Procedures for developing a simple scoring method based on unsophisticated criteria for screening children for tuberculosis.

OBJECTIVE: To develop a scoring system for screening children for tuberculosis (TB) and for selecting suspects for further investigation in tuberculosis control programmes. Application of the score model, which would not require sophisticated or expensive technology, would be directed towards resource-poor countries with high prevalences of tuberculosis, where health care workers have to deal with diagnostic problems away from district hospitals or diagnostic facilities. DESIGN: Based on contributions from members of an IUATLD task group from 10 countries on the use of diagnostic criteria in childhood tuberculosis, criteria were selected to be used as elements in a score model. Data were collected by standardised questionnaire on 879 subjects aged under 15 years. Of these, 794 were considered probable or confirmed cases of tuberculosis by the diagnosing doctors. From each record, the criteria/procedures used in the diagnosis of probable/confirmed TB and regarded by the doctors as relevant criteria were selected. Bacteriology, histology and chest radiography were used either singly or collectively as the definitive reference (gold standard) against which the more subjective criteria (symptoms, clinical signs, skin test) would be evaluated. The latter criteria cited as relevant were then ranked and further explored for inclusion in the score model. The relative importance of each criterion to every other criterion on the list was expressed as weights, determined by employing a logarithmic least squares method to solve the ratio scale estimation problem which underlies decision-making involving more than one criterion. The resultant values were then assigned to each criterion in the final score model. RESULTS: The five clinical criteria thought to be most relevant as predictors of disease in children were history of contact with a case of tuberculosis, positive skin test, persistent cough, low weight for age, and unexplained/prolonged fever. In selecting the optimal cut-off points for the model at which tuberculosis would be suspected, low sensitivity and specificity (below 70%) but reasonably good positive predictive values (60%-77%) were obtained, depending on age group and epidemiological setting. In low tuberculosis prevalence settings, heavy reliance is placed by the model on a history of contact with a household case of tuberculosis and on a positive skin test, both of which have to be true. For high prevalence settings, more or less equal weighting is assigned to all five elements. Case contact and skin tests are less important, with low body weight, prolonged fever and cough being more indicative of tuberculosis. CONCLUSION: The model provides for epidemiological differences between target populations and should prove successful as a screening tool to select children for further investigation by radiography and bacteriology.

Survival of lung cancer in East London: a prospective survey.

Five hundred men and 76 women all under the care of one physician at the London Chest Hospital were diagnosed as having bronchogenic carcinoma and admitted to a prospective survey between May 1966 and April 1978. The survey was completed in December 1984 when all but 19 of the 500 men had died. None was lost to follow up. The longest period of surveillance was 18 years 7 months, the shortest 6 years 8 months. The five-year survival of the group of 500 men was 7.6% (38), and 22% (32) for the 145 patients who had had resections. Of the 78 patients (63 men, 15 women) who had small cell carcinoma, only one survived 3 years; the others died in under 2 years, giving a median survival of 5 months. The median survival of the 21 untreated cases in this group of small cell carcinoma was 2 months.

Spread of tuberculosis within a family.

A man aged 22 was admitted to hospital with active pulmonary tuberculosis. Routine contact examination and close follow-up of his family detected fourteen members who had been infected. Thorough follow-up of all close contacts of patients with infectious tuberculosis is vital to the control of tuberculosis. Efficient contact procedure depends on close liaison between chest clinic, health visitor, and district community physician.

Relation between lung cancer, chronic bronchitis, and airways obstruction.

Since cigarette smoking is an important cause of lung cancer and chronic bronchitis both conditions should occur together more often in cigarette smokers than would result from chance. If they do commonly occur together then severe airways obstruction, which is often associated with chronic bronchitis, should also be often associated with lung cancer. To discover whether this were so three groups of patients were studied at the London Chest Hospital. Two hundred men and 43 women who presented with lung cancer provided information on the prevalence of defined chronic bronchitis and airways obstruction in those suffering from lung cancer. The third group consisted of 233 men presenting with defined chronic bronchitis who were kept under observation to discover how many would die from lung cancer. The results suggested that simple bronchitis and lung cancer often occur together but that obstructive bronchitis and lung cancer do not often occur together. The lack of association between lung cancer and severe airways obstruction requires an explanation.

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.

Humoral response to defined epitopes of tubercle bacilli in adult pulmonary and child tuberculosis.

In order to investigate the humoral response to tuberculosis in different categories of patients, serum antibody levels to six epitopes of Mycobacterium tuberculosis in adult pulmonary and child tuberculosis were determined. Serum antibody titres were determined by competitive inhibition with radio-labelled murine monoclonal antibodies in 67 adults and 85 children with tuberculosis and in 79 age-matched controls. BCG vaccination (n = 39) and self-healed tuberculosis (n = 11) in adults gave rise to higher antibody titres to TB68, TB23 and TB72 epitopes (all p less than 0.003) when compared to non-vaccinated controls (n = 18). TB68 titres were higher (p = 0.006) in self-healed than in vaccinated adults. Adult sputum-negative patients (n = 15) had higher titres to TB71 (p = 0.015) and ML34 (p = 0.02) epitopes compared to BCG-vaccinated healthy controls, while sputum-positive patients (n = 41) had higher titres to all epitopes tested (all p less than 10(-4]. The diagnostic sensitivity, with a 95% specificity, was best with the combination of probes TB23, TB68, TB72 for sputum-positive (85%) and TB78, ML34 (53%) for sputum-negative patients. Antibody titres in children with tuberculosis were lower than in adult patients; diagnostic sensitivity in histologically or microbiologically proven cases (n = 18) was only 44%, while that in mediastinal lymph-adenitis (n = 67) was 13.5%. This study suggests that the magnitude and specificity of the humoral response to tubercle bacilli varies with site and severity of infection; the implications for pathogenesis or protective immunity are discussed.