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Biomedical subjects

H S Margolis

Publications and source records attributed to H S Margolis.

At least 37 records · Page 2Linked to original sources
PubMed1999

Antigenic epitopes of the hepatitis A virus polyprotein.

Forty-two antigenic domains were identified across the hepatitis A virus (HAV) polyprotein by using a set of 237 overlapping 20-mer synthetic peptides spanning the entire HAV polyprotein and a panel of serum samples from acutely HAV-infected patients. The term "antigenic domain" is used in this study to define a protein region spanned with consecutive overlapping immunoreactive peptides. Nineteen antigenic domains were found within the structural proteins, and 22 were found within the nonstructural proteins, with 1 domain spanning the junction of VP1 and P2A proteins. Five of these domains were considered immunodominant, as judged by both the breadth and the strength of their immunoreactivity. One domain is located within the VP2 protein at position 57-90 aa. A second domain, located at position 767-842 aa, contains the C-terminal part of the VP1 protein and the entire P2A protein. A third domain, located at position 1403-1456 aa, comprises the C-terminal part of the P2C protein and the N-terminal half of the P3A protein. The fourth domain, located at position 1500-1519 aa, includes almost the entire P3B, and the last domain, located at position 1719-1764 aa, contains the C-terminal region of the P3C protein and the N-terminal region of the P3D protein. It is interesting to note that four of the five most immunoreactive domains are derived from small HAV proteins and/or encompass protein cleavage sites separating different HAV proteins. The HAV-specific immunoreactivity of each antigenically reactive peptide was confirmed by using seven HAV seroconversion panels. Collectively, these data demonstrate that HAV structural and nonstructural proteins contain antigenic epitopes that can be efficiently modeled with short synthetic peptides.

Amino Acid Sequence↗
PubMed1999

Strategies to prevent and control hepatitis B and C virus infections: a global perspective.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major causes of acute and chronic liver disease worldwide. Chronic infection with these viruses often leads to chronic liver disease, including cirrhosis or primary hepatocellular carcinoma. Both HBV and HCV are bloodborne viruses; however, HBV is transmitted efficiently by both percutaneous and mucosal exposures, and HCV is transmitted predominantly by percutaneous exposures. Because the relative importance of various modes of transmission of these viruses differs by country, the choice of specific prevention and control strategies depends primarily on the epidemiology of infection in a particular country. Comprehensive hepatitis B prevention strategies should include (1) prevention of perinatal HBV transmission, (2) hepatitis B vaccination at critical ages to interrupt transmission and (3) prevention of nosocomial HBV transmission. The prevention of hepatitis C is problematic because a vaccine to prevent HCV infection is not expected to be developed in the foreseeable future. From a global perspective, the greatest impact on the disease burden associated with HCV infection will most likely be achieved by focusing efforts on primary prevention strategies to reduce or eliminate the risk for transmission from nosocomial exposures (e.g. blood transfusion, unsafe injection practices) and high-risk practices (e.g. injecting drug use).

Hepatitis B↗
PubMed1999

A multistate, foodborne outbreak of hepatitis A. National Hepatitis A Investigation Team.

BACKGROUND: We investigated a large, foodborne outbreak of hepatitis A that occurred in February and March 1997 in Michigan and then extended the investigation to determine whether it was related to sporadic cases reported in other states among persons who had consumed frozen strawberries, the food suspected of causing the outbreak. METHODS: The cases of hepatitis A were serologically confirmed. Epidemiologic studies were conducted in the two states with sufficient numbers of cases, Michigan and Maine. Hepatitis A virus RNA detected in clinical specimens was sequenced to determine the relatedness of the virus from outbreak-related cases and other cases. RESULTS: A total of 213 cases of hepatitis A were reported from 23 schools in Michigan and 29 cases from 13 schools in Maine, with the median rate of attack ranging from 0.2 to 14 percent. Hepatitis A was associated with the consumption of frozen strawberries in a case-control study (odds ratio for the disease, 8.3; 95 percent confidence interval, 2.1 to 33) and a cohort study (relative risk of infection, 7.5; 95 percent confidence interval, 1.1 to 53) in Michigan and in a case-control study in Maine (odds ratio for infection, 3.4; 95 percent confidence interval, 1.0 to 14). The genetic sequences of viruses from 126 patients in Michigan and Maine were identical to one another and to those from 5 patients in Wisconsin and 7 patients in Arizona, all of whom attended schools where frozen strawberries from the same processor had been served, and to those in 2 patients from Louisiana, both of whom had consumed commercially prepared products containing frozen strawberries from the same processor. CONCLUSIONS: We describe a large outbreak of hepatitis A in Michigan that was associated with the consumption of frozen strawberries. We found apparently sporadic cases in other states that could be linked to the same source by viral genetic analysis.

Adolescent↗
PubMed1999

Molecular confirmation of hepatitis A virus from well water: epidemiology and public health implications.

An outbreak of hepatitis A in a rural river-island community was found to be associated with consumption of contaminated well water. Specimens from case-patients, the implicated well, and a cesspool suspected to be the source of contamination were all positive for hepatitis A virus (HAV) RNA by immunocapture reverse-transcription polymerase chain reaction. All isolates were identical over about 400 bases from two capsid-encoding regions of the genome, identifying the chain of transmission. Other wells up to 60 m from the cesspool also contained HAV RNA. In addition, HAV RNA was detected in the contamination source well 6 months after the initial contamination, when fecal coliform bacteria were no longer present. These findings demonstrate the utility of viral detection techniques to evaluate contaminated ground water.

Adolescent↗
PubMed1999

Hepatitis B vaccine administered to children and adolescents at yearly intervals.

OBJECTIVE: Hepatitis B vaccines are usually administered on a schedule of 0, 1 to 2, and 6 months. Longer intervals between the second and third doses have been studied, but the effectiveness of hepatitis B vaccine administered at intervals of >2 months between the first and second doses have not been studied. Our objective was to compare the antibody response in recipients of Engerix-B hepatitis B vaccine administered at 12-month intervals to the response to vaccine administered at 0-, 1-, and 6-month intervals. METHODS: A total of 389 children, 5 through 16 years of age, were randomized to receive Engerix-B (10 mg) at a schedule of either 0-, 1-, and 6-month intervals or 0-, 12-, and 24-month intervals. Blood was drawn before and 1 month after the third dose. RESULTS: Immediately before the third dose of vaccine, 92.3% of children who received vaccine on the 0-, 1-, and 6-month schedule and 88.8% of children who received the 0-, 12-, and 24-month schedule had antibody to hepatitis B surface (anti-HBs) antigen concentrations >/=10 mIU/mL. Of the children in the 0-, 1-, and 6-month schedule, 95% received the third dose according to protocol versus 90% of those in the 0-, 12-, 24-month schedule. The geometric mean anti-HBs concentration just before the third dose for recipients of the 0-, 1-, and 6-month schedule (117.9 mIU/mL) was somewhat lower than that for the children who had received vaccine on the 0-, 12-, and 24-month schedule (162.1 mIU/mL). One month after the third dose, >98% of all children had anti-HBs concentrations >/=10 mIU/mL and high geometric mean antibody concentrations were observed in both groups: 5687 mIU/mL for children on the 0-, 1-, and 6-month schedule and 3159 mIU/mL for children on the 0-, 12-, and 24-month schedule. Body mass index was correlated inversely with final antibody concentration, but age was not a factor after adjustment for body mass index. DISCUSSION: Engerix-B administered on a 0-, 12-, and 24-month schedule is highly immunogenic. Providers should consider this alternate immunization schedule for children who are at low risk of immediate exposure to hepatitis B infections.

Acute Disease↗
PubMed1999

Prevalence of hepatitis B virus infection in the United States: the National Health and Nutrition Examination Surveys, 1976 through 1994.

OBJECTIVE: Data from 2 National Health and Nutrition Examination Surveys (NHANES), NHANES II (1976-1980) and NHANES III (1988-1994), were analyzed to examine trends in the prevalence of hepatitis B infection in the United States. METHODS: Serum specimens were tested for markers of hepatitis B virus infection, and risk factors were determined from questionnaires. RESULTS: The overall age-adjusted prevalence of hepatitis B virus infection was 5.5% (95% confidence interval [CI] = 4.8, 6.2) in NHANES II, as compared with 4.9% (95% CI = 4.3, 5.6) in NHANES III. In both surveys, Black participants had the highest prevalence of infection (NHANES II, 15.8%; NHANES III, 11.9%). No differences in infection were found in the major racial groups between surveys, except for a decrease among those older than 50 years. Black race, increasing number of lifetime sexual partners, and foreign birth had the strongest independent associations with hepatitis B virus infection. CONCLUSIONS: Testing of participants in 2 national surveys demonstrates no significant decrease in hepatitis B virus infection, despite the availability of hepatitis B vaccine.

Adolescent↗
PubMed1998

Immunoglobulin- and hepatitis B surface antigen-specific circulating immune complexes in chronic hepatitis B virus infection.

For assessing the role of circulating immune complexes (CIC) in chronic hepatitis B virus (HBV) infection, CICs containing IgM, IgG, and HBsAg were determined by C1q and conglutinin (K) assays in 216 patients with chronic HBV infection and 54 healthy controls. The concentration of each type of CIC in patients is higher than in controls (P = 0.0001). CIC is a common feature of chronic HBV infection with 95.8% of cases having at least one abnormal test result. At least one type of HBsAg-CIC is positive in 54.2% of patients. HBsAg-CIC positivity is associated with HBeAg positivity (P = 0.0001), higher aminotransferase levels (P < 0.002), and younger age (P = 0.001). IgG-CIC or IgM-HBsAg-CIC correlates with higher aminotransferase activity (P = 0.001). In conclusion, HBsAg-CIC correlates with HBV replication. IgG-CIC and/or IgM-HBsAg-CIC correlate with disease activity. Immune-mediated injury may play a role in the pathogenesis of chronic HBV infection.

Adult↗
PubMed1998

Hepatitis B vaccination of adolescent and adult high-risk groups in the United States.

Substantial progress has been made in implementing routine infant hepatitis B vaccination in the United States. However, in 1996, an estimated 65,000 acute hepatitis B cases occurred, the majority of which were among young adults in high-risk groups. Recent surveys have found very low vaccination coverage among several high-risk groups, including men who have sex with men and patients with sexually transmitted diseases (STDs). Targeted vaccination of persons with risk factors for hepatitis B virus (HBV) infection can be provided in a variety of settings including family planning clinics, STD clinics, drug treatment centres, detention centres, jails and prisons. However, vaccination programmes have been infrequently implemented in these settings and the majority of persons with acute hepatitis B cases have had a missed opportunity for vaccination in the past. Thus, in order to accelerate elimination of HBV transmission in the United States, increased efforts are needed to implement effective hepatitis B vaccination programmes targeted to adolescents and adults in high-risk groups.

Adolescent↗
PubMed1998

Progress toward elimination of hepatitis B virus transmission in the United States.

The strategy to eliminate hepatitis B virus (HBV) transmission in the United States is comprised of the following components: (1) preventing perinatal transmission, (2) routine infant vaccination, (3) catch-up vaccination of children in high-risk groups at any age, (4) catch-up vaccination of all children at 11-12 years of age and (5) vaccination of adolescents and adults in high-risk groups. According to recent surveys, > 85% of pregnant women are screened for hepatitis B surface antigen (HBsAg). Of infants born to HBsAg-positive women identified in 1995, 93% received appropriate immunoprophylaxis at birth; however, only 69% were fully vaccinated by 6-8 months of age. From 1991 (when routine infant hepatitis B vaccination was first recommended) to 1996, the proportion of 19-35-month-old children who have received three doses of hepatitis B vaccine has increased from < 10 to 83%. During this time, rates of acute hepatitis B in children 7-10 years of age have declined by 27% and rates among children 3-6 years of age have declined by 62%. Implementation of programmes for catch-up vaccination of all adolescents at 11-12 years of age and for vaccination of adolescents and adults in high-risk groups have only recently begun and no data are available to assess the progress of these programmes. However, 26% (13/50) of states now have laws requiring adolescents to be vaccinated in order to enter school. Current data indicate that substantial progress has been made in implementing a strategy to eliminate HBV transmission in the United States. Future efforts need to be focused on improving complete immunoprophylaxis of infants of HBsAg-positive mothers, increasing vaccine coverage among 11-12 year old children and implementing programmes to vaccine adolescents and adults in high-risk groups.

Adolescent↗
PubMed1998

Hepatitis C.

Hepatitis C virus (HCV) has emerged as a major cause of chronic liver disease worldwide. The widespread endemicity of HCV infection is the result of a combination of factors, including those related to the genetic diversity of the virus and the host response and those related to the specific settings and behaviors that have facilitated transmission. Most people who contract HCV infection become persistently infected, and the mechanism by which persistent infection is established seems to be related to the lack of development of an effective neutralizing immune response. The magnitude of the spread of HCV infection primarily is related to specific risk factors for transmission. The most important human behavior related to the transmission of HCV has been injection drug use, which in many developed countries has been the leading source of HCV infection during the past 20 to 30 years. The recognition of the clinical importance of HCV infection has resulted in a substantial amount of attention and resources rapidly directed toward developing new and improved therapies. The perception, however, of the public health importance of HCV infection is still limited. Despite the knowledge that injection drug use is the major source of HCV infection in the United States, this message has not been included in prevention and treatment programs, and the resources needed to support strong public health programs have yet to be identified.

Antiviral Agents↗
PubMed1998

The diverse patterns of hepatitis A epidemiology in the United States-implications for vaccination strategies.

Hepatitis A is the most frequently reported vaccine-preventable disease in the United States. Hepatitis A incidence and risk factors during 1983-1995 were examined among cases reported to the study's Sentinel Counties: Denver County, Colorado; Pierce County, Washington; Jefferson County, Alabama; and Pinellas County, Florida. Of 4897 serologically confirmed cases, 611 patients (13%) were hospitalized and 9 (0.2%) died. The average incidence was 14.7/100, 000 (range, 0.6-100.7/100,000, depending on county and year). The frequency of reported sources of infection varied by county, but the largest single group overall (52%) did not report a source. During 3-year communitywide outbreaks in Denver (1991-1993) and Pierce (1987-1989) Counties, rates increased 4- and 13-fold, respectively, and increased in all age, racial/ethnic, and risk groups. During communitywide outbreaks, hepatitis A is not limited to specific risk groups; sustained nationwide reductions in incidence are more likely to result from routine childhood vaccination than from targeted vaccination of high-risk groups.

Adolescent↗
PubMed1998

Incidence of hepatitis B virus infection in the United States, 1976-1994: estimates from the National Health and Nutrition Examination Surveys.

Precise estimates of the incidence of hepatitis B virus (HBV) infection are required to assess the impact of immunization and other prevention strategies in the United States. Race- and age-specific prevalence data obtained from the second and third National Health and Nutrition Examination Surveys (NHANES II, 1976-1980, and NHANES III, 1988-1994) were used to estimate the annual incidence of HBV infection by catalytic modeling. During the period covered by NHANES II, an estimated 323,462 persons were infected annually, and 334,863 were infected annually during the period covered by NHANES III. No statistically significant declines in prevalence of HBV infection occurred between the two surveys, a period during which hepatitis B vaccination targeted only limited numbers of high-risk adults.

Adolescent↗
PubMed1997

Acute non-A-E hepatitis in the United States and the role of hepatitis G virus infection. Sentinel Counties Viral Hepatitis Study Team.

BACKGROUND: Little is known about the relation of the newly discovered hepatitis G virus (HGV) to the cause and clinical course of acute and chronic viral hepatitis. METHODS: We selected patients from a surveillance study of acute viral hepatitis in four U.S. counties who had acute disease during 1985 to 1986 or 1991 to 1995. Serum samples were tested for HGV RNA by the polymerase chain reaction. RESULTS: HGV RNA was detected in 4 of 45 patients with a diagnosis of non-A-E hepatitis (9 percent), 23 of 116 patients with hepatitis C (20 percent), 25 of 100 patients with hepatitis A (25 percent), and 32 of 100 patients with hepatitis B (32 percent) (P<0.05 for the comparison of hepatitis B with hepatitis non-A-E or C). The clinical characteristics of the acute illness were similar for patients with HGV alone and those with hepatitis A, B, or C with or without HGV infection. During a follow-up period of one to nine years, chronic hepatitis did not develop in any of the patients with HGV alone, but 75 percent were persistently positive for HGV RNA, as were 87 percent of those with both hepatitis C and HGV infection. The rates of chronic hepatitis were similar in patients with hepatitis C alone (60 percent) and those with both hepatitis C and HGV infection (61 percent). CONCLUSIONS: The evidence from this surveillance study does not implicate HGV as an etiologic agent of non-A-E hepatitis. Persistent infection with HGV was common, but it did not lead to chronic disease and did not affect the clinical course in patients with hepatitis A, B, or C.

Acute Disease↗
PubMed1997

Detection of hepatitis A virus RNA in oyster meat.

Detection of low concentrations of viruses in shellfish is possible with nucleic acid amplification by PCR. Hepatitis A virus (HAV) has been detected in oyster meat by reverse transcription-PCR (RT-PCR). We developed a method to identify HAV RNA by RT-PCR of total RNA extracted from oyster meat contaminated by adsorption, bioaccumulation, or injection. With dot blot hybridization detection of amplicons from the RT-PCR, rapid screening of a large number of samples is feasible. As few as 8 PFU of HAV/g of oyster meat can be detected.

Animals↗
PubMed1996

IgM and IgG antibodies to hepatitis E virus (HEV) detected by an enzyme immunoassay based on an HEV-specific artificial recombinant mosaic protein.

To develop an enzyme immunoassay (EIA) for IgM antibody to hepatitis E virus (HEV) (IgM anti-HEV) and IgG antibody to HEV (IgG anti-HEV), a synthetic gene encoding several liner immunodominant antigenic epitopes from HEV structural proteins was assembled as a chimeric recombinant mosaic protein (Mpr) with glutathione S-transferase and used as an immunodiagnostic target. In addition, a neutralization confirmation test was developed using individual synthetic peptides. Among 614 patients with acute hepatitis from 10 geographically distinct outbreaks, IgG anti-HEV was found in 546 (88.9%), with a range of 77-100% depending on the outbreak. Of 130 patients tested for IgM anti-HEV, 126 (96.9%) were positive. Among patients tested within 4 months of onset of jaundice, 37/37 (100%) were IgG anti-HEV positive. For patients from whom sera were collected 1-16 days after onset of jaundice, the geometric mean IgG titer (GMT) was 1:47,000; the GMT increased to 1:70,710 30-40 days after onset of jaundice and decreased to 1:1,778 3-4 months after the onset of jaundice. For patients tested 6-8 months after onset of jaundice, 11/12 (92%) were IgG anti-HEV positive, and the GMT was 1:2,908. IgM anti-HEV was detected in 43/43 (100%) sera collected 1-40 days after onset of jaundice, and the GMT for IgM anti-HEV was 1:10,000 at that time. For sera collected 3-4 and 6-12 months after onset of jaundice, 7/14 (50%) and 5/12 (40%) respectively, were IgM anti-HEV positive. In conclusion, an artificial mosaic protein composed of linear antigenic epitopes from open reading frame 2 (ORF2) and ORF3 of HEV has been successfully applied to the development of a sensitive and specific EIA for the detection of IgG and IgM anti-HEV activity. These assays were used for the verification of HEV infection in outbreak settings and for the diagnosis of HEV infection in sporadic cases.

Acute Disease↗