Interventions for Tuberculosis Control and Elimination 2002

article. The experiences in Edinburgh of Sir John Crofton and collaborators
were relegated to the correspondence section of the American Review
of Tuberculosis (figure 44). 477 The efficacy of this approach seemed convincing,
although a randomized trial would surely have been indicated to
remove any lingering doubts about biased selection and ascertainment. A
subsequent study of the British Medical Research Council, begun in 1956,
added a streptomycin supplement until susceptibility to PAS was demon-
Per cent positive
100
80
60
40
20
0
0 2 4 6 8 10 12
Months of chemotherapy
Figure 44. Sputum culture conversion in patients with pulmonary tuberculosis due
to susceptible organsisms, with triple therapy consisting of streptomycin, paraaminosalicylic
acid, and isoniazid. Reproduced from 477 by the permission of the
publisher American Thoracic Society at the American Lung Association.
strated. 496 This indicates that the importance of a resistance-preventing
component in the intensive phase was not yet fully appreciated. In the
report on US Public Health Service trial 4, it was explicitly stated that there
was no advantage of using all three drugs in cases of recent origin. 482 In
US Public Health Service trial 3, a comparison of the combination streptomycin
plus isoniazid with streptomycin plus PAS was made; it demonstrated
the superior ability of the isoniazid-containing regimen to induce
culture conversion (figure 45). 481 However, the difference between a regimen
of streptomycin plus para-aminosalicylic acid plus isoniazid versus
streptomycin plus para-aminosalicylic acid was not ascertained.
Nevertheless, common sense prevailed and by the end of the 1950s,
the regimen that had been used in Edinburgh became, at least in the United
63