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Development of Novel Therapeutics for Neglected Tropical Disease Leishmaniasis

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Technical Report,30 Sep 2014,29 Sep 2015

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US Naval Medical Research Unit No. Six Bellavist Peru

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The leishmaniases comprise a number of diseases caused by obligate intracellular parasites of the genus Leishmania. More than 350 million people worldwide are at risk of contracting leishmaniasis. Cutaneous leishmaniasis CL is the most common form of infection, which manifests as localized skin lesions that may heal or become chronic, leading to significant tissue destruction and disfigurement. Other forms of infections are diffuse cutaneous leishmaniasis DCL, mucosal leishmaniasis ML, or potentially life-threatening visceral leishmaniasis VL, which is characterized by dissemination of the parasites to the liver, spleen and bone marrow. Several drugs including pentavalent antimonials Sb, Amphotericin B, miltefosine and paromomycin are used to treat leishmaniasis. However, all these drugs suffer from significant drawbacks, including the need for parenteral routes of administration, poor patient compliance due to long treatment lengths and toxicity, andor high cost, which limits their use in disease endemic regions. In addition, the emergence of antimonial-resistant strains of VL is rapidly increasing worldwide. Therefore, there is a strong need for new anti-leishmanial drugs that are safe, affordable, and have broad-spectrum activity against different species of Leishmania, including Sb-resistant parasites.

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