Treatment failure in leishmaniasis: Drug-resistance or another (epi-) phenotype?

Expert Review of Anti-Infective Therapy

Volumn 12, Issue 8, 2014, Pages 937-946

  Vanaerschot, Manu ^a   Dumetz, Franck ^a   Roy, Syamal ^b   Ponte Sucre, Alicia ^c   Arevalo, Jorge ^d   Dujardin, Jean Claude ^a,e  

^a INSTITUTE OF TROPICAL MEDICINE   (Belgium)

^b INDIAN INSTITUTE OF CHEMICAL BIOLOGY   (India)

^c UNIVERSIDAD CENTRAL DE VENEZUELA   (Venezuela)

^d UNIVERSIDAD PERUANA CAYETANO HEREDIA   (Peru)

^e UNIVERSITY OF ANTWERP   (Belgium)

Author keywords

drug resistance; leishmania; leishmaniasis; miltefosine; pentavalent antimonials; treatment failure

Indexed keywords

ANTILEISHMANIAL AGENT; PENTAVALENT ANTIMONIAL DERIVATIVE; UNCLASSIFIED DRUG; ANTIPROTOZOAL AGENT; MILTEFOSINE; PHOSPHORYLCHOLINE;

DRUG EFFICACY; DRUG TREATMENT FAILURE; EPIDEMIOLOGICAL DATA; HOST; HUMAN; IN VITRO STUDY; LEISHMANIA BRAZILIENSIS; LEISHMANIA DONOVANI; LEISHMANIASIS; NONHUMAN; PARASITE SURVIVAL; PHENOTYPE; PUBLIC HEALTH; RELAPSE; REVIEW; TREATMENT RESPONSE; ANALOGS AND DERIVATIVES; ANIMAL; DISEASE CARRIER; DRUG EFFECTS; DRUG RESISTANCE; GROWTH, DEVELOPMENT AND AGING; LEISHMANIA; PARASITOLOGY; PATHOGENICITY; PSYCHODIDAE; RECURRENT DISEASE; TREATMENT FAILURE;

ANIMALS; ANTIPROTOZOAL AGENTS; DRUG RESISTANCE; HUMANS; INSECT VECTORS; LEISHMANIA; LEISHMANIASIS; PHOSPHORYLCHOLINE; PSYCHODIDAE; RECURRENCE; TREATMENT FAILURE;

EID: 84903997671     PISSN: 14787210     EISSN: 17448336     Source Type: Journal    
DOI: 10.1586/14787210.2014.916614     Document Type: Review

References (78)

1. Zerpa O, Ponte-Sucre A. American tegumentary leishmaniasis. In: Ponte-Sucre A, Diaz E, Padron-Nieves M, editors. Drug resistance in Leishmania parasites. Consequences, molecular mechanisms and possible treatments. Springer Verlag; Wien: 2013. p. 199-211
2. Banuls AL, Bastien P, Pomares C, et al. Clinical pleiomorphism in human leishmaniases, with special mention of asymptomatic infection. Clin Microbiol Infect 2011;17(10):1451-61
3. Haldar AK, Sen P, Roy S. Use of antimony in the treatment of leishmaniasis: current status and future directions. Mol Biol Int 2011;2011:571242
4. Burza S, Sinha PK, Mahajan R, et al. Five-year field results and long-term effectiveness of 20 mg/kg liposomal amphotericin B (Ambisome) for visceral leishmaniasis in Bihar, India. PLoS Negl Trop Dis 2014;8(1):e2603
5. World Health Organization. Regional strategic framework for elimination of kala-azar from the South-East Asia region (2005-2015). World Health Organization; Manesar, India: 2005
6. Sundar S, Olliaro PL. Miltefosine in the treatment of leishmaniasis: clinical evidence for informed clinical risk management. Ther Clin Risk Manag 2007;3(5):733-40
7. Rijal S, Ostyn B, Uranw S, et al. 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 2013; 56(11):1530-8
8. Sundar S, Singh A, Rai M, et al. Efficacy of miltefosine in the treatment of visceral leishmaniasis in India after a decade of use. Clin Infect Dis 2012;55(4):543-50
9. Musa A, Khalil E, Hailu A, et al. Sodium stibogluconate (SSG) & paromomycin combination compared to SSG for visceral leishmaniasis in East Africa: a randomised controlled trial. PLoS Negl Trop Dis 2012; 6(6):e1674
10. Mueller M, Ritmeijer K, Balasegaram M, et al. Unresponsiveness to AmBisome in some Sudanese patients with kala-azar. Trans R Soc Trop Med Hyg 2007;101(1): 19-24
11. Ritmeijer K, Dejenie A, Assefa Y, et al. A comparison of miltefosine and sodium stibogluconate for treatment of visceral leishmaniasis in an Ethiopian population with high prevalence of HIV infection. Clin Infect Dis 2006;43(3):357-64
12. Gradoni L, Soteriadou K, Louzir H, et al. Drug regimens for visceral leishmaniasis in Mediterranean countries. Trop Med Int Health 2008;13(10):1272-6
13. Berg M, Mannaert A, Vanaerschot M, et al. (Post-) Genomic approaches to tackle drug resistance in Leishmania. Parasitology 2013; 140(12):1492-505
14. Mannaert A, Downing T, Imamura H, Dujardin JC. Adaptive mechanisms in pathogens: universal aneuploidy in Leishmania. Trends Parasitol 2012;28(9): 370-6
15. Yardley V, Croft SL, De DS, et al. The sensitivity of clinical isolates of Leishmania from Peru and Nepal to miltefosine. Am J Trop Med Hyg 2005;73(2):272-5
16. Vermeersch M, da Luz RI, Tote K, et al. In vitro susceptibilities of Leishmania donovani promastigote and amastigote stages to antileishmanial reference drugs: practical relevance of stage-specific differences. Antimicrob Agents Chemother 2009;53(9): 3855-9
17. Vanaerschot M, Decuypere S, Berg M, et al. Drug-resistant microorganisms with a higher fitness - can medicines boost pathogens? Crit Rev Microbiol 2013;39(4): 384-94
18. Rijal S, Yardley V, Chappuis F, et al. Antimonial treatment of visceral leishmaniasis: are current in vitro susceptibility assays adequate for prognosis of in vivo therapy outcome? Microbes Infect 2007;9(4):529-35
19. Yardley V, Ortuno N, Llanos-Cuentas A, et al. American tegumentary leishmaniasis: is antimonial treatment outcome related to parasite drug susceptibility? J Infect Dis 2006;194(8):1168-75
20. Dorlo TP, Balasegaram M, Beijnen JH, de Vries PJ. Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. J Antimicrob Chemother 2012;67(11):2576-97
21. Dorlo TP, Rijal S, Ostyn B, et al. Failure of miltefosine in visceral leishmaniasis is associated with low drug exposure. J Infect Dis 2014; In press
22. Rai K, Cuypers B, Bhattarai NR, et al. Relapse after treatment with miltefosine for visceral leishmaniasis is associated with increased infectivity of the infecting Leishmania donovani strain. MBio 2013; 4(5):e00611-13
23. Bogdan C, Rollinghoff M. The immune response to Leishmania: mechanisms of parasite control and evasion. Int J Parasitol 1998;28(1):121-34
24. Nylen S, Sacks D. Interleukin-10 and the pathogenesis of human visceral leishmaniasis. Trends Immunol 2007;28(9): 378-84
25. Rai AK, Thakur CP, Singh A, et al. Regulatory T cells suppress T cell activation at the pathologic site of human visceral leishmaniasis. PLoS One 2012;7(2):e31551
26. Mukherjee B, Mukhopadhyay R, Bannerjee B, et al. Antimony-resistant but not antimony-sensitive Leishmania donovani up-regulates host IL-10 to overexpress multidrug-resistant protein 1. Proc Natl Acad Sci USA 2013;110(7):E575-82
27. Saha S, Mondal S, Ravindran R, et al. IL-10- and TGF-beta-mediated susceptibility in kala-azar and post-kala-azar dermal leishmaniasis: the significance of amphotericin B in the control of Leishmania donovani infection in India. J Immunol 2007;179(8):5592-603
28. Ganguly S, Mukhopadhyay D, Das NK, et al. Enhanced lesional Foxp3 expression and peripheral anergic lymphocytes indicate a role for regulatory T cells in Indian post-kala-azar dermal leishmaniasis. J Invest Dermatol 2010;130(4):1013-22
29. Guha R, Das S, Sundar S, et al. Antimony resistant Leishmania donovani but not sensitive ones drives greater frequency of potent T-regs: role of IL-10 and LAP/TGFbeta in early immune response (abstract). 5th World Congress on Leishmaniasis; 2013
30. Ghosh M, Roy K, Roy S. Immunomodulatory effects of antileishmanial drugs. J Antimicrob Chemother 2013;68(12):2834-8
31. Teva A, Porrozzi R, Oliveira-Neto MP, Grimaldi GJ. Responses of Leishmania (Viannia) braziliensis cutaneous infection to N-methylglucamine antimoniate in the rhesus monkey (Macaca mulatta) model. J Parasitol 2005;91(4):976-8
32. Belli A, Rodriguez B, Aviles H, Harris E. Simplified polymerase chain reaction detection of new world Leishmania in clinical specimens of cutaneous leishmaniasis. Am J Trop Med Hyg 1998; 58(1):102-9
33. Guevara P, Rojas E, Gonzalez N, et al. Presence of Leishmania braziliensis in blood samples from cured patients or at different stages of immunotherapy. Clin Diagn Lab Immunol 1994;1(4):385-9
34. Veland N, Espinosa D, Valencia BM, et al. Polymerase chain reaction detection of Leishmania kDNA from the urine of Peruvian patients with cutaneous and mucocutaneous leishmaniasis. Am J Trop Med Hyg 2011;84(4):556-61
35. Figueroa RA, Lozano LE, Romero IC, et al. Detection of Leishmania in unaffected mucosal tissues of patients with cutaneous leishmaniasis caused by Leishmania (Viannia) species. J Infect Dis 2009;200(4): 638-46
36. Prina E, Roux E, Mattei D, Milon G. Leishmania DNA is rapidly degraded following parasite death: an analysis by microscopy and real-time PCR. Microbes Infect 2007;9(11):1307-15
37. Deborggraeve S, Boelaert M, Rijal S, et al. Diagnostic accuracy of a new Leishmania PCR for clinical visceral leishmaniasis in Nepal and its role in diagnosis of disease. Trop Med Int Health 2008;13(11):1378-83
38. Mukhopadhyay D, Dalton JE, Kaye PM, Chatterjee M. Post kala-azar dermal leishmaniasis: an unresolved mystery. Trends Parasitol 2014;30(2):65-74
39. Friedrich K, Vieira FA, Porrozzi R, et al. Disposition of antimony in rhesus monkeys infected with Leishmania braziliensis and treated with meglumine antimoniate. J Toxicol Environ Health A 2012;75(2):63-75
40. Mondal D, Khan MG. Recent advances in post-kala-azar dermal leishmaniasis. Curr Opin Infect Dis 2011;24(5):418-22
41. Bogdan C, Donhauser N, Doring R, et al. Fibroblasts as host cells in latent leishmaniosis. J Exp Med 2000;191(12): 2121-30
42. Fauvart M, De Groote VN, Michiels J. Role of persister cells in chronic infections: clinical relevance and perspectives on anti-persister therapies. J Med Microbiol 2011;60(Pt 6):699-709
43. Wakamoto Y, Dhar N, Chait R, et al. Dynamic persistence of antibiotic-stressed mycobacteria. Science 2013;339(6115):91-5
44. Berman JD, Gallalee JV, Hansen BD. Leishmania mexicana: uptake of sodium stibogluconate (Pentostam) and pentamidine by parasite and macrophages. Exp Parasitol 1987;64(1):127-31
45. Wheeler RJ, Gluenz E, Gull K. The limits on trypanosomatid morphological diversity. PLoS One 2013;8(11):e79581
46. Alcolea PJ, Alonso A, Gomez MJ, et al. Transcriptomics throughout the life cycle of Leishmania infantum: high down-regulation rate in the amastigote stage. Int J Parasitol 2010;40(13):1497-516
47. Michel G, Ferrua B, Lang T, et al. Luciferase-expressing Leishmania infantum allows the monitoring of amastigote population size, in vivo, ex vivo and in vitro. PLoS Negl Trop Dis 2011;5(9):e1323
48. Biyani N, Madhubala R. Quantitative proteomic profiling of the promastigotes and the intracellular amastigotes of Leishmania donovani isolates identifies novel proteins having a role in Leishmania differentiation and intracellular survival. Biochim Biophys Acta 2012;1824(12): 1342-50
49. Cloutier S, Laverdiere M, Chou MN, et al. Translational control through eIF2alpha phosphorylation during the Leishmania differentiation process. PLoS One 2012; 7(5):e35085
50. Ouakad M, Vanaerschot M, Rijal S, et al. Increased metacyclogenesis of antimony-resistant Leishmania donovani clinical lines. Parasitology 2011;138(11): 1392-9
51. Vanaerschot M, Maes I, Ouakad M, et al. Linking in vitro and in vivo survival of clinical Leishmania donovani strains. PLoS One 2010;5(8):e12211
52. Vanaerschot M, De DS, Rijal S, et al. Antimonial resistance in Leishmania donovani is associated with increased in vivo parasite burden. PLoS One 2011;6(8): e23120
53. Alves CF, de Amorim IF, Moura EP, et al. Expression of IFN-gamma, TNF-alpha, IL-10 and TGF-beta in lymph nodes associates with parasite load and clinical form of disease in dogs naturally infected with Leishmania (Leishmania) chagasi. Vet Immunol Immunopathol 2009;128(4): 349-58
54. Manna L, Reale S, Vitale F, Gravino AE. Evidence for a relationship between Leishmania load and clinical manifestations. Res Vet Sci 2009;87(1):76-8
55. Rijal S, Bhandari S, Koirala S, et al. Clinical risk factors for therapeutic failure in kala-azar patients treated with pentavalent antimonials in Nepal. Trans R Soc Trop Med Hyg 2010;104(3):225-9
56. Thakur CP, Mitra DK, Narayan S. Skewing of cytokine profiles towards T helper cell type 2 response in visceral leishmaniasis patients unresponsive to sodium antimony gluconate. Trans R Soc Trop Med Hyg 2003;97(4):409-12
57. Verma S, Kumar R, Katara GK, et al. Quantification of parasite load in clinical samples of leishmaniasis patients: IL-10 level correlates with parasite load in visceral leishmaniasis. PLoS One 2010;5(4):e10107
58. Arevalo J, Ramirez L, Adaui V, et al. Influence of Leishmania (Viannia) species on the response to antimonial treatment in patients with American tegumentary leishmaniasis. J Infect Dis 2007;195(12): 1846-51
59. Romero GA, Guerra MV, Paes MG, Macedo VO. Comparison of cutaneous leishmaniasis due to Leishmania (Viannia) braziliensis and L. (V.) guyanensis in Brazil: therapeutic response to meglumine antimoniate. Am J Trop Med Hyg 2001; 65(5):456-65
60. Zerpa O, Convit J. Diffuse cutaneous leishmaniasis in Venezuela. Gazeta Médica da Bahia 2009;79(Suppl 3):30-4
61. Rojas R, Valderrama L, Valderrama M, et al. Resistance to antimony and treatment failure in human Leishmania (Viannia) infection. J Infect Dis 2006;193(10): 1375-83
62. Natera S, Machuca C, Padron-Nieves M, et al. Leishmania spp.: proficiency of drug-resistant parasites. Int J Antimicrob Agents 2007;29(6):637-42
63. Ponte-Sucre A, Diaz E, Padron-Nieves M. The concept of fitness and drug resistance in Leishmania. In: Ponte-Sucre A, Diaz E, Padron-Nieves M, editors. Drug resistance in Leishmania parasites. Consequences, molecular mechanisms and possible treatments. Springer Verlag; Wien: 2013. p. 431-49
64. Costa DL, Carregaro V, Lima-Junior DS, et al. BALB/c mice infected with antimony treatment refractory isolate of Leishmania braziliensis present severe lesions due to IL-4 production. PLoS Negl Trop Dis 2011;5(3):e965
65. Souza AS, Giudice A, Pereira JM, et al. Resistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-alpha production. BMC Infect Dis 2010;10:209
66. Giudice A, Camada I, Leopoldo PT, et al. Resistance of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis to nitric oxide correlates with disease severity in Tegumentary Leishmaniasis. BMC Infect Dis 2007;7:7
67. Ives A, Ronet C, Prevel F, et al. Leishmania RNA virus controls the severity of mucocutaneous leishmaniasis. Science 2011; 331(6018):775-8
68. Gupta S. Visceral leishmaniasis: experimental models for drug discovery. Indian J Med Res 2011;133:27-39
69. Seifert K, Escobar P, Croft SL. In vitro activity of anti-leishmanial drugs against Leishmania donovani is host cell dependent. J Antimicrob Chemother 2010;65(3): 508-11
70. Wilson ME, Jeronimo SM, Pearson RD. Immunopathogenesis of infection with the visceralizing Leishmania species. Microb Pathog 2005;38(4):147-60
71. Fulton JD, Joyner LP, Chandler RJ. Studies on protozoa. Part II: the golden hamster (Cricetus auratus) and cotton rat (Sigmodon hispidus) as experimental hosts for Leishmania donovani. Trans R Soc Trop Med Hyg 1950;44(1):105-12
72. Dorlo TP, Huitema AD, Beijnen JH, de Vries PJ. Optimal dosing of miltefosine in children and adults with visceral leishmaniasis. Antimicrob Agents Chemother 2012;56(7):3864-72
73. Ghosh J, Das S, Guha R, et al. Hyperlipidemia offers protection against Leishmania donovani infection: role of membrane cholesterol. J Lipid Res 2012; 53(12):2560-72
74. Ghosh J, Guha R, Das S, Roy S. Liposomal cholesterol delivery activates the macrophage innate immune arm to facilitate intracellular Leishmania donovani killing. Infect Immun 2014;82(2):607-17
75. Goto H, Lindoso JA. Current diagnosis and treatment of cutaneous and mucocutaneous leishmaniasis. Expert Rev Anti Infect Ther 2010;8(4):419-33
76. Mukherjee S, Mukherjee B, Mukhopadhyay R, et al. Imipramine is an orally active drug against both antimony sensitive and resistant Leishmania donovani clinical isolates in experimental infection. PLoS Negl Trop Dis 2012;6(12):e1987
77. Perry MR, Wyllie S, Raab A, et al. Chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis. Proc Natl Acad Sci USA 2013;110(49):19932-7
78. Vanaerschot M, Huijben S, Van den Broeck F, Dujardin JC. Drug resistance in vectorborne parasites: multiple actors and scenarios for an evolutionary arms race. FEMS Microbiol Rev 2014; 38(1):41-55