Skip to main content

Advertisement

SpringerLink
Log in

Leishmaniasis treatment—a challenge that remains: a review

  • Review
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

Leishmaniasis is a disease caused by flagellate protozoan Leishmania spp. and represents an emergent illness with high morbidity and mortality in the tropics and subtropics. Since the discovery of the first drugs for Leishmaniasis treatment (i.e., pentavalent antimonials), until the current days, the search for substances with antileishmanial activity, without toxic effects, and able to overcome the emergence of drug resistant strains still remains as the current goal. This article reports the development of new chemotherapies through the rational design of new drugs, the use of products derived from microorganisms and plants, and treatments related to immunity as new alternatives for the chemotherapy of leishmaniasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Alexander J, Russel DG (1992) The interaction of Leishmania species macrophages. In: Baker JR, Muller R (eds) Advances in parasitology. vol. 131. Academic, New York, USA, pp 175–254

    Google Scholar 

  • Arruda DC, Dalexandri FL, Katzin AM, Uliana SRB (2005) Antileishmanial activity of terpene nerolidol. Antimicrob Agents Chemother 49:1679–1687

    Article  PubMed  CAS  Google Scholar 

  • Barral A, Pedral-Sampaio D, Grimaldi G Jr., Momen H, Mc Mahon-Pratt D, Ribeiro de Jesus A, Almeida R, Badaró R, Barral-Neto M, Carvalho EM, Johnson WD Jr (1991) Leishmaniasis in Bahia, Brazil: evidence that Leishmania amazonensis produces a wide spectrum of clinical disease. Am J Trop Med Hyg 44:536–546

    PubMed  CAS  Google Scholar 

  • Berengener J, Gomez-Campdera F, Padilha B (1998) Visceral leishmaniasis (Kala-Azar) in transplant recipients: case report and review. Transplantation 65:1401–1404

    Article  Google Scholar 

  • Berman JD (1988) Chemotherapy for leishmaniasis: biochemical mechanisms, clinical efficacy and future strategies. Rev Infect Dis 10:560–586

    PubMed  CAS  Google Scholar 

  • Bogdan C, Rollinghoff M, Solbato W (1990) Evasion strategies of leishmania parasite. Parasitol Today 6:183–187

    Article  PubMed  CAS  Google Scholar 

  • Bogdan C, Gessner A, Solbach W, Rollinghoff M (1996) Invasion, control and persistence of leishmania parasites. Curr Opin Immunol 8:517–525

    Article  PubMed  CAS  Google Scholar 

  • Bray PG, Barrett MP, Ward SA, Koning HP (2003) Pentamidine uptake and resistance in pathogenic protozoa: past, present and future. Trends Parasitol 19:232–239

    Article  PubMed  CAS  Google Scholar 

  • Carvalho PB, Arribas MAG, Ferreira EI (2000) Leishmaniasis. What do we know about its chemotherapy? Braz J Pharm Sci 36:69–96

    Google Scholar 

  • Chang KP (1990) Cell biology of leishmania. In: Wyler DW (ed) Modem parasite biology cellular, immunological and molecular aspects. Freeman, New York, pp 79–90

    Google Scholar 

  • Corte-Real S, Santos CB, Meirelles MNL (1995) Differential expression of the plasma membrane Mg2+ ATPase and Ca2+ ATPase activity during adhesion and interiorization of Leishmania amazonensis in fibroblasts in vitro. J Submicrosc Cytol Pathol 27(3):359–366

    PubMed  CAS  Google Scholar 

  • Coura JR, Galvão-Castro B, Grimaldi JG (1987) Disseminated American cutaneous leishmaniasis in a patient with AIDS. Mem Inst Osw Cruz 82:581–582

    CAS  Google Scholar 

  • Croft Sl, Seifert K, Yardley V (2006) Current scenario of drug development for leishmaniasis. Indian J Med Res 123(3):399–410

    PubMed  CAS  Google Scholar 

  • Deane LM, Grimaldi G (1985) Leishmaniasis in Brazil. In: Chang KP, Bray RS (eds) Leishmaniasis. Elsevier, Amsterdam, pp 247–281

    Google Scholar 

  • Delorenzi JC, Attias M, Gattass C, Andrade M, Rezende C, Pinto AC, Henriques AT, Bou-Habib DC, Saraiva EM (2001) Antileishmanial activity of na índole alkaloid from Peschiera australis. Antimicrob Agents Chemother 45(5):1349–1354

    Article  PubMed  CAS  Google Scholar 

  • Desjeux P, Alvar J (2003) Leishmania/HIV. Co-infections: epidemiology in Europe. Ann Trop Med Parasitol 97(suppp.1):3–15

    Article  PubMed  Google Scholar 

  • Dey T, Anam K, Afrin F, Ali N (2000) Antileishmanial activities of stearylamina-bearing liposomes. Antimicrob Agents Chemother 44(6):1739–1742

    Article  PubMed  CAS  Google Scholar 

  • Escobar P, Yardley V, Croft SL (2001) Activities of hexadecylphosphocholine (miltefosine), ambisome, and sodium stibogluconate (Pentostam) against Leishmania donovani in immunodeficient scid mice. Antimicrob Agents Chemother 45(6):1872–1875

    Article  PubMed  CAS  Google Scholar 

  • Golenser J, Frankenburg S, Ehrenfreund T, Domb AJ (1999) Efficacious treatment of experimental leishmaniasis with amphotericin b-arabinogalactan water-soluble derivatives. Antimicrob Agents Chemother 43(9):2209–2214

    PubMed  CAS  Google Scholar 

  • Gontijo B, Carvalho MLR (2003) Leishmaniose Tegumentar Americana. Revista de Sociedade Brasileira de Medicina Tropical 36(1):71–80

    Google Scholar 

  • Gontijo CMF, Melo MN (2004) Leishmaniose Visceral no Brasil: Quadro Atual, Desafios e Perspectivas. Rev Bras Epidemiol 7(3):338–349

    Article  Google Scholar 

  • Green SJ, Meltzer MS Jr, Hibbs JB, Nacy CA (1990) Activated macrophages destroy intracellular Leishmania major amastigotes by an l-arginine-dependent killing mechanism. J Immunol 144:278–283

    PubMed  CAS  Google Scholar 

  • Grimaldi G Jr., Mc-Mahon-Pratt D, Sun T (1991) Leishmaniasis and its etiologic agents in the New World: an overview. Prog Clin Parasitol 2:73–118

    PubMed  Google Scholar 

  • Grimaldi G Jr., Corte-Real S, Pinho RT (1983) Interactions between Leishmania mexicana mexicana promastigotes and amastigotes and murine peritoneal macrophages in vitro. Mem Inst Osw Cruz 78:136–146

    Google Scholar 

  • Hespanhol RC, Soeiro MNC, Corte-Real S (2005) The expression of mannose-receptor in skin fibroblast and their involvement in Leishmania (L.) amazonensis invasion. J Histochem Cytochem 53(1):35–44

    Article  PubMed  CAS  Google Scholar 

  • Kar S, Kar K, Bhattacharya PK, Ghosh DK (1993) Experimental visceral leishmaniasis: role of trans-aconitic acid in combined chemotherapy. Antimicrob Agents Chemother 37(11):2459–2465

    PubMed  CAS  Google Scholar 

  • Kayser O, Kiderlen AF, Bertels S, Siems K (2001) Antileishmanial activities of aphidicolin and its semisynthetic derivatives. Antimicrob Agents Chemother 45(1):288–292

    Article  PubMed  CAS  Google Scholar 

  • Kuhlencord A, Maniera T, Eibl H, Unger C (1992) Hexadecylphosphocholine: oral treatment of visceral leishmaniasis in mice. Antimicrob Agents Chemother 36(8):1630–1634

    PubMed  CAS  Google Scholar 

  • Larabi M, Yardley V, Loiseau PM, Appel M, Legrand P, Gulik A, Bories C, Croft SL, Barratt G (2003) Toxicity and antileishmanial activity of a new stable lipid suspension of amphotericin B. Antimicrob Agents Chemother 47(12):3774–3779

    Article  PubMed  CAS  Google Scholar 

  • Liew FY, O’Donnell CA (1993) Immunology of leishmaniasis. Adv Parasitol 32:161–259

    Article  PubMed  CAS  Google Scholar 

  • Lima LM, Barreiro EJ (2005) Bioisosterism: a useful strategy for molecular modification and drug design. Curr Med chem 12(1):23–49

    PubMed  CAS  Google Scholar 

  • Liñares GE, Ravaschino EL, Rodriguez JB (2006) Progresses in the field of drug design to combat tropical protozoan parasitic diseases. Curr Med Chem 13:335–360

    Article  PubMed  Google Scholar 

  • Ma G, Khan SI, Jacob MR, Tekwani BL, Li Z, Pasco DS, Walker LA, Khan IA (2004) Antimicrobial and antileishmanial activities of hipocrellins A and B. Antimicrob Agents Chemother 8(11):4450–4452

    Article  CAS  Google Scholar 

  • Mai A, Cerbara I, Valente S, Massa S, Walker LA, Tekwani BL (2004) Antimalarial and antileishmanial activities of aroyl-pyrrolyl-hydroxyamides, a new class of histone deacetylas inhibitors. Antimicrob Agents Chemother 48(4):1435–1436

    Article  PubMed  CAS  Google Scholar 

  • Mcgregor A (1998) WHO warns of epidemic Leishmania? Lancet 351:575–575

    Article  PubMed  CAS  Google Scholar 

  • Molina R, Gradoni L, Alvar J (2003) HIV and the transmission of Leishmania. Ann Trop Med Parasitol 97(Suppl. 1):29–45

    Article  PubMed  Google Scholar 

  • Morales P, Torres JJ, Salavert M, Peman J, Lacruz J, Sole A (2003) Visceral leishmaniasis in lung transplantation. Transplant Proc 35:2001–2003

    Article  PubMed  CAS  Google Scholar 

  • Mukhopadhyay S, Bhattacharyya S, Majhi R, De T, Naskar K, Majumdar S, Roy S (2000) Use of attenuated leishmanial parasite as an immunoprophylactic and immunotherapeutic agent against murine visceral leishmaniasis. Clin Diagn Lab Immunol 7(2):233–240

    Article  PubMed  CAS  Google Scholar 

  • Murray HW, Brooks EB, Devecchio JL, Heinzel FP (2003) Immunoenhancement combined with amphotericin B as treatment for experimental visceral leishmaniasis. Antimicrob Agents Chemother 47(8):2513–2517

    Article  PubMed  CAS  Google Scholar 

  • Oliveira CC, Lacerda HG, Martins DR, Barbosa JD, Monteiro GR, Queiroz JW, Sousa JM, Ximenesf MF, Jerônimo SM (2004) Changing epidemiology of American cutaneous leishmaniasis (ACL) in Brazil: a disease of the urban–rural interface. Acta Trop 90(2):155–162

    Article  PubMed  Google Scholar 

  • Olliaro PL, Bryceson ADM (1993) Practical progress and new drugs for changing patterns of leishmaniasis. Parasitol Today 9:323–328

    Article  PubMed  CAS  Google Scholar 

  • Pal S, Ravindran R, Ali N (2004) Combination therapy using sodium antimony gluconate in stearylamine-bearing liposomes against established and chronic Leishmania donovani infection in BALB/c mice. Antimicrob Agents Chemother 48(9):3591–3593

    Article  PubMed  CAS  Google Scholar 

  • Raht S, Trivellin A, Imbrunito TR, Tomazela DM, Jesus MN, Marzal P, Junior HFA (2003) Tempone, A.G. Antimoniais Empregados no Tratamento da Leishmaniose: Estado de Arte. Quim Nova 26:550–557

    Google Scholar 

  • Ramos H, Milhaud J, Cohen BE, Bolard J (1990) Enhanced action of anphotericin B on Leishmania mexicana resulting from heat transformation. Antimicrob Agents Chemother 34(8):1584–1589

    PubMed  CAS  Google Scholar 

  • Ritting MG, Bogdan C (2000) Leishmania host–cell interaction: complexities and alternative views. Parasitol Today 16:292–297

    Article  Google Scholar 

  • Roberts W, McMurray W, Rainey P (1998) Characterization of the antimonial antileishmanial agent meglumine antimonate (Glucantime). Antimicrob Agents Chemother 42(5):1076–1082

    PubMed  CAS  Google Scholar 

  • Rosa MSS, Mendonça-Filho RR, Bizzo HR, Rodrigues IA, Soares RM, Padrón TS, Alviano CS, Lopes AHCS (2003) Antileishmanial activity of a linalool-rich essential oil from Cróton cajucara. Antimicrob Agents Chemother 47(6):1895–1901

    Article  CAS  Google Scholar 

  • Sereno D, Alegre AM, Silvestre R, Vergnes B, Ouaissi A (2005) In vitro antileishmanial activity of nicotinamide. Antimicrob Agents Chemother 49(2):808–812

    Article  PubMed  CAS  Google Scholar 

  • Shapiro TA, Were JB, Danso K, Nelson DJ, Desjardins RE, Pamplin CL (1991) Pharmacokinetics and metabolism of allopurinol riboside. Clin Pharmacol Ther 49(5):506–514

    PubMed  CAS  Google Scholar 

  • Silva ES, Pacheco RS, Gontijo CM, Carvalho IR, Brazil RP (2002) Visceral leishmaniasis caused by Leishmania (viannia) braziliensis in a patient infected with human immunodeficiency virus. Rev Inst Med Trop São Paulo 44:145–149

    PubMed  Google Scholar 

  • Singh S, Sivakumar R (2004) Challenges and new discoveries in the treatment of leishmaniasis. J Infect Chemother 10(6):307–315

    Article  PubMed  Google Scholar 

  • Soong L, Duboise SM, Kima P, Mcmahon-Pratt D (1995) Leishmania pifanoi amastigote antigens protect mice against cutaneous leishmaniasis. Infection and Imunnity 63(9):3559–3566

    CAS  Google Scholar 

  • Tempone AG, Silva ACMP, Brandt CA, Martinez FS, Borborema SET, Silveira MAB, Andrade HF Jr (2005) Synthesis and antileishmanial activities of novel 3-substituted quinolones. Antimicrob Agents Chemother 49(3):1076–1080

    Article  PubMed  CAS  Google Scholar 

  • Tiuman TS, Nakamura TU, Cortez DAG, Filho BPD, Diaz JAM, Souza W, Nakamura CV (2005) Antileishmanial activity of parthenolide, a sesquiterpene lactone isolated from Tanacetum parthenium. Antimicrob Agents Chemother 49(1):176–182

    Article  PubMed  CAS  Google Scholar 

  • Weniger B, Robledo S, Arango GJ, Deharo E, Aragon R, Munoz V, Callapa J, Lobstein A, Anton R (2001) Antiprotozoal activities of Colombian plants. J Ethnopharmacol 78(2–3):193–200

    Article  PubMed  CAS  Google Scholar 

  • WHO (2001) Tropical disease research: progress 1999–2000. World Health Organization, Geneva

  • WHO (1990) Tropical disease research progress. AIDS, leishmaniasis dangers of clash highlighted. TDR News. 36:1–11. World Health Organization

    Google Scholar 

  • WHO (1991) Tropical disease research progress. Antimonials large-scale failure in Leishmaniasis “alarming”. TDR News. 34:17. World Health Organization

    Google Scholar 

  • Yardley V, Khan AA, Martin MB, Slifer TR, Araujo FG, Moreno SNJ, Docampo R, Croft SL, Oldfield E (2002) In vivo activities of farnesyl pyrophosphate synthase inhibitors against Leishmania donovani and Toxoplama gondii. Antimicrob Agents Chemother 46(3):929–931

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The authors thank UFF, FIOCRUZ, CNPq, and FAPERJ for financial support and fellowships.

Author information

Authors and Affiliations

  1. Laboratório de Biopatógenos e Ativação Celular (LaBiopAc), Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense (UFF), Av. Barros-Terra s/n Valonguinho, Niterói, Rio de Janeiro, CEP 24001-970, Brazil

    Dilvani O. Santos, Carlos E. R. Coutinho, Carolina G. Bottino, Rodrigo T. Vieira, Samara B. Nascimento, Saulo C. Bourguignon & Helena C. Castro

  2. Instituto de Pesquisa Clínica Evandro Chagas (IPEC), Fundação Oswaldo Cruz- FIOCRUZ, Av. Brasil, 4365, Manguinhos, Rio de Janeiro, CEP 21045-900, Brazil

    Maria F. Madeira

  3. Instituto de Química, UFF, Av. Barros-Terra s/n Valonguinho, Niterói, Rio de Janeiro, CEP 24001-970, Brazil

    Alice Bernardino

  4. Laboratório de Imunologia Clínica, Instituto Oswaldo Cruz, FIOCRUZ-Av. Brasil 4365, Manguinhos, Rio de Janeiro, CEP 21045-900, Brazil

    Suzana Corte-Real & Rosa T. Pinho

  5. Laboratório de Modelagem Molecular e QSAR (ModMolQSAR), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, CEP 21941-590, Rio de Janeiro, Rio de Janeiro, Brazil

    Carlos Rangel Rodrigues

Authors
  1. Dilvani O. Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carlos E. R. Coutinho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria F. Madeira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carolina G. Bottino
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rodrigo T. Vieira
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Samara B. Nascimento
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alice Bernardino
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Saulo C. Bourguignon
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Suzana Corte-Real
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Rosa T. Pinho
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Carlos Rangel Rodrigues
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Helena C. Castro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dilvani O. Santos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Santos, D.O., Coutinho, C.E.R., Madeira, M.F. et al. Leishmaniasis treatment—a challenge that remains: a review. Parasitol Res 103, 1–10 (2008). https://doi.org/10.1007/s00436-008-0943-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-008-0943-2

Keywords

Search

Navigation