Tubercle最新文献

In an effort to study the immunological responses to antigens of tubercle bacilli, 49 tuberculin positive and 41 tuberculin negative hospital contacts aged 20–29 years (staff nurses and students working in Government Rajaji Hospital, Madurai, South India) were studied for serum antibodies (IgG, IgM and IgA classes) to BCG by ELISA and diameter of induration to PPD by Mantoux procedures. The two immunological parameters were correlated in regression analysis. The results have revealed higher anti-BCG serum antibody levels in hospital contacts than in non-contacts, significantly higher antibodies in tuberculin negative hospital contacts than in tuberculin positive hospital contacts, an inverse correlation of tuberculin reactivity and antibodies and a bimodal decline (regression) of antibodies against the increase in skin test induration. This study has thus suggested the existence of an immunological spectrum in hospital contacts from south India; persons at one pole of the spectrum were tuberculin negative and possessed significantly elevated antibody levels and those at the other pole of the spectrum were tuberculin positive and possessed low antibody levels. Thus the spectrum of immune reactivity may be due to an inherent susceptibility/ resistance of an individual to Mycobacterium tuberculosis.

A 33-year-old man with AIDS and pleuro-pulmonary tuberculosis was treated with a combination of antituberculous medications for 12 months and with continuation of isoniazid. A total of 2 months after completing combination therapy the patient developed fever, malaise, and anorexia. Mycobacterial blood cultures grew M. tuberculosis and the patient improved with the readministration of rifampicin and pyrazinamide. Phage typing of the patient's isolates of M. tuberculosis confirmed that he had experienced a relapse and not a reinfection. The patient had received 5 months of his treatment while hospitalised. We believe he was compliant with therapy outside the hospital because he attended all of his clinic appointments. Follow-up studies of HIV-infected patients with tuberculosis are therefore needed.

Fibreoptic bronchoscopy (FOB) showed that of 82 patients who had ‘typical’ X-ray pictures of tuberculosis (fibronodular infiltrate in the upper lobe), 40 had active tuberculosis, 30 had inactive tuberculosis and 12 had non-specific fibrosis of undetermined origin. The remaining 16 patients with other specific aetiologies of the upper lobe lesions (e.g. carcinoma) had different X-ray pictures such as a mass or alveolar filling of lobar distribution. In communities with a high prevalence of tuberculosis FOB is therefore unlikely to reveal any specific aetiology (apart from tuberculosis) in immunologically competent patients who have ‘typical’ X-ray picture of tuberculosis.

We document, however, that in sputum-producing patients with active tuberculosis, FOB was the exclusive means of diagnosis in $\text{11}\text{27}$ (41 %), compared with $\text{10}\text{13}$ (77%) in nonsputum-producers. An immediate diagnosis was made in 22% and 38% of cases respectively.

Two chemotherapy regimens of 28 weeks (6M) and 36 weeks (8M) duration were compared in patients with previously untreated pulmonary tuberculosis in 30 health districts of Algeria. In the 6M regimen, patients received isoniazid plus rifampicin daily throughout with streptomycin and pyrazinamide in addition for the first 8 weeks. In the 8M regimen patients received isoniazid daily throughout plus rifampicin for the first 16 weeks and streptomycin and pyrazinamide as well for the first 8 weeks. The districts were allocated to apply either the 6M or the 8M regimen to all eligible patients. However, 22% of eligible patients were not admitted, the most common reason being oversight on the part of the personnel in the local health centres.

A total of 2218 (977 6M,1241 8M) patients was admitted and the results were assessed 2 years after the due date of completion of chemotherapy, irrespective of whether or not management had deviated from the study protocol. An appreciable proportion of patients (25% of 6M, 29% of 8M) could not be assessed because they failed to attend for follow-up or the collection of specimens was overlooked or because of difficulties in the transport of specimens to the reference laboratory in Algiers, and a further 5% and 4% of patients died. Of those who were assessable 7 (1 %) of 731 6M and 15 (2%) of 875 8M were classified as having an unfavourable response during or after chemotherapy because they had one or more positive cultures. In addition 16 (2%) 6M and 18 (2%) 8M patients had received additional chemotherapy for failure, relapse or the development of non-pulmonary lesions but had achieved a favourable status.

Of 1018 (488 6M, 530 8M) patients assessed who had fully sensitive strains pretreatment and completed treatment as planned, 97% in both series had a favourable status 2 years after their chemotherapy was due to be completed. In patients with initial strains resistant to isoniazid the results were less good in the 8M than the 6M series: none of the 19 6M compared with 5 of 26 in the 8M series having an unfavourable outcome suggesting that the duration of rifampicin may have been important in patients with initial isoniazid resistance.

A slightly higher proportion of patients on the 8M regimen defaulted during chemotherapy (9.3% compared with 6.7% in the 6M regimen) but there was no difference between the regimens in other measures of compliance.

Upper intestinal obstruction caused by tuberculosis is relatively rare, and the diagnosis is often missed. Two cases are described that were diagnosed by frozen section during laparotomy. It might be thought that endoscopy would have eliminated these difficulties, but this is not in fact the case. Many laboratory safety codes forbid the use of frozen sections on tuberculous material, but in endemic areas this restriction is not practical. Special facilities are required so that all frozen sections can be handled safely.

In order to solve the problem of poor patient compliance, attempts were made to prolong the bioavailability of anti mycobacterial drugs after a single administration. A single implant of polylactic-co-glycolic acid (PLGA) co-polymer containing isoniazid ensured its sustained release up to 6 weeks. The levels are comparable with those obtained from daily doses. Homogenates of liver and lungs from animals killed at 6 weeks after a single implant showed high antimycobacterial activity against Mycobacterium tuberculosis. Sera from the implant and daily dose group animals showed no significant difference in renal, hepatic and haematological parameters. The implant caused no local or systemic toxicity.

As the interpretation of tuberculin skin tests is controversial in subjects who have received BCG vaccine, we administered Mantoux tests to 2588 randomly selected Saudi children aged 5–13,1945 of whom had been vaccinated with BCG at birth and 643 were unvaccinated. Only 7.8% of the BCG-vaccinated children were Mantoux positive (⩾10 mm induration) at the age of 5 years, which was not significantly different from the unvaccinated children.

The tuberculin sensitivity rose more steeply with age in the BCG-vaccinated than the unvaccinated children so that the difference between both groups became statistically significant in those aged 12 and 13 (20% versus 3.9%,15.5% versus 4.1 % respectively). These findings support the previously expressed theoretical postulates that BCG-vaccinated subjects display an increased ability to respond immunologically to encounters with environmental mycobacteria. In communities with low prevalence of environmental mycobacteria, this would result in a slow but persistent rise of skin reactivity to tuberculin which, if given time, will become greater than that of unvaccinated subjects.

This review describes the recent advances in knowledge of the nature and range of physiological changes that occur in the skin at the site of a positive tuberculin reaction. The infiltration of T-cells and monocyte/macrophages shows a marked compartmentalisation suggesting that the.functions of particular cell types depend on their localisation. The extent of cutaneous oedema (detectable as induration) is not closely related to other features of the reaction or to systemic indicators of cell mediated immunity. The intensity of hyperaemia is maximal at the centre of the reaction and is correlated in most cases with the density of cellular infiltration in the dermis suggesting a functional coordination. Despite this correlation between cell numbers and velocity of blood flow, the reaction normally shows hypoxia, hypercapnia and local acidosis, but this metabolic modification may not be a wholly disadvantageous effect since these conditions appear to facilitate the growth and metabolism of activated lymphocytes and macrophages. In very strong reactions, there is central relative slowing of the circulation and this may lead to necrosis in extreme cases.

There are however a minority of cases where cell infiltration occurs but induration is not palpable: this situation has been named pseudoanergy, and its pathogenesis has not yet been established. The occurrence of pseudoanergy must throw some doubt on the conventional criteria for positivity in the reading of tuberculin skin tests (induration >5 mm) and this may have relevance to future strategies for assessment of new vaccines.

The human tuberculin reaction should prove a valuable model for coordinating knowledge of the cellular and molecular mechanisms induced by mycobacterial immunity with the pathogenesis of tissue reactions in clinical tuberculosis. This should lead to the rational development of therapy for limiting inflammatory and scarring damage in antibiotic treated mycobacterial disease.

We investigated as supervised out-patient treatment programme, operating in a predominantly rural area of KwaZulu, South Africa, for black tuberculosis patients. In particular, we evaluated treatment outcomes over a 3-year period (July 1987 to December 1989) and community involvement in the programme. In 1987 there were 118 patients (67 males, 31 females and 20 children) on the programme; 188 patients (106 males, 46 females and 36 children) in 1988; and 230 patients (112 males, 49 females and 69 children) in 1989. Analysis of treatment outcomes showed. that 88% completed treatment, 8.5% defaulted and 3.4% died in 1987; 93% completed treatment, 4% defaulted and 3% died in 1988; 94% completed treatment, 3% defaulted and 3% died in 1989. The majority of patients were supervised by Voluntary Health Workers (68% in 1987,82% in 1988 and 83% in 1989). Only four patients were readmitted to the hospital due to an unreliable health worker in this 3-year period. These findings suggest that the supervised out-patient treatment programme is meeting the ultimate aims of control; namely, holding and curing patients through community involvement and responsible participation.

In 204 patients with smear-positive pulmonary tuberculosis HLA-A10, 138 and DR2 were more frequently found than in 404 control subjects (p=0.01); the greatest attributable risk (0.29) was associated with HLA-DR2. The radiographic extent of disease was also associated with HLA-DR2 (p = 0.0001). In 152 patients with smear-negative pulmonary tuberculosis, the frequencies of HLA-A10 and B8, but not DR2, were greater in the control subjects (p = 0.001 and 0.01 respectively). HLA-DR2 may be involved in the pathogenesis of advanced pulmonary tuberculosis. Study of endogamous, genetically disparate populations (caste) revealed other HLA associations (A3, B12 and DR4) unique to them, suggesting that genes linked with the HLA complex might also be significant in the pathogenesis of tuberculosis.