Volume 87, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Regional variations in susceptibility of clinical isolates have been reported to antimonials but not other antileishmanial drugs. Therefore, we evaluated the susceptibility of four antileishmanial drugs in clinical use in 28 clinical isolates from endemic and non-endemic regions in the J774A.1 macrophage cell line, and we found increased tolerance of miltefosine and paromomycin in isolates from a patient from a high endemic region. Effective dose for 90% killing (ED) values were significantly higher for miltefosine ( = 0.005) and paromomycin ( = 0.02) in isolates from the high endemic region, although there were no significant differences between ED values for paromomycin, miltefosine, and amphotericin B in the non- versus endemic region isolates. This report is the first of higher ED values for miltefosine and paromomycin indicating susceptibility difference between regions for these newly introduced drugs by the parasite, and their use should be carefully monitored through directly observed therapy or multidrug treatment to preserve their efficacy for longer periods.


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  1. 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]
  2. Sundar S, , 2001. Drug resistance in Indian visceral leishmaniasis. Trop Med Int Health 6: 849854.[Crossref] [Google Scholar]
  3. Lira R, Sundar S, Makharia A, Kenney R, Gam A, Saraiva E, Sacks D, , 1999. Evidence that the high incidence of treatment failures in Indian kala-azar is due to the emergence of antimony-resistant strains of Leishmania donovani . J Infect Dis 180: 564567.[Crossref] [Google Scholar]
  4. Mueller M, Ritmeijer K, Balasegaram M, Koummuki Y, Santana MR, Davidson R, , 2007. Unresponsiveness to AmBisome in some Sudanese patients with kala-azar. Trans R Soc Trop Med Hyg 101: 1924.[Crossref] [Google Scholar]
  5. Yardley V, Croft SL, De Doncker S, Dujardin JC, Koirala S, Rijal S, Miranda C, Llanos-Cuentas A, Chappuis F, , 2005. The sensitivity of clinical isolates of Leishmania from Peru and Nepal to miltefosine. Am J Trop Med Hyg 73: 272275. [Google Scholar]
  6. Coombs GH, Hart DT, Capaldo J, , 1983. Leishmania mexicana: drug sensitivities of promastigotes and transforming amastigotes. J Antimicrob Chemother 11: 151162.[Crossref] [Google Scholar]
  7. Sereno D, Lemesre JL, , 1997. Axenically cultured amastigote forms as an in vitro model for investigation of antileishmanial agents. Antimicrob Agents Chemother 41: 972976. [Google Scholar]
  8. Das P, Samuels S, Desjeux P, Mittal A, Topno R, Siddiqui NA, Sur D, Pandey A, Sarnoff R, , 2010. Annual incidence of visceral leishmaniasis in an endemic area of Bihar, India. Trop Med Int Health 15 (Suppl 2): 411.[Crossref] [Google Scholar]
  9. Sundar S, Rai M, , 2002. Laboratory diagnosis of visceral leishmaniasis. Clin Diagn Lab Immunol 9: 951958. [Google Scholar]
  10. 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]
  11. Montalvo AM, Fraga J, Monzote L, Montano I, De Doncker S, Dujardin JC, Van der Auwera G, , 2010. Heat-shock protein 70 PCR-RFLP: a universal simple tool for Leishmania species discrimination in the New and Old World. Parasitology 137: 11591168.[Crossref] [Google Scholar]
  12. 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]
  13. Manandhar KD, Yadav TP, Prajapati VK, Kumar S, Rai M, Dube A, Srivastava ON, Sundar S, , 2008. Antileishmanial activity of nano-amphotericin B deoxycholate. J Antimicrob Chemother 62: 376380.[Crossref] [Google Scholar]
  14. 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]
  15. Seifert K, Croft SL, , 2006. In vitro and in vivo interactions between miltefosine and other antileishmanial drugs. Antimicrob Agents Chemother 50: 7379.[Crossref] [Google Scholar]
  16. Sundar S, Jha TK, Thakur CP, Sinha PK, Bhattacharya SK, , 2007. Injectable paromomycin for visceral leishmaniasis in India. N Engl J Med 356: 25712581.[Crossref] [Google Scholar]
  17. Fumarola L, Spinelli R, Brandonisio O, , 2004. In vitro assays for evaluation of drug activity against Leishmania spp. Res Microbiol 155: 224230.[Crossref] [Google Scholar]
  18. Mbongo N, Loiseau PM, Billion MA, Robert-Gero M, , 1998. Mechanism of amphotericin B resistance in Leishmania donovani promastigotes. Antimicrob Agents Chemother 42: 352357. [Google Scholar]
  19. Srivastava P, Prajapati VK, Rai M, Sundar S, , 2011. Unusual case of resistance to amphotericin B in visceral leishmaniasis in a region in India where leishmaniasis is not endemic. J Clin Microbiol 49: 30883091.[Crossref] [Google Scholar]
  20. 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]
  21. Perez-Victoria FJ, Sanchez-Canete MP, Seifert K, Croft SL, Sundar S, Castanys S, Gamarro F, , 2006. Mechanisms of experimental resistance of Leishmania to miltefosine: implications for clinical use. Drug Resist Updat 9: 2639.[Crossref] [Google Scholar]
  22. Sundar S, Murray HW, , 2005. Availability of miltefosine for the treatment of kala-azar in India. Bull World Health Organ 83: 394395. [Google Scholar]
  23. World Health Organization, 2010. Control of the Leishmaniasis: Report of a Meeting of the WHO Expert Committee on the Control of Leishmaniases G. WHO Technical Report Series 949. Geneva, Switzerland: World Health Organization. [Google Scholar]
  24. Sundar S, Chakravarty J, Agarwal D, Rai M, Murray HW, , 2010. Single-dose liposomal amphotericin B for visceral leishmaniasis in India. N Engl J Med 362: 504512.[Crossref] [Google Scholar]
  25. Sundar S, Sinha PK, Rai M, Verma DK, Nawin K, Alam S, Chakravarty J, Vaillant M, Verma N, Pandey K, Kumari P, Lal CS, Arora R, Sharma B, Ellis S, Strub-Wourgaft N, Balasegaram M, Olliaro P, Das P, Modabber F, , 2011. Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India: an open-label, non-inferiority, randomised controlled trial. Lancet 377: 477486.[Crossref] [Google Scholar]

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  • Received : 09 Jan 2012
  • Accepted : 29 Mar 2012
  • Published online : 03 Oct 2012

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