Ediciones > Año 1951 > Artículo No. 1

Thiosemicarbazone (TB-1) ln the treatment of leprosy
Preliminary Communication

Martin Vegas; Jacinto Convit
International Journal of Leprosy. 18: 451-455, 1951
REVISTA: Publicaciones - Dr. Jacinto Convit

NUMERO: Año 1951

TITULO: Thiosemicarbazone (TB-1) ln the treatment of leprosy Preliminary Communication

AUTORES: Martin Vegas; Jacinto Convit

RESUMEN:

PALABRAS CLAVE:

Reprinted from the lNTERNAT. J. LEPROSY Vol. 18, 1951, No. 4 INTERNATIONAL • JOURNAL OF LEPROSY VOLUME 18, NUMBER 4 ÚCTOBER-DECEMBER, 1950 THIOSEMICARBAZONE (TB-1) lN-THE TREATMENT OF LEPROSY PRELIMINARY COMMUNICATION MARTIN VEGAS PTofessor of Dermatowgy, University of Caracas JACINTO CONVIT Chief of the Leprosy Division, Venezuela AND JOSE ANTONIO MEDINA AND ELENA DE BLOMENFIELD Director and Resident of the Cabo Blanco Leprosarium The favorable results obtained in Germany with the thiosemicarbazone called TB-1-or "conteben"-in the treatment of tuberculosis, based on the experimental work of Domagk (1), suggested the possibility that this drug might be therapeutically active in leprosy. With respect to that disease there has as yet been only one report, by Hohenner (2), of the treatment of a single- case. During December 1949, Professor Domagk was in Venezuela and visited the Cabo Blanco leprosy hospital with us. After a discussion regarding the possible therapeutic action of thiosemicarbazone in leprosy, the possibility that tolerance of the drug might be better in leprosy than in tuberculosis, and the possibility that in leprosy it might prove superior in its effects to the already known sulfa drugs, it was agreed that an experimental trial of it should be made at Cabo Blanco, the drug to be supplied without charge by the Bayer Laboratories of Leverkusen, Germany. The writers thereupon established a program based on the norms laid down by the Fifth International Leprosy Congress, the known pharmacological data of this new drug, and the experience in its use in the treatment of tuberculosis, as well as the rules which since 1945 have been followed in Cabo Blanco in the treatment of leprosy with sulfa drugs generally. 451 452 lnternational Journal of Leprosy 1950 MATERIALS AND METHODS Acquisition of the drug.- During the first week of March we received from the Bayer Laboratories an amount of drug equivalent to 9,000 tablets of 0.05 gm. each. This amount, we calculated, was enough to treat 40 patients for only 4 months, which was obviously an insufficient period of time to determine the value of the drug. W e therefore asked our Health Department to buy the amount required to continue the experiment for one year, and that was done, thus assuring the continuity of the experiment. Selection of cases.- For the experiment we selected 42 cases of the lepromatous type of varying degrees of severity, from those which presented merely macules to quite advanced (L3) forms. The major problem encountered was to find suitable cases which had had no previous treatment, for in Venezuela there are practically no leprosy patients in confinement who have not been treated. The group selected has the advantage that it containll, a certain number of women and chíldren, purposely included so as to obtain data regarding their tolerance of the drug. The 43 cases comprise 37 males and 6 females; and there are 7 children. Examinations.-All of the patients were examined clinically, and proper records made, with regard to lesiona of the skin, mucous rnernbranes, and eyes, as well as of the peripheral nerves. Bacteriological exarninations of the skin and nasal mucosa were rnade, the Mitsuda test was applied, biopsy specimens of the skin were removed for histopathological exarnination, and photographs were taken. Clinical and radiological examinations of the thorax were also rnade. Laboratory examinations were made of the blood (cell counts and sedimentation rates), the urine, the feces, the liver function (bromsulphothalein, Takata-Ara, and Uko tests), and blood sugar and urea nitrogen determinations were made. Reexaminations.-It was decided that, for purposes of control, every three months the dermatological and bacteriological examinations should be repeated; that every six months the histopathological examinations should be repeated and new photographs taken; and that each year new neurological and immunological examinations' should be rnade. For laboratory ci>ntrol, it was decided that every two weeks the blood counts, sedimentation-rate determinations, and urine examinations should be repeated; that every four weeks, urea nitrogen and blood sugar exarninations should be made; and that every 8 weeks tests of liver function should be pe;rformed. Dosage.-Care was taken that the doses of the drug given should be in accord with the age and weight of the patients. With the adults, the beginning dose was set at 25 mgm., and with the children 5 mgm. For the former, the dose was increased by 25 mgm. weekly; for the latter, the original dose was maintained for the first month and then slowly increased until 25 mgm. was reached. It was our expectation, which has been confirmed by our experience so far, that in leprosy it would be possible to reach 18,4 Vegas, et al: Thiosemica,rbazone in Leprosy 453 much higher dose levels than in tuberculosis. It appears that the majority of German workers who have been using TB-1 have concluded that the intolerance observed in tuberculosis patients ís due to the liberation of toxins by the destruction of large quantities of bacilli, but in leprosy-at least lepromatous leprosy, with its anergy to the bacillary products-it is to be expected that the destruction of Mycobacterium leprae will not be followed by effects which could be ascribed to any such process. Our experience has led to a modification of the original schedule of increase of doses, because of lack of intolerance of the drug. Consequently, 1n sorne of our patients the dose has been increased at the rate of 50 mgm. per week instead of 25 mgm. At present the distribution of the daily dosage schedule is as follows : _ 900 mgm. (18 tablets) 1 patient 750 mgm. (15 tableta) 2 patienta 700 mgm. (14 tableta) 3 patienta 650 mgm. (13 tablets) 6 patients 600 mgm. (12 tableta) 4 patienta 550 mgm. (11 tablets) 5 patients 500 mgm. (10 tableta) 1 patient 350 mgm. ( 7 tableta) 6 patienta 300 mgm. ( 6 tablets) 2 patients 200 mgm. ( 4 tablets) 2 patients 150 mgm. ( 3 tablets) 3 patients 100 mgm. ( 2 tablets) 6 patients 50 mgm. ( 1 tablet ) 2 patients Because we have riot observed any blood changes, or liver disfunction, or other indications of visceral lesions, we have increased the daily dose in 28 patients above 300 mgm. which is the dose commonly used in tuberculosis. The total amounts of the drug taken iri the six months which ha ve elapsed since the experiment was started are as follow: Over 1,600 tablets (over 80 gm.) 1 patient 1000-1,100 tablets ( 50---55 gm.) 5 patients 900-1,000 tablets ( 45-50 gm.) 7 patients 800- 900 tablets ( 40-45 gm.) 7 patients 700- 800 tablets ( 35-40 gm.) 4 patients 600- 700 tablets ( 30-35 gm.) 3 patients 500- 600 tablets ( 25-30 gm.) 4 patients 400- 500 tablets ( 20-25 gm.) 6 patients 300- 400 tablets ( 15-20 gm.) 2 patients 200- 300 tablets ( 10-15 gm.) 2 patients 100- 200 tablets ( 5-10 gm.) 2 patients 454 lnternational Journal of Leprosy 1950 RESULTS OBTAINED At the time of this preliminary report, September 8, 1950, the duration of the treatment period, begun on March 7, was 6 months in 30 cases, 5 months in 4 cases, 4 months in one case, 3 months in 7 cases, 2 months in one case. Regression of skin lesions.-Regression of erythematous macules, nodules and infiltrations (in "plaques" and diffuse), was evident after the second month. At the end of the fourth month, erythematous macules as well as nodules had disappeared in a considerable number of patients, the infiltrations had regressed appreciably, and the lesions of the mucosa were notably better. The statistics of these changes are as follows: In five and m months: ~ Very important regression of lesiona ............ 21 patients Important regression of lesions ........................ 7 patients Partial regression ................................................ 6 patients In three and tour months: Very important regression of lesiona ............ 1 patient Important regression of lesiona ........................ 2 patients Partial regression ........................ ,....................... 5 patients In two months: Partial regression of lesiona .............................. 1 patient These data show that all of the patients treated for more than two months had evident regression of their lesions, varying from very important to only partial. . Bacteriological changes.-Bacteriological examinations showed that in only 4 cases was there appreciable decrease in the number of bacilli. However, fragmentation of bacilli was observed in sorne cases. Other observations.-The sedimentation rate decreased in an important manner in 16 of the patients treated, in keeping with their improvement. Twenty-seven of the patients (63%) have had reaction during the course of treatment. In two cases, the reactions necessitated suspension of the drug. In the rest of the patients the reactions were mild and subsided after the reduction in the dose. In one case the treatment was started during a mild lepra reaction and was continued without exacerbation of the process. CONCLUSIONS At the Cabo Blanco.leprosarium, in Venezuela, an experiment is under way in the treatment of leprosy with a thiosemicarbazone, "TB-1." It was considered probable, because of results 18,4 Vegas, et al: Thiosemicarbazone in Leprosy 455 already obtained in Germany in tuberculosis, and also in one leprosy patient treated for a short period of time, that this drug would be active in leprosy. This experiment was set up with a program of the necessary control examinations during the course of the treatment, in order to observe the patients' tolerance to the drug and its therapeutic effects. At the time of writing 42lepromatous cases have been treated for periods of 3 to 6 months (March to September 1950). The initial results observed indica te marked therapeutic activity; during the short period of experiment to date notable clinical regression of leprous lesions has been observed. No manifestations of intolerance have been observed with respect to blood changes or disturbance of the liyer or other • Vlscera. This preliminary communication is published because of our conviction that much benefit may be derived from the application of this thiosemicarbazone in the treatment of leprosy. REFERENCES 1. DOMAGK, G. Investigations on the antituberculous activity of the thiosemicarbazones in viú-o and in vivo. American Rev. Tuberc. 61 (1960) 8-19; (abstracted, l. J. L. 18 (1960) 129). 2. HOHENNER, K. Ein Behandlungsversuch der Lepra mit dem Thiosemicarbazon TB 1/698. Med. Klin. 44 (1949) 1378-1381.
  Ediciones > Año 1951 > Artículo No. 1
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