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American tegumentary leishmaniasis in Brazil: a critical review of the current therapeutic approach with systemic meglumine antimoniate and short-term possibilities for an alternative treatment.
Trop Med Int Health. 2019 04; 24(4):380-391.TM

Abstract

OBJECTIVES

Meglumine antimoniate (MA; Glucantime®), the 80-year-old first-line systemic treatment for all forms of American tegumentary leishmaniasis (ATL) caused by Leishmania (Viannia) braziliensis, Leishmania (Viannia) guyanensis and Leishmania (Leishmania) amazonensis, is highly toxic, presents adverse side-effects and may not attain clinical and parasitological cure. This critical review examines the necessity for intramuscular/intravenous administration of MA, the alternatives to this approach, and the possibilities of developing affordable, accessible and non-toxic drugs or new delivery methods.

METHOD

PubMed searches were performed using the terms 'cutaneous leishmaniasis' or 'American tegumentary leishmaniasis' in combination with 'meglumine antimoniate' or 'N-methyl glucamine' or 'drug repositioning' or 'nanotechnology'. Searches covered a period of 20 years of peer reviewed journals and technical bulletins. We explored the mode of action, pharmacokinetics, toxicity and efficacy of MA, evaluated the progress of ATL therapy in Brazil, and examined the potential of drug repositioning and nanotechnology in accelerating the introduction and/or optimisation of an alternative treatment.

RESULTS

The evidence suggests that ATL therapy will continue to rely on systemic MA in the foreseeable future even though an intralesional subcutaneous route has evolved over the last 10 years. The chances of developing a novel drug for ATL or a new mode of delivery of MA are low. While MA nanocarriers afford a promising approach, this technology is still in its infancy. A more immediate solution would be the production of a bioequivalent of miltefosine, an efficacious oral agent no longer protected by patent.

CONCLUSION

Development of a contemporary treatment requires governmental commitment in bringing together private and public sectors.

Authors+Show Affiliations

Serviço de Doenças Infecciosas e Parasitárias, Hospital Eduardo de Menezes, Fundação Hospitalar do Estado de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.Departamento do Medicamento, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, Bahia, Brazil.Departamento de Medicina, Universidade José do Rosário Vellano-Unifenas, Belo Horizonte, Minas Gerais, Brazil.Serviço de Doenças Infecciosas e Parasitárias, Hospital Eduardo de Menezes, Fundação Hospitalar do Estado de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.Escola Superior de Ciências da Santa Casa de Misericórdia de Vitória, Vitória, Espírito Santo, Brazil.Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

30681239

Citation

Carvalho, Sílvia H., et al. "American Tegumentary Leishmaniasis in Brazil: a Critical Review of the Current Therapeutic Approach With Systemic Meglumine Antimoniate and Short-term Possibilities for an Alternative Treatment." Tropical Medicine & International Health : TM & IH, vol. 24, no. 4, 2019, pp. 380-391.
Carvalho SH, Frézard F, Pereira NP, et al. American tegumentary leishmaniasis in Brazil: a critical review of the current therapeutic approach with systemic meglumine antimoniate and short-term possibilities for an alternative treatment. Trop Med Int Health. 2019;24(4):380-391.
Carvalho, S. H., Frézard, F., Pereira, N. P., Moura, A. S., Ramos, L. M. Q. C., Carvalho, G. B., & Rocha, M. O. C. (2019). American tegumentary leishmaniasis in Brazil: a critical review of the current therapeutic approach with systemic meglumine antimoniate and short-term possibilities for an alternative treatment. Tropical Medicine & International Health : TM & IH, 24(4), 380-391. https://doi.org/10.1111/tmi.13210
Carvalho SH, et al. American Tegumentary Leishmaniasis in Brazil: a Critical Review of the Current Therapeutic Approach With Systemic Meglumine Antimoniate and Short-term Possibilities for an Alternative Treatment. Trop Med Int Health. 2019;24(4):380-391. PubMed PMID: 30681239.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - American tegumentary leishmaniasis in Brazil: a critical review of the current therapeutic approach with systemic meglumine antimoniate and short-term possibilities for an alternative treatment. AU - Carvalho,Sílvia H, AU - Frézard,Frédéric, AU - Pereira,Neila P, AU - Moura,Alexandre S, AU - Ramos,Lucinéia M Q C, AU - Carvalho,Gabriel B, AU - Rocha,Manoel O C, Y1 - 2019/02/19/ PY - 2019/1/27/pubmed PY - 2019/10/28/medline PY - 2019/1/26/entrez KW - N-methyl glucamine KW - N-méthyl glucamine KW - antimoine pentavalent KW - cutaneous leishmaniasis KW - drug repositioning KW - leishmaniose cutanée KW - nanomedicine KW - nanomédecine KW - pentavalent antimonial KW - repositionnement de médicament SP - 380 EP - 391 JF - Tropical medicine & international health : TM & IH JO - Trop Med Int Health VL - 24 IS - 4 N2 - OBJECTIVES: Meglumine antimoniate (MA; Glucantime®), the 80-year-old first-line systemic treatment for all forms of American tegumentary leishmaniasis (ATL) caused by Leishmania (Viannia) braziliensis, Leishmania (Viannia) guyanensis and Leishmania (Leishmania) amazonensis, is highly toxic, presents adverse side-effects and may not attain clinical and parasitological cure. This critical review examines the necessity for intramuscular/intravenous administration of MA, the alternatives to this approach, and the possibilities of developing affordable, accessible and non-toxic drugs or new delivery methods. METHOD: PubMed searches were performed using the terms 'cutaneous leishmaniasis' or 'American tegumentary leishmaniasis' in combination with 'meglumine antimoniate' or 'N-methyl glucamine' or 'drug repositioning' or 'nanotechnology'. Searches covered a period of 20 years of peer reviewed journals and technical bulletins. We explored the mode of action, pharmacokinetics, toxicity and efficacy of MA, evaluated the progress of ATL therapy in Brazil, and examined the potential of drug repositioning and nanotechnology in accelerating the introduction and/or optimisation of an alternative treatment. RESULTS: The evidence suggests that ATL therapy will continue to rely on systemic MA in the foreseeable future even though an intralesional subcutaneous route has evolved over the last 10 years. The chances of developing a novel drug for ATL or a new mode of delivery of MA are low. While MA nanocarriers afford a promising approach, this technology is still in its infancy. A more immediate solution would be the production of a bioequivalent of miltefosine, an efficacious oral agent no longer protected by patent. CONCLUSION: Development of a contemporary treatment requires governmental commitment in bringing together private and public sectors. SN - 1365-3156 UR - https://www.unboundmedicine.com/medline/citation/30681239/American_tegumentary_leishmaniasis_in_Brazil:_a_critical_review_of_the_current_therapeutic_approach_with_systemic_meglumine_antimoniate_and_short_term_possibilities_for_an_alternative_treatment_ L2 - https://doi.org/10.1111/tmi.13210 DB - PRIME DP - Unbound Medicine ER -