{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:15:23Z","timestamp":1790302523389,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2018,12,9]],"date-time":"2018-12-09T00:00:00Z","timestamp":1544313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"personal research","award":["PRG_SR2014-PRG_SR2016"],"award-info":[{"award-number":["PRG_SR2014-PRG_SR2016"]}]},{"DOI":"10.13039\/501100001412","name":"CSIR","doi-asserted-by":"publisher","award":["09\/599 (0055)2K1-EMR-I."],"award-info":[{"award-number":["09\/599 (0055)2K1-EMR-I."]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Artesunate-sulfadoxine-pyrimethamine (ASSP) is the frontline artemisinin combination therapy (ACT) in India. Random, irrational, subtherapeutic artemisinin doses and self-medication with ACT along with predominance of sulfadoxine-pyrimethamine resistance parasite invoked a strong possibility of emerging artemisinin-resistant malaria parasites.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This study involved 226 patients with uncomplicated Plasmodium falciparum infection who had successfully completed the 42 days follow-up after ASSP combination therapy from April 2014 to January 2016. We assessed the ASSP treatment efficacy by evaluating parasite clearance half-life, pfkelch13, and other (pfdhfr, pfdhps, pfmdr1, pfcrt) gene mutations and survival of parasites as detected by an ex vivo ring-stage survival assay (RSA).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Findings<\/jats:title>\n                  <jats:p>Slow-clearing infections with longer parasite clearance half-lives (&gt;5 hours) were observed in 12% isolates. Cure rate after ASSP treatment was declining to about 84.1%. ASSP failure was recorded in 15.9% (early treatment failure, 7.9%; late treatment failure, 7.9%) of isolates. In sum, 24 patients (10.6%) had parasite clearance half-lives greater than 5 hours with pfkelch13 polymorphism after 441 codon; in 15 of those patients (6.6%), parasites had not cleared by 72 hours after initiation of therapy. Median ex vivo ring-stage survival rate of these isolates was very high (12.2%; 95% confidence interval [CI], 10.9\u201313.8) from that of cured patients (0.9%; 95% CI, 0.09\u20131.07). Of these 15 patients, 13 patients had pfkelch13 G625R polymorphism, whereas 2 patients contained R539T polymorphism. As per the World Health Organization guideline, these 15 isolates were true artemisinin-resistant isolates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Interpretation<\/jats:title>\n                  <jats:p>Identification of artemisinin-resistant isolates in India together with new mutations and increasing combination therapy failures blow alarms for urgent malaria control.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciy1038","type":"journal-article","created":{"date-parts":[[2018,12,6]],"date-time":"2018-12-06T17:08:28Z","timestamp":1544116108000},"page":"1144-1152","source":"Crossref","is-referenced-by-count":68,"title":["Novel pfkelch13 Gene Polymorphism Associates With Artemisinin Resistance in Eastern India"],"prefix":"10.1093","volume":"69","author":[{"given":"Sabyasachi","family":"Das","sequence":"first","affiliation":[{"name":"Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore, West Bengal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhankar","family":"Manna","sequence":"additional","affiliation":[{"name":"Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore, West Bengal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhaskar","family":"Saha","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science, Ganeshkhind, Pune"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amiya Kumar","family":"Hati","sequence":"additional","affiliation":[{"name":"Calcutta School of Tropical Medicine, Kolkata, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somenath","family":"Roy","sequence":"additional","affiliation":[{"name":"Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore, West Bengal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,12,9]]},"reference":[{"key":"2019091313020752500_CIT0001","volume-title":"World malaria report","author":"World Health Organization","year":"2009"},{"key":"2019091313020752500_CIT0002","volume-title":"Guidelines for diagnosis and treatment of malaria in India","year":"2009"},{"key":"2019091313020752500_CIT0003","doi-asserted-by":"crossref","first-page":"e309","DOI":"10.1371\/journal.pmed.0040309","article-title":"Impact of artemisinin-based combination therapy and insecticide-treated nets on malaria burden in Zanzibar","volume":"4","author":"Bhattarai","year":"2007","journal-title":"PLoS Med"},{"key":"2019091313020752500_CIT0004","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1056\/NEJMc0805011","article-title":"Evidence of artemisinin-resistant malaria in western Cambodia","volume":"359","author":"Noedl","year":"2008","journal-title":"N Engl J Med"},{"key":"2019091313020752500_CIT0005","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1056\/NEJMoa0808859","article-title":"Artemisinin resistance in Plasmodium falciparum malaria","volume":"361","author":"Dondorp","year":"2009","journal-title":"N Engl J Med"},{"key":"2019091313020752500_CIT0006","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/S1473-3099(13)70252-4","article-title":"Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies","volume":"13","author":"Witkowski","year":"2013","journal-title":"Lancet Infect Dis"},{"key":"2019091313020752500_CIT0007","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/nature12876","article-title":"A molecular marker of artemisinin-resistant Plasmodium falciparum malaria","volume":"505","author":"Ariey","year":"2014","journal-title":"Nature"},{"key":"2019091313020752500_CIT0008","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1056\/NEJMoa1314981","article-title":"Spread of artemisinin resistance in Plasmodium falciparum malaria","volume":"371","author":"Ashley","year":"2014","journal-title":"N Engl J Med"},{"key":"2019091313020752500_CIT0009","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3189","article-title":"Genetic architecture of artemisinin-resistant Plasmodium falciparum","author":"Miotto","year":"2015","journal-title":"Nat Gen"},{"key":"2019091313020752500_CIT0010","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1126\/science.1260867","article-title":"Drug resistance. 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