How is resistant visceral leishmaniasis treated?

Updated: Feb 18, 2020
  • Author: Craig G Stark, MD, FACP, FFTM, RCPS(Glasg), FISTM; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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Answer

Drug resistance can be primary or secondary. Causes include (1) delayed diagnosis (prolonged duration of illness), (2) interrupted and low-dose treatment, (3) immunologic failure, (4) emergence of resistant strains of parasites, and (5) leishmaniasis associated with acquired immunodeficiency syndrome (AIDS).

Patients with stibogluconate-resistant disease should be treated with alternative agents, such as liposomal amphotericin (0.5-3 mg/kg) on alternate days until a dose of 20 mg/kg or pentamidine (2-4 mg/kg) on alternate days for 15 doses. Pentamidine is available in 2 preparations: pentamidine isethionate (Pentam 300) and pentamidine dimethane sulphonate (Lomidine). However, the effectiveness of pentamidine has recently declined.

Liposomal amphotericin has reported cure rates of more than 90% in various studies. However, the high cost of this drug is a disadvantage to its use in areas where visceral leishmaniasis is prevalent.

Another alternative agent is oral miltefosine. Miltefosine did not prevent visceral relapse in patients co-infected with human immunodeficiency virus (HIV) but remained effective with retreatment and over prolonged periods of therapy. [54]

A shift from monotherapy to multidrug combinations in short courses delivered at no or affordable cost, through directly observed therapy, appears to be the only way to effectively treat and prevent drug resistance. Combination therapy of stibogluconate with drugs such as aminosidine and interferon gamma has also produced good results in patients who with a poor response to stibogluconate therapy alone. Aminosidine, an aminoglycoside identical to paromomycin, has also been found to be effective in trials in India.

Guidelines for prevention and treatment of opportunistic diseases in patients with HIV infection have been established. [27, 28] Visceral leishmaniasis is an important opportunistic infection associated with AIDS, and patients co-infected with HIV can develop unusual manifestations of leishmaniasis. Research is being carried out on newer drug delivery systems for amphotericin, including the use of nanoparticles and cochleates, but these investigations have yet to enter human trials. [55]


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