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.
Acne is one of the most common disorders affecting mankind. Although acne does not cause death, it however produces a lot of discomfort, disfigurement and psychological trauma, particularly in teenagers. Acne vulgaris is a chronic condition involving the pilosebaceous unit of the skin. It is characterised by the presence of comedones, inflammatory papules, pustules or cysts, and eventually by scarring. The end result of acne varies from hyperpigmentation, slight pitting, to extremely disfiguring scars that may develop into keloids. Acne fulminans is a rare disorder and is characterised by sudden explosive appearance of highly inflammatory, tender, crusted, ulcerated lesions involving the back, chest and face. It is one of the most scarring acute dermatologic disorders of young people. A case of acne fulminans in a young female who developed haemolysis due to dapsone is reported here.
The proliferative responses of peripheral blood mononuclear cells (PBMC) to Mycobacterium leprae and BCG were studied in two groups of leprosy patients: a group of 8 lepromatous patients who had been on treatment for more than 20 years (TLL) and a group of 8 untreated lepromatous leprosy patients (ULL). The mean response to M. leprae of the TLL group was 6195 cpm with 5 of the 8 patients responding positively. The mean response to M. leprae of the ULL group was 617 cpm, with only 1 patient showing a positive response. The corresponding proliferative responses to BCG were 19,908 cpm in the TLL group and 7908 in the ULL group. Thirteen M. leprae reactive clones were established from 2 TLL patients and 5 M. leprae reactive clones were established from 2 tuberculoid leprosy patients. Seven of these clones, 4 from the TLL patients and 3 from the tuberculoid (TT) patients could be studied further. Three of the TLL clones responded specifically to M. leprae, while one of the clones exhibited a broad cross-reactivity to other mycobacteria. All of these clones were of the CD4+CD8- phenotype. Our findings suggest that responsiveness to M. leprae can be detected in vitro in a proportion of LL patients who have undergone prolonged chemotherapy, and that this response involves M. leprae reactive CD8+CD8- T cells, of which some appear to be specific to M. leprae.
A high-performance liquid chromatographic method was developed to enable dapsone, monoacetyl dapsone and pyrimethamine to be measured simultaneously in plasma samples from volunteers in England and Malaysia who had been dosed with Maloprim. Mean half-lives of 25 and 80 h were calculated for dapsone and pyrimethamine, respectively, but there was wide individual variation. All subjects were found to be classifiable as "slow acetylators".
In view of the problems caused by the chloroquine-resistance of some strains of Plasmodium falciparum, the authors have investigated the effectiveness of diaphenylsulfone against two such resistant strains, from Malaya and Viet-Nam. They found that diaphenylsulfone given during acute attacks of malaria had a blood schizontocidal activity against the Malayan resistant strain but was not rapidly effective in terminating acute attacks in non-immune persons, and that, when the drug was given prophylactically in relatively small doses, it was substantially effective in preventing patency of mosquito-induced infection with the same strain. The protective effect of diaphenylsulfone is that of a clinical prophylactic or suppressive drug; it does not appear to be a true causal prophylactic. It was also found that the protective effect is vitiated by the concurrent administration of paraaminobenzoic acid.These studies indicate a need for further assessment of the antimalarial value of sulfones and sulfonamides, both alone and in combination with other drugs, for prevention and cure.
An account is given of the first hundred consecutive proven cases of sulphone resistance in leprosy, detected in Malaysia between 1963 and 1974. Proof of resistance was clinical in eighty patients and was obtained by drug-sensitivity testing in mice in ninety-six patients; 76 cases were proved both clinically and experimentally, and there was no discrepancy between the two methods. Sulphone resistance was confined to patients with lepromatous-type leprosy--i.e., patients with a large bacterial population. Clinical evidence of relapse due to drug resistance appeared 5-24 years after the start of sulphone treatment. Low dosage favoured the appearance of resistance; therefore regular treatment of lepromatous leprosy with dapsone in full dosage is recommended. The attainment of "skin smears negative for leprosy bacilli" is no test of cure of lepromatous leprosy.
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.