Study of the morphological modifications of Mycobacterium leprae during chemotherapy.

In furtherance of our investigations on the effects of chemotherapeutic agents on the morphology of Mycobacterium leprae, in patients under treatment with sulfones, thiosemicarbazone and isonicotinic acid hydrazide, we have complemented the direct electron microscope observation used in our earlier study with the "shadow-casting" technique. This method offers advantages when one wishes to ascertain the surface changes occurring in the germs subjected to treatment. In our earlier reports (6, 7) we dealt with the morphology of M. leprae from untreated patients and from 6 patients under the effects, in different degrees, of sulfones. Those reports are now complemented with findings in new cases selected from more than 30 patients studied, using particularly the shadow-casting technique which has given us interesting results. We are aware that many investigators have studied, by classical optics, the bacterial lysis of M. leprae as a result of treatment with various kinds of sulfones. Thus in our earlier reports we cited the work of Chaussinand (2), Gomes (4), Fernandez and Carboni (3), and Cochrane (1) bearing on this matter. As had others, Lowe and Smith (5) asserted in 1949 that chemotherapy causes the bacillary body to become thinner and to stain weakly, even though frequently one can find largesized, intensely-stained granules, these changes appearing after a few months of treatment. Later the bacilli show a fragmented appearance, and finally they become undetectable. In 1951, Wheate (8) noted two fundamental facts under similar conditions: (1) There is a marked tendency of the globi and bacillus masses to disintegrate, the latter seeming less clearcut, less compact, and of smaller size, these changes appearing within nine months of 8ulphetrone treatment. Furthermore, the isolated bacilli all showed bipolar staining and were granular and dispersed due, the author believed, to the disintegration of the globi 01' bacillary conglomerations. (2) In addition, there is an increase of intracellular bacilli.