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Biomedical subjects

J E Maynard

Publications and source records attributed to J E Maynard.

At least 37 records · Page 2Linked to original sources

Long-term immunogenicity and efficacy of hepatitis B vaccine in homosexual men.

To study the duration of antibody persistence and protection provided by the hepatitis B vaccine, we followed 773 homosexual men for five years after completion of vaccination. Among the 635 participants in whom antibody levels above 9.9 sample ratio units (SRU) developed after vaccination, 15 percent lost antibody altogether, and in another 27 percent, antibody levels declined below 10 SRU within five years. The extent of the maximal antibody response strongly predicted the persistence of protective antibody. Hepatitis B infection occurred in 55 men; 8 of these infections were clinically important (characterized by the presence of the hepatitis B surface antigen and elevation of liver-enzyme levels), and two of the patients became hepatitis B virus carriers. The long-term risk of hepatitis B infection was inversely related to the maximal antibody response to vaccine. Most severe infections occurred among those who responded poorly or had no response to the vaccination. The risk of late infection with hepatitis B in those with an initially adequate vaccine response increased markedly when antibody levels decreased below 10 SRU, but only 1 of 34 late infections resulted in viremia and liver inflammation. A second series of vaccinations induced a moderate antibody response in 50 percent of the subjects who initially had no response or a poor response; however, the persistence of antibody was poor. Both antibody loss and the risk of severe disease should be considered when booster-dose strategies for the hepatitis B vaccine are being designed.

Carrier State↗

Lethal outbreak of hepatitis B in a dental practice.

Between April 1, 1984, and Feb 1, 1985, nine cases of hepatitis B occurred in the patients of a dentist practicing in a rural Indiana county (population, 35,000). This was over 20 times the mean annual incidence for the county in the previous decade. All of the patients had been treated by the dentist two to five months before illness. Although the dentist had never had hepatitis symptoms, his serum was positive for hepatitis B surface antigen and hepatitis B e antigen and negative for anti-hepatitis B core IgM antibody, indicating that he was probably a hepatitis B carrier. Two patients (22%) died of fulminant hepatitis; the case-fatality ratio was over ten times the reported US mean for hepatitis B. Using a case definition based on anti-hepatitis B core IgM antibody positivity and exposure to the dentist during a defined time period, a serosurvey of the dentist's patients identified 15 asymptomatic cases (overall attack rate, 3.2%). Infection risk was related to the amount of trauma involved in the cases' dental procedures. No cause was found for the unusual lethality of the outbreak.

Adult↗

A Community-wide epidemic of hepatitis A in Ohio.

Between June 1, 1983 and August 30, 1984, an epidemic involving 313 cases of hepatitis A occurred in Muskingum County, Ohio. One hundred ninety-seven cases occurred in the city of Zanesville, with 34.7% of cases concentrated in two neighborhoods in the eastern part of the city. Case characteristics were similar to those reported in previous community-wide outbreaks, including a maximum attack rate among 5-9-year-olds and a very low attack rate in adults over 30 years. Case households were larger, and their members were less educated than the mean for households in the city. Forty-eight per cent of the cases reported exposures to other cases which temporally could have been the source of infection. A case-control study failed to show differences in several behavioral factors between case and control households, but did confirm that lower socioeconomic status was a risk factor for the disease. Broad use of immunoglobulin was effective in preventing clinical disease among family contacts, but did not stop the outbreak. This outbreak typifies a genre of hepatitis A epidemic transmitted from person to person in which exact routes of spread are poorly understood and control is difficult. Lower socioeconomic status may be a marker for some unidentified behaviors that promote hepatitis A transmission.

Adolescent↗

Adsorption, purification, and growth characteristics of hepatitis A virus strain HAS-15 propagated in fetal rhesus monkey kidney cells.

A human fecal isolate of hepatitis A virus strain HAS-15 was adapted to rapid growth in FRhK-4 cells by more than 20 7-day passages. A cell culture-derived inoculum of strain HAS-15 was used at a multiplicity of infection of 80 radioimmunofocus-forming units per cell, and a one-step growth curve was determined. Both intracellular production and supernatant release of infectious virions were evaluated. Detection of virus release into the medium directly corresponded to intracellular production of infectious virions. A classical eclipse period was not observed during the growth curve determinations; however, detectable infectious virion production was absent for approximately 20 h after infection. This 20-h period was immediately followed by a 4-day logarithmic phase of virus production. A maximum intracellular virus titer of 10(9) radioimmunofocus-forming units per ml was achieved, and this level remained essentially constant for up to 14 days after infection. The infectious virus and viral antigen produced during the growth cycle were ascertained by a radioimmunofocus assay and by a radioimmunoassay, respectively. Cell culture supernatants were negative for viral antigen as determined by the radioimmunoassay, even though as many as 10(8) hepatitis A virus radioimmunofocus-forming units per ml were found. An adsorption study was also performed with strain HAS-15 by using FRhK-4 cells. More than 99.9% of the infectious virus was adsorbed at 25 degrees C in less than 20 min.

Adsorption↗

Nosocomial transmission of delta hepatitis.

A previously asymptomatic carrier of hepatitis B virus receiving chronic hemodialysis developed acute delta hepatitis. The patient regularly received dialysis treatments on the same machine as a parenteral drug abuser with hepatitis B surface antigen (HBsAg)-positive chronic hepatitis whose serum was strongly positive for delta antibody. The drug abuser had a major bleeding episode that caused extensive environmental contamination 3 months before onset of illness in the index patient. No other patients receiving dialysis or staff members had evidence of delta infection. A surgeon previously infected with hepatitis B from the same parenteral drug abuser also had delta antibody. Testing for delta virus is indicated for both HBsAg-positive parenteral drug abusers and patients with hemophilia receiving chronic hemodialysis. All patients who are HBsAg- and delta-positive should receive dialysis separately from patients who are HBsAg-positive and delta-negative. Susceptible patients on dialysis and staff should receive hepatitis B vaccine to protect against both hepatitis B and delta virus infection.

Adult↗

Experimental transmission of the delta virus to a hepatitis B chronic carrier chimpanzee with the development of persistent delta carriage.

A delta virus (DV) infection was experimentally transmitted to a hepatitis B chronic carrier chimpanzee. The infection was monitored by the examination of liver biopsy materials with the use of FITC-labeled human anti-delta IgG or by an indirect immunoperoxidase staining technique and by measurement of the serum alanine aminotransferase (ALT) activity. Three different antibody enzyme immunoassays (EIAs) were developed for assessment of the serologic response: 1) blocking assay, 2) IgM-specific capture assay, and 3) IgG-specific capture assay. An antigen-specific EIA was also developed for monitoring delta antigen in the serum. The results indicate that a superinfection with the DV produced a biphasic ALT response concomitant with the appearance of the delta antigen in biopsy materials. The persistence of these markers over the observation period (350 days) indicates the development of a persistent DV infection.

Alanine Transaminase↗

Hepatitis B vaccine use in chronic hemodialysis centers in the United States.

The Centers for Disease Control surveyed 1,255 chronic hemodialysis centers in the United States in 1983 to assess the use of hepatitis B vaccine as well as the risk of acquiring hepatitis B among both patients and staff. The response rate to a mailed questionnaire was 90%. Seventy-one percent of the centers reported that they gave vaccine, but only an estimated 6% of susceptible patients and 32% of susceptible staff received all three doses of vaccine. Centers more likely to give vaccine included those that provided dialysis to large patient populations and those that provided dialysis for hepatitis B surface antigen-positive patients. As a result of vaccine administration, the overall prevalence of antibody to hepatitis B surface antigen increased significantly, to 18% for patients and 39% for staff. Extensive use of the vaccine in the future, combined with infection control practices, could virtually eliminate the risk of acquiring hepatitis B virus infection in hemodialysis centers.

Ambulatory Care Facilities↗

Transmission of hepatitis B virus to classroom contacts of mentally retarded carriers.

The risk of the spread of hepatitis B virus infection from deinstitutionalized, mentally retarded carriers to pupil and staff school contacts in the New York City public school system was measured serologically in a three-phase study from 1978 to 1982. In the third phase, undertaken in 1982, blood samples were drawn and questionnaires were completed on students and staff tested in either of the first two phases and on comparison groups with intermediate and no known school exposure to deinstitutionalized carriers. Univariate and logistic regression analyses revealed that staff and pupils with a history of classroom exposure to a hepatitis B virus carrier had significantly increased prevalences of hepatitis B virus infection (13.4%, odds ratio = 1.9; 9.3%, odds ratio = 2.5, respectively). Similarly, yearly seroconversion rates of 1.3% and 0.67% indicate that staff and, to a lesser extent, pupils are at increased risk of infection.

Adolescent↗

Enzyme-antibody conjugation by a heterobifunctional reagent and its application in enzyme-linked immunosorbent assay (ELISA) for the detection of hepatitis B surface antigen.

The heterobifunctional reagent 3-(2-pyridyl-dithio)propionate (SPDP) was used to prepare defined conjugates composed of horseradish peroxidase (HRP) and goat anti-HBs IgG. The modification of HRP and IgG with SPDP was dependent on both the SPDP: protein molar ratio and the pH of the buffer. Conjugates were separated by a single affinity chromatographic step using concanavalin A-Sepharose 4B equilibrated with 0.1 M Tris-HCl buffer, pH 7.4, containing 0.5 M KCl and 1 mM EDTA. The conjugate was eluted with 10 or 100 mM alpha-methyl-D-mannoside and appropriate pools were made reflecting various HRP/IgG molar ratios. Each pool was examined for performance in an enzyme-linked immunosorbent assay for HBsAg. Conjugate composed of an HRP/IgG molar ratio of 2.5-4 yielded the greatest sensitivity.

Antibodies, Viral↗

Occupational risk of hepatitis B infection in hospital workers.

To estimate the risk of hepatitis B virus (HBV) infection among hospital workers, we measured the prevalence of HBV infection in employees in five hospitals in different parts of the country and examined the effect of occupational and non-occupational factors on HBV prevalence. Among 5,697 persons studied, serologic markers of HBV infection were found in 807 (14%). Prevalence of infection was strongly related to race (Asian greater than Black greater than White), sex (male greater than female) and increasing age. Risk related to health occupation, studied by examining the change in HBV prevalence with duration in occupational group, was most strongly correlated with frequency of contact with blood during work. Workers having frequent blood contact had the highest estimated infection rate (1.05 per 100 person-years) and those with moderate contact an intermediate infection rate, compared to a negligible infection rate in workers with no blood contact. Frequency of needle accidents had an independent, positive effect on HBV infection rates, while degree of patient contact had no effect. Infection risk was uniform among all hospitals for groups with frequent blood contact. Among different occupation groups, risk of HBV infection also correlated closely with degree of blood-needle contact during daily work. This study provides a general approach to assessing risk of HBV infection in hospital personnel, and indicates that risk may be most easily estimated by quantitating degree of blood-needle contact during daily work.

Adolescent↗

Acute hepatitis B virus infection: relation of age to the clinical expression of disease and subsequent development of the carrier state.

Yupik Eskimos of southwestern Alaska have the highest known prevalence of hepatitis B virus infection of any general population in the United States. Prospective serological surveys of 1,280 seronegative Yupik Eskimos, performed between 1971 and 1976, identified 189 (14.8%) who developed serological evidence of hepatitis B virus infection. Twenty-six (13.8%) developed clinical hepatitis during the interval when seroconversion occurred. The proportion of patients with clinically apparent hepatitis increased with age (P less than .01), ranging from 9.5% of infections in patients who were four years of age or less to 33.3% of infections in patients who were 30 years of age or older. Twenty-five (13.3%) of the 188 individuals who were studied became chronic carriers of hepatitis B surface antigen. The risk of becoming a carrier was inversely related to the age of the patient at the time of infection (P = .02). Among patients who were four years of age or less when infected, 28.8% became chronic carriers of hepatitis B, as compared with 7.7% of those who were 30 years of age or older.

Acute Disease↗

The control of hepatitis B virus infection with vaccine in Yupik Eskimos. Demonstration of safety, immunogenicity, and efficacy under field conditions.

In 1981, a hepatitis B vaccine demonstration project was initiated among Yupik Eskimos of southwest Alaska to demonstrate that, under field conditions, the vaccine was safe, immunogenic, and efficacious. Laboratory tests for serologic markers of hepatitis B virus infection (HBsAg, anti-HBs, and anti-HBc) performed on sera collected in May 1981 from 3,988 residents of 17 remote Eskimo villages revealed that 2,645 (66.3%) had no evidence of hepatitis B virus infection. Because of a limited supply of vaccine, specific criteria for selection were used so that those at highest risk of infection would be immunized first. In November 1981, the first dose of vaccine was administered to 1,693 carefully selected individuals. The second dose was administered to 1,678 (99.1%) of those who received the first dose, and the final dose was administered to 1,630 persons (96.3%). Serologic follow-up showed the vaccine to be safe (0.4% experienced minor adverse reactions) and immunogenic (97.4% developed antibody). Vaccine-induced antibody levels were significantly higher for persons less than 30 years of age (p less than 0.001) and for females (p less than 0.001). Vaccine recipients were also protected from hepatitis B virus infection (p = 0.002). This public health measure proved to be feasible and effective in this remote arctic population despite difficult conditions for delivery and administration of this temperature-sensitive vaccine. This strategy for immunization is now being applied on a larger scale in Alaska as part of a program for the primary prevention of this infection and its sequelae.

Adolescent↗

Posttransfusion non-A, non-B hepatitis in chimpanzees. Physicochemical evidence that the tubule-forming agent is a small, enveloped virus.

Posttransfusion non-A, non-B hepatitis associated with the formation of hepatocyte cytoplasmic tubules was experimentally transmitted to chimpanzees by intravenous inoculation of a proven-infectious plasma that had been pelleted and microfiltrated, or purified by a combination of pelleting and rate-zonal banding. The results of these studies indicate that a factor VIII-derived non-A, non-B tubule-forming agent will pass through an 80-nm membrane filter and that it can be recovered from infected plasma by use of a purification procedure that assumes the non-A, non-B tubule-forming agent is a small, enveloped virus. Our findings, in combination with the known sensitivity of the non-A, non-B tubule-forming agent to chloroform and its apparent lack of nucleic acid homology with hepatitis B virus, further suggest that at least one etiologic agent of human posttransfusion non-A, non-B hepatitis may be a small, enveloped RNA virus.

Animals↗

Prevention of perinatal acquisition of hepatitis B virus carriage using vaccine: preliminary report of a randomized, double-blind placebo-controlled and comparative trial.

Hepatitis B is a serious disease of global significance. In developing countries, hepatitis B virus (HBV) infection and its sequelae rank among the public health problems of highest priority. Infants born to mothers who are chronic carriers of HBV are at particularly high risk of acquiring infection and becoming chronic HBV carriers. The efficacy of hepatitis B vaccine alone in preventing the transmission of HBV to infants born to HBV carrier mothers was determined in a double-blind placebo-controlled trial. Infants received plasma-derived vaccine at birth, 1 month, and 6 months of age. Of 180 infants born to hepatitis B surface antigen (HBsAg)-positive mothers, equal numbers received National Institute of Allergy and Infectious Disease (NIAID) vaccine, Beijing Institute of Vaccine and Serum (BIVS) vaccine, and placebo. The cumulative seroconversion to the vaccines at 1 year of age was 95% and 75%, respectively. Vaccine efficacy as measured by the prevention of HBsAg-positive events was 88% for the NIAID vaccine and 51% for the BIVS vaccine. Vaccine efficacy was similar among infants born to hepatitis Be antigen-positive mothers. Because of the low efficacy of the BIVS vaccine, an additional group of 28 infants was given vaccine and hepatitis B immune globulin at birth. The resulting efficacy was 83%. The results of this trial indicate that hepatitis B vaccine alone can substantially reduce perinatally acquired HBV infection and the resulting chronic carrier state.

Carrier State↗