Author:
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-
1.
Foglia Manzillo V, Di Muccio T, Cappiello S, Scalone A, Paparcone R, Fiorentino E, Gizzarelli M, Gramiccia M, Gradoni L, Oliva G, 2013. Prospective study on the incidence and progression of clinical signs in naive dogs naturally infected by Leishmania infantum. PLoS Negl Trop Dis 7: e2225.
-
2.
Solano-Gallego L, Miró G, Koutinas A, Cardoso L, Pennisi MG, Ferrer L, Bourdeau P, Oliva G, Baneth G; The LeishVet Group, 2011. LeishVet guidelines for the practical management of canine leishmaniosis. Parasit Vectors 4: 86.
-
3.
Frézard F, Demicheli C, Ribeiro RR, 2009. Pentavalent antimonials: New perspectives for old drugs. Molecules 14: 2317–2336.
-
4.
Miltefosine labelAvailable at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/204684s006lbl.pdf. Accessed January 8, 2025.
-
5.
Ministério da Agricultura e Pecuária, 2016. Nota técnica no 11/2016/CPV/DFIP/SDA/GM/MAPA. Available at: https://Www.Gov.Br/Agricultura/Pt-Br/Assuntos/Insumos-Agropecuarios/Insumos-Pecuarios/Produtos-Veterinarios/Legislacao-1/Notas-Tecnicas/Nota-Tecnica-No-11-2016-Cpv-Dfip-Sda-Gm-Mapa-de-1-09-2016.Pdf. Accessed January 8, 2025.
-
6.
Fortin A, Caridha DP, Leed S, Ngundam F, Sena J, Bosschaerts T, Parriott S, Hickman MR, Hudson TH, Grogl M, 2014. Direct comparison of the efficacy and safety of oral treatments with oleylphosphocholine (OlPC) and miltefosine in a mouse model of L. major cutaneous leishmaniasis. PLoS Negl Trop Dis 8: e3144.
-
7.
Van Bocxlaer K, Dixon J, Platteeuw JJ, Van Den Heuvel D, Mcarthur KN, Harris A, Alavijeh M, Croft SL, Yardley VJ, 2023. Efficacy of oleylphosphocholine in experimental cutaneous leishmaniasis.J Antimicrob Chemother 78: 1723–1731.
-
8.
Fortin A, Hendrickx S, Yardley V, Cos P, Jansen H, Maes L, 2012. Efficacy and tolerability of oleylphosphocholine (OlPC) in a laboratory model of visceral leishmaniasis. J Antimicrob Chemother 67: 2707–2712.
-
9.
Hernández L, Gálvez R, Montoya A, Checa R, Bello A, Bosschaerts T, Jansen H, Rupérez C, Fortin A, Miró G, 2014. First study on efficacy and tolerability of a new alkylphosphocholine molecule (oleylphosphocholine-OlPC) in the treatment of canine leishmaniosis due to Leishmania infantum. Parasitol Res 113: 157–164.
-
10.
Solcà MS et al., 2016. Circulating biomarkers of immune activation, oxidative stress and inflammation characterize severe canine visceral leishmaniasis. Sci Rep 6: 32619.
-
11.
Barrouin-Melo SM, Larangeira DF, de Andrade Filho FA, Trigo J, Julião FS, Franke CR, Palis Aguiar PH, Conrado dos-Santos WL, Pontes-de-Carvalho L, 2006. Can spleen aspirations be safely used for the parasitological diagnosis of canine visceral leishmaniosis? A study on assymptomatic and polysymptomatic animals. Vet J 171: 331–339.
-
12.
Rampazzo RCP, Solcà MDS, Santos LCS, Pereira LN, Guedes JCO Jr., Veras PST, Fraga DBM, Krieger MA, Costa ADT, 2017. A ready-to-use duplex qPCR to detect Leishmania infantum DNA in naturally infected dogs. Vet Parasitol 246: 100–107.
-
13.
Sindermann H, Engel J, 2006. Development of miltefosine as an oral treatment for leishmaniasis. Trans R Soc Trop Med Hyg 100 Suppl 1: S17–S20.
-
14.
Woerly V, Maynard L, Sanquer A, Eun H-M, 2009. Clinical efficacy and tolerance of miltefosine in the treatment of canine leishmaniosis. Parasitol Res 105: 463–469.
-
15.
Nogueira F, Avino V, Galvis-Ovallos F, Pereira-Chioccola V, Batistella M, Paula M, Romariz M, Molla L, Menz I, 2019. Use of miltefosine to treat canine visceral leishmaniasis caused by Leishmania infantum in Brazil. Parasit Vectors 12: 79.
-
16.
Ramos R, Giannelii A, Fasquelle F, Scuoptto A, Betbeder D, 2023. Effective immuno-therapeutic treatment of Canine Leishmaniasis. PLoS Negl Trop Dis 17: e0011360.
-
17.
Miró G, Oliva G, Cruz I, Cañavate C, Mortarino M, Vischer C, Bianciardi P, 2009. Multicentric, controlled clinical study to evaluate effectiveness and safety of miltefosine and allopurinol for canine leishmaniosis. Vet Dermatol 20: 397–404.
-
18.
Manna L, Corso R, Galiero G, Cerrone A, Muzj P, Gravino AE, 2015. Long-term follow-up of dogs with leishmaniosis treated with meglumine antimoniate plus allopurinol versus miltefosine plus allopurinol. Parasit Vectors 8: 289.
-
19.
Vaz T, Quareswma P, Rego F, Souza C, Fontes G, Gontijo C, 2023. Clinical and laboratory response of domiciled dogs with visceral leishmaniasis treated with miltefosine and allopurinol. Trop Med Infect Dis 8: 472.
-
20.
Gizzarelli M, Foglia Manzillo V, Inglese A, Montagnaro S, Oliva G, 2023. Retrospective long-term evaluation of miltefosine-allopurinol treatment in canine leishmaniosis. Pathogens 12: 864.
-
21.
Dantas-Torres F et al., 2019. Canine leishmaniasis control in the context of one health. Emerg Infect Dis 25: 1–4.
-
22.
Andrade HM et al., 2011. Evaluation of miltefosine for the treatment of dogs naturally infected with L. infantum (=L. chagasi) in Brazil. Vet Parasitol 181: 83–90.
| Past two years | Past Year | Past 30 Days | |
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| Abstract Views | 20079 | 20079 | 672 |
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| PDF Downloads | 42 | 42 | 17 |
Oleylphosphocholine versus Miltefosine for Canine Leishmaniasis
Isadora Lima
isadoraslima@hotmail.com
Isadora Lima
Fiocruz, Gonçalo Moniz Institute, Salvador, Brazil;
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Deborah Fraga
Deborah Fraga
Fiocruz, Gonçalo Moniz Institute, Salvador, Brazil;
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Jonathan Berman
Jonathan Berman
AB Foundation for Medical Research, North Bethesda, Maryland
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ABSTRACT.
Oleylphosphocholine (OlPC) is a miltefosine derivative that is more effective than miltefosine against Leishmania infections in rodent models. Because canines are a natural host for Leishmania, the improved treatment of canine leishmaniasis is essential both for veterinary medicine and as a large animal model for clinical development. Oleylphosphocholine, at a dosage of 4 mg/kg/day for 28 days, was compared with the approved canine regimen of miltefosine at a dosage of 2 mg/kg/day for 28 days in 33 naturally infected Brazilian dogs (17 randomly assigned to receive OlPC versus 16 designated to receive miltefosine). The animals were followed for 5 months posttreatment. The primary endpoint was the clinical score, which was calculated as the sum of scores for each of 23 clinical parameters graded 0 (normal), 1 (somewhat abnormal), or 2 (markedly abnormal) by a blinded observer. A higher clinical score signified more severe disease. The mean (SD) clinical scores for the OlPC versus miltefosine groups are as follows: pretherapy, 10.1 (5.6) versus 7.7 (4.5; P = 0.19); 3 months posttherapy, 4.3 (4.1) versus 9.5 (4.9; P <0.01); 5 months posttherapy, 3.9 (3.8) versus 8.9 (4.7; P <0.01). Scores for lymph nodes, ear crusts, and splenic parasites were statistically lower for the OlPC group versus the miltefosine group, suggesting that both visceral and cutaneous parameters contributed to OlPC’s statistically greater efficacy. One OlPC animal, with minimal splenic parasites pretreatment and zero parasites at the end of treatment, died of kidney failure due to immune-complex deposition, which was presumably already present pretreatment. The increase in blood creatinine values observed in OlPC animals warrants further study in future experiments. The superior clinical effect of OlPC in comparison to miltefosine in this canine study primes OlPC for development as an oral treatment for canine and human leishmaniasis.
Author Notes
Financial support: Grant from the
Disclosures: J. Berman is on the Scientific Advisory Board of Oblita Therapeutics, the sponsor of oleylphosphocholine, and is an officer of the AB Foundation. The experiments were conducted in accordance with Fiocruz standards for animal manipulation and experimentation (http://www.castelo.fiocruz.br/vpplr/comissoes_camaras-tecnicas/Manual_procedimentos.pdf) and the law on animal experimentation, Law N° 11.794, of October 8, 2008 (http://www.planalto.gov.br/ccivil_03/_ato2007-2010/2008/lei/l11794.htm). This study was approved by the Animal Research Ethics Committee of CPqGM-FIOCRUZ (CEUA no. 009/2020).
Current contact information: Isadora Lima and Deborah Fraga, Fiocruz, Gonçalo Moniz Institute, Salvador, Brazil, E-mails: isadoraslima@hotmail.com and deborah.fraga@fiocruz.br. Jonathan Berman, AB Foundation for Medical Research, North Bethesda, MD, E-mail: jbe9320457@aol.com.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Foglia Manzillo V, Di Muccio T, Cappiello S, Scalone A, Paparcone R, Fiorentino E, Gizzarelli M, Gramiccia M, Gradoni L, Oliva G, 2013. Prospective study on the incidence and progression of clinical signs in naive dogs naturally infected by Leishmania infantum. PLoS Negl Trop Dis 7: e2225.
-
2.
Solano-Gallego L, Miró G, Koutinas A, Cardoso L, Pennisi MG, Ferrer L, Bourdeau P, Oliva G, Baneth G; The LeishVet Group, 2011. LeishVet guidelines for the practical management of canine leishmaniosis. Parasit Vectors 4: 86.
-
3.
Frézard F, Demicheli C, Ribeiro RR, 2009. Pentavalent antimonials: New perspectives for old drugs. Molecules 14: 2317–2336.
-
4.
Miltefosine labelAvailable at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/204684s006lbl.pdf. Accessed January 8, 2025.
-
5.
Ministério da Agricultura e Pecuária, 2016. Nota técnica no 11/2016/CPV/DFIP/SDA/GM/MAPA. Available at: https://Www.Gov.Br/Agricultura/Pt-Br/Assuntos/Insumos-Agropecuarios/Insumos-Pecuarios/Produtos-Veterinarios/Legislacao-1/Notas-Tecnicas/Nota-Tecnica-No-11-2016-Cpv-Dfip-Sda-Gm-Mapa-de-1-09-2016.Pdf. Accessed January 8, 2025.
-
6.
Fortin A, Caridha DP, Leed S, Ngundam F, Sena J, Bosschaerts T, Parriott S, Hickman MR, Hudson TH, Grogl M, 2014. Direct comparison of the efficacy and safety of oral treatments with oleylphosphocholine (OlPC) and miltefosine in a mouse model of L. major cutaneous leishmaniasis. PLoS Negl Trop Dis 8: e3144.
-
7.
Van Bocxlaer K, Dixon J, Platteeuw JJ, Van Den Heuvel D, Mcarthur KN, Harris A, Alavijeh M, Croft SL, Yardley VJ, 2023. Efficacy of oleylphosphocholine in experimental cutaneous leishmaniasis.J Antimicrob Chemother 78: 1723–1731.
-
8.
Fortin A, Hendrickx S, Yardley V, Cos P, Jansen H, Maes L, 2012. Efficacy and tolerability of oleylphosphocholine (OlPC) in a laboratory model of visceral leishmaniasis. J Antimicrob Chemother 67: 2707–2712.
-
9.
Hernández L, Gálvez R, Montoya A, Checa R, Bello A, Bosschaerts T, Jansen H, Rupérez C, Fortin A, Miró G, 2014. First study on efficacy and tolerability of a new alkylphosphocholine molecule (oleylphosphocholine-OlPC) in the treatment of canine leishmaniosis due to Leishmania infantum. Parasitol Res 113: 157–164.
-
10.
Solcà MS et al., 2016. Circulating biomarkers of immune activation, oxidative stress and inflammation characterize severe canine visceral leishmaniasis. Sci Rep 6: 32619.
-
11.
Barrouin-Melo SM, Larangeira DF, de Andrade Filho FA, Trigo J, Julião FS, Franke CR, Palis Aguiar PH, Conrado dos-Santos WL, Pontes-de-Carvalho L, 2006. Can spleen aspirations be safely used for the parasitological diagnosis of canine visceral leishmaniosis? A study on assymptomatic and polysymptomatic animals. Vet J 171: 331–339.
-
12.
Rampazzo RCP, Solcà MDS, Santos LCS, Pereira LN, Guedes JCO Jr., Veras PST, Fraga DBM, Krieger MA, Costa ADT, 2017. A ready-to-use duplex qPCR to detect Leishmania infantum DNA in naturally infected dogs. Vet Parasitol 246: 100–107.
-
13.
Sindermann H, Engel J, 2006. Development of miltefosine as an oral treatment for leishmaniasis. Trans R Soc Trop Med Hyg 100 Suppl 1: S17–S20.
-
14.
Woerly V, Maynard L, Sanquer A, Eun H-M, 2009. Clinical efficacy and tolerance of miltefosine in the treatment of canine leishmaniosis. Parasitol Res 105: 463–469.
-
15.
Nogueira F, Avino V, Galvis-Ovallos F, Pereira-Chioccola V, Batistella M, Paula M, Romariz M, Molla L, Menz I, 2019. Use of miltefosine to treat canine visceral leishmaniasis caused by Leishmania infantum in Brazil. Parasit Vectors 12: 79.
-
16.
Ramos R, Giannelii A, Fasquelle F, Scuoptto A, Betbeder D, 2023. Effective immuno-therapeutic treatment of Canine Leishmaniasis. PLoS Negl Trop Dis 17: e0011360.
-
17.
Miró G, Oliva G, Cruz I, Cañavate C, Mortarino M, Vischer C, Bianciardi P, 2009. Multicentric, controlled clinical study to evaluate effectiveness and safety of miltefosine and allopurinol for canine leishmaniosis. Vet Dermatol 20: 397–404.
-
18.
Manna L, Corso R, Galiero G, Cerrone A, Muzj P, Gravino AE, 2015. Long-term follow-up of dogs with leishmaniosis treated with meglumine antimoniate plus allopurinol versus miltefosine plus allopurinol. Parasit Vectors 8: 289.
-
19.
Vaz T, Quareswma P, Rego F, Souza C, Fontes G, Gontijo C, 2023. Clinical and laboratory response of domiciled dogs with visceral leishmaniasis treated with miltefosine and allopurinol. Trop Med Infect Dis 8: 472.
-
20.
Gizzarelli M, Foglia Manzillo V, Inglese A, Montagnaro S, Oliva G, 2023. Retrospective long-term evaluation of miltefosine-allopurinol treatment in canine leishmaniosis. Pathogens 12: 864.
-
21.
Dantas-Torres F et al., 2019. Canine leishmaniasis control in the context of one health. Emerg Infect Dis 25: 1–4.
-
22.
Andrade HM et al., 2011. Evaluation of miltefosine for the treatment of dogs naturally infected with L. infantum (=L. chagasi) in Brazil. Vet Parasitol 181: 83–90.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 20079 | 20079 | 672 |
| Full Text Views | 54 | 54 | 10 |
| PDF Downloads | 42 | 42 | 17 |