KA is the most fetal disease if left untreated 1, 2, 3, 4, 5. The disease, Visceral Leishmaniasis (VL) or Kala-azar (KA) is endemic in the Indian subcontinent and broadening its base on the Gangetic plains of Bangladesh, India and Nepal. Thus, these phenotypic expressions of experimental model may be considered similar to that of the MIL unresponsive patients. The splenocytes of these animals failed to proliferate anti leishmanial T-cells and lack of cell mediated immunity hampered recovery. The splenic and hepatic stamps smears of MIL-R infected hamsters revealed the retention of parasite load of about 51.45%. In vivo hamster model with this MIL-R isolate showed much lesser reduction in liver weight (17.5%) compared to average reduction in liver weight (40.2%) of the animals infected with MIL-S isolates. Th1/Th2 cytokines, ROS and NO, FACS dot plots and mitochondrial trans membrane potential measurement were performed. The expressions of LdMT and LdRos3 genes of this isolate were found down regulated. While checking the MIL sensitivity of the recent KA clinical isolates (n = 26), we came across one isolate which showed four times more EC 50 for MIL than that of MIL-Sensitive (MIL-S) isolates and considered as putative MIL-Resistant (MIL-R). Within years, resistance to MIL has been reported.

In this bleak situation, Miltefosine (MIL) was introduced to treat mainly antimonial unresponsive cases. Emergence of resistance to drugs used to treat the Indian Kala-azar patients makes control strategy shattered.

Evolve stage 2 kala