Leishmania donovani: a model of unresponsiveness to sodium stibogluconate

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Hamad SH
Khalil EAG
Musa AM
Ibrahim ME
El-Hassan AM
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University of Khartoum
Objective:To develop a model of sodium stibogluconate (SSG)-unresponsive L. donovani. Design: Experimental study. Setting:Institute of Endemic Diseases, University of Khartoum. Subjects:Isolates of L. donovani from visceral leishmaniasis endemic areas in eastern Sudan. Methods: Thirty leishmania donovani complex isolates were made unresponsive to sodium stibogluconate (SSG) by exposure to increasing concentrations of the drug in a cell-free system. Results: The initial drug concentrations that inhibited the growth of 50% and 90% (IC50 and IC90) of the isolates were calculated as 0.4±0.04 mg/ml and 0.8±0.1 mg/ml respectively. Following induction of resistance, IC50 and IC90 rose to 50 and 35 folds of the initial values respectively (p<0.05). The time and the number of passages required for the isolates to recover to early log phase following exposure to SSG increased initially with increasing SSG concentrations and later declined despite continued increasing concentrations. SSG unresponsiveness was abolished when the SSG concentration was increased to three folds. Conclusion:In vitro resistance to SSG was successfully induced in L. donovani isolates that can serve as a model for studying underlying molecular basis of SSG-unresponsiveness. SSG-unresponsiveness probably develops in the wild over time as a result of repeated exposure to low SSG concentrations.