RESUMO
BACKGROUND: Children have a lower response rate to antimonial drugs and higher elimination rate of antimony (Sb) than adults. Oral miltefosine has not been evaluated for pediatric cutaneous leishmaniasis. METHODS: A randomized, noninferiority clinical trial with masked evaluation was conducted at 3 locations in Colombia where Leishmania panamensis and Leishmania guyanensis predominated. One hundred sixteen children aged 2-12 years with parasitologically confirmed cutaneous leishmaniasis were randomized to directly observed treatment with meglumine antimoniate (20 mg Sb/kg/d for 20 days; intramuscular) (n = 58) or miltefosine (1.8-2.5 mg/kg/d for 28 days; by mouth) (n = 58). Primary outcome was treatment failure at or before week 26 after initiation of treatment. Miltefosine was noninferior if the proportion of treatment failures was ≤15% higher than achieved with meglumine antimoniate (1-sided test, α = .05). RESULTS: Ninety-five percent of children (111/116) completed follow-up evaluation. By intention-to-treat analysis, failure rate was 17.2% (98% confidence interval [CI], 5.7%-28.7%) for miltefosine and 31% (98% CI, 16.9%-45.2%) for meglumine antimoniate. The difference between treatment groups was 13.8%, (98% CI, -4.5% to 32%) (P = .04). Adverse events were mild for both treatments. CONCLUSIONS: Miltefosine is noninferior to meglumine antimoniate for treatment of pediatric cutaneous leishmaniasis caused by Leishmania (Viannia) species. Advantages of oral administration and low toxicity favor use of miltefosine in children. CLINICAL TRIAL REGISTRATION: NCT00487253.
Assuntos
Antiprotozoários/administração & dosagem , Leishmania/isolamento & purificação , Leishmaniose Cutânea/tratamento farmacológico , Meglumina/administração & dosagem , Compostos Organometálicos/administração & dosagem , Fosforilcolina/análogos & derivados , Administração Oral , Antiprotozoários/efeitos adversos , Criança , Pré-Escolar , Colômbia , Feminino , Humanos , Masculino , Meglumina/efeitos adversos , Antimoniato de Meglumina , Compostos Organometálicos/efeitos adversos , Fosforilcolina/administração & dosagem , Fosforilcolina/efeitos adversos , Falha de TratamentoRESUMO
A 74-year-old man from the rural area of Caicedonia, Valle del Cauca Province, was diagnosed with uncontrolled hypertension, stage IV chronic renal failure and severe anemia. Fifteen years earlier, while living in Guaviare Province, he was diagnosed with leishmaniasis-with lesions located on the right upper and lower eyelids, left auricle and limbs. At that time, he received an incomplete treatment with antimonials. The patient had experienced 8 years of progressive mucosal lesions located in the upper lip, nasal mucosa and right upper and lower eyelids (figure 1). A histopathological diagnosis of leishmaniasis was made and confirmed by polymerase chain reaction (figure 2). Treatment with antimonials (Glucantime) was contraindicated due to the patient's comorbidities. Inpatient supervised treatment with miltefosine (Impavido 50 mg capsules) was initiated according to the national guidelines of 1.8 mg/kg/day for 28 days. Clinical follow up and routine laboratory tests (creatinine, BUN, liver function tests and complete blood counts) were done during and after treatment; no complications were reported. Medical follow up was continued until the Internal medicine, ophthalmology, and plastic surgery consultations were provided for subsequent management of the pathology. Mucocutaneous leishmaniasis is a serious preventable complication of cutaneous leishmaniasis. This case illustrated a failure in opportune diagnosis and treatment of this disease as a consequence of an inadequate leishmaniasis control program. The case indicated the effectiveness of miltefosine as a therapeutic option in patients for whom antimonial treatment is contraindicated.
Assuntos
Antiprotozoários/uso terapêutico , Leishmaniose Cutânea/complicações , Leishmaniose Mucocutânea/etiologia , Fosforilcolina/análogos & derivados , Idoso , Anemia/complicações , Contraindicações , Doenças Palpebrais/tratamento farmacológico , Doenças Palpebrais/etiologia , Doenças Palpebrais/parasitologia , Humanos , Hipertensão/complicações , Falência Renal Crônica/complicações , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Mucocutânea/tratamento farmacológico , Doenças Labiais/tratamento farmacológico , Doenças Labiais/etiologia , Doenças Labiais/parasitologia , Masculino , Meglumina , Antimoniato de Meglumina , Doenças Nasais/tratamento farmacológico , Doenças Nasais/etiologia , Doenças Nasais/parasitologia , Compostos Organometálicos , Fosforilcolina/uso terapêuticoRESUMO
BACKGROUND: Leishmania (Viannia) species are the principal cause of mucosal leishmaniasis. The natural history and pathogenesis of mucosal disease are enigmatic. Parasitological evaluation of mucosal tissues has been constrained by the invasiveness of conventional sampling methods. METHODS: We evaluated the presence of Leishmania in the mucosa of 26 patients with cutaneous leishmaniasis and 2 patients with mucocutaneous leishmaniasis. Swab samples of the nasal mucosa, tonsils, and conjunctiva were analyzed using polymerase chain reaction with LV-B1 primers and Southern blot hybridization. RESULTS: Two patients with mucocutaneous leishmaniasis and 21 (81%) of 26 patients with cutaneous leishmaniasis had Leishmania kinetoplast minicircle DNA (kDNA) in mucosal tissues. kDNA was amplified from swab samples of nasal mucosa from 14 (58%) of 24 patients, tonsils from 13 (46%) of 28 patients, and conjunctiva from 6 (25%) of 24 patients. kDNA was detected in the mucosa of patients with cutaneous disease caused by Leishmania panamensis, Leishmania guyanensis, and Leishmania braziliensis. CONCLUSION: The asymptomatic presence of parasites in mucosal tissues may be common in patients with Leishmania (Viannia) infection.
Assuntos
Leishmania , Leishmaniose Cutânea/parasitologia , Mucosa/parasitologia , Adulto , Idoso , Animais , Southern Blotting , Feminino , Humanos , Leishmaniose Cutânea/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade , Especificidade da Espécie , Adulto JovemRESUMO
American cutaneous leishmaniasis (ACL) has been characterized as a zoonotic disease. However, peridomestic and domestic transmission have been recorded in at least nine countries in Central and South America. The present study was undertaken to identify the etiologic agent of a peridomestic epidemic of ACL in the Department of Tolima, Colombia. Leishmania isolates were obtained during the diagnosis of 56 patients with ACL who consulted the local leishmaniasis control program in three municipalities in Tolima. Species were identified using monoclonal antibodies and isoenzyme electrophoresis. A total of 53 (94.6%) of 56 isolates were identified as Leishmania (Viannia) guyanensis. Three isolates (5.4%) were identified as L. (V.) panamensis. Leishmania (V.) guyanensis is the probable etiologic agent of the largest epidemic of cutaneous leishmaniasis recorded in Colombia. This species has not previously been reported outside the Amazon and southeastern regions of Colombia, and has not been described in the peridomestic setting or linked with an epidemic.