What is the treatment for leishmaniasis?

Treatment of Leishmaniasis

Liposomal amphotericin B (L-AmB) is the first-line treatment for visceral leishmaniasis in North America, while treatment for cutaneous and mucosal forms depends on species, lesion characteristics, and risk of mucosal involvement. 1, 2

Visceral Leishmaniasis (VL) Treatment

Immunocompetent Patients

• L-AmB is the drug of choice with an FDA-approved regimen of 3 mg/kg/day IV on days 1-5,14, and 21 (total dose: 21 mg/kg). 2
• For VL acquired in East Africa, higher doses (≥40 mg/kg total) may be necessary due to regional variations in treatment response. 2
• Cure rates with L-AmB exceed 90-95% for both L. infantum-chagasi and L. donovani infections in most endemic regions. 2

Immunocompromised Patients (Including HIV/AIDS)

• L-AmB at 4 mg/kg/day IV on days 1-5,10,17,24,31, and 38 (total dose: 40 mg/kg) is recommended. 1, 2
• Antiretroviral therapy (ART) should be initiated or optimized as soon as the patient is sufficiently stable to tolerate it, either during or soon after initial VL therapy. 1
• Secondary prophylaxis (chronic maintenance therapy) is mandatory for HIV/AIDS patients with CD4 counts <200 cells/mm³ to prevent post-treatment relapse. 1
• Combination therapy (L-AmB plus miltefosine) may be considered for refractory cases, though optimal duration remains undefined. 1

Alternative Agents in Low Antimony Resistance Areas

• In regions with <10% antimony resistance, sodium stibogluconate (SSG) at 20 mg SbV/kg/day IV or IM for 28 days is an alternative first-line option. 2
• Efficacy rates exceed 90-95% in East Africa, Brazil, and Greece with pentavalent antimonials. 2

Treatment Failure Management

• For L-AmB failures, use an alternative drug, higher dose, or longer course of L-AmB. 1
• For miltefosine or pentavalent antimonial failures, switch to L-AmB or an alternative agent. 1
• For relapses after initial response, use an alternative drug or another course with the initial drug (consider higher L-AmB doses if it was used initially). 1

Cutaneous Leishmaniasis (CL) Treatment

Simple vs. Complex Classification

• Simple CL: Small lesions in non-cosmetically important areas without species associated with mucosal risk may be observed if healing spontaneously or treated with local therapy. 3
• Complex CL: Requires systemic therapy, particularly for infections with species associated with mucosal leishmaniasis risk (Viannia subgenus). 3

Systemic Treatment Options

• Miltefosine (FDA-approved): Target dose 2.5 mg/kg/day (maximum 150 mg/day) for 28 days. 1, 4

  • Weight-based dosing: 15-29 kg receive 50 mg once daily; 30-45 kg receive 50 mg twice daily; >46 kg receive 50 mg three times daily. 4
  • Definite cure rates: 66% overall (82% in Colombia, 48% in Guatemala for L. braziliensis/panamensis). 4
  • For L. guyanensis in Brazil: 67.5% cure rate in Manaus, 85% in Bahia. 4
  • Must be taken with food to reduce gastrointestinal side effects. 4
  • Women of reproductive potential must use effective contraception during therapy and for 5 months after completion. 4

• Pentavalent antimonials (SSG): 20 mg SbV/kg/day IV or IM for 20 days is the traditional regimen. 2

  • Avoid intralesional SSG on fingers, nose, ears, eyelids, near lips, or areas with vascular compromise risk. 2

• L-AmB: Used regularly for treatment failures or as alternative to antimonials, with cumulative doses ranging from 20-60 mg/kg. 1, 5

Treatment Failure Approach

• Monitor lesions for 6-12 months post-treatment; by 4-6 weeks, lesion size should decrease >50%, with complete healing by 3 months. 3
• For therapeutic failure, confirm diagnosis and identify parasite species if not done previously. 1
• Options include: repeating antimonial course, adding immunomodulators (imiquimod, pentoxifylline), switching to L-AmB, or combination therapy. 1
• For L. guyanensis infection, repeat pentamidine course may be effective. 1

Mucosal Leishmaniasis (ML) Treatment

All Cases Require Systemic Therapy

• All clinically manifest American ML requires systemic antileishmanial therapy to prevent morbidity (disfigurement) and mortality (aspiration pneumonia, respiratory obstruction). 1
• Complete naso-oropharyngeal/laryngeal examination by a specialist is mandatory before treatment to assess anatomic extension and clinical severity. 1

Treatment Regimens

• Pentavalent antimonials: 20 mg SbV/kg daily IV or IM for 28-30 days. 1
• Amphotericin B deoxycholate: 0.5-1.0 mg/kg per dose IV, daily or every other day, for cumulative total of 20-45 mg/kg. 1
• L-AmB: Cumulative total dose ranging from 20-60 mg/kg. 1
• Miltefosine: Approximately 2.5 mg/kg/day (maximum 150 mg/day) for 28 days. 1, 4
  • Cure rate of 62% at 12 months in Bolivia for L. braziliensis. 4

Critical Safety Measures

• Inpatient monitoring and prophylactic corticosteroid therapy are required for laryngeal/pharyngeal disease with respiratory obstruction risk due to potential inflammatory reactions after initiating antileishmanial therapy. 1

Monitoring and Follow-up

Response Assessment

• Clinical parameters correlate well with parasitologic responses and should be used to monitor treatment response. 2
• For CL: Lesion flattening and >50% size decrease by 4-6 weeks, complete reepithelization by 3 months. 2, 3
• For VL: Monitor indefinitely (until effective immune reconstitution in HIV patients) for post-treatment relapse evidence. 1

Common Pitfalls

• Avoid switching to amphotericin B deoxycholate in patients with L-AmB contraindications or toxicity, as it is almost always associated with more toxicity. 2
• Corticosteroids (topical and systemic) are associated with CL recurrence and should be avoided unless specifically indicated for inflammatory reactions. 1
• TNF-α inhibitors are associated with therapeutic failure and disease recurrence. 1
• Consider immune deficiency if CL is rapidly progressive, unresponsive to various therapies, or highly atypical in presentation. 1