[Success of hepatitis B vaccination].
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Biomedical subjects
Publications and source records attributed to F Deinhardt.
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The delta agent seems to be a defective RNA virus which is dependent on a helper function provided by hepatitis B-virus. Delta agent infection occurs by parenteral transmission either together with hepatitis B-virus, or superimposed on chronic HBV infection. In the first case biphasic hepatitis may result, whereas in the second case mostly an acute delta agent infection develops, which is often followed by chronic delta hepatitis. The delta agent is endemic to certain areas, and also in certain risk groups such as drug addicts, hemophiliacs and polytransfused patients. A delta agent infection should be suspected in case of acute hepatitis in a hitherto clinical inapparent chronic carrier, especially if he belongs to one of the above mentioned risk groups. There is no specific therapy for delta infection, the only prophylactic measure is vaccination against hepatitis B.
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The characteristics of 86 patients with acute non-A, non-B hepatitis were compared to 23 patients with acute hepatitis A and 76 with acute hepatitis B by medical record reviews of patients seen at 5 hospitals in Baltimore, Maryland, as part of case-control study of viral hepatitis. Results of serum aminotransferase levels, bilirubin, albumin, and prothrombin times alone could not distinguish the type of viral hepatitis because of extensive overlap. The alanine aminotransferase range for non-A, non-B hepatitis was 56 to 1819 IU/liters, for hepatitis A 250 to 1995 IU/liters, and for hepatitis B 203 to 2120 IU/liters. The ranges of aspartate aminotransferase and bilirubin for the types of hepatitis also overlapped. Fewer patients with non-A, non-B hepatitis or hepatitis A had a prolonged prothrombin time compared to patients with hepatitis B. Hepatic encephalopathy was seen only in two patients with hepatitis B. Forty-two percent of non-A, non-B hepatitis patients followed for 6 months or longer continued to have elevated alanine aminotransferase levels. Chronic alanine aminotransferase elevation was independent of the source of infection: transfusion, parenteral drug use, or all other sources. Prolonged follow-up is necessary to evaluate chronicity in patients with non-A, non-B hepatitis.
One hundred sixty-three persons immunised against hepatitis B with a vaccine containing HBsAg either of adw or ayw subtype were examined for antibodies against the a, d, and y determinants of HBsAg. Sera were tested for antibodies against HBsAg adw and HBsAg ayw separately by a solid-phase radioimmunoassay using polystyrene beads coated with HBsAg of either adw or ayw subtype, and the relative amounts of antibodies against the single determinants were calculated. After the third immunisation, all vaccinees had antibodies against the common determinant a. A quantitative evaluation showed that on average about 50% of HBsAg-specific antibodies were directed against the a determinant, and about 50% against d or y, respectively. However, as only anti-a is protective against cross-infection with other HBsAg subtypes, the degree of immunity of a person vaccinated against hepatitis B should be evaluated by the determination of antibodies to a rather than antibodies against total HBsAg.
Intradermal inoculation of hepatitis B vaccine (HBsAg subtype adw) caused no side effects, but the vaccine was less immunogenic than following intramuscular administration. Intradermal inoculation does not, therefore, offer a major advantage to the generally used intramuscular immunization. A single multisite intradermal administration of a reduced dose of vaccine did not result in a more rapid seroconversion compared to intramuscular inoculation. Although the antibody levels were similar after two intradermal or intradermal or intramuscular injections given 1 month apart, the booster (third injection) at 6 months resulted in anti-HBs levels that were about 10 times higher following intramuscular inoculation as compared to intradermal. All persons immunized developed anti-HBs. The levels of anti-HBs (a and w) were about 30-40% of the total anti-HBs, and the proportion did not change significantly during the course of immunization. Cross-protection against all HBV strains is thus also assured after intradermal administration of vaccine containing only one HBsAg subtype (adw). A skin reaction was elicited only in a small proportion of anti-HBs-positive individuals, and the reaction correlated roughly with the immune responses.
The influence of donor age on the production of interferon (IFN) alpha and IFN gamma by human peripheral blood mononuclear cells in vitro has been studied. The results demonstrate an age-related decline of the capacity to synthesize and secrete antiviral activity. Yields of virus-induced IFN alpha and lectin-induced IFN gamma were significantly decreased in mononuclear cell cultures from older subjects (greater than 50 years) when compared to those of younger subjects (less than 50 years). The observed deficiency of IFN production may be involved in the increased susceptibility of aged humans to viral infections and malignant diseases.
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RNA extracted from highly purified hepatitis A virus (HAV) particles was translated in an RNA-dependent, cell-free reticulocyte lysate system, and the products were analyzed by SDS-polyacrylamide gel electrophoresis and compared with proteins translated from RNA of poliovirus. The efficiency of translation in vitro of HAV RNA was comparable to that of poliovirus RNA. Processing of the putative precursor molecules of HAV proteins, studied in pulse-chase experiments, was impaired when compared with that of poliovirus. By radioimmunoprecipitation it was shown that most proteins produced by translation in vitro were related immunologically to the viral structural proteins of the virion.
The relationship between NK active and IFN alpha-producing cells in human peripheral blood was studied with a monoclonal antibody with specificity for NK cells (anti-Leu11b). Removal of Leu11b antigen expressing leukocytes with antibody-mediated complement-dependent lysis resulted in a marked reduction of NK activity. In contrast, the depletion of Leu11b positive cells did not affect the production of IFN alpha in response to influenza A/X31 virus, Corynebacterium parvum, or Molt 4 human leukemic cells. The results indicate that NK activity and synthesis of IFN alpha are mediated by different leukocyte subpopulations. The findings further suggest that the augmentation of the cytotoxic activity of NK cells by IFN may not be the consequence of positive self-regulation, but rather of cellular cooperation.
No differences in eventual immune-response rates were found between 325 subjects immunized passively/actively against hepatitis B and a control group of 108 subjects vaccinated only actively. The geometric mean titers of antibodies to hepatitis B surface antigen were nearly identical in controls and in a group of 87 individuals immunized passively/actively with the same vaccine lot. Lower geometric mean titers of antibodies to hepatitis B surface antigen were seen in 238 individuals who were vaccinated passively/actively with a different vaccine lot, a difference that may be explained by a somewhat lower immunogenicity in this particular lot. The mean half-life of hepatitis B immunoglobulin was calculated as 24.8 days, and in approximately 90% of vaccines 300,000 mIU of hepatitis B immunoglobulin provided protection until an active immune response had developed.
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Different population groups from the Shanghai area were surveyed by radioimmunoassay for serologic markers of previous infections with hepatitis A virus and hepatitis B virus. There were no significant differences in the prevalence of antibodies to hepatitis A virus (anti-HAV) in males and females, or in persons living in rural or urban areas. The prevalence of anti-HAV showed a biphasic increase with age, approaching 100% above age 50 years whereas the geometric mean titers declined. The rate of infection (attack rate) with hepatitis A among susceptibles in Shanghai declined appreciably between 1950 and 1960. The prevalence of hepatitis B markers also did not differ in the sexes, or in rural and urban populations. The patterns of prevalence of hepatitis B markers at different ages were compared to various theoretical mathematical models, and the data fitted best a model constructed from the assumption that two subpopulations of approximately equal size, one at low and the other at high risk, existed in the population groups studied. It was estimated that in Shanghai up to 12% of all individuals infected with hepatitis B became chronic hepatitis B surface antigen (HBsAg) carriers, although the overall prevalence of HBsAg carriers was only 6.9%. All HBsAg-positive individuals subtyped had been infected with hepatitis B virus of the subtype ad; 41.7% of HBsAg carriers also had hepatitis B e antigen (HBeAg), whereas in 32% of HBsAg carriers antibodies to HBe were present. Antibodies to HBsAg appeared to be lower in titer than in Western populations and to decline with age, and age-specific prevalence data indicated a relatively longer persistence of antibodies to hepatitis B core antigen.
Hepatitis A virus (HAV), when inoculated into cultures of the PLC/PRF/5 cell line which produces the surface antigen of hepatitis B virus (HBsAg), showed growth characteristics different from those of other picornaviruses. Antigen of HAV (HAAg) is expressed only about 10 days after infection. No major impact on the overall macromolecular biosynthesis of the host cells is observed. The growth rate of HAV-infected and uninfected cells was comparable, although the plating efficiency of infected cells was lower. Different hormonal factors were tested for their ability to stimulate viral antigen expression. Dexamethasone or prostaglandin E1 added to the culture medium increased HAAg expression; insulin reduced expression. Persistent infection of hepatoma cells by HAV never led to a cytolytic infection. In temperature-shift experiments, an adverse effect on the expression of HAAg and HBsAg was observed. In all experiments, the amounts of HBsAg in HAV-infected cells were reduced. On the whole, no major influence on host-cell metabolism is observed in cells persistently infected with HAV. Cell-mediated immunological response as a mechanism of pathological changes in HAV-infected liver is, therefore, more likely than a cytopathological effect.
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