High prevalence of HGV/GBV-C infection in polytransfused patients with thalassemia major.
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Biomedical subjects
Publications and source records attributed to A R Zanetti.
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To assess the rate of mother-to-infant transmission of hepatitis C virus (HCV) and to identify potential risk factors for transmission, we followed up (mean 22.4 months, range 1-7.5 years) a cohort of 291 babies born to anti-HCV-positive mothers, 40 of whom were also HIV coinfected. Seventeen (5.8%) babies acquired HCV infection, but none became icteric. All babies developed chronic HCV infection with 16 babies showing elevated levels of ALT. The rate of transmission was higher in babies born to mothers coinfected with HIV than in those born to mothers with HCV alone (22.5 vs. 3.2%, p < 0.0001). No association was seen between a specific maternal HCV genotype and an increased risk of neonatal infection. The median level of HCV-RNA was higher in mothers who transmitted infection than in those who did not, although the ranges overlapped. In this study, maternal history of chronic liver disease, mode of delivery and type of feeding were not predictive of HCV infection.
Controversial data were recently published concerning the association of hepatitis B virus (HBV) variants with fulminant hepatitis (FH). In this study, we first analyzed the complete nucleotide sequences of HBV genomes isolated from serum samples from a surgeon and his mother, who was accidentally infected by the son; both died of FH. The infecting viruses were genetically almost identical in both patients; all the clones examined carried a double nucleotide mutation in the start codon of the pre-S2 region that prevented the synthesis of the corresponding protein. Analyses of different serum samples from the son revealed only wild-type precore sequences in a high viremic serum, whereas hepatitis B e antigen (HBeAg)-defective strains were prevalent when the viremia had decreased. Subsequently, we extended the analysis to the viral genomes isolated from 18 additional patients with acute HBV infection and different clinical behaviors: 3 of 5 patients with FH and without previous liver disease had pre-S2 start codon mutations preventing pre-S2 protein synthesis, whereas none of the 13 control cases had similar genomic rearrangements. Analysis of the precore region showed that viral populations normally producing HBeAg were the only or the prevalent viral strains in all of these cases. In summary, our results support the hypothesis that the pre-S2 protein is not essential for HBV infectivity. They also show that infection by pre-S2-defective virus is frequently associated with FH, indicating that this variant might play a pathogenetic role in cases of acute liver failure. Finally, they suggest that the emergence of HBeAg-defective viruses might be a late event in the course of FH, occurring when HBeAg-producing viruses have been mostly cleared.
Hepatitis B virus (HBV) variants with amino acid mutations in the a epitope of the major surface protein have been identified, and questions have been raised regarding their biologic properties. Dilutions of serum that contained the first such described HBV mutant, with an Arg-for-Gly substitution at codon 145 of the S gene, were inoculated into 6 seronegative chimpanzees. Five of the animals developed serologic and/or biochemical evidence of hepatitis B. A polymerase chain reaction-based assay that discriminated between the wild type and mutant viral genomes revealed that a pure population of the mutant genome was present in the 10(-6) and 10(-7) dilutions of the index serum, resulting in infection of the chimpanzees receiving these dilutions only with the mutant virus. A clone of the mutant virus replicated normally following transfection in vitro. Thus, this HBV surface gene mutant is viable, infectious, and pathogenic in chimpanzees.
To assess the risk of mother-to-infant transmission of hepatitis C virus (HCV), we followed up 116 babies of anti-HCV positive mothers, of whom 22 were coinfected with HIV and 94 had HCV alone. None of the babies whose mothers had HCV alone acquired HCV, while 8 babies (36%; p < 0.001) of mothers co-infected with HIV acquired HCV (5 babies) or HCV and HIV (3). There was no association between any specific maternal HCV genotype and enhanced risk of neonatal infection. HCV-RNA levels were significantly higher (p < 0.05) in mothers with HIV coinfection than in those with HCV alone. These data indicate that maternal HIV status correlates with enhanced level of viraemia which favours neonatal infection.
We studied a familial cluster of adult HBV chronic carriers characterized by serological markers of active viral replication, normal or slightly elevated ALT levels and, in four out of five cases, absence of anti-HBc reactivity. The nucleotide sequence of the pre-C/C region of HBV was analyzed in three patients, showing the presence of wild-type HBV sequences accompanied by different deleted molecules. Some of the variant genomes were able to encode proteins retaining HBcAg and/or HBeAg reactivity, whereas others contained deletions leading to the synthesis of truncated proteins that could not be immunoprecipitated by anti-HBc or anti-HBe mono- and polyclonal antibodies. Defective molecules encoded by the variant C gene sequences might play a role in the determination of the clinical profile observed in the analyzed patients.
The seroprevalence of antibodies to HEV was determined in three different Italian populations (volunteer blood donors, normal healthy individuals, and intravenous drug users [IVDUs]). The seroprevalence in the populations ranged from 0.74% to 1.94%, with higher rates among IVDUs and individuals over 40 years of age. None of 35 patients diagnosed with acute hepatitis A but 10 of 153 (6.5%) patients with acute nonA, nonB, nonC hepatitis were found to be positive for anti-HEV antibody. One of these antibody positive cases was linked to travel, while the remaining 9 were not associated with travel to endemic areas. These data suggest a possible low circulation of HEV in Italy.
We have compared the prevalence of antibody to HAV in sera collected from healthy individuals of Milan in 1958, 1977 and 1992 respectively. The results show a dramatic reduction of HAV circulation likely due to the considerable improvement of socioeconomic and hygienic living conditions which have occurred in Italy during the last decades.
BACKGROUND: Several studies carried out in the USA and in Europe have shown the presence of HTLV-I/II antibodies in subjects belonging to high-risk groups for HIV infection as well as blood donors. Concern about the presence of HTLV-I/II markers in the normal population, as well as the efficient transmission of HTLV-I/II by whole blood or infected blood cells have led several countries to include screening for anti-HTLV-I/II among the mandatory serological testing of blood donors. OBJECTIVE: In order to assess the risk of HTLV-I/II infection related to blood transfusions, a multicentric survey for antibodies against HTLV-I and HTLV-II was carried out involving 10 Italian sites during the spring of 1991. STUDY DESIGN: Serum specimens were collected from 14,598 blood donors, 1,411 injecting drug users, 1,015 thalassemics, 142 hemophiliacs and 138 hemodialysis patients. HTLV antibodies were detected by a screening EIA which combines a viral lysate with a recombinant HTLV-I env protein (p21e). The serological confirmation was performed by a semi-automated dot-blot immunoassay that detects gag p19 and p24 and env p21e specific antibodies, while the discrimination of HTLV-I and HTLV-II reactivities was carried out by EIAs employing synthetic peptides of the ENV region specific for each virus. RESULTS: The seroprevalence of confirmed positives was 0.034% among blood donors and 3.61% among IDUs, while no sample of the other categories could be confirmed, although several were indeterminate and one thalassemic reacted against HTLV-I on peptide testing. HTLV-I reactivity was observed in one blood donor, while all 38 of the 51 confirmed seropositive IDU's reacted only to the HTLV-II synthetic peptide. CONCLUSIONS: These data confirm a high prevalence of HTLV-II among Italian IDUs and show an HTLV-I/II seroprevalence among blood donors very similar to that which was found in the USA volunteer blood donors. A surveillance program among blood donors seems advisable in order to establish the possible need of a mandatory screening for HTLV-I/II.
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We studied the relations between genetic heterogeneity of pre-C region of hepatitis B virus (HBV) DNA and outcome of HBV infection in 5 infants with perinatal infection, 3 born to anti-hepatitis B e antigen (HBeAg), and 2 to HBeAg positive mothers. HBV infection developed in the babies at 3-4 months of age, but it resolved with seroconversion to anti-HBs in infants born to anti-HBe positive mothers, while the infection became chronic in the 2 babies born to HBeAg positive mothers. HBV-DNA extracted from the first hepatitis B surface antigen (HBsAg) positive serum sample of each baby was amplified and directly sequenced for the pre-core region. HBV-DNA sequences from 3 babies born to anti-HBe positive mothers showed at position 1896 the contemporary presence of 2 nucleotides (G+A), indicating a mixture of wild-type and "e minus" variant HBV. These findings suggest a possible co-transmission of the 2 viruses from anti-HBe positive mothers to newborns. HBV-DNA from babies born to HBeAg positive mothers showed wild-type sequences only. The results of this study suggest that the outcome of HBV infection in newborns depends not only on the host's immunocompetence and on viremia level in maternal blood, but also on heterogeneity of HBV. Transmission of mixed HBV populations appears associated with an early immunoelimination of the virus, while infection with wild-type HBV alone contributes to induction of chronicity.
Hepatitis type C is the major aetiological cause of both parenterally transmitted and cryptogenic, sporadic or community acquired nonAnonB hepatitis. The lack of known parenteral risk factors in a consistent number of cases with nonAnonB hepatitis has stimulated the search of other possible modes of viral transmission. The aim of this report is to review the evidence both for and against vertical/perinatal transmission of HCV from anti-HCV positive mothers to infants.
Viral hepatitis B, which is a major health problem worldwide, is endemic in Italy. In response to this, vaccination became compulsory in 1991. Vaccine is administered to neonates and 12-year-old adolescents; in 12 years time, all Italians under the age of 24 will be immune to HBV.
We have evaluated the intrafamilial transmission of hepatitis C virus (HCV) by studying 1) the 107 household contacts of 43 patients with chronic HCV liver disease, 2) the household contacts of 30 anti-HCV-positive donors without liver disease, and 3) 3108 blood donors. We also studied the possible manner of the intrafamilial transmission. The prevalence of anti-HCV positivity in the families of index patients was significantly higher than in donors (14.9% as against to 1.7%). All the family members of the anti-HCV-positive donors were anti-HCV negative. We conclude that the person-to-person transmission of HCV is possible and most probable in contacts of anti-HCV-positive patients with liver disease.
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Using two sources of primary antibodies, we immunohistochemically stained hepatitis C virus-related antigen(s) on fixed-embedded liver specimens. These antigens were localized in the cytoplasm of hepatocytes. The results obtained serologically correlated well with immunohistochemistry.
The seroprevalence of HTLV-I/II was evaluated in 1247 Italian individuals at high risk for HIV infection. The population studied consisted of 985 intravenous drug users (IVDUs), 474 of whom on methadone maintenance and 511 in a therapeutic community, 110 HIV-infected patients in various stages of HIV-related disease and 152 hemophiliacs. Sera were screened for antibody to HTLV-I/II by enzyme immunoassay (EIA) and confirmed by Western blot and radioimmunoprecipitation assay. Confirmed positive samples were further differentiated by EIA using HTLV-I and HTLV-II specific peptides. The overall prevalence of anti-HTLV-I/II was 4.0% in IVDUs, with the highest prevalence (8.2%) among HIV-infected symptomatic patients. None of the hemophiliacs was anti-HTLV-I/II positive, even though 63.1% tested positive for HIV antibodies. The trend of seroprevalence in drug users and the evaluation of possible risk factors demonstrated that HTLV-I/II infection has been present in Italy before the onset of HIV epidemic. The overall seroprevalence showed no significant changes during the 10 year period covered by this survey but correlated with HIV seropositivity, age and duration of drug use. Peptide testing showed that HTLV infection was mainly due to HTLV-II.
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