Wolf Szmuness

Hepatitis B vaccine. Demonstration of efficacy in a controlled clinical trial in a high-risk population in the United States.

A variant HBsAg protein of fragment thereof displaying the antigenicity of Hepatitis B virus surface antigen is disclosed, in which the variant protein or fragment thereof (vHBsAg) comprises a modified a determinant in which there is an amino acid other than glycine at position 145 of the HBsAg sequence. A vaccine comprising the vHBsAg is provided, as it is a kit for diagnostic in vitro detection of anti-vHBsAg antibodies and an antibody preparation comprising anti-vHBsAg antibodies.

Serum alanine aminotransferase of donors in relation to the risk of non-A, non-B hepatitis in recipients. The Transfusion-Transmitted Viruses Study.

To evaluate the incidence of post-transfusion hepatitis and factors influencing its occurrence, the Transfusion-Transmitted Viruses Study prospectively followed 1513 transfusion recipients from 1974 through 1979. The attack rate for non-A,non-B hepatitis was 10 per cent. The incidence of hepatitis was directly related to the alanine aminotransferase (ALT) level in blood donors. In recipients of multiple transfusions of blood that had no donor-ALT level above 29 IU per liter the attack rate was 6 per cent or less; at higher donor-ALT levels the attack rate increased progressively, reaching 45 per cent in recipients of units with an ALT of 60 IU or greater. A similar relation was observed among recipients of single units of blood. Moreover, hepatitis developed in 10 of 11 recipients of two units with an ALT level of 45 IU or greater. These data indicate that screening blood for ALT levels would reduce the incidence of non-A,non-B post-transfusion hepatitis.

Hepatitis B vaccine in patients receiving hemodialysis: immunogenicity and efficacy

We evaluated the immunogenicity and efficacy of hepatitis B vaccine (Heptavax-B) in a randomized, double-blind, placebo-controlled trial involving 1311 patients receiving hemodialysis in the United States. After three doses of vaccine (40 micrograms each) had been administered, 63 per cent of the patients were antibody-positive. After correction for possible passive transfer of antibodies by blood transfusion, only 50 per cent of vaccine recipients were considered vaccine responders. The incidence of hepatitis B viral infection during the 25 months of the trial was much lower than had been anticipated and was virtually the same in the vaccine and placebo recipients (6.4 and 5.4 per cent, respectively). Four cases of hepatitis B occurred in patients who had an apparent antibody response to the vaccine, but in each case either antibody had reached low or undetectable levels before hepatitis B surface antigen was detected or the patient had been receiving immunosuppressive therapy. This study did not demonstrate the efficacy of the vaccine in a population of patients receiving dialysis in whom both the rate of antibody response to hepatitis B vaccine and the viral attack rate were low. Other measures to control transmission of hepatitis B virus in dialysis units, including surveillance for hepatitis B surface antigen and isolation of patients who are positive for the antigen, must be continued.

Hepatitis B Virus Antibody in Blood Donors and the Occurrence of Non-A, Non-B Hepatitis in Transfusion Recipients: An Analysis of the Transfusion-Transmitted Viruses Study

Patients who received transfusions and nontransfused control patients were followed to assess the incidence and cause of post-transfusion hepatitis and to identify donor factors that might relate to risk of hepatitis. We evaluated as risk factors in donors the presence of antibody to hepatitis B virus compared with elevated alanine aminotransferase (ALT) level. Units of blood that were positive for antibody to hepatitis B core antigen (anti-HBc) were associated with a twofold to threefold greater risk of non-A, non-B hepatitis in the recipients than were units without anti-HBc. In the absence of specific serologic tests for non-A, non-B agents, screening of donors for anti-HBc might be considered. Our data suggest that the incidence of non-A, non-B hepatitis might have been reduced by about one third by such screening. However, elevated ALT levels in donors had a similar association with non-A, non-B hepatitis in recipients but would have resulted in fewer units of blood being discarded than would screening for anti-HBc.

Hepatitis B vaccine in medical staff of hemodialysis units: efficacy and subtype cross-protection.

We evaluated the efficacy of hepatitis B vaccine (Heptavax-B) containing only the ad subtype in a randomized, placebo-controlled, double-blind trial among 865 staff members of 43 hemodialysis units in the United States. Surface antibody developed in 92.6 per cent of the subjects after two doses of vaccine and in 96 per cent after the six-month booster. The incidence of infections with hepatitis B virus (with or without hepatitis) was 9.9 per cent in placebo recipients and 2.2 per cent in vaccine recipients (P less than 0.01). The two cases of hepatitis B among vaccine recipients did not occur in subjects in whom antibody had developed. In 81 per cent of the hepatitis events, the virus was of the ay subtype. The indicence of ay virus was 8.2 per cent among placebo recipients and 1.2 per cent among vaccine recipients (P less than 0.005). We conclude that these data confirm the efficacy of the vaccine and demonstrate subtype cross-protection.

On the Role of Sexual Behavior in the Spread of Hepatitis B Infection

There is a significant excess of serologic evidence of hepatitis type B infection in two high-promiscuity populations: patients with venereal diseases and their unrelated sexual contacts (15% to 18%) and male, but not female, homosexuals (37% to 51%). Spouses of asymptomatic chronic carriers of antigen had a higher prevalence (26% to 28%) than spouses of noncarriers (10% to 11%); however, the prevalence in the former is relatively low when compared with rates seen in other relatives of carriers. Persons who had a higher-than-average probability of exposure to potentially infective partners or whose patterns of sexual behavior made such exposure more likely (large numbers of sexual partners, long duration of homosexuality, involvement in predominantly anal intercourse) were found to have serologic evidence of hepatitis B more frequently than those with other patterns of sexual behavior. This study showed a strong association between serologic evidence of type B hepatitis and patterns of sexual behavior. However, whether or not transmission of hepatitis type B virus occurs through vaginal intercourse could not be ascertained.

Distribution of Antibody to Hepatitis A Antigen in Urban Adult Populations

To investigate the prevalence and distribution of antibody to hepatitis A antigen we tested 947 randomly selected people in the Greater New York City area; 45 per cent were antigen positive, as determined by the immune adherence method. Antibody was detected two to three times more frequently in lower social classes (72 to 80 per cent) than in middle and upper-middle classes (18 to 30 per cent). The rate of antibody detection was strongly correlated with age; the prevalence gradually increased throughout adulthood and reached its peak level in people 50 years of age and older. Those with serologic evidence of past exposure to hepatitis B virus were significantly more often antibody positive than those without such evidence (61 vs. 40 per cent; P less than 0.001). Very few of the positive subjects had had hepatitis. The prevalence of this antibody varies among different population groups, increases with age, decreases with rise in socioeconomic status, is independent on sex and race, and correlates with serologic evidence of hepatitis B virus infections.

HEPATITIS B IMMUNE GLOBULIN (HBIG) EFFICACY IN THE INTERRUPTION OF PERINATAL TRANSMISSION OF HEPATITIS B VIRUS CARRIER STATE: Initial Report of a Randomised Double-Blind Placebo-Controlled Trial

Abstract A randomised double-blind placebo-controlled efficacy trial of hepatitis B immune globulin (HBIG) for prevention of the vertically transmitted HBsAg carrier state was conducted in Taiwan where the carrier rate in the general population is 15-20%. HBIG was given immediately after birth to infants of e antigen positive HBsAg carrier mothers and all infants were followed for 15 months or more. Among 35 placebo-treated infants the carrier rate was 91%. This compares with the carrier rate of only 23% among 40 infants who received 0·5 ml HBIG at birth, three months, and six months and the 45% carrier rate among 42 infants receiving a single 10 ml dose of HBIG at birth only. Efficacy was 75% and 45% respectively for the two treatment schedules. Significantly, the most common response of HBIG-treated infants was passive-active immunisation.

Familial clustering of hepatitis B infection.

Abstract In a survey among 449 family contacts of blood donors from 197 households containing carriers of hepatitis B antigen, 6.7 per cent were antigen positive, as compared with 0.8 per cent in control households. The greatest prevalence of B antigen was among siblings (19.7 per cent) and other genetic family contacts (8 per cent). In spouses B antigen was less frequently detected (3.4 per cent). Hepatitis B antibody was detected three times more frequently in the study households than in control households. No differences in prevalence of hepatitis B antibody between specific relatives of antigen carriers were seen. Familial clustering does not appear to be correlated with the presence or absence of liver damage in the asymptomatic donor carrier. Neither venereal nor Maternal-Fetal transmission seems to be of primary importance in the spread of hepatitis B infections in these surveyed families. The evidence supports the hypothesis that hepatitis B virus can be transmitted nonparenterally. (N Engl J Med...

Non-A, non-B hepatitis transmission in chimpanzees: a project of the Transfusion-transmitted Viruses Study Group.

Experimental transmission of non-A, non-B hepatitis was apparently accomplished in 5 chimpanzees following inoculation with presumably infectious human sera. Administration of sera from implicated donors with normal alanine aminotransferase (ALT) values, as well as from those with abnormal ALT levels, resulted in the development of ALT abnormalities in the inoculated chimpanzees. Transmission from donors with normal ALT values implies that healthy carriers of non-A, non-B virus exist. Evidence is presented which indicates that a period of viremia precedes the clinical illness by at least 12 days.