{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T06:48:51Z","timestamp":1777445331878,"version":"3.51.4"},"reference-count":24,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"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":[[2015,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            In 2002 and 2006, respectively, miltefosine (MIL) and paromomycin (PMM) were licensed in the Indian subcontinent for treatment of visceral leishmaniasis; however, their future routine use might become jeopardized by the development of drug resistance. Although experimental selection of resistant strains\n            <jats:italic>in vitro<\/jats:italic>\n            has repeatedly been reported using the less relevant promastigote vector stage, the outcome of resistance selection on intracellular amastigotes was reported to be protocol and species dependent. To corroborate these\n            <jats:italic>in vitro<\/jats:italic>\n            findings, selection of resistance in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania donovani<\/jats:named-content>\n            and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania infantum<\/jats:named-content>\n            was achieved by successive treatment\/relapse cycles in infected Syrian golden hamsters. For PMM, resistant amastigotes were already obtained within 3 treatment\/relapse cycles, while their promastigotes retained full susceptibility, thereby sharing the same phenotypic characteristics as\n            <jats:italic>in vitro<\/jats:italic>\n            -generated PMM-resistant strains. For MIL, even five treatment\/relapse cycles failed to induce significant susceptibility changes in either species, which also corresponds with the\n            <jats:italic>in vitro<\/jats:italic>\n            observations where selection of an MIL-resistant phenotype proved to be quite challenging. In conclusion, these results argue for cautious use of PMM in the field to avoid rapid emergence of primary resistance and highlight the need for additional research on the mechanisms and dynamics of MIL resistance selection.\n          <\/jats:p>","DOI":"10.1128\/aac.00707-15","type":"journal-article","created":{"date-parts":[[2015,5,27]],"date-time":"2015-05-27T15:24:53Z","timestamp":1432740293000},"page":"4714-4718","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["<i>In Vivo<\/i>\n            Selection of Paromomycin and Miltefosine Resistance in Leishmania donovani and L. infantum in a Syrian Hamster Model"],"prefix":"10.1128","volume":"59","author":[{"given":"S.","family":"Hendrickx","sequence":"first","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Mondelaers","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Eberhardt","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Delputte","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Cos","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Maes","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"issue":"10","key":"e_1_3_2_2_2","first-page":"664, 666","article-title":"Kala-azar elimination programme in India","volume":"106","author":"Dhillon GP","year":"2008","unstructured":"Dhillon GP, Sharma SN, Nair B. 2008. 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