{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T04:55:10Z","timestamp":1773809710315,"version":"3.50.1"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T00:00:00Z","timestamp":1717459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T00:00:00Z","timestamp":1717459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"crossref","award":["6\/9-7(188)2018-ECDII"],"award-info":[{"award-number":["6\/9-7(188)2018-ECDII"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,6,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Post-kala-azar dermal leishmaniasis (PKDL) patients are a key source of\n              <jats:italic>Leishmania donovani<\/jats:italic>\n              parasites, hindering the goal of eliminating visceral leishmaniasis (VL). Monitoring treatment response and parasite susceptibility is essential due to increasing drug resistance. We assessed the drug susceptibility of PKDL isolates (\n              <jats:italic>n<\/jats:italic>\n              = 18) from pre-miltefosine (MIL) era (1997\u20132004) with isolates (\n              <jats:italic>n<\/jats:italic>\n              = 16) from the post-miltefosine era (2010\u20132019) and post-miltefosine treatment relapse isolates (\n              <jats:italic>n<\/jats:italic>\n              = 5) towards miltefosine and amphotericin B (AmB) at promastigote stage and towards sodium antimony gluconate (SAG) at amastigote stage. PKDL isolates were examined for mutation in gene-encoding AQP1 transporter, C26882T mutation on chromosome 24, and miltefosine-transporter (MT). PKDL isolates from the post-miltefosine era were significantly more susceptible to SAG than SAG-resistant isolates from the pre-miltefosine era (\n              <jats:italic>P<\/jats:italic>\n              = 0.0002). There was no significant difference in the susceptibility of parasites to miltefosine between pre- and post-miltefosine era isolates. The susceptibility of PKDL isolates towards AmB remained unchanged between the pre- and post-miltefosine era. However, the post-miltefosine era isolates had a higher IC\n              <jats:sub>50<\/jats:sub>\n              value towards AmB compared with PKDL relapse isolates. We did not find any association between AQP1 gene sequence variation and susceptibility to SAG, or between miltefosine susceptibility and single nucleotide polymorphisms (SNPs in the MT gene. This study demonstrates that recent isolates of\n              <jats:italic>Leishmania<\/jats:italic>\n              have resumed susceptibility to antimonials\n              <jats:italic>in vitro<\/jats:italic>\n              . The study also offers significant insights into the intrinsic drug susceptibility of\n              <jats:italic>Leishmania<\/jats:italic>\n              parasites over the past two decades, covering the period before the introduction of miltefosine and after its extensive use.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Post-kala-azar dermal leishmaniasis (PKDL) patients, a key source of\n              <jats:italic>Leishmania donovani<\/jats:italic>\n              parasites, hinder eliminating visceral-leishmaniasis. Assessment of the susceptibility of PKDL isolates to antimony, miltefosine (MIL), and amphotericin-B indicated that recent isolates remain susceptible to antimony, enabling its use with other drugs for treating PKDL.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.04026-23","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T13:00:22Z","timestamp":1715086822000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Antimony susceptible\n            <i>Leishmania donovani<\/i>\n            : evidence from\n            <i>in vitro<\/i>\n            drug susceptibility of parasites isolated from patients of post-kala-azar dermal leishmaniasis in pre- and post-miltefosine era"],"prefix":"10.1128","volume":"12","author":[{"given":"Sushmita","family":"Ghosh","sequence":"first","affiliation":[{"name":"ICMR, National Institute of Pathology, Safdarjung Hospital Campus, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aditya","family":"Verma","sequence":"additional","affiliation":[{"name":"ICMR, National Institute of Pathology, Safdarjung Hospital Campus, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhiraj","family":"Kumar","sequence":"additional","affiliation":[{"name":"ICMR, National Institute of Pathology, Safdarjung Hospital Campus, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepak Kumar","family":"Deep","sequence":"additional","affiliation":[{"name":"ICMR, National Institute of Pathology, Safdarjung Hospital Campus, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Ramesh","sequence":"additional","affiliation":[{"name":"Department of Dermatology and STD, Safdarjung Hospital, Vardhman Mahavir Medical College, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4057-4872","authenticated-orcid":false,"given":"Poonam","family":"Salotra","sequence":"additional","affiliation":[{"name":"ICMR, National Institute of Pathology, Safdarjung Hospital Campus, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8094-4703","authenticated-orcid":false,"given":"Ruchi","family":"Singh","sequence":"additional","affiliation":[{"name":"ICMR, National Institute of Pathology, Safdarjung Hospital Campus, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/s1473-3099(03)00517-6"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-6-196"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12889-015-2424-8"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005196"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.4103\/ijd.IJD_264_20"},{"key":"e_1_3_5_7_2","unstructured":"National centre for vector borne diseases control. National Kala- Azar elimination program. 2023. Available from: https:\/\/ncvbdc.mohfw.gov.in\/index4.php?lang=1&level=0&linkid=469&lid=3752. Retrieved 20 Nov 2023."},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004093"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz486"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/505079"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.04782.x"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp468"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.123430.111"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis424"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2006.04.001"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-017-1969-z"},{"key":"e_1_3_5_17_2","first-page":"307","volume-title":"Immunology of infection","author":"Pascale K","year":"2010","unstructured":"Pascale K, Ulrich DK, Matthew R, Thomas EC, Ingrid M. 2010. 13 - the leishmaniasis model, p 307\u2013328. In Dieter K, StefanHEK (ed), Immunology of infection. Vol. 37. Academic Press."},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01233-08"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00548-09"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-012-3212-3"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001657"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2019.06.007"},{"key":"e_1_3_5_23_2","first-page":"166","article-title":"Epidemiological, clinical & pharmacological study of antimony-resistant visceral leishmaniasis in Bihar, India","volume":"120","author":"Thakur CP","year":"2004","unstructured":"Thakur CP, Narayan S, Ranjan A. 2004. Epidemiological, clinical & pharmacological study of antimony-resistant visceral leishmaniasis in Bihar, India. Indian J Med Res 120:166\u2013172.","journal-title":"Indian J Med Res"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofad231"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy172"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.25259\/IJDVL_410_19"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.04026-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.04026-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T14:14:02Z","timestamp":1717510442000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.04026-23"}},"subtitle":[],"editor":[{"given":"Pradip","family":"Sen","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,6,4]]},"references-count":25,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6,4]]}},"alternative-id":["10.1128\/spectrum.04026-23"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.04026-23","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,4]]},"assertion":[{"value":"2023-11-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e04026-23"}}