About this Journal Submit a Manuscript Table of Contents
Journal of Biomedicine and Biotechnology
Volume 2010 (2010), Article ID 617521, 8 pages
http://dx.doi.org/10.1155/2010/617521
Review Article

Drug Resistance in Visceral Leishmaniasis

Department for Interventions in Health-Care Facilities, Hellenic Center for Disease Control and Prevention, 15123 Athens, Greece

Received 29 June 2009; Revised 10 August 2009; Accepted 30 August 2009

Academic Editor: Abhay R. Satoskar

Copyright © 2010 Helena C. Maltezou. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. World Health Organization, “Leishmaniasis: burden of disease,” August 2009, http://www.who.int/leishmaniasis/burden/en.
  2. H. C. Maltezou, C. Siafas, M. Mavrikou, et al., “Visceral leishmaniasis during childhood in Southern Greece,” Clinical Infectious Diseases, vol. 31, no. 5, pp. 1139–1143, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. P. Minodier, R. Piarroux, J.-M. Garnier, D. Unal, H. Perrimond, and H. Dumon, “Pediatric visceral leishmaniasis in Southern France,” Pediatric Infectious Disease Journal, vol. 17, no. 8, pp. 701–704, 1998. View at Scopus
  4. M.-E. Raguenaud, A. Jansson, V. Vanlerberghe, et al., “Epidemiology and clinical features of patients with visceral leishmaniasis treated by an MSF clinic in Bakool Region, Somalia, 2004–2006,” PLoS Neglected Tropical Diseases, vol. 1, no. 1, article e85, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. World Health Organization, “Global plan to combat neglected tropical diseases 2008–2015,” August 2009,http://whqlibdoc.who.int/hq/2007/WHO_CDS_NTD_2007.3_eng.pdf.
  6. S. Sundar, J. Chakravarty, V. K. Rai, et al., “Amphotericin B treatment for Indian visceral leishmaniasis: response to 15 daily versus alternate-day infusions,” Clinical Infectious Diseases, vol. 45, no. 5, pp. 556–561, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  7. J. Alvar, P. Aparicio, A. Aseffa, et al., “The relationship between leishmaniasis and AIDS: the second 10 years,” Clinical Microbiology Reviews, vol. 21, no. 2, pp. 334–359, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  8. S. Saha, S. Mondal, A. Banerjee, J. Ghose, S. Bhowmick, and N. Ali, “Immune responses in kala-azar,” Indian Journal of Medical Research, vol. 123, no. 3, pp. 245–266, 2006. View at Scopus
  9. R. C. Jochim and C. Teixeira, “Leishmania commandeers the host inflammatory response through neutrophils,” Trends in Parasitology, vol. 25, no. 4, pp. 145–147, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  10. E. McFarlane, C. Perez, M. Charmoy, et al., “Neutrophils contribute to development of a protective immune response during onset of infection with Leishmania donovani,” Infection and Immunity, vol. 76, no. 2, pp. 532–541, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  11. L. Lachaud, N. Bourgeois, M. Plourde, P. Leprohon, P. Bastien, and M. Ouellette, “Parasite susceptibility to amphotericin B in failures of treatment for visceral leishmaniasis in patients coinfected with HIV type 1 and Leishmania infantum,” Clinical Infectious Diseases, vol. 48, no. 2, pp. e16–e22, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  12. N. Marques, R. Sá, F. Coelho, J. Oliveira, J. Saraiva Da Cunha, and A. Melico-Silvestre, “Miltefosine for visceral leishmaniasis relapse treatment and secondary prophylaxis in HIV-infected patients,” Scandinavian Journal of Infectious Diseases, vol. 40, no. 6-7, pp. 523–526, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  13. S. Nylen and D. Sacks, “Interleukin-10 and the pathogenesis of human visceral leishmaniasis,” Trends in Immunology, vol. 28, no. 9, pp. 378–384, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. H. W. Murray, C. M. Lu, S. Mauze, et al., “Interleukin-10 (IL-10) in experimental visceral leishmaniasis and IL-10 receptor blockade as immunotherapy,” Infection and Immunity, vol. 70, no. 11, pp. 6284–6293, 2002. View at Publisher · View at Google Scholar · View at Scopus
  15. N. Rolao, S. Cortes, S. Gomes-Pereira, and L. Campino, “Leishmania infantum: mixed T-helper-1/T-helper-2 immune response in experimentally infected BALB/c mice,” Experimental Parasitology, vol. 115, no. 3, pp. 270–276, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  16. J. Alexander, K. Christine-Carter, N. Al-Fasi, A. Satoskar, and F. Brombacher, “Endogenous IL-4 is necessary for effective drug therapy against visceral leishmaniasis,” European Journal of Immunology, vol. 30, no. 10, pp. 2935–2943, 2000. View at Publisher · View at Google Scholar · View at Scopus
  17. R. Basu, S. Bhaumik, A. K. Haldar, et al., “Hybrid cell vaccination resolves Leishmania donovani infection by eliciting a strong CD8+ cytotoxic T-lymphocyte response with concomitant suppression of interleukin-10 (IL-10) but not IL-4 or IL-13,” Infection and Immunity, vol. 75, no. 12, pp. 5956–5966, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  18. H. Kothari, P. Kumar, S. Sundar, and N. Singh, “Possibility of membrane modification as a mechanism of antimony resistance in Leishmania donovani,” Parasitology International, vol. 56, no. 1, pp. 77–80, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  19. K. C. Carter, S. Hutchison, F. L. Henriquez, et al., “Resistance of Leishmania donovani to sodium stibogluconate is related to the expression of host and parasite γ-glutamylcysteine synthetase,” Antimicrobial Agents and Chemotherapy, vol. 50, no. 1, pp. 88–95, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  20. N. Singh, “Drug resistance mechanisms in clinical isolates of Leishmania donovani,” Indian Journal of Medical Research, vol. 123, no. 3, pp. 411–422, 2006. View at Scopus
  21. K. Choudhury, D. Zander, M. Kube, R. Reinhardt, and J. Clos, “Identification of a Leishmania infantum gene mediating resistance to miltefosine and SbIII,” International Journal for Parasitology, vol. 38, no. 12, pp. 1411–1423, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. S. Wyllie, T. J. Vickers, and A. H. Fairlamb, “Roles of trypanothione S-transferase and tryparedoxin peroxidase in resistance to antimonials,” Antimicrobial Agents and Chemotherapy, vol. 52, no. 4, pp. 1359–1365, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  23. S. Sundar, D. K. More, M. K. Singh, et al., “Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the Indian epidemic,” Clinical Infectious Diseases, vol. 31, no. 4, pp. 1104–1107, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  24. R. Singh, D. Kumar, V. Ramesh, N. S. Negi, S. Singh, and P. Salotra, “Visceral leishmaniasis, or Kala Azar (KA): high incidence of refractoriness to antimony is contributed by anthroponotic transmission via post-KA dermal leishmaniasis,” Journal of Infectious Diseases, vol. 194, no. 3, pp. 302–306, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  25. S. Sundar, B. B. Thakur, A. K. Tandon, et al., “Clinicoepidemiological study of drug resistance in Indian kala-azar,” British Medical Journal, vol. 308, no. 6924, p. 307, 1994. View at Scopus
  26. M. G. Abdo, W. M. Elamin, E. A. G. Khalil, and M. M. Mukhtar, “Antimony-resistant Leishmania donovani in eastern Sudan: incidence and in vitro correlation,” Eastern Mediterranean Health Journal, vol. 9, no. 4, pp. 837–843, 2003. View at Scopus
  27. L. Gradoni, K. Soteriadou, H. Louzir, et al., “Drug regimens for visceral leishmaniasis in Mediterranean countries,” Tropical Medicine and International Health, vol. 13, no. 10, pp. 1272–1276, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. S. Decuypere, S. Rijal, V. Yardley, et al., “Gene expression analysis of the mechanism of natural Sb(V) resistance in Leishmania donovani isolates from Nepal,” Antimicrobial Agents and Chemotherapy, vol. 49, no. 11, pp. 4616–4621, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. A. H. Sharief, E. A. Gasim-Khalil, T. G. Theander, A. Kharazmi, S. A. Omer, and M. E. Ibrahim, “Leishmania donovani: an in vitro study of antimony-resistant amphotericin B-sensitive isolates,” Experimental Parasitology, vol. 114, no. 4, pp. 247–252, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  30. K. Choudhury, D. Zander, M. Kube, R. Reinhardt, and J. Clos, “Identification of a Leishmania infantum gene mediating resistance to miltefosine and SbIII,” International Journal for Parasitology, vol. 38, no. 12, pp. 1411–1423, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  31. A. Mukherjee, P. K. Padmanabhan, S. Singh, et al., “Role of ABC transporter MRPA, γ-glutamylcysteine synthetase and ornithine decarboxylase in natural antimony-resistant isolates of Leishmania donovani,” Journal of Antimicrobial Chemotherapy, vol. 59, no. 2, pp. 204–211, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  32. F. Cortés-Selva, I. A. Jiménez, F. Muñoz-Martínez, et al., “Dihidro-β-agarofuran sesquiterpenes: a new class of reversal agents of the multidrug resistance phenotype mediated by P-glycoprotein in the protozoan parasite Leishmania,” Current Pharmaceutical Design, vol. 11, no. 24, pp. 3125–3159, 2005. View at Publisher · View at Google Scholar · View at Scopus
  33. M. K. Mittal, S. Rai, A. Ravinger, S. Gupta, S. Sundar, and N. Goyal, “Characterization of natural antimony resistance in Leishmania donovani isolates,” American Journal of Tropical Medicine and Hygiene, vol. 76, no. 4, pp. 681–688, 2007. View at Scopus
  34. G. Mandal, A. Sarkar, P. Saha, N. Singh, S. Sundar, and M. Chatterjee, “Functionality of drug efflux pumps in antimonial resistant Leishmania donovani field isolates,” Indian Journal of Biochemistry and Biophysics, vol. 46, no. 1, pp. 86–92, 2009. View at Scopus
  35. J. M. Basu, A. Mookerjee, R. Banerjee, et al., “Inhibition of ABC transporters abolishes antimony resistance in Leishmania infection,” Antimicrobial Agents and Chemotherapy, vol. 52, no. 3, pp. 1080–1093, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  36. I. L. Wong, K.-F. Chan, B. A. Burkett, et al., “Flavonoid dimers as bivalent modulators for pentamidine and sodium stiboglucanate resistance in Leishmania,” Antimicrobial Agents and Chemotherapy, vol. 51, no. 3, pp. 930–940, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  37. T. Laurent, S. Rijal, V. Yardley, et al., “Epidemiological dynamics of antimonial resistance in Leishmania donovani: genotyping reveals a polyclonal population structure among naturally-resistant clinical isolates from Nepal,” Infection, Genetics and Evolution, vol. 7, no. 2, pp. 206–212, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  38. A. Kumar, V. R. Boggula, S. Sundar, A. K. Shasany, and A. Dube, “Identification of genetic markers in sodium antimony gluconate (SAG) sensitive and resistant Indian clinical isolates of Leishmania donovani through amplified fragment length polymorphism (AFLP),” Acta Tropica, vol. 110, no. 1, pp. 80–85, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. C. P. Thakur, A. K. Pandey, G. P. Sinha, S. Roy, K. Behbehani, and P. Olliaro, “Comparison of three treatment regimens with liposomal amphotericin B (AmBisome) for visceral leishmaniasis in India: a randomized dose-finding study,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 90, no. 3, pp. 319–322, 1996. View at Publisher · View at Google Scholar · View at Scopus
  40. S. Sundar, T. K. Jha, C. P. Thakur, M. Mishra, V. R. Singh, and R. Buffels, “Low-dose liposomal amphotericin B in refractory Indian visceral leishmaniasis: a multicenter study,” American Journal of Tropical Medicine and Hygiene, vol. 66, no. 2, pp. 143–146, 2002. View at Scopus
  41. K. D. Manandhar, T. P. Yadav, V. K. Prajapati, et al., “Antileishmanial activity of nano-amphotericin B deoxycholate,” Journal of Antimicrobial Chemotherapy, vol. 62, no. 2, pp. 376–380, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  42. L. Ordóñez-Gutiérrez, R. Espada-Fernández, M. A. Dea-Ayuela, J. J. Torrado, F. Bolás-Fernandez, and J. M. Alunda, “In vitro effect of new formulations of amphotericin B on amastigote and promastigote forms of Leishmania infantum,” International Journal of Antimicrobial Agents, vol. 30, no. 4, pp. 325–329, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  43. J. J. Torrado, R. Espada, M. P. Ballesteros, and S. Torrado-Santiago, “Amphotericin B formulations and drug targeting,” Journal of Pharmaceutical Sciences, vol. 97, no. 7, pp. 2405–2425, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  44. S. Gupta, A. Dube, and S. P. Vyas, “Antileishmanial efficacy of amphotericin B bearing emulsomes against experimental visceral leishmaniasis,” Journal of Drug Targeting, vol. 15, no. 6, pp. 437–444, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  45. A. Dube, N. Singh, S. Sundar, and N. Singh, “Refractoriness to the treatment of sodium stibogluconate in Indian kala-azar field isolates persist in in vitro and in vivo experimental models,” Parasitology Research, vol. 96, no. 4, pp. 216–223, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  46. K. Ritmeijer, A. Dejenie, Y. Assefa, et al., “A comparison of miltefosine and sodium stibogluconate for treatment of visceral leishmaniasis in an Ethiopian population with high prevalence of HIV infection,” Clinical Infectious Diseases, vol. 43, no. 3, pp. 357–364, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  47. S. K. Bhattacharya, P. K. Sinha, S. Sundar, et al., “Phase 4 trial of miltefosine for the treatment of Indian visceral leishmaniasis,” Journal of Infectious Diseases, vol. 196, no. 4, pp. 591–598, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. F. J. Pérez-Victoria, M. P. Sanchez-Canete, K. Seifert, et al., “Mechanisms of experimental resistance of Leishmania to miltefosine: implications for clinical use,” Drug Resistance Updates, vol. 9, no. 1-2, pp. 26–39, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  49. P. Wadhone, M. Maiti, R. Agarwal, V. Kamat, S. Martin, and B. Saha, “Miltefosine promotes IFN-gamma-dominated anti-leishmanial immune response,” Journal of Immunology, vol. 182, no. 11, pp. 7146–7154, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  50. K. Seifert, F. J. Pérez-Victoria, M. Stettler, et al., “Inactivation of the miltefosine transporter, LdMT, causes miltefosine resistance that is conferred to the amastigote stage of Leishmania donovani and persists in vivo,” International Journal of Antimicrobial Agents, vol. 30, no. 3, pp. 229–235, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  51. K. Seifert, S. Matu, F. J. Pérez-Victoria, S. Castanys, F. Gamarro, and S. L. Croft, “Characterisation of Leishmania donovani promastigotes resistant to hexadecylphosphocholine (miltefosine),” International Journal of Antimicrobial Agents, vol. 22, no. 4, pp. 380–387, 2003. View at Publisher · View at Google Scholar · View at Scopus
  52. E. Castanys-Munoz, J. M. Pérez-Victoria, F. Gamarro, and S. Castanys, “Characterization of an ABCG-like transporter from the protozoan parasite Leishmania with a role in drug resistance and transbilayer lipid movement,” Antimicrobial Agents and Chemotherapy, vol. 52, no. 10, pp. 3573–3579, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  53. J. M. Pérez-Victoria, F. Cortes-Selva, A. Parodi-Talice, et al., “Combination of suboptimal doses of inhibitors targeting different domains of LtrMDR1 efficiently overcomes resistance of Leishmania spp. to miltefosine by inhibiting drug efflux,” Antimicrobial Agents and Chemotherapy, vol. 50, no. 9, pp. 3102–3110, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  54. M. Rakotomanga, M. Saint-Pierre-Chazalet, and P. M. Loiseau, “Alteration of fatty acid and sterol metabolism in miltefosine-resistant Leishmania donovani promastigotes and consequences for drug-membrane interactions,” Antimicrobial Agents and Chemotherapy, vol. 49, no. 7, pp. 2677–2686, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  55. B. D. Pandey, K. Pandey, O. Kaneko, T. Yanagi, and K. Hirayama, “Relapse of visceral leishmaniasis after miltefosine treatment in a Nepalese patient,” American Journal of Tropical Medicine and Hygiene, vol. 80, no. 4, pp. 580–582, 2009. View at Scopus
  56. S. Sundar, T. K. Jha, C. P. Thakur, P. K. Sinha, and S. K. Bhattacharya, “Injectable paromomycin for visceral leishmaniasis in India,” New England Journal of Medicine, vol. 356, no. 25, pp. 2571–2581, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  57. A. Jhingran, B. Chawla, S. Saxena, M. P. Barrett, and R. Madhubala, “Paromomycin: uptake and resistance in Leishmania donovani,” Molecular and Biochemical Parasitology, vol. 164, no. 2, pp. 111–117, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  58. Y. Melaku, S. M. Collin, F. Gatluak, K. Ritmeijer, and R. N. Davidson, “Treatment of kala-azar in Southern Sudan using a 17-day regimen of sodium stibogluconate combined with paromomycin: a retrospective comparison with 30-day sodium stibogluconate monotherapy,” American Journal of Tropical Medicine and Hygiene, vol. 77, no. 1, pp. 89–94, 2007. View at Scopus
  59. K. Seifert and S. L. Croft, “In vitro and in vivo interactions between miltefosine and other antileishmanial drugs,” Antimicrobial Agents and Chemotherapy, vol. 50, no. 1, pp. 73–79, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  60. S. Sundar, M. Rai, J. Chakravarty, et al., “New treatment approach in Indian visceral leishmaniasis: single-dose liposomal amphotericin B followed by short-course oral miltefosine,” Clinical Infectious Diseases, vol. 47, no. 8, pp. 1000–1006, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  61. H. C. Maltezou, “Visceral leishmaniasis: advances in treatment,” Recent Patents on Anti-Infective Drug Discovery, vol. 3, no. 3, pp. 192–198, 2008. View at Scopus
  62. S. Gupta, S. C. Ramesh, and V. M. Srivastava, “Efficacy of picroliv in combination with miltefosine, an orally effective antileishmanial drug against experimental visceral leishmaniasis,” Acta Tropica, vol. 94, no. 1, pp. 41–47, 2005. View at Publisher · View at Google Scholar · View at Scopus
  63. R. Valiathan, M. L. Dubey, R. C. Mahajan, and N. Malla, “Leishmania donovani: effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of Indian clinical isolates to sodium stibogluconate,” Experimental Parasitology, vol. 114, no. 2, pp. 103–108, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  64. A. K. Haldar, S. Banerjee, K. Naskar, D. Kalita, N. S. Islam, and S. Roy, “Sub-optimal dose of sodium antimony gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-γ to IL-10 ratio,” Experimental Parasitology, vol. 122, no. 2, pp. 145–154, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  65. C. P. Thakur, S. Thakur, S. Narayan, and A. Sinha, “Comparison of treament regimens of kala-azar based on culture and sensitivity amastigotes to sodium antimony gluconate,” Indian Journal of Medical Research, vol. 127, no. 6, pp. 582–588, 2008. View at Scopus