Circulating immunoglobulin levels in patients with pulmonary tuberculosis with special reference to IgE.

This study has demonstrated high levels of circulating IgE in a group of patients with pulmonary tuberculosis compared with a control group. There was little or no specific binding of circulating IgE to M. tuberculosis but when the serum was heated to 56 degrees C for 1 hour 5/20 of the patients investigated showed appreciable levels of binding. It is suggested that the IgE which binds to M. tuberculosis exists in a heat-labile complex with an anti IgE antibody and that this complex formation may represent a protective host mechanism.

Immune responses and immunostimulation in tuberculosis therapy.

Despite a reasonably extensive literature on cellular and humoral immune responses in tuberculous disease, abnormalities tend to be secondary rather than predisposing to disease. No discrete immune deficiency or failure, which would explain the progression from non-infection to infection with Mycobacterium tuberculosis to tuberculous disease, has been identified. There is evidence that tuberculous disease occurs in a spectrum, analogous to leprosy, and it would seem that if immunostimulants, as adjuncts to standard therapy, are to be of any value in the treatment of tuberculosis, they should be used for non-reactive tuberculosis patients. The range of immunostimulants currently available tends to be indiscriminate in action and their targets in tuberculous disease largely uncertain; their role in therapy in discussed.

Effects of clofazimine alone or combined with dapsone on neutrophil and lymphocyte functions in normal individuals and patients with lepromatous leprosy.

The effects of clofazimine on neutrophil activities such as random motility, migration to the leukoattractants endotoxin-activated serum and N-formyl-L-methionyl-L-leucyl-L-phenylalanine phagocytosis of Candida albicans, postphagocytic hexose-monophosphate shunt activity, and myeloperoxidase-mediated iodination and the effects of clofazimine on lymphocyte transformation to mitogens were assessed in vitro and after ingestion of the drug by normal individuals and patients with lepromatous leprosy. For in vitro studies, the concentration range of the drug investigated was 10(-6) M to 10(-2) M. for in vivo studies, subjects ingested 200 mg of clofazimine daily for a period of 5 days. At concentrations of 5 X 10(-6) M to 5 X 10(-3) M clofazimine caused a progressive dose-dependent inhibition of neutrophil motility without detectable effects on phagocytosis, postphagocytic hexose-monophosphate shunt activity, or myeloperoxidase-mediated iodination. Over the same concentration range, clofazimine inhibited lymphocyte transformation. The inhibitory effect on neutrophil motility was associated with a spontaneous stimulation of oxidative metabolism and could be prevented by coincubation of dapsone with clofazimine. after ingestion of clofazimine responsiveness of lymphocytes to mitogens was decreased in normal volunteers and leprosy patients: neutrophil motility in normal individuals was likewise inhibited.

The pattern of age-specific tuberculin hypersensitivity in two groups of South African schoolchildren.

In epidemiological studies on tuberculosis we have observed a decrease in the prevalence of positive tuberculin reactions around the age of 13. This decrease was apparent in a variety of populations studied. Statistical analysis of the tuberculin testing data demonstrates the significance of the decrease in the proportion of positive reactors at age 13 and also of a reduction in size of reactions. The possibility of suppression of the delayed hypersensitivity reaction at about puberty is considered.

In vitro and in vivo effects of dapsone on neutrophil and lymphocyte functions in normal individuals and patients with lepromatous leprosy.

The effects of dapsone on polymorphonuclear leukocyte functions and lymphocyte mitogen-induced transformation were assessed in vitro and in vivo in normal individuals and in newly diagnosed untreated patients with lepromatous leprosy. The effects of dapsone on the cell-free generation of superoxide by the xanthine: xanthine oxidase system and iodination of bovine serum albumin by horseradish peroxidase were also investigated. In normal individuals dapsone mediated stimulation of polymorphonuclear leukocyte migration in vitro and vivo. Dapsone had no effect on postphagocytic hexose monophosphate shunt activity in vivo. Similar effects were found in patients with lepromatous leprosy. Dapsone also decreased the inhibitory activity of serum from patients with lepromatous leprosy on normal polymorphonuclear leukocyte migration in vitro. Progressive loss of serum-mediated inhibition of migration was observed after ingestion of dapsone by the patients. Further experiments showed that stimulation of polymorphonuclear leukocyte motility was related to inhibition of lymphocyte transformation at high concentrations in vitro, but had slight stimulatory activity on phytohemagglutinin-induced transformation in controls and patients in vivo.

Levamisole augmentation of PPD-induced lymphocyte proliferation.

The effect of levamisole (LMS) on PPD-induced lymphocyte proliferation in vitro has been investigated in 12 patients with pulmonary tuberculosis and 7 healthy tuberculin-positive control subjects. The augmentative effect of LMS was variable when used directly in vitro and also after pre-incubation of the donor cells with LMS. After ingestion of a single 150 mg dose of LMS, lymphocytes from the control subjects showed significant increased responses in PHA- and PPD-induced lymphocyte proliferation.

Follow-up tuberculosis prevalence survey of Transkei.

After 5 years a follow-up prevalence survey was conducted in Transkei on a randomly selected sample of the rural population. The parameters investigated were bacteriological prevalence of tubercle bacilli in sputum, radiological prevalence of chest abnormalities associated with tuberculosis in adults, and hypersensitivity to tuberculin in children. Bacteriological positivity was 2.1% on smear microscopy and 4.3% on culture. Radiological evidence of tuberculosis was demonstrable in 12.5% of subjects, of whom 8.7% were considered active and 3.8% inactive. The mean prevalence of tuberculin positivity according to the Mantoux test was 30.1%. An annual risk of infection of 4% was calculated, showing a continuous decrease of 5% per year on the 7% risk of infection encountered in 1972. Compared with the first survey, a general reduction in prevalence of tuberculosis is evident.

An in vitro assessment of cellular and humoral immune function in pulmonary tuberculosis: correction of defective neutrophil motility by ascorbate, levamisole, metoprolol and propranolol.

Fifty-six tuberculosis patients and twenty-eight control subjects were evaluated in a comprehensive investigation of cellular and humoral immune function in pulmonary TB. The patient group showed significantly higher levels of secretory IgA and serum IgG, IgA and IgM than did the control group but 7% of patients displayed a selective secretory IgA deficiency. Levels of alpha-1-antitrypsin were also significantly higher in the patient group. There were no significant differences in levels of total haemolytic complement, C'3 and C'4. In moderate to moderately advanced TB patients there were no significant differences in T and B cell numbers nor in mitogen-induced lymphocyte transformation and lymphokine production, when compared with the control group. The range of PPD-induced lymphocyte transformation and lymphokine production levels encountered was similar in both groups although certain patients did not respond to the PPD antigen. Neutrophils from TB patients showed increased random motility in vitro but eight out of ten patients showed impaired directed motility (chemotaxis). Phagocytic and anti-microbial functions were normal in the patient group. The neutrophil chemotactic defect was reversible and could be corrected in vitro when the patients' cells were treated with sodium and calcium ascorbate, levamisole, metoprolol and propranolol.

Correlation of the results of X-ray and sputum culture in tuberculosis prevalence surveys.

In the course of 6 tuberculosis prevalence surveys carried out in South Africa, 5477 persons were investigated by sputum culture and chest X-ray. The X-ray was reported to show evidence of tuberculosis in 723 cases, and of these the sputum culture was positive in only 100 (13.8%). The sputum culture was also positive in another 76 (1.5%) cases in which the chest X-ray was negative. The reasons for these discrepancies are discussed.