Leishmaniasis: Treatment

1. Visceral Leishmaniasis (VL / Kala-Azar)

General Principles

First-Line Drugs by Region

Drug Details

• Two preparations: sodium stibogluconate (Pentostam, 100 mg SbV/mL) and meglumine antimoniate (Glucantime, 85 mg SbV/mL)
• Dose: 20 mg/kg/day IV or IM for 28-30 days
• Cure rates >90% in Africa, Americas, and most of the Old World
• Cure rates <50% in Bihar, India due to resistance
• Mechanism: inhibition of parasite glycolysis and fatty acid oxidation
• Adverse effects: arthralgia, myalgia, elevated aminotransferases, QT prolongation (QT >0.5 s may herald ventricular arrhythmia), chemical pancreatitis (common but usually mild), pain at injection site
• Harrison's 2025; Fitzpatrick's Dermatology; Katzung's Pharmacology

• Conventional deoxycholate: 0.75-1.0 mg/kg on alternate days for 15 infusions (total ~15 doses)
• Mechanism: binds ergosterol-like sterols in the parasite membrane, altering permeability
• Has become the preferred treatment in India due to high-level antimonial resistance
• Adverse effects: fever with chills (nearly universal), nausea, vomiting, thrombophlebitis, nephrotoxicity, anemia; premedicate with antihistamines and antipyretics before each infusion

• Dose regimens include: 3 mg/kg/day IV on days 1-5, 14, and 21; or 4 doses of 5 mg/kg over 4-10 days; or a single dose of 10 mg/kg (now standard in India)
• Less nephrotoxicity than conventional AmB
• Single-dose therapy is highly effective in India but shows lower efficacy in Africa and other regions, where multiple-dose regimens are required
• Katzung's Basic and Clinical Pharmacology 16e

• First and only oral drug approved for VL
• An alkylphosphocholine analog; inhibits phosphatidylcholine biosynthesis in parasites
• Dose: 2.5 mg/kg/day orally for 28 days (or 1.5-2.5 mg/kg/day)
• Cure rates of 94-97% at 6 months in VL due to L. donovani (Indian subcontinent)
• Contraindicated in pregnancy (teratogenic in animals; avoid in women who may become pregnant within 2 months of treatment)
• Adverse effects: vomiting and diarrhea (common but usually short-lived), transient liver enzyme elevations, nephrotoxicity
• Resistance develops readily in vitro - resistance may limit use as monotherapy
• Katzung; Medical Microbiology 9e; Harrison's 2025

• Aminoglycoside antibiotic; parenteral formulation for VL
• Dose: 11 mg/kg IM daily for 21 days (India trial: 95% cure rate, noninferior to AmB)
• Much less expensive than AmB or miltefosine - important advantage for resource-limited settings
• Showed poorer efficacy in Africa (inferior to sodium stibogluconate in African trials)
• Adverse effects: mild injection pain, uncommon ototoxicity, reversible liver enzyme elevations, no significant nephrotoxicity
• Katzung's Pharmacology 16e

Drug Combinations for VL

• Single-dose LAMB + 7-day miltefosine
• Single-dose LAMB + 10-day paromomycin
• 10-day miltefosine + 10-day paromomycin

Post-Kala-Azar Dermal Leishmaniasis (PKDL)

• Occurs after successful VL treatment due to L. donovani; more common in Sudan and South East Asia
• Preferred treatment: miltefosine 50 mg orally once daily (if <25 kg) or 50 mg twice daily (if >25 kg) for 12 weeks
• Alternative: liposomal amphotericin B
• Goldman-Cecil Medicine

VL in HIV Co-infected Patients

• Relapse rates are high; secondary prophylaxis with LAMB (every 3-4 weeks) is often required until CD4 count recovers with antiretroviral therapy
• Antimonials are less effective and more toxic in HIV co-infected patients

2. Cutaneous Leishmaniasis (CL)

When to Treat

• Lesions on the face, hands, or joints
• Multiple or large ulcers (>4 cm or >3 lesions)
• Lymphatic spread
• New World CL with potential for mucosal spread (especially L. braziliensis)
• Immunosuppressed patients (HIV, transplant)
• Persistent, recurrent, or progressive lesions

Treatment Options

• Pentavalent antimonials: 20 mg/kg/day for 20 days (first-line for most CL)
• Miltefosine 2.5 mg/kg/day orally for 28 days - increasingly preferred, especially for New World CL
  • PAHO guidelines strongly recommend miltefosine for CL due to L. panamensis, L. mexicana, L. guyanensis, and L. braziliensis
• Pentamidine isethionate (2 injections of 4 mg salt/kg, 48 h apart): drug of choice for L. guyanensis
• Liposomal amphotericin B: for refractory cases or when antimonials are contraindicated

• Fluconazole 200 mg/day for 6 weeks: effective for L. major (79% cure vs. 34% placebo)
• Ketoconazole 600 mg/day for 28 days: 76-90% effective for L. panamensis and L. mexicana

• Intralesional pentavalent antimonials: weekly injections sufficient to blanch lesion (0.2-2.0 mL); suitable for lesions ≤3 cm
• Paromomycin 15% ointment (with or without 0.5% gentamicin or 12% methylbenzonium chloride): cures 70-82% of L. major lesions in 20 days
• Topical imiquimod 5-7.5% (plus parenteral antimonials in Peru): speeds cure compared to antimonials alone
• Heat therapy (RF generator) and cryotherapy (liquid nitrogen): used successfully

• L. aethiopica CL: paromomycin 16 mg/kg daily (does NOT respond to antimonials)
• L. tropica CL: azoles preferred, then LAMB, then antimonials ± allopurinol
• L. major CL: miltefosine, fluconazole, or ketoconazole; LAMB if needed

• Rare form caused by L. amazonensis/mexicana (Americas) and L. aethiopica (Africa)
• Very difficult to treat; high relapse rates; combination antimonial + pentamidine may be needed

3. Mucosal Leishmaniasis (ML)

• Caused predominantly by L. braziliensis (New World)
• Requires systemic treatment - never self-heals
• Pentavalent antimonials 20 mg/kg/day for 28-30 days (first-line)
• Liposomal amphotericin B is the treatment of choice for ML (drug of choice per Fitzpatrick's and PAHO)
• Miltefosine: increasingly used in ML; PAHO recommends it for New World ML
• Pentoxifylline 400 mg 2-3 times/day may be added to antimonials (inhibits TNF-a, improves outcomes)
• Treatment failure or relapse is common; secondary prophylaxis may be needed in immunosuppressed patients

Species-Based Treatment Summary (Fitzpatrick's Dermatology)

Quick Drug Reference Table