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Biomedical subjects

H S Margolis

Publications and source records attributed to H S Margolis.

At least 73 records · Page 4Linked to original sources

Secular trends in hepatitis A virus infection among Alaska Natives.

To assess the epidemiologic characteristics of the population susceptible to hepatitis A virus (HAV) infection and determine the natural history of infection, a retrospective survey was done using banked serum specimens. A random sample of 4030 Alaska Natives statewide was selected, stratified by year of birth and community of residence. Overall, 1988 serum samples (49.3%) tested positive for antibody to HAV (anti-HAV). Past HAV infection was strongly age-related, increasing from 7% in persons born since 1975 to 85% among persons born before 1945. Prevalence of infection also varied between regions. In small communities, a clear demarcation typically existed between previously infected older persons and younger anti-HAV-negative persons. This indicated that village-wide outbreaks of HAV infection have been the norm and appear to be dependent on the presence of a young susceptible population. Widespread vaccination with hepatitis A vaccine to maintain a high proportion of young anti-HAV-positive persons may be successful in preventing future epidemics.

Alaska↗

Blood exposure and the risk of hepatitis B virus infection in firefighters.

The risk of infection with bloodborne pathogens among public safety workers is not well defined. This survey assessed personal and occupational risk factors among uniformed fire department employees by a self-administered questionnaire and hepatitis B virus (HBV) infection status by serologic testing. Overall, 46 (7.8%) of 592 employees had past or current hepatitis B virus infection. Employees reporting blood contact with skin had been infected more often than employees without this exposure (11% vs 5.8%, prevalence ratio = 1.9, 95% confidence interval, 1.1, 3.3). Prevalence of infection did not differ by age, years on the job, or job duties. The adjusted prevalence of hepatitis B virus infection among male employees (4.5%) was not significantly different than the prevalence in American men (6.8%) (P = .17). Although the overall risk of hepatitis B virus infection is not greater among fire department employees than the general population, blood contact with skin may elevate this risk.

Adult↗

The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team.

BACKGROUND: Chronic liver disease develops in more than half of patients with post-transfusion hepatitis C, but little is known about the natural history of community-acquired hepatitis C. METHODS: In 1985 and 1986 we identified adults with acute non-A, non-B hepatitis in four counties in the United States and followed them prospectively. We used three markers to detect hepatitis C virus (HCV) infection in stored samples of serum: antibody to HCV (anti-HCV) detected by second-generation serologic assays; HCV RNA detected by polymerase-chain-reaction assay; and antibody to HCV antigen (anti-HCVAg) detected by fluorescent-antibody-blocking assay. RESULTS: Of 130 patients with non-A, non-B hepatitis, 106 (82 percent) had HCV infection, 93 were positive for anti-HCV, and 13 were positive only for HCV RNA or anti-HCVAg. Chronic hepatitis developed in 60 (62 percent) of 97 HCV-infected patients followed for 9 to 48 months, with no relation to the risk factors for infection. Ten of the 30 patients who had liver biopsies had chronic active hepatitis. In samples collected 42 to 48 months after the onset of hepatitis, HCV RNA was detected in 12 of 13 tested patients with chronic hepatitis and in all 15 tested patients with hepatitis that had resolved. Anti-HCV persisted in all but two of the initially positive patients, for a rate of antibody loss of 0.6 per 100 person-years. CONCLUSIONS: Patients with community-acquired hepatitis C have a high rate of chronic hepatitis. HCV may be a major cause of chronic liver disease in the United States, and in most patients HCV infection seems to persist for at least several years, even in the absence of active liver disease.

Adolescent↗

Nosocomial transmission of hepatitis B virus associated with the use of a spring-loaded finger-stick device.

BACKGROUND AND METHODS: From June 1989 through March 1990, 26 patients, of whom 23 had diabetes, contracted acute hepatitis B virus (HBV) infection in a hospital in California. All 26 patients and one HBV carrier (also a diabetic) had been admitted to a single medical ward during the six months before the case patients became infected with HBV. To determine the source of the infection, we conducted a retrospective cohort study of the 72 patients with diabetes who had been admitted to the ward from January through December 1989 and a case-control study comparing the 3 nondiabetic patients who contracted hepatitis with 20 nondiabetic controls. RESULTS: The retrospective cohort study of all the patients with diabetes who were admitted to the ward during 1989 found that those who underwent capillary blood sampling by finger stick with a spring-loaded lancet device were more likely to contract HBV infection than those who did not have finger sticks (attack rate, 42 percent vs. 0 percent; P = 0.08). In addition, a dose-response relation was observed between the number of finger sticks received and the frequency of hepatitis B (P = 0.002). The case-control study found that all 3 of the nondiabetic patients who contracted hepatitis underwent finger-stick blood sampling with the device, as compared with none of the 20 nondiabetic controls (P = 0.0006). A review of nursing procedures indicated that the platform of the device was not routinely changed after each use; this finding suggested that contamination of the platform by HBV-infected blood was the mechanism of percutaneous transmission of HBV. CONCLUSIONS: Proper use of finger-stick devices as well as strict adherence to universal precautions to avoid contamination by blood are required to decrease the possibility of transmission of blood-borne pathogens among hospitalized patients.

Acute Disease↗

Prevention of perinatal transmission of the hepatitis B virus. Outcome of infants in a community prevention program.

OBJECTIVE: To assess the outcome of infants born to hepatitis B surface antigen (HBsAg)-positive mothers who received prenatal and infant care in a large, public health care system. DESIGN: Follow-up of a cohort of infants born to HBsAg-positive mothers. SETTING: Large, urban hospital providing prenatal care and obstetric services to county health departments. PARTICIPANTS: Forty-two infants born to HBsAg-positive women. INTERVENTIONS: Prenatal testing of women and immunoprophylaxis of infants with hepatitis B immune globulin at birth and hepatitis B vaccine at birth and ages 1 and 6 months. RESULTS: All 42 infants received hepatitis B immune globulin and the first dose of vaccine. Of forty-one infants (98%) who received the second dose of vaccine, 37 received it by age 4 months. Thirty-two infants (76%) completed the three-dose vaccine series by age 12 months, and 34 infants (81%) completed the series by age 18 months. The rate of completion of the hepatitis B vaccine series was comparable to that of infants receiving the third dose of diphtheria-pertussis-tetanus vaccine. Of 26 infants who completed the hepatitis B vaccine series and had follow-up serologic testing, 24 (92%) had adequate levels of antibody to HBsAg. Only one infant who did not complete the vaccine series had serologic evidence of hepatitis B virus infection. No infant was HBsAg-positive. CONCLUSIONS: Public programs serving urban populations can effectively deliver hepatitis B immunoprophylaxis to infants born to HBsAg-positive mothers.

Adolescent↗

Hepatitis C virus in the etiology of chronic hepatitis and liver cirrhosis: possibility of mixed viral infections due to parenteral transmission.

Sera obtained from 381 patients with chronic liver disease from four cities within the USSR were studied for HBV, HDV, and HCV markers of infection. Anti-HCV activity was detected in 41.2% of non-A, non-B cases. The etiological distribution of chronic hepatitis in Moscow and Dushanbe was similar with an approximate 20% prevalence for HBV, HDV, and HCV infections, whereas in Yakutsk 40% of cases were caused by HDV infections. The etiology of disease remained unrecognized in approximately 40% of patients with chronic liver disease in Moscow and Dushanbe and in 15% in Yakutsk. Anti-HCV activity was detected in 18.8% of patients with chronic HBV infections and in 8.3% of patients with chronic HDV infections. Anti-HCV activity was detected in 41% of patients without markers of HBV or HDV infections. The reasons for the observed differences in HCV prevalence among patients chronically infected with HDV are discussed.

Hepacivirus↗

Serologic identification of hepatitis E virus infections in epidemic and endemic settings.

Recombinant chimeric protein C2 containing the N-terminal region of trpE (37 kilodaltons [kDa]) and the C-terminal half (46.8 kDa) of the polypeptide encoded by ORF2 of the hepatitis E virus (HEV) genome was used for the construction of a Western blot diagnostic test for IgG and IgM antibodies to the virus (anti-HEV). (The C2 protein and the trpE protein devoid of C2 activity and used as a control for non-specific reactions were purified by recovery from sodium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE] and used for preparation of strips). Specificity of the test was proven with sera obtained from patients with acute hepatitis non-A, non-B, non-C (NANBNC) from outbreaks in different geographic regions of the world. IgG antibodies reactive to the recombinant C2 protein were detected in 93% of patients with acute hepatitis NANBNC and remained detectable in 89-100% of these patients 1-24 months after onset of jaundice. IgM antibodies were detected in 73% of patients within 26 days after onset of jaundice, in 50% 1-4 months after onset, in 6% 6-7 months after onset, and in no patients by 8 months after onset. When this test was used to identify sporadic hepatitis E cases in different regions of the world, such cases were found almost exclusively in areas where outbreaks of the disease had occurred and rarely in any other regions.

Adolescent↗

Identification of amino acids located in the antibody binding sites of human hepatitis A virus.

Antigenic mutants of human hepatitis A virus (human-HAV) were isolated by their resistance to neutralizing monoclonal antibodies raised to human-HAV. The nucleotide sequence determined for the capsid regions of 12 mutants identified amino acid changes that clustered in three non-overlapping sites; one in VP3 and two in VP1. All mutants had a change at amino acid residue 70 in VP3, indicating its primary importance for antibody binding. Ten mutants had two amino acid changes occurring in the VP3 site as well as one in one of the two VP1 sites. These data suggest that both sites in VP1 interact with the single VP3 site to form the immunodominant epitope of HAV. The amino acid changes found in the antigenic mutants of human-HAV selected in this study were located in the same positions as changes found in strains of HAV isolated from Old World monkeys. These simian strains of HAV are not recognized by most monoclonal antibodies raised to human-HAV, suggesting that the observed amino acid changes are part of the antibody binding site.

Amino Acids↗

Epidemiology of hepatitis A: seroepidemiology and risk groups in the USA.

Surveillance and seroepidemiological data are important in determining optimal hepatitis A vaccine strategies. In the USA, after a decade of declining rates, reported hepatitis A rates gradually increased from 9.2 cases per 100,000 population in 1983 to a peak of 14.4 per 100,000 in 1989. In 1991, 23,144 cases were reported, for a rate of 9.1 per 100,000. Since 1983, rates in males have been consistently 20% higher than in females. Rates in children, adolescents and adults up to 39 years old have been roughly equivalent and approximately threefold higher than for persons > or = 40 years old. Among reported cases in 1989, the most commonly reported risk factor was personal contact with a hepatitis A case (26%), followed by employment or attendance at a day-care centre (14%), a history of injecting drug use (11%), a history of recent international travel (4%), and association with a suspected food or waterborne outbreak (3%). Of cases, 42% had no known risk factor for infection. The prevalence of antibody to hepatitis A virus in the general US population was 38.2%, based upon testing of 9516 participants from the second National Health and Nutrition Examination Survey conducted from 1976 to 1980. Prevalence increased steadily with age, ranging from 11% in persons < 5 years of age to 74% in persons > or = 50 years old. Because some groups may be difficult to vaccinate prior to disease exposure (contacts of cases) or are difficult to reach (drug users or persons with unidentified risk), a selected risk group vaccination strategy may not be successful in reducing the disease burden in the USA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Who should receive hepatitis A vaccine? Considerations for the development of an immunization strategy.

The availability of efficacious hepatitis A vaccines should greatly facilitate the prevention of hepatitis A virus (HAV) infection. Groups at high risk of HAV infection have been identified from epidemiological studies and include both children and adults. While certain high-risk adults, such as travellers, could be a convenient target for vaccination, selective immunization of high-risk adults would not be expected to lower the overall rates of infection in most countries. Because a significant proportion of HAV infections occur in children, the eventual objective should be the integration of hepatitis A vaccine into 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 cyclical patterns of hepatitis A observed in many countries are related to levels of immunity in the population. The elimination of the susceptibility of a population to HAV infection through immunization could eliminate this well known human disease. This suggests that eradication of HAV infection should be attainable with effective hepatitis A vaccines.

Adult↗

Serological approaches to distinguish immune response to hepatitis A vaccine and natural infection.

Currently, the immune status of an individual exposed to hepatitis A virus (HAV) is determined by assays which measure antibodies against the capsid proteins. These assays indicate exposure to the viral capsid that could result from either infection or from vaccination. Recent data indicate that proteins from the non-structural genome region of the virus (P2 or P3), which are only produced during active virus replication, generate antibodies after clinical disease. A sub-genomic cDNA segment of HAV corresponding to the P2 region was used for in vitro transcription-translation followed by immune precipitation of the translated products under non-denaturing conditions. Serial serum specimens from experimentally infected chimpanzees and humans naturally infected with hepatitis A verified the development of antibodies to P2 proteins following infection. A serosurvey of individuals positive for antibodies to the HAV capsid (HAV AB assay, Abbott Laboratories) revealed that 50-60% of children and 16-32% of adults had no detectable antibodies to the P2 antigen by immune precipitation. These results may reflect subclinical infections resulting in a lower level of antibodies against the non-structural antigens or may represent a greater sensitivity of the competitive assay (HAV AB) used to detect capsid antibodies compared to the immunoprecipitation assay used to detect non-structural antigens.

Adult↗

Outbreak of hemodialysis-associated non-A, non-B hepatitis and correlation with antibody to hepatitis C virus.

Between January 1987 and October 1988, 35 (45%) of 77 patients undergoing chronic hemodialysis at one unit developed serum alanine aminotransferase (ALT) elevations suggestive of non-A, non-B hepatitis (NANBH). Patients were grouped by level of ALT elevation and presence of other etiologies for liver injury. All dialysis patients and staff were tested for antibody to hepatitis C virus (anti-HCV) by enzyme immunoassay on three occasions, 9 months apart; anti-HCV repeatedly reactive specimens were tested by the HCV neutralization assay. Household and sexual contacts of patients were tested once for anti-HCV. Case-patients were classified on the basis of clinical case definitions as probable, possible, questionable, and noncases, and by anti-HCV testing. Case-patients who had no history of transfusions or parenteral drug use were compared with noncases for common exposures. A total of 35% (27/77) of patients and none (0/24) of staff were anti-HCV-positive. Anti-HCV was found in 82% of probable cases, compared with 44% of possible cases, 44% of questionable cases, and 12% of noncases (P less than 0.01). Neither a common source nor direct person-to-person transmission could be documented; however, inadequate infection control measures demonstrated by lack of glove use and poor handwashing occurred during the exposure period. The incidence of HCV infection in patients over an 18-month period was 5%. Transmission of HCV to household or sexual contacts of patients did not appear to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Genetic relatedness of hepatitis A virus strains recovered from different geographical regions.

A pairwise comparison of the nucleic acid sequence of 168 bases from 152 wild-type or unique cell culture-adapted strains of hepatitis A virus (HAV) revealed that HAV strains can be differentiated genetically into seven unique genotypes (I to VII). In general, the nucleotide sequence of viruses in different genotypes differs at 15 to 25% of positions within this segment of the genome. Viruses from four of the genotypes (I, II, III and VII) were recovered from cases of hepatitis A in humans, whereas viruses from the other three genotypes (IV, V and VI) were isolated only from simian species developing a hepatitis A-like illness during captivity. Among non-epidemiologically related human HAV strains, 81 were characterized as genotype I, and 19 as genotype III. Within each of these major genotypes, there were two distinct groups (subgenotypes), which differed in sequence at approximately 7.5% of base positions. Each genotype and subgenotype has a characteristic amino acid sequence in this region of the polyprotein, with the most divergent genotypes differing at 10 of 56 residues. Strains recovered from some geographical regions belonged to a common (endemic) genotype, whereas strains from other regions belonged to several, probably imported, genotypes. Thus, HAV strains recovered in North America were for the most part closely related at the nucleotide sequence level, whereas in other regions, such as Japan and Western Europe, HAV strains were derived from multiple genotypes or sub-genotypes. These data indicate that patterns of endemic transmission can be differentiated from situations in which infections are imported due to travel.

Amino Acid Sequence↗

Histopathology of community acquired chronic hepatitis C. The Sentinel Counties Chronic Non-A, Non-B Hepatitis Study Team.

As part of a study of community-acquired non-A, non-B hepatitis, liver biopsy specimens of 29 anti-HCV positive and four anti-HCV negative patients were evaluated in order to characterize the histopathologic changes of chronic hepatitis C. Liver biopsies were performed 6 to 46 mo after onset of the disease and repeat biopsies were obtained in 10 anti-HCV positive patients. The histologic diagnoses were chronic persistent hepatitis (45%), chronic active hepatitis (35%), and chronic lobular hepatitis (21%). Irrespective of the tissue diagnosis, the majority of the patients showed characteristic histologic abnormalities in the liver, particularly damage of the small and medium-sized bile ducts (76%), lymphoid aggregates in portal tracts (45%), enlarged macrophages (48%), and steatosis (31%). In 59% of the patients, two or more of these histologic abnormalities were combined. Similar histologic changes have previously been observed in non-A, non-B hepatitis, but only uncommonly in hepatitis A or hepatitis B. We conclude that the histopathologic findings in chronic hepatitis C are highly characteristic, although not pathognomonic.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

Impact of hepatitis B virus infection on women and children.

HBV infection acquired during infancy and early childhood has a high likelihood of progressing to chronic infection, which can lead to chronic hepatitis, cirrhosis, and primary hepatocellular carcinoma. In areas of the world where HBV infection occurs predominantly in infants and young children, routine infant immunization with hepatitis B vaccine is the most appropriate vaccination strategy. In the United States, the majority of HBV infections occur in adults with behaviors or occupations that put them at risk for HBV infection. Nevertheless, infection acquired during infancy and early childhood contributes significantly to the burden of chronic liver disease in the United States. Until recently, the vaccination strategy in the United States has included HBsAg screening of pregnant women and vaccination of infants born to infected women and vaccination of people in groups at high risk for HBV infection. Because of the difficulties in accessing and vaccinating persons from high-risk groups and the recent findings that HBV infection occurs more commonly among children in some groups in the United States than previously appreciated, the Immunization Practices Advisory Committee of the US Public Health Service and the American Academy of Pediatrics in 1991 endorsed a strategy of universal immunization of infants for hepatitis B. This strategy has the advantages of accessing infants in the United States through preexisting vaccine delivery systems and vaccinating individuals prior to their engaging in high-risk behavior. Continued screening of pregnant women for HBsAg is necessary to prevent perinatal HBV transmission and to identify for vaccination those household and sexual contacts of HBV carriers, a group that is also at high risk of HBV infection.

Acute Disease↗