Evidence that the high incidence of treatment failures in Indian kala-azaris due to the emergence of antimony-resistant strains of Leishmania donovani

The possibility that the high frequency of treatment failures in Indian kal a-azar might be due to infection with antimony-resistant strains of Leishma nia donovani has not been experimentally addressed. L. donovani isolates we re obtained from splenic aspiration smears of 24 patients in Bihar, India, who either did not respond (15) or did respond (9) to 1 or more full course s of treatment with sodium antimony gluconate (SAG), A strong correlation ( P < .001) between clinical response and SAG sensitivity in vitro was observ ed only when strains were assayed as intracellular amastigotes: responsive isolates ED50 = 2.4 +/- 2.6, ED90 = 6.4 +/- 7.8 mu g SAG/mL; unresponsive i solates ED50 = 7.4 +/- 3.7 mu g SAG/mL, ED90 = 29.1 +/- 11.1 SAG/mL. No cor relation with clinical response was found by use of extracellular promastig otes (ED50 = 48 +/- 22 vs. 52 +/- 29 mu g/mL). The emergence of antimony-re sistant L. donovani strains appears to be a cause of treatment failures in India.