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Biomedical subjects

H S Margolis

Publications and source records attributed to H S Margolis.

At least 19 recordsLinked to original sources

Duration of viremia in hepatitis A virus infection.

The duration of viremia and time course for development of IgM antibodies were determined prospectively in natural and experimental hepatitis A virus (HAV) infection. Serial serum samples from HAV-infected men (n=13) and experimentally infected chimpanzees (n=5) were examined by nested reverse-transcriptase polymerase chain reaction analysis to detect HAV RNA and by ELISA to detect IgM antibodies to HAV. Among infected humans, HAV RNA was detected an average of 17 days before the alanine aminotransferase peak, and viremia persisted for an average of 79 days after the liver enzyme peak. The average duration of viremia was 95 days (range, 36-391 days). Results were similar in chimpanzees. In addition, HAV RNA was detected in serum of humans and chimpanzees several days before IgM antibodies to HAV were detected. These results indicate that adults with HAV infection are viremic for as long as 30 days before the onset of symptoms and that the duration of viremia may be longer than previously described.

Animals↗

Identification of hepatitis B virus indigenous to chimpanzees.

Hepatitis B viruses (HBV) and related viruses, classified in the Hepadnaviridae family, are found in a wide variety of mammals and birds. Although the chimpanzee has been the primary experimental model of HBV infection, this species has not been considered a natural host for the virus. Retrospective analysis of 13 predominantly wild-caught chimpanzees with chronic HBV infection identified a unique chimpanzee HBV strain in 11 animals. Nucleotide and derived amino acid analysis of the complete HBV genome and the gene coding for the hepatitis B surface antigen (S gene) identified sequence patterns that could be used to reliably identify chimpanzee HBV. This analysis indicated that chimpanzee HBV is distinct from known human HBV genotypes and is closely related to HBVs previously isolated from a chimpanzee, gibbons, gorillas, and orangutans.

Amino Acid Sequence↗

The cost-effectiveness of adolescent hepatitis A vaccination in states with the highest disease rates.

BACKGROUND: The Advisory Committee on Immunization Practices has recommended routine childhood hepatitis A vaccination in states and communities where the incidence of disease exceeds the national average, but most adolescents are currently unprotected from infection. OBJECTIVE: To estimate clinical and economic consequences of vaccinating adolescents against hepatitis A in the 10 states with the highest disease rates. DESIGN: Decision analysis was used to assess cost-effectiveness from societal and health system perspectives. Parameter estimates were obtained from national surveillance data, a study of hepatitis A cases, and an expert panel. MAIN OUTCOME MEASURES: Reduction in disease incidence; costs of vaccination, treatment, and work loss; years of life saved (YOLS); and costs per YOLS. RESULTS: In states with the highest disease rates, vaccination of adolescents against hepatitis A would reduce the lifetime risk of symptomatic infection from 3.3% to 0.7% and prevent loss of 2117 years of life. Vaccination of a single birth cohort would cost $30.9 million, yet treatment and work loss costs would decline $14.2 million and $23.8 million, respectively. Hepatitis A vaccination would cost the health system $7902 per YOLS or $13,722 per discounted YOLS. Results are most sensitive to variation in the discount rate and assumptions regarding long-term vaccine protective efficacy. CONCLUSIONS: Hepatitis A vaccination of adolescents in states with high disease rates would reduce costs to society. Although health system costs would increase, cost-effectiveness is comparable to other recommended vaccines and superior to many commonly used medical interventions. Arch Pediatr Adolesc Med. 2000;154:763-770

Adolescent↗

The past incidence of hepatitis C virus infection: implications for the future burden of chronic liver disease in the United States.

Because chronic liver disease may develop many years after acute hepatitis C virus (HCV) infection, the past incidence of acute infections is a major determinant of the future burden of HCV-associated complications. We estimated past incidence of acute HCV infection using national seroprevalence data and relative age-specific incidence data from a sentinel counties surveillance system. Projections of the future prevalence of HCV-infected patients were derived from models that included an 85% drop in HCV infection incidence as observed for reported cases in the early 1990s. The models showed a large increase in the incidence of HCV infections from the late 1960s to the early 1980s. The degree of increase was dependent on the assumed rate of antibody loss; a model with 2.5% annual antibody loss showed annual incidence increasing from 45,000 infections (95% confidence interval [95% CI]: 0-110,000) in the early 1960s to 380,000 infections (95% CI: 250,000 to 500, 000) in the 1980s. Projections showed that although the prevalence of HCV infection may be declining currently because of the decline in incidence in the 1990s, the number of persons infected for >/=20 years could increase substantially before peaking in 2015. If the incidence of new HCV infections does not increase in the future, persons born between 1940 and 1965 will be at highest lifetime risk of acquiring the infection.

Adolescent↗

Evaluation of office-based intervention to improve prevention counseling for patients at risk for sexually acquired hepatitis B virus infection. Hepatitis B-WARE Study Group.

The aim of this study was to determine the effectiveness of tools to identify and counsel patients at risk for sexually transmitted hepatitis B virus infection. Physicians were randomly assigned to either an intervention group or a control group. The intervention group was provided with materials intended to encourage patients to return for counseling and to guide counseling concerning prevention of hepatitis B virus infection. Baseline data on 457 patients at risk for hepatitis B virus infection showed that 7% had received prevention counseling and 2% had begun hepatitis B vaccination. Counseling was least likely to occur in obstetric-gynecologic practices, among uninsured patients, and among patients whose only risk factor was a diagnosis of a sexually transmitted disease. After a 6-month intervention period 26% of the intervention group patients and 7% of the control group patients had been counseled (P <.01). Vaccination was more likely among intervention group patients (8% vs <1%; P <.001). The use of tools to identify and counsel patients at risk for sexually transmitted hepatitis B virus infection resulted in increased office-based prevention activities.

Adolescent↗

Evaluation of the effectiveness of targeted lookback for HCV infection in the United States-interim results.

BACKGROUND: As part of a nationwide program to identify persons at increased risk for HCV infection, persons who received blood from donors who later tested positive for anti-HCV are being directly notified. STUDY DESIGN AND METHODS: In December 1999, all 198 blood collection establishments (BCEs) and 5442 hospital transfusion services (TSs) in the United States were surveyed by mailed questionnaire to evaluate their progress in carrying out this notification. RESULTS: Eighty-one percent of the BCEs and 64 percent of the TSs responded. After correcting for nonresponse, an estimated 98,484 components at potential risk for transmitting HCV, according to previous testing of multiantigen-screened donors, were identified nationwide, of which 85 percent had been transfused to recipients. Lookback for these recipients was completed for 80 percent, of whom 69 percent had died. Of those living, 78 percent were successfully notified. An estimated 49.5 percent of those notified were tested; 18.9 percent of those tested were anti-HCV positive, and 32 percent of that group knew they were positive before notification. On the basis of an 85.5 percent reported completion rate for component notifications back through 1988, an estimated 1520 persons will have been newly identified as anti-HCV-positive when lookback related to multiantigen screening of donors is completed. CONCLUSION: Targeted lookback related to previous multiantigen screening of donors will identify <1 percent of the estimated 300,000 HCV-positive persons in the United States who may have acquired their infection via blood transfusion.

DNA, Viral↗

Elimination of new chronic hepatitis B virus infections: results of the Alaska immunization program.

An immunization assessment and a serologic survey were conducted to evaluate the effectiveness of a hepatitis B immunization program in eliminating hepatitis B virus (HBV) transmission among Alaska Natives in a region in which HBV infection is endemic. Hepatitis B vaccine coverage was 93% among 567 children </=10 years old residing in the study villages, and catch-up vaccine coverage among 582 susceptible persons 11-30 years old was 62%. None of 271 tested children </=10 years old were chronically infected with HBV, and just 4 (1.5%) had evidence of resolved infection. In contrast, 16% of 332 persons 11-30 years old (those born before implementation of routine infant hepatitis B vaccination) were chronically infected. A hepatitis B immunization program that includes prevention of perinatal HBV infection, routine infant vaccination, and catch-up vaccination of older children and adults can eliminate new chronic HBV infections in a population with a high rate of chronic infection.

Adolescent↗

Prevalence of antibody to hepatitis E virus among rodents in the United States.

The recent identification of antibody to hepatitis E virus (HEV) in pigs, sheep, and cattle and characterization of an HEV isolated from domestic pigs suggest animal reservoirs for this virus. To investigate whether rodents might be a natural reservoir of HEV, the prevalence of anti-HEV was determined among a variety of species throughout the United States. Serum samples were obtained from 806 rodents of 26 species in 15 genera. Anti-HEV prevalence was assessed by 2 EIAs (mosaic protein- and 55-kDa protein-based), which gave concordant results. The highest prevalence of antibody was found in the genus Rattus (59.7%; 166/278). Overall, rodents from urban habitats had a significantly higher prevalence of anti-HEV than did animals captured from rural areas. A high prevalence of anti-HEV was found in animals captured on mainland versus barrier islands. The results from this study provide convincing evidence of widespread HEV or HEV-like infection in rodents of the United States.

Animals↗

Genetic relatedness of hepatitis A virus isolates during a community-wide outbreak.

In 1993-94, a community-wide outbreak of hepatitis A occurred in Stanislaus County, California. Stool specimens collected from a sample of 33 case patients were used to evaluate the duration of hepatitis A virus (HAV) excretion and the genetic relatedness of HAV isolates. Twenty-four percent of the patients had a stool sample positive for HAV antigen by enzyme immunoassay, whereas 91% had at least one stool positive for HAV RNA by RT-PCR amplification. Children were found to excrete low levels of HAV RNA for up to 10 weeks after the onset of symptoms. Analysis of the HAV VP1 amino terminus and VP1/P2A regions showed that a limited number of HAV isolates circulated during the epidemic and the majority of the cases were infected with the same strain.

Adolescent↗

The prevalence of hepatitis C virus infection in the United States, 1988 through 1994.

BACKGROUND: Because many persons with chronic hepatitis C virus (HCV) infection are asymptomatic, population-based serologic studies are needed to estimate the prevalence of the infection and to develop and evaluate prevention efforts. METHODS: We performed tests for antibody to HCV (anti-HCV) on serum samples from 21,241 persons six years old or older who participated in the third National Health and Nutrition Examination Survey, conducted during 1988 through 1994. We determined the prevalence of HCV RNA by means of nucleic acid amplification and the genotype by means of sequencing. RESULTS: The overall prevalence of anti-HCV was 1.8 percent, corresponding to an estimated 3.9 million persons nationwide (95 percent confidence interval, 3.1 million to 4.8 million) with HCV infection. Sixty-five percent of the persons with HCV infection were 30 to 49 years old. Seventy-four percent were positive for HCV RNA, indicating that an estimated 2.7 million persons in the United States (95 percent confidence interval, 2.4 million to 3.0 million) were chronically infected, of whom 73.7 percent were infected with genotype 1 (56.7 percent with genotype 1a, and 17.0 percent with genotype 1b). Among subjects 17 to 59 years of age, the strongest factors independently associated with HCV infection were illegal drug use and high-risk sexual behavior. Other factors independently associated with infection included poverty, having had 12 or fewer years of education, and having been divorced or separated. Neither sex nor racial-ethnic group was independently associated with HCV infection. CONCLUSIONS: In the United States, about 2.7 million persons are chronically infected with HCV. People who use illegal drugs or engage in high-risk sexual behavior account for most persons with HCV infection.

Adolescent↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗