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Review
. 2014 Jan;4(1):10-9.
doi: 10.4103/2229-5070.129143.

The lost hope of elimination of Kala-azar (visceral leishmaniasis) by 2010 and cyclic occurrence of its outbreak in India, blame falls on vector control practices or co-infection with human immunodeficiency virus or therapeutic modalities?

Affiliations
Review

The lost hope of elimination of Kala-azar (visceral leishmaniasis) by 2010 and cyclic occurrence of its outbreak in India, blame falls on vector control practices or co-infection with human immunodeficiency virus or therapeutic modalities?

Mayilsamy Muniaraj. Trop Parasitol. 2014 Jan.

Abstract

The Kala-azar/visceral leishmaniasis (VL) turns epidemic form once in every 15 years in the endemic regions of Indian subcontinent. The goal of elimination of Kala-azar from India by 2010 was lost despite paramount efforts taken by the Government of India and World Health Organization and Regional Office for South East Asia. The main objective of this review was to elucidate the possible reason for the failure of Kala-azar elimination program and to suggest possible remedial measures to achieve the goal in future. The annual numbers of VL cases and deaths recorded in India since 1977 were plotted on a graph, to see if the temporal trends could be associated with changes in the vector control practices or co-infection with human immunodeficiency virus (HIV) or therapeutic modalities used against VL. The VL cases flares up whenever the effect of dichlorodiphenyltrichloroethane (DDT) diminished after the withdrawal of spray. The fading effectiveness was clearly correlated with an increasing number of VL cases. Therapeutic modalities were found to be highly correlating with VL mortality not with VL morbidity. The diminishing efficacy of first and second line drugs and the introduction of new drugs and drugs combination were responsible for ups and downs in the VL mortality. The VL mortality is constantly declining since 1993, but cases started increasing from 2003 to 2007 and then recently again from 2010 to 2011. This shows a serious lacuna in the vector control practices applied. The extent of HIV co-infection did not show any correlation with number/trend of VL cases or death over the study period. It is concluded that, by strict vector control practices, the VL cases can be reduced and by applying proper therapeutic strategies, the VL mortality can be reduced. HIV-VL co-infection does not seem to be in a worried stage.

Keywords: Co-infection; Kala-azar; cyclic occurrence; elimination; human immunodeficiency virus; therapeutic modalities; vector control practices; visceral leishmaniasis.

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Conflict of interest statement

Conflict of Interest: None declared.

Figures

Figure 1
Figure 1
The visceral leishmaniasis hot zone of India
Figure 2
Figure 2
Kala-azar re-emerges whenever the effect of dichlorodiphenyltrichloroethane (DDT) diminishes. In the period under study (1977-2011), DDT spray was carried out three times (1, 2 and 3) when visceral leishmaniasis (VL) cases flared up. The first spray operation was carried out in 1977, 1978 and discontinued in 1979. The effect of DDT was persistent up to 1982.[18] During this period the VL cases declined (green arrow 4) from as high as 41,953 in 1978 to 14,388 in 1982.[21] When the cases peaked an ever high level of 77,099[16] the second spray operation was started, continued through 1992-1994 and discontinued in 1995 and the effect was persistent up to 2001.[18] In the corresponding period, the VL cases declined from 77,099 in 1992 to 12,176 in 2001[16] (green arrow 5). Third spray operation was carried out in the mid 2007 with corresponding declining [green arrow 6] of cases from 44,508 to 24,169 in 2009.[17] But this decline was only short lived and the cases started to resurge to 25,060 in 2010 and 33,108 in 2011[17] (red arrow 9). After the withdrawal of DDT spray and fading residual effect of sprayed DDT, the VL started to re-emerge as happened in 1983 and 2003 (red arrow 7 and 8). Although reports of improper[11] spray with insufficient concentration of DDT,[2425] no data is presently available about withdrawal of spray that started in 2007. The declining of cases (green arrows) always correlates with corresponding DDT spray and its residual effect periods. The absence of DDT spray and no residual effect always correlates with the resurgence of cases. Surprisingly, the deaths did show any correlation with DDT spray operations
Figure 3
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%.[4748] 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.[1449] (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[1617]

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