154
Views
32
CrossRef citations to date
0
Altmetric
Review

Leishmaniasis: treatment, drug resistance and emerging therapies

, &
Pages 1-10 | Received 26 Dec 2017, Accepted 18 Nov 2018, Published online: 05 Dec 2018

References

  • WHO. Control of the leishmaniasis. Geneva: World Health Organization; 2010.
  • Sundar S, Chakravarty J. Leishmaniasis: an update of current pharmacotherapy. Expert Opin Pharmacother. 2013;14(1):53–63.
  • Thakur C, Kumar K. Post kala-azar dermal leishmaniasis: a neglected aspect of kala-azar control programmes. Ann Trop Med Parasitol. 1992;86(4):355–359.
  • Zijlstra EE, Musa AM, Khalil EA, et al. Post-kala-azar dermal leishmaniasis. Lancet Infect Dis. 2003;3(2):87–98.
  • National Vector Borne Disease Control Programme (NVBDCP). Operational guidelines on Kala-Azar (Visceral Leishmaniasis) elimination in India - 2015. Ministry of Health and Family Welfare, Government of India, 2015.
  • Alvar J, Canavate C, Gutierrez-Solar B, et al. Leishmania and human immunodeficiency virus coinfection: the first 10 years. Clin Microbiol Rev. 1997;10(2):298–319.
  • Desjeux P, Alvar J. Leishmania/HIV co-infections: epidemiology in Europe. Ann Trop Med Parasitol. 2003;97(Suppl 1):3–15.
  • Alvar J, Aparicio P, Aseffa A, et al. The relationship between leishmaniasis and AIDS: the second 10 years. Clin Microbiol Rev. 2008;21(2):334–359. table of contents.
  • 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.
  • Burza S, Mahajan R, Sanz MG, et al. HIV and visceral leishmaniasis coinfection in Bihar, India: an underrecognized and underdiagnosed threat against elimination. Clin Infect Dis. 2014;59(4):552–555.
  • Cota GF, de Sousa MR, de Mendonca AL, et al. Leishmania-HIV co-infection: clinical presentation and outcomes in an urban area in Brazil. PLoS Negl Trop Dis. 2014;8(4):e2816.
  • Luz JGG, Naves DB, Carvalho AG, et al. Visceral leishmaniasis in a Brazilian endemic area: an overview of occurrence, HIV coinfection and lethality. Rev Inst Med Trop Sao Paulo. 2018;60:e12.
  • Mengesha B, Endris M, Takele Y, et al. Prevalence of malnutrition and associated risk factors among adult visceral leishmaniasis patients in Northwest Ethiopia: a cross sectional study. BMC Res Notes. 2014;7:75.
  • Mengistu G, Ayele B. Visceral Leishmaniasis and HIV co-infection in patients admitted to Gondar University Hospital, Northwest Ethiopia. Ethiop J Health Dev. 2007;21(1):53–60.
  • Alvar J, Velez ID, Bern C, et al. Leishmaniasis worldwide and global estimates of its incidence. PLoS One. 2012;7(5):e35671.
  • Freitas-Junior LH, Chatelain E, Kim HA, et al. Visceral leishmaniasis treatment: what do we have, what do we need and how to deliver it? Int J Parasitol Drugs Drug Resist. 2012;2:11–19.
  • Tiuman TS, Santos AO, Ueda-Nakamura T, et al. Recent advances in leishmaniasis treatment. Int J Infect Dis. 2011;15(8):e525–32.
  • Aikat BK, Sahaya S, Pathania AG, et al. Clinical profile of cases of kala-azar in Bihar. Indian J Med Res. 1979;70:563–570.
  • Thakur CP, Kumar M, Singh SK, et al. Comparison of regimens of treatment with sodium stibogluconate in kala-azar. Br Med J (Clin Res Ed). 1984;288(6421):895–897.
  • Jha TKSN, Jha SN. Therapeutic use of sodium stibogluconate in kala-azar from some hyperendemic districts of N. Bihar, India. J Assoc Physicians India. 1992;40:868.
  • Faraut-Gambarelli F, Piarroux R, Deniau M, et al. In vitro and in vivo resistance of Leishmania infantum to meglumine antimoniate: a study of 37 strains collected from patients with visceral leishmaniasis. Antimicrob Agents Chemother. 1997;41(4):827–830.
  • Rijal S, Chappuis F, Singh R, et al. Treatment of visceral leishmaniasis in south-eastern Nepal: decreasing efficacy of sodium stibogluconate and need for a policy to limit further decline. Trans R Soc Trop Med Hyg. 2003;97(3):350–354.
  • Sundar S, Thakur BB, Tandon AK, et al. Clinicoepidemiological study of drug resistance in Indian kala-azar. Bmj. 1994;308(6924):307.
  • 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):357–364.
  • Diro E, Lynen L, Mohammed R, et al. High parasitological failure rate of visceral leishmaniasis to sodium stibogluconate among HIV co-infected adults in Ethiopia. PLoS Negl Trop Dis. 2014;8(5):e2875.
  • Ponte-Sucre A, Gamarro F, Dujardin J-C, et al. Drug resistance and treatment failure in leishmaniasis: a 21st century challenge. PLoS Negl Trop Dis. 2017;11(12):e0006052.
  • Thakur C, Singh R, Hassan S, et al. Amphotericin B deoxycholate treatment of visceral leishmaniasis with newer modes of administration and precautions: a study of 938 cases. Trans R Soc Trop Med Hyg. 1999;93(3):319–323.
  • Mishra M, Biswas UK, Jha DN, et al. Amphotericin versus pentamidine in antimony-unresponsive kala-azar. Lancet. 1992;340(8830):1256–1257.
  • 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.
  • Tamiru A, Tigabu B, Yifru S, et al. Safety and efficacy of liposomal amphotericin B for treatment of complicated visceral leishmaniasis in patients without HIV, North-West Ethiopia. BMC Infect Dis. 2016;16(1):548.
  • Ritmeijer K, Ter Horst R, Chane S, et al. Limited effectiveness of high-dose liposomal amphotericin B (AmBisome) for treatment of visceral leishmaniasis in an Ethiopian population with high HIV prevalence. Clin Infect Dis. 2011;53(12):e152–8.
  • Solomon M, Pavlotsky F, Leshem E, et al. Liposomal amphotericin B treatment of cutaneous leishmaniasis due to Leishmania tropica. J Eur Acad Dermatol Venereol. 2011;25(8):973–977.
  • Layegh P, Rajabi O, Jafari MR, et al. Efficacy of topical liposomal amphotericin B versus intralesional meglumine antimoniate (Glucantime) in the treatment of cutaneous leishmaniasis. J Parasitol Res. 2011;2011:656523.
  • Amato VS, Tuon FF, Camargo RA, et al. Can we use a lower dose of liposomal amphotericin B for the treatment of mucosal American leishmaniasis? Am J Trop Med Hyg. 2011;85(5):818–819.
  • Amato VS, Tuon FF, Siqueira AM, et al. Treatment of mucosal leishmaniasis in Latin America: systematic review. Am J Trop Med Hyg. 2007;77(2):266–274.
  • Rocio C, Amato VS, Camargo RA, et al. Liposomal formulation of amphotericin B for the treatment of mucosal leishmaniasis in HIV-negative patients. Trans R Soc Trop Med Hyg. 2014;108(3):176–178.
  • Srivastava P, Prajapati VK, Rai M, et al. Unusual case of resistance to amphotericin B in visceral leishmaniasis in a region in India where leishmaniasis is not endemic. J Clin Microbiol. 2011;49(8):3088–3091.
  • Morizot G, Jouffroy R, Faye A, et al. Antimony to cure visceral leishmaniasis unresponsive to liposomal amphotericin B. PLoS Negl Trop Dis. 2016;10(1):e0004304.
  • Purkait B, Kumar A, Nandi N, et al. Mechanism of amphotericin B resistance in clinical isolates of Leishmania donovani. Antimicrob Agents Chemother. 2012;56(2):1031–1041.
  • Eichenberger A, Buechi AE, Neumayr A, et al. A severe case of visceral leishmaniasis and liposomal amphotericin B treatment failure in an immunosuppressed patient 15 years after exposure. BMC Infect Dis. 2017;17(1):81.
  • Dorlo TP, Balasegaram M, Beijnen JH, et al. Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. J Antimicrob Chemother. 2012;67(11):2576–2597.
  • 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):543–550.
  • 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. Clinl Infect Dis. 2013;56(11):1530–1538.
  • Rahman M, Ahmed B-N, Faiz MA, et al. Phase IV trial of miltefosine in adults and children for treatment of visceral leishmaniasis (kala-azar) in Bangladesh. Am J Trop Med Hyg. 2011;85(1):66–69.
  • Ostyn B, Hasker E, Dorlo TP, et al. Failure of miltefosine treatment for visceral leishmaniasis in children and men in South-East Asia. PLoS One. 2014;9(6):e100220.
  • 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.
  • Srivastava S, Mishra J, Gupta AK, et al. Laboratory confirmed miltefosine resistant cases of visceral leishmaniasis from India. Parasit Vectors. 2017;10(1):49.
  • Sundar S, Chakravarty J. An update on pharmacotherapy for leishmaniasis. Expert Opin Pharmacother. 2015;16(2):237–252.
  • Sundar S, Jha T, Thakur CP, et al. Injectable paromomycin for visceral leishmaniasis in India. N Engl J Med. 2007;356(25):2571–2581.
  • Krause G, Kroeger A. Topical treatment of American cutaneous leishmaniasis with paramomycin and methylbenzethonium chloride: a clinical study under field conditions in Ecuador. Trans R Soc Trop Med Hyg. 1994;88(1):92–94.
  • El-On J, Halevy S, Grunwald MH, et al. Topical treatment of Old World cutaneous leishmaniasis caused by Leishmania major: a double-blind control study. J Am Acad Dermatol. 1992;27(2):227–231.
  • Kim DH, Chung HJ, Bleys J, et al. Is paromomycin an effective and safe treatment against cutaneous leishmaniasis? A meta-analysis of 14 randomized controlled trials. PLoS Negl Trop Dis. 2009;3(2):e381.
  • Correia D, Macedo V, Carvalho E, et al. Comparative study of meglumine antimoniate, pentamidine isethionate and aminosidine sulfate in the treatment of primary skin lesions caused by Leishmania (Viannia) braziliensis. Rev Soc Bras Med Trop. 1996;29(5):447–453.
  • Romero G, Lessa H, Macedo V, et al. Open therapeutic study with aminosidine sulfate in mucosal leishmaniasis caused by Leishmania (Viannia) braziliensis. Rev Soc Bras Med Trop. 1996;29(6):557–565.
  • Romero GA, Lessa HA, Orge MG, et al. Mucosal leishmaniasis treatment with aminosidine sulfate: results of two year follow-up. Rev Soc Bras Med Trop. 1998;31(6):511–516.
  • Llanos-Cuentas A, Echevarria J, Seas C, et al. Parenteral aminosidine is not effective for Peruvian mucocutaneous leishmaniasis. Am J Trop Med Hyg. 2007;76(6):1128–1131.
  • Chakravarty J, Sundar S. Drug resistance in leishmaniasis. J Glob Infect Dis. 2010;2(2):167.
  • Alrajhi AA, Ibrahim EA, De Vol EB, et al. Fluconazole for the treatment of cutaneous leishmaniasis caused by Leishmania major. N Engl J Med. 2002;346(12):891–895.
  • Dogra J, Saxena V. Itraconazole and leishmaniasis: a randomised double-blind trial in cutaneous disease. Int J Parasitol. 1996;26(12):1413–1415.
  • Momeni AZ, Jalayer T, Emamjomeh M, et al. Treatment of cutaneous leishmaniasis with itraconazole: randomized double-blind study. Arch Dermatol. 1996;132(7):784–786.
  • Nassiri‐Kashani M, Firooz A, Khamesipour A, et al. A randomized, double‐blind, placebo‐controlled clinical trial of itraconazole in the treatment of cutaneous leishmaniasis. J Eur Acad Dermatol Venereol. 2005;19(1):80–83.
  • Olliaro PL, Guerin PJ, Gerstl S, et al. Treatment options for visceral leishmaniasis: a systematic review of clinical studies done in India, 1980–2004. Lancet Infect Dis. 2005;5(12):763–774.
  • Melaku Y, Collin SM, 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.
  • Kimutai R, Musa AM, Njoroge S, et al. Safety and effectiveness of sodium stibogluconate and paromomycin combination for the treatment of visceral leishmaniasis in Eastern Africa: results from a pharmacovigilance programme. Clin Drug Investig. 2017;37(3):259–272.
  • Seifert K, Croft SL. In vitro and in vivo interactions between miltefosine and other antileishmanial drugs. Antimicrob Agents Chemother. 2006;50(1):73–79.
  • Sundar S, Rai M, Chakravarty J, et al. New treatment approach in Indian visceral leishmaniasis: single-dose liposomal amphotericin B followed by short-course oral miltefosine. Clinl Infect Dis. 2008;47(8):1000–1006.
  • 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.
  • Rahman R, Goyal V, Haque R, et al. Safety and efficacy of short course combination regimens with AmBisome, miltefosine and paromomycin for the treatment of visceral leishmaniasis (VL) in Bangladesh. PLoS Negl Trop Dis. 2017;11(5):e0005635.
  • Wasunna M, Njenga S, Balasegaram M, et al. Efficacy and safety of AmBisome in combination with sodium stibogluconate or miltefosine and miltefosine monotherapy for African visceral leishmaniasis: phase II randomized trial. PLoS Negl Trop Dis. 2016;10(9):e0004880.
  • Romero GAS, Costa DL, Costa CHN, et al. Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: a multicenter, randomized, open label trial. PLoS Negl Trop Dis. 2017;11(6):e0005706.
  • Hendrickx S, Beyers J, Mondelaers A, et al. Evidence of a drug-specific impact of experimentally selected paromomycin and miltefosine resistance on parasite fitness in Leishmania infantum. J Antimicrob Chemother. 2016;71(7):1914–1921.
  • Hendrickx S, Van Den Kerkhof M, Mabille D, et al. Combined treatment of miltefosine and paromomycin delays the onset of experimental drug resistance in Leishmania infantum. PLoS Negl Trop Dis. 2017;11(5):e0005620.
  • Brito G, Dourado M, Guimarães LH, et al. Oral pentoxifylline associated with pentavalent antimony: a randomized trial for cutaneous leishmaniasis. Am J Trop Med Hyg. 2017;96(5):1155–1159.
  • Lessa HA, Machado P, Lima F, et al. Successful treatment of refractory mucosal leishmaniasis with pentoxifylline plus antimony. Am J Trop Med Hyg. 2001;65(2):87–89.
  • Machado PR, Lessa H, Lessa M, et al. Oral pentoxifylline combined with pentavalent antimony: a randomized trial for mucosal leishmaniasis. Clinl Infect Dis. 2007;44(6):788–793.
  • Ventin F, Cincurá C, Machado PRL. Safety and efficacy of miltefosine monotherapy and pentoxifylline associated with pentavalent antimony in treating mucosal leishmaniasis. Expert Rev Anti Infect Ther. 2018;16(3):219–225.
  • Arellano JLP, Cabrera MH, Alamo EP, et al. Tratamiento de las enfermedades parasitarias (I): protozoosis. Información Terapéutica del Sistema Nacional de Salud. 2007;31(1):3–16.
  • Jameson MB, Rischin D, Pegram M, et al. A phase I trial of PR-104, a nitrogen mustard prodrug activated by both hypoxia and aldo-keto reductase 1C3, in patients with solid tumors. Cancer Chemother Pharmacol. 2010;65(4):791–801.
  • Wilkinson RS, Bot C, Kelly MJ, et al. Trypanocidal activity of nitroaromatic prodrugs: current treatments and future perspectives. Curr Top Med Chem. 2011;11(16):2072–2084.
  • Denny WA. Prodrugs for gene-directed enzyme-prodrug therapy (suicide gene therapy). Biomed Res Int. 2003;2003(1):48–70.
  • Chen Y, Hu L. Design of anticancer prodrugs for reductive activation. Med Res Rev. 2009;29(1):29–64.
  • DNDi. Trial to determine efficacy of fexinidazole in visceral leihmaniasis patients in sudan. [cited 2013 Nov 12]. Available from: http://clinicaltrials.gov/show/NCT01980199
  • DNDi. Fexinidazole/miltefosine combination (VL). [cited 2016]. Available from: https://www.dndi.org/diseases-projects/portfolio/completed-projects/fexinidazole-vl/
  • Diacon AH, Dawson R, Du Bois J, et al. A phase II dose-ranging trial of the early bactericidal activity of PA-824. Antimicrob Agents Chemother. 2012;AAC:06111–06125.
  • Sundar S, Chakravarty J. Investigational drugs for visceral leishmaniasis. Expert Opin Investig Drugs. 2015;24(1):43–59.
  • Kumar R, Sahoo GCPandey K, et al. Plga-peg encapsulated sitamaquine nanoparticles drug delivery system against leishmania donovani. Jsir. 2014;3:85-90.
  • Gutiérrez V, Seabra AB, Reguera RM, et al. New approaches from nanomedicine for treating leishmaniasis. Chem Soc Rev. 2016;45(1):152–168.
  • Pham T, Loiseau P, Barratt G. Strategies for the design of orally bioavailable antileishmanial treatments. Int J Pharm. 2013;454(1):539–552.
  • Saudagar P, Dubey VK. Carbon nanotube based betulin formulation shows better efficacy against Leishmania parasite. Parasitol Int. 2014;63(6):772–776.
  • Prajapati VK, Awasthi K, Yadav TP, et al. An oral formulation of amphotericin B attached to functionalized carbon nanotubes is an effective treatment for experimental visceral leishmaniasis. J Infect Dis. 2011;205(2):333–336.
  • López L, Vélez I, Asela C, et al. A phase II study to evaluate the safety and efficacy of topical 3% amphotericin B cream (Anfoleish) for the treatment of uncomplicated cutaneous leishmaniasis in Colombia. PLoS Negl Trop Dis. 2018;12(7):e0006653.
  • Akbari M, Oryan A, Hatam G. Application of nanotechnology in treatment of leishmaniasis: a review. Acta Trop. 2017;172:86–90.
  • Rodriguez F, Iniguez E, Pena GC, et al. Development of thiophene compounds as potent chemotherapies for the treatment of cutaneous leishmaniasis caused by leishmania major. Molecules. 2018;23:7.
  • Teixeira de Macedo Silva S, Visbal G, Lima Prado Godinho J, et al. In vitro antileishmanial activity of ravuconazole, a triazole antifungal drug, as a potential treatment for leishmaniasis. J Antimicrob Chemother. 2018.
  • DNDi. Miltefosine/Paromomycin combination for africa. [cited 2018 Aug]. Available from: https://www.dndi.org/diseases-projects/portfolio/miltefosine-paromomycin-combo/
  • DNDi. New treatments for HIV/VL. [cited 2018 Aug]. Available from: https://www.dndi.org/diseases-projects/portfolio/hivvl/
  • CTRI. A randomized trial of AmBisome® single therapy and combination of AmBisome® and miltefosine for the treatment of Kala Azar in HIV positive patients in India. [ cited 2017 Jan]. Available from: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=11735
  • Ramesh V, Katara G, Verma S, et al. Miltefosine as an effective choice in the treatment of post‐kala‐azar dermal leishmaniasis. Br J Dermatol. 2011;165(2):411–414.
  • DNDi. An open label, randomized, parallel arm clinical trial of two regimens to assess the safety and efficacy for treatment of Post Kala-azar Dermal Leishmaniasis (PKDL) patients in Sudan. [cited 2018 Aug 22]. Available from: https://ichgcp.net/clinical-trials-registry/NCT03399955

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.