Trends in Parasitology
Leishmaniasis– current chemotherapy and recent advances in the search for novel drugs
Section snippets
Current recommendations
The drugs currently recommended for the treatment of leishmaniasis [7] include the pentavalent antimonials sodium stibogluconate [Pentostam™, GlaxoSmithKline (GSK); http://www.gsk.com] and meglumine antimoniate (Glucantime, Aventis, http://www.aventis.com), amphotericin B (Bristol-Myers Squibb; http://www.bms.com/) and its lipid formulation AmBisome® (Gilead; http://www.gilead.com/), and pentamidine (Aventis) (Table 2 and Figure 2). The antimonials were first introduced in 1945 and remain
Immunomodulation
Cure of leishmaniasis, probably even during chemotherapy, appears to be dependent upon the development of an effective immune response that activates macrophages to produce toxic nitrogen and oxygen metabolites to kill the intracellular amastigotes 6, 33, 34. This process is suppressed by the infection itself which downregulates the requisite signalling between macrophage and T cells, for example, the production of interleukin (IL)-12 or the presentation of major histocompatibility complex
Rational approach: possibilities and problems
New antileishmanial drugs are required and the favoured approach adopted by many to achieve this goal is to identify potential drug targets (either through biochemical studies or, increasingly, by mining the L. major genome database), validating them either chemically or genetically [40], and then identifying inhibitors that can serve as lead compounds to enter a drug development process. Much of this approach is similar to that being applied with many other pathogens (see Cowman and Crabb;
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