Pharmacotherapy for Leishmaniasis in the United States: Focus on Miltefosine

Abstract

Leishmaniasis is a protozoan infection native to various countries, including those in South America and Southeast Asia. Although the incidence of leishmaniasis is low in the United States, it is an important cause of infection in individuals traveling to endemic areas. Various treatment modalities are available, depending on their availability in the geographic region. In the United States, the treatment of choice is considered to be liposomal amphotericin, although other therapies have been explored. In 2014, miltefosine became the first orally available medication approved for the treatment of leishmaniasis in the United States. Based on available data, miltefosine is a first-line option for the treatment of leishmaniasis. Miltefosine is equally efficacious to and may be as tolerable as liposomal amphotericin B. The most common adverse effects of miltefosine are vomiting, diarrhea, and transient liver enzyme level elevation. Miltefosine has not been readily available in the United States due to marketing delays and is expected to become available later this year. In the meantime, the drug may be obtained through the Centers for Disease Control and Prevention expanded-access investigational new drug protocol.

Effects of nitro-heterocyclic derivatives against Leishmania (Leishmania) infantum promastigotes and intracellular amastigotes

“…Initially, the compounds series in our study showed a dose-dependent behavior, and these results were confirmed when analyzed on cytotoxicity assay. Two series of L.L.infantum promastigotes were highlighted, BSF-NO 2 and BSF-Cl, which presented better activity/structure value, although amphotericin B was one of the most active antileishmanial drugs (Kaur et al, 2015;Lucero et al, 2015;Sundar et al, 2015;Vakil et al, 2015;Yesilova et al, 2015). During cytotoxicity assessment in THP1 macrophages with the compounds, it was observed that BSF-H and BSF-NO 2 compounds showed a much higher selectivity index compared to amphotericin B, and these compounds were 13-and 18-fold more active against parasites than THP1 cells.…”

“…When comparing the EC 50 of our compounds with amphotericin B (EC 50 : 0,022 mM), it is noted that the latter has lower EC 50 , ad is more effective when compared to the number of compounds used. This point is crucial, since amphotericin B has been shown as one of the most active antileishmanial drugs ever described (Sesana et al, 2011;Lucero et al, 2015;Yesilova et al, 2015), but other drugs with lower antileishmanial activity are widely used in the treatment of leishmaniasis, such as miltefosine (Kaur et al, 2015;Sundar et al, 2015;Vakil et al, 2015).…”

Parasitic Diseases With Cutaneous Manifestations

“…If the species is unknown or is associated with ML, systemic therapy is indicated [15]. Most countries consider pentavalent antimonials to be first-line systemic therapy, but liposomal amphotericin B is commonly used in the United States [15,17,18]. Second-line systemic options include amphotericin B deoxycholate, liposomal amphotericin B, oral miltefosine, and pentamidine (if the patient does not respond to the first-line therapy or is intolerant to antimonials) [15,17,18].…”

Emerging infectious diseases with cutaneous manifestations

“…31 Alternatives to pentavalent antimonials include liposomal amphotericin 35 and miltefosine, a broad-spectrum alkyllysophospholipid analogue with activity against promastigote and amastigote stages of Leishmania organisms. 36 Azole agents, such as ketoconazole and fluconazole, have also been reported to be efficacious. 36 Topical paromycin ointment is an alternative for Old World leishmaniasis.…”

“…36 Azole agents, such as ketoconazole and fluconazole, have also been reported to be efficacious. 36 Topical paromycin ointment is an alternative for Old World leishmaniasis. 34 Chagas disease Key points d Acute infection is typically asymptomatic d May see a local furuncle-like violaceous lesion (chagoma) d Unilateral periorbital swelling (the Romaña sign) can occur d Chronic infection may lead to cardiac and gastrointestinal symptoms…”