Recent advances in the treatment of visceral leishmaniasis

Abstract

Pentavalent antimonials (sodium stibogluconate and meglumine antimoniate) There is increasing resistance to pentavalent antimonials (Sb”) in many countries. Pre-treatment isolates of Leishmania donovani vary considerably in their sensitivity to Sb” and resistance may be induced by prior inadequate courses of Sb” (GROGL et al., 1989,1992). The World Health Organization (WHO) guidelines (WHO, 1990) reflect the increasing unresponsiveness to Sb”, and 20 mg Sb”/kg/d for 220 d is recommended. In India primary Sb” resistance occurs in about 10% of cases and a regimen of 20 mg Sb”/kg/d for 240 d is recommended (THAKUR et al., 1988). HERWALDT & BERMAN (1992) recommended that the traditional daily maximum of 850 mg Sb” be abandoned, as the toxicity of Sb” may have been over-emphasized in the past. The rapid urinary elimination of sodium stibogluconate (REES et al., 1980) means that Sb” may be more effective if given more frequently than once daily (BRYCESON, 1987). ZIJLSTRA et al. (1991) showed that Sb” 10 mgikg every 12 h for 15 d was better than 20 mgikgld for 30 d, and both CHULAY et al. (1983) and GACHIHI et al. (1992a) showed that 10 mg SbV/kg every 8 h for 10 d was better than 20 mgikgid for 30d. The mechanism of clinical antimony resistance has not been established, though studies in vitro suggest the presence of P-glycoprotein in Sb” resistant parasites, which could be reversed experimentally by verapamil (NEAL et al., 1989). However, in humans verapamil had no effect in reversing Sb” resistance, nor in improving the response rate to Sb” in previously untreated cases of VL (THAKUR & KUMAR. 1992). The choice between sodium stibogluconate and’ meglumine antimoniate in the treatment of VL has been determined by regional availability and cost of the drugs; there is no published comparative clinical study. Experimental studies have not shown significant differences (NEAL, 1987). There is, however, known variation in potency between manufactured lots.