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.
Proof that a patient is suffering from sulfone-resistant leprosy depends on demonstrating that his bacilli can multiply in the mouse foot pad even when the mice are fed sulfone in the diet. Hitherto the maximal dose of DDS tolerated by the mouse has been used in such tests. This paper concerns a patient whose bacilli multiplied in mice fed lower doses of DDS, but were inhibited when the maximal dose was used . His clinical features are distinctive and probably characteristic of this type of "partial" resistance. It is likely that more cases of this type will be found . Recommendations are made concerning the investigation of possible DDS-resistant leprosy patients and their treatment.
Using a trial design previously evolved at Sungei Buloh Leprosarium, a pilot trial was performed of B.663, in the dosage of 100 mgm. twice weekly, in eight patients with previously untreated lepromatous leprosy. The therapeutic results, as measured by clinical, bacteriologic and histologic assessment, and especially by the rate of fall of the morphologic index, were similar to those obtained with sulfone therapy or with 0.663 in the dosage of 300 mgm. daily. Although B.663 pigmentation was produced in all eight patients, it developed more slowly and was less intense than with standard dosage. Difficulties resulting from skin discoloration in assessing the clinical progress of patients on B.663 are discussed.
In certain areas of Sabah, East Malaysia, local houses are frequently built without walls or with incomplete walls. Also, the people in these areas often refuse permission for their houses to be sprayed inside with insecticide (DDT). These special conditions are the reason for the persistence of malaria transmission under a WHO malaria eradication programme.Field trials were conducted in specially constructed huts, similar to the local houses, in which all-night collections of mosquitos were made, both those biting human baits and those resting on walls, in order to determine (1) the effectiveness of spraying DDT in houses without, or with incomplete, walls; and (2) the best way to protect people against mosquito bites with DDT-spraying where the house-owners have refused indoor spraying.The results indicate that (1) as expected, DDT-spraying inside a hut with incomplete walls is less effective than in a hut with complete walls, especially 6 months or more after spraying; (2) external spraying of walls with DDT at double the normal dose (i.e., 4 g/m(2)) greatly reduced contacts between man and mosquito and thereby limited transmission of malaria.
Fifteen patients with pure lepromatous leprosy were treated for 12 months with DDS at 50 mgm. twice weekly. The drug was fully effective in this dose, and the incidence and severity of ENL were not less than on larger doses