RESUMEN
BACKGROUND: Current therapies for cutaneous leishmaniasis are limited by poor efficacy, long-term course of treatment, and the development of resistance. We evaluated if pentavalent antimony (an anti-parasitic drug) combined with imiquimod (an immunomodulator) was more effective than pentavalent antimony alone in patients who had not previously been treated. METHODS: A randomized double-blind clinical trial involving 80 cutaneous leishmaniasis patients was conducted in Peru. The study subjects were recruited in Lima and Cusco (20 experimental and 20 control subjects at each site). Experimental arm: Standard dose of pentavalent antimony plus 5% imiquimod cream applied to each lesion three times per week for 20 days. Control arm: Standard dose of pentavalent antimony plus placebo (vehicle cream) applied as above. The primary outcome was cure defined as complete re-epithelization with no inflammation assessed during the 12 months post-treatment period. RESULTS: Of the 80 subjects enrolled, 75 completed the study. The overall cure rate at the 12-month follow-up for the intention-to-treat analysis was 75% (30/40) in the experimental arm and 58% (23/40) in the control arm (p = 0.098). Subgroup analyses suggested that combination treatment benefits were most often observed at the Cusco site, where L. braziliensis is the prevalent species. Over the study period, only one adverse event (rash) was recorded, in the experimental arm. CONCLUSION: The combination treatment of imiquimod plus pentavalent antimony performed better than placebo plus pentavalent antimony, but the difference was not statistically significant. TRIAL REGISTRATION: Clinical Trials.gov NCT00257530.
Asunto(s)
Aminoquinolinas/uso terapéutico , Antimonio/uso terapéutico , Antiprotozoarios/uso terapéutico , Factores Inmunológicos/uso terapéutico , Leishmaniasis Cutánea/tratamiento farmacológico , Receptor Toll-Like 7/agonistas , Adolescente , Adulto , Anciano , Niño , Preescolar , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Imiquimod , Masculino , Persona de Mediana Edad , Perú , Resultado del Tratamiento , Adulto JovenRESUMEN
Molecular methods such as PCR have become attractive tools for diagnosis of cutaneous leishmaniasis (CL), both for their high sensitivity and for their specificity. However, their practical use in routine diagnosis is limited due to the infrastructural requirements and the lack of any standardization. Recently, a simplified and standardized PCR format for molecular detection of Leishmania was developed. The Leishmania OligoC-TesT is based on simple and rapid detection using a dipstick with PCR-amplified Leishmania DNA. In this study, we estimated the diagnostic accuracy of the Leishmania OligoC-TesT for 61 specimens from 44 CL-suspected patients presenting at the leishmaniasis clinic of the Instituto de Medicina Tropical Alexander von Humboldt, Peru. On the basis of parasitological detection and the leishmanin skin test (LST), patients were classified as (i) confirmed CL cases, (ii) LST-positive cases, and (iii) LST-negative cases. The sensitivities of the Leishmania OligoC-TesT was 74% (95% confidence interval (CI), 60.5% to 84.1%) for lesion aspirates and 92% (95% CI, 81.2% to 96.9%) for scrapings. A significantly higher sensitivity was observed with a conventional PCR targeting the kinetoplast DNA on the aspirates (94%) (P = 0.001), while there was no significant difference in sensitivity for the lesion scrapings (88%) (P = 0.317). In addition, the Leishmania OligoC-TesT was evaluated for 13 CL-suspected patients in two different peripheral health centers in the central jungle of Peru. Our findings clearly indicate the high accuracy of the Leishmania OligoC-TesT for lesion scrapings for simple and rapid molecular diagnosis of CL in Peru.
Asunto(s)
Leishmania/aislamiento & purificación , Leishmaniasis Cutánea/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Reacción en Cadena de la Polimerasa/métodos , Juego de Reactivos para Diagnóstico , Animales , Humanos , Leishmania/genética , Leishmaniasis Cutánea/parasitología , Perú , Sensibilidad y Especificidad , Piel/parasitologíaRESUMEN
Traditional culture of Leishmania parasites is labor-intensive and shows poor sensitivity. We evaluated microculture and novel miniculture methods for diagnosis of cutaneous leishmaniasis (CL). Consecutive patients who came to the Leishmaniasis Clinic, Hospital Nacional Cayetano Heredia, Lima, Peru, were enrolled. Lesion aspirates were cultured in traditional tubes containing Novy-MacNeal-Nicolle medium and in miniculture tubes (Eppendorf, Hamburg, Germany) and capillary tubes (microculture) containing RPMI 1640 medium containing 20% fetal bovine serum. The reference standard was positive results in two of four tests (smear, culture, polymerase chain reaction, or leishmanin skin test). Outcome measures were sensitivity and time to positivity. Fifty-five patients with 74 lesions were enrolled. Of 59 lesions that fulfilled reference criteria for CL, 50 were positive by microculture (sensitivity=84.7%; P=0.001), 45 by miniculture (sensitivity=76.3%; P=0.042), and 35 by traditional culture (sensitivity=59.3%). Median time to positivity was three days by microculture and miniculture and five days by traditional culture (P<0.001). Microculture and miniculture are sensitive and efficient means of diagnosing CL.
Asunto(s)
Técnicas de Cultivo/métodos , Leishmania/aislamiento & purificación , Leishmaniasis Cutánea/diagnóstico , Piel/parasitología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Niño , Preescolar , Femenino , Humanos , Leishmaniasis Cutánea/epidemiología , Leishmaniasis Cutánea/parasitología , Masculino , Persona de Mediana Edad , Perú/epidemiología , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Treatment for cutaneous leishmaniasis (CL) with standard pentavalent antimonial therapy is hampered by cumbersome administration, toxicity, and potential failure. Knowledge of factors influencing treatment outcome is essential for successful management. METHODS: A case-control study of incident cases was performed with patients experiencing their first CL episode. The standard treatment for CL for these patients was 20 mg/kg/day of sodium stibogluconate for 20 days. Clinical and epidemiological data were recorded, and parasite isolates were species typed. Patients were followed up for 6 months to assess treatment outcome. Clinical cure was defined as complete wound closure and re-epithelization without inflammation or infiltration; new lesions, wound reopening, or signs of activity were classified as treatment failure. Descriptive, bivariate, and logistic regression analyses were performed. RESULTS: One hundred twenty-seven patients were recruited; 63 (49.6%) were infected with Leishmania (Viannia) peruviana, 29 (22.8%) were infected with Leishmania (Viannia) braziliensis, 27 (21.3%) were infected with Leishmania (Viannia) guyanensis, and 8 (6.3%) were infected with other species. Only patients infected with the 3 most common species were selected for risk-factor analysis (n=119). Final failure rate at 6 months was 24.4% (95% confidence interval [CI], 16.5%-32.1%), with 96% of failures occurring within the first 3 months of follow-up assessment. Risk factors for treatment failure identified in the final multivariate model were age (per year, odds ratio [OR], 0.95; 95% CI, 0.92-0.99; P=.017), stay of <72 months in area of disease acquisition (OR, 30.45; 95% CI, 2.38-389.25; P=.009), duration of disease <5 weeks (OR, 4.39; 95% CI, 1.12-17.23; P=.034), additional lesion (per lesion, OR, 2.06; 95% CI, 1.3-3.28; P=.002), infection with L. (V.) peruviana (OR, 9.85; 95% CI, 1.01-95.65; P=.049), and infection with L. (V.) braziliensis (OR, 22.36; 95% CI, 1.89-263.96; P=.014). CONCLUSIONS: The identification of parasite species and clinical risk factors for antimonial treatment failure should lead to an improved management of CL in patients in Peru.
Asunto(s)
Gluconato de Sodio Antimonio/administración & dosificación , Antiprotozoarios/administración & dosificación , Leishmania/aislamiento & purificación , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/parasitología , Adolescente , Adulto , Factores de Edad , Animales , Gluconato de Sodio Antimonio/efectos adversos , Antiprotozoarios/efectos adversos , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , Perú , Estudios Prospectivos , Factores de Riesgo , Insuficiencia del TratamientoRESUMEN
Traditional culture of Leishmania spp. is labor intensive and has poor sensitivity. We evaluated a microculture method for the diagnosis of cutaneous leishmaniasis in consecutive patients presenting to the Leishmaniasis Clinic at the Instituto de Medicina Tropical Alexander von Humboldt, Peru, for evaluation of skin lesions. Lesion aspirates were cultured in duplicate and parallel in traditional culture tubes containing modified Novy-MacNeal-Nicolle (NNN) medium or Roswell Park Memorial Institute medium 1640 with 10% fetal bovine serum (10% RPMI) and in 70-microl capillary tubes containing a mixture of lesion aspirate and 10% RPMI. For sensitivity analysis, the consensus standard was considered to be a positive result in any two of the following four tests: Giemsa-stained lesion smear, culture, kinetoplast DNA PCR, or leishmanin skin test. The outcome measures were sensitivity and time to culture positivity. Forty-five patients with 62 skin lesions were enrolled in the study, of which 53 lesions fulfilled the consensus criteria for a final diagnosis of cutaneous leishmaniasis. Of these 53 lesions, 39 were culture positive: 38 in capillary tubes, 29 in traditional culture tubes with modified NNN medium, and 19 in traditional culture tubes with 10% RPMI medium. The sensitivity of microculture was 71.7%, versus 54.7% for traditional culture with NNN (P, 0.038) and 35.8% with 10% RPMI (P, <0.001). The mean times to culture positivity were 4.2 days by microculture, 5.2 days in NNN, and 6 days in 10% RPMI (P, 0.009). We have demonstrated that microculture is a more sensitive and time-efficient means of isolating Leishmania parasites from cutaneous lesions than traditional culture.
Asunto(s)
Leishmania/aislamiento & purificación , Leishmaniasis Cutánea/diagnóstico , Piel/parasitología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Niño , Preescolar , ADN Protozoario/análisis , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Pentavalent antimonials (SbV) are the first-line chemotherapy for American tegumentary leishmaniasis (ATL). There are, however, reports of the occurrence of treatment failure with these drugs. Few studies in Latin America have compared the response to SbV treatment in ATL caused by different Leishmania species. METHODS: Clinical parameters and response to SbV chemotherapy were studied in 103 patients with cutaneous leishmaniasis (CL) in Peru. Leishmania isolates were collected before treatment and typed by multilocus polymerase-chain-reaction restriction fragment-length polymorphism analysis. RESULTS: The 103 isolates were identified as L. (Viannia) peruviana (47.6%), L. (V.) guyanensis (23.3%), L. (V.) braziliensis (22.3%), L. (V.) lainsoni (4.9%), L. (Leishmania) mexicana (1%), and a putative hybrid, L. (V.) braziliensis/L. (V.) peruviana (1%). L. (V.) guyanensis was most abundant in central Peru. Of patients infected with the 3 former species, 21 (21.9%) did not respond to SbV chemotherapy. The proportions of treatment failure (after 12 months of follow-up) were 30.4%, 24.5%, and 8.3% in patients infected with L. (V.) braziliensis, L. (V.) peruviana, and L. (V.) guyanensis, respectively. Infection with L. (V.) guyanensis was associated with significantly less treatment failure than L. (V.) braziliensis, as determined by multiple logistic regression analysis (odds ratio, 0.07 [95% confidence interval, 0.007-0.8]; P=.03). CONCLUSIONS: Leishmania species can influence SbV treatment outcome in patients with CL. Therefore, parasite identification is of utmost clinical importance, because it should lead to a species-oriented treatment.
Asunto(s)
Antimonio/uso terapéutico , Antiprotozoarios/uso terapéutico , Leishmania/aislamiento & purificación , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/parasitología , Meglumina/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Animales , Geografía , Humanos , Leishmania/clasificación , Leishmania/patogenicidad , Leishmaniasis Cutánea/epidemiología , Antimoniato de Meglumina , Perú/epidemiología , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Especificidad de la Especie , Insuficiencia del TratamientoRESUMEN
Pentamidine was compared with meglumine antimoniate (Glucantime) for 80 patients with cutaneous leishmaniasis due to Leishmania braziliensis in Peru. Of the 40 patients administered Glucantime (20 mg of antimony [Sb]/kg/day intravenously for 20 days), 31 cured (78%), 6 failed (15%), of which 5 were due to relapse, and 3 were lost to follow-up (7%). Of the 40 patients administered pentamidine (2 mg/kg every other day for seven injections), 14 were cured (35%), 23 failed (58%), and 3 were lost to follow-up (7%). Five pentamidine failures were due to relapse, and 14 failures were due to the presence of parasites two weeks after therapy. Both regimens were well tolerated. Gastrointestinal, musculoskeletal, and total adverse events were not statistically different in either group. Elevations in levels of liver enzymes and pancreatic enzymes were statistically higher in the Glucantime group, but no patient terminated therapy prematurely. In this study, Glucantime was more effective than pentamidine for treatment of L. braziliensis cutaneous leishmaniasis in Peru based on parasitologic as well as clinical criteria.