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Biomedical subjects

H S Margolis

Publications and source records attributed to H S Margolis.

At least 55 records · Page 3Linked to original sources
PubMed1996

Increased IgM class circulating immune complexes in acute hepatitis A virus infection.

For assessing the role of circulating immune complexes (CIC) in acute hepatitis A, IgM- and IgG-specific CIC were determined, by C1q and conglutinin (K) assays, in 205 patients with acute hepatitis A and 60 healthy controls. The concentration of each type of CIC in patients was higher than healthy controls (P=0.0001). CIC was a common feature of acute hepatitis A with 95.6% of cases having at least one abnormal test result. The prevalence of abnormal IgM class CIC was significantly higher than IgG class CIC. There were significantly inverse correlations between levels of IgM class CIC and interval between onset of symptoms and patient presentation. The prevalence of abnormal IgM CIC was higher in patients with higher alanine aminotransferase (P=0.001) and patients with jaundice (P=0.0002). In conclusion, IgM class CIC is the predominant CIC in acute hepatitis A and correlated with disease activity. CIC may play a role in the pathogenesis of acute hepatitis A.

Acute Disease↗
PubMed1996

Hepatitis B surface antigen- and immunoglobulin-specific circulating immune complexes in acute hepatitis B virus infection.

For assessing the role of circulating immune complexes (CICs) in acute hepatitis B, CICs containing HBsAg, IgM, and IgG were determined, by C1q and conglutinin (K) assays, in 242 patients with acute hepatitis B and 60 healthy controls. CIC is a common feature of acute hepatitis B with 90.9% of cases having at least one abnormal test result. Patients with shorter interval (< 1 week) between onset of symptoms and patient presentation have significantly higher frequency of abnormal IgM class CIC, HBsAg-specific CIC, and higher frequency of raised alanine aminotransferase activity (> 30-fold upper limit of normal). The prevalence of raised alanine aminotransferase in patients with CIC containing HBsAg and IgM is higher than those without (P = 0.001). There is significant association between HBsAg-CIC and C1q-CIC. In conclusion, HBsAg-CIC and IgM class CIC correlate with disease activity. C1q-binding CIC is the predominant CIC that may play a role in the pathogenesis of acute hepatitis B.

Acute Disease↗
PubMed1996

Sequence-specific, single-primer amplification and detection of PCR products for identification of hepatitis viruses.

A simple system to detect polymerase chain reaction (PCR) amplification products was developed. This detection method has the sensitivity and the specificity of nested primer PCR amplification or Southern blot hybridization of PCR product. Digoxigenin-labeled PCR products were hybridized with a biotinylated probe in liquid phase and captured on to microtiter wells coated with antidigoxigenin followed by detection with streptavidin-peroxidase. The sensitivity of this assay for the detection of hepatitis A virus, hepatitis B virus, and hepatitis C virus is equal to that of existing nucleic acid detection systems.

DNA Primers↗
PubMed1996

Safety and immunogenicity of a recombinant hepatitis B vaccine administered to infants at 2, 4 and 6 months of age. The Kaiser-UCLA Vaccine Study Group.

A recombinant hepatitis B vaccine was administered to over 5000 infants in a prospective, randomized and blinded study. Infants were given either recombinant hepatitis B vaccine (Engerix-B, SmithKline Beecham Pharmaceuticals, 10 micrograms dose-1) or a Haemophilus influenzae type b (Hib) conjugate vaccine at 2, 4 and 6 months of age simultaneously with diphtheria-tetanus-pertussis and oral polio vaccines. Adverse reactions were ascertained by parental reports and interviews, and review of medical records. Blood specimens collected from 269 infants given hepatitis B vaccine were assayed for antibody to hepatitis B surface antigen (anti-HBs) by enzyme immunoassay. Infants given hepatitis B vaccine experienced low rates of adverse reactions that were similar or lower than the rates in infants given Hib conjugate vaccine. The geometric mean anti-HBs concentrations were 9.6 mIU ml-1 after one dose, 333 mIU ml-1 after two doses and 1812 mIU ml-1 after three doses (99% had levels > or = 10 mIU ml-1). Antibody responses to diphtheria and tetanus toxoids were unaffected by simultaneous administration of hepatitis B or Hib conjugate vaccine. Engerix-B vaccine was safe and immunogenic when given with other routine childhood immunizations at 2, 4 and 6 months of age, and should provide long-term protection against hepatitis B virus infection.

Antibodies, Bacterial↗
PubMed1996

Comparative safety and immunogenicity of two recombinant hepatitis B vaccines given to infants at two, four and six months of age.

OBJECTIVES: To evaluate the relative safety and immunogenicity of the two recombinant hepatitis B vaccines licensed in the United States with doses recommended for routine immunization of low risk infants and a schedule that corresponds with routine pediatric visits. METHODS: Healthy infants were immunized at 2, 4 and 6 months of age with hepatitis B vaccine manufactured by either SmithKline Beecham (Engerix-B, 10 micrograms/dose, n = 228) or Merck and Co. (Recombivax HB, 2.5 micrograms/dose, n = 200). Adverse reactions were ascertained by parental reports and interviews and by review of medical records. Antibody concentrations to hepatitis B surface antigen (anti-HBs) were measured in sequential serum specimens by enzyme immunoassay. RESULTS: Adverse reactions were mild and the rates were not significantly different between the two groups. After the first and second doses the rates of seropositivity (> or = 10 mIU/ml) and seroprotection (> or = 10 mIU/ml) were significantly higher in infants given SmithKline Beecham vaccine (P < 0.01). After the second and third doses infants given SmithKline Beecham vaccine also had significantly higher geometric mean anti-HBs concentrations compared with those given Merck vaccine (348.0 mIU/ml vs. 66.9 and 1914.8 mIU/ml vs. 514.8 mIU/ml, respectively, P < 0.001). Nevertheless after the third dose 99% of infants in both vaccine groups achieved seroprotective antibody concentrations. CONCLUSIONS: Both recombinant hepatitis B vaccines were safe and immunogenic when administered concurrently with other pediatric vaccines at 2, 4 and 6 months of age, but earlier protective responses were observed with the SmithKline Beecham vaccine than with the Merck vaccine.

Consumer Product Safety↗
PubMed1996

Guidelines for prevention and control of hepatitis A in American Indian and Alaska Native communities.

The Aberdeen Area Indian Health Service, South Dakota Department of Health, and the Centers for Disease Control and Prevention have collaborated since 1985 to investigate hepatitis A in Indian communities in the Northern Plains and to implement clinical trials of hepatitis A vaccine. After licensure of the hepatitis A vaccine in February 1995, community wide immunization programs have been implemented effectively in several communities experiencing hepatitis A outbreaks. The state health department, tribal health departments, Indian Health Service facilities, Head Start programs and schools have provided hepatitis A immunizations to children aged 2-12 years in each of these communities after obtaining parental consent. Culturally-specific educational materials were developed and extensive health education efforts were provided by IHS and tribal programs. Hepatitis A contacts age 2-12 were offered the hepatitis A vaccine at the same time they were offered passive immunization with immune globulin. To date over 70% of parents contacted by letter or in person have returned consent forms to have their children immunized. Higher response rates were obtained in communities where home visits were made to explain this program in more detail. The outbreaks appear to have stopped after 70% or more of the children aged 2-12 years were immunized. Immunization programs are being implemented in all Northern Plains Indian communities utilizing hepatitis. A vaccine from the Vaccine For Children Program. These efforts will likely eliminate hepatitis A as a health problem for Indian communities.

Adolescent↗
PubMed1995

Prevention of hepatitis B virus transmission by immunization. An economic analysis of current recommendations.

OBJECTIVE: To evaluate the outcome of immunization strategies to prevent hepatitis B virus (HBV) transmission. DESIGN AND SETTING: A decision model was used to determine the incremental effects of the following hepatitis B immunization strategies in a birth cohort receiving immunization services in the public sector: (1) prevention of perinatal HBV infection, (2) routine infant vaccination, or (3) routine adolescent vaccination. MAIN OUTCOME MEASURES: Over the lifetime of the cohort, the reduction in infections and medical and work-loss costs of HBV-related liver disease were determined for each strategy and compared with the outcome without immunization. RESULTS: Prevention of perinatal infection and routine infant vaccination would lower the 4.8% lifetime risk of HBV infection by at least 68%, compared with a 45% reduction for adolescent vaccination. From a societal perspective, each strategy was found to be cost saving, but was not cost saving with respect to direct medical costs. The estimated cost per year of life saved was $164 to prevent perinatal HBV infection, $1522 for infant vaccination, and $3730 for adolescent vaccination. CONCLUSIONS: Routine vaccination of infants in successive birth cohorts to prevent HBV transmission is cost-effective over a wide range of assumptions. While economically less attractive than infant vaccination, adolescent vaccination could serve to protect those children who were not vaccinated as infants.

Adolescent↗
PubMed1995

Circulating immune complexes in chronic hepatitis related to hepatitis C and B viruses infection.

Circulating immune complexes (CIC) may be involved in tissue damage and/or viral clearance in viral hepatitis. To assess the frequency of raised CIC in chronic hepatitis related to hepatitis B and C, IgM, IgG, and hepatitis B surface antigen (HBsAg) containing CIC were determined, by conglutinin (K) and C1q assays, in 101 patients with chronic hepatitis B alone, 24 patients with chronic hepatitis B and C, 48 patients with chronic hepatitis C alone, and 54 healthy controls. Compared to patients with hepatitis B alone, patients with dual infection had higher frequency of raised IgM-C1q CIC (P < 0.001) and IgM-K CIC (P < 0.01). There is no difference in the prevalence of HBsAg-CIC between patients with hepatitis B alone and those with dual infection. Among patients with chronic hepatitis C alone, conglutinin-binding CIC is the predominant type of raised CIC and correlated with more severe liver damage. In conclusion, CIC may play a role in the pathogenesis of chronic hepatitis C virus infection.

Adult↗
PubMed1995

Long-term efficacy of active postexposure immunization of infants for prevention of hepatitis B virus infection. United States-People's Republic of China Study Group on Hepatitis B.

Perinatal transmission of hepatitis B virus (HBV) contributes to the high prevalence of chronic infection in China and many other countries. In a placebo-controlled trial among 166 infants, the 12-month efficacy of active postexposure prophylaxis to prevent chronic perinatal HBV infection varied by vaccine (range, 45%-89%). In a 5-year follow-up study, 2 additional infants became chronically infected with HBV, and the efficacy of active prophylaxis was estimated to be 38% and 72% for the two vaccines at 5 years. In addition, 80% of immunized infants continued to have protective levels of antibody at the end of 5 years. However, among 27 infants who received passive-active immunoprophylaxis with high-dose hepatitis B immune globulin, only 60% (11/19) had protective antibody levels. These data indicate that active postexposure immunization initiated soon after birth continues to provide protection during early childhood when there is a high risk of chronic HBV infection.

Chronic Disease↗
PubMed1994

Effect of postexposure vaccination in a chimpanzee model of hepatitis A virus infection.

Passive transfer of antibodies to hepatitis A virus (HAV) in immune globulin (IG) effectively prevents hepatitis A when given after exposure, but does not provide lasting protection from infection. Hepatitis A vaccines have been shown to generate quickly levels of antibody equivalent to those found after IG administration. The effect of hepatitis A vaccine in preventing infection following fecal-oral exposure was evaluated in a chimpanzee model of HAV infection. Two animals were vaccinated 1 and 3 days, respectively following inoculation and two inoculated animals served as unprotected controls. Of the two immunized animals, one had no evidence of HAV infection, while the other had an attenuated infection with no evidence of virus shedding. These results suggest that while postexposure hepatitis A vaccination may be infection permissive, it attenuates disease expression and prevents virus shedding.

Alanine Transaminase↗
PubMed1993

Antibody response to nonstructural proteins of hepatitis A virus following infection.

The nonstructural proteins of hepatitis A virus (HAV), produced during active virus replication, are alternative antigens that could be used to differentiate disease from inactivated vaccine-induced antibodies. An assay based on immune precipitation of proteins translated from transcripts of the P2 region of viral cDNA was used to evaluate the development of antibodies after natural infection or vaccination. Antibodies against P2 proteins were found in all sera from clinical cases of hepatitis A following the acute phase. Chimpanzees vaccinated with inactivated or cell-adapted HAV had no detectable antibodies against P2 products, either before or after wild type virus challenge. A serosurvey of sera positive for total anti-HAV (HAVAB, Abbott Laboratories, North Chicago) suggested that some individuals had no detectable antibodies to the P2 antigen by immune precipitation. These results were attributed to the lower sensitivity of the immunoprecipitation assay, since antibodies to capsid proteins, as measured by immunoprecipitation, were also not detected in most of these sera.

Adult↗
PubMed1993

The sequence of hepatitis E virus isolated directly from a single source during an outbreak in China.

In this study an IgM antibody-mediated antigen-capture procedure for direct extraction of hepatitis E virus (HEV) RNA from clinical specimens was developed and used with an efficient method for generating viral cDNA that was subsequently sequenced using the dideoxy chain termination method. This is the first time the complete HEV genome has been isolated directly from a single human clinical specimen obtained during an outbreak of enterically transmitted non-A, non-B hepatitis. When the Chinese-derived sequence was compared with the original isolate of Burmese HEV from an experimentally infected cynomolgus macaque, the homology between the two sequences was 94% and 98.5% at the nucleotide and amino acid levels, respectively. The methods we developed for generating and sequencing genomic HEV cDNA dramatically improved the efficiency of cloning the viral genome and should be helpful for continued analysis of this virus as well as other RNA viruses that have proven to be difficult to clone and sequence directly.

Base Sequence↗
PubMed1993

Worldwide epidemiology of hepatitis A virus infection.

Patterns of hepatitis A virus (HAV) infection and clinical disease differ worldwide, and correlate with socioeconomic conditions (and hygienic and sanitary conditions) of each geographic area. In least developed countries with very poor sanitary and hygienic conditions, HAV spreads readily, and most persons are infected as young children. Because most persons become infected at an age when HAV infection is often asymptomatic, reported disease rates in these areas are low and outbreaks of disease are rare. In developing countries and some regions of developed countries, sanitary conditions are variable, and transmission can predominate in children, adolescents or adults, depending on the geographic region. Paradoxically, since HAV transmission occurs in these areas in older age groups compared with least developed countries where HAV transmission is highly endemic, reported rates of hepatitis A can be higher. In developed countries, sanitation and hygienic conditions are good, and infection rates in children are generally low. Communitywide epidemics can contribute significantly to the burden of disease, as can occasional day care center and common-source outbreaks. In some areas, disease tends to be among specific risk groups, such as travellers to hepatitis A endemic areas, and intravenous drug users among whom hygienic practices may be poor. As countries develop economically with improvement of sanitary conditions, overall endemicity of HAV infection decreases, and disease patterns may change. As the endemicity of HAV transmission decreases, the reported rate of clinical hepatitis A can increase, due to the shift in the average age of infection to an age when clinical illness is more frequent.

Hepatitis A↗
PubMed1993

Considerations for the development of recommendations for the use of hepatitis A vaccine.

The prevention of hepatitis A virus (HAV) infection should be greatly facilitated with the expected licensure of inactivated hepatitis A vaccines. In countries with a low endemicity of infection a number of high risk groups have been identified in which HAV infection occurs, and include both children and adults. In most other countries HAV infection occurs primarily in children. Thus, selective immunization of high-risk adults or children would not be expected to lower the overall rates of infection in most countries, and the eventual objective should be the integration of hepatitis A vaccine into the routine childhood immunization schedules. This would reduce disease incidence by preventing infections in children and by preventing infections in adults that are acquired from children. The elimination of a population susceptible to HAV infection through immunization could eliminate this well-known human disease, and the epidemiology of HAV infection suggests that eradication could be attainable with effective vaccines.

Hepatitis A Vaccines↗
PubMed1993

Prevention of acute and chronic liver disease through immunization: hepatitis B and beyond.

Liver disease caused by hepatotrophic viruses imposes a substantial burden on health care resources. Persistent infections from hepatitis B virus (HBV), hepatitis C virus, and hepatitis delta virus result in chronic liver disease, while hepatitis A virus and hepatitis E virus produce a self-limited disease. Effective hepatitis B vaccines that provide long-term protection against chronic HBV infection have been available for > 10 years, while inactivated hepatitis A vaccines have recently been shown to prevent acute disease. To prevent transmission of HBV, scientifically and epidemiologically sound recommendations call for vaccination of all infants in successive birth cohorts worldwide. For hepatitis A vaccines, recommendations will be developed in the near future and should reflect vaccine performance and the epidemiology of hepatitis A. A number of policy, health care financing, and educational issues must be addressed to ensure the effective use of both of these vaccines.

Acute Disease↗