Volume 89, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Promastigote miltefosine (MIL) susceptibility was performed on isolates from Indian patients with visceral leishmaniasis treated with MIL. Isolates that were obtained before the onset of MIL treatment, after completion of treatment (29th day), or at the time of treatment failure, were screened using promastigote assay. The MIL susceptibility of the pre-treatment isolates ( = 24, mean IC ± SEM = 3.74 ± 0.38 μM) was significantly higher than that of the post-treatment group ( = 26, mean IC ± SEM = 6.15 ± 0.52 μM; = 0.0006) but was similar in the cured patients ( = 22, mean IC ± SEM = 5.58 ± 0.56 μM) and those who failed treatment ( = 28, mean IC ± SEM = 4.53 ± 0.47 μM). The pre/post-treatment results thus showed a 2-fold difference, whereas isolated from cured versus failed patients showed a similar susceptibility, suggesting that this higher tolerance is not responsible for MIL-treatment failure. Our work highlights the need for careful monitoring of MIL susceptibility for implementation in national VL elimination programs.


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  1. Alvar J, Velez ID, Herrero M, Desjeux P, Cano J, Janin J, den Boer M, WHO Leishmaniasis Control Team; , 2012. Leishmaniasis worldwide and global estimates of its incidence. PLoS ONE 7: e35671.[Crossref] [Google Scholar]
  2. Guerin PJ, Olliaro P, Sundar S, Boelaert M, Croft SL, Desjeux P, Wasunna MK, Bryceson AD, , 2002. Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda. Lancet Infect Dis 2: 494501.[Crossref] [Google Scholar]
  3. Joshi A, Narain JP, Prasittisuk C, Bhatia R, Hashim G, Jorge A, Banjara M, Kroeger A, , 2008. Can visceral leishmaniasis be eliminated from Asia? J Vector Borne Dis 45: 105111. [Google Scholar]
  4. WHO, 2005. Expert Committee on Regional Strategic Framework for Elimination of Kala-azar from the South-East Asia Region (2005–2015). New Delhi: WHO regional Office for South-East Asia. [Google Scholar]
  5. Prajapati VK, Awasthi K, Gautam S, Yadav TP, Rai M, Srivastava ON, Sundar S, , 2011. Targeted killing of Leishmania donovani in vivo and in vitro with amphotericin B attached to functionalized carbon nanotubes. J Antimicrob Chemother 66: 874879.[Crossref] [Google Scholar]
  6. Sundar S, Jha TK, Thakur CP, Engel J, Sindermann H, Fischer C, Junge K, Bryceson A, Berman J, , 2002. Oral miltefosine for Indian visceral leishmaniasis. N Engl J Med 347: 17391746.[Crossref] [Google Scholar]
  7. Jha TK, Sundar S, Thakur CP, Bachmann P, Karbwang J, Fischer C, Voss A, Berman J, , 1999. Miltefosine, an oral agent, for the treatment of Indian visceral leishmaniasis. N Engl J Med 341: 17951800.[Crossref] [Google Scholar]
  8. Sundar S, Singh A, Rai M, Prajapati VK, Singh AK, Ostyn B, Boelaert M, Dujardin JC, Chakravarty J, , 2012. Efficacy of miltefosine in the treatment of visceral leishmaniasis in India after a decade of use. Clin Infect Dis 55: 543550.[Crossref] [Google Scholar]
  9. Rijal S, Ostyn B, Uranw S, Rai K, Bhattarai NR, Dorlo TP, Beijnen JH, Vanaerschot M, Decuypere S, Dhakal SS, Das ML, Karki P, Singh R, Boelaert M, Dujardin JC, , 2013. Increasing failure of Miltefosine in the treatment of kala-azar in Nepal and the potential role of parasite drug resistance, reinfection, or noncompliance. Clin Infect Dis 56: 15301538.[Crossref] [Google Scholar]
  10. Kumar D, Kulshrestha A, Singh R, Salotra P, , 2009. In vitro susceptibility of field isolates of Leishmania donovani to Miltefosine and amphotericin B: correlation with sodium antimony gluconate susceptibility and implications for treatment in areas of endemicity. Antimicrob Agents Chemother 53: 835838.[Crossref] [Google Scholar]
  11. Prajapati VK, Mehrotra S, Gautam S, Rai M, Sundar S, , 2012. In vitro antileishmanial drug susceptibility of clinical isolates from patients with Indian visceral leishmaniasis–status of newly introduced drugs. Am J Trop Med Hyg 87: 655657.[Crossref] [Google Scholar]
  12. Kulshrestha A, Bhandari V, Mukhopadhyay R, Ramesh V, Sundar S, Maes L, Dujardin JC, Roy S, Salotra P, , 2013. Validation of a simple resazurin-based promastigote assay for the routine monitoring of miltefosine susceptibility in clinical isolates of Leishmania donovani . Parasitol Res 112: 825828.[Crossref] [Google Scholar]
  13. Maurya R, Mehrotra S, Prajapati VK, Nylen S, Sacks D, Sundar S, , 2010. Evaluation of blood agar microtiter plates for culturing Leishmania parasites to titrate parasite burden in spleen and peripheral blood of patients with visceral leishmaniasis. J Clin Microbiol 48: 19321934.[Crossref] [Google Scholar]
  14. Srivastava P, Prajapati VK, Vanaerschot M, Van der Auwera G, Dujardin JC, Sundar S, , 2010. Detection of Leptomonas sp. parasites in clinical isolates of Kala-azar patients from India. Infect Genet Evol 10: 11451150.[Crossref] [Google Scholar]
  15. Bhandari V, Kulshrestha A, Deep DK, Stark O, Prajapati VK, Ramesh V, Sundar S, Schonian G, Dujardin JC, Salotra P, , 2012. Drug susceptibility in Leishmania isolates following miltefosine treatment in cases of visceral leishmaniasis and post kala-azar dermal leishmaniasis. PLoS Negl Trop Dis 6: e1657.[Crossref] [Google Scholar]
  16. Leprohon P, Legare D, Raymond F, Madore E, Hardiman G, Corbeil J, Ouellette M, , 2009. Gene expression modulation is associated with gene amplification, supernumerary chromosomes and chromosome loss in antimony-resistant Leishmania infantum . Nucleic Acids Res 37: 13871399.[Crossref] [Google Scholar]

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  • Received : 21 Feb 2013
  • Accepted : 28 May 2013
  • Published online : 09 Oct 2013

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