What is the recommended treatment for Leishmania donovani infection?

Treatment for Leishmania donovani Infection

Liposomal amphotericin B (L-AmB) is the first-line treatment for visceral leishmaniasis caused by Leishmania donovani, with the FDA-approved regimen of 3 mg/kg/day IV on days 1-5,14, and 21 (total dose 21 mg/kg). 1

First-Line Treatment Options

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
• Geographic considerations:
  • For L. donovani acquired in the Indian subcontinent: Total doses of 10-15 mg/kg have shown 96-98% efficacy 1
  • For L. donovani acquired in East Africa: Higher doses (30-40 mg/kg) may be necessary due to lower response rates 1
• Advantages: Highest efficacy, fewer adverse reactions compared to other formulations 1

Alternative First-Line Option for Indian Subcontinent Cases

For patients with L. donovani acquired in the Indian subcontinent who are ≥12 years of age, weigh ≥30 kg, and are not pregnant or breastfeeding:

• Miltefosine: 2.5 mg/kg/day orally (maximum 150 mg in 3 divided doses) for 28 days 1, 2
• Particularly effective for patients weighing <75 kg 1
• Important warning: Contraindicated in pregnancy due to embryo-fetal toxicity; effective contraception required during therapy and for 5 months after completion 2

Second-Line Treatment Options

Pentavalent Antimonials

• Dosage: 20 mg SbV/kg/day IV or IM for 28 days 1
• Only recommended in areas with low antimony resistance (<10%) 1
• Not recommended in regions with high resistance (e.g., northeastern India, Bangladesh, Nepal) 1

Amphotericin B Formulations

• Not recommended: Switching to amphotericin B deoxycholate in patients who cannot tolerate L-AmB due to higher toxicity 1
• Exception: For patients who develop liposome-induced complement activation-related pseudoallergy (CARPA), amphotericin B lipid complex may be considered 1

Treatment Monitoring

• Clinical parameters correlate well with parasitologic responses and should be used to monitor treatment response 1
• Key indicators of response:
  • Fever typically resolves within 1 week of effective treatment 1
  • Organomegaly (spleen/liver enlargement) resolves more slowly (3-6 months) 1
• Parasitologic confirmation of response (repeat bone marrow aspiration) is not routinely recommended if clinical response is adequate 1

Special Populations

Immunocompromised Patients (including HIV/AIDS)

• L-AmB: 4 mg/kg/day IV on days 1-5,10,17,24,31, and 38 (total dose 40 mg/kg) 1
• Consider combination therapy (e.g., L-AmB plus miltefosine) for refractory cases 1
• Secondary prophylaxis recommended for patients with HIV/AIDS with CD4 counts <200 cells/mm³ 1
• Initiate or optimize antiretroviral therapy as soon as the patient is stable 1

Treatment Failure

If initial treatment fails:

1. Consider alternative drug regimens
2. Consider longer treatment duration or higher doses
3. Consider combination therapy
4. Consult with a leishmaniasis expert 1

Common Pitfalls and Caveats

1. Geographic variations in response: Treatment efficacy varies significantly by region, particularly for East African versus Indian subcontinent strains 1

2. Pregnancy considerations: Miltefosine is contraindicated in pregnancy; must confirm negative pregnancy test before prescribing and ensure effective contraception during and for 5 months after treatment 2

3. Formulation confusion: Other lipid-associated formulations of amphotericin B (ABLC, amphotericin B colloidal dispersion) have different pharmacokinetic profiles and are not bioequivalent to L-AmB 1

4. Post-kala-azar dermal leishmaniasis (PKDL): Can occur during or after treatment of L. donovani infection in up to 10-27.5% of patients in India and requires additional management 1

5. Monitoring for toxicity: L-AmB has significantly fewer adverse reactions than conventional amphotericin B deoxycholate, but monitoring for infusion-related reactions, nephrotoxicity, and electrolyte abnormalities is still necessary 1