A preliminary study of the effect of contact with environmental mycobacteria on the pattern of sensitivity to a range of new Tuberculins amongst Ugandan adults

Stanford, J. L.; Paul, R. C.; Penketh, Andrea; Thurlow, Susan; Carswell, John; Barker, D. J. P.; Barot, Saroj

doi:10.1017/s0022172400055108

Cited by 25 publications

(8 citation statements)

References 6 publications

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“…Skin tests with a soluble new tuberculin called Vaccin prepared from Myco. vaccae showed that people living in the environment from whence it was cultured reacted to it (Stanford et al 1976). Such sensitization may have primed the immune system for effective BCG vaccination (Stanford et al 1981a).…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy with mycobacterium vaccae in the treatment of tuberculosis

Stanford

Stanford²,

Grange³

2004

Front Biosci

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All the trials of immunotherapy of tuberculosis with killed Mycobacterium vaccae, published or not, that are known to the authors are reviewed here. Following an introduction giving a brief account of some earlier immunotherapies for tuberculosis, the origins of the concept of immunotherapy with M.vaccae are considered. Progress is traced from the early work with irradiation-killed organisms in leprosy to the study in London of modulation of tuberculin skin-test responses, and the first comparative trials in The Gambia and Kuwait. In the last of these studies, dosages and different preparations were compared. As a result of this subsequent studies have used 109 heat-killed organisms, equivalent to 1mg wet-weight of bacilli, as a standard dose. A series of small trials in Argentina, India, Nigeria, Romania, South Africa and Vietnam have pioneered the way forward, disclosing geographic variability, with South Africa as the only country where almost no effects were recorded. Together the studies have shown that a single dose may not be sufficient. These studies have confirmed the mode of action of M.vaccae to be regulation of cell-mediated immunity with enhancement of Th1 and down-regulation of Th2, and they have shown benefits in faster bacteriological conversion, reduction in ESR, recovery of body weight and resolution of radiological opacities, leading to better recovery from the disease even when given to patients receiving directly observed therapy, short-course (DOTS). Three major randomised, placebo-controlled and partly blinded trials have been carried out in Africa. The first, in South Africa showed no M.vaccae-related effects. The second trial, in Uganda, confirmed the observations made in the earlier studies of faster sputum conversion and better radiological clearance. The third trial, in Zambia and Malawi, showed a trend towards benefits in the treatment of HIV seronegative patients but failed to show beneficial effects in HIV seropositive patients. Studies in patients with multi-drug-resistant tuberculosis have shown that multiple doses of immunotherapy are required in most cases, and that these markedly improve cure-rates for these patients. This is especially so when they are also treated with chemotherapy tailored to the resistance pattern of their infecting organisms. A small study has just commenced in which repeated doses of M.vaccae are being administered to a group of patients who have failed treatment with DOTS-Plus (directly observed therapy with drugs selected on the basis of drug susceptibility profiles). Late in the investigation came publications from China supporting and confirming the data in both drug-sensitive and drug-resistant disease, by the use of multiple injections of their own different preparation of M.vaccae. The trial that is now beginning in Vietnam of 3 doses of M.vaccae in the treatment of newly diagnosed pulmonary tuberculosis, is accompanied by a chemotherapeutic regimen with a shortened continuation phase. If this important study is successful, immunotherapy with kille...

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Section: Introductionmentioning

confidence: 99%

Immunotherapy with mycobacterium vaccae in the treatment of tuberculosis

Stanford

Stanford²,

Grange³

2004

Front Biosci

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“…This may be partially responsible for the high proportion of new herd breakdowns identified in cattle tuberculosis control measures, where up to 60% of slaughtered animals have no visible lesions and are negative on culture (Wilesmith et al 1982). However, the greatest importance of environmental mycobacteria is believed to be their role in the immunological priming of humans and animals, thereby modifying their immune response to subsequent exposure to pathogenic species or to Mycobucterium bovis BCG (Stanford et al 1976;Shield 1983;Pallen 1984;Brown et al 1985;Grange 1986Grange , 1987Lyons and Naafs 1987;Stanford et al 1987).…”

Section: Introductionmentioning

confidence: 99%

A longitudinal study of environmental mycobacteria on a farm in south-west England

1997

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Soil, stream beds and cattle drinking troughs were sampled every 3 months over 3 years. More than 750 putative mycobacteria were isolated and grouped into more than 50 biotypes pending full identification. Samples from woodland and farmed land yielded fewer isolates per site compared with other terrains (P < 0.05). Some seasonal effects were noted but the greatest difference was between years 1 and 3. This appeared not to be due to differences in temperature, rainfall or experimental procedure, but coincided with the introduction of organic farming practices. In year 3 there was a significant increase in nitrate‐reducing slow growers, both pigmented (P≤ 0.006) and non‐pigmented strains (P≤ 0.002), and a shift in biotypes was noted. In contrast, all fast growers declined with time, as did those slow growers unable to reduce nitrate. Changing farming practice may alter the profile of environmental mycobacteria, which has important implications for the immunological priming of humans and animals.

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“…They have been used in studies of leprosy (Paul, Stanford & (Carswell, 1975) and Mycobacterium ulcerans infection (Stanford, Revill, Gunthorpe & Grange, 1975), and have also been used to measure the effect of BCG immunization and of geographical locality on both school children (Paul, Stanford, Misljenovic & Lefering, 1975) and adults (Stanford et al 1976). In J. L. STANFORD AND OTEERS to environmental mycobacteria was found among the school children coming from the desert regions of Lodwar in Kenya and Karamoja in Uganda (not published).…”

Section: Introductionmentioning

confidence: 99%

The effect of desert conditions on the reactivity of Libyan schoolchildren to a range of new tuberculins

Stanford

Shield

Paul

et al. 1976

J. Hyg.

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SUTMARYThis study was carried out to investigate the effect of desert conditions on the pattern of delayed hypersensitivity to mycobacteria in school children aged 6-10 and 11-18 years. A new range of tuberculins prepared from ultrasonic lysates of living mycobacteria belonging to 12 different species was employed. Three centres were chosen for study, a sea port and two desert towns differing greatly from each other. The results obtained were compared with those of a previous study using the same reagents in Kenya.As expected both the range of mycobacterial species to which the children reacted, the rate of acquisition of specific hypersensitivity with age and the total percentage of children reacting to individual reagents differed from centre to centre. The harsh desert conditions ofAjdabia produced the least, and the proximity of the people's dwellings to those of their farm animals in Kufra produced the most positive reactors to essentially environmental species. The greatest number of reactors to our Tuberculin were found in Benghazi where the cosmopolitan urban conditions probably lead to a high contact with open cases of tuberculosis. As assessed by skin test reactivity, immunization with BCG in Libya was much less effective than in Kenya. The interpretation of the differences between the results from the different test centres and between those for Libya and Kenya are discussed.

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A preliminary study of the effect of contact with environmental mycobacteria on the pattern of sensitivity to a range of new Tuberculins amongst Ugandan adults

Cited by 25 publications

References 6 publications

Immunotherapy with mycobacterium vaccae in the treatment of tuberculosis

Immunotherapy with mycobacterium vaccae in the treatment of tuberculosis

A longitudinal study of environmental mycobacteria on a farm in south-west England

The effect of desert conditions on the reactivity of Libyan schoolchildren to a range of new tuberculins

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