Navigating Treatment: What is the drug of choice for all forms of leishmaniasis?

October 11, 2025 •

3 min read

Over 12 million people are infected with leishmaniasis worldwide, a disease caused by more than 20 Leishmania species. A single, universal regimen is not possible, as the question of what is the drug of choice for all forms of leishmaniasis depends on the specific clinical manifestation and geographic location of the infection.

Quick Summary

Treatment for leishmaniasis depends on the type of disease, infecting parasite species, and geography. Key systemic medications include liposomal amphotericin B, miltefosine, and pentavalent antimonials, with local therapies also used for cutaneous forms.

Key Points

No Single Drug of Choice: Treatment for leishmaniasis is complex and depends on the specific clinical form (visceral, cutaneous, mucosal), infecting Leishmania species, geographic location, and the patient’s immune status.
Liposomal Amphotericin B for VL: For visceral leishmaniasis, liposomal amphotericin B (Ambisome) is often the first-line treatment, especially in regions with high antimony resistance or in immunocompromised patients.
Miltefosine for Accessibility: Miltefosine is the only oral option for leishmaniasis and is effective for specific species, particularly in the Indian subcontinent. However, it is teratogenic and can cause gastrointestinal side effects.
Antimonials Face Resistance: Older pentavalent antimonials are still used in some regions but have been rendered ineffective in areas like the Indian subcontinent due to widespread drug resistance.
Local vs. Systemic for CL: For cutaneous leishmaniasis, simple lesions can be treated with local therapies like cryotherapy or topical creams, while more severe or high-risk cases require systemic medication.
Combination Therapy is Advancing: Modern strategies increasingly involve combination therapy to boost efficacy, shorten treatment courses, and mitigate the risk of drug resistance.

The Diverse Nature of Leishmaniasis Treatment

Leishmaniasis is a complex disease with multiple clinical presentations, including visceral (VL), cutaneous (CL), and mucocutaneous (ML) forms. The optimal treatment approach is highly nuanced and individualized, making it impossible to name a single "drug of choice" for all forms. Factors such as the infecting Leishmania species, the geographic origin of the infection, local drug resistance patterns, and the patient's immune status significantly influence the therapeutic strategy.

Medications for Visceral Leishmaniasis (VL)

VL, the most severe form of the disease, requires systemic treatment. The primary drugs used for VL are liposomal amphotericin B, miltefosine, and pentavalent antimonials.

Liposomal Amphotericin B (Ambisome)

Considered a first-line treatment in many regions, particularly for immunocompromised patients or those with antimony-resistant infections.
Administered intravenously, it is generally better tolerated and less toxic than conventional amphotericin B.
Dosage protocols vary significantly by geographic region.
Its high cost can be a barrier to access in developing areas.

Miltefosine

The only oral treatment available, offering a convenient outpatient option.
Effective against certain Leishmania species, notably L. donovani causing VL in the Indian subcontinent.
Approved by the FDA in 2014 for specific Leishmania species causing VL, CL, and ML in adults and adolescents over 12 years.
Common side effects include gastrointestinal issues. It is teratogenic and must be avoided during pregnancy.

Pentavalent Antimonials (Sodium Stibogluconate/Pentostam and Meglumine Antimoniate)

Historically the standard treatment, these injections are still used in areas where drug resistance is not prevalent.
High resistance rates, particularly in the Indian subcontinent, limit their use in many regions.
Known for significant side effects like cardiotoxicity.

Treatment for Cutaneous (CL) and Mucocutaneous (ML) Leishmaniasis

Treatment for CL and ML depends on lesion characteristics, the infecting species, and the risk of mucosal involvement.

Localized CL: Simple lesions from low-risk species can often be treated with local methods or may heal naturally. Options include topical paromomycin, cryotherapy, thermotherapy, or intralesional antimonials.
Systemic Treatment for CL/ML: More severe cases or infections with species prone to causing ML require systemic therapy. Miltefosine and liposomal amphotericin B are commonly used, alongside pentavalent antimonials in some areas.

Combination Therapy and Future Directions

Combination approaches are increasingly used to enhance effectiveness, shorten treatment duration, minimize toxicity, and combat resistance. Research is ongoing to develop new drugs and delivery methods.

Comparison of Leishmaniasis Treatments


Feature	Liposomal Amphotericin B (L-AmB)	Miltefosine	Pentavalent Antimonials (SbV)	Local Therapies (Cryo/Thermo/Topical)
Route of Administration	Intravenous infusion	Oral capsules	Intramuscular or intravenous injection	Direct application (topical, intralesional, heat)
Primary Indication	VL, severe/refractory CL/ML, HIV co-infection	VL, CL, ML (species-dependent)	All forms in certain regions where resistance is low	Simple, uncomplicated CL lesions
Main Advantage	Highly effective, well-tolerated systemic therapy	Oral administration, outpatient option	Historically effective, available in many endemic areas	Easy administration, avoids systemic side effects
Major Disadvantage	High cost, parenteral administration required	Teratogenic, GI side effects, variable efficacy by region	Significant toxicity, widespread resistance	Only for specific CL cases, requires skill and experience
FDA Status (USA)	Approved for VL	Approved for VL, CL, ML (species-specific)	Investigational New Drug (IND) via CDC	Cryo/thermotherapy approved for specific CL

Conclusion

In summary, there is no single drug of choice for all forms of leishmaniasis. Treatment is tailored to the specific clinical presentation, parasite species, geographic context, and patient factors. Liposomal amphotericin B and miltefosine are key systemic treatments, while pentavalent antimonials remain relevant where resistance is low. Local therapies are an option for some cutaneous cases. The best approach is always an individualized one based on current guidelines.

Frequently Asked Questions

There is no single drug of choice because treatment effectiveness is highly dependent on the type of leishmaniasis (visceral, cutaneous, or mucosal), the specific Leishmania parasite species, the geographic region where the infection was acquired, and local patterns of drug resistance.

Liposomal amphotericin B (Ambisome) is often the first-choice treatment for visceral leishmaniasis (VL), particularly in areas with antimony resistance or for immunocompromised patients. In some regions, miltefosine or combination therapies are also used.

No, not always. For simple cutaneous lesions caused by species with a low risk of spreading, local therapies like cryotherapy or topical treatments may suffice. However, more severe lesions or infections from species known to cause mucosal spread require systemic therapy.

Miltefosine is advantageous because it is the only oral medication for leishmaniasis, allowing for outpatient treatment. Its disadvantages include potential gastrointestinal side effects and its teratogenic nature, which requires strict contraception for women of childbearing age.

Pentavalent antimonials, historically the standard, are no longer used universally due to the emergence of widespread drug resistance in many endemic areas, especially parts of India and East Africa.

Combination therapy is an evolving strategy aimed at increasing cure rates, reducing the duration of treatment, and preventing drug resistance. Regimens combining drugs like liposomal amphotericin B and miltefosine are increasingly recommended in specific regions.

HIV co-infection complicates leishmaniasis treatment, as patients are more prone to resistance and relapse. Liposomal amphotericin B is the preferred regimen for HIV-coinfected patients, often requiring prolonged courses or secondary prophylaxis.