Studies on the treatment of tuberculosis undertaken by the British Medical Research Council Tuberculosis Units, 1946-1986, with relevant subsequent publications.

This review describes the studies on the treatment of tuberculosis carried out by the British Medical Research Council's tuberculosis units and their many collaborators throughout the world during the period from their formation in 1946 to their closure in 1986. References to all publications on studies during the period are listed. The review also includes selected publications by members of their staff who have continued the studies since closure of the units. The review is under four main headings: 1) controlled trials of chemotherapy, 2) bacteriological studies, 3) pharmacological studies, and 4) studies of surveillance and policies relevant to the control of tuberculosis.Major events in the development of modern chemotherapy and the control of tuberculosis are as follows:1 1946: The initial trial assessing the value of the addition of streptomycin to bed rest.2 1948: The demonstration that the emergence of bacterial resistance to either streptomycin or p-aminosalicylic acid (PAS) alone was greatly decreased when combined treatment was given with both drugs.3 1952-1955: Exploration of treatment with isoniazid alone and in combination with PAS or streptomycin.4 1958-1967: The search for affordable regimens for developing countries that led to the substitution of thiacetazone for PAS.5 1959: The demonstration that chemotherapy given at home was as effective as when given in a sanatorium and did not lead to any increase in the rate of infection in family contacts.6 1958 onwards: Initiation of the policy of full supervision of chemotherapy (directly observed treatment-DOT) and its later implementation in Hong Kong and Madras.7 1961 onwards: Exploration of intermittent regimens of chemotherapy to assist implementation of full supervision.8 1970: The first demonstration that inclusion of rifampicin or pyrazinamide in a regimen of streptomycin and isoniazid substantially reduced the subsequent relapse rate.9 1972-1974: Demonstration that the period of treatment could be shortened to 6 months by the inclusion of rifampicin and pyrazinamide in the regimen.10 1976: Delineation of modern short-course chemotherapy regimens by showing that the sterilising activity of pyrazinamide was confined to the first 2 months of treatment during the intensive phase, whereas the sterilising activity of rifampicin persisted throughout the continuation phase.11 1977 onwards: Demonstration of the value of intermittency in short-course regimens, particularly that three times weekly treatment throughout was as effective as, and less toxic and expensive than daily regimens.When the units were closed in 1986, all of the measures necessary for successful programmes for the control of tuberculosis had been delineated, particularly the regimens of treatment to be used, the need for full supervision of drug-taking (DOT) and the use of surveys to measure the extent to which national programmes were finding and treating infectious disease. These tools were then available to national organisations and to international organisations such as the World Health Organisation (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD), to implement in control programmes.