{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:29:51Z","timestamp":1787016591081,"version":"build-2736575974"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,1]]},"abstract":"ABSTRACT<\/jats:title>\n \n Treatment failure and parasite drug susceptibility in dermal leishmaniasis caused by\n Leishmania<\/jats:named-content>\n (\n Viannia<\/jats:named-content>\n ) species are poorly understood. Prospective evaluation of drug susceptibility of strains isolated from individual patients before drug exposure and at clinical failure allows intrinsic and acquired differences in susceptibility to be discerned and analyzed. To determine whether intrinsic susceptibility or loss of susceptibility to miltefosine contributed to treatment failure, we evaluated the miltefosine susceptibility of intracellular amastigotes and promastigotes of six\n Leishmania<\/jats:named-content>\n (\n Viannia<\/jats:named-content>\n )\n braziliensis<\/jats:named-content>\n and six\n Leishmania<\/jats:named-content>\n (\n Viannia<\/jats:named-content>\n )\n panamensis<\/jats:named-content>\n strains isolated sequentially, at diagnosis and treatment failure, from two children and four adults \u226555 years old with concurrent conditions. Four patients presented only cutaneous lesions, one had mucosal disease, and one had disseminated mucocutaneous disease. Expression of the\n Leishmania<\/jats:named-content>\n drug transporter genes\n abca2<\/jats:italic>\n ,\n abca3<\/jats:italic>\n ,\n abcc2<\/jats:italic>\n ,\n abcc3<\/jats:italic>\n ,\n abcg4<\/jats:italic>\n ,\n abcg6<\/jats:italic>\n , and\n LbMT<\/jats:italic>\n was evaluated by quantitative reverse transcription-PCR (qRT-PCR). Intracellular amastigotes (median 50% effective concentration [EC\n 50<\/jats:sub>\n ], 10.7 \u03bcmol\/liter) were more susceptible to miltefosine than promastigotes (median EC\n 50<\/jats:sub>\n , 55.3 \u03bcmol\/liter) (\n P<\/jats:italic>\n < 0.0001). Loss of susceptibility at failure, demonstrated by a miltefosine EC\n 50<\/jats:sub>\n of >32 \u03bcmol\/liter (the upper limit of intracellular amastigote assay), occurred in\n L. panamensis<\/jats:named-content>\n infection in a child and in\n L. braziliensis<\/jats:named-content>\n infection in an adult and was accompanied by decreased expression of the miltefosine transporter LbMT (LbMT\/\u03b2-tubulin, 0.42- to 0.26-fold [\n P<\/jats:italic>\n = 0.039] and 0.70- to 0.57-fold [\n P<\/jats:italic>\n = 0.009], respectively). LbMT gene polymorphisms were not associated with susceptibility phenotype.\n Leishmania<\/jats:named-content>\n ABCA3 transporter expression was inversely correlated with miltefosine susceptibility (\n r<\/jats:italic>\n = \u22120.605;\n P<\/jats:italic>\n = 0.037). Loss of susceptibility is one of multiple factors involved in failure of miltefosine treatment in dermal leishmaniasis.\n <\/jats:p>","DOI":"10.1128\/aac.01023-13","type":"journal-article","created":{"date-parts":[[2013,10,21]],"date-time":"2013-10-21T22:41:14Z","timestamp":1382395274000},"page":"144-152","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":49,"title":["Treatment Failure and Miltefosine Susceptibility in Dermal Leishmaniasis Caused by Leishmania Subgenus Viannia Species"],"prefix":"10.1128","volume":"58","author":[{"given":"Ricardo","family":"Obonaga","sequence":"first","affiliation":[{"name":"Centro Internacional de Entrenamiento e Investigaciones M\u00e9dicas (CIDEIM), Cali, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga Luc\u00eda","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Centro Internacional de Entrenamiento e Investigaciones M\u00e9dicas (CIDEIM), Cali, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Valderrama","sequence":"additional","affiliation":[{"name":"Centro Internacional de Entrenamiento e Investigaciones M\u00e9dicas (CIDEIM), Cali, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa Consuelo","family":"Rubiano","sequence":"additional","affiliation":[{"name":"Centro Internacional de Entrenamiento e Investigaciones M\u00e9dicas (CIDEIM), Cali, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria del Mar","family":"Castro","sequence":"additional","affiliation":[{"name":"Centro Internacional de Entrenamiento e Investigaciones M\u00e9dicas (CIDEIM), Cali, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Claudia","family":"Barrera","sequence":"additional","affiliation":[{"name":"Centro Internacional de Entrenamiento e Investigaciones M\u00e9dicas (CIDEIM), Cali, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Adelaida","family":"Gomez","sequence":"additional","affiliation":[{"name":"Centro Internacional de Entrenamiento e Investigaciones M\u00e9dicas (CIDEIM), Cali, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Gore Saravia","sequence":"additional","affiliation":[{"name":"Centro Internacional de Entrenamiento e Investigaciones M\u00e9dicas (CIDEIM), Cali, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.6.8.1381"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/383321"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2010.10-0060"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir816"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3156.2001.00795.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00014-08"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2005.73.272"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01694-08"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308352200"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00580-11"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1086\/313805"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1086\/345476"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1985.34.714"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(00)00270-X"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00216-12"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/172.4.1157"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05653.x"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00587-08"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001657"},{"key":"e_1_3_2_21_2","first-page":"697","volume-title":"Proceedings of European Grid Conference 2005","volume":"2","author":"Rakotomalala R","year":"2005","unstructured":"RakotomalalaR. 2005. 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