MANEJO TERAPEUTICO de las DIFERENTES FORMAS CLINICAS de las LEISHMANIASIS en el ECUADOR

Manuel Calvopia H.
Centro de Biomedicina Universidad Central del Ecuador

Ecuador showing the geographic locations (regions and provinces) of Leishmania species identified in this study. The shaded area shows the Andean plateau (>1,000 m altitude). Dotted areas show highland jungle or Andean slopes (4001,000 m elevation). The tropical rainforest of Pacific coastal and Amazon regions are shown in white. Each letter represents one isolate.

MANEJO DE LAS LEISHMANIASIS CUTANEAS (LC)

1. Observacin, cura clnica espontnea

2. Tratamiento local de LC 2.2.1. Tratamiento local con medios fsicos 2.2.2. Tratamientos local con frmacos tpicos. 3. Tratamiento intralesional con antimoniales. 4. Tratamiento sistmico de LC 2.4.1. Tratamiento oral. 2.4.2. Tratamiento parenteral. 5. Tratamiento mixto de las LC (local mas parenteral con antimoniales).

ECUADOR: Cutnea y sus variantes

Ulceras

Andes-type, Uta

L. Recidivans cutis

L. Erysipeloid

L. Disseminated Sporotrichoid or pian-bois Diffuse CL

LC ANDINA

1. Observacin, cura clnica espontnea 2. Tratamiento local de LC 2.2.1. Tratamiento local con medios fsicos 2.2.2. Tratamientos local con frmacos tpicos.

Ulcerosa

1. Observacin, cura clnica espontnea 2. Tratamiento local de LC 2.2.1. Tratamiento local con medios fsicos 2.2.2. Tratamientos local con frmacos tpicos. 3. Tratamiento intralesional con antimoniales.

Acta Tropica 91 (2004) 153160

Comparison of the effectiveness of two topical paromomycin treatments versus meglumine antimoniate for New World cutaneous leishmaniasis
Rodrigo X. Armijos, M. Margaret Weigel, Manuel Calvopia, Manuel Mancheno, Roberto Rodriguez.
Abstract The randomized, controlled study compared the therapeutic efficacy and safety of two paromomycin-containing topical preparations with the gold treatment standard, meglumine antimoniate, and with each other in 120 Ecuadorian patients with ulcerated lesions. The two paromomycin treatment comparisons were double-blinded. Group 1 (n = 40) received 15% paromomycin plus 12% methylbenzonium chloride (PRMBCL) dissolved in a soft white paraffin base, applied twice daily for 30 days. Group 2 (n = 40) was also treated for 30 days with 15% paromomycin plus 10% urea (PRU) dissolved in the same paraffin base. Group 3 (n = 40) received 20 mg/kg/day of IM meglumine antimoniate (MA) for 10 days as per Ecuadorian Ministry of Public Health recommendations at the time of the study. The 10-day treatment was completed by 90% of the MA group compared to 72.5% of the PRMBCL (X2 = 4.0, P = 0.045) and 75% of the PMU (X2 = 3.1, P > 0.05) groups whose treatment regime lasted 20 days longer than the MA treatment. Post-treatment lesion burning, redness, inflammation, and soreness were more common in the two paromomycin groups compared to MA group (P < 0.05). The frequency of treatment-related side effects in the two paromomycin groups was similar. Six weeks after the start of treatment, 80.6% of MA subjects were clinically cured compared to 48.3% in the PRMBCL (X2 = 6.1, P = 0.014) and 40% in the PMU groups (X2 = 12.6, P = 0.002). By 12 weeks, the proportion of clinically cured subjects in the MA (91.7%) compared to PMMBCL (79.3%) or PMU (70%) groups was notsignificantly different (P > 0.05). MA-treated subjects clinically cured by 12 weeks had a faster mean healing time (29.512.2 days) compared to those in the PMMBCL (versus 43.1 14.4 days, t = 3.7, P = 0.001) or PRU groups (43.5 17 days; t = 3.2, P = 0.002). During the 48-week post-treatment follow-up period, infection reactivation was observed in 15.2% of the MA subjects compared to 17.4% in the PMMBCL and 10.5% PMU of subjects diagnosed as clinically healed by 12 weeks (P > 0.05). The results suggest that although the time required for the clinical healing of ulcerated lesions takes longer, topical paromomycin may be an acceptable therapeutic alternative in endemic areas where meglumine antimoniate is not available, is too costly or medically contraindicated.

ERISIPELOIDE y DISEMINADA

Glucantime intramuscular, full tratamiento

Recidiva cutis

Tratamiento intralesional con antimoniales

GLUCANTIME INTRALESIONAL

Indicaciones precisas: C. recidiva cutis Unica Pequea No sitios dolorosos Precauciones Asepsia Jeringuilla y aguja de insulina Infiltracion en + Intervalo de 5-7 dias.

TRATAMIENTO DE LA RECIDIVA CUTIS

Glucantime + mercurio cromo topico ???

TRATAMIENTO DE LA LEISHMANIASIS MUCOCUTANEA

Dificil de tratar, con ms del 42% de recidivas a los antimoniales. Introduccion del miltefosine, Anfotericina B liposomal, la combinacion de antimoniales con pentoxifilina y la inmunoterapia han abierto esperanzas en su curacion. E n 2 estudios desde Brasil se reporta el 90 y 100% de eficacia del Antimonial (20 mg/kg/d) mas Pentoxifilina oral (400 mg TID) por 30 d en la curacion de 9/10 y 11/11 pacientes, mientras que el grupo control de 12 tratados solo con antimonial curaron pero necesitaron 2 ciclos de 30 d; los tratados con la combinacion curaron en 83 (36 d) de administracion, mientras que el grupo del antimonial solo curaron en 145 (99 d), (Lessa HA et al. 2001; Machado et al. 2007). Una reciente publicacion en pacientes Bolivianos producido por L. braziliensis demostro que miltefosine (2.5 mg/kg/d x 28 d) curo el 83% de 36 pacientes con enfermedad leve y el 58% de 36 con LMC extensiva (Soto et al. 2007). En Brasil, la anfotericina B liposomal (AmBisome, 2-3 mg/kg x 5 d) curo 6 pacientes con leishmaniasis mucosa que no habian respondido al Glucantime (Ribeiro RN & Davis P, 1997) inclusive en pacientes VIH co-infectados (Amato et al. 2000a), El uso de Anfotericina B (Fungizone) en LMC aunque muy efectivo (Sampaio SA et al. 1971) esta casi abandonado debido a sus frecuentes y graves efectos adversos, necesitandose de la hospitalizacion del paciente. El pentostam se reporto como ineficaz en LMC que involucra boca y nariz en Per, curando apenas 2 (10%)/21 pacientes (Franke ED et al. 1990); en otro estudio su administracin durante 40 d, revelo la misma eficacia de 28 d, 63% a los 12 meses de seguimiento (Franke ED et al. 1994). En este mismo pais, el antimoniato de meglumina (20 mg/kg/d x 28d) curo 8 (47%)/17 pacientes con LMC moderada (Llanos-Cuentas et al. 2007). Nosotros tratamos con Itraconazol oral (400 mg/d por 3 meses) 13 personas con LMC provenientes de la Amazonia ecuatoriana, curando clinica y parasitologicamente 3 que tenian evolucion temprana de la enfermedad (Calvopina et al. 2004); un estudio previo en Brasil usando esta misma droga (400 mg/d por 6 sem) curo 6/10 pacientes (Amato et al. 2000b). Azitromicina, antibiotico macrolido de amplio espectro, fue empleado en 3 pacientes brasilenos, ellos recibieron 3 cursos orales de 500 mg/d por 10 d cada curso, todos cicatrizaron pero 1 reactivo y fue tratado nuevamente (Silva-Vergara et al. 2004). La inmunoterapia empleando promastigotes de Leishmania muertos por pasteurizacion asociada a BCG (Bacillus de Calmette-Guerin) ha sido empleada en Venezuela en pocos pacientes con LMC (Convit et al. 2004). Otro estudio usando 3 peptidos de Leishmania mas el adjuvante MPL curo 10 pacientes brasilenos con LMC (Coler & Reed, 2005). Aminosidine Pentamidine (Pentam o Pentacarinat) La ciruga plastica

International Journal of Dermatology 2004, 43, 659663. Itraconazole in the treatment of New World mucocutaneous leishmaniasis
Manuel Calvopina, Angel G. Guevara, Rodrigo X. Armijos, Yoshihisa Hashiguchi, Robert N. Davidson, and Philip J. Cooper.

Abstract
Background A well-tolerated oral drug is required for the treatment of mucocutaneous leishmaniasis (MCL). Current parenteral treatment regimens with pentavalent antimonials are associated with marked toxicity and significant rates of relapse. Aim To evaluate the efficacy and tolerability of high-dose itraconazole for the treatment of MCL. Methods An uncontrolled treatment study was performed in 13 Ecuadorian patients with MCL. Each patient received a daily dosage of 400 mg of itraconazole for a minimum of 3 months. Results All 13 subjects responded to itraconazole during the first month of treatment, but by 12 months after treatment the complete resolution of MCL lesions was observed in only three (23%) subjects. No adverse effects of treatment were reported. Response to treatment was associated with a short evolution of the disease and mild to moderate disease severity. Conclusion Prolonged and high-dose treatment regimens with itraconazole are not effective for the treatment of the majority of patients with MCL.

TRATAMIENTO DE LA L. CUTANEODIFUSA (LCD)

Al presente no existe terapia disponible para esta progresiva e incapacitante forma clinica. Los antimoniales no han demostrado eficacia, excepto en 1 caso anecdotico en Colombia producido por L. panamensis (Velez I et al. 1994). Nosotros tratamos con miltefosine un paciente infectado en Esmeraldas causado por L. mexicana y a pesar de administrar 2.5 mg/kg (150 mg/d) y por 5 meses, luego de 2 meses reactivo la enfermedad y no cedio a un segundo ciclo (Calvopina et al. 2006b); similar reactivaciones en 15/16 casos se observaron en Venezuela luego de administrar miltefosine (2.0-2.5 mg/kg/d) por periodos variables de 75218 dias (Zerpa et al. 2007). En Africa, aminosidine (14 mg/kg/d) mas pentostam (10 mg/kg/d) por 60 d cur 3 pacientes multiresistentes por L. aethiopica, con efectos indeseables mnimos (Teklemariam S et al. 1994). La termoterapia, 39-41 oC, curo clinicamente 3 casos de LCD en R. Dominicana, pero reactivaron posteriormente (Neva FA et al. 1984).

TREATMENT Miltefosine in DCL

Am J Trop Med Hyg. 2006 Dec;75(6):1074-7. Relapse of new world diffuse cutaneous leishmaniasis caused by Leishmania (Leishmania) mexicana after miltefosine treatment. Calvopina M, Gomez EA, Sindermann H, Cooper PJ, Hashiguchi Y. A 35-year-old man with a 19-year history of slowly evolving diffuse cutaneous leishmaniasis was treated with oral miltefosine, 50 mg three times a day. The patient responded after four months of miltefosine treatment with clearance of all nodular lesions and plaques from the entire body surface and had negative slit-skin smears and cultures for Leishmania. However, two months after stopping miltefosine, skin lesions reappeared and parasites were observed in samples. The relapsed lesions did not respond to an additional two-month course of miltefosine. No laboratory or clinical adverse events to miltefosine were observed. Parasites from skin lesions were cultured and identified as Leishmania (Leishmania) mexicana by isoenzyme electrophoresis.

TRATAMIENTO DE LA ULCERA DE CHICLERO

Glucantime intramuscular, full tratamiento Glucantime intramuscular + intralesional Glucantime topico + mercurio cromo???

Ulcera de chiclero

Glucantime intramuscular + intralesional

GLUCANTIME + MERCURIO CROMO LOCION (TTO TOPICO)