Actualización en tratamiento de la lepra / no disponible

El tratamiento de la lepra ha variado, crecido y mejorado ostensiblemente en los últimos años y ello ha ayudado a eliminar esta enfermedad como problema de Salud Pública en muchos países. Sin embargo, son necesarios aún más estudios para el desarrollo de nuevos tratamientos. La llegada de nuevas drogas al arsenal terapéutico, como el ofloxacino o la minociclian, van sin dudas a reducir el tiempo de tratamiento, así como disminuir la aparición de efectos colaterales frecuentes en los esquemas hasta ahora recomendados. La talidomida, redescubierta en la actualidad como droga muy importante, no sólo para las leprorreacciones sino además para otras muchas patologías con importante componente inmunológico/inflamatorio, es objeto de numerosas investigaciones en la actualidad. Y, sobre todo, reconocer esta enfermedad que es la lepra como la expresión de una complicada – pero cada vez mejor conocida- cascada de acontecimientos inmunológicos, ha abierto un sinfín de nuevas posibilidades en el campo de la terapéutica, los inmunomoduladores, que también desempeñan un importante papel durante los episodios reacciónales, los cuales continúan siendo, a pesar de los avances actuales, el auténtico problema para el paciente bajo tratamiento. Como esta enfermedad infecciosa, la vacuna debe ser al final el objeto de todas las investigaciones, pues con la desaparición de la susceptibilidad de la población, el resto de los tratamientos, si no existen pacientes, poco han de aportar. Nuevas vacunas están haciendo su aparición en el abanico terapéutico de la lepra, de forma aislada o sumadas a los tratamientos por vía oral. Basado en las informaciones de textos de leprología actuales, así como en búsquedas en Internet acerca de investigaciones en curso sobre los nuevos tratamientos, este trabajo intenta mostrar un estudio cuidadoso de los esquemas terapéuticos en la actualidad y de las nuevas posibilidades que están surgiendo en los campos de la Farmacología y la Inmunología

The leprosy treatment has changed, grown and improved especially in the last few years, and this factor has helped to eliminate this disease as a Public Health problema inmany countries. Since the time the leprosy patients were espelled society until our days has improved very much. Although our country still has a big problem, and yet is necessary to do more research to develop new treatments. The introduction of new drugs to the therapeutic “arsenal”, as the ofloxacín or the minocicline, no doubt will reduce the time treatment, as to reduce the appearance of side-effect in the therapeutic plans recommended until now. The thalidomide, rediscovered nowadays as a drug very valued not only for the leprosy reactions as for the many other diseases with a very important immunological component/inflammatory is a target for many recent research. And for all, recognize this disease that is the leprosy as difficult expression but after all better known as an immunological cascade happening has opened many possibilities without an end in the therapeutically area, the immunomodulators, that develop a very important role during the reaction episodes, that continue to be, besides of the modern advances, the real treatment for the patients on treatment. As an infectious disease, the vaccine has to be the main objective of all the research, because with the with draw of the population susceptibility, the rest of the therapeutic if, doesn´t exist one sick, it won´t be necessary to add very much to it. New vaccines are appearing in the therapeutically leprosy cast, alone or together with the oral treatment. Based on the papers information about modern leprosy, as in research in the internet after information about new heading treatments, this paper is willing to show a new synthesized vision of the way followed in pharmacology for the leprosy treatment, studying carefully the therapeutically plans nowadays and showing new possibilities that are being evaluated in the pharmacology and immunology areas

A clinical trial of ethionamide and prothionamide for treatment of lepromatous leprosy.

In 1982-1984 we conducted a six-month clinical trial in 50 previously untreated lepromatous leprosy patients randomly assigned to directly observed monotherapy with one of two thioamides, ethionamide or prothionamide, each given six times a week at doses of either 250 mg or 500 mg. The findings of this study have only recently been analyzed, and the potential for the use of these thioamides in leprosy patients placed in perspective. However, because of the small number of patients included in this study, the results must be interpreted with some caution. Clinical improvement was noted in 74% of the patients treated with ethionamide and in 83% of those treated with prothionamide. Therapy was well tolerated and drug-related hepatotoxicity did not require discontinuation of therapy. The 500-mg dose of both ethionamide and prothionamide resulted in loss in Mycobacterium leprae viability more rapidly than did the 250-mg dose, and prothionamide at both dose levels was superior to the equivalent dose of ethionamide. Overall killing of M. leprae in this study was found to be similar to that obtained previously with dapsone and clofazimine, but less than was obtained with rifampin, minocycline, clarithromycin, pefloxacin, and ofloxacin.

A case study in Hansen's disease acquired after heart transplant.

Hansen's disease, leprosy, is a chronic infectious disease caused by the acid-fast bacillus Mycobacterium leprae. There are multiple forms of the disease ranging from the relatively benign to the progressive, malignant lepromatous leprosy. There is effective antimicrobial treatment available that is capable of curing the disease. We report the case of a post heart transplant patient acquiring Hansen's disease.

Daily multidrug therapy for leprosy; results of a fourteen-year experience.

Between 1980 and 1994, 67 new or relapsing leprosy patients were treated by daily administered multidrug regimens. Tuberculoid patients (23 TT/BT) received either bitherapy [rifampin + dapsone or clofazimine (RMP + DDS or CLO)] or tritherapy [RMP + DDS and/or CLO and/or ethionamide (ETH)] until clinical cure. Lepromatous patients (44 BB/BL/LL) received tritherapy (RMP + DDS and/or CLO and/or ETH) at least until bacteriological negativity. Of the 23 tuberculoid patients only one patient (5%) was cured at 6 months and about 70% needed between 6 and 24 months of treatment to obtain clinical cure (mean 19.5 months). In the 44 lepromatous patients, the achievement of bacteriological negativity was significantly linked to the initial bacterial index (BI), and it occurred after 2 to 7 years (mean 66.5 months) of multidrug therapy (MDT). The average BI decrease per year was 1.1+ during the first year, 0.9+ the second year, and then < 0.5+ per year. Reactional states significantly (p < 0.01) influenced the BI course: reversal reactions (RR) accelerated while erythema nodosum leprosum (ENL) delayed the BI decrease. Three of the 23 (13%) tuberculoid and 19 of the 44 (43%) lepromatous patients (p < 0.02) exhibited a RR and 18 of 44 (41%) lepromatous patients had ENL during MDT. A late RR (LRR) was observed in 1 (5%) and 6 (17%) of our tuberculoid and lepromatous patients, respectively, and 3 (8%) of our lepromatous patients suffered post-MDT ENL. No confirmed relapse has been observed within a follow-up period of 6 months to 7 years and 3 months [59 person-years at risk (PYR)] for TT/BT patients and of 4 months to 5 years and 10 months (100 PYR) for BB/BL/LL patients. When compared to the recommended WHO/MDT, it appears that daily MDT does not increase the clinical or the bacteriological cure rates either at 6 months in paucibacillary tuberculoid patients or at 2d years in multibacillary lepromatous patients. Moreover, as does the WHO/MDT, our regimens show a high frequency of reactional states both during and after treatment. This fact constitutes the main new problem of the actual treatment of leprosy.

Resistência medicamentosa múltipla secundária na hanseníase / Secundary multidrug resistence in leprosy

Säo apresentados 4 pacientes com resistência a mais de uma das drogas que fazem parte dos esquemas terapêuticos preconizados pela OMS contra a hanseníase. Os autores discutem o modo de aparecimento dessa múltipla resistência e consideram a possibilidade de ocorrer esse fenômeno de maneira inicial, isto é, paciente que se infectam com bacilos já resistentes a mais de uma droga. Lembram o que está acontecendo nos Estados Unidos com a tuberculose, onde aumentou consideravalmente o número de casos com resistência inicial a múltiplos fármacos e admitem a possibilidade da AIDS que é responsável pela maior parte dessa situaçäo, vir a ter papel semelhante na hanseníase. Alertam também para o fato de drogas ainda em fase experimental e que já se acham disponíveis no comércio, começarem a ser utilizadas indevidamente, comprometendo o seu uso no futuro

[Late reversal reactions in leprosy]. / Les réactions de réversion tardives au cours de la lèpre.

Since the application of short duration multidrug therapy (MDT) in leprosy, it has been reported that reversal reactions (RR) may occur after withdrawal of treatment. Surprisingly, such "late reversal reactions" have quite never been described after monosulphonotherapy. Such RR, especially in endemic areas, may represent diagnostic and therapeutic difficult problems. We report 5 cases of late RR. In 4 cases (1 BT patient and 3 BL-LLs patients), the RR occurred 1 month 1/2 to 3 years after cessation of MDT. In the last case (form LLs), the RR happened 6 months after that a 14 years monosulphonotherapy has been stopped. These observations strengthen the need of a complete clinical, bacteriological and immunological evaluation at the time of the diagnostic, more useful than a single bacteriological study, to differentiate late RR from relapses. Moreover, the last case confirms that late RR may occur after monosulphonotherapy.

Etionamida na multidrogaterapia; estudos preliminares / Ethionamide in combined chemoterapy: preliminary studies

Os autores estudam a aplicabilidade da etionamida da hanseníase nas susas diversas formas clínicas, em regime de multidrogaterapia

[Supervised bimonthly quadruple chemotherapy in 72 paucibacillary leprosy patients in French Guyana]. / Quadruple chimiothérapie bimensuelle supervisée chez 72 paucibacillaires en Guyane française.

In French Guyana we have treated 72 paucibacillary leprosy with an association of Rifadine + Lamprene + Trecator + Disulone given twice monthly under supervision during 6 months. Results have been satisfying and side effects rare. The sequential character of treatment shows a substantial advantage on the operational side but may appear to be favorable to bacterial resistance.

Feasibility of multidrug therapy (MDT) in Hansen's disease in an urban population--Curupaiti State Hospital, Rio de Janeiro, Brazil.

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.

Short term combination therapy for paucibacillary leprosy--histological evaluation & follow-up study.

68 patients with paucibacillary disease were started on various regimes of multi drug therapy, consisting of ethionamide, rifampicin or clofazimine administered with dapsone. Serial skin biopsies were taken from 32 patients at one, two and three years and even later after the initial pre treatment biopsy. Actual material was available for study from 9 patients. All regimens were tolerated well except the one with ethionamide. However the therapeutic response was equal in all combination therapies as supported by histopathology. Compared to that with dapsone monotherapy the response was quicker with combination. Dapsone plus rifampicin combination was best tolerated and it worked out to be economical as well. No relapse was noted in any group during two or more years follow up.

[5-year assessment of daily multi-drug therapy of leprosy in Guadeloupe since 1980]. / Bilan à 5 ans de la polychimiothérapie quotidienne de la lèpre en Guadeloupe depuis 1980.

In Guadeloupe, from January 1980 to December 1984, 420 leprosy patients were put under daily multidrug therapy: 10 mg/kg RMP plus 100 mg DDS during six months for paucibacillary patients, 10 mg/kg RMP plus 100 mg DDS during 24 months supplemented during the 12 first months with 10 mg/kg of a thioamide, ethionamide or protionamide, for multibacillary patients. The approval to the treatment was satisfactory in all the patients with active leprosy, new cases and relapse cases, less in the inactive patients already treated with dapsone only. The patients's compliance to treatment was satisfactory too. The lepra reactions were observed with a 19% frequency which is not different of the 15% frequency of lepra reactions observed in patients treated with DDS only. Hepatitis were observed only in multibacillary patients treated with PTH and RMP with a 14% frequency. Discontinuing treatment with RMP and PTH but not DDS resulted in recovery. When RMP was resumed without PTH, the hepatitis did not recur. All patients responded favorably under multidrug therapy and no relapse was observed among the 45 paucibacillary patients after a four year-surveillance and among the 16 multibacillary patients after a three year-surveillance.

[Efficacy of combined treatments comprising 6 months' administration of rifampicin in multibacillary leprosy]. / Efficacité de traitements combinés comportant six mois d'administration de rifampicine dans la lèpre multibacillaire.

Ten patients infected with mouse proven DDS-resistant bacilli were treated with the following combined regimen: RMP 600 2/7 6 months, ETH 500 7/7 6 months and DDS 100 7/7 12 months. Follow up was for 27-54 months, without relapses. Added to patients from previous study (Int. J. Lepr. 1984, 52, 297-303) the 95% confidence limit decreases from 12 to 9%.

[Multi-drug therapy trials for leprosy in Senegal: first observations relative to liver tolerance of multibacillary patients. Therapeutic consequences]. / Essais de polychimiothérapie de la lèpre au Sénégal: premières observations relatives à la tolérance hépatique des maladies multibacillaires--conséquences thérapeutiques.

The authors have studied tolerance of multibacillary patients to 4 MDT regimens. These 4 regimens consist of: One supervised part in which RMP-ETH combination in once-monthly administered; furthermore, in 2 of these regimens, is included one "starter phase" with daily doses of that combination for 2 months. One self-administered part during which CLO is associated either to DDS for new cases, or to ETH for relapses. Clinical Supervision: Out to 310 multibacillary patients, 7 cases of hepatitis with or without icterus, but no death due to the treatment. Interruptions of MDT have been temporary and have been observed in 0.9 to 5.6% of the patients according to the therapeutic regimen. Checking SGOT: The SGOT were abnormally high in 16.3% of the patients before treatment. These pre-existing liver damages do not favour the appearance of intolerance disorders. During MDT, abnormal increases in SGOT are observed in 27% of the patients but there is no exact correlation between the absorbed doses of ETH and the frequency in SGOT increases. The clinical or biological evidence of liver damages occur rather early (1st, 2nd month) in regimens with "starter phase", and later (4th-8th month) in those without "starter phase". But introduction of "Starter phase" does not increase the global frequency of such intolerance accidents. ETH combined with RMP, must be used under steady clinical and biological supervision. Recalling the results of a previous survey, the authors consider that a long duration of MDT is not necessary. For the multibacillary leprosy treatment, they propose a diphasic regimen, more easily applicable in the field than the WHO protocols. In this diphasic regimen, the only part which must be supervised is the initial "starter phase" of 2 month. It consists of daily administration of 3 antibacillary drug among which RMP and ETH. The second phase is a relay treatment using 2 drugs, CLO combined with DDS or ETH, self-administered until smear negativity.

[A new plan in the campaign against leprosy in Anjouan. Preliminary results]. / Nouveau plan de lutte contre la lèpre à Anjouan. Premiers résultats.

Treatment of PB leprosy patients with 10 weekly doses of RMP 600 mg gave a cure rate of 88% or more at 3 years as judged by histopathology. There were no severe neurological complications. The future will show if this regimen also prevents relapses. In MB leprosy a 2 months regimen of daily RMP, ETH, DDS followed by 10 months of daily ETH, DDS with weekly RMP gave excellent clinical and bacteriological results. There were no relapses during 2 and 3 years after the end of therapy among 111 newly diagnosed and previously treated patients (95% confidence interval 3.3%) of whom 67 were new patients (95% confidence interval 5.3%). The hepatotoxicity of this regimen has to be followed closely. The results illustrate the possibility to cure MB leprosy by a treatment of finite duration.

Antibodies to phenolic glycolipid-1 and to whole Mycobacterium leprae in leprosy patients: evolution during therapy.

Sera from 92 patients were tested by the ELISA method for the presence of IgM antibodies to phenolic glycolipid-1 (PGL-1) of Mycobacterium leprae, and of both IgM and IgG antibodies to the whole M. leprae bacillus. All untreated lepromatous patients exhibited high antibody levels in all three assays. A sharp decline of IgM antibodies to PGL-1 and whole M. leprae was observed during the first two years of therapy, while IgG antibodies to whole M. leprae showed a progressive decrease only over a number of years. Low titers of IgM antibodies to PGL-1 and IgG antibodies to whole M. leprae could be detected in about 50% and 75% of patients, respectively, after more than ten years of treatment, with only 15% showing persisting IgM antibodies to the whole bacillus. Antibody levels as measured by the three assays used were correlated with the bacterial index in patients treated for less than four years. In patients treated longer than four years, only IgM antibodies, whether directed to PGL-1 or to whole M. leprae, remained correlated to the bacillary load. Tuberculoid patients exhibited a different antibody pattern, showing a lower frequency (and lower levels) of antibodies of PGL-1 and of IgG antibodies to whole M. leprae than lepromatous patients, and no detectable IgM antibodies to the whole bacillus. IgG antibodies to whole M. leprae were more frequently noted than antibodies to PGL-1, the latter declining more rapidly during therapy.

Prospective study on the relationship between intensive bactericidal therapy and leprosy reactions.

A systematic study was performed on the reactions occurring during several short-course therapy regimens for the treatment of paucibacillary and multibacillary patients. Most type 1 upgrading reactions in paucibacillary (PB) leprosy were mild to moderate and of short duration, while the time of onset was extremely variable. Their incidence was higher in the regimen rifampin (RMP) 900 mg once weekly for ten weeks than when a single dose of RMP 40 mg/kg body weight was given or 1500 mg in one dose followed by one year of dapsone (DDS) 100 mg daily. In multibacillary (MB) leprosy, three regimens were compared: MB-WHO regimen; regimen C, consisting of daily RMP 600 mg, ethionamide (ETH) 500 mg, and DDS or clofazimine (CLO) 100 mg for six months, followed by six months of daily DDS or CLO; and regimen D, identical to regimen C but comprising daily DDS or CLO plus ETH 500 mg during the second semester. Type 1 upgrading reactions occurred more frequently in MB patients and were more severe than in PB patients. They occurred more frequently and were more severe in regimens C and D than in the MB-WHO regimen. CLO 100 mg daily prevented type 1 reactions in MB patients and rendered them less severe. ENL was also more frequent in regimens C and D and was not prevented by CLO in the dosage used. Although there is some correlation between type 1 reactions and the total amount of RMP administered, other aspects of RMP administration.(ABSTRACT TRUNCATED AT 250 WORDS)