In the first randomized comparison of three standard treatments for New World mucosal leishmaniasis, miltefosine achieved the highest cure rate at 57%, but all three drugs achieved cure in fewer than 60% of patients over 24 months. Success depended more on whether patients had prior treatment failure than on which drug was chosen.
Researchers compared three drugs recommended by clinical guidelines for treating New World mucosal leishmaniasis (ML), a parasitic infection caused primarily by *Leishmania braziliensis*. The infection damages mucous membranes in the nose, mouth, pharynx, and larynx, and can progress to severe tissue destruction if untreated. This was the first randomized controlled trial to directly compare all three standard agents with extended follow-up.
The three treatments tested were: pentavalent antimony (Glucantime, given intravenously), liposomal amphotericin B (LAMB, intravenous), and miltefosine (oral). Cure was defined as at least 90% reduction in disease severity score 24 months after treatment completion. Miltefosine produced the highest cure rate at 23 of 40 patients (57%), followed by antimony at 20 of 40 (50%) and LAMB at 18 of 40 (45%). However, these differences were not statistically significant, meaning the observed variation could reasonably be due to chance. The modest gap between the best and worst performer represents a clinically meaningful but not dramatic difference.
A far more important finding emerged when researchers stratified results by treatment history. Among patients receiving treatment for the first time, cure rates were strong across all three drugs: 71% overall (39 of 55 patients). In contrast, patients undergoing repeat treatment after prior failure had dramatically worse outcomes, with only 35% achieving cure (22 of 63 patients). This difference was so pronounced that it overshadowed any drug-specific effects. The primary reason repeat patients failed was laryngeal involvement at enrollment, suggesting that disease location in the larynx is inherently more difficult to treat than oro-nasal-palatal or pharyngeal lesions.
An encouraging practical finding was that patients achieving cure by 2-6 months of follow-up remained cured at 24-month assessment with 94% probability. This early indicator could help clinicians identify treatment success without waiting nearly two years. A sobering detail was that 14 treatment failures (25% of all failures) occurred more than 24 months after therapy ended, classified as late relapses. This underscores the need for prolonged monitoring even after apparent cure.
Tolerability varied meaningfully between treatments. Patients on antimony and LAMB experienced myalgias, arthralgias, and general bodily discomfort. LAMB and antimony also produced electrocardiogram abnormalities in some patients, occasionally severe. Miltefosine patients had different adverse effects: diarrhea and motion sickness were the primary complaints. The shift from parenteral to oral administration with miltefosine eliminates injection burden, though gastrointestinal tolerability remains an individual issue.
This trial has limited direct application for most readers, as mucosal leishmaniasis is endemic to Central and South America and affects relatively few people globally. However, several principles are worth noting:
First treatment matters most. If you or a family member requires treatment for this infection, the data strongly suggest that first-line therapy works substantially better than salvage therapy. This emphasizes the importance of initial diagnosis and prompt, appropriate treatment rather than waiting or pursuing less-established options.
Treatment selection should be individualized. Since cure rates were similar across all three drugs when used for initial treatment (roughly 70%), the choice logically depends on factors beyond drug efficacy: tolerability profile, route of administration (daily oral versus intravenous dosing), access to cardiac monitoring, cost, and disease location. A patient who cannot tolerate frequent injections might prefer miltefosine despite gastrointestinal side effects. Conversely, someone with cardiac risk factors might avoid antimony and LAMB due to ECG changes.
Laryngeal disease signals difficulty. If disease involves the larynx, expectations should be more conservative regardless of drug choice. The data suggest laryngeal involvement predicts poorer outcomes, and this should inform both treatment planning and follow-up intensity.
Long-term monitoring is essential. Late relapses occurring beyond 24 months were not uncommon. Standard practice should include follow-up visits extending at least 24 months post-treatment, even in apparent cure cases.
| Item | Details |
|---|---|
| Study Type | Randomized controlled trial |
| Sample Size | 118 patients (40 per treatment group) |
| Treatments | Pentavalent antimony, liposomal amphotericin B, miltefosine |
| Follow-up Duration | 24 months post-treatment completion |
| Primary Outcome | Cure defined as >= 90% reduction in disease severity score |
| Published | American Journal of Tropical Medicine and Hygiene |
| PubMed ID | 41818822 |
Arevalo J, et al. Treatment of New World Mucosal Leishmaniasis: Randomized Comparison of Glucantime, Liposomal Amphotericin B, and Miltefosine. *American Journal of Tropical Medicine and Hygiene*. PubMed: 41818822
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