Experimental studies on environmental contamination with infected blood during haemodialysis.
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To assess the relative importance of different postulated modes of spread of hepatitis B in dialysis units, blood charged with various tracer organisms was used in simulated haemodialysis runs in four laboratories, and the resulting contamination of equipment and environment was measured semi-quantitatively. Some airborne spread of the tracer organism occurred when tubing containing contaminated blood was needled as the "patient" went on and came off the dialyser. Virtually no small airborne particles could be demonstrated however in simulated emergencies in which a blood line was disconnected, or even when bottles of blood were dropped on to a hard floor from a height of 2 metres. Bacillus globigii spores from contaminated blood leaked in small numbers into the dialysing fluid through apparently intact coils. T3 phage, with a particle size of the same order as hepatitis B virus, passed in small quantities through the membrane of a Kiil dialyser from blood to dialysing fluid and also in the reverse direction when added to the header tank. A number of other dialysers were also permeable to phage. Visual assessment of the appropriate moment for inserting the venous line into the "patient" at the onset of dialysis was shown to be unreliable, as the displaced fluid from the end of the venous line was already contaminated before it contained visible red blood cells. Considerable contamination of exposed surfaces and of the buttons on the proportionating unit cabinet occurred. Minor visible splashing of blood was a common-place of the laboratory experiments and was shown to be also a common event during routine haemodialysis in two of the dialysis units taking part in the studies. (+info)
Progress in coverage with hepatitis B vaccine among US children, 1994-1997.
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OBJECTIVES: This study was done to assess progress in hepatitis B vaccination of children from 1994 through 1997. METHODS: We used data from the National Immunization Survey (NIS), a random-digit-dialed telephone survey that includes a mail survey to verify vaccination providers' records. The NIS is conducted in 78 geographic areas (50 states and 28 selected urban areas) in the United States. RESULTS: A total of 32,433 household interviews were completed in the 1997 NIS. An estimated 83.7% of children aged 19 to 35 months received 3 or more doses of hepatitis B vaccine. Coverage with 3 doses was greater (86.7%) among children in states that had day care entry requirements for hepatitis B vaccination than among children in states without such requirements (83.0%) and was greater among children from families with incomes at or above the poverty level (85.0%) than among children below the poverty level (80.6%). Hepatitis B vaccination of children increased from 1994 through 1996, from 41% to 84%, but coverage reached a constant level of 84% to 85% in 1996/97. CONCLUSION: Although substantial progress has been made in fully vaccinating children against hepatitis B, greater efforts are needed to ensure that all infants receive 3 doses of hepatitis B vaccine. (+info)
The Denver school-based adolescent hepatitis B vaccination program: a cost analysis with risk simulation.
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OBJECTIVES: This study sought to compare the cost-effectiveness of a school-based hepatitis B vaccine delivery program with that of a vaccine delivery program associated with a network health maintenance organization (HMO). METHODS: The vaccination program enrolled 3359 sixth-grade students from 18 middle schools in Denver, Colo. Immunization status and direct and indirect program costs were compiled. The sensitivity of the outcomes was assessed by simulation methods. RESULTS: The per-dose cost-effectiveness ratio for the school-based delivery system was $31. This cost-effectiveness ratio remained stable when the model was simulated with costs that were underestimated or overestimated by 20%. In the network HMO, the direct cost per dose was $68 and the societal cost was $118 when the child's father worked full-time and the mother worked part-time. There is less than a 5% chance that the network HMO-based vaccination program could be more cost-effective than the school-based program. CONCLUSIONS: The cost per dose of the school-based program was significantly less than that of the network HMO-based program, because in the school program government-purchased vaccine was available at a lower cost and parents did not incur work-loss costs. (+info)
Subtype-independent immature secretion and subtype-dependent replication deficiency of a highly frequent, naturally occurring mutation of human hepatitis B virus core antigen.
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The most frequent mutation of the human hepatitis B virus (HBV) core antigen occurs at amino acid 97. Recently, a phenylalanine (F)-to-leucine (L) mutation at this position (mutant F97L) in HBV surface antigen subtype ayw has been shown to result in an immature secretion phenotype, which is characterized by the nonselective export of an excessive amount of virions containing minus-strand, single-stranded HBV DNA. While subtype ayw mutant F97L has been found in Europe, the major reservoir of HBV resides in Asia and Africa. We report here that the immature secretion phenotype indeed can be found in an HBV strain (subtype adr) prevalent in Asia, changing from an isoleucine (I) to a leucine (mutant I97L). Despite its immature secretion phenotype, the adr variant I97L replicates as well as its parental adr wild-type I97I, supporting the conclusion that the extracellular phenotype of immature secretion is not a consequence of the intracellular HBV DNA replication defect. Further studies demonstrated that it is the acquisition of a leucine, rather than the loss of a wild-type amino acid at codon 97, that is important for immature secretion. We conclude that immature secretion is a subtype-independent phenotype and deficiency in intracellular DNA synthesis is a subtype-dependent phenotype. The former is caused by the trans-acting effect of a mutant core protein, while the latter by a cis-acting effect of a mutated nucleotide on the ayw genome. These immature secretion variants provide an important tool for studying the regulation of HBV virion assembly and secretion. (+info)
Hepatitis B virus genomes from long-term immunosuppressed virus carriers are modified by specific mutations in several regions.
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There is increasing evidence that hepatitis B virus (HBV) infection of an immunosuppressed host is associated with the appearance of virus mutants. To characterize the virus circulating in patients in detail, eleven full-length HBV genomes, isolated from the serum of five highly viraemic renal transplant recipients with liver disease, were cloned and sequenced. The genomes contained deletions in the C gene, deletions in the pre-S1/2 region frequently removing the pre-S2 initiation codon, premature termination codons in the pre-S1 or S region, and/or deletions/insertions in the X gene/core promoter. The mutations occurred at different positions and in various combinations; even mutant genomes circulating within a patient differed strikingly. It is concluded that long-term immunosuppression is associated with the occurrence of heterogeneous populations of partially defective HBV characterized by a specific mutation pattern. Efficient intracellular trans-complementation probably enables high virus replication in vivo. (+info)
Replication of hepatitis B virus in first-degree relatives of patients with hepatocellular carcinoma.
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Hepatocellular carcinoma (HCC) may occur in family clusters. No genetic mechanism has been identified as responsible for this familial tendency. We suspected that a longer hepatitis B virus (HBV) replication phase might be the reason for a higher risk of HCC in families with this disease. We performed liver biochemical tests, test for viral hepatitis markers and hepatitis B e antigen (HBeAg), and liver ultrasonography in relatives of patients with HCC. A total of 1,885 first-degree relatives from 688 families participated in this study. Seven hundred fifty-two relatives were found to be carriers of hepatitis B surface antigen (HBsAg) and 675 of them were tested for HBeAg. The prevalence of HBeAg was 27.4% in relatives of those with HCC and 20% in asymptomatic HBsAg carriers. The HBeAg prevalence rate was higher in relatives of those with HCC > or = 40 years old than in asymptomatic HBsAg carriers. Moreover, HBeAg was more likely to persist in men than in women > or = 40 years old. We conclude that families with HCC showed a prolonged HBV replication phase that may be one of the cofactors for a familial tendency for HCC. (+info)
Prevalences of hepatitis A, B, C and E viruses in Behcet's disease.
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OBJECTIVE: To determine whether Behcet's disease (BD), being a systemic vasculitis of unknown aetiology, is associated with hepatitis viruses (HAV, HBV, HCV and HEV). METHODS: In addition to 124 patients [male:female (M/F): 73/51], all fulfilling the diagnostic criteria of the International Study Group for BD (1991), 14 patients with systemic necrotizing vasculitis (M/F: 7/7), 47 patients with ankylosing spondylitis (M/F: 36/11) and 51 healthy controls (M/F: 22/29) were also included in this study. Serological markers of four different types of hepatitis (anti-HAV IgM, total anti-HAV, HBsAg, anti-HBs, total anti-HBc, anti-HBc IgM, anti-HCV and anti-HEV) were studied in all cases. RESULTS: There was no difference between the groups with respect to HAV, HCV and HEV serologies. Anti-HBs positivity was observed less frequently in BD compared with healthy controls and systemic vasculitis (P<0.05). CONCLUSION: Serological evidence of previous HAV, HCV and HEV infections was not significantly different between Behcet's patients and other groups. However, previous HBV infection was found in a significantly lower number of BD patients as compared with healthy controls and systemic vasculitic patients. (+info)
Aberrant fragile histidine triad gene transcripts in primary hepatocellular carcinoma and liver cirrhosis.
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To determine whether transcriptional alterations of the fragile histidine triad (FHIT) gene play a role in the development and progression of human hepatocellular carcinoma (HCC) we used reverse transcription-PCR to examine mRNA FHIT expression in 28 paired samples of HCC (24 in cirrhotic and 4 in noncirrhotic livers) and matched noncancerous tissue and in 10 normal livers. We also assessed loss of heterozygosity of the polymorphic D3S1300 microsatellite marker in the intron between exons 5 and 6 of the FHIT gene. Abnormal FHIT transcripts were detected in 13 cases (46.4%): 10 in the cancerous tissue only, 1 with the same pattern in both cancerous and matched noncancerous tissue, and 2 in the noncancerous tissue only. The four HCCs that arose in noncirrhotic liver all showed abnormal FHIT transcripts. No alterations were found in normal livers. Sequence analysis of abnormally sized transcripts revealed that they were generated by the fusion of exons 3 or 4 with exons 8 or 9. Among the cancerous specimens, one case showed only an abnormal sized transcript derived from the fusion of exons 4 and 9 in the absence of any normal-sized transcript, and another case showed deletion of a sequence comprised between nucleotides -35 and 399 resulting in an exon 4-9 fusion not respecting the exons' bounds. Loss of heterozygosity was found in two cases with abnormal FHIT transcripts and in only one case with normal transcript. Patients with aberrant FHIT transcripts showed a significantly higher relapse rate and shorter recurrence time (P = 0.001). This could be related to a primary genomic instability affecting particularly susceptible regions like FRA3B and could be associated with an increasing risk of recurrence without involving a causative role. (+info)