after one (five cases) or two (one case) courses. The trial is open for patient accrual.

Hepatitis A infection: a seroepidemiological study in young adults in North-East Italy.

During the period from January to May 1994, the prevalence of antibodies to hepatitis A virus infection (anti-HAV) was tested by immunoenzyme assay in the serum samples of 620 apparently healthy subjects (81% males, 19% females), from 10 to 29 years old, resident in North-East Italy (Pordenone and surrounding district). The overall prevalence of anti-HAV was 3.7%. There was a significant lower prevalence in the group aged 10-19 than in the one aged 20-29 years (0.7% vs 6%; p < 0.001). Moreover, a significant sex difference was observed for the 20-29 year age group (p < 0.001). Among the various risk factors considered, family size and travelling abroad to endemic areas were significantly associated with HAV infection. Since a valid and effective vaccine against HAV infection has recently become available, anti-HAV vaccination campaigns can feasibly be programmed. However, different geographical regions present different epidemiological situations, so its use should be adapted to each region, with special attention to the cost-effectiveness of the immunisation programme. Our data suggest that in our region such vaccination could initially be proposed to high-risk subjects such as those travelling to endemic areas.

Immunity status to polioviruses among non-European union immigrants in Veneto Region (North-East Italy).

Widespread use of poliovirus vaccines has lead to a dramatic decline on the incidence of paralytic poliomyelitis in the Western Hemisphere. In Italy, the use of live attenuated vaccine (OPV) has lead to virtual eradication of poliomyelitis. However, wild poliovirus is still endemic in some less developed countries, and there is still a risk of importation of wild-virus poliomyelitis as result of immigration from these areas. Therefore, a serologic study of the immunologic status to poliovirus was carried out in 242 immigrants from less developed countries in the Veneto Region (North-East Italy). The overall prevalence of serum neutralizing antibodies was 98.3 percent for poliovirus type 1, 99.6 percent for type 2, and 95.9 percent for type 3. The modal titres were 1:128 (21.1 percent), 1:512 (26.4 percent), and 1:32 (22.3 percent) for poliovirus type 1, type 2, and type 3, respectively. No subject was simultaneously lacking neutralizing antibodies to all three polioviruses. The mean duration of stay in Italy before testing was 1.53 years (range 1 month to 7 years). These results show a good level of the immunity status, similar to those found in the Veneto general population. Although the risk of paralytic poliomyelitis in our population is very low, seronegative immigrants originating from areas of high endemicity could reintroduce wild poliovirus. It is therefore important to maintain a careful surveillance system on the importation of wild poliovirus and to plan vaccination programs for unprotected immigrants.

Two different dosages of yeast derived recombinant hepatitis B vaccines: a comparison of immunogenicity.

The efficacy of a 10 or 20 micrograms antigen load of HB recombinant vaccines is still being debated. A comparison of anti-HBs titres in two groups of healthy subjects vaccinated by the same schedule (0, 1 and 6 months) employing recombinant HB vaccines with different antigen loads, 20 micrograms (group A, 251 subjects) and 10 micrograms (group B, 256 subjects) was carried out. A seroprotection rate of 99.6 and 99.2% was observed for group A and group B, respectively, at the end of primary immunization. No statistically significant difference in seroprotection rate was observed. Group A showed significantly higher GMTs than group B for all age groups and for both sexes except for males above 25 years. The difference was more marked for younger age groups and for the female sex. These data support the higher immunogenicity of vaccine with 20 micrograms antigen load as compared to vaccines with 10 micrograms antigen load.

Response to an extra dose of hepatitis B vaccine and specific antibody persistence in non-responders to primary immunization.

BACKGROUND: In a campaign to vaccinate health care workers, a three-dose schedule (0, 1, and 6 months) and a four-dose schedule (0, 1, 2, and 14 months) with hepatitis B (HB) vaccine were used. After primary immunization 26 subjects vaccinated with the 3-dose schedule and 4 subjects vaccinated with the 4-dose schedule had undetectable anti-HBs titres. METHODS: All these 30 non-responders received an extra dose of the same vaccine 2 months after primary immunization and a booster dose with a yeast-derived vaccine 6 years later. Anti-HBs levels were evaluated 1 month after the extra dose and after the booster dose. RESULTS: One month after the extra dose 26.9% (7 of 26) of the subjects vaccinated with the 3-dose schedule became positive for anti-HBs. Six years later only two of these subjects had detectable anti-HBs. After the booster dose the seven subjects who responded to the extra dose showed an anamnestic type of response, and five additional subjects became positive for anti-HBs. Responders to the extra dose were significantly younger than the non-responders. In the four-dose group only one subject responded to the extra dose, and that subject maintained protective anti-HBs. CONCLUSION: About 25% of non-responders to primary HB vaccination could benefit from an extra dose, and these subjects show an anamnestic type of response to HBs antigen even after 6 years. This response seems to be influenced by age.

Poliovirus neutralizing antibody persistence after vaccination with the Sabin vaccine: a follow-up study.

In 1976, a cohort survey on the persistence of neutralizing antibodies in children regularly immunized 1 to 4 years earlier with the Sabin attenuated vaccine (OPV) was undertaken in the Venice mainland. Subsequent serological evaluations in the same cohort were carried out in 1983 and 1993. A macroneutralization test using a 1:4 initial serum dilution was utilized in the 1976 and 1983 survey years. In the 1993 survey a microneutralization test using a 1:2 initial dilution was utilized. In this survey, however, sera were tested using both the latter microneutralization test and the former test. Using the former method, the results indicate that the OPV-induced humoral immunity to poliovirus 1 and 2 remain fairly stable after the initial decrease, whereas antibodies to poliovirus 3 are further declining. Using the latter more sensitive method the seropositivity rates were found to be equal or close to 100 percent. The results of our follow-up survey thus indicate that the OPV-induced humoral immunity is long-lasting when tested with a highly sensitive and reproducible method. The clinical protection that ensues after OPV-immunization is probably lifelong similar to that which follows the natural infection.

Persistence of anti-HBs antibodies in health care personnel vaccinated with plasma-derived hepatitis B vaccine and response to recombinant DNA HB booster vaccine.

Long-term persistence of specific antibodies after primary immunization against HBV infection has been reported. In this study, we evaluated the persistence of anti-HBs in vaccinees 6 years after primary immunization and the response to a booster dose using a recombinant DNA yeast-derived HB vaccine. An 85.4% seroprotection rate was observed after 6 years with a significantly higher seroprotective rate in those subjects who received four doses of vaccine primary immunization as compared with those who received three doses (93.9% versus 67.2%, p < 0.001). One month after receiving the booster dose, 98.6% of the subjects had an anamnestic type of response. The GMTs were found to decrease progressively with increasing age. The antibody levels after booster dose were higher than those attained at the end of primary immunization and reflected the trend seen before the administration of the booster. These results are consistent with the existence of an effective immunological memory in HB vaccine responders. Subjects who received four doses during primary immunization were better seroprotected and had a higher seroprotection rate after the booster dose.

Immunity status to poliovirus in Veneto region (north-east Italy). A seroepidemiological survey.

The immunity state to poliovirus types 1, 2, and 3 of a population aged 2 to 75 years was determined by examining 274 sera collected in the Venice mainland (North-East Italy). Altogether, the neutralizing antibody prevalences (at a titre > or = 1:2) for poliovirus 1, 2, and 3 were 99.0 percent (geometrical mean titres [GMT]: 72.1), 99.6 percent (GMT: 95.9) and 98.2 percent (GMT: 17.3), respectively, and all the age groups also showed very good levels of humoral immunity. High antibody titres (> or = 1:256) to one or more types of poliovirus were demonstrated in older age groups also, possibly indicating exposure to natural polioviruses or contact with vaccine strains. Although probably all the older subjects had practically acquired their antibodies as a result of natural infection and those under 30 through vaccination, these results indicate that the humoral immunity against poliomyelitis in our population is satisfactory, and the maintenance of such good protection level depends on an effective immunization program.

Low prevalence of anti-HCV antibody among Italian children.

The seroprevalence of anti-HCV antibody was studied among 2,749 children and teenagers (1,438 males and 1,311 females) living in Italy. Anti-HCV antibody testing was positive by both EIA and RIBA in ten (0.36%) subjects. The positivity rate increased with age, ranging from 0 among children less than 6 years of age to 0.8% among those aged 17-19 years chi 2 linear regression = 0.038). Anti-HCV prevalence ranged from 0.2% in northeastern regions and in Apulia to 0.6% in Sicily and Sardinia (p > 0.005), and no difference was seen between males (0.35%, C.I. 95%: 0.04-0.66) and females (0.38%, C.I. 95%: 0.04-0.66) (Fisher's exact test = 0.565). From these data it appears that in Italy HCV infection is an uncommon event during childhood.

Seroepidemiology of pertussis in Italy.

During 1988 and 1989 the prevalence of serum IgG antibodies to pertussis toxin in a sample of 3,875 unvaccinated, apparently healthy persons between the ages of 1 year to 19 years was estimated by enzyme-linked immunosorbent assay. The participants were recruited by means of systematic cluster sampling from public and private schools in five geographic areas of Italy. The overall prevalence of IgG antibodies was 80.8%, with a steady increase from 33.5% among 1- to 3-year-old children to 95% among 17- to 19-year-old individuals. The prevalence of natural immunity was 50% and 75% at the ages of 4 and 6 years, respectively. No gender-related difference in immunity was observed. For children greater than 10 years of age, the seroprevalence of pertussis antibodies was significantly higher in northern regions than in southern regions until the age of 17-19 years, when the pattern reversed. There was no association of a child's immune status with the father's number of years of schooling or with family size. For children aged 1-3 years, serologic studies showed that the history of pertussis reported by parents in questionnaires was highly specific (97.6%) in predicting antibody status, with positive and negative predictive values of 90.5% and 79.2%, respectively. However, 20.8% of children had antibodies to pertussis toxin even though they had no history of whooping cough.

Hepatitis C virus infection in homosexual men: a seroepidemiological study in gay clubs in north-east Italy.

Seroprevalence of Hepatitis C virus (HCV), Hepatitis B virus (HBV) and HIV antibodies was studied in a group of 259 apparently healthy homosexual men of the Veneto Region (Italy). Subjects were recruited between 1987 and 1989 from homosexual men's clubs. Seropositivity was evaluated in relation to main risk factors associated with the lifestyle and sexual behaviours of this population. Serological evaluation revealed an overall prevalence of HCV infection of 18.9% in the study population as a whole, but on breaking the samples down into three subgroups according to optical density (O.D.) values and to the year of sera collection, different seroprevalences were observed. Prevalence of anti-HCV was higher in 1987 and steadily decreased in 1988 and 1989; 4.1% of subjects gave positive results at O.D. greater than 2.0, while 6.2% were positive at O.D. between 0.8 and 2.0 and 9.6% at O.D. between cut-off and 0.8. Anti-HCV positivity was not correlated with HIV nor HBV positivity. No correlation was found between HCV seropositivity and either the type of anogenital intercourse or sexual promiscuity, but the prevalence increased (p = n.s.), as observed for HIV (p less than 0.05) and HBV (p = n.s.), with the number of intercourses per month. Epidemiological and preventive aspects arising from the investigation are discussed herein.

Prevalence of cytomegalovirus infection in Italy.

Between 1987 and 1989, the prevalence of antibody to cytomegalovirus (CMV) was determined, by the ELISA method, in serum samples from 1494 apparently healthy subjects, 3-18 years old. Subjects were selected by a systematic cluster sampling from five geographical areas in Italy. The overall prevalence of antibody was 64.2%, increasing from 54.4% in 4-6-year-olds to 73.3% in subjects 17-18 years old (P less than 0.01). Prevalence of antibody was significantly higher in females (P less than 0.05) and in subjects residing in the South of Italy (P less than 0.01). A significant association was found with sociodemographic factors. Subjects belonging to a household with six or more persons had a 1.5-fold risk (C.I. 95% = 1.11-2.04) and subjects whose fathers had less than 6 years of schooling had a 1.4-fold risk (C.I. 95% = 1.1-1.87) of previous exposure to CMV infection. The high prevalence (74.4%) of young women who are naturally immune when entering childbearing years does not guarantee that there will be a low risk of fetal infection.

Prevalence of Toxoplasma gondii antibodies among children and teenagers in Italy.

Between 1987 and 1989, the prevalence of antibodies to Toxoplasma gondii was determined by ELISA in serum samples from 1,494 apparently healthy subjects, 3-18 years old. Subjects were selected by a systematic cluster sampling from five geographical areas in Italy. The overall prevalence of antibodies was 17.9%, increasing from 4.7% in 4-6 year olds to 28.4% in 17-18 year olds (P less than 0.01). A slight predominance was observed among males (18.2% vs. 17.5% in females), as well as among subjects residing in Southern Italy and the Islands (21.9% vs. 19.2% in subjects residing in the North), but neither difference was statistically significant. Toxoplasma infection was associated with sociodemographic factors. Subjects belonging to a household with six or more persons had a 1.8-fold risk (C.I. 95% = 1.3-2.6) and subjects whose fathers had less than six years of schooling had a 2.7-fold rosk (C.I. 95% = 1.8-3.9) of previous exposure to toxoplasma infection. Considering the large proportion (70%) of young women entering childbearing age without toxoplasma antibodies, it appears that the risk of congenital toxoplasmosis will not be negligible in Italy in forthcoming years.

Changing epidemiology of hepatitis A virus (HAV) infection: a comparative seroepidemiological study (1979 vs 1989) in north-east Italy.

A comparative seroepidemiological study (1979 vs 1989) on HAV infection, was carried out in children and adolescents from North-East Italy. Anti-HAV was tested in 850 subjects 6 to 8 years of age and the results were compared to those observed in 1979, in 462 subjects of the same age range and from the same geographical area. Overall anti-HAV prevalence was 1.9% (ranging from 0.5 to 5.2) in 1989 vs 32.5% (ranging from 7.8 to 70.7) in 1979. This dramatic decline of HAV infection in children and adolescents reflects the improved sanitation standard of our country but, on the other hand, indicates that the number of non-immune adults is increasing, with a higher risk of symptomatic infection in the near future.

Changing pattern of hepatitis B infection in children: a comparative seroepidemiological study (1979 vs 1989) in north-east Italy.

Hepatitis B infection was endemic in Italy and household transmission has been considered to be the main mode of HBV spread. Prevalence of HBsAg positive subjects was therefore higher in children than in adults. Serum samples from 500 children (aged 6-15 year) without overt liver disease were tested for HBV serum markers in 1979. Serological evidence of HBV infection was present in 16% of the subjects. To verify a possible decline of HBV infection we designed a seroepidemiological study in school children from the same town. Three classes of age (6 yrs, 10 yrs, 14 yrs) were selected. Children were recruited from those attending primary and secondary schools using a systematic cluster sampling. After parents' informed consent sera were collected in May 1989. All were tested for anti-HBc: anti-HBc + ve sera were then tested for HBsAg and anti-HBs (EIA Abbott Lab., Chicago, Ill. USA). Of the 1635 children one was HBsAg positive and 21 were positive for any HBV marker. Both the prevalence of HBsAg and that of any HBV marker were significantly lower (p less than 0.001) in 1989 when compared to the corresponding age-class of 1979.

Persistence of poliovirus-neutralizing antibodies 2-16 years after immunization with live attenuated vaccine. A seroepidemiologic survey in the mainland of Venice.

A seroepidemiological survey was conducted on subjects who had received a full vaccination course with live attenuated poliovirus 2-16 years before. For strains 1 and 2 prevalence of seropositives and median values dropped gradually during the first 10 years; strain 3 showed a much earlier decline. Environmental displacement of wild poliovirus by the attenuated, less immunogenic strain might eventually induce a 'gap', should complacency hamper needed vaccination efforts.

Prevalence of poliovirus neutralizing antibodies. A seroepidemiologic survey of vaccinated and unvaccinated women of fertile age.

The Authors tested a group of 232 women of fertile age, living in the Venice mainland, for presence of detectable protective serum antibodies against poliovirus strains 1, 2 and 3, according to vaccination status with living, attenuated poliovirus. Overall, unvaccinated subjects had a slightly higher prevalence of seropositivity as well as higher geometric mean titres than the women who had undergone a full vaccination course fifteen to twenty years before. Particularly worrisome was lack of protection against poliovirus 3, found in 23% of vaccinated and 15% of unvaccinated study participants. Break in herd immunity might end up in localized outbreaks of poliomyelitis, a not too distant possibility in Italy, where a steady flow of immigrants from North Africa and the Near East provide a source of wild poliovirus strains.

[A case of congenital cytomegalic disease: clinical and virological study]. / Un caso di malattia citomegalica congenita: studio clinico e virologico.

A case of congenital cytomegalovirus infection is reported and its clinical and diagnostic problems are considered. Perinatal and intrauterine transmission of CMV is discussed.

The risk of hepatitis A virus infection for hospital staff.

The prevalence of antiHA was assessed in 594 hospital employees and in control groups comprising 932 "healthy" adults not working in the hospital, selected from different socioeconomic classes. Age specific antiHA prevalence which was lower in doctors than in nurses and ancillary staff, was also found to be lower in each group than in the respective controls, matched according to socioeconomic criteria. It is concluded that in our population (i.e. high risk area) the hospital environment does not involve an increased risk of HAV infection for personnel. However, precautions should be taken when working in high risk department, as this study demonstrated that a considerable proportion of health care workers (above all doctors) are still susceptible to Hepatitis A virus infection.

Hepatitis A and hepatitis B virus infection in children and adolescents in north-east Italy.

The sera of 722 children and adolescents without overt liver disease were tested for hepatitis B surface antigen (HBsAg), antiHBs and anti-hepatitis B core anti-HBc; 658 of the sera were also tested for anti-hepatitis A virus anti-HAV. Except for the "passive" antibody peak observed in babies, the anti-HAV age-specific prevalence was negligible until the age of 3; it then increased, reaching 35% by the age of 15. Serological evidence of HBV was present in 16% of the subjects: this prevalence was almost constant at all ages. The HBsAg carrier rate was highest in children under 5 years of age (7.6%) and decreased with age. However, only one HBsAg carrier was under 1 year of age. Anti-HBs age-specific prevalence increased progressively from 2.7% to 11.4%. Anti-HBc alone was present in 4.1% of the subjects. No significant sex differences were found in the prevalence of HBV serum markers or in the HBsAg carrier rate. Neither HAV nor HBV infection was significantly influenced by place of residence or socioeconomic status. It is concluded that in this area both HAV and HBV are endemic, but while HAV is mainly acquired at school, most of the HBV infections occur within the household. The results suggest that not only perinatal transmission, but also intrafamilial horizontal infection, plays a role in HBV spread among infants.