Immunotherapy and targeted therapies in treatment of visceral leishmaniasis: Current status and future prospects

Frontiers in Immunology

Volumn 5, Issue JUN, 2014, Pages

  Singh, Om Prakash ^a   Sundar, Shyam ^a  

^a BANARAS HINDU UNIVERSITY   (India)

Author keywords

Anti IL 10 mAb; IL 10; Immunotherapy; Resistance; Treatment; Visceral leishmaniasis

Indexed keywords

EID: 84905642320     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2014.00296     Document Type: Review

References (103)

1. Desjeux P. Leishmaniasis. Public health aspects and control. Clin Dermatol (1996) 14:417-23. doi: 10.1016/0738-081X(96)00057-0
2. World Health Organization. Eliminating Visceral Leishmaniasis: A Multi-Pronged Approach. Available at: http://www.who.int/tdr/news/2011/vl-elimination/en/ Alvar J, Velez ID, Bern C, Herrero M, Desjeux P, Cano J, et al. Leishmaniasis worldwide and global estimates of its incidence. PLoS One (2012) 7:e35671. doi:10.1371/journal.pone.0035671
3. Alvar J, Velez ID, Bern C, Herrero M, Desjeux P, Cano J, et al. Leishmaniasis worldwide and global estimates of its incidence. PLoS One (2012) 7:e35671. doi:10.1371/journal.pone.0035671
4. Addy M, Nandy A. Ten years of kala-azar in West Bengal, part I. Did post-kala-azar dermal leishmaniasis initiate the outbreak in 24-parganas? Bull World Health Organ (1992) 70:341-6.
5. Bern C, Hightower AW, Chowdhury R, Ali M, Amann J, Wagatsuma Y, et al. Risk factors for kala-azar in Bangladesh. Emerg Infect Dis (2005) 11:655-62. doi:10.3201/eid1105.040718
6. Alvar J, Yactayo S, Bern C. Leishmaniasis and poverty. Trends Parasitol (2006) 22:552-7. doi:10.1016/j.pt.2006.09.004
7. Meheus F, Boelaert M, Baltussen R, Sundar S. Costs of patient management of visceral leishmaniasis in Muzaffarpur, Bihar, India. Trop Med Int Health (2006) 11:1715-24. doi:10.1111/j.1365-3156.2006.01732.x
8. Croft SL, Sundar S, Fairlamb AH. Drug resistance in leishmaniasis. Clin Microbiol Rev (2006) 19:111-26. doi:10.1128/CMR.19.1.111-126.2006
9. Sundar S, More DK, Singh MK, Singh VP, Sharma S, Makharia A, et al. Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the Indian epidemic. Clin Infect Dis (2000) 31:1104-7. doi:10.1086/318121
10. Pandey BD, Pandey K, Kaneko O, Yanagi T, Hirayama K. Relapse of visceral leishmaniasis after miltefosine treatment in a Nepalese patient. Am J Trop Med Hyg (2009) 80:580-2.
11. Sundar S, Rai M. Treatment of visceral leishmaniasis. Expert Opin Pharmacother (2005) 6:2821-9. doi:10.1517/14656566.6.16.2821
12. Jha TK. Drug unresponsiveness & combination therapy for kala-azar. Indian J Med Res (2006) 123:389-98.
13. Sundar S, Chakravarty J, Agarwal D, Rai M, Murray HW. Single-dose liposomal amphotericin B for visceral leishmaniasis in India. N Engl J Med (2010) 11:504-12. doi:10.1056/NEJMoa0903627
14. Sundar S, Singh A. What steps can be taken to counter the increasing failure of miltefosine to treat visceral leishmaniasis? Expert Rev Anti Infect Ther (2013) 11:117-9. doi:10.1586/eri.12.170
15. Sundar S, Singh A, Rai M, Prajapati VK, Singh AK, Ostyn B, et al. Efficacy of miltefosine in the treatment of visceral leishmaniasis in India after a decade of use. Clin Infect Dis (2012) 55:543-50. doi:10.1093/cid/cis474
16. Croft SL, Olliaro P. Leishmaniasis chemotherapy - challenges and opportunities. Clin Microbiol Infect (2011) 17:1478-83. doi:10.1111/j.1469-0691.2011.03630.x
17. Singh N, Singh RT, Sundar S. Novel mechanism of drug resistance in kala azar field isolates. J Infect Dis (2003) 188:600-7. doi:10.1086/377133
18. Sundar S, Chakravarty J, Rai VK, Agrawal N, Singh SP, Chauhan V, et al. Amphotericin B treatment for Indian visceral leishmaniasis: response to 15 daily versus alternate-day infusions. Clin Infect Dis (2007) 45:556-61. doi:10.1086/520665
19. Sundar S, Kumar K, Chakravarty J, Agrawal D, Agrawal S, Chhabra A, et al. Cure of antimony-unresponsive Indian post-kala-azar dermal leishmaniasis with oral miltefosine. Trans R Soc Trop Med Hyg (2006) 100:698-700. doi:10.1016/j.trstmh.2005.09.015
20. Jhingran A, Chawla B, Saxena S, Barrett MP, Madhubala R. Paromomycin: uptake and resistance in Leishmania donovani. Mol Biochem Parasitol (2009) 164:111-7. doi:10.1016/j.molbiopara.2008.12.007
21. Sundar S, Jha TK, Thakur CP, Sinha PK, Bhattacharya SK. Injectable paromomycin for visceral leishmaniasis in India. N Engl J Med (2007) 356:2571-81. doi:10.1056/NEJMoa066536
22. Sundar S, Chakravarty J. Paromomycin in the treatment of leishmaniasis. Expert Opin Investig Drugs (2008) 17:787-94. doi:10.1517/13543784.17.5.787
23. Das VN, Ranjan A, Sinha AN, Verma N, Lal CS, Gupta AK, et al. A randomized clinical trial of low dosage combination of pentamidine and allopurinol in the treatment of antimony unresponsive cases of visceral leishmaniasis. J Assoc Physicians India (2001) 49:609-13.
24. Das VN, Siddiqui NA, Pandey K, Singh VP, Topno RK, Singh D, et al. A controlled, randomized nonblinded clinical trial to assess the efficacy of amphotericin B deoxycholate as compared to pentamidine for the treatment of antimony unresponsive visceral leishmaniasis cases in Bihar, India. Ther Clin Risk Manag (2009) 5:117-24. doi:10.2147/TCRM.S3581
25. Das A, Ali N. Vaccine development against Leishmania donovani. Front Immunol (2012) 3:99. doi:10.3389/fimmu.2012.00099
26. Singh OP, Stober CB, Singh AK, Blackwell JM, Sundar S. Cytokine responses to novel antigens in an Indian population living in an area endemic for visceral leishmaniasis. PLoS Negl Trop Dis (2012) 6:e1874. doi:10.1371/journal.pntd.0001874
27. Janeway CA, Medzhitov R. Innate immune recognition. Annu Rev Immunol (2002) 20:197-216. doi:10.1146/annurev.immunol.20.083001.084359
28. Sacks D, Noben-Trauth N. The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol (2002) 2:845-58. doi:10.1038/nri933
29. Ghalib HW, Piuvezam MR, Skeiky YA, Siddig M, Hashim FA, el-Hassan AM, et al. Interleukin 10 production correlates with pathology in human Leishmania donovani infections. J Clin Invest (1993) 92:324-9. doi:10.1172/JCI116570
30. Karp CL, el-Safi SH, Wynn TA, Satti MM, Kordofani AM, Hashim FA, et al. In vivo cytokine profiles in patients with kala-azar. Marked elevation of both interleukin-10 and interferon-gamma. J Clin Invest (1993) 91:1644-8. doi:10.1172/JCI116372
31. Kenney RT, Sacks DL, Gam AA, Murray HW, Sundar S. Splenic cytokine responses in Indian kala-azar before and after treatment. J Infect Dis (1998) 177:815-8. doi:10.1086/517817
32. Bhattacharya P, Ali N. Involvement and interactions of different immune cells and their cytokines in human visceral leishmaniasis. Rev Soc Bras Med Trop (2013) 46:128-34. doi:10.1590/0037-8682-0022-2012
33. Cummings HE, Tuladhar R, Satoskar A. Cytokines and their STATs in cutaneous and visceral leishmaniasis. J Biomed Biotechnol (2010) 2010:294389. doi:10.1155/2010/294389
34. Basu A, Chakrabarti G, Saha A, Bandyopadhyay S. Modulation of CD11C+ splenic dendritic cell functions in murine visceral leishmaniasis: correlation with parasite replication in the spleen. Immunology (2000) 99:305-13. doi:10.1046/j.1365-2567.2000.00939.x
35. Schwarz T, Remer KA, Nahrendorf W, Masic A, Siewe L, Müller W, et al. T cell-derived IL-10 determines leishmaniasis disease outcome and is suppressed by a dendritic cell based vaccine. PLoS Pathog (2013) 9:e1003476. doi:10.1371/journal.ppat.1003476
36. Bacellar O, Brodskyn C, Guerreiro J, Barral-Netto M, Costa CH, Coffman RL, et al. Interleukin-12 restores interferon-gamma production and cytotoxic responses in visceral leishmaniasis. J Infect Dis (1996) 173:1515-8. doi:10.1093/infdis/173.6.1515
37. Ghalib HW, Whittle JA, Kubin M, Hashim FA, el-Hassan AM, Grabstein KH, et al. IL-12 enhances Th1-type responses in human Leishmania donovani infections. J Immunol (1995) 154:4623-9.
38. Kobayashi M, Fitz L, Ryan M, Hewick RM, Clark SC, Chan S, et al. Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J Exp Med (1989) 170(3):827-45. doi:10.1084/jem.170.3.827
39. Scharton TM, Scott P. Natural killer cells are a source of interferon gamma that drives differentiation of CD4+ T cell subsets and induces early resistance to Leishmania major in mice. J Exp Med (1993) 178:567-77. doi:10.1084/jem.178.2.567
40. Trinchieri G. Interleukin-12 and its role in the generation of TH1 cells. Immunol Today (1993) 14(7):335-8. doi:10.1016/0167-5699(93)90230-I
41. Heinzel FP, Schoenhaut DS, Rerko RM, Rosser LE, Gately MK. Recombinant interleukin 12 cures mice infected with Leishmania major. J Exp Med (1993) 177:1505-9. doi:10.1084/jem.177.5.1505
42. Murray HW, Hariprashad J, Coffman RL. Behavior of visceral Leishmania donovani in an experimentally induced T helper cell 2 (Th2)-associated response model. J Exp Med (1997) 185:867-74. doi:10.1084/jem.185.5.867
43. Ahuja SS, Reddick RL, Sato N, Montalbo E, Kostecki V, Zhao W, et al. Dendritic cell (DC)-based anti-infective strategies: DCs engineered to secrete IL-12 are a potent vaccine in a murine model of an intracellular infection. J Immunol (1999) 163:3890-7.
44. Alexander CE, Kaye PM, Engwerda CR. CD95 is required for the early control of parasite burden in the liver of Leishmania donovani-infected mice. Eur J Immunol (2001) 31:1199-210. doi:10.1002/1521-4141(200104)31:4<1199::AID-IMMU1199>3.0.CO;2-6
45. De Almeida Silva L, Romero HD, Prata A, Costa RT, Nascimento E, Carvalho SF, et al. Immunologic tests in patients after clinical cure of visceral leishmaniasis. Am J Trop Med Hyg (2006) 75:739-43.
46. Hailu A. Pre- and post-treatment antibody levels in visceral leishmaniasis. Trans R Soc Trop Med Hyg (1990) 84:673-5. doi:10.1016/0035-9203(90)90141-Z
47. Gidwani K, Picado A, Ostyn B, Singh SP, Kumar R, Khanal B, et al. Persistence of Leishmania donovani antibodies in past visceral leishmaniasis cases in India. Clin Vaccine Immunol (2010) 18:346-8. doi:10.1128/CVI.00473-10
48. Hoerauf A, Solbach W, Lohoff M, Rollinghoff M. The Xid defect determines an improved clinical course of murine leishmaniasis in susceptible mice. Int Immunol (1994) 6:1117-24. doi:10.1093/intimm/6.8.1117
49. Hasker E, Malaviya P, Gidwani K, Picado A, Ostyn B, Kansal S, et al. Strong association between serological status and probability of progression to clinical visceral leishmaniasis in prospective cohort studies in India and Nepal. PLoS Negl Trop Dis (2014) 8(1):e2657. doi:10.1371/journal.pntd.0002657
50. Bhattacharyya T, Bowes DE, El-Safi S, Sundar S, Falconar AK, Singh OP, et al. Significantly lower anti-Leishmania IgG responses in Sudanese versus Indian visceral leishmaniasis. PLoS Negl Trop Dis (2014) 8(2):e2675. doi:10.1371/journal.pntd.0002675
51. El-On J. Current status and perspectives of the immunotherapy of leishmaniasis. Isr Med Assoc J (2009) 11:623-8.
52. Sundar S, Rosenkaimer F, Lesser ML, Murray HW. Immunochemotherapy for a systemic intracellular infection: accelerated response using interferon-gamma in visceral leishmaniasis. J Infect Dis (1995) 171:992-6. doi:10.1093/infdis/171.4.992
53. Badaro R, Falcoff E, Badaro FS, Carvalho EM, Pedral-Sampaio D, Barral A, et al. Treatment of visceral leishmaniasis with pentavalent antimony and interferon gamma. N Engl J Med (1990) 322:16-21. doi:10.1056/NEJM199001043220104
54. Almeida RP, Brito J, Machado PL, De Jesus AR, Schriefer A, Guimarães LH, et al. Successful treatment of refractory cutaneous leishmaniasis with GM-CSF and antimonials. Am J Trop Med Hyg (2005) 73:79-81.
55. Mayrink W, Botelho AC, Magalhães PA, Batista SM, Lima Ade O, Genaro O, et al. Immunotherapy, immunochemotherapy, and chemotherapy for American cutaneous leishmaniasis treatment. Rev Soc Bras Med Trop (2006) 39:14-21. doi:10.1590/S0037-86822006000100003
56. Badaro R, Lobo I, Munos A, Netto EM, Modabber F, Campos-Neto A, et al. Immunotherapy for drug-refractory mucosal leishmaniasis. J Infect Dis (2006) 194:1151-9. doi:10.1086/507708
57. Machado-Pinto J, Pinto J, da Costa CA, Genaro O, Marques MJ, Modabber F, et al. Immunochemotherapy for cutaneous leishmaniasis: a controlled trial using killed Leishmania (Leishmania) amazonensis vaccine plus antimonial. Int J Dermatol (2002) 41:73-8. doi:10.1046/j.1365-4362.2002.01336.x
58. García Bustos MF, Barrio AB, Parodi Ramoneda CM, Ramos F, Mora MC, Convit J, et al. Immunological correlates of cure in the first American cutaneous leishmaniasis patient treated by immunotherapy in Argentina. A case report. Invest Clin (2013) 52:365-75.
59. Arevalo I, Tulliano G, Quispe A, Spaeth G, Matlashewski G, Llanos-Cuentas A, et al. Role of imiquimod and parenteral meglumine antimoniate in the initial treatment of cutaneous leishmaniasis. Clin Infect Dis (2007) 44:1549-54. doi:10.1086/518172
60. Squires KE, Rosenkaimer F, Sherwood JA, Forni AL, Were JB, Murray HW. Immunochemotherapy for visceral leishmaniasis: a controlled pilot trial of antimony versus antimony plus interferon-gamma. Am J Trop Med Hyg (1993) 48:666-9.
61. Musa AM, Khalil EA, Mahgoub FA, Elgawi SH, Modabber F, Elkadaru AE, et al. Immunochemotherapy of persistent post-kala-azar dermal leishmaniasis: a novel approach to treatment. Trans R Soc Trop Med Hyg (2008) 102:58-63. doi:10.1016/j.trstmh.2007.08.006
62. Firooz A, Khamesipour A, Ghoorchi MH, Nassiri-Kashani M, Eskandari SE, Khatami A, et al. Imiquimod in combination with meglumine antimoniate for cutaneous leishmaniasis: a randomized assessor-blind controlled trial. Arch Dermatol (2006) 142:1575-9. doi:10.1001/archderm.142.12.1575
63. Sergiev VP, Shuikina EE, Kuznetsov VP, Beliaev DL, Fediainova IE, Norbadalov MT, et al. The use of leukinferon in treating zoonotic cutaneous leishmaniasis. 2. Patient treatment. Med Parazitol (Mosk) (1993) (1):42-3.
64. Convit J, Ulrich M, Zerpa O, Borges R, Aranzazu N, Valera M, et al. Immunotherapy of American cutaneous leishmaniasis in Venezuela during the period 1990-99. Trans R Soc Trop Med Hyg (2003) 97:469-72. doi:10.1016/S0035-9203(03)90093-9
65. O'Daly JA, Spinetti HM, Gleason J, Rodríguez MB. Clinical and immunological analysis of cutaneous leishmaniasis before and after different treatments. J Parasitol Res (2013) 2013:657016. doi:10.1155/2013/657016
66. Convit J, Ulrich M, Polegre MA, Avila A, Rodríguez N, Mazzedo MI, et al. Therapy of Venezuelan patients with severe mucocutaneous or early lesions of diffuse cutaneous leishmaniasis with a vaccine containing pasteurized Leishmania promastigotes and bacillus Calmette-Guerin: preliminary report. Mem Inst Oswaldo Cruz (2004) 99:57-62. doi:10.1590/S0074-02762004000100010
67. Laskay T, van Zandbergen G, Solbach W. Neutrophil granulocytes as host cells and transport vehicles for intracellular pathogens: apoptosis as infection-promoting factor. Immunobiology (2008) 213:183-91. doi:10.1016/j.imbio.2007.11.010
68. Aga E, Katschinski DM, van Zandbergen G, Laufs H, Hansen B, Müller K, et al. Inhibition of the spontaneous apoptosis of neutrophil granulocytes by the intracellular parasite Leishmania major. J Immunol (2002) 169:898-905. doi:10.4049/jimmunol.169.2.898
69. Laufs H, Müller K, Fleischer J, Reiling N, Jahnke N, Jensenius JC, et al. Intracellular survival of Leishmania major in neutrophil granulocytes after uptake in the absence of heat-labile serum factors. Infect Immun (2002) 70:826-35. doi:10.1128/IAI.70.2.826-835.2002
70. Saha P, Bhattacharjee S, Sarkar A, Manna A, Majumder S, Chatterjee M. Berberine chloride mediates its anti-leishmanial activity via differential regulation of the mitogen activated protein kinase pathway in macrophages. PLoS One (2011) 6:e18467. doi:10.1371/journal.pone.0018467
71. Muniz-Junqueira MI, de Paula-Coelho VN. Meglumine antimonate directly increases phagocytosis, superoxide anion and TNF-alpha production, but only via TNF-alpha it indirectly increases nitric oxide production by phagocytes of healthy individuals, in vitro. Int Immunopharmacol (2008) 8:1633-8. doi:10.1016/j.intimp.2008.07.011
72. Shadab M, Ali N. Evasion of host defence by Leishmania donovani: subversion of signaling pathways. Mol Biol Int (2011) 2011:343961. doi:10.4061/2011/343961
73. Oghumu S, Gupta G, Snider HM, Varikuti S, Terrazas CA, Papenfuss TL, et al. STAT4 is critical for immunity but not for antileishmanial activity of antimonials in experimental visceral leishmaniasis. Eur J Immunol (2013) 44(2):450-9. doi:10.1002/eji.201343477
74. Nylén S, Maurya R, Eidsmo L, Manandhar KD, Sundar S, Sacks D. Splenic accumulation of IL-10 mRNA in T cells distinct from CD4+CD25+ (Foxp3) regulatory T cells in human visceral leishmaniasis. J Exp Med (2007) 204:805-17. doi:10.1084/jem.20061141
75. Peters N, Sacks D. Immune privilege in sites of chronic infection: Leishmania and regulatory T cells. Immunol Rev (2006) 213:159-79. doi:10.1111/j.1600-065X.2006.00432.x
76. Olivier M, Gregory DJ, Forget G. Subversion mechanisms by which Leishmania parasites can escape the host immune response: a signaling point of view. Clin Microbiol Rev (2005) 18:293-305. doi:10.1128/CMR.18.2.293-305.2005
77. Brandonisio O, Spinelli R, Pepe M. Dendritic cells in Leishmania infection. Microbes Infect (2004) 6:1402-9. doi:10.1016/j.micinf.2004.10.004
78. Joshi T, Rodriguez S, Perovic V, Cockburn IA, Stager S. B7-H1 blockade increases survival of dysfunctional CD8 (+) T cells and confers protection against Leishmania donovani infections. PLoS Pathog (2009) 5(5):e1000431. doi:10.1371/journal.ppat.1000431
79. Murray HW, Lu CM, Brooks EB, Fichtl RE, DeVecchio JL, Heinzel FP. Modulation of T-cell costimulation as immunotherapy or immunochemotherapy in experimental visceral leishmaniasis. Infect Immun (2003) 71:6453-62. doi:10.1128/IAI.71.11.6453-6462.2003
80. Murray HW, Moreira AL, Lu CM, DeVecchio JL, Matsuhashi M, Ma X, et al. Determinants of response to interleukin-10 receptor blockade immunotherapy in experimental visceral leishmaniasis. J Infect Dis (2003) 188:458-64. doi:10.1086/376510
81. Sundar S, Murray HW. Effect of treatment with interferon-gamma alone in visceral leishmaniasis. J Infect Dis (1995) 172:1627-9. doi:10.1093/infdis/172.6.1627
82. Murray HW, Flanders KC, Donaldson DD, Sypek JP, Gotwals PJ, Liu J, et al. Antagonizing deactivating cytokines to enhance host defense and chemotherapy in experimental visceral leishmaniasis. Infect Immun (2005) 73:3903-11. doi:10.1128/IAI.73.7.3903-3911.2005
83. Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol (2001) 19:683-765. doi:10.1146/annurev.immunol.19.1.683
84. Murphy ML, Wille U, Villegas EN, Hunter CA, Farrell JP. IL-10 mediates susceptibility to Leishmania donovani infection. Eur J Immunol (2001) 31:2848-56. doi:10.1002/1521-4141(2001010)31:10<2848::AID-IMMU2848>3.0.CO;2-T
85. Murray HW. Interleukin 10 receptor blockade - pentavalent antimony treatment in experimental visceral leishmaniasis. Acta Trop (2005) 93:295-301. doi:10.1016/j.actatropica.2004.11.008
86. Murray HW, Brooks EB, DeVecchio JL, Heinzel FP. Immunoenhancement combined with amphotericin B as treatment for experimental visceral leishmaniasis. Antimicrob Agents Chemother (2003) 47:2513-7. doi:10.1128/AAC.47.8.2513-2517.2003
87. Nylen S, Sacks D. Interleukin-10 and the pathogenesis of human visceral leishmaniasis. Trends Immunol (2007) 28:378-84. doi:10.1016/j.it.2007.07.004
88. Ansari NA, Kumar R, Gautam S, Nylén S, Singh OP, Sundar S, et al. IL-27 and IL-21 are associated with T cell IL-10 responses in human visceral leishmaniasis. J Immunol (2011) 186:3977-85. doi:10.4049/jimmunol.1003588
89. Gautam S, Kumar R, Maurya R, Nylén S, Ansari N, Rai M, et al. IL-10 neutralization promotes parasite clearance in splenic aspirate cells from patients with visceral leishmaniasis. J Infect Dis (2011) 204:1134-7. doi:10.1093/infdis/jir461
90. Anderson CF, Oukka M, Kuchroo VJ, Sacks D. CD4(+)CD25(-)Foxp3(-) Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis. J Exp Med (2007) 204:285-97. doi:10.1084/jem.20061886
91. Belkaid Y, Piccirillo CA, Mendez S, Shevach EM, Sacks DL. CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature (2002) 420:502-7. doi:10.1038/nature01152
92. Holaday BJ. Role of CD8+ T cells in endogenous interleukin-10 secretion associated with visceral leishmaniasis. Mem Inst Oswaldo Cruz (2000) 95:217-20. doi:10.1590/S0074-02762000000200013
93. Singh OP, Gidwani K, Kumar R, Nylén S, Jones SL, Boelaert M, et al. Reassessment of immune correlates in human visceral leishmaniasis as defined by cytokine release in whole blood. Clin Vaccine Immunol (2012) 19:961-6. doi:10.1128/CVI.00143-12
94. Singh OP, Sundar S. Whole blood assay and visceral leishmaniasis: challenges and promises. Immunobiology (2014) 219:323-8. doi:10.1016/j.imbio.2014.01.005
95. Carvalho EM, Bacellar O, Brownell C, Regis T, Coffman RL, Reed SG. Restoration of IFN-gamma production and lymphocyte proliferation in visceral leishmaniasis. J Immunol (1994) 152:5949-56.
96. Moll H. Dendritic cells and host resistance to infection. Cell Microbiol (2003) 5(8):493-500. doi:10.1046/j.1462-5822.2003.00291.x
97. Colmenares M, Corbi AL, Turco SJ, Rivas L. The dendritic cell receptor DC-SIGN discriminates among species and life cycle forms of Leishmania. J Immunol (2004) 172:1186-90. doi:10.4049/jimmunol.172.2.1186
98. Ghosh M, Pal C, Ray M, Maitra S, Mandal L, Bandyopadhyay S. Dendritic cell-based immunotherapy combined with antimony-based chemotherapy cures established murine visceral leishmaniasis. J Immunol (2003) 170:5625-9. doi:10.4049/jimmunol.170.11.5625
99. Meheus F, Balasegaram M, Olliaro P, Sundar S, Rijal S, Faiz MA, et al. Cost-effectiveness analysis of combination therapies for visceral leishmaniasis in the Indian subcontinent. PLoS Negl Trop Dis (2010) 4(9):e818. doi:10.1371/journal.pntd.0000818
100. Bryceson A. A policy for leishmaniasis with respect to the prevention and control of drug resistance. Trop Med Int Health (2001) 6:928-34. doi:10.1046/j.1365-3156.2001.00795.x
101. Davis AJ, Murray HW, Handman E. Drugs against leishmaniasis: a synergy of technology and partnerships. Trends Parasitol (2004) 20:73-6. doi:10.1016/j.pt.2003.11.006
102. Smith AC, Yardley V, Rhodes J, Croft SL. Activity of the novel immunomodulatory compound tucaresol against experimental visceral leishmaniasis. Antimicrob Agents Chemother (2000) 44:1494-8. doi:10.1128/AAC.44.6.1494-1498.2000
103. Sundar S, Chatterjee M. Visceral leishmaniasis - current therapeutic modalities. Indian J Med Res (2006) 123:345-52.