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Biomedical subjects

G H Bothamley

Publications and source records attributed to G H Bothamley.

At least 19 recordsLinked to original sources
PubMed2005

Interferon-gamma responses to ESAT-6 in tuberculosis patients early into and after anti-tuberculosis treatment.

OBJECTIVE: To investigate T-cell responses to ESAT-6 by an interferon-gamma (IFN-gamma) ex vivo enzyme-linked immunospot (ELISpot) assay in tuberculosis (TB) patients early during treatment and in patients who have completed a course of anti-tuberculosis chemotherapy. DESIGN: T-cell responses following overnight stimulation with 6-kD early secretory antigenic target (ESAT-6) antigen were compared to responses obtained using cells cultured with ESAT-6 for 6 days, using an ELISpot assay. RESULTS: In the ex vivo ELISpot assay, the median IFN-gamma responses in TB patients, irrespective of treatment status, were significantly higher than in healthy BCG-vaccinated controls. In the 6-day ELISpot assay, median IFN-gamma responses were significantly higher in TB patients who had completed treatment than in patients early during therapy. There was considerable individual variability in the degree of expansion of ESAT-6 specific T-cells from day 1 to day 6 in both treatment groups. CONCLUSION: Further studies are required to assess which type of assay provides the best indicator of a memory T-cell response and how ESAT-6 specific T-cells relate to protective immunity in TB infection.

Adult↗
PubMed2002

Screening for tuberculosis: the port of arrival scheme compared with screening in general practice and the homeless.

BACKGROUND: Tuberculosis is increasing in London, especially in those recently entering the UK from an area of high incidence. Screening through the port of arrival scheme has a poor yield and has been considered discriminatory. METHODS: A study was undertaken to compare the yield and costs of screening new entrants in a hospital based new entrants' clinic (1262 referrals from the port of arrival), general practice (1311 new registrations), and centres for the homeless (267 individuals) using a symptom questionnaire and tuberculin testing if indicated. Clinical outcome measures were cases of tuberculosis, tuberculin reactors requiring chemoprophylaxis and BCG vaccinations. Cost outcomes were cost per individual screened and cost per individual per case of tuberculosis prevented. RESULTS: Verbal screening limited tuberculin testing to 16% of those in general practice; most were tested at the other two locations. Intervention (BCG vaccination, chemoprophylaxis or treatment) occurred in 27% of those who received tuberculin testing. Attendance for screening was 17% of the port of arrival notifications (63% had registered with a GP), 54% in primary care, and 67% in the homeless (42% registered with a GP). Costs for screening an individual in general practice, hostels for the homeless, and the new entrants' clinic were 1.26 pounds sterling, 13.17 pounds sterling and 96.36 pounds sterling, respectively, while the cost per person screened per case of tuberculosis prevented was 6.32 pounds sterling, 23.00 pounds sterling, and 10.00 pounds sterling, respectively. The benefit of screening was highly sensitive to the number of cases of tuberculosis identified and case holding during treatment. CONCLUSION: Screening for tuberculosis in primary care is feasible and could replace hospital screening of new arrivals for those registered with a GP.

Adolescent↗
PubMed2000

Tuberculosis preventive therapy: perspective from a multi-ethnic community.

This study explores the knowledge, attitudes and perception of tuberculosis (TB) and how they affect adherence to preventive treatment. A qualitative study of 24 subjects taking preventive therapy for TB was undertaken. Interviews were conducted in English using a structured questionnaire in a private room adjoining the outpatient clinic before the subject's appointment. The questionnaire included; (i) demographic details; (ii) background information on TB; (iii) knowledge and perception of TB and chemoprophylaxis. Data was analysed descriptively and thematically and subjected to statistical evaluation where appropriate. Outcome was assessed >6 months after the start of preventive treatment. The sample was representative of the ethnic mix of those attending the clinic. Knowledge of TB-was gained outside the family and covered transmission but few symptoms of active TB were recognized. The perceived threat from TB was high, although the estimated risk was low. Knowledge of preventive therapy exceeded the general knowledge of TB, although the latter was associated with better adherence. Most denied knowledge of the risk of hepatitis from isoniazid. Defaulters failed to attend their first appointment, attributed more side effects to isoniazid and perceived a longer waiting time in clinic. Adherence is better with a general knowledge of TB and attendance at the first appointment and could be improved by a single daily tablet, warnings about dizziness and discussion of the difficulties of taking a 6 month course of treatment.

Adolescent↗
PubMed1995

Delayed hypersensitivity and HLA in smear-positive pulmonary tuberculosis.

Tuberculin responses were quantified by induration of the skin, velocity of blood flow in dermal microcirculation and composition of the cellular infiltrate in 125 patients with tuberculosis and 39 healty controls. The diameters of the tuberculin responses were greater in HLA-DR15-positive patients than in DR15-negative patients. The density of infiltrating CD(4+)-positive cells showed a positive correlation with induration in DR15-negative subjects (r = 0.54). A fraction of DR15-positive patients gave large tuberculin responses (> or = 15 mm) but with few CD4+ cells in the test site (< 500/mm2); these patients had a greater percentage of cells in the diffuse dermal infiltrate than in the perivascular region, greater blood flow velocities in the tuberculin response but more frequently with central relative slowing of blood flow and had higher total IgG and specific antimycobacterial antibody levels compared to other DR15-positive patients. If the inflammatory infiltrate in the lungs parallels that in the tuberculin skin test, the lack of immunocompetent cells and tissue hypoxia could permit pulmonary cavitation and explain the association of HLA-DR15 with smear-positive pulmonary tuberculosis.

Blood Flow Velocity↗
PubMed1995

Serological diagnosis of tuberculosis.

The past decade has seen dramatic developments in serological tests for tuberculosis. The long history of serological tests for tuberculosis is a testimony to the need for a sensitive diagnostic test, especially when the sputum smear is unhelpful. New reagents, both purified antigens and monoclonal antibodies, provide the means to obtain a sensitivity and specificity to rival the tuberculin skin test and equal other commonly used diagnostic blood tests. Evaluation with sera from patients with smear-positive pulmonary tuberculosis has identified one antigen (antigen 5, the 38 kDa antigen) as a potential screening reagent for infectious tuberculosis and another (16 kDa antigen) for monitoring compliance. A monoclonal antibody competition assay anti-38 kDa antibody is the most sensitive serological test for smear-negative tuberculosis so far. Tests for tuberculous meningitis need clinical evaluation. Serological tests for human immunodeficiency virus (HIV)-related tuberculosis are disappointing. In general, antibody levels in primary tuberculosis are low and appear directed towards cytoplasmic antigens, whilst in post-primary disease antibody levels are higher and appear to bind to secreted antigens. No single reagent gives a 100% sensitivity; future research should identify the best combination of antigens for the serodiagnosis of tuberculosis.

AIDS-Related Opportunistic Infections↗
PubMed1994

Clinical evaluation of a serological assay using a monoclonal antibody (TB72) to the 38 kDa antigen of Mycobacterium tuberculosis.

We examined an enzyme-linked immunosorbent assay (ELISA) modification of a radioimmunoassay, using the TB72 monoclonal antibody, as a serological test for tuberculosis in a clinical setting. Sera were obtained from 238 patients with suspected pulmonary tuberculosis, 30 patients treated for tuberculosis, 28 contacts, and 480 random samples from inpatients. Antibody levels were measured as the dilution of serum causing 50% inhibition of binding of the TB72 monoclonal antibody, which binds to an epitope of the 38 kDa antigen specific to the Mycobacterium tuberculosis complex, a positive titre being > 3. Positive antibody titres were present in 21 out of 25 (84%) patients with smear-positive and 22 out of 27 (82%) patients with smear-negative, culture-positive tuberculosis, and 37 out of 41 (90%) patients successfully treated for tuberculosis but without bacteriological confirmation of disease. Three out of 82 (4%) patients with a firm alternative diagnosis to tuberculosis gave a positive result. Serological tests were negative within 2.5 yrs of successful treatment. Patients without a definite diagnosis one year after tuberculosis had been suspected, and those who had received inadequate treatment for tuberculosis, were frequently positive (21 out of 31 and 21 out of 32, respectively). Positive tests concurred with tuberculin reactivity in 8 out of 11 contacts given chemoprophylaxis. Screening of 480 random serum samples gave 22 positive titres, 16 of which were not associated with tuberculosis; none of these 16 had an antibody titre > 10. We conclude that the TB72 test provides additional information in the diagnosis and treatment of tuberculosis. Antibody titres > 10 suggests active tuberculosis; titres of 3-10 merit observation.

Adult↗
PubMed1992

Specificity of antibodies and tuberculin response after occupational exposure to tuberculosis.

Specific antibody levels and delayed-type hypersensitivity skin responses to antigens of Mycobacterium tuberculosis in 39 hospital staff who were heavily exposed to tuberculosis (TB) were compared with those in 36 factory employees from Indonesia. Antibody levels to the TB68 epitope of the 14-kDa antigen were significantly greater, while titers to the TB23 (19-kDa) and TB72 (38-kDa) epitopes and lipoarabinomannan (LAM) were lower in exposed than in nonexposed subjects (all P less than .02). The intensity of tuberculin responses correlated positively with anti-LAM and negatively with anti-19-kDa antibody levels. Possible reasons for the selective humoral response of chronically exposed healthy subjects to the 14-kDa antigen, but not to other antigens immunogenic in patients with tuberculosis, are discussed.

Antibodies, Bacterial↗
PubMed1992

Clinical value of the measurement of Mycobacterium tuberculosis specific antibody in pulmonary tuberculosis.

BACKGROUND: A serological test that could help to diagnose tuberculosis, especially smear negative disease, would contribute to patient management. METHODS: Levels of antibody to distinct antigens of Mycobacterium tuberculosis were assessed for their value in the diagnosis and management of pulmonary tuberculosis. Serum was taken from 52 patients who were smear positive, from 27 patients who were smear negative but with evidence of active tuberculosis (sputum culture positive in 16, response to antituberculosis chemotherapy in 11), from 11 patients with old healed tuberculosis (pre-antibiotic era), and from 39 healthy subjects vaccinated with BCG. RESULTS: In smear positive tuberculosis an enzyme linked immunosorbent assay using a single 38 kDa antigen gave a diagnostic sensitivity of 80% with a 100% specificity. In smear negative pulmonary tuberculosis, however, combination of the 19 kDa antigen, lipoarabinomannan (ML 34 epitope), and hsp 65 (TB 78 epitope) was needed to achieve a sensitivity of 64% with a specificity of 95%. Recurrent and extensive radiographic disease with a poor prognosis was associated with high anti-38 kDa and low anti-14 kDa antibody levels in patients with active disease. Patients with less pulmonary cavitation had high anti-19 kDa titres. Bacteriological relapse during treatment was indicated by a rise in anti-14 kDa (TB68 epitope) antibodies. Four patients with non-tuberculous mycobacterial infection showed no anti-38 kDa antibody. CONCLUSION: Antigen or epitope specific serology may help in the diagnosis, assessment of prognosis, and monitoring of chemotherapy in patients with pulmonary tuberculosis.

Antibodies, Bacterial↗