Treatment of visceral leishmaniasis

Growing antimony resistance in patients with visceral leishmaniasis (VL) ov er last two decades, especially in Indian subcontinent, renders this cheap and easily available drug useless for a vast majority of patients, Use of t he second line drug pentamidine isethionate, a toxic drug with declining ef ficacy, has largely been abandoned. Thus, in these areas amphotericin B rem ains the only drug; although it cures > 97% patients, infusion-related adve rse events are common and occasionally serious toxicity, such as myocarditi s, or death can occur. In recent years India has been the center for clinic al development of new anti-leishmanial drugs like lipid formulations of amp hotericin B, new drugs like parenterally administered aminosidine and oral miltefosine. The alkyl phospholipid compound miltefosine is the first effec tive oral compound for VL and is likely to be marketed soon. In addition to the monotherapy, efforts in development of combination chemotherapy are ne eded if the menace of drug resistance is to be contained. Pentavalent antimonial compound sodium stibogluconate (Sb-v) or meglumine a ntimoniate have been the mainstay in the treatment of kala-azar, being used as first-line drug [2]. In late seventies it was realized that the prevail ing Sb-v regimen of 10 mg/kg for 6-10 days left a large proportion of patie nts unresponsive [14]. This led to successive recommendations to increase t he dosage and duration of the drug [27, 28] and currently 20 mg/kg daily fo r 30-40 days form the standard therapy. Increased dosage and duration of Sb -v treatment seemed to work initially; however, the current data show incre asing antimony unresponsiveness with these regimen [22, 26, 8]. Increase in the total quantity of Sbv to six times or more from previous levels has re sulted in increased severe toxicity (7-10%) and deaths (5-10%) [22, 26, 15, 18]. Investigations to look at the in vitro sensitivity patterns of the pa rasites, recovered from patients responding to Sb-v and non-responders, poi nts strongly to the emergence of antimony-resistant strains in India [10].