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ABSTRACT: One hundred and one of 255 recipients of a plasma-derived hepatitis B vaccine were evaluated in 1990, 9 years after the first vaccine dose in a study in Zambia to evaluate the efficacy of one, two, or three doses. In 1983, 2 years after the first vaccine dose, antibody to the hepatitis B surface antigen (anti-HBs) had been detectable in 90 of these 101 participants (89%). In 1990, anti-HBs was still detectable in 72 of 101 (71%), and was present at a protective level (> or = 10 mIU/mL) in 68 of 101 (67%). Although the original vaccine study elicited a protective level of antibody in a greater percentage of children and adolescents than in adults, there were no significant differences among the three groups at 9 years. (In 1990, anti-HBs was still detectable in 52 of 70 [74%] who had had no serologic markers of the hepatitis B virus in 1981, and a protective level was detected in 47 of 70 [67%].) A protective level of anti-HBs was detected in 1990 in 26 of 36 (72%) recipients of three doses and in 23 of 31 (74%) recipients of two doses; the slightly lower prevalence among recipients of one dose (19 of 34 [56%]) was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Medical Virology 08/1993; 40(3):204-9. · 2.82 Impact Factor
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ABSTRACT: A field trial of a plasma-derived hepatitis B vaccine in five rural villages in Zambia was analyzed to determine if adults in a rural African setting respond to this vaccine as well as adults in Western countries and to determine the immunogenicity of fewer than the recommended three doses; 255 residents, including 171 who were susceptible to hepatitis B, were vaccinated. Among those who received three vaccine doses, protective levels of antibody to hepatitis B surface antigen (anti-HBs) developed in 67% of adults (ages 21 to 70 years), 87% of adolescents (ages 12 to 19 years), and 100% of children (ages 0 to 11 years). The 67% of vaccinated adults who developed anti-HBs at the protective level was lower than the 96% reported among adults receiving the same vaccine at the same dose and dosage schedule in studies in Western countries. No difference was seen in the response of those receiving two doses compared with those receiving three doses among adults and adolescents, suggesting that a two-dose regimen may be acceptable in these age groups in developing countries to reduce costs and improve compliance. Use of hepatitis B vaccine in a region where prevaccination hepatitis B serologic screening was not available did not appear to increase the number of severity of adverse reactions.
Journal of Medical Virology 11/1990; 32(2):134-8. · 2.82 Impact Factor
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JAMA The Journal of the American Medical Association 09/1990; 264(6):691-2. · 30.03 Impact Factor
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ABSTRACT: To study experimentally the protective effect of post-exposure prophylaxis against hepatitis B (HB), a special preparation of hepatitis B immune globulin (HBIG) was injected intravenously (i.v.) into three chimpanzees simultaneously with, or at different time intervals after, intravenous injection of a titred inoculum of hepatitis B virus (HBV). The HBIG was given either simultaneously with the HBV inoculum, at 4 hours after, or at both 4 hours and 4 weeks after the HBV injection. A fourth chimpanzee received a standard preparation of HBIG intramuscularly (i.m.) at both 4 hours and 4 weeks after receiving the HBV injection. A fifth animal received HBIG i.v. 4 hours after the HBV inoculum and at the same time received its first of three HB vaccine injections. All chimpanzees were followed for 1 year. The animals which received HBIG simultaneously with HBV or received HBIG plus vaccine had no serological or biochemical sign of HB during follow-up. The three animals which received HBIG after HBV inoculation all developed HBs-antigenemia and serum aminotransferase (ALT) elevations. HBsAg did however appear in serum several weeks later than expected for the HBV inoculum used. Post-exposure prophylaxis with HBIG did protect the HBV-exposed chimpanzees, only if HBIG was combined with HB-vaccination or if HBIG was given simultaneously with the HBV inoculum.
Journal of Hepatology 10/1989; 9(2):198-203. · 9.26 Impact Factor
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ABSTRACT: To study the effect of postexposure vaccination, four chimpanzees were vaccinated with hepatitis B (HB) vaccine 4, 8, 48, and 72 hr, respectively, after intravenous injection of an infectious hepatitis B virus (HBV) inoculum. The second and third vaccine inoculations were given 2 and 6 weeks later, i.e., at considerably shorter intervals than recommended either for ordinary prophylactic vaccination or for postexposure vaccination in combination with hepatitis B immune globulin (HBIG). The chimpanzees were followed for 1 year. None showed HBs-antigenemia, liver enzyme elevation (ALT), or histopathological alterations in liver biopsies. Late appearance of anti-HBc was observed only in the serum of the animal whose series of vaccination started 72 hr after HBV inoculation. An unvaccinated control chimpanzee, which received the HBV inoculum only, developed clinical hepatitis B with ALT-elevations and HBs-antigenemia within 2 months of the experimental HBV inoculation. These results indicate that postexposure vaccination against hepatitis B begun within 48 hr after HBV exposure, with short intervals between the vaccine injections, can protect against hepatitis B infection also when concomitant HBIG-prophylaxis is not given.
Journal of Medical Virology 09/1988; 25(4):433-9. · 2.82 Impact Factor
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ABSTRACT: A glycoprotein was isolated and purified to homogeneity from the serum of a patient with chronic non-A, non-B hepatitis. NaDodSO4/PAGE of the glycoprotein revealed a single major band at Mr approximately 77,000. Antibodies to this glycoprotein were shown to possess the following immunoreactivity: (i) they reacted by radioimmunoassay with sera obtained at the time of diagnosis from 17 of 42 patients with non-A, non-B hepatitis and with only 2 of 58 sera from either matched controls or patients with hepatitis A or hepatitis B, (ii) they reacted with sucrose gradient fractions from a proven infectious non-A, non-B hepatitis serum at a peak density of 1.14 g/ml and in the soluble protein fractions on top of the gradient, and (iii) they reacted in ELISA with disrupted human T-cell lymphocytotropic virus type III (HTLV-III), and (iv) they reacted in immunoblots with a protein of Mr 74,000 derived from HTLV-III.
Proceedings of the National Academy of Sciences 09/1985; 82(15):4934-8. · 9.68 Impact Factor
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ABSTRACT: A total of 343 sera from Balinese subjects in different age groups and geographic locations were tested by radioimmunoassay (RIA) for serum antibodies to hepatitis B surface antigen (anti-HBs) and hepatitis B core antigen (anti-HBc); most sera were also tested for hepatitis B surface antigen (HBsAg), and for antibody to hepatitis A virus (anti-HAV). One hundred percent of the adult population was found to have anti-HAV, with antibody acquisition beginning in early childhood and reaching a level of 95% by the age of 10 years. Antibodies to hepatitis B virus were also frequent in young children, rapidly peaking to near 80% in older children and adolescents, then declining to a plateau that fluctuated between 40% and 60% throughout adult life. Overall, anti-HBc (49%) was detected slightly more often than anti-HBs (45%), but the relative frequencies of the 2 antibodies varied considerably from group to group. Despite these high antibody prevalences, HBsAg was detected in only 1.5% of the general population, and in no woman of child-bearing age. In utero infection is thus far less likely to account for the early acquisition of antibody to hepatitis B virus than inapparent percutaneous transmission occurring under conditions of close personal contact.
The American journal of tropical medicine and hygiene 06/1985; 34(3):616-9. · 2.59 Impact Factor
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ABSTRACT: Retrovirus-like particles 60-85 nm in diameter were observed in the cytoplasm of hepatocytes in liver biopsies obtained during the acute and chronic phases of non-A, non-B hepatitis (NANBH) in three patients with transfusion-acquired disease. The particles appeared in dilated endoplasmic reticulum cisternae as well as in enlarged Golgi vesicles. No such particles were seen in hepatocytes in liver biopsies similarly obtained during the acute or chronic phases of NANBH from 11 additional patients with NANBH who did not acquire their disease following blood transfusion. Particle-associated reverse transcriptase activity (peak activity at a density of 1.14 gm/ml) was present in the sera of all three "particle-positive" patients and also in 42% of the "particle-negative" patients. The retrovirus-like particles described here were apparently unrelated to the previously described human T cell lymphocytotropic retroviruses (HTLV), since none of the 14 patients studied had antibodies in their serum directed against antigens of any of the three known HTLVs.
Journal of Medical Virology 06/1985; 16(1):37-45. · 2.82 Impact Factor
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ABSTRACT: Two study chimpanzees were inoculated intravenously with approximately 1,000 chimpanzee infectious doses of hepatitis B virus (HBV), one with subtype adr and one with subtype ayw, each previously incubated with 0.1 ml of a murine monoclonal antibody (IgG 1(K) class) directed against a single epitope on hepatitis B surface antigen common to most or all HBV. Two control chimpanzees received identical doses of HBV not incubated with the murine anti-HBs. Neither study chimpanzee developed HBV infection during 12 months of follow-up as judged by normal serum aminotransferase activity, normal liver biopsies, and negative serological tests for HBV-associated antigens and antibodies. In contrast, both control chimpanzees became infected by HBV as evidenced by elevated serum aminotransferase activity, liver biopsy changes characteristic of viral hepatitis, and the appearance of hepatitis B surface antigen (HBsAg) in their sera. Both study chimpanzees were shown to be fully susceptible to infection with these same HBV inocula when challenged 15 months after the initial inoculations at a time when passively administered anti-HBs was no longer detectable. Prior to challenge with HBV, one of the two study chimpanzees received a second injection of the same volume of the murine monoclonal anti-HBs. The survival of this anti-HBs in serum was reduced from six weeks (after the initial injection) to approximately two weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Medical Virology 06/1985; 16(1):89-96. · 2.82 Impact Factor
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ABSTRACT: Although antibody to the hepatitis B surface antigen usually provides protection against hepatitis B virus (HBV) infection, recent reports indicate that this is not always the case. To study the possible role of immune responses to hepatitis B core antigen in immunity to HBV infection, chimpanzees were immunized with chimpanzee liver-derived or genetically cloned hepatitis B core antigen and later challenged with known infectious HBV. Two chimpanzees, which received liver-derived or cloned hepatitis B core antigen in Freund's adjuvant and developed hepatitis B core antibody and low-titer hepatitis B e antibody, were completely protected against HBV infection following challenge. In contrast, another chimpanzee, which received liver-derived hepatitis B core antigen without adjuvant, developed hepatitis B core antibody only in serum and had a subclinical HBV infection when challenged. These findings demonstrate that protection against HBV infection can be induced by immunization with hepatitis B core antigen in adjuvant and that protection, in this case, is not solely dependent on hepatitis B surface antibody. This fact has important implications in our understanding of the biology of HBV infection and in the design of future hepatitis B vaccines.
Gastroenterology 04/1985; 88(3):763-7. · 11.68 Impact Factor
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ABSTRACT: To determine whether horizontal transmission of the hepatitis B virus contributes to the high prevalence of infection with this virus in an endemic region, residents of five villages in Zambia were tested for hepatitis B serologic markers. The prevalence of hepatitis B was determined by testing samples from 620 residents. By examining paired serum samples from 79 children and 80 adults, it was determined that new infections occurred during the five years of this study in at least 14 children (18%) (aged 4-17 years) and ten adults (12%) (aged 23-65 years). These 24 new infections were distributed among 20 households and were not associated with active HBV infections in the mother or, in most cases, other family members. Intervention to prevent hepatitis B in regions such as rural Zambia will require vaccination of susceptible children and adults as well as newborn infants.
Journal of Medical Virology 03/1985; 15(2):113-20. · 2.82 Impact Factor
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ABSTRACT: A human agent of non-A, non-B hepatitis (Inoculum I) was transmitted to chimpanzees and alterations in liver and lymphocytes were studied by electron microscopy and by cytochemical techniques during the acute phase of the disease. Three types of cytoplasmic alterations, consisting of a membraneous and an amorphous part were observed in the hepatocytes. The density of the amorphous constituent decreased after treatment with pronase, but not after treatment with ribonuclease (RNase) or deoxyribonuclease (DNase). The wall of C-III, but not C-II had fibrils with a periodicity the contrast of which markedly increased after pronase treatment. Cytochemical data suggest that the inclusions (C-I-III) represent a cellular reaction to the infectious agent rather than the virus itself. Intranuclear vermicular inclusions (INI) were observed in hepatocytes and lymphocytes as well, mainly in degenerating cells. Tubuloreticular inclusions (TRS) did not appear in circulating lymphocytes during acute infection; however, they could be induced by human alpha interferon treatment in vitro. Increased numbers of lymphocytes with parallel tubular arrays (PTA) were noted at the peak of serum aminotransferase elevations. The latter two alterations (TRS and PTA) most likely represent immunologic reactions of the host to the infectious agent.
Journal of experimental pathology 02/1985; 2(1):25-36.
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The Lancet 02/1985; 1(8419):46. · 38.28 Impact Factor
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ABSTRACT: Particle-associated reverse transcriptase activity was detected in four human serum specimens and in two plasma-derived products, all of which had been shown to transmit non-A, non-B hepatitis (NANBH) to other human beings and/or chimpanzees. Reverse transcriptase activity was also detected in all twelve sera from patients with acute or chronic NANBH. In contrast, reverse transcriptase activity was found in only 2 of 49 serum specimens from healthy plasma donors and laboratory workers. Sucrose density gradient fractions of two of the infectious human sera (peak reverse transcriptase activity at 1.14 g/ml) transmitted NANBH to chimpanzees. Biochemical and enzymatic data indicate that the NANBH agent(s) is a retrovirus or is retrovirus-like.
The Lancet 11/1984; 2(8409):941-3. · 38.28 Impact Factor
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Annals of internal medicine 09/1984; 101(2):277. · 16.73 Impact Factor
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ABSTRACT: 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.
Journal of Medical Virology 02/1984; 13(2):125-30. · 2.82 Impact Factor
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ABSTRACT: Four chimpanzees experimentally infected with an agent of human non-A, non-B hepatitis were studied to determine the sequence of ultrastructural alterations in hepatocytes during infection. Three of the four types of cytoplasmic alterations previously described in association with non-A, non-B hepatitis were observed in the hepatocytes. Sponge-like cytoplasmic inclusions (designated C-I) were detected at or near the time of peak serum aminotransferase elevations in two of the four chimpanzees. Undulating membranes (designated C-II) were observed in all four chimpanzees, at the time of the first elevation of serum aminotransferase levels. Cytoplasmic tubules (designated C-III) were first observed four, eight, and twelve weeks, respectively, after inoculation in three of the chimpanzees. Four weeks after the peak of serum aminotransferase elevations, cytoplasmic alterations could no longer be detected in hepatocytes of the four chimpanzees. Intranuclear inclusions consisting of 20-27 nm granules and vermicular particles were observed in hepatocytes from preinoculation liver biopsy specimens, as well as biopsies obtained during non-A, non-B hepatitis. The number of these particles was greatest near the time of peak elevation of serum aminotransferase levels, however. Tubulo-crystalline inclusions were noted as well in the endothelial cells from both preinoculated and infected chimpanzees. Cytoplasmic alterations in hepatocytes of chimpanzees experimentally infected with an agent of non-A, non-B hepatitis appear characteristic of infection with this agent. In contrast, intranuclear particles were not specifically related to the non-A, non-B hepatitis infection.
Virchows Archiv B Cell Pathology 02/1984; 45(3):301-12.
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The Lancet 02/1984; 1(8369):172. · 38.28 Impact Factor
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ABSTRACT: Both hepatitis B surface antigen (HBsAg) and its antibody (anti-HBs) were found in 13 patients. Nine patients had HBsAg subtype ad, and 7 had anti-HBs monotypic subtype anti-y. Nine patients had HBsAg before detectable levels of anti-HBs were present. Of the 6 patients whose serum contained subtypes of both HBsAg and anti-HBs, 4 had HBsAg before development of the monotypic antibody. All patients have remained positive for HBsAg and anti-HBs (mean duration, 55.5 weeks). Nine patients were positive for HBeAg, and 7 had renal disease. Six of these seven patients are on hemodialysis. Because of the differing subtype specificities of the circulating HBsAg and anti-HBs, we conclude that HBsAg and anti-HBs occur concomitantly. The presence of HBeAg, which indicates infectivity, is common in our study group, suggesting that these patients are a reservoir for transmission of hepatitis-B-virus infection. Therefore, the presence of anti-HBs alone does not indicate a noninfectious serum. Concomitant HBsAg and anti-HBs seems to be particularly common in patients with renal disease who are on hemodialysis.
Annals of internal medicine 11/1983; 99(4):460-3. · 16.73 Impact Factor
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The Lancet 07/1983; 1(8337):1336. · 38.28 Impact Factor
