From an extensive search of one of the largest inpatient leprosaria in the world, at Sungei Buloh, Malaysia, nine patients with lepromatous leprosy were discovered who gave prima facie evidence of sulfone resistance. The evidence was based on a failure to show clinical improvement over at least five years despite treatment with sulfones and an absence of a satisfactory fall in the bacteriologic (BI) or the morphologic (MI) index. The selected patients were admitted to our Research Unit for (a) a further six month, rigorously controlled, trial period on DDS (as injectable sulfone, 300 mgm. twice weekly) and (b) DDS sensitivity tests, based on use of the foot pad infection in mice with bacilli obtained from skin biopsies. The response of the nine patients to the six month trial period on DDS was assessed clinically, bacteriologically and histologically, and revealed that only four of the patients failed to respond satisfactorily. Furthermore, the sensitivity tests in the mouse foot pad infection showed that only the strains of M. leprae from the four patients who failed to improve were insensitive to DDS. Thus there was a good correlation between the results of the clinical and experimental studies and for the first time direct proof for the existence of DDS resistant strain s of M. leprae. The MI proved to be the most sensitive of the assessments used to determine the response of the selected patients to a trial period on DDS. The histology of patients with drug resistance is essentially that of relapsing or very acute leprosy. Its features have much in common with those of "histoid" lesions, the latter being distinguished mainly by the absence of cytologic maturation. Classification is complicated by the presence of borderline features in otherwise lepromatous lesions.
The first three patients with proven DDS-resistant leprosy infections were treated for one year with the riminophenazine
derivative B.663 (300 mgm. daily for six days a week). All of them showed satisfactory clinical, bacteriologic and histologic
improvement, which at the time of writing has been maintained for a total period of 28 months. The results show that
active leprosy resulting from resistance to one drug can still respond satisfactorily to a different type of drug, as is the case with drug resistance in other bacterial infections. In this limited study B.663 showed no toxicity, but the degree of skin discoloration was disconcerting to Chinese patients.