{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:46:38Z","timestamp":1790174798193,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0006225","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T00:00:00Z","timestamp":1521072000000}}],"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2018,2,26]],"date-time":"2018-02-26T00:00:00Z","timestamp":1519603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"DOI":"10.1371\/journal.pntd.0006225","type":"journal-article","created":{"date-parts":[[2018,2,26]],"date-time":"2018-02-26T13:25:40Z","timestamp":1519651540000},"page":"e0006225","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["Failure of fluconazole in treating cutaneous leishmaniasis caused by Leishmania guyanensis in the Brazilian Amazon: An open, nonrandomized phase 2 trial"],"prefix":"10.1371","volume":"12","author":[{"given":"Valeska Albuquerque","family":"Francesconi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6381-3584","authenticated-orcid":true,"given":"Fabio","family":"Francesconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajendranath","family":"Ramasawmy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo Adolfo Sierra","family":"Romero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria das Gra\u00e7as Costa","family":"Alecrim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2018,2,26]]},"reference":[{"key":"ref1","unstructured":"World Health O. Leishmaniasis\u2014Epidemiological situation2014 (accessed May 7, 2017)."},{"issue":"11","key":"ref2","first-page":"1","article-title":"Exploring Spatial and Temporal Distribution of Cutaneous Leishmaniasis in the Americas, 2001\u20132011","volume":"10","author":"AN Maia-Elkhoury","year":"2016","journal-title":"PLoS neglected tropical diseases"},{"key":"ref3","unstructured":"World Health O. Brazil, Leishmaniasis cutaneous and mucosa2015 (accessed May 7, 2017)."},{"issue":"1","key":"ref4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/clinids\/22.1.1","article-title":"Clinical spectrum of Leishmaniasis","volume":"22","author":"RD Pearson","year":"1996","journal-title":"Clinical infectious diseases"},{"issue":"3","key":"ref5","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1590\/S0074-02761994000300027","article-title":"The dermal leishmaniases of Brazil, with special reference to the eco-epidemiology of the disease in Amazonia","volume":"89","author":"R Lainson","year":"1994","journal-title":"Memorias do Instituto Oswaldo Cruz"},{"issue":"1","key":"ref6","doi-asserted-by":"crossref","first-page":"81","DOI":"10.4269\/ajtmh.2006.74.81","article-title":"Ecology of the <italic>Leishmania<\/italic> species in the Guianan ecoregion complex","volume":"74","author":"B Rotureau","year":"2006","journal-title":"The American Journal of Tropical Medicine and Hygiene"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s41182-017-0045-x","article-title":"Cutaneous leishmaniasis in French Guiana: revising epidemiology with PCR-RFLP","volume":"45","author":"S Simon","year":"2017","journal-title":"Tropical medicine and health"},{"issue":"9","key":"ref8","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1086\/319990","article-title":"Comparison of cutaneous leishmaniasis due to <italic>Leishmania (Viannia) braziliensis<\/italic> and <italic>L<\/italic>. <italic>(V<\/italic>.<italic>) guyanensis<\/italic> in Brazil: clinical findings and diagnostic approach","volume":"32","author":"GA Romero","year":"2001","journal-title":"Clinical infectious diseases: an official publication of the Infectious Diseases Society of America"},{"issue":"3","key":"ref9","doi-asserted-by":"crossref","first-page":"e980","DOI":"10.1371\/journal.pntd.0000980","article-title":"Mucosal Leishmaniasis caused by <italic>Leishmania (Viannia) braziliensis<\/italic> and <italic>Leishmania (Viannia)<\/italic> guyanensis in the Brazilian Amazon","volume":"5","author":"JA Guerra","year":"2011","journal-title":"PLoS neglected tropical diseases"},{"issue":"5","key":"ref10","doi-asserted-by":"crossref","first-page":"558","DOI":"10.4269\/ajtmh.2004.71.558","article-title":"Disseminated cutaneous leishmaniasis due to <italic>Leishmania guyanensis<\/italic>: case of a patient with 425 lesions","volume":"71","author":"P Couppie","year":"2004","journal-title":"The American journal of tropical medicine and hygiene"},{"issue":"12","key":"ref11","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1093\/cid\/ciw742","article-title":"Diagnosis and Treatment of Leishmaniasis: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH)","volume":"63","author":"N Aronson","year":"2016","journal-title":"Clinical infectious diseases"},{"issue":"2","key":"ref12","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.jaad.2009.06.088","article-title":"New World cutaneous leishmaniasis: updated review of current and future diagnosis and treatment","volume":"63","author":"P Mitropoulos","year":"2010","journal-title":"Journal of the American Academy of Dermatology"},{"issue":"6","key":"ref13","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1590\/S0365-05962011000600005","article-title":"A randomized clinical trial comparing meglumine antimoniate, pentamidine and amphotericin B for the treatment of cutaneous leishmaniasis by <italic>Leishmania guyanensis<\/italic>","volume":"86","author":"LO Neves","year":"2011","journal-title":"Anais brasileiros de dermatologia"},{"issue":"5","key":"ref14","doi-asserted-by":"crossref","first-page":"456","DOI":"10.4269\/ajtmh.2001.65.456","article-title":"Comparison of cutaneous leishmaniasis due to <italic>Leishmania (Viannia) braziliensis<\/italic> and <italic>L<\/italic>. <italic>(V<\/italic>.<italic>) guyanensis<\/italic> in Brazil: therapeutic response to meglumine antimoniate","volume":"65","author":"GA Romero","year":"2001","journal-title":"The American Journal of Tropical Medicine and Hygiene"},{"issue":"2","key":"ref15","doi-asserted-by":"crossref","first-page":"255","DOI":"10.4269\/ajtmh.2011.10-0155","article-title":"Randomized controlled clinical trial to access efficacy and safety of miltefosine in the treatment of cutaneous leishmaniasis caused by <italic>Leishmania (Viannia)<\/italic> guyanensis in Manaus, Brazil","volume":"84","author":"A Chrusciak-Talhari","year":"2011","journal-title":"The American Journal of Tropical Medicine and Hygiene"},{"issue":"4","key":"ref16","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1093\/infdis\/jir816","article-title":"Noninferiority of miltefosine versus meglumine antimoniate for cutaneous leishmaniasis in children","volume":"205","author":"LC Rubiano","year":"2012","journal-title":"The Journal of Infectious Diseases"},{"issue":"1","key":"ref17","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0166-6851(86)90145-3","article-title":"Effects of ketoconazole on sterol biosynthesis by <italic>Leishmania mexicana mexicana<\/italic> amastigotes in murine macrophage tumor cells","volume":"20","author":"JD Berman","year":"1986","journal-title":"Mol Biochem Parasitol"},{"issue":"3","key":"ref18","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1440-0960.2010.00642.x","article-title":"Cutaneous leishmaniasis in a child treated with oral fluconazole","volume":"51","author":"AV Sklavos","year":"2010","journal-title":"The Australasian Journal of Dermatology"},{"issue":"1","key":"ref19","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/pde.12321","article-title":"Cutaneous leishmaniasis: treatment with low-dose oral fluconazole with an excellent cosmetic result","volume":"32","author":"O Aerts","year":"2015","journal-title":"Pediatric dermatology"},{"issue":"7","key":"ref20","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1128\/JCM.41.7.3147-3153.2003","article-title":"Identification and differentiation of <italic>Leishmania<\/italic> species in clinical samples by PCR amplification of the miniexon sequence and subsequent restriction fragment length polymorphism analysis","volume":"41","author":"J Marfurt","year":"2003","journal-title":"Journal of Clinical Microbiology"},{"key":"ref21","unstructured":"Institute NC. Common Terminology Criteria for Adverse Events v4.0 (CTCAE). National Institutes of Health: National Cancer Institute, 2010."},{"issue":"3","key":"ref22","doi-asserted-by":"crossref","first-page":"e2130","DOI":"10.1371\/journal.pntd.0002130","article-title":"<italic>Methodology<\/italic> of clinical trials aimed at assessing interventions for cutaneous leishmaniasis","volume":"7","author":"P Olliaro","year":"2013","journal-title":"PLoS Neglected Tropical Diseases"},{"issue":"7","key":"ref23","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1093\/cid\/cir496","article-title":"High-dose oral fluconazole therapy effective for cutaneous leishmaniasis due to <italic>Leishmania (Vianna) braziliensis<\/italic>","volume":"53","author":"AQ Sousa","year":"2011","journal-title":"Clinical infectious diseases"},{"key":"ref24","unstructured":"Administration FaD. Guidance for Industry. Adaptive Design Clinical Trials for Drugs and Biologics. In: Services USDoHaH, editor. 2010."},{"issue":"3858","key":"ref25","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1126\/science.162.3858.1146","article-title":"2-Amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3, 4-thiadiazole: a new antimicrobial agent","volume":"162","author":"G Berkelhammer","year":"1968","journal-title":"Science"},{"issue":"6","key":"ref26","first-page":"495","article-title":"Trial of CIBA 32,644-Ba on visceral leishmaniasis in the hamster","volume":"40","author":"NS Mansour","year":"1965","journal-title":"The Journal of the Egyptian Public Health Association"},{"issue":"1","key":"ref27","first-page":"75","article-title":"Management of American mucocutaneous leishmaniasis using 1-(5-nitro-2-thiazolyl)-2-imidazolidinone","volume":"75","author":"TA Furtado","year":"1969","journal-title":"Hospital"},{"issue":"4","key":"ref28","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1590\/S0037-86821970000400004","article-title":"Tratamento da Leishmaniose Tegumentar Americana pelo Niridazol","volume":"IV","author":"MC Baranski","year":"1970","journal-title":"Revista da Sociedade Brasileira de Medicina Tropical"},{"issue":"3","key":"ref29","doi-asserted-by":"crossref","first-page":"566","DOI":"10.4269\/ajtmh.1981.30.566","article-title":"Activity of imidazoles against <italic>Leishmania tropica<\/italic> in human macrophage cultures","volume":"30","author":"JD Berman","year":"1981","journal-title":"The American Journal of Tropical Medicine and Hygiene"},{"issue":"1","key":"ref30","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/0035-9203(86)90239-7","article-title":"Failure to cure <italic>Leishmania braziliensis guyanensis<\/italic> cutaneous leishmaniasis with oral ketoconazole","volume":"80","author":"JP Dedet","year":"1986","journal-title":"Transactions of the Royal Society of Tropical Medicine and Hygiene"},{"issue":"1","key":"ref31","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/j.1365-2230.1986.tb00425.x","article-title":"Cutaneous leishmaniasis from Belize\u2014treatment with ketoconazole","volume":"11","author":"DS Jolliffe","year":"1986","journal-title":"Clinical and Experimental Dermatology"},{"issue":"2","key":"ref32","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/0002-9343(90)90292-L","article-title":"Efficacy of ketoconazole against <italic>Leishmania braziliensis panamensis<\/italic> cutaneous leishmaniasis","volume":"89","author":"RE Saenz","year":"1990","journal-title":"The American Journal of Medicine"},{"issue":"3","key":"ref33","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S1201-9712(00)90077-8","article-title":"Use of itraconazole in the treatment of mucocutaneous leishmaniasis: a pilot study","volume":"4","author":"VS Amato","year":"2000","journal-title":"International Journal of Infectious Diseases"},{"issue":"9","key":"ref34","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1111\/j.1365-4632.2004.02183.x","article-title":"Itraconazole in the treatment of New World mucocutaneous leishmaniasis","volume":"43","author":"M Calvopina","year":"2004","journal-title":"International Journal of Dermatology"},{"issue":"9027","key":"ref35","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/S0140-6736(05)64828-3","article-title":"Treatment of kala-azar with oral fluconazole","volume":"348","author":"S Sundar","year":"1996","journal-title":"Lancet"},{"issue":"12","key":"ref36","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1056\/NEJMoa011882","article-title":"Fluconazole for the treatment of cutaneous leishmaniasis caused by I","volume":"346","author":"AA Alrajhi","year":"2002","journal-title":"The New England Journal of Medicine"},{"issue":"3","key":"ref37","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.jaad.2010.04.014","article-title":"Superior efficacy of oral fluconazole 400 mg daily versus oral fluconazole 200 mg daily in the treatment of cutaneous <italic>Leishmania major<\/italic> infection: a randomized clinical trial","volume":"64","author":"M Emad","year":"2011","journal-title":"Journal of the American Academy of Dermatology"},{"issue":"145","key":"ref38","first-page":"1","article-title":"Adaptive trial designs: a review of barriers and opportunities","volume":"13","author":"AJ Kairalla","year":"2012","journal-title":"Trials"},{"issue":"1","key":"ref39","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/cid\/ciw662","article-title":"Fluconazole in the Treatment of Cutaneous Leishmaniasis Caused by <italic>Leishmania braziliensis<\/italic>: A Randomized Controlled Trial","volume":"64","author":"FV Prates","year":"2017","journal-title":"Clinical infectious diseases"},{"issue":"4","key":"ref40","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1093\/trstmh\/trt002","article-title":"Early enlargement of an ulcerated area during leishmaniasis treatment with meglumine antimoniate in Brazil","volume":"107","author":"GA Romero","year":"2013","journal-title":"Transactions of the Royal Society of Tropical Medicine and Hygiene"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0006225","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T00:00:00Z","timestamp":1521072000000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pntd.0006225","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T17:59:37Z","timestamp":1570816777000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0006225"}},"subtitle":[],"editor":[{"given":"Gregory","family":"Deye","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,2,26]]},"references-count":40,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2018,2,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0006225","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pntd.0006225","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,26]]}}}