Clinical evaluation studies in lepromatous leprosy fourth series: 4, Butoxy-4dimethylaminodiphenyl thiourea (DPT), amodiaquin, and 4-4 diaminodiphenyl sulfone (DDS) 2.5 mgm. and 4 mgm. per kg. of body weight

In a duplicate experiment on lepromatous leprosy carried out at two leprosaria in the Philippines, Central Luzon Sanitarium near Manila and Eversley Childs Sanitarium near Cebu City, four groups of patients were treated respectively with 4 butoxy - 4' dimethylaminodiphenyl thiourea (SU 1906), amodiaquin (camoquin), a higher dose of DDS (4 mgm. per kgm. of body weight) and a lower dose of DDS (2.5 mgm. per kgm.) Treatment was continued for 96 weeks, except in the amodiaquin group in which the drug was discontinued at 72 weeks; most of the patients of this group were continued on DDS. At both institutions the superiority of DDS over amodiaquin was evident from the physical examinations at 72 weeks, and this was confirmed at 96 weeks in spite of the fact that most of the amodiaquin patients had received DDS from the 73rd week. SU 1906 likewise was superior to amodiaquin. In comparison with both higher and lower doses of DDS, however, SU 1906 showed consistently lower rates of improvement at each examination, but the differences were small. The patients on the higher dosage of DDS did not improve in greater proportion than those in the lower dose, as far as the clinical evidence goes. As had been found in our previous studies, healing of ulceration of the nasal septum took longer than is usually supposed, and new ulcerations occurred under continuous therapy with either DDS or SU 1906. At Eversley Childs, where the treatment schedules were more closely adhered to than at Central Luzon the value of sulfone treatment was indicated by a higher percentage of healing and a lower frequency of patients developing new ulcerations...

Clinical evaluation studies in lepromatous leprosy. Third series: nicotinamide, and BCG vaccination as supplements to diaminodiphenyl sulfone (DDS)

In a triplicate therapeutic experiment on lepromatous leprosy carried out at two leprosaria in the Philippines and one in the Union of South Africa, two major groups of patients at each institution were treated respectively with diaminodiphenyl sulfone (DDS), and with DDS plus nicotinamide. Tuberculin-negative patients of each group were divided into two subclasses. The patients of one subclass were vaccinated at least once with BCG; those of the other were left unvaccinated. Treatment was continued for 48 weeks. No evidence was found that either supplementary therapy with nicotinamide or vaccination with BCG was advantagenous. Patients of all subclasses showed clinical and bacteriologic improvement, but those treated only with DDS and not vaccinated showed about the same progress as others. Observed clinical improvement was limited to dermatologic lesions; there were no significant changes in the extent of anesthesis associated with any of the therapies. Only 6 of 434 patients at all institutions developed lepromin reactivity of the MItsuda type, and in all of these the size of the reaction was small. The occurrence of the reactional condition, erythema nodosum leprosum, was not associated with either clinical or bacteriologic improvement. It was equally frequent in the two principal therapy groups, was not evoked by BCG vaccination, and was not associated with reactivity to PPD (0.0001 mgm.).

Results of six months supplementary treatment of lepromatous patients with mycobacterium marianum vaccine

Twenty leprosy patients were each given intradermal injections of 0.1 cc. marianum antigen, at monthly intervals for six injections, as a supplement to the regular treatment with DDS. Twenty-four other patients treated with DDs only, constituted a control group. These patients were all classified as lepromatous, but in actually some of them were borderline far advanced toward lepromatous. Clinical improvement occurred in 70 er cent of the vaccinated patients and in 79 per cent of the control group. No significant bacteriological improvement occurred in either group during the epriod of about six months. Changes in reactivity to lepromin were not of a striking nature. Such differences as were noted are not of statistical significance, although, on their face, the figures suggest a tendency toward greater increase of reactivity among the vaccinated patients. There appears to have been a tendency for the tuberculin-positive patients to exhibit bigger local reactions to the marianun vaccine than the tuberculin negatives. There is no relation between the sizes of the reaction to marianum and that to tuberculin, they being of very different natures.

Clinical evaluation studies in lepromatous leprosy second series: isoniazid and diasone (diamidin) isoniazid and dihydrostreptomycin also a pilot study with streptohydrazid

1- There is described a controllled therapeutic study of lepromatous leprosy which was carried out concurrently at the Central Luzon Sanitarium and the Eversley Childs Sanitarium in the PHilippines, and the Westfort Institution in South Africa. At Central Luzon, 213 patients commenced and 187 completed 48 weeks of treatment; at Eversley Childs, 234 commenced and 202 completed; and at Westfort, 119 commenced and 111 completed. 2- At each institution the patients were dicided into three matched groups, A, B, and C, taking into consideration sex, age, stage of disease, prior sulfone therapy and certain other factors. Group A received diasone (diamidin) in the Standard dosage; Group B received diasone in the same dosage as A, plus isoniazid (INH), 10 mgm. daily per kgm. of body weight; Group C received the same dosage of INH as B, plus 1 gm. dihydrostreptomycin (DHSM) intramuscularly twice weekly. 3- All therapies were well tolerated. The principal cause for discontinuance of treatment was departure from the institution without permission. As the groups were constituted at the end, however, they were comparable to one another inasfar as this could be determined. 4- On completion of treatment the proportion of each group, at each institution, showing clinical improvement was approximately the same. This was true of general improvement and of improvement in specified lesions such as infiltration, ulcers, nodules and others. A very small proportion became worse, and in this respect there was no evident relationship to any particular therapy. 5- No evidence was obtained that clinical improvement may be related to age, sex or other background factors, except prior sulfone therapy and stage of the disease. At all institutions, patients who had received little or no sulfone therapy before entering the study showed a higher clinical improvement rate than those who had been treated for a year or more. Also at all institutions the L2 and L3 patients taken together showed higher proportions of improvemment than those classed as L1. The patients in whom the disease was more advanced, however, were likewise those who on the average had received less sulfones before entering the study. Unfortunately the numbers of cases were too small to yield improvement rates for patients in various stages of the disease classified as to amount of prior sulfone therapy...