What is the recommended treatment for Leishmaniasis?

Treatment of Leishmaniasis

For visceral leishmaniasis (VL), liposomal amphotericin B (L-AmB) is the recommended first-line treatment with an FDA-approved regimen of 3 mg/kg/day IV on days 1-5,14, and 21 (total dose 21 mg/kg). 1, 2

Treatment Approach Based on Clinical Form

Visceral Leishmaniasis (VL)

• First-line therapy: Liposomal amphotericin B (L-AmB)

  • Standard FDA-approved regimen: 3 mg/kg/day IV on days 1-5,14, and 21 (total dose 21 mg/kg) 1, 2
  • Geographic considerations:
    • Indian subcontinent: Lower doses (10-15 mg/kg total) may be effective 2, 3
    • East Africa: Higher doses (30-40 mg/kg total) may be necessary 2
  • For immunocompromised patients: Higher dose regimen of 4 mg/kg/day IV on days 1-5,10,17,24,31, and 38 (total dose 40 mg/kg) 1

• Alternative therapy options:

  • Miltefosine (oral) for patients ≥12 years weighing ≥30 kg 4:
    • 30-44 kg: 50 mg twice daily with food
    • ≥45 kg: 50 mg three times daily with food
    • Treatment duration: 28 days
  • Pentavalent antimonials (20 mg SbV/kg/day IV or IM for 28 days) only in areas with low antimony resistance (<10%) 1

Cutaneous Leishmaniasis (CL)

• Treatment depends on Leishmania species, lesion characteristics, and risk of mucosal involvement
• Miltefosine is FDA-approved for CL caused by L. braziliensis, L. guyanensis, and L. panamensis 4
• Systemic therapy is indicated for:
  • Multiple or large lesions (>4 cm)
  • Lesions on cosmetically sensitive areas
  • Species with risk of mucosal involvement (especially Viannia subgenus)

Mucosal Leishmaniasis (ML)

• Always requires systemic therapy
• Miltefosine is FDA-approved for ML caused by L. braziliensis 4

Monitoring Treatment Response

Visceral Leishmaniasis

• Clinical parameters correlate well with parasitologic responses 1:
  • Fever typically resolves within 1 week
  • Decreased liver and spleen size
  • Improvement in blood counts (leukocytes, hemoglobin, platelets)
  • Increased appetite and weight gain
• Parasitologic confirmation of response (repeat bone marrow aspiration) is not routinely recommended if clinical response is adequate 1

Cutaneous/Mucosal Leishmaniasis

• Monitor for flattening of skin lesions within 4-6 weeks
• Lesion size should decrease by >50% by 4-6 weeks
• Complete epithelialization typically occurs by 3 months

Special Considerations

Immunocompromised Patients

• Higher doses and longer durations of therapy may be needed 1, 5
• For HIV co-infection:
  • Initiate or optimize antiretroviral therapy as soon as patient is stable 1
  • Secondary prophylaxis recommended for patients with CD4 <200 cells/mm³ 2
  • Consider combination therapy (L-AmB plus miltefosine) for refractory cases 1

Treatment Failure

• For patients who fail initial L-AmB therapy:
  • Use alternative drug or higher dose/longer course of L-AmB 1
• For patients who fail miltefosine or antimonial therapy:
  • Switch to L-AmB 1
• For relapse after initial response:
  • Use alternative drug or another course of initial drug (possibly longer duration) 1

Important Cautions

• Miltefosine is contraindicated in pregnancy (embryo-fetal toxicity) 4
• Obtain pregnancy test before prescribing miltefosine to women of reproductive potential 4
• Women must use effective contraception during miltefosine therapy and for 5 months after 4
• Combination therapy approaches (e.g., single-dose L-AmB followed by short-course miltefosine) show promise but require further evaluation 6
• Post-kala-azar dermal leishmaniasis (PKDL) can occur after treatment of L. donovani infection and may require additional management 1

The treatment of leishmaniasis must consider the clinical form (visceral, cutaneous, mucosal), geographic region of acquisition, Leishmania species, host immune status, and drug availability. Early and appropriate treatment is essential to reduce mortality in VL and prevent disfigurement in CL/ML.