A vaccine against hepatitis A--at last.
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Biomedical subjects
Publications and source records attributed to I D Gust.
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The prevalence of infection with human T lymphotropic virus type I (HTLV-I) in 19,975 blood samples from Australia and the western Pacific was determined by measuring the presence of specific antibody (anti-HTLV-I) by enzyme-linked immunosorbent assay (ELISA) with confirmation by western blot and/or radioimmunoprecipitation techniques. In Australia no evidence of HTLV-I infection was found in injecting drug users, patients with the acquired immunodeficiency syndrome (AIDS), subjects attending a sexually transmitted diseases clinic, female prostitutes, or transfusion recipients. A low prevalence of infection was detected in people with haemophilia (0.5%) and in male homosexuals (0.5%-1%). No antibody was detected in sera from Vanuatu, Kiribati, American Samoa, the Cook Islands, New Caledonia, the Federated States of Micronesia, French Polynesia and Fiji, but a low frequency of anti-HTLV-I was detected in sera from the Solomon Islands (1.2%) and Nauru (0.6%).
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OBJECTIVE: To elucidate the seroepidemiology of hepatitis C in patients with clotting disorders in comparison with other blood borne infections; to examine the effects of hepatitis C on liver function; and to assess the effectiveness of current screening and inactivation procedures used in preventing the transmission of blood borne viruses by clotting factor preparations. DESIGN: A retrospective analysis of the prevalence of antibodies to hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV) by means of commercially available enzyme immunoassays (for antibodies to HCV and HIV) or radioimmunoassays (for HBV antibodies and surface antigen). An analysis was made of serum transaminase levels where such information was available and this was correlated with HCV status. PATIENTS AND SETTING: Panels of sera were collected from adults and children with clotting disorders attending two Melbourne haemophilia treatment centres in 1973 (n = 33), 1980 (n = 33), 1984-1985 (n = 111) and 1987-1990 (n = 217) and tested for antibodies to HCV, HBV and HIV. RESULTS: The prevalence of antibodies to HCV in the four panels tested was 45%, 74%, 75% and 76%, and the prevalence of markers of infection with HBV was 66%, 74%, 62% and 65% respectively. No antibodies to HIV were found in sera in Panels I and II but the prevalence in Panels III and IV was 23% and 36% respectively. In subjects in whom liver function test results were available, there was a significant association between the presence of antibodies to HCV and raised transaminase levels. Since heat inactivation of clotting factors was commenced in Australia in 1984, no new cases of transmission of HIV by clotting factors has been detected, but transmission of HCV in 19 subjects and HBV in one subject could not be excluded. CONCLUSIONS: Hepatitis C infection in haemophiliacs has been a very frequent event, and the presence of antibodies to HCV is associated with an increased incidence of raised transaminase levels. Screening and heat inactivation of clotting factors has prevented further HIV transmission, but exposure to HBV and HCV has not been eliminated.
OBJECTIVE: To determine the relationship between the development of hepatitis C antibody (anti-HCV) and the clinical symptoms in acute hepatitis C. DESIGN: Retrospective analysis of sera from patients with acute non-A non-B hepatitis. SETTING AND PATIENTS: Patients admitted to Fairfield Hospital with the diagnosis of acute non-A non-B hepatitis between 1979 and 1989. Inclusion criteria included a typical clinical illness, accompanied by an alanine aminotransferase level of more than 2.5 times the upper limit of normal (normal, less than or equal to 40 U/L) and negative serological test results for acute hepatitis A and B. MAIN OUTCOME MEASURE: Time to develop anti-HCV after the onset of symptoms in patients with acute hepatitis C. RESULTS: Seroconversion was demonstrated in 26 of the 128 patients who fulfilled the inclusion criteria. In these patients, antibody was detected between one week and 32 weeks after the onset of dark urine; more than half the patients (54%) had seroconverted by four weeks and a third (34%) developed antibodies within two weeks. Of 20 patients who had sera collected within four weeks of the onset of dark urine, 14 (70%) had developed antibody. CONCLUSION: These results suggest that in patients with community-acquired hepatitis C, seroconversion occurs significantly earlier than is observed in patients who have been infected by blood transfusion. Sera taken shortly after the onset of symptomatic hepatitis C may be useful in the diagnosis of this condition.
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Serological surveys in many communities show a high prevalence of antibodies to hepatitis A virus (HAV) in people over the age of 50 years. However, few of that age can recall a previous episode of hepatitis, indicating that subclinical infections are common. The outcome of infection with HAV depends on the age at which infection occurs and, perhaps, the infectious dose. Fulminant disease is well recorded, with the frequency varying from one to eight per 1000 cases. Information on the frequency of hepatitis A can be obtained by analysing hospital records and notifications to health authorities or by serological surveys. In many countries, these data are limited and seriously underestimate the true frequency of the disease. At a conservative estimate, the incidence of disease in most developed countries is probably four to five times higher than the number of notifications. HAV appears to circulate in most parts of the world and to be responsible for both epidemic and sporadic disease. Three major patterns of infection are known which reflect different epidemiological situations. These are demonstrated by different patterns of the age-specific prevalence of antibodies to HAV which reflect standards of hygiene and sanitation, the degree of crowding of the population and opportunities for the virus to survive and spread.
The prevalence of antibodies to hepatitis C virus (anti-HCV) was measured in a number of groups known to be at increased risk of blood-borne viral infections, using an enzyme-linked immunosorbent assay (EIA) based on a nonstructural peptide generated by recombinant DNA technology. The assay was repeatably reactive in 75.6% of men with haemophilia, 61.9% of intravenous drug users, 34.1% of homosexual men who were regular attenders at a gay sauna and 30.8% of prisoners. A lower reactivity was detected in sera collected from female prostitutes (10.4%), patients undergoing maintenance haemodialysis (5.9%), or renal transplantation (6.9%) and patients attending a sexually transmitted diseases clinic (6.2%). We also measured reactivity among inmates of a large institution for the mentally handicapped in which hepatitis B is known to be endemic, and in panels of sera which had been stored for 25-35 years. The test was positive in 41.1% of mentally handicapped patients with Down's syndrome and 7% of subjects with other forms of mental retardation. Similarly some 23% and 20% of sera collected in 1954 and 1964 from patients with a variety of illnesses were found to be reactive. As most diagnostic assays suffer from some degree of non-specificity and confirmatory tests for the anti-HCV assay were not initially available in Australia, we analysed the distribution of optical density (OD) values in the different groups, in an attempt to obtain an insight into the specificity of the results being obtained. Whereas the ODs of sera collected from patients with haemophilia and IVDU had a bimodal pattern, with two well separated sets of results on either side of the cut-off.(ABSTRACT TRUNCATED AT 250 WORDS)
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To determine whether active viral replication is associated with increased morbidity and mortality in chronic carriers of hepatitis B virus (HBV) undergoing renal transplantation, we reviewed 23 years of experience at our hospital. Over the period 1966-1989, 42 chronic carriers of hepatitis B surface antigen (HBsAg) received renal transplants, 32 of whom had functioning grafts for 12 months or longer. Stored sera were tested for markers of hepatitis B virus, hepatitis C virus (HCV), and hepatitis delta virus (HDV) infection, and the serologic findings were correlated with clinical and biochemical data. The presence of HBV DNA and/or hepatitis Be antigen (HBeAg) in serum samples collected prior to transplantation was associated with an increased probability of death from liver disease. Whereas 5 of 10 patients in this group died of chronic liver disease, only 1 of 15 patients who were HBV DNA and/or HBeAg negative prior to transplantation died of liver disease. This difference is highly significant (P less than 0.02). No difference in outcome was attributable to age at transplantation, gender, country of birth, or the presence of abnormal hepatic transaminase levels prior to transplantation.
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To determine whether saliva is a potentially useful sample for screening for HIV infection when serum is not obtainable, saliva and serum samples from 50 HIV-infected and 50 uninfected subjects were tested for antibody to HIV-1 (anti-HIV-1) using a second-generation enzyme-linked immunosorbent assay (ELISA; Abbott) and prototype antibody-capture ELISA (Wellcome). Of saliva specimens from HIV-infected people, six gave negative results on the Abbott and one on the Wellcome assays; all specimens from uninfected people were negative by both assays. Sensitivity for the Abbott assay was therefore 88.0% [95% confidence interval (Cl) 76.2-94.4%], an unacceptable level for screening purposes. Sensitivity for the Wellcome assay was 98% (95% Cl 89.5-99.6%), a more satisfactory level for population screening. Further validation of this technique is necessary, and of methods for collection of saliva specimens in particular.
Parenterally transmitted non-A, non-B (NANB) hepatitis virus or hepatitis C virus is a common cause of both acute and chronic hepatitis. Using a recently developed enzyme-linked immunosorbent assay we looked at the prevalence of antibodies to hepatis C virus (anti-HCV) in a number of groups. People with haemophilia (75.6%) and intravenous drug users (61.9%) had the highest prevalence, while homosexual men attending a sauna (34.1%) and prisoners (30.8%) had a moderately high prevalence of anti-HCV. A lower prevalence of antibody was detected in female prostitutes (10.4%), institutionalised mentally retarded subjects (9.5%), homosexual men requesting human immunodeficiency virus (HIV) testing through their local doctor (8.8%), dialysis patients (5.9%), renal transplant patients (6.9%), and patients referred from a sexually transmitted diseases clinic (6.2%). The lowest prevalence of anti-HCV was recorded in women attending a provincial hospital for antenatal care (0.4%). The predominance of anti-HCV in groups of people exposed to blood-borne and sexually transmitted infections suggests that these routes may be primarily involved in the spread of hepatitis C virus infection.
There is an urgent need for new, powerful adjuvants suitable for use with sub-unit and peptide vaccines in humans. We have measured the humoral immune response in BALB/c mice to vaccine formulations using recombinant HBsAg antigens, and gamma inulin and alum adjuvants. Using Merck, Sharpe & Dohme (MSD) HBsAg at 10 micrograms/mL, high levels of anti-HBs were generated and geometric mean S/N ratios of 88, 133 and 107 were obtained for alum absorbed vaccine, gamma inulin, and a mixture of the two adjuvants, respectively. A dilution series produced ED50 values of 0.08, 0.15 and 0.22 micrograms/mL respectively. In a second series of experiments comparing alum and algamulin (a complex of gamma inulin and alum), MSD HBsAg induced anti-HBs levels of 81 and 52, and ED50 values of 0.3 and 0.4 when used in conjunction with alum and algamulin, respectively. SKF HBsAg induced anti-HBs levels of 126 and 111 with alum and algamulin, and ED50 values of 0.11 and 0.075. The class, subclass and level of antibody produced in mice boosted with a second dose of vaccine at 21 days was also examined. Both alum and gamma inulin induced higher levels of total antibody, IgG1 and minor IgG subclasses than algamulin, or HBsAg alone. Overall, gamma inulin appears to be an equivalent adjuvant to alum, although their mechanisms of action are different. Mixtures or complexes of the two adjuvants appear to be less effective in inducing humoral immune responses in mice than either alone.
Acyclovir (ACV)-resistant herpes simplex virus type 2 (HSV-2) was isolated from a patient with acquired immunodeficiency syndrome after long-term but intermittent ACV therapy. These thymidine kinase-defective isolates were sensitive in vitro to foscarnet. While combined therapy with ACV and interferon produced only partial clinical improvement, the in vitro effect of this combination against an ACV-resistant isolate from the patient was strongly synergistic. A short course (10-12 days) of intravenous foscarnet controlled severe ulceration, and clinical improvement lasted 6 months. After recurrence and further courses of foscarnet, however, the patient responded poorly, and subsequent HSV isolates were resistant to both ACV and foscarnet and hypersensitive to aphidicolin.
Hepatitis A is a major public health problem in many rapidly developing countries and it is still an important disease in many developed countries. Isolation of the virus in cell culture and access to reliable animal models has led to the development of several candidate vaccines. Both inactivated and attenuated vaccines have been developed which appear to be safe, antigenic and protective in laboratory animals. If studies in man support the data which have been obtained in other primates, the first commercially available vaccines are likely to be licensed within the next two years.