In Vivo Antileishmanial Efficacy of Miltefosine Against Leishmania (Leishmania) amazonensis
Leishmaniasis, a disease caused by parasites of the Leishmania genus, constitutes a significant health and social problem in many countries and is increasing worldwide. The conventional treatment, meglumine antimoniate (MA), presents numerous disadvantages, including invasiveness, toxicity, and freq...
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| Veröffentlicht in: | The Journal of parasitology 2014-12, Vol.100 (6), p.840-847 |
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| creator | García Bustos, María F Barrio, Alejandra Prieto, Gabriela G de Raspi, Emma M Cimino, Rubén O Cardozo, Rubén M Parada, Luis A Yeo, Matthew Soto, Jaime Uncos, Delfor A Parodi, Cecilia Basombrío, Miguel A |
| description | Leishmaniasis, a disease caused by parasites of the Leishmania genus, constitutes a significant health and social problem in many countries and is increasing worldwide. The conventional treatment, meglumine antimoniate (MA), presents numerous disadvantages, including invasiveness, toxicity, and frequent therapeutic failure, justifying the attempts at finding alternatives to the first-line therapy. We have studied the comparative long-term efficacy of MA against miltefosine (MF) in Leishmania infection in experimental mice. The criteria for efficacy evaluation were footpad lesion size, anti-Leishmania antibodies level, histopathology of the site of inoculation (right footpad, RFP), splenic index (SI), and the presence of parasites in RFP, spleen, and liver, determined by polymerase chain reaction (PCR). Swiss mice, infected with Leishmania (Leishmania) amazonensis were treated, at different time points (5 and 40 days after infection) with either MA or MF. The efficacy of MF was better than that of MA for inhibiting lesions and for reducing tissue damage and presence/load of amastigotes in spleen and liver. Moreover, early administration of MF produced a clear reduction in splenomegaly and was equal in reducing antibody titles in comparison with MA. Our results demonstrated that MF is an effective and safe therapeutic alternative for leishmaniasis by L. (L.) amazonensis and is more efficacious than MA. |
| doi_str_mv | 10.1645/13-376.1 |
| format | Article |
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The conventional treatment, meglumine antimoniate (MA), presents numerous disadvantages, including invasiveness, toxicity, and frequent therapeutic failure, justifying the attempts at finding alternatives to the first-line therapy. We have studied the comparative long-term efficacy of MA against miltefosine (MF) in Leishmania infection in experimental mice. The criteria for efficacy evaluation were footpad lesion size, anti-Leishmania antibodies level, histopathology of the site of inoculation (right footpad, RFP), splenic index (SI), and the presence of parasites in RFP, spleen, and liver, determined by polymerase chain reaction (PCR). Swiss mice, infected with Leishmania (Leishmania) amazonensis were treated, at different time points (5 and 40 days after infection) with either MA or MF. The efficacy of MF was better than that of MA for inhibiting lesions and for reducing tissue damage and presence/load of amastigotes in spleen and liver. Moreover, early administration of MF produced a clear reduction in splenomegaly and was equal in reducing antibody titles in comparison with MA. Our results demonstrated that MF is an effective and safe therapeutic alternative for leishmaniasis by L. (L.) amazonensis and is more efficacious than MA.</description><identifier>ISSN: 0022-3395</identifier><identifier>EISSN: 1937-2345</identifier><identifier>DOI: 10.1645/13-376.1</identifier><identifier>PMID: 25014108</identifier><language>eng</language><publisher>United States: American Society of Parasitologists</publisher><subject>Amastigotes ; Animals ; Antibodies ; Antiprotozoal Agents - administration & dosage ; Antiprotozoal Agents - pharmacology ; Antiprotozoal Agents - therapeutic use ; Dosage ; histopathology ; Infections ; Leishmania amazonensis ; Leishmania mexicana - drug effects ; Leishmaniasis ; Leishmaniasis, Cutaneous - drug therapy ; Leishmaniasis, Cutaneous - parasitology ; Leishmaniasis, Cutaneous - pathology ; Lesions ; Liver ; Male ; Medical treatment ; Meglumine - administration & dosage ; Meglumine - pharmacology ; Meglumine - therapeutic use ; Mice ; Organometallic Compounds - administration & dosage ; Organometallic Compounds - pharmacology ; Organometallic Compounds - therapeutic use ; Parasites ; Phosphorylcholine - administration & dosage ; Phosphorylcholine - analogs & derivatives ; Phosphorylcholine - pharmacology ; Phosphorylcholine - therapeutic use ; polymerase chain reaction ; Spleen ; Spleen - pathology ; splenomegaly ; therapeutics ; THERAPEUTICS-DIAGNOSTICS ; toxicity</subject><ispartof>The Journal of parasitology, 2014-12, Vol.100 (6), p.840-847</ispartof><rights>American Society of Parasitologists 2014</rights><rights>Copyright Allen Press Publishing Services Dec 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b421t-17c6dede2e637a9b4f0a8279f4ffec6ca8347dafb7a4d4532caa1f9c5a39db1a3</citedby><cites>FETCH-LOGICAL-b421t-17c6dede2e637a9b4f0a8279f4ffec6ca8347dafb7a4d4532caa1f9c5a39db1a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/24625288$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/24625288$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,778,782,801,27907,27908,58000,58233</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25014108$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>García Bustos, María F</creatorcontrib><creatorcontrib>Barrio, Alejandra</creatorcontrib><creatorcontrib>Prieto, Gabriela G</creatorcontrib><creatorcontrib>de Raspi, Emma M</creatorcontrib><creatorcontrib>Cimino, Rubén O</creatorcontrib><creatorcontrib>Cardozo, Rubén M</creatorcontrib><creatorcontrib>Parada, Luis A</creatorcontrib><creatorcontrib>Yeo, Matthew</creatorcontrib><creatorcontrib>Soto, Jaime</creatorcontrib><creatorcontrib>Uncos, Delfor A</creatorcontrib><creatorcontrib>Parodi, Cecilia</creatorcontrib><creatorcontrib>Basombrío, Miguel A</creatorcontrib><title>In Vivo Antileishmanial Efficacy of Miltefosine Against Leishmania (Leishmania) amazonensis</title><title>The Journal of parasitology</title><addtitle>J Parasitol</addtitle><description>Leishmaniasis, a disease caused by parasites of the Leishmania genus, constitutes a significant health and social problem in many countries and is increasing worldwide. The conventional treatment, meglumine antimoniate (MA), presents numerous disadvantages, including invasiveness, toxicity, and frequent therapeutic failure, justifying the attempts at finding alternatives to the first-line therapy. We have studied the comparative long-term efficacy of MA against miltefosine (MF) in Leishmania infection in experimental mice. The criteria for efficacy evaluation were footpad lesion size, anti-Leishmania antibodies level, histopathology of the site of inoculation (right footpad, RFP), splenic index (SI), and the presence of parasites in RFP, spleen, and liver, determined by polymerase chain reaction (PCR). Swiss mice, infected with Leishmania (Leishmania) amazonensis were treated, at different time points (5 and 40 days after infection) with either MA or MF. The efficacy of MF was better than that of MA for inhibiting lesions and for reducing tissue damage and presence/load of amastigotes in spleen and liver. Moreover, early administration of MF produced a clear reduction in splenomegaly and was equal in reducing antibody titles in comparison with MA. Our results demonstrated that MF is an effective and safe therapeutic alternative for leishmaniasis by L. (L.) amazonensis and is more efficacious than MA.</description><subject>Amastigotes</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antiprotozoal Agents - administration & dosage</subject><subject>Antiprotozoal Agents - pharmacology</subject><subject>Antiprotozoal Agents - therapeutic use</subject><subject>Dosage</subject><subject>histopathology</subject><subject>Infections</subject><subject>Leishmania amazonensis</subject><subject>Leishmania mexicana - drug effects</subject><subject>Leishmaniasis</subject><subject>Leishmaniasis, Cutaneous - drug therapy</subject><subject>Leishmaniasis, Cutaneous - parasitology</subject><subject>Leishmaniasis, Cutaneous - pathology</subject><subject>Lesions</subject><subject>Liver</subject><subject>Male</subject><subject>Medical treatment</subject><subject>Meglumine - administration & dosage</subject><subject>Meglumine - pharmacology</subject><subject>Meglumine - therapeutic use</subject><subject>Mice</subject><subject>Organometallic Compounds - administration & dosage</subject><subject>Organometallic Compounds - pharmacology</subject><subject>Organometallic Compounds - therapeutic use</subject><subject>Parasites</subject><subject>Phosphorylcholine - administration & dosage</subject><subject>Phosphorylcholine - analogs & derivatives</subject><subject>Phosphorylcholine - pharmacology</subject><subject>Phosphorylcholine - therapeutic use</subject><subject>polymerase chain reaction</subject><subject>Spleen</subject><subject>Spleen - pathology</subject><subject>splenomegaly</subject><subject>therapeutics</subject><subject>THERAPEUTICS-DIAGNOSTICS</subject><subject>toxicity</subject><issn>0022-3395</issn><issn>1937-2345</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kc1L7DAUxYMoOo6C_4AaEB66qOY77XIQ31MYceHHxkW5TRPN0CbadAT961-HUQcEF5d74fw4HM5FaI-SU6qEPKM841qd0jU0ogXXGeNCrqMRIYxlnBdyC22nNCOEyGE20RaThApK8hF6vAr4wb9FPAm9b6xPzy0EDw2-cM4bMO84Onztm966mHywePIEPqQeT79ZfLy6TzC08BGDDcmnHbThoEl293OP0f3fi7vzy2x68-_qfDLNKsFon1FtVG1ry6ziGopKOAI504UTzlmjDORc6BpcpUHUQnJmAKgrjARe1BUFPkbHS9-XLr7OberL1idjmwaCjfNUUiWFUioX-YAe_UBncd6FId1ACaaU1JKsDE0XU-qsK18630L3XlKy4GRJeTkUPqwxOvg0nFetrb_Br4YHYH8JzFIfu5UuFJMsX-iHS91BLOGp86m8v2WEysXzVK4Xaf4sicrHodnfs_wHePSZbA</recordid><startdate>20141201</startdate><enddate>20141201</enddate><creator>García Bustos, María F</creator><creator>Barrio, Alejandra</creator><creator>Prieto, Gabriela G</creator><creator>de Raspi, Emma M</creator><creator>Cimino, Rubén O</creator><creator>Cardozo, Rubén M</creator><creator>Parada, Luis A</creator><creator>Yeo, Matthew</creator><creator>Soto, Jaime</creator><creator>Uncos, Delfor A</creator><creator>Parodi, Cecilia</creator><creator>Basombrío, Miguel A</creator><general>American Society of Parasitologists</general><general>Allen Press Inc</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7SN</scope><scope>7SS</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope></search><sort><creationdate>20141201</creationdate><title>In Vivo Antileishmanial Efficacy of Miltefosine Against Leishmania (Leishmania) amazonensis</title><author>García Bustos, María F ; Barrio, Alejandra ; Prieto, Gabriela G ; de Raspi, Emma M ; Cimino, Rubén O ; Cardozo, Rubén M ; Parada, Luis A ; Yeo, Matthew ; Soto, Jaime ; Uncos, Delfor A ; Parodi, Cecilia ; Basombrío, Miguel A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b421t-17c6dede2e637a9b4f0a8279f4ffec6ca8347dafb7a4d4532caa1f9c5a39db1a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Amastigotes</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antiprotozoal Agents - administration & dosage</topic><topic>Antiprotozoal Agents - pharmacology</topic><topic>Antiprotozoal Agents - therapeutic use</topic><topic>Dosage</topic><topic>histopathology</topic><topic>Infections</topic><topic>Leishmania amazonensis</topic><topic>Leishmania mexicana - drug effects</topic><topic>Leishmaniasis</topic><topic>Leishmaniasis, Cutaneous - drug therapy</topic><topic>Leishmaniasis, Cutaneous - parasitology</topic><topic>Leishmaniasis, Cutaneous - pathology</topic><topic>Lesions</topic><topic>Liver</topic><topic>Male</topic><topic>Medical treatment</topic><topic>Meglumine - administration & dosage</topic><topic>Meglumine - pharmacology</topic><topic>Meglumine - therapeutic use</topic><topic>Mice</topic><topic>Organometallic Compounds - administration & dosage</topic><topic>Organometallic Compounds - pharmacology</topic><topic>Organometallic Compounds - therapeutic use</topic><topic>Parasites</topic><topic>Phosphorylcholine - administration & dosage</topic><topic>Phosphorylcholine - 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The conventional treatment, meglumine antimoniate (MA), presents numerous disadvantages, including invasiveness, toxicity, and frequent therapeutic failure, justifying the attempts at finding alternatives to the first-line therapy. We have studied the comparative long-term efficacy of MA against miltefosine (MF) in Leishmania infection in experimental mice. The criteria for efficacy evaluation were footpad lesion size, anti-Leishmania antibodies level, histopathology of the site of inoculation (right footpad, RFP), splenic index (SI), and the presence of parasites in RFP, spleen, and liver, determined by polymerase chain reaction (PCR). Swiss mice, infected with Leishmania (Leishmania) amazonensis were treated, at different time points (5 and 40 days after infection) with either MA or MF. The efficacy of MF was better than that of MA for inhibiting lesions and for reducing tissue damage and presence/load of amastigotes in spleen and liver. Moreover, early administration of MF produced a clear reduction in splenomegaly and was equal in reducing antibody titles in comparison with MA. Our results demonstrated that MF is an effective and safe therapeutic alternative for leishmaniasis by L. (L.) amazonensis and is more efficacious than MA.</abstract><cop>United States</cop><pub>American Society of Parasitologists</pub><pmid>25014108</pmid><doi>10.1645/13-376.1</doi><tpages>8</tpages></addata></record> |
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| ispartof | The Journal of parasitology, 2014-12, Vol.100 (6), p.840-847 |
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| subjects | Amastigotes Animals Antibodies Antiprotozoal Agents - administration & dosage Antiprotozoal Agents - pharmacology Antiprotozoal Agents - therapeutic use Dosage histopathology Infections Leishmania amazonensis Leishmania mexicana - drug effects Leishmaniasis Leishmaniasis, Cutaneous - drug therapy Leishmaniasis, Cutaneous - parasitology Leishmaniasis, Cutaneous - pathology Lesions Liver Male Medical treatment Meglumine - administration & dosage Meglumine - pharmacology Meglumine - therapeutic use Mice Organometallic Compounds - administration & dosage Organometallic Compounds - pharmacology Organometallic Compounds - therapeutic use Parasites Phosphorylcholine - administration & dosage Phosphorylcholine - analogs & derivatives Phosphorylcholine - pharmacology Phosphorylcholine - therapeutic use polymerase chain reaction Spleen Spleen - pathology splenomegaly therapeutics THERAPEUTICS-DIAGNOSTICS toxicity |
| title | In Vivo Antileishmanial Efficacy of Miltefosine Against Leishmania (Leishmania) amazonensis |
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