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Figure 3: Visceral leishmaniasis (VL) mortality in response to changing therapeutic modalities. (1) The exacerbated mortality was due to an acute shortage of drugs necessary for treatment which was mainly due to local firms' decision to limit their production in India. Then it was restored by the intervention of World Health Organization (WHO) and Government of India.[37] (2) The unexpected rise in the mortality during 1996 was due to the usage of defective lot of sodium stibogluconate (SbV).[56] (3) In 1977, around 30% cases were unresponsive to SbV.[36] (4) An expert committee recommended to use 10 mg/kg for two 10 day courses and the cure rate was significantly improved initially,[38] but in 1983, the cure rate was declined to 86%.[39] (5) In 1984, WHO expert committee recommended to increase daily dose from 10 to 20 mg/kg and (6) in 1990 duration from 20 days to 40 days. This dose escalation policy did not prevent the emergence of drug resistance; ultimately the cure rate was declined to 35% in 2001.[45] (7) In 2001, the use of SbV was abandoned in the endemic areas.[45] (8) In 1983, pentamidine was introduced with cure rate of 99% and this brought down the mortality from 135 in 1983 to 67 in 1984. In early 1990s the efficacy of pentamidine had dwindled and the cure rate was declined to 70-75%.[47,48] The combined effect of unresponsive SbV and pentamidine was responsible for the paramount increase of deaths in 1992. The pentamidine was ultimately abandoned in 2003.[14,49] (10) In 1993, amphotericin B was beginning to be used with a cure rate of 99-100%[50] and it maintained its cure rate constantly from 97% to 100%.[52] (11) But recently it was shown that the efficacy of amphotericin B was declined to 93%.[53] (12) In 1998, liposomal amphotericin B was introduced with cure rate of 100%[51] and (13) maintains its cure rate at 98.8% in 2010.[55] (14) Miltefosine was introduced in India in 2002 with >95% cure rate.[15] (15) But the cure rate of miltefosine was also declined subsequently, in 2010, its cure rate was 90.3%. (16) A new concept of multidrug treatment which was introduced in 2011 holds much promises for future VL control.[53] The death due to VL has slowly reduced from 706 in 1993 to 80 in 2011 with the combined effect of amphotericin B, liposomal amphotericin B, miltefosine and after the introduction of amphotericin B multidrug treatments. At the same time number of VL cases increased from 12,066 in 2002 to 45,508 in 2007[16,17]

Figure 3: Visceral leishmaniasis (VL) mortality in response to changing therapeutic modalities. (1) The exacerbated mortality was due to an acute shortage of drugs necessary for treatment which was mainly due to local firms' decision to limit their production in India. Then it was restored by the intervention of World Health Organization (WHO) and Government of India.[37] (2) The unexpected rise in the mortality during 1996 was due to the usage of defective lot of sodium stibogluconate (SbV).[56] (3) In 1977, around 30% cases were unresponsive to SbV.[36] (4) An expert committee recommended to use 10 mg/kg for two 10 day courses and the cure rate was significantly improved initially,[38] but in 1983, the cure rate was declined to 86%.[39] (5) In 1984, WHO expert committee recommended to increase daily dose from 10 to 20 mg/kg and (6) in 1990 duration from 20 days to 40 days. This dose escalation policy did not prevent the emergence of drug resistance; ultimately the cure rate was declined to 35% in 2001.[45] (7) In 2001, the use of SbV was abandoned in the endemic areas.[45] (8) In 1983, pentamidine was introduced with cure rate of 99% and this brought down the mortality from 135 in 1983 to 67 in 1984. In early 1990s the efficacy of pentamidine had dwindled and the cure rate was declined to 70-75%.[47,48] The combined effect of unresponsive SbV and pentamidine was responsible for the paramount increase of deaths in 1992. The pentamidine was ultimately abandoned in 2003.[14,49] (10) In 1993, amphotericin B was beginning to be used with a cure rate of 99-100%[50] and it maintained its cure rate constantly from 97% to 100%.[52] (11) But recently it was shown that the efficacy of amphotericin B was declined to 93%.[53] (12) In 1998, liposomal amphotericin B was introduced with cure rate of 100%[51] and (13) maintains its cure rate at 98.8% in 2010.[55] (14) Miltefosine was introduced in India in 2002 with >95% cure rate.[15] (15) But the cure rate of miltefosine was also declined subsequently, in 2010, its cure rate was 90.3%. (16) A new concept of multidrug treatment which was introduced in 2011 holds much promises for future VL control.[53] The death due to VL has slowly reduced from 706 in 1993 to 80 in 2011 with the combined effect of amphotericin B, liposomal amphotericin B, miltefosine and after the introduction of amphotericin B multidrug treatments. At the same time number of VL cases increased from 12,066 in 2002 to 45,508 in 2007[16,17]