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A. Visceral Leishmaniasis
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The treatment of choice for visceral leishmaniasis on the Indian subcontinent is liposomal amphotericin B (approved by the FDA), which is generally effective and well tolerated but expensive. Standard dosing is 3 mg/kg/day intravenously on days 1–5, 14, and 21. Simpler regimens that have shown good efficacy in India include four doses of 5 mg/kg over 4–10 days and a single dose of 15 mg/kg, but efficacies of shorter regimens have been lower outside India. A single infusion of an amphotericin B lipid emulsion, which is more affordable than liposomal preparations, showed excellent efficacy, albeit lower than that of the liposomal formulation. Conventional amphotericin B deoxycholate, which is much less expensive, is also highly effective but with more toxicity. It is administered as a slow intravenous infusion of 1 mg/kg/day for 15–20 days or 0.5–1 mg/kg every second day for up to 8 weeks. Infusion-related side effects with conventional or liposomal amphotericin B include gastrointestinal symptoms, fever, chills, dyspnea, hypotension, and hepatic and renal toxicity.
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Pentavalent antimonials remain the most commonly used drugs to treat leishmaniasis in most areas. Response rates are good outside India, but in India, resistance is a major problem. Two preparations are available, sodium stibogluconate in the United States and many other areas and meglumine antimonate in Latin America and francophone countries; the compounds appear to have comparable activities. In the United States, sodium stibogluconate can be obtained from the CDC Drug Service (www.cdc.gov/laboratory/drugservice). Standard dosing for either antimonial is 20 mg/kg once daily intravenously (preferred) or intramuscularly for 20 days for cutaneous leishmaniasis and 28 days for visceral or mucocutaneous disease. Toxicity increases over time, with development of gastrointestinal symptoms, fever, headache, myalgias, arthralgias, pancreatitis, and rash. Intramuscular injections can cause sterile abscesses. Monitoring should include serial ECGs, and changes are indications for discontinuation to avoid progression to serious arrhythmias.
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The efficacy of amphotericin B is lower in East Africa than in Asia, and the standard treatment is a combination of sodium stibogluconate (20 mg/kg/day intravenously) plus paromomycin (15 mg/kg/day intramuscularly) for 17 days, with demonstrated excellent efficacy; liposomal amphotericin B may be considered in elderly or pregnant patients due to toxicity concerns.
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Miltefosine is the first oral drug for the treatment of leishmaniasis, and it is registered in India for this indication. It initially demonstrated excellent results in India, but efficacy is decreasing due to drug resistance. It can be administered at a daily oral dose of 2.5 mg/kg in two divided doses for 28 days. A 28-day course of miltefosine (2.5 mg/kg/day) is also effective for the treatment of New World cutaneous leishmaniasis. Vomiting, diarrhea, and elevations in transaminases and kidney function studies are common, but generally short-lived, side effects.
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Pentamidine isethionate is an alternative therapy for visceral leishmaniasis, given daily or on alternate days for 15 doses of 2–4 mg/kg intramuscularly or intravenously, but it is no longer widely used. Side effects are as described for the treatment of African trypanosomiasis.
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The aminoglycoside paromomycin (11 mg/kg/day intramuscularly for 21 days) was shown to be similarly efficacious to amphotericin B for the treatment of visceral disease in India, where it is approved for this indication. It is much less expensive than liposomal amphotericin B or miltefosine. The drug is well tolerated; side effects include ototoxicity and reversible elevations in liver enzymes.
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The use of drug combinations to improve treatment efficacy, shorten treatment courses, and reduce the selection of resistant parasites has been actively studied. In India, compared to a standard 30-day (treatment on alternate days) course of amphotericin, noninferior efficacy and decreased adverse events were seen with a single dose of liposomal amphotericin plus a 7-day course of miltefosine, a single dose of liposomal amphotericin plus a 10-day course of paromomycin, or a 10-day course of miltefosine plus paromomycin. A combination of sodium stibogluconate and paromomycin is the standard treatment in East Africa.
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B. Cutaneous Leishmaniasis
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In the Old World, cutaneous leishmaniasis is generally self-healing over some months and does not metastasize to the mucosa, so it may be justified to withhold treatment in regions without mucocutaneous disease if lesions are small and cosmetically unimportant. Lesions on the face or hands are generally treated. New World leishmaniasis has a greater risk of progression to mucocutaneous disease, so treatment is more often warranted. Standard therapy is with pentavalent antimonials for 20 days, as described above. Other treatments include those discussed above for visceral disease, azole antifungals, and allopurinol. In studies in South America, a 28-day course of miltefosine was superior to a 20-day course of meglumine antimoniate, and oral fluconazole also showed good efficacy. Topical therapy has included intralesional antimony, intralesional pentamidine, paromomycin ointment, cryotherapy, local heat, and surgical removal. Diffuse cutaneous leishmaniasis and related chronic skin processes generally respond poorly to therapy.
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C. Mucocutaneous Leishmaniasis
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Cutaneous infections from regions where parasites include those that cause mucocutaneous disease (eg, L braziliensis in parts of Latin America) should all be treated to help prevent disease progression. Treatment of mucocutaneous disease with antimonials is disappointing, with responses in only about 60% in Brazil. Other therapies listed above for visceral leishmaniasis may also be used, although they have not been well studied for this indication.