What is the treatment for visceral leishmaniasis?

Treatment of Visceral Leishmaniasis

Liposomal amphotericin B (L-AmB) is the recommended first-line treatment for visceral leishmaniasis in immunocompetent patients, administered at 3 mg/kg/day IV on days 1-5,14, and 21 (total dose 21 mg/kg). 1

Primary Treatment for Immunocompetent Patients

First-Line Therapy: Liposomal Amphotericin B

• L-AmB is the FDA-approved and strongly recommended treatment with a total dose of 21 mg/kg given over specific days (days 1-5,14, and 21), representing the highest quality evidence (strong recommendation, high-quality evidence) 1

• Geographic considerations are critical: Standard 18-21 mg/kg total doses are effective in most regions, but patients with VL acquired in East Africa require higher doses of 40 mg/kg or more due to regional parasite resistance patterns 1

• Other lipid formulations (amphotericin B lipid complex, amphotericin B colloidal dispersion) are not recommended as they lack FDA approval for VL and have insufficient evidence of bioequivalence 1

Alternative Oral Therapy: Miltefosine

• Miltefosine is an acceptable alternative for patients ≥12 years old, weighing ≥30 kg, with L. donovani infection acquired in the Indian subcontinent (South Asia), who are not pregnant or breastfeeding 1

• Dosing: 2.5 mg/kg/day (maximum 150 mg in 3 divided doses) for 28 days 1

  • Patients <45 kg: 50 mg twice daily 2
  • Patients ≥45 kg: 50 mg three times daily 2

• Final cure rate: 94% in clinical trials conducted in India, with 3% relapse rate at 6 months 2

• Critical contraindication: Absolutely avoid in women of reproductive potential unless using effective contraception during and for 2 months after therapy due to reproductive toxicity 2

Second-Line Therapy: Pentavalent Antimonials

• Pentavalent antimonial therapy (20 mg SbV/kg/day IV or IM for 28 days) is recommended only in areas where antimony-resistant Leishmania prevalence is low (<10%) 1

• This represents a strong recommendation with high-quality evidence but is geographically restricted due to widespread resistance, particularly in the Indian subcontinent 1

Treatment of HIV/AIDS-Associated VL

Immunocompromised Patients Require Modified Approach

• L-AmB remains the recommended treatment but with a higher total dose: 4 mg/kg/day IV on days 1-5,10,17,24,31, and 38 (total 40 mg/kg over 38 days) 1

• Antiretroviral therapy (ART) must be initiated or optimized as soon as the patient is sufficiently stable, either during or soon after initial VL therapy, as immune reconstitution is critical for treatment success 1

• Secondary prophylaxis (chronic maintenance therapy) is mandatory for patients with CD4 counts <200 cells/mm³ to prevent relapse 1

• Combination therapy (L-AmB plus miltefosine) may be considered for refractory cases, though optimal regimens remain undefined 1

• Indefinite monitoring is required until effective immune reconstitution occurs, as relapse rates remain high (50-78% at 1 year) even with prophylaxis 1

Essential Ancillary Care

All VL Patients Require Comprehensive Support

• Nutritional support is critical given the progressive wasting associated with untreated VL 1

• Screen and treat concurrent infections: tuberculosis, malaria, bacterial or parasitic dysentery 1

• Blood transfusions as needed for severe anemia or bleeding complications 1

• Assess for HIV/AIDS or other immunosuppression in all newly diagnosed VL patients 1

Monitoring Treatment Response

Clinical Parameters Are Sufficient

• Clinical parameters correlate well with parasitologic response and should be used to monitor treatment efficacy (strong recommendation) 1

• Repeat bone marrow aspiration is NOT recommended in patients showing timely clinical response 1

• Antibody levels decline slowly over many months and should not be used for immediate treatment response assessment 1

Management of Treatment Failure or Relapse

Immunocompetent Patients

• If L-AmB fails: Switch to an alternative drug OR use higher dose/longer course of L-AmB 1

• If miltefosine or pentavalent antimonial fails: Switch to L-AmB or alternative agent 1

• For relapse after initial response: Use alternative drug OR repeat therapy with initial drug (potentially longer course); if L-AmB was used initially, consider higher dose 1

HIV/AIDS-Coinfected Patients

• Relapses typically represent immunologic failure, not drug resistance, so reinduction with L-AmB is usually justified 1

• Serial relapses at progressively shorter intervals may indicate chronic refractory VL requiring combination therapy 1

Critical Pitfalls to Avoid

• Never use amphotericin B deoxycholate as first-line due to higher toxicity and irreversible adverse effects compared to liposomal formulation 1

• Do not prescribe miltefosine to women of childbearing potential without confirmed effective contraception and negative pregnancy test 2

• Do not assume standard L-AmB doses work in East Africa—these patients require 40 mg/kg or higher 1

• Do not discontinue secondary prophylaxis in HIV patients based solely on clinical improvement; continue until CD4 >200 cells/mm³ with sustained immune reconstitution 1

• Asymptomatic visceral infection in immunocompetent persons can be monitored closely without immediate treatment, as most self-resolve, but initiate therapy if clinical VL develops 1