Current and emerging therapies for the treatment of leishmaniasis

References

• Brindha J, Balamurali MM, Chanda K. An overview on the therapeutics of neglected infectious diseases-Leishmaniasis and Chagas diseases. Front Chem. 2021;9:622286. doi: 10.3389/fchem.2021.622286
   PubMed Web of Science ®Google Scholar
• eBiomedicine, Leishmania: an urgent need for new treatments. EBioMedicine. 2023;87:104440. doi: 10.1016/j.ebiom.2023.104440
   PubMed Web of Science ®Google Scholar
• Scorza BM, Carvalho EM, Wilson ME. Cutaneous manifestations of human and murine leishmaniasis. Int J Mol Sci. 2017;18(6):1296. doi: 10.3390/ijms18061296
   PubMed Web of Science ®Google Scholar
• Volpedo G, Pacheco-Fernandez T, Holcomb EA, et al. Mechanisms of immunopathogenesis in cutaneous leishmaniasis and post kala-azar dermal leishmaniasis (PKDL). Front Cell Infect Microbiol. 2021;11:512. doi: 10.3389/fcimb.2021.685296
   Web of Science ®Google Scholar
• David C, Dimier-David L, Vargas F, et al. Fifteen years of cutaneous and mucocutaneous leishmaniasis in Bolivia: a retrospective study. Trans R Soc Trop Med. 1993;87(1):7–9. doi: 10.1016/0035-9203(93)90398-A
   PubMed Web of Science ®Google Scholar
• Marra F, Chiappetta MC, Vincenti V. Ear, nose and throat manifestations of mucocutaneous leishmaniasis: a literature review. Acta Biomed. 2014;85(1):3–7.
   PubMedGoogle Scholar
• Abadías-Granado I, Diago A, Cerro PA, et al. Leishmaniasis cutánea y mucocutánea. Actas Dermo-Sifiliográficas. 2021;112(7):601–618. doi: 10.1016/j.ad.2021.02.008
   Google Scholar
• Singh S, Sharma U, Mishra J. Post‐kala‐azar dermal leishmaniasis: recent developments. Int J Dermatol. 2011;50(9):1099–1108. doi: 10.1111/j.1365-4632.2011.04925.x
   PubMed Web of Science ®Google Scholar
• Dixit KK, Ramesh V, Upadhyay S, et al. Utility of blood as the clinical specimen for the molecular diagnosis of post-kala-azar dermal leishmaniasis. J Clin Microbiol. 2021;59(9): doi: 10.1128/JCM.00132-21
   PubMed Web of Science ®Google Scholar
• Jafarzadeh A, Jafarzadeh S, Sharifi I, et al. The importance of T cell-derived cytokines in post-kala-azar dermal leishmaniasis. Cytokine. 2021;147:155321. doi: 10.1016/j.cyto.2020.155321
   PubMed Web of Science ®Google Scholar
• Singh OP, Tiwary P, Kushwaha AK, et al. Xenodiagnosis to evaluate the infectiousness of humans to sandflies in an area endemic for visceral leishmaniasis in Bihar, India: a transmission-dynamics study. Lancet Microbe. 2021;2(1):e23–e31. doi: 10.1016/S2666-5247(20)30166-X
   PubMedGoogle Scholar
• Kumar A, Singh VK, Tiwari R, et al. Post kala-azar dermal leishmaniasis in the Indian sub-continent: challenges and strategies for elimination. Front Immunol. 2023;14:1236952. doi: 10.3389/fimmu.2023.1236952
   PubMed Web of Science ®Google Scholar
• Roatt BM, de Oliveira Cardoso JM, de Brito RCF, et al. Recent advances and new strategies on leishmaniasis treatment. Appl Microbiol Biotechnol. 2020;104(21):8965–8977. doi: 10.1007/s00253-020-10856-w
   PubMed Web of Science ®Google Scholar
• Chakravarty J, Sundar S. Drug resistance in leishmaniasis. J Glob Infect Dis. 2010;2(2):167–176. doi: 10.4103/0974-777X.62887
   PubMedGoogle Scholar
• Sundar S, Chakravarty J, Agarwal D, et al. Single-dose liposomal amphotericin B for visceral leishmaniasis in India. N Engl J Med. 2010;362(6):504–512. doi: 10.1056/NEJMoa0903627
   PubMed Web of Science ®Google Scholar
• World Health Organization. WHO and-Gilead-sciences-extend-collaborative-agreement-to-enhance-access-to-treatment-for visceral-leishmaniasis. Geneva, Switzerland: World Health Organization; 2023.
   Google Scholar
• 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. doi: 10.1371/journal.pntd.0001674
   PubMed Web of Science ®Google Scholar
• Musa AM, Mbui J, Mohammed R, et al. Paromomycin and miltefosine combination as an alternative to treat patients with visceral leishmaniasis in eastern Africa: a randomized, controlled, multicountry trial. Clinical Infectious Diseases. 2023;76(3):e1177–e1185. doi: 10.1093/cid/ciac643
   PubMed Web of Science ®Google Scholar
• Navin TR, Arana BA, Arana FE, et al. Placebo-controlled clinical trial of sodium stibogluconate (Pentostam) versus ketoconazole for treating cutaneous leishmaniasis in Guatemala. J Infect Dis. 1992;165(3):528–534. doi: 10.1093/infdis/165.3.528
   PubMed Web of Science ®Google Scholar
• 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):1846–1851. doi: 10.1086/518041
   PubMed Web of Science ®Google Scholar
• Romero G, Paes MG, Macêdo VO, et al. 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):456–465. doi: 10.4269/ajtmh.2001.65.456
   PubMed Web of Science ®Google Scholar
• Ballou WR, Gordon D, Andujar J, et al. Safety and efficacy of high-dose sodium stibogluconate therapy of American cutaneous leishmaniasis. Lancet. 1987;330(8549):13–16. doi: 10.1016/S0140-6736(87)93053-4
   Google Scholar
• Reithinger R, Dujardin J-C, Louzir H, et al. Cutaneous leishmaniasis. the lancet infectious diseases. Lancet Infect Dis. 2007;7(9):581–596. doi: 10.1016/S1473-3099(07)70209-8
   PubMed Web of Science ®Google Scholar
• Oliveira LF, Schubach AO, Martins MM, et al. Systematic review of the adverse effects of cutaneous leishmaniasis treatment in the new world. Acta tropica. 2011;118(2):87–96. doi: 10.1016/j.actatropica.2011.02.007
   PubMed Web of Science ®Google Scholar
• Soto J, Toledo J, Gutierrez P, et al. Treatment of American cutaneous leishmaniasis with miltefosine, an oral agent. Clinic Infect Dis. 2001;33(7):e57–e61. doi: 10.1086/322689
   PubMedGoogle Scholar
• Soto J, Arana BA, Toledo J, et al. Miltefosine for new world cutaneous leishmaniasis. Clin Infec Dis. 2004;38(9):1266–1272. doi: 10.1086/383321
   PubMed Web of Science ®Google Scholar
• Chrusciak-Talhari A, Talhari S, Chrusciak Talhari C, et al. Randomized controlled clinical trial to access efficacy and safety of miltefosine in the treatment of cutaneous leishmaniasis caused by leishmania (viannia) guyanensis in Manaus, Brazil. Am J Trop Med Hyg. 2011;84(2):255. doi: 10.4269/ajtmh.2011.10-0155
   PubMed Web of Science ®Google Scholar
• Machado PR, Ampuero J, Guimarães LH, et al. Miltefosine in the treatment of cutaneous leishmaniasis caused by Leishmania braziliensis in Brazil: a randomized and controlled trial. PLoS negl trop dis. 2010;4(12):e912. doi: 10.1371/journal.pntd.0000912
   PubMed Web of Science ®Google Scholar
• Ono M, Takahashi K, Taira K, et al. Cutaneous leishmaniasis in a Japanese returnee from West Africa successfully treated with liposomal amphotericin B. J Dermatol. 2011;38(11):1062–1065. doi: 10.1111/j.1346-8138.2011.01270.x
   PubMed Web of Science ®Google Scholar
• Solomon M, Pavlotzky F, Barzilai A, et al. Liposomal amphotericin B in comparison to sodium stibogluconate for Leishmania braziliensis cutaneous leishmaniasis in travelers. J Am Acad Dermatol. 2013;68(2):284–289. doi: 10.1016/j.jaad.2012.06.014
   PubMed Web of Science ®Google Scholar
• Hervás JA, Martín-Santiago A, Hervás D, et al. Old world leishmania infantum cutaneous leishmaniasis unresponsive to liposomal amphotericin B treated with topical imiquimod. Pediatr Infect Dis J. 2012;31(1):97–100. doi: 10.1097/INF.0b013e31822dfbf7
   PubMed Web of Science ®Google Scholar
• Gadelha EPN, Ramasawmy R, da Costa Oliveira B, et al. An open label randomized clinical trial comparing the safety and effectiveness of one, two or three weekly pentamidine isethionate doses (seven milligrams per kilogram) in the treatment of cutaneous leishmaniasis in the Amazon region. PLoS negl trop dis. 2018;12(10):e0006850. doi: 10.1371/journal.pntd.0006850
   PubMed Web of Science ®Google Scholar
• Christen J-R, Bourreau E, Demar M, et al. Use of the intramuscular route to administer pentamidine isethionate in Leishmania guyanensis cutaneous leishmaniasis increases the risk of treatment failure. Travel Med Infect Dis. 2018;24:31–36. doi: 10.1016/j.tmaid.2018.02.010
   PubMed Web of Science ®Google Scholar
• Berman J, Toledo J, Soto J, et al. Intralesional pentamidine: a novel therapy for single lesions of Bolivian cutaneous leishmaniasis. Am J Trop Med Hyg. 2016;94(4):852. doi: 10.4269/ajtmh.15-0640
   PubMed Web of Science ®Google Scholar
• Saenz RE, Paz H, Berman JD. Efficacy of ketoconazole against Leishmania braziliensis panamensis cutaneous leishmaniasis. Am J Med. 1990;89(2):147–155. doi: 10.1016/0002-9343(90)90292-L
   PubMed Web of Science ®Google Scholar
• Abahusein A, Larbi EB, Al-Khawajah A, et al. Evaluation of topical ketoconazole in cutaneous leishmaniasis. East Afr Med J. 1992;69(1):14–17.
   PubMed Web of Science ®Google Scholar
• Dogra J, Saxena V. Itraconazole and leishmaniasis: a randomised double-blind trial in cutaneous disease. Int J Parasitol. 1996;26(12):1413–1415. doi: 10.1016/S0020-7519(96)00128-2
   PubMed Web of Science ®Google Scholar
• Zakai HA, Zimmo SK. Effects of itraconazole and terbinafine on leishmania major lesions in BALB/c mice. Ann Trop Med Parasitol. 2000;94(8):787–791. doi: 10.1080/00034983.2000.11813603
   PubMed Web of Science ®Google Scholar
• Shokri A, Emami S, Fakhar M, et al. In vitro antileishmanial activity of novel azoles (3-imidazolylflavanones) against promastigote and amastigote stages of leishmania major. Acta tropica. 2017;167:73–78. doi: 10.1016/j.actatropica.2016.12.027
   PubMed Web of Science ®Google Scholar
• Oryan A, Bahrami S, Bemani E. Efficacy of voriconazole on leishmaniasis by leishmania major: an: in vitro: and: in vivo: study. Asian Pac J Trop Med. 2018;11(10):562–569. doi: 10.4103/1995-7645.244516
   Web of Science ®Google Scholar
• Shokri A, Abastabar M, Keighobadi M, et al. Promising antileishmanial activity of novel imidazole antifungal drug luliconazole against Leishmania major: In vitro and in silico studies. Asian Pac J Trop Med. 2018;14:260–265. doi: 10.1016/j.jgar.2018.05.007
   Google Scholar
• Sundar S. Leishmaniasis. Harrison’s principles of Internal Medicine. 21st ed. Vol. 1. NewYork, NY: McGraw-Hill Education; 2022. p. 1741–1748.
   Google Scholar
• Carvalho JDP, Silva SN, Freire ML, et al. The cure rate after different treatments for mucosal leishmaniasis in the Americas: a systematic review. PLoS negl trop dis. 2022;16(11):e0010931. doi: 10.1371/journal.pntd.0010931
   PubMed Web of Science ®Google Scholar
• Chakravarty J, Sundar S. Current and emerging medications for the treatment of leishmaniasis. Expert Opin Pharmacother. 2019;20(10):1251–1265. doi: 10.1080/14656566.2019.1609940
   PubMed Web of Science ®Google Scholar
• Asilian A, Sharif A, Faghihi G, et al. Evaluation of CO2 laser efficacy in the treatment of cutaneous leishmaniasis. Int J Dermatology. 2004;43(10):736–738. doi: 10.1111/j.1365-4632.2004.02349.x
   PubMed Web of Science ®Google Scholar
• Valencia BM, Miller D, Witzig RS, et al. Novel low-cost thermotherapy for cutaneous leishmaniasis in Peru. PLoS negl trop dis. 2013;7(5):e2196. doi: 10.1371/journal.pntd.0002196
   PubMed Web of Science ®Google Scholar
• Sadeghian G, Nilfroushzadeh M, Iraji F. Efficacy of local heat therapy by radiofrequency in the treatment of cutaneous leishmaniasis, compared with intralesional injection of meglumine antimoniate. Clin Exp Dermatol. 2007;32(4):371–374. doi: 10.1111/j.1365-2230.2007.02405.x
   PubMed Web of Science ®Google Scholar
• Bassiouny A, Meshad M, Talaat M, et al. Cryosurgery in cutaneous leishmaniasis. Br J Dermatol. 1982;107(4):467–474. doi: 10.1111/j.1365-2133.1982.tb00390.x
   PubMed Web of Science ®Google Scholar
• Negera E, Gadisa E, Hussein J, et al. Treatment response of cutaneous leishmaniasis due to leishmania aethiopica to cryotherapy and generic sodium stibogluconate from patients in Silti, Ethiopia. Trans R Soc Trop Med. 2012;106(8):496–503. doi: 10.1016/j.trstmh.2012.02.006
   PubMed Web of Science ®Google Scholar
• Chakravarty J, Sundar S. Current and emerging medications for the treatment of leishmaniasis. Expert Opin Pharmacother. 2019;20(10):1251–1265. doi: 10.1080/14656566.2019.1609940
   PubMed Web of Science ®Google Scholar
• MacMicking J, Xie Q-W, Nathan C. Nitric oxide and macrophage function. Annu Rev Immunol. 1997;15(1):323–350. doi: 10.1146/annurev.immunol.15.1.323
   PubMedGoogle Scholar
• Lopez-Jaramillo P, Ruano C, Rivera J, et al. Treatment of cutaneous leishmaniasis with nitric-oxide donor. Lancet. 1998;351(9110):1176–1177. doi: 10.1016/S0140-6736(05)79119-4
   PubMed Web of Science ®Google Scholar
• López-Jaramillo P, García RG, Vélez ID, et al. A controlled, randomized-blinded clinical trial to assess the efficacy of a nitric oxide releasing patch in the treatment of cutaneous leishmaniasis by leishmania (V.) panamensis. Am J Trop Med Hyg. 2010;83(1):97. doi: 10.4269/ajtmh.2010.09-0287
   PubMed Web of Science ®Google Scholar
• Sundar S, Sinha PK, Rai M, et al. Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India: an open-label, non-inferiority, randomised controlled trial. Lancet. 2011;377(9764):477–486. doi: 10.1016/S0140-6736(10)62050-8
   PubMed Web of Science ®Google Scholar
• Melaku Y, Gatluak F, Keus K, et al. 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. Am J Trop Med Hyg. 2007;77(1):89–94. doi: 10.4269/ajtmh.2007.77.89
   PubMed Web of Science ®Google Scholar
• Mahajan R, das P, Isaakidis P, et al. Combination treatment for visceral leishmaniasis patients coinfected with human immunodeficiency virus in India. Clinical Infec Dis. 2015;61(8):1255–1262. doi: 10.1093/cid/civ530
   PubMed Web of Science ®Google Scholar
• World Health Organization. WHO guideline for the treatment of visceral leishmaniasis in HIV coinfected patients in East Africa and South-East Asia [internet]. Geneva: World Health Organization; 2022.
   Google Scholar
• Sundar S, Murray HW. Effect of treatment with interferon-γ alone in visceral leishmaniasis. J Infect Dis. 1995;172(6):1627–1629. doi: 10.1093/infdis/172.6.1627
   PubMed Web of Science ®Google Scholar
• Sundar S, Rosenkaimer F, Murray HW. Successful treatment of refractory visceral leishmaniasis in India using antimony plus interferon-ã. J Infect Dis. 1994;170(3):659–662. doi: 10.1093/infdis/170.3.659
   PubMed Web of Science ®Google Scholar
• Convit J, Ulrich M, Zerpa O, et al. Immunotherapy of American cutaneous leishmaniasis in Venezuela during the period 1990–1999. Trans R Soc Trop Med. 2003;97(4):469–472. doi: 10.1016/S0035-9203(03)90093-9
   PubMed Web of Science ®Google Scholar
• Mayrink W, Botelho ACDC, Magalhães PA, et al. Immunotherapy, immunochemotherapy and chemotherapy for American cutaneous leishmaniasis treatment. Rev Soc Bras Med Trop. 2006;39(1):14–21. doi: 10.1590/S0037-86822006000100003
   PubMed Web of Science ®Google Scholar
• Machado‐Pinto J, Pinto J, da Costa CA, et al. Immunochemotherapy for cutaneous leishmaniasis: a controlled trial using killed leishmania (leishmania) amazonensis vaccine plus antimonial. Int J Dermatology. 2002;41(2):73–78. doi: 10.1046/j.1365-4362.2002.01336.x
   PubMed Web of Science ®Google Scholar
• Cabrera M, Blackwell J, Castes M, et al. Immunotherapy with live BCG plus heat killed leishmania induces a T helper 1‐like response in American cutaneous leishmaniasis patients. Parasite Immunol. 2000;22(2):73–79. doi: 10.1046/j.1365-3024.2000.00278.x
   PubMed Web of Science ®Google Scholar
• Saleem K, Khursheed Z, Hano C, et al. Applications of nanomaterials in leishmaniasis: a focus on recent advances and challenges. Nanomaterials. 2019;9(12):1749. doi: 10.3390/nano9121749
   Web of Science ®Google Scholar
• Momeni A, Rasoolian M, Momeni A, et al. Development of liposomes loaded with anti-leishmanial drugs for the treatment of cutaneous leishmaniasis. J Liposome Res. 2013;23(2):134–144. doi: 10.3109/08982104.2012.762519
   PubMed Web of Science ®Google Scholar
• Borborema SET, Schwendener RA, Osso Junior JA, et al. Uptake and antileishmanial activity of meglumine antimoniate-containing liposomes in Leishmania (Leishmania) major-infected macrophages. Int J Antimicrob Agents. 2011;38(4):341–347. doi: 10.1016/j.ijantimicag.2011.05.012
   PubMed Web of Science ®Google Scholar
• Maggi RG, Krämer F. A review on the occurrence of companion vector-borne diseases in pet animals in Latin America. Parasites Vectors. 2019;12(1):1–37. doi: 10.1186/s13071-019-3407-x
   PubMedGoogle Scholar
• Moreira RA, Mendanha SA, Fernandes KS, et al. Miltefosine increases lipid and protein dynamics in Leishmania membranes at similar concentrations to those needed for cytotoxicity activity. Antimicrob Agents Chemother. 2014;58(6):3021–3028. doi: 10.1128/AAC.01332-13
   PubMed Web of Science ®Google Scholar
• Kumar R, Pandey K, Sahoo GC, et al. Development of high efficacy peptide coated iron oxide nanoparticles encapsulated amphotericin B drug delivery system against visceral leishmaniasis. Mater Sci Eng C. 2017;75:1465–1471. doi: 10.1016/j.msec.2017.02.145
   PubMed Web of Science ®Google Scholar
• Georgopoulou K, Smirlis D, Bisti S, et al. In vitro activity of 10-deacetylbaccatin III against leishmania donovani promastigotes and intracellular amastigotes. Planta Med. 2007;73(10):1081–1088. doi: 10.1055/s-2007-981579
   PubMed Web of Science ®Google Scholar
• Fanti JR, Tomiotto-Pellissier F, Miranda-Sapla MM, et al. Biogenic silver nanoparticles inducing Leishmania amazonensis promastigote and amastigote death in vitro. Acta tropica. 2018;178:46–54. doi: 10.1016/j.actatropica.2017.10.027
   PubMed Web of Science ®Google Scholar
• Sazgarnia A, Taheri AR, Soudmand S, et al. Antiparasitic effects of gold nanoparticles with microwave radiation on promastigotes and amastigotes of Leishmania major. Int J Hyperthermia. 2013;29(1):79–86. doi: 10.3109/02656736.2012.758875
   PubMed Web of Science ®Google Scholar
• Khatami M, Alijani H, Sharifi I, et al. Leishmanicidal activity of biogenic Fe3O4 nanoparticles. Sci Pharm. 2017;85(4):36. doi: 10.3390/scipharm85040036
   PubMed Web of Science ®Google Scholar
• Delavari M, Dalimi A, Ghaffarifar F, et al. In vitro study on cytotoxic effects of ZnO nanoparticles on promastigote and amastigote forms of Leishmania major (MRHO/IR/75/ER). Iran J Parasitol. 2014;9(1):6.
   PubMed Web of Science ®Google Scholar
• Sumaira, Siddique Afridi M, et al. Comparative antileishmanial efficacy of the biosynthesised ZnO NPs from genus verbena. IET Nanobiotechnol. 2018;12(8):1067–1073. doi: 10.1049/iet-nbt.2018.5076
   PubMed Web of Science ®Google Scholar
• Allahverdiyev AM, Abamor EŞ, et al. Antileishmanial effect of silver nanoparticles and their enhanced antiparasitic activity under ultraviolet light. Int J Nanomed. 2011;2705–2714. doi: 10.2147/IJN.S23883
   PubMed Web of Science ®Google Scholar
• Zielińska A, Carreiró F, Oliveira AM, et al. Polymeric nanoparticles: production, characterization toxicology and ecotoxicology. Molecules. 2020;25(16):25(16. doi: 10.3390/molecules25163731
   Web of Science ®Google Scholar
• Sirisha V, D’Souza JS. Polysaccharide-based nanoparticles as drug delivery systems. Marine OMICS. 2016;31:641–682. doi: 10.1201/9781315372303-32
   Google Scholar
• Tiwari R, Gupta RP, Singh VK, et al. Nanotechnology-based strategies in parasitic disease management: from prevention to diagnosis and treatment. ACS Omega. 2023;8(45):42014–42027. doi: 10.1021/acsomega.3c04587
   PubMed Web of Science ®Google Scholar
• Müller RH, Mäder K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery–a review of the state of the art. Eur J Pharm Biopharm. 2000;50(1):161–177. doi: 10.1016/S0939-6411(00)00087-4
   PubMed Web of Science ®Google Scholar
• Barros D, Costa Lima SA, Cordeiro-da-Silva A. Surface functionalization of polymeric nanospheres modulates macrophage activation: relevance in leishmaniasis therapy. Nanomedicine. 2015;10(3):387–403. doi: 10.2217/nnm.14.116
   PubMed Web of Science ®Google Scholar
• Saudagar P, Dubey VK. Carbon nanotube based betulin formulation shows better efficacy against leishmania parasite. Parasitol Int. 2014;63(6):772–776. doi: 10.1016/j.parint.2014.07.008
   PubMed Web of Science ®Google Scholar
• Wu W, Wieckowski S, Pastorin G, et al. Targeted delivery of amphotericin B to cells by using functionalized carbon nanotubes. Angewandte Chemie. 2005;44(39):6358–6362. doi: 10.1002/anie.200501613
   Google Scholar
• Gedda MR, Madhukar P, Vishwakarma AK, et al. Evaluation of safety and antileishmanial efficacy of amine functionalized carbon-based composite nanoparticle appended with amphotericin B: an in vitro and preclinical study. Front Chem. 2020;8:8. doi: 10.3389/fchem.2020.00510
   PubMed Web of Science ®Google Scholar
• Sundar S, Singh B. Emerging therapeutic targets for treatment of leishmaniasis. Expert Opin Ther Targets. 2018;22(6):467–486. doi: 10.1080/14728222.2018.1472241
   PubMed Web of Science ®Google Scholar
• Tiuman TS, Santos AO, Ueda-Nakamura T, et al. Recent advances in leishmaniasis treatment. Inter J Infect Dis. 2011;15(8):e525–e532. doi: 10.1016/j.ijid.2011.03.021
   PubMed Web of Science ®Google Scholar
• da Silva S, Costa SS, Mendonça SCF, et al. Therapeutic effect of oral kalanchoe pinnata leaf extract in murine leishmaniasis. Acta tropica. 1995;60(3):201–210. doi: 10.1016/0001-706X(95)00128-2
   PubMed Web of Science ®Google Scholar
• Dutta A, Bandyopadhyay S, Mandal C, et al. Aloe vera leaf exudate induces a caspase-independent cell death in Leishmania donovani promastigotes. Journal of Medical Microbiology. 2007;56(5):629–636. doi: 10.1099/jmm.0.47039-0
   PubMed Web of Science ®Google Scholar
• Yung SC, Murphy PM. Antimicrobial chemokines. Front Immunol. 2012;3:276. doi: 10.3389/fimmu.2012.00276
   PubMed Web of Science ®Google Scholar
• Luque-Ortega JR, Rivero-Lezcano OM, Croft SL, et al. In vivo monitoring of intracellular ATP levels in Leishmania donovani promastigotes as a rapid method to screen drugs targeting bioenergetic metabolism. Antimicrob Agents Chemother. 2001;45(4):1121–1125. doi: 10.1128/AAC.45.4.1121-1125.2001
   PubMed Web of Science ®Google Scholar
• Moreno SN, Docampo R. Calcium regulation in protozoan parasites. Curr Opin Microbiol. 2003;6(4):359–364. doi: 10.1016/S1369-5274(03)00091-2
   PubMed Web of Science ®Google Scholar
• Alberola J, Rodriguez A, Francino O, et al. Safety and efficacy of antimicrobial peptides against naturally acquired leishmaniasis. Antimicrob Agents Chemother. 2004;48(2):641–643. doi: 10.1128/AAC.48.2.641-643.2004
   PubMed Web of Science ®Google Scholar
• Verlinde CL, Hannaert V, Blonski C, et al. Glycolysis as a target for the design of new anti-trypanosome drugs. Drug Resist Updat. 2001;4(1):50–65. doi: 10.1054/drup.2000.0177
   PubMed Web of Science ®Google Scholar
• Aisen P, Enns C, Wessling-Resnick M. Chemistry and biology of eukaryotic iron metabolism. Int J Biochem Cell Biol. 2001;33(10):940–959. doi: 10.1016/S1357-2725(01)00063-2
   PubMed Web of Science ®Google Scholar
• Lee N, Bertholet S, Debrabant A, et al. Programmed cell death in the unicellular protozoan parasite leishmania. Cell Death Differ. 2002;9(1):53–64. doi: 10.1038/sj.cdd.4400952
   PubMed Web of Science ®Google Scholar
• Zhai L, Chen M, Blom J, et al. The antileishmanial activity of novel oxygenated chalcones and their mechanism of action. J Antimicrob Chemother. 1999;43(6):793–803. doi: 10.1093/jac/43.6.793
   PubMed Web of Science ®Google Scholar
• Ortiz D, Forquer I, Boitz J, et al. Targeting the cytochrome bc1 complex of leishmania parasites for discovery of novel drugs. Antimicrob Agents Chemother. 2016;60(8):4972–4982. doi: 10.1128/AAC.00850-16
   PubMed Web of Science ®Google Scholar
• Dinesh N, Palleria DSR, Kaur PK, et al. Exploring leishmania donovani 3-hydroxy-3-methylglutaryl coenzyme a reductase (HMGR) as a potential drug target by biochemical, biophysical and inhibition studies. Amsterdam, Netherlands: Microb Pathog; 2014;66:14–23
   Google Scholar
• Andrade-Neto VV, Pereira TM, Canto-Cavalheiro MD, et al. Imipramine alters the sterol profile in Leishmania amazonensis and increases its sensitivity to miconazole. Parasites Vectors. 2016;9(1):183. doi: 10.1186/s13071-016-1467-8
   PubMedGoogle Scholar
• Fox JT, Stover PJ. Folate-mediated one-carbon metabolism. Vol. 79. Cambridge, Massachusetts: Vitam Horm; 2008. p. 1–44.
   Google Scholar
• Jastrab JB, Darwin KH. Bacterial proteasomes. Annu Rev Microbiol. 2015;69(1):109–127. doi: 10.1146/annurev-micro-091014-104201
   PubMedGoogle Scholar
• Wyllie S, Brand S, Thomas M, et al. Preclinical candidate for the treatment of visceral leishmaniasis that acts through proteasome inhibition. Proc Natl Acad Sci U S A. 2019;116(19):9318–9323. doi: 10.1073/pnas.1820175116
   PubMed Web of Science ®Google Scholar
• Khare S, Nagle AS, Biggart A, et al. Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness. Nature. 2016;537(7619):229–233. doi: 10.1038/nature19339
   PubMed Web of Science ®Google Scholar
• Nagle A, Biggart A, Be C, et al. Discovery and characterization of clinical Candidate LXE408 as a kinetoplastid-selective proteasome inhibitor for the treatment of Leishmaniases. J Med Chem. 2020;63(19):10773–10781. doi: 10.1021/acs.jmedchem.0c00499
   PubMed Web of Science ®Google Scholar
• Xingi E, Smirlis D, Myrianthopoulos V, et al. 6-br-5methylindirubin-3′oxime (5-me-6-BIO) targeting the leishmanial glycogen synthase kinase-3 (GSK-3) short form affects cell-cycle progression and induces apoptosis-like death: exploitation of GSK-3 for treating leishmaniasis. Int J Parasitol Drugs Drug Resist. 2009;39(12):1289–1303. doi: 10.1016/j.ijpara.2009.04.005
   Google Scholar
• McConville MJ, Mullin KA, Ilgoutz SC, et al. Secretory pathway of trypanosomatid parasites. Microbiol Mol Biol Rev. 2002;66(1):122–154. doi: 10.1128/MMBR.66.1.122-154.2002 table of contents
   PubMed Web of Science ®Google Scholar
• Debrabant A, Lee N, Pogue GP, et al. Expression of calreticulin P-domain results in impairment of secretory pathway in Leishmania donovani and reduced parasite survival in macrophages. Int J Parasitol. 2002;32(11):1423–1434. doi: 10.1016/S0020-7519(02)00134-0
   PubMed Web of Science ®Google Scholar
• Marr AK, MacIsaac JL, Jiang R, et al. Leishmania donovani infection causes distinct epigenetic DNA methylation changes in host macrophages. PLoS Pathog. 2014;10(10):e1004419. doi: 10.1371/journal.ppat.1004419
   PubMed Web of Science ®Google Scholar
• Mittra B, Cortez M, Haydock A, et al. Iron uptake controls the generation of Leishmania infective forms through regulation of ROS levels. J Exp Med. 2013;210(2):401–416. doi: 10.1084/jem.20121368
   PubMed Web of Science ®Google Scholar
• Mittra B, Laranjeira-Silva MF, Miguel DC, et al. The iron-dependent mitochondrial superoxide dismutase SODA promotes leishmania virulence. J Biol Chem. 2017;292(29):12324–12338. doi: 10.1074/jbc.M116.772624
   PubMed Web of Science ®Google Scholar
• Martínez-García M, Campos-Salinas J, Cabello-Donayre M, et al. LmABCB3, an atypical mitochondrial ABC transporter essential for Leishmania major virulence, acts in heme and cytosolic iron/sulfur clusters biogenesis. Parasites Vectors. 2016;9(1):7. doi: 10.1186/s13071-015-1284-5
   PubMedGoogle Scholar
• Mol M, Patole MS, Singh S. Immune signal transduction in leishmaniasis from natural to artificial systems: role of feedback loop insertion. Biochim Biophys Acta. 2014;1840(1):71–79. doi: 10.1016/j.bbagen.2013.08.018
   PubMed Web of Science ®Google Scholar
• Engh RA, Bossemeyer D. Structural aspects of protein kinase control-role of conformational flexibility. Pharmacol Ther. 2002;93(2–3):99–111. doi: 10.1016/S0163-7258(02)00180-8
   PubMed Web of Science ®Google Scholar
• Durieu E, Prina E, Leclercq O, et al. From drug screening to target deconvolution: a target-based drug discovery pipeline using leishmania casein kinase 1 Isoform 2 to identify compounds with antileishmanial activity. Antimicrob Agents Chemother. 2016;60(5):2822–2833. doi: 10.1128/AAC.00021-16
   PubMed Web of Science ®Google Scholar
• Téllez-Iñón MT, Ulloa RM, Torruella M, et al. Calmodulin and Ca2±dependent cyclic AMP phosphodiesterase activity in Trypanosoma cruzi. Molecular and Biochemical Parasitology. 1985;17(2):143–153. doi: 10.1016/0166-6851(85)90013-1
   PubMed Web of Science ®Google Scholar
• Gundersen RE, Nelson DL. A novel Ca2 + - dependent protein kinase from Paramecium tetraurelia. J Biol Chem. 1987;262(10):4602–4609. doi: 10.1016/S0021-9258(18)61236-0
   PubMed Web of Science ®Google Scholar
• Kakiuchi S, Sobue K, Yamazaki R, et al. Ca2 + - dependent modulator proteins from Tetrahymena pyriformis, sea anemone, and scallop and guanylate cyclase activation. Jour Biologic Chem. 1981;256(1):19–22. doi: 10.1016/S0021-9258(19)70088-X
   PubMed Web of Science ®Google Scholar
• Docampo R, Moreno SN. The acidocalcisome. Mol Biochem Parasitol. 2001;114(2):151–159. doi: 10.1016/S0166-6851(01)00246-8
   PubMed Web of Science ®Google Scholar
• Benaim G, Bermudez R, Urbina JA. Ca2+ transport in isolated mitochondrial vesicles from Leishmania braziliensis promastigotes. Mol Biochem Parasitol. 1990;39(1):61–68. doi: 10.1016/0166-6851(90)90008-A
   PubMed Web of Science ®Google Scholar
• Docampo R, Vercesi AE. Ca2+ transport by coupled Trypanosoma cruzi mitochondria in situ. J Biol Chem. 1989;264(1):108–111. doi: 10.1016/S0021-9258(17)31229-2
   PubMed Web of Science ®Google Scholar
• Lu HG, Zhong L, Chang K-P, et al. Intracellular Ca2+ pool content and signaling and expression of a calcium pump are linked to virulence in Leishmania mexicana amazonensis amastigotes. J Biol Chem. 1997;272(14):9464–9473. doi: 10.1074/jbc.272.14.9464
   PubMed Web of Science ®Google Scholar
• Prasad A, Kaur S, Malla N, et al. Ca2+ signaling in the transformation of promastigotes to axenic amastigotes of leishmania donovani. Mol Cell Biochem. 2001;224(1–2):39–44. doi: 10.1023/A:1011965109446
   PubMed Web of Science ®Google Scholar
• Rodriguez NM, Docampo R, Lu H-G, et al. Overexpression of the leishmania amazonensis Ca2 + - ATPase gene lmaa1 enhances virulence. Cell Microbiol. 2002;4(2):117–126. doi: 10.1046/j.1462-5822.2002.00175.x
   PubMed Web of Science ®Google Scholar
• Reimão JQ, Colombo FA, Pereira-Chioccola VL, et al. In vitro and experimental therapeutic studies of the calcium channel blocker bepridil: detection of viable leishmania (L.) chagasi by real-time PCR. Exp Parasitol. 2011;128(2):111–115. doi: 10.1016/j.exppara.2011.02.021
   PubMed Web of Science ®Google Scholar
• Shokri A, Sharifi I, Khamesipour A, et al. The effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of leishmania tropica to meglumine antimoniate. Parasitol Res. 2012;110(3):1113–1117. doi: 10.1007/s00436-011-2599-6
   PubMed Web of Science ®Google Scholar
• World Health Organization. Control of the leishmaniases WHO TRS n° 949. Geneva, Switzerland. 2010.
   Google Scholar
• Sundar S, Singh J, Dinkar A, et al. Safety and effectiveness of miltefosine in post–Kala-Azar dermal leishmaniasis: an observational study. Open Forum Infect Dis. 2023;10(5):ofad231. doi: 10.1093/ofid/ofad231
   PubMed Web of Science ®Google Scholar