BACKGROUND:Visceral leishmaniasis (kala-azar) is a worldwide, disseminated intracellular protozoal infection for which prolonged, conventional therapy with pentavalent antimony has become increasingly less effective. OBJECTIVE: To determine the efficacy and minimal effective dose of short-course therapy with amphotericin B lipid complex in visceral leishmaniasis. DESIGN: A randomized, open-label study. SETTING: Inpatient kala-azar treatment unit in the state of Bihar in northeast India, where visceral leishmaniasis is endemic. PATIENTS: 60 patients with active infection who had not responded to or who had relapse after receiving conventional (> 30 days) treatment withpentavalent antimony. INTERVENTION: Intravenous amphotericin B lipid complex was given once daily for 5 consecutive days by 2-hour infusion. Patients were randomly assigned to receive 1, 2, or 3 mg/kg of body weight per day (total doses of 5, 10, or 15 mg/kg, respectively). MEASUREMENTS: Clinical and parasitologic responses (the latter were measured by parasite density score of the splenic aspirate) were determined 14 days after treatment. Definitive responses were assessed 6 months after treatment according to clinical outcomes and findings on examination of bone marrow aspirate. RESULTS: All 60 patients responded to 5 days of treatment. Fourteen days after therapy, all patients had parasite-free splenic aspirates and were considered to have an apparent clinical and parasitologic response. Six months after therapy, definitive responses were documented in 16 of 19 (84% [95% Cl, 60% to 97%]), 18 of 20 (90% [Cl, 68% to 99%]), and 21 of 21 (100% [Cl, 84% to 100%]) patients who received total doses of 5, 10, and 15 mg/kg, respectively. CONCLUSION: Short-course therapy with low-dose amphotericin B lipid complex is effective for visceral leishmaniasis and is an important therapeutic alternative in the management of this serious intracellular protozoal infection.
RCT Entities:
BACKGROUND:Visceral leishmaniasis (kala-azar) is a worldwide, disseminated intracellular protozoal infection for which prolonged, conventional therapy with pentavalent antimony has become increasingly less effective. OBJECTIVE: To determine the efficacy and minimal effective dose of short-course therapy with amphotericin B lipid complex in visceral leishmaniasis. DESIGN: A randomized, open-label study. SETTING: Inpatient kala-azar treatment unit in the state of Bihar in northeast India, where visceral leishmaniasis is endemic. PATIENTS: 60 patients with active infection who had not responded to or who had relapse after receiving conventional (> 30 days) treatment with pentavalent antimony. INTERVENTION: Intravenous amphotericin B lipid complex was given once daily for 5 consecutive days by 2-hour infusion. Patients were randomly assigned to receive 1, 2, or 3 mg/kg of body weight per day (total doses of 5, 10, or 15 mg/kg, respectively). MEASUREMENTS: Clinical and parasitologic responses (the latter were measured by parasite density score of the splenic aspirate) were determined 14 days after treatment. Definitive responses were assessed 6 months after treatment according to clinical outcomes and findings on examination of bone marrow aspirate. RESULTS: All 60 patients responded to 5 days of treatment. Fourteen days after therapy, all patients had parasite-free splenic aspirates and were considered to have an apparent clinical and parasitologic response. Six months after therapy, definitive responses were documented in 16 of 19 (84% [95% Cl, 60% to 97%]), 18 of 20 (90% [Cl, 68% to 99%]), and 21 of 21 (100% [Cl, 84% to 100%]) patients who received total doses of 5, 10, and 15 mg/kg, respectively. CONCLUSION: Short-course therapy with low-dose amphotericin B lipid complex is effective for visceral leishmaniasis and is an important therapeutic alternative in the management of this serious intracellular protozoal infection.