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Sodium stibogluconate resistance in leishmania donovani correlates with greater tolerance to macrophage antileishmanial responses and trivalent antimony therapy

Carter, K.C. and Hutchison, S. and Boitelle, A. and Murray, H.W. and Sundar, S. and Mullen, A. (2005) Sodium stibogluconate resistance in leishmania donovani correlates with greater tolerance to macrophage antileishmanial responses and trivalent antimony therapy. Parasitology, 131 (6). pp. 747-757. ISSN 0031-1820

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Abstract

Co-treatment of mice infected with different strains of Leishmania donovani with a non-ionic surfactant vesicle formulation of buthionine sulfoximine (BSO-NIV), and sodium stibogluconate (SSG), did not alter indicators of Th1 or Th2 responses but did result in a significant strain-independent up-regulation of IL6 and nitrite levels by stimulated splenocytes from treated mice compared to controls. The efficacy of BSO-NIV/SSG treatment was dependent on the host being able to mount a respiratory burst indicating that macrophages are important in controlling the outcome of treatment. In vitro studies showed that SSG resistance was associated with a greater resistance to killing by activated macrophages, treatment with hydrogen peroxide or potassium antimony tartrate. Longitudinal studies showed that a SSG resistant (SSG-R) strain was more virulent than a SSG susceptible (SSG-S) strain, resulting in significantly higher parasite burdens by 4 months post-infection. These results indicate that SSG exposure may favour the emergence of more virulent strains.