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.
A detailed account and definition is given of the previously inadequately described "giant reactions" to tuberculin occasionally seen in leprosy patients. The reaction is an accelerated and exaggerated response to species-specific antigens of Mycobacterium tuberculosis found in both PPD and New tuberculin. Our studies were performed in Malaysia, Uganda, Spain, and England. There was a significantly higher incidence of the phenomenon in Malaysia than in the other centers, but this may have been because there alone previously untreated lepromatous (LL and BL) patients were serially tested for up to three years after starting chemotherapy. Of the 28 patients exhibiting giant reactions, 27 occurred among lepromatous patients (24 LL and 3 BL), of which only 3 (1 LL and 2 BL) were untreated. One treated BL patient had developed, and one untreated BL patient was a family contact of, active tuberculosis. Giant reactions are uncommon in untreated and in very long-term treated LL patients, but may occur in up to a fifth of those receiving their first 1-3 years of chemotherapy. Although the mechanism is not yet understood, it appears to be a coincidence of delayed hypersensitivity of the tuberculin type and a less-delayed phenomenon of excessive local edema associated with local lymphadenopathy and short-lasting symptoms of malaise and pyrexia. It is suggested that the majority of giant reactions occur during a period of temporary lack of immune regulation associated with changing levels of antigenic load.
A controlled clinical trial, using the "double blind " technic, is reported of combined dapsone and ditophal therapy compared with dapsone and placebo in the treatment of pure lepromatous and near lepromatous leprosy. Twenty-five untreated, matched pairs were admitted, and the final analysis was made on 23 pairs and 47 patients studied for one year. Dapsone and ditophal were commenced simultaneously, and over the treatment period 0-1.5 months, a statistically significant (at the 1 per cent level) greater decrease in the percentage of solid-staining bacilli occurred in the smears of pure lepromatous patients treated with ditophal and dapsone than occurred in the smears of patients treated with placebo and dapsone. Therefore, it is evident that combined therapy resulted in a faster rate of killing of leprosy bacilli than did dapsone alone. However, only one method of clinical assessment of the pure lepromatous pairs favored combined therapy; the two other methods of clinical assessment used, and the bacterial index and biopsy index results, all failed to reveal any significant differences between the two treatment groups. In addition, the incidence and severity of erythema nodosum leprosum did not differ in the two groups. Since the more rapid death of bacilli early in treatment had little effect on the rate of improvement of patients after 12 months, the widespread use of ditophal with dapsone does not appear to be justified. Special circumstances are envisaged, however, in which ditophal would be a useful adjunct to treatment. The small number (11) of near-lepromatous patients studied showed a high incidence of lepra reactions, and 4 underwent histologic change during their year in the trial. There was no evidence that the addition of ditophal to dapsone treatment increased the rate of improvement, clinically, histologically or bacteriologically, in this type of leprosy, which, because it is so unstable, appears unsuitable for formal clinical drug trials. Although the majority of the patients included were light-skinned Chinese, no contact dermatitis or other toxic effects of ditophal were observed.