Treatments for tegumentar leishmaniasis in children: a systematic review
DOI:
https://doi.org/10.17058/n5r23915Keywords:
Pharmaceutical Preparations, Leishmaniasis, PediatricsAbstract
Introduction: American Tegumentary Leishmaniasis (ATL) is a non-contagious infectious disease caused by protozoa of the genus Leishmania, which causes ulcerative lesions on the skin and mucous membranes. The therapeutic management of this condition is diverse and particularly suitable for vulnerable populations, such as pregnant and lactating women, children, the elderly, and individuals with comorbidities or immunosuppression. Objective: To investigate the main treatments used for American Cutaneous Leishmaniasis in children and their implications. Method: A systematic literature review was conducted focusing on drugs used to treat TL in pediatric patients. The literature search was conducted in LILACS, SCIELO, and PUBMED databases. The electronic search combined the descriptors "cutaneous Leishmaniasis," "treatment," and "children" with the Boolean operator AND. Articles published between 2018 and 2023 that specifically addressed the treatment of leishmaniasis in children were included, and those not focused on this topic were excluded. Results: The review identified five primary treatments for leishmaniasis in pediatric patients: pentavalent antimonials, amphotericins, pentamidine, miltefosine, and azoles. The results highlight the significant concern regarding the toxicity and adverse effects of these medications, especially in children. Pentavalent antimonials were identified as the main culprits of adverse reactions and toxicity. Conclusion: Amphotericins and miltefosine demonstrated high therapeutic potential for the treatment of ATL in pediatric patients. However, it is essential to emphasize the need for research with larger sample sizes to validate the viability and applicability of these drugs and their potential implications.
Downloads
References
1. Brasil. Ministério da Saúde. Manual de vigilância da leishmaniose tegumentar americana. 2ª ed. Brasília: Ministério da Saúde, 2013.
2. Vargas Brasil AM, Franco AMR. Aspectos epidemiológicos da Leishmaniose Tegumentar Americana no Brasil em 2022. Peer Review, 2023; 5(11):294–305.
3. Brasil. Ministério da Saúde. Manual de vigilância da leishmaniose tegumentar. Secretaria de Vigilância em Saúde, Departamento de Vigilância das Doenças Transmissíveis. Brasília: Ministério da Saúde, 2017.
4. Burza S, Croft SL, Boelaert M. Leishmaniasis. Lancet, 2018; 392:951-970. doi: https://doi.org/10.1016/s0140-6736(18)31204-2.
5. Rosa MEA, Machado PRL. Disseminated Leishmaniasis: Clinical, Immunological and Therapeutic Aspects. Drug Development Research, 2019; 94(1):09-16. doi: http://dx.doi.org/10.1590/abd1806-4841.20198775.
6. Pirmez C, Yamamura M, Uyemura K, Paes-Oliveira M, Conceição-Silva F, Modlin RL. Cytokine patterns in the pathogenesis of human Leishmaniasis. J Clin Invest. 1993; 91: 1390-95. doi: https://doi.org/10.1172/jci116341.
7. Coler RN, Reed SG. Second-generation vaccines against Leishmaniasis. Trends Parasitol. 2005; 21: 244- 49. doi: https://doi.org/10.1016/j.pt.2005.03.006.
8. Khamesipour A, Dowlati Y, Asilian A, Hashemi-Fesharki R, Javadi A, Noazin S, Modabber F. Leishmanization: use of an old method for evaluation of candidate vaccines against Leishmaniasis. Vaccine. 2005; 23: 3642-3648. doi: https://doi.org/10.1016/j.vaccine.2005.02.015.
9. Moreira Borges BF; Silva de Oliveira Júnior G; Logrado Júnior V; Almeida da Silva Rosa RT, Fernandes da Costa N. Indicadores epidemiológicos da leishmaniose tegumentar americana no estado do Tocantins no período de 2001 a 2018. Revista de Patologia do Tocantins. 2021; 8(1):42–7. doi: https://doi.org/10.20873/10.20873/uft.2446-6492.2021v8n1p42.
10. Abbas AK, Lichtman AH, Shiv Pillai, Al E. Imunologia celular e molecular. Rio de Janeiro: Elsevier; 2019.
11. Brito FF, Pinto ACVD, Cavalcante MLLL, Silva GV, Wachholz PA, Nascimento DC. Estudo clínico, epidemiológico e imunológico para Leishmaniose Tegumentar Americana em centro de referência em dermatologia. Hansenologia Internationalis, 2015; 30;40(1):17–24. doi: https://doi.org/10.47878/hi.2015.v40.35004.
12. Galvão TF, Pereira MG. Revisões sistemáticas da literatura: passos para sua elaboração. Epidemiologia e Serviços de Saúde, 2014; 23(1):183–4.
13. Galvão TF, Pansani TSA, Harrad D. Principais itens para relatar Revisões sistemáticas e Meta-análises: A recomendação PRISMA. Epidemiol. Serv. Saúde. 2015; 24(2).
14. Brasil. Ministério da Saúde. Diretrizes metodológicas: Sistema GRADE. Manual de graduação da qualidade da evidência e força de recomendação para tomada de decisão em saúde. Brasília: Ministério da Saúde, 2014.
15. Maio I, Teixeira C, Prior C, Machado S, Selores M, Marques L. Cutaneous Leishmaniasis - two cases, two perspectives. Birth and Growth Medical Journal, 2019; 28(2): 90-92.
16. Huanca Huanca ML, Calderon Lopez ME, Rojas Cabrera E, Saavedra Borda CR. Anfotericina B Liposomal, Tratamiento Pediátrico en Leishmaniasis Cutánea con Falla Terapéutica. Gaceta Médica Boliviana, 2021; 44(2):254-259.
17. Castro M del M, Rode J, Machado PRL, Llanos-Cuentas A, Hueb M, Cota G, Rojas IV, Orobio Y, Sarmiento OO, Rojas E, Quintero J, Pimentel MIF, Soto J, Suprien C, Alvarez F, Ramos AP, Arantes RBS, Silva RE, Arenas CM, Vélez ID, Lyra MR, Saravia NG, Arana B, Alexander N. Cutaneous Leishmaniasis treatment and therapeutic outcomes in special populations: A collaborative retrospective study. PLOS Neglected Tropical Diseases. 2023; 17(1):e0011029. doi: https://doi.org/10.1371/journal.pntd.0011029.
18. Hill N, Irwin A, Graham N, Leung C, Francis JR, Wall N, Nourse C. Treatment of Cutaneous Leishmaniasis in a Nonendemic Country: A Case Series of Children in Australia. The Pediatric infectious disease journal. 2021; 41(4):e177–81. doi: https://doi.org/10.1097/inf.0000000000003445.
19. Rezaee N; Raissi V; Rajaeipour A; Nazari M, Getso M, Taghipour A, Ibrahim A. Epidemiology, Associated Factors and Treatment Methods of Cutaneous Leishmaniasis Based on Previous Data from 2013 to 2018 in Ilam, Western Iran. Acta Parasitologica. 2020; 65(3):760–7. doi: https://doi.org/10.2478/s11686-020-00198-y.
20. Knapp C, Vaz L, Onoday H, Small A. Dual treatment of cutaneous Leishmaniasis with topical amphotericin B and photodynamic therapy in a pediatric patient. Pediatric dermatology. 2022; 39(5):761–3. doi: https://doi.org/10.1111/pde.15042.
21. Ubals M, Bosch-Nicolau P, Sánchez-Montalvá A, Salvador F, Aparicio-Español G, Sulleiro E, Silgado A, Soriano-Arandes A, Espiau M, Ferrer B, Pou D, Treviño B, Molina I, García-Patos V. Treatment of Complex Cutaneous Leishmaniasis with Liposomal Amphotericin B. Pathogens. 2021; 10(10):1253. doi: https://doi.org/10.3390/pathogens10101253.
22. Hussein NR, Salih HM. The efficacy and safety of intralesional sodium stibogluconate for the treatment of cutaneous Leishmaniasis in children under the age of two years. Mediterranean Journal of Hematology and Infectious Diseases. 2020; 12(1):e2020027–7. doi: https://doi.org/10.4084/mjhid.2020.027.
23. Van Kesteren L; Maniewski U; Bottieau E; Cnops L, Huits R. Cutaneous Leishmaniasis in Syrian Refugee Children. Pediatric Infectious Disease Journal. 2020; 39(7):e154–6. doi: https://doi.org/10.1097/inf.0000000000002676.
24. Renert-Yuval Y, Enk CD, Murad S, Yofe V, Gozal D, Molho-Pessach V. Intralesional sodium stibogluconate under inhaled anesthesia for the treatment of cutaneous Leishmaniasis in children: A retrospective cohort. Journal of the American Academy of Dermatology. 2019; 81(4):1013–5. doi: https://doi.org/10.1016/j.jaad.2019.01.083.
25. Heleine M, Elenga N, Njuieyon F, Martin E, Piat C, Pansart C, Couppie P, Hernandez M, Demar M, Blaizot R. Using pentamidine to treat cutaneous Leishmaniasis in children: a 10-year study in French Guiana. Clinical and experimental dermatology, 2023; 48(8):913–5. doi: https://doi.org/10.1093/ced/llad146.
26. Hilerowicz Y, Koren A, Mashiah J, Katz O, Sprecher E, Artzi O. Fractional ablative carbon dioxide laser followed by topical sodium stibogluconate application: A treatment option for pediatric cutaneous Leishmaniasis. Pediatric Dermatology. 2018; 35(3):366–9. doi: https://doi.org/10.1111/pde.13457.
27. Rather S, Yaseen A, Shah FY, Wani M, Krishan K, Zirak S, Sharma R, Hassan I, Dogra D, Rishi R.Pediatric cutaneous Leishmaniasis: A clinico-epidemiological study from North India. Indian Dermatology Online Journal. 2021; 12(6):852. doi: https://doi.org/10.4103/idoj.IDOJ_49_21.
28. Hussein NR. A Clinicoepidemiological Study of Pediatric Cutaneous Leishmaniasis in Sinjar Province, Iraq. The American Journal of Tropical Medicine and Hygiene. 2019; 101(5):1111–3. doi: https://doi.org/10.4269/ajtmh.19-0508.
29. Ollech A, Solomon M, Horev A, Reiss-Huss S, Ben-Amitai D, Zvulunov A, Friedland R, Atar-Snir V, Pessach-Molcho V, Barzilai A, Greenberger S. Cutaneous Leishmaniasis Treated with Miltefosine: A Case Series of 10 Paediatric Patients. Acta Derm Venereol. 2020; 100(18):adv00322. doi: https://doi.org/10.2340/00015555-3669.
30. Michelerio A, Barruscotti S, Bossi G, Brazzelli V. Pediatric Old World cutaneous Leishmaniasis treated with oral fluconazole: A case series. Pediatric Dermatology. 2018; 35(3):384–7. doi: https://doi.org/10.1111/pde.13493.
31. Senna TCR, Pimentel MIF, Oliveira LFA, Lyra MR, Saheki MN, Salgueiro MM, Valete-Rosalino CM, Martins ACC, Schubach AO, Bedoya-Pacheco SJ. Clinical features and therapeutic response in adult and pediatric patients with American Tegumentary Leishmaniasis in Rio de Janeiro. Trans R Soc Trop Med Hyg. 2020; 114(1):1-6. doi: https://doi.org/10.1093/trstmh/trz095.
32. Arteaga-Livias K, Santos-Huerta M, Dámaso-Mata B, Panduro-Correa V, Gonzales-Zamora JA, Rodriguez-Morales AJ. Disseminated Cutaneous Leishmaniasis in a Pediatric Patient from Peru. Journal of Tropical Pediatrics. 2020; 67(3). doi: https://doi.org/10.1093/tropej/fmaa051.
33. Noyman Y, Levi A, Amitai DB, Huss SR, Sabbah F, Hodak E, Mimouni T, Friedland R. Treating pediatric cutaneous Leishmania tropica with systemic liposomal amphotericin B: A retrospective, single‐center study. Dermatologic therapy. 2021; 35(1). doi: https://doi.org/10.1111/dth.15185.
34. Jubulis J, Goddard A, Seiverling E, Kimball M, McCarthy C. Everything old is new again: a case series of pediatric cutaneous Leishmaniasis in Portland, Maine. Journal of Tropical Pediatrics. 2022; 69(1). doi: https://doi.org/10.1093/tropej/fmad003.
35. Johanning PL, Elizondo EP, Morales LA, Zúñiga CW, Torres MS. Leishmaniasis: Opciones terapéuticas en la población pediátrica. 2018; 35(1):52–64.
36. Detoni MB, Lima DM, Silva TP, Machado LF, Tomiotto-Pellissier F, Costa IN, Pavanelli WR, Oliveira FJA, Custódio LA, Conchon-Costa I, Melanda FN. Temporal and spatial distribution of American Tegumentary Leishmaniasis in north Paraná: 2010-2015. Revista da Sociedade Brasileira de Medicina Tropical, 2019; 52:e20180119. doi: https://doi.org/10.1590/0037-8682-0119-2018.
37. Iglesias Cataldo J, Antônio LF, Schubach AO, Marzochi MCA, Valete-Rosalino CM, Pimentel MIF, Lyra MR, Oliveira RVC, Barros JHS, Pacheco RS, Madeira MF. Favorable responses to treatment with 5 mg Sbv/kg/day meglumine antimoniate in patients with American tegumentary Leishmaniasis acquired in different Brazilian regions. Revista da Sociedade Brasileira de Medicina Tropical, 2018; 51(6):769–80. doi: https://doi.org/10.1590/0037-8682-0464-2017.
38. de Vries HJC, Schallig HD. Cutaneous Leishmaniasis: A 2022 Updated Narrative Review into Diagnosis and Management Developments. American Journal of Clinical Dermatology. 2022; 1–18. doi: https://doi.org/10.1007/s40257-022-00726-8.
39. Ubals M, Bosch-Nicolau P, Sánchez-Montalvá A, Salvador F, Aparicio-Español G, Sulleiro E, Silgado A, Soriano-Arandes A, Espiau M, Ferrer B, Pou D, Treviño B, Molina I, García-Patos V. Interventions to treat cutaneous Leishmaniasis in children: A systematic review. PLoS Neglected Tropical Diseases. 2018; 12(12):e0006986. doi: https://doi.org/10.3390/pathogens10101253.
40. Ferreira DT. Leishmaniose visceral em crianças: dispensação e controle da utilização dos medicamentos antimoniato de meglumina e anfotericinas b lipossomal no tratamento específico da leishmaniose visceral em um hospital de referência no Mato Grosso do Sul. Mestrado Profissional em Pesquisa Clínica [Dissertação]. Campo Grande (MS): Universidade Federal do Rio Grande do Sul; 2019.
41. Machado PRL, Prates FVO, Boaventura V, Lago T, Guimarães LH, Schriefer A, Corte TWF, Penna G, Barral A, Barral-Netto M, Carvalho EM. A Double-blind, Randomized Trial to Evaluate Miltefosine and Topical Granulocyte Macrophage Colony-stimulating Factor in the Treatment of Cutaneous Leishmaniasis Caused by Leishmania braziliensis in Brazil. Clinical Infectious Diseases. 2020; 73(7):e2465–9. doi: https://doi.org/10.1093/cid/ciaa1337.
42. Suprien C, Rocha PN, Teixeira M, Carvalho LP, Guimarães LH, Bonvoisin T, Machado PRL, Carvalho EM. Clinical Presentation and Response to Therapy in Children with Cutaneous Leishmaniasis. Am J Trop Med Hyg. 2020; 102(4):777-781. doi: https://doi.org/10.4269/ajtmh.19-0531.
43. Lima EB, Porto C, Motta JOC, Sampaio RNR. Tratamento da leishmaniose tegumentar americana. An Bras Dermatol. 2007; 82(2):111–24. doi: https://doi.org/10.1590/S0365-05962007000200002.
44. Bomfim G, Nascimento C, Costa J, Carvalho EM, Barral-Netto M, Barral A. Variation of Cytokine Patterns Related to Therapeutic Response in Diffuse Cutaneous Leishmaniasis. Experimental Parasitology. 1996; 84(2):188–94. doi: https://doi.org/10.1006/expr.1996.0104.
45. Ness T, Martin-Blais R, Weatherhead JE. How I Approach Leishmaniasis: Diagnosis and Treatment in the United States. Journal of the Pediatric Infectious Diseases Society. 2022; 11(11):525–32. doi: https://doi.org/10.1093/jpids/piac087.
46. Peixoto F, Nascimento MT, Costa R, Silva J, Renard G, Guimarães LH, Penna G., Barral-Netto M, Carvalho LP, Machado PRL, Carvalho EM. Evaluation of the Ability of Miltefosine Associated with Topical GM-CSF in Modulating the Immune Response of Patients with Cutaneous Leishmaniasis. Journal of immunology research. 2020; 2020:1–9. doi: https://doi.org/10.1155/2020/2789859.
47. Francesconi VA, Francesconi F, Ramasawmy R, Romero GAS, Alecrim MGC. Failure of fluconazole in treating cutaneous Leishmaniasis caused by Leishmania guyanensis in the Brazilian Amazon: An open, nonrandomized phase 2 trial. Deye G, editor. PLOS Neglected Tropical Diseases. 2018; 12(2):e0006225. doi: https://doi.org/10.1371/journal.pntd.0006225.
Downloads
Published
Issue
Section
License
A submissão de originais para este periódico implica na transferência, pelos autores, dos direitos de publicação impressa e digital. Os direitos autorais para os artigos publicados são do autor, com direitos do periódico sobre a primeira publicação. Os autores somente poderão utilizar os mesmos resultados em outras publicações indicando claramente este periódico como o meio da publicação original. Em virtude de sermos um periódico de acesso aberto, permite-se o uso gratuito dos artigos em aplicações educacionais e científicas desde que citada a fonte conforme a licença CC-BY da Creative Commons.
