Immunotherapy with Mycobacterium vaccae as an adjunct to chemotherapy in the treatment of pulmonary tuberculosis.

47 patients with adult-type pulmonary tuberculosis attending the Chest Diseases Hospital in Kuwait were given a single injection of 10(9) irradiation-killed M. vaccae after 1 month of a 9-month course of chemotherapy. The patients were followed-up for 3 more months in double blind comparison with 65 patients given an injection of saline (placebo). The immunotherapeutic injection produced a small local lesion in 44/47 patients, 18 of which ulcerated and produced small scars. Immunotherapy made no measurable difference to the bacteriological, biochemical, haematological, or radiological parameters measured. However it was associated with significantly improved weight gain, reduced size of skin test response to Tuberculin, increased lymphocyte proliferation to common mycobacterial antigens, and increased antibody levels to mycobacterial antigens. The changes in skin test and LTT responses were related and occurred in 29% of patients whose recognition of common mycobacterial antigens returned to normal. The remaining patients did not differ in these respects from those receiving placebo. The proportion of patients whose responses were improved was very similar to that achieved using the same immunotherapeutic agent in a group of treated multibacillary leprosy patients.

HLA-DR and tuberculin tests in rheumatoid arthritis and tuberculosis.

Responses to four new tuberculins were found to be significantly reduced in 46 patients with rheumatoid arthritis in comparison with a control group of 79. Except for tuberculin itself, the same was found in 111 patients with tuberculosis. In common with patients with tuberculosis and leprosy, those with rheumatoid arthritis did not respond to common mycobacterial (group i) antigen. Three DR haplotypes were found to have significant effects on skin test responsiveness of the rheumatoid patients but had little or no effect on that of the patients with tuberculosis and none on that of the healthy control group. Rheumatoid patients with the HLA-DR4 haplotype had significantly greater responses to all four reagents than did non-DR4 patients, but their responses to leprosin A and scrofulin remained significantly lower than those of the control group. Possession of HLA-DR3 haplotype was associated with skin test positivity approaching normal, but the sizes of responses were reduced. Possession of DR7 was associated with an unexpected reduction in skin test positivity, especially in the case of tuberculin. These results support the hypothesis that mycobacteria, or autoantigens cross reactive with mycobacteria, may be involved in the aetiology of rheumatoid arthritis. The results also show that the regulation and specificity of responsiveness to mycobacterial antigens are different in patients with rheumatoid arthritis with different HLA-DR haplotypes.

Unexpected findings amongst the skin test responses to mycobacteria of BCG vaccinated Kuwaiti school children.

A multiple skin test survey was carried out in Kuwait on 1200 school children aged 8-11 years, and on 1228 children aged 12-16 years. With only 15 exceptions, all these children had received vaccination with Japanese BCG just before they started school, 5 years and 9 years earlier respectively. Tuberculin positivity was almost 90% in both groups, with a mean response size of 8.7 mm. This was associated with remarkably high responsiveness to many of the other mycobacterial species investigated. Since this high reactivity was also to Mycobacterium ulcerans, a species most unlikely to be present in Kuwait, it is proposed that this might be due to responsiveness to group ii antigen which is present in all slow growing species. Only M. flavescens and M. rhodesiae amongst the fast growing species, were absent as sensitising organisms. After correction for the supposed reactivity to group ii antigen, M. avium B, M. gordonae, M. ulcerans and M. xenopi amongst the slow growing species, also appeared to be absent from the Kuwait environment. The species most commonly encountered were M. leprae, M. chitae, M. neoaurum, M. diernhoferi, and M. vaccae in this order. This was a remarkable finding for a country assumed to be poor in contact with environmental species, and known to have a very low prevalence of leprosy. As previously reported from Iran, but not confirmed in other places, there was a 95% correlation between responsiveness to Leprosin A and Vaccin. Amongst the slow growing species M. avium A, M. intracellulare, and M. kansasii appear to be frequent sensitising agents, in common with many other places.