prothionamide and Leprosy

Topics: Adult; Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Male; Prospective Studies; Prothionamide; Random Allocation; Rifampin

Topics: Animals; Clinical Trials as Topic; Clofazimine; Dapsone; Female; Humans; Leprostatic Agents; Leprosy; Male; Mice; Prothionamide; Rifampin

Topics: Clinical Trials as Topic; Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Male; Prothionamide; Rifampin

Topics: Clinical Trials as Topic; Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Mycobacterium leprae; Prothionamide; Rifampin

Topics: Clinical Trials as Topic; Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Male; Malta; Prothionamide; Rifampin

Topics: Adolescent; Adult; Aged; Child; Clinical Trials as Topic; Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Isonicotinic Acids; Leprosy; Male; Middle Aged; Prothionamide; Rifampin

Topics: Adolescent; Adult; Child; Child, Preschool; Clinical Trials as Topic; Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Male; Middle Aged; Prothionamide; Rifampin

Topics: Clinical Trials as Topic; Dapsone; Drug Combinations; Drug Therapy, Combination; Ethiopia; Female; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Male; Prothionamide; Rifampin

The Malta Leprosy Eradication Project (MLEP) was proposed in 1971 by Freerksen with the aim of eradicating leprosy in Malta. The project involved re-treatment of all known cases in Malta as of 1972 and all new cases thereafter with a regimen consisting of Isoprodian (a combination of dapsone, prothionamide and isoniazid) and rifampicin for varying intervals depending on the severity of their disease and their response to treatment. Overall the response to therapy was excellent with an extremely low relapse rate. During the 30 years of the project the incidence of leprosy steadily decreased continuing a decline that had started at least two decades earlier and Freerksen declared the disease eradicated from Malta in 2001. Although given the long incubation period of leprosy cases may still be occasionally detected in the future, the disease has been basically eradicated at this time and there are no patients currently receiving treatment. This work was done at the leprosy clinic, Boffa Hospital, Floriana, Malta.

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; Isoniazid; Leprostatic Agents; Leprosy; Male; Malta; Program Evaluation; Prothionamide; Rifampin; Treatment Outcome

Thioamide drugs, ethionamide (ETH) and prothionamide (PTH), are clinically effective in the treatment of Mycobacterium tuberculosis, M. leprae, and M. avium complex infections. Although generally considered second-line drugs for tuberculosis, their use has increased considerably as the number of multidrug resistant and extensively drug resistant tuberculosis cases continues to rise. Despite the widespread use of thioamide drugs to treat tuberculosis and leprosy, their precise mechanisms of action remain unknown. Using a cell-based activation method, we now have definitive evidence that both thioamides form covalent adducts with nicotinamide adenine dinucleotide (NAD) and that these adducts are tight-binding inhibitors of M. tuberculosis and M. leprae InhA. The crystal structures of the inhibited M. leprae and M. tuberculosis InhA complexes provide the molecular details of target-drug interactions. The purified ETH-NAD and PTH-NAD adducts both showed nanomolar Kis against M. tuberculosis and M. leprae InhA. Knowledge of the precise structures and mechanisms of action of these drugs provides insights into designing new drugs that can overcome drug resistance.

Topics: Antitubercular Agents; Bacterial Proteins; Crystallography, X-Ray; Drug Design; Drug Resistance, Multiple, Bacterial; Ethionamide; Humans; In Vitro Techniques; Leprostatic Agents; Leprosy; Models, Molecular; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycobacterium leprae; Mycobacterium tuberculosis; NAD; Oxidoreductases; Prothionamide; Tuberculosis; Tuberculosis, Multidrug-Resistant

Topics: Adolescent; Adult; Aged; Child; Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; Isoniazid; Leprostatic Agents; Leprosy; Male; Middle Aged; Prothionamide; Rural Health

The introduction briefly describes the pathogenesis, classification, diagnosis and modern treatment possibilities. In Africa leprosy is considered endemic. The World Health Organization estimates the total number of cases at 3.5 million. Over the last 20 years, however, the recorded number of cases has decreased dramatically. Increasing mobility on the part of the population, relocation from countryside to the cities, and a tendency towards urbanization are introducing a new dimension to leprosy distribution and the fight against the disease in Africa. Despite the not-inconsiderable financial, material and human resources that have so far been made available--mostly from outside the country--only a small percentage of the presumptive number of leprosy sufferers are receiving an adequate, modern combination therapy. This means that leprosy continues to represent a serious public and individual health problem in Africa.

Topics: Adolescent; Adult; Africa; Child; Cross-Sectional Studies; Drug Therapy, Combination; Humans; Isoniazid; Leprosy; Leprosy, Lepromatous; Leprosy, Tuberculoid; Prothionamide; Rifampin; Trimethoprim

Topics: Animals; Clofazimine; Dapsone; Drug Resistance, Microbial; Drug Therapy, Combination; Ethionamide; Humans; Leprosy; Mycobacterium leprae; Prothionamide; Rifampin

In Paraguay, the National Leprosy/Tuberculosis Program is based on a combined chemotherapy with isoprodian and rifampicin. The aim of this descriptive study was to investigate the therapy durations used so far in the treatment of 475 leprosy patients and to analyze the criteria responsible for the wide-ranging differences in therapy durations. As initial criteria, the following parameters were identified to have a significant influence on the therapy duration: Patients never treated before or pretreated, clinical classification and initial bacteriological index (BI) value. During therapy, conditions like the attendance and BI decrease/year showed a significant correlation with the therapy duration. Even though the studied criteria did not allow to draw a definite conclusion with regard to an 'ideal' therapy duration, they proved to be reliable, as only 2 patients have relapsed so far.

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Leprosy, Borderline; Leprosy, Lepromatous; Leprosy, Tuberculoid; Mycobacterium leprae; Paraguay; Patient Compliance; Prothionamide; Rifampin; Time Factors

Since 1970, when the lifelong monotherapy with dapsone (DDS) in leprosy could be replaced by short-term combination therapy with rifampicin + isoniazid + protionamide + DDS (Isoprodian-RMP), chemotherapeutic research was faced with two problems: (1) to find alternative treatment regimens for cases of intolerance, and (2) to work out forms of therapy allowing a further reduction of the average treatment time of 2 years. The present paper describes the attempts made to find solutions to these problems. With two new combinations, alternatives have become available, and the average treatment time is shortened to 6 months. Both combinations are also effective in tuberculosis.

Topics: Drug Therapy, Combination; Humans; Isoniazid; Isonicotinic Acids; Leprosy; Prothionamide; Sulfamethoxazole; Trimethoprim

Topics: Animals; Clofazimine; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Humans; Isonicotinic Acids; Leprosy; Mice; Prothionamide; Rifampin

Mice inoculated with 4800 Mycobacterium leprae in the left hind foot pad were treated from day 62 to day 150 after infection with 50 mg or 150 mg of ofloxacin per kg body weight, 150 mg pefloxacin per kg, or 50 mg prothionamide per kg. These drugs were administered by esophageal cannula 5 days weekly with dapsone (0.01 g per 100 g diet). Multiplication of M. leprae in the treated and in untreated control mice was assessed by monthly harvests. The treatment of mice with the smaller dosage ofloxacin, with pefloxacin, prothionamide, or dapsone uniformly resulted in a delay of multiplication of 4 months, compared to the multiplication of M. leprae in the untreated controls. The delay of multiplication (4 months) being 1 month longer than the duration of drug administration (3 months), all of the treatments may be considered as bacteriopausal or moderately bactericidal. In contast with these results, treatment of mice with 150 mg ofloxacin per kg resulted in no growth of the organisms whatever as late as 18 months after inoculation, strongly suggesting that, in that dosage, ofloxacin had killed all of the M. leprae. Such a profound killing activity has been observed only with rifampin. Although the pharmacokinetic characteristics of ofloxacin are different in man from those in the mouse, the daily dosage of 150 mg ofloxacin per kg body weight in the mouse is equivalent to 400 mg per day in man which is the usual therapeutic dosage; thus, the results obtained in the mouse may be extrapolated to man. Therefore, ofloxacin appears a very promising drug for the chemotherapy of leprosy.

Topics: Animals; Anti-Bacterial Agents; Dapsone; Female; Leprosy; Mice; Mycobacterium leprae; Norfloxacin; Ofloxacin; Oxazines; Pefloxacin; Prothionamide

The acceptance of the WHO regimen in a group of 220 patients was approximately 84.5%. Only 11% abandoned the treatment, and the substitution of ethionamide or prothionamide for clofazimine due to excessive hyperpigmentation was necessary in only eight cases. The WHO regimens adopted provided a more frequent (monthly) relationship between the patients and their health service. It was necessary to: a) reorganize the technical-administrative infrastructure, with the intention of providing an improved service to the patients for treatment and control; and b) pay more attention to the problem of deformities and health education activities. As for the side effects of the drugs, 54 patients showed alterations in their liver function tests, which were usually mild and which resolved despite continuation of the treatment. Of the reactional episodes observed during MDT, it would not appear that the therapeutic regimens contributed to their occurrence or aggravation.

Topics: Adolescent; Adult; Brazil; Clofazimine; Dapsone; Drug Therapy, Combination; Ethionamide; Female; Humans; Leprostatic Agents; Leprosy; Male; Patient Acceptance of Health Care; Patient Compliance; Prednisolone; Prothionamide; Rifampin; Urban Population

Topics: Adolescent; Adult; Aged; Dapsone; Drug Therapy, Combination; Ethionamide; Female; Humans; Isoniazid; Isonicotinic Acids; Leprosy; Male; Middle Aged; Patient Compliance; Prothionamide; Self Administration; Thioacetazone

Topics: Adolescent; Adult; Child; Child, Preschool; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Prothionamide; Recurrence; Rifampin

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Male; Middle Aged; Prothionamide; Rifampin

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Evaluation Studies as Topic; Follow-Up Studies; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Malta; Prothionamide; Recurrence; Rifampin

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Leprostatic Agents; Leprosy; Paraguay; Prothionamide; Rifampin; Tuberculosis

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Male; Prothionamide; Rifampin; Tanzania

Topics: Dapsone; Drug Interactions; Humans; Isonicotinic Acids; Kinetics; Leprosy; Prothionamide; Rifampin

Topics: Clofazimine; Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Leprostatic Agents; Leprosy; Mycobacterium leprae; Prothionamide; Rifampin

Because a 13% incidence of hepatotoxicity was observed in a first study of multibacillary leprosy patients treated daily with dapsone, rifampin, and 10 mg/kg thioamide, the patients were treated in a second study with 5 mg/kg thioamide in daily combination with dapsone and rifampin. In this study, monthly assessments of liver function were performed in order to detect early hepatic disturbances. Despite the reduced dosage of thioamide, a 16.5% incidence of hepatotoxicity was observed among 110 multibacillary patients. However, jaundice was observed in only 2 out of 18 cases of hepatotoxicity (11%); whereas it was observed in 5 out of the 7 cases of hepatotoxicity (71%) in the first study (p less than 0.05). The decrease in the thioamide dosage and the performance of monthly assessments of liver function did not decrease the incidence of hepatotoxicity but did decrease its severity. It is concluded that thioamide should not be used in daily combination with rifampin unless the daily dose is 5 mg/kg and monthly assessments of liver function are routinely performed.

Topics: Adolescent; Adult; Aged; Body Weight; Chemical and Drug Induced Liver Injury; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Isonicotinic Acids; Leprosy; Liver; Male; Middle Aged; Prothionamide; Rifampin

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy; Male; Prothionamide; Rifampin; Sex Ratio; Time Factors

Topics: Adult; Aged; Chemical and Drug Induced Liver Injury; China; Drug Therapy, Combination; Female; Humans; Isonicotinic Acids; Leprosy; Male; Middle Aged; Prothionamide; Rifampin

Topics: Dapsone; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Prothionamide; Recurrence; Rifampin

Two therapeutic regimens of one-year duration were administered to two groups of 20 previously untreated multibacillary leprosy patients. Regimen A was rifampin 600 mg twice weekly, prothionamide 500 mg, and dapsone (DDS) 100 mg daily for six months, followed by 100 mg DDS daily for another six months. Regimen B was identical to Regimen A but without prothionamide. Follow-up was for 4 1/2 and 5 years in 15 and 14 patients, respectively. Clinical improvement was rapid, and the bacterial index (BI) of the patients diminished by one unit per year after stopping treatment. Five patients were skin-smear negative at 54 months. The BI in the nasal mucosa became negative after 48 months. There were many attacks of erythema nodosum leprosum between month 3 of treatment until 13 and 21 months. Up to now no relapses have been observed. These results have confidence limits of 20% and 23%, respectively. However, when the results of the two regimens are added, the confidence limit for six months' twice weekly rifampin together with DDS and followed by six months of DDS and 4 1/2 years follow-up is 12%.

Topics: Adolescent; Adult; Dapsone; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Isonicotinic Acids; Leprosy; Male; Middle Aged; Prothionamide; Rifampin

Topics: Adult; Animals; Clofazimine; Dapsone; Drug Resistance, Microbial; Erythema Nodosum; Ethionamide; Humans; Leprosy; Mycobacterium leprae; Patient Compliance; Prothionamide; Rifampin

Topics: Humans; Isoniazid; Leprostatic Agents; Leprosy; Prothionamide

Topics: Clofazimine; Dapsone; Drug Packaging; Ethionamide; Humans; Leprostatic Agents; Leprosy; Prothionamide; Rifampin; Tablets

Topics: Clofazimine; Costs and Cost Analysis; Dapsone; Drug Resistance, Microbial; Humans; Leprostatic Agents; Leprosy; Prothionamide; Rifampin

Topics: Animals; Isonicotinic Acids; Leprostatic Agents; Leprosy; Mice; Mice, Inbred Strains; Mycobacterium leprae; Mycobacterium tuberculosis; Niacinamide; Prothionamide

No additive effect was found at the addition of isoniazid to either dapsone or protionamide against M. leprae and against highly dapsone-sensitive in vitro growing Mycobacterium sp. strains. It is concluded that the indication of the administration of isoniazid in leprosy is extremely limited and could only be envisaged as a companion drug in combined therapy of dapsone-resistant multibacillary leprosy in light-skinned people, when aminoglycosides cannot be administered.

Topics: Animals; Dapsone; Drug Interactions; Drug Therapy, Combination; Isoniazid; Isonicotinic Acids; Leprosy; Mice; Mycobacterium; Mycobacterium leprae; Prothionamide

Topics: Acedapsone; Animals; Dapsone; Drug Therapy, Combination; Ethionamide; Humans; Leprostatic Agents; Leprosy; Mice; Prothionamide; Rifampin; Thioacetazone

Topics: Animals; Dapsone; Drug Therapy, Combination; Leprosy; Mice; Mycobacterium leprae; Prothionamide; Streptomycin; Thiosemicarbazones

Topics: Clofazimine; Drug Resistance, Microbial; Ethionamide; Humans; Leprostatic Agents; Leprosy; Prothionamide; Rifampin

This report is based on data obtained from 64 lepromatous cases. Despite many years of DDS monotherapy, the homogenates from biopsies of these patients revealed 10(4) or more bacteria. From the beginning of combination therapy with synergistic-acting substances (rifampicin + isoprodian (INH + PTH + DDS) the logarithms of the number of bacteria in the homogenates decreased, both during treatment period and during treatment-free observation period (Figs. 3--8). During the whole time biopsies were taken almost monthly. A considerable regression of the bacterial mass or even "negativity" could be observed within a relatively short time. Once started, the process of reduction of bacteria continued also after termination of therapy. To be able to evaluate a medication, therapy-free observation periods (for a minimum of 5 years) are indispensable.

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Leprostatic Agents; Leprosy; Prothionamide; Rifampin

Topics: Animals; Drug Therapy, Combination; Ethionamide; Isonicotinic Acids; Leprosy; Mice; Prothionamide

Topics: Animals; Ethionamide; Isonicotinic Acids; Leprosy; Mice; Prothionamide

Topics: Adolescent; Adult; Aged; Bacteriological Techniques; Child; Dapsone; Drug Therapy, Combination; Female; Humans; Isoniazid; Leprosy; Male; Malta; Middle Aged; Prothionamide; Rifampin; Time Factors

"Leprosy Relief through Leprosy Research" means that the results of research are made available for curing and eradicating the disease. The "Marinum Model" and the "planter test in mice" are, along with determination of serum activity in healthy test subjects, part of a complex of experiments for the assessment of the therapeutic value of an antimycobacterial substance. This replaces the "controlled studies" which, in their proper form, are scarcely possible for leprosy. With the recently developed forms of combination therapy, the duration of leprosy treatment is reduced to a few years. Because of the relationship of Mycobacterium leprae to Mycobacterium tuberculosis, certain types of combination therapy can be used in both diseases at the same time.

Topics: Animals; Armadillos; Dapsone; Drug Therapy, Combination; Humans; Isoniazid; Leprosy; Mice; Models, Biological; Mycobacterium; Prothionamide; Rifampin

Two groups of patients were chosen for this treatment; the first group of 14 patients was treated with a daily dose of 600 mg. of Rifampicine and the second group with Rifampicine associated with Isoprodian (1-2 tablets). In the first group clinical and bacteriological improvement was apparent. This was parallel in bacteriological and morphological index. Two patients became negative in nasal mucous. Tolerance was good and number of leprosy reactions 65%. In the second group clinical improvement was good in general but one case that presented a continuous polyneuritis and hepatic intolerance. Bacteriological results were lightly lower than the first group and the number of leprosy reactions 85%. This treatment is considered inferior to the sulfons, which is very expensive. A longer period of time will be needed to appriase results.

Topics: Dapsone; Drug Combinations; Drug Evaluation; Humans; Isoniazid; Isonicotinic Acids; Leprosy; Prothionamide; Rifampin; Tablets

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Prothionamide; Rifampin

Topics: Adolescent; Adult; Child; Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; India; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Male; Middle Aged; Prothionamide; Rifampin