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Biomedical subjects

A G Shattock

Publications and source records attributed to A G Shattock.

At least 19 recordsLinked to original sources

Cost-effective analysis of hepatitis A prevention in Ireland.

OBJECTIVE: The purpose of this study was to determine the most cost-effective prevention strategy against hepatitis A virus (HAV) infection for healthcare workers and the general population at risk in Ireland. METHODS: Four prevention strategies were compared: active immunization with Havrix Monodose (1440E.U); screening for anti-HAV antibody and then vaccinating; passive immunization; screening for anti-HAV antibody and then passive immunization. The cost-effective ratio was calculated for each prevention strategy. Threshold analysis, sensitivity analysis, and model extension to include indirect cost from work days lost and secondary attack rates through horizontal transmission were also derived. RESULTS: The medical costs were lowest and the infection rate highest when no preventive action was taken. Vaccination was most cost effective when the prevalence of immunity was 45% or less, reducing the infection rate by 98% when compared to nonprevention. Screening before vaccination was most cost effective when the prevalence of immunity was greater than 45%. Passive immunization and screening before passive immunization were not comparable to the other strategies in cost effectiveness. Sensitivity analysis showed that the cost-effective ratio for vaccination was dependent on vaccine price, incidence of HAV, and prevalence of immunity in the target group. Extending the model to include indirect costs further increased the cost effectiveness of vaccination. CONCLUSION: The best cost-effective strategy relates to target group immunity. Where HAV immunity is 45% or less, vaccination is the strategy of choice and when immunity is greater than 45%, then screening followed by vaccination should be used. This study can be used to provide a framework within which choices can be made to achieve better health for less cost.

Adolescent↗

Transmission of a homogenous hepatitis B virus population of A1896-containing strains leading to mild resolving acute hepatitis and seroconversion to hepatitis B e antigen antibodies in an adult.

The pre-core variant, A1896, which switches off hepatitis B e antigen (HBeAg) production, is common in hepatitis B e antigen antibody (anti-HBe)-positive chronic hepatitis patients. It has been observed in occasional case reports of acute hepatitis. However, transmission in the absence of HBeAg-producing strains, leading to acute nonfulminant hepatitis and clearance in adults, has not been reported. Here, we show that this event can occur, further confirming that A1896 strains are "wild-type" and can lead to all the same outcomes as G1896 strains. This is in keeping with phylogenetic evidence that A1896 is transmitted independently on a large scale in the population and explains anti-HBe- positive persons who have not had an HBeAg-positive phase documented.

DNA Primers↗

The reliability of saliva as a sample for the detection of hepatitis A immunoglobulins under various sampling conditions.

BACKGROUND: Saliva is increasingly being investigated as an alternative to serum for diagnostic and epidemiological testing even though antibody levels are substantially lower in buccal cavity fluids. However, there has been little study on whether buccal cavity activity and/or the timing of saliva sampling affects the diagnostic outcome, particularly in seropositive subjects. The absence of influence by these factors may be critical to the use of saliva for pre-vaccination screening for example. OBJECTIVES: The effects of eating, brushing of teeth and circadian rhythm on the measureable salivary immune status of 42 healthy individuals known to be serum and saliva anti-HAV positive were examined. STUDY DESIGN: A total of 141 saliva samples obtained from the 42 healthy subjects, before and after meals, before and after brushing of teeth and at various timepoints throughout the day, were assayed for total anti-HAV using an in-house saliva based enzyme-immunoassay, previously shown to have a 100% correlation in terms of sensitivity and specificity with a serum based assay. RESULTS: The results indicated that total anti-HAV titres varied according to the time of day and that eating had no significant effect on the total anti-HAV titre, but brushing of teeth did. Titres never varied to the extent that a result was falsely negative at any timepoint. CONCLUSION: These results confirm the usefulness of saliva as a diagnostic sample for the detection of hepatitis A antibody, regardless of sampling times, eating or tooth-brushing.

Antibodies, Viral↗

Capture immunoassay for the diagnosis of bovine mastitis using a monoclonal antibody to polymorphonuclear granulocytes.

A direct capture enzyme-linked immunosorbent assay (ELISA) was developed to measure elevated polymorphonuclear granulocyte (PMN) antigens using horseradish peroxidase (EC 1.11.1.7) conjugated rabbit polyclonal anti-PMN antisera and a monoclonal antibody specific for PMN cells. Optical densities obtained in the ELISA were used to predict the cell counts of milk samples. Predicted counts were not significantly different from actual somatic cell counts (SCC). In a total of 156 bovine milk samples the correlation coefficient between somatic cell counting, taking greater than 500,000 cells/ml as being indicative of mastitis, and the assay was 0.94, yielding an assay sensitivity of 95.2% and a specificity of 97.3%. In further trials the ELISA could detect elevated PMN antigens in milk with SCC as low as 100,000 cells/ml. The results indicate that the monoclonal antibody based direct ELISA has excellent potential in the detection and determination of bovine mastitis.

Animals↗

Evaluation of commercial enzyme immunoassays for detection of hepatitis delta antigen and anti-hepatitis delta virus (HDV) and immunoglobulin M anti-HDV antibodies.

Panels of hepatitis B virus surface antigen-positive sera from drug abusers were used to evaluate 14 commercial enzyme immunoassays from six companies for detecting hepatitis delta virus (HDV) markers. For detecting hepatitis delta virus antigen (HDAg), the Wellcome, Pasteur and Noctech assays had 100% sensitivity for all 42 HDAg-positive serum specimens that were confirmed in-house; the Organon reagents gave 59.5% sensitivity without detergent and 64.3% sensitivity with detergent, but there were 14 discrepant results with and without detergent. The Sorin assay detected HDAg in only 10 of the positive samples (23.8% sensitivity). For the detection of antibody to HDV (anti-HDV) all six commercial enzyme immunoassays were reactive with all 36 anti-HDV-positive specimens that were confirmed in-house. There were no false-positive results with the Wellcome, Noctech, or Sorin assay, but one specimen was false positive by the Organon assay. One HDAg-positive specimen gave a false anti-HDV-positive result in the Abbott assay and an equivocal result in the Pasteur assay (97.8% specificity). For the detection of immunoglobulin M anti-HDV, the Wellcome, Noctech, and Sorin assays agreed for the 38 positives confirmed in-house, except for one false negative with the Sorin test. We conclude that there has been a substantial improvement over previously evaluated assays in sensitivity and specificity of commercial assays for anti-HDV detection, and the sensitivities of immunoglobulin M anti-HDV assays are also comparable. However, there are still major differences in sensitivity among some assays for HDAg detection.

Antibodies, Viral↗

Progressive multifocal leukoencephalopathy-remission with cytarabine.

A 51-year-old woman who was in complete remission from non-Hodgkin's lymphoma, developed a rapidly progressive dementia. Progressive multifocal leukoencephalopathy (PML) was diagnosed on the basis of a rising antibody titre to JC polyomavirus in cerebro-spinal fluid and serum and the presence of diffuse white matter changes on magnetic resonance imaging. She was treated initially with intravenous cytarabine and showed minimal improvement. Rapid improvement occurred when intrathecal cytarabine was added and the patient is in complete remission from both lymphoma and PML 20 months later.

Cytarabine↗

Changes in incidence of hepatitis B in Ireland from 1970-1987.

This paper analyses data on 2,226 cases of Hepatitis B virus (HBV) infection detected during the years 1970 to 1987. Of those where information on risk-group was available (1,301), infection among intravenous drug-abusers accounted for the largest proportion (49%). Most became infected during and since an outbreak of hepatitis B and Delta hepatitis which originated in this group in 1980. A comparison of the data before and after the start of the outbreak among drug-abusers shows a marked increase in the number of HBV infections in non drug users, including haemophiliacs, homosexuals and health-care staff, and a dramatic decrease in hepatitis B following blood transfusion. A larger group (165 cases), many of whom are long-term healthy hepatitis B surface antigen carriers, were patients in institutions for the mentally handicapped (IMH). Most were detected recently during pre-vaccination sampling programmes. Others affected included visitors to and from high-incidence areas, tattooed persons, dialysis patients, persons born to infected mothers, and members of the security forces dealing with drug-abusers. In all, 8.4% of the hepatitis B cases detected were found to be carriers and 67% of these remained carriers in 1987 The mean duration of carriage was 3.25 years. Intravenous drug-abusers and IMH patients constituted the two largest groups of carriers. The running-three-yearly mean incidence of new cases of hepatitis B has levelled off below the peak of 1981. Although the number of cases among drug-abusers has apparently decreased, the number of cases among non drug-abusing groups has increased by 50%. (ABSTRACT TRUNCATED AT 250 WORDS)

Cohort Studies↗

The serology of delta hepatitis and the detection of IgM anti-HD by EIA using serum derived delta antigen.

A sensitive and specific capture assay for IgM antibody to hepatitis D virus (HDV) was developed employing serum-derived delta antigen (HDAg). In a retrospective and prospective study of an outbreak of hepatitis B (HB), 135 hepatitis B surface antigen (HBsAg) positive drug-abusers with acute hepatitis and 18 HBsAg carriers, attending various hospitals and clinics in Dublin, were found to be infected with HDV. Serological follow-up was available from 24 of those with acute hepatitis allowing a comparison of the duration and level of IgM anti-HD with the more commonly used markers, HDAg and anti-delta (anti-HD), and an assessment of the usefulness of each. HDV and HB serology was grossly altered by human immunodeficiency virus (HIV) in two patients, with severe clinical manifestation in one. All 135 patients with HDV co-infection had delta antigenaemia. In co-infections with optimum sampling times, the mean duration of delta antigenaemia was 21 days. IgM anti-HD was always found between HDAg and sero-conversion to anti-delta and was the only 'window' marker present in five cases. The mean duration of IgM anti-HD was four weeks (optimum at 2.8 weeks) and was of moderate or low titre and occurred simultaneously with HDAg in 78%. In HDV-infected HBsAg carriers, high-titre IgM anti-HD (greater than 1/10,000) persisted for the duration of the study and is a useful indicator of chronic HDV infection. IgM anti-HD was not found in 202 random blood donors nor in 205 patients with non-B hepatitis or other disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody Specificity↗

Prolonged IgM antibodies and histopathological evidence of chronicity in hepatitis A.

The case of a young man with hepatitis A and a chronic course is presented. The patient received a short course of steroid therapy for recurrence of symptoms following acute hepatitis A. Thereafter, liver enzymes have remained marginally elevated for 4 years and annual liver biopsies have shown evidence of chronicity. HAV IgM Ab persisted for 1034 days with subsequent development of HAV IgG Ab. The possibility of other viruses in the aetiology and the role of steroids in the development of chronicity are discussed.

Adult↗

Increased severity and morbidity of acute hepatitis in drug abusers with simultaneously acquired hepatitis B and hepatitis D virus infections.

Hepatitis D virus (delta agent) markers were present in 111 (36%) of 308 intravenous drug abusers who were positive for hepatitis B surface antigen (HBsAg), 52 of these having hepatitis D virus antigenaemia. IgM antibody to hepatitis B core antigen (anti-HBc IgM) was present in 92 out of 95 subjects tested, indicating that hepatitis D virus and hepatitis B virus infections had been acquired simultaneously. Hepatitis D virus markers were present in three out of four patients with fulminant hepatitis, and in 80 of 223 (36%) with mild or moderate hepatitis compared with four of 29 (14%) of those who were asymptomatic. These proportional differences were significant (p less than 0.001). Hepatitis D virus markers were present in twice as many patients positive for anti-HBc IgM requiring admission to hospital with acute hepatitis compared with outpatients attending a drug treatment centre. Tests on one patient showed complete disappearance of HBsAg, but hepatitis D antigen (HDAg or delta antigen) and hepatitis B e antigen (HBeAg) were still present in serum samples. All five patients with chronic active hepatitis had hepatitis D antibody (anti-HD) compared with seven of 24 (29%) with chronic persistent hepatitis (p = 0.008). Blocking anti-HD persisted for long periods after simultaneous infections with hepatitis B virus and hepatitis D virus but at lower titres than in patients with chronic liver disease.

Acute Disease↗

Sensitive enzyme immunoassay for the detection of delta antigen and anti-delta, using serum as the delta antigen source.

A sensitive enzyme-linked immunosorbent assay (ELISA, EIA) was developed for the detection of delta antigen in serum treated with Tween 20. The serum delta antigen so derived was used in an ELISA for anti-delta. Both tests were specific and more sensitive than radioimmunoassay (RIA) when applied to testing parenteral drug abusers. It is concluded that the different sources of delta-antigen used may account for the different sensitivities noted, and that delta antigenaemia in acute infection may be more frequently detectable than was first thought, amounting to 71% of those with delta infection in this study and that these sera are a convenient alternative source of antigen.

Antibodies, Viral↗