{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T20:57:34Z","timestamp":1771707454455,"version":"3.50.1"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T00:00:00Z","timestamp":1701475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Antimalarial drug resistance surveillance and containment are crucial for countries aiming to eliminate malaria. Monitoring resistance evolution through studies before and after treatment policy changes is essential.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A total of 939 Plasmodium falciparum-positive blood samples were collected between 2014 and 2015 across 10 sites in India, categorized into 4 geographic clusters. Polymerase chain reaction-amplified products were sequenced to identify point mutations at drug resistance-conferring genes (Pfdhfr, Pfdhps, Pfmdr1, and Pfk13).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Triple Pfdhfr mutants were found only in northeast India bordering Myanmar, while the wild type (WT) was dominant in central India. Pfdhps WTs were prevalent in all areas, and no double mutants were found. Except in northwest India, Pfmdr1 WT was dominant in all clusters. Nonsynonymous double mutations were only found in northwest India. Only synonymous mutations occurred in Pfk13. These were found in central India at a low frequency. The pattern of linkage disequilibrium and principal component analysis reflects low pressure for drug resistance and heterogeneity between the geographic clusters.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Resistance levels were highest in northeast India, close to the Myanmar border, where resistance is common. Primaquine has been widely used as a gametocidal and schizonticidal drug, likely contributing to maintaining low drug resistance levels and preventing strong selection for resistance.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiad553","type":"journal-article","created":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T07:35:39Z","timestamp":1701329739000},"page":"1574-1583","source":"Crossref","is-referenced-by-count":4,"title":["Low Prevalence of Antimalarial Resistance Mutations in India During 2014\u20132015: Impact of Combining First-line Therapy With Primaquine"],"prefix":"10.1093","volume":"229","author":[{"given":"Nazia A","family":"Ali","sequence":"first","affiliation":[{"name":"Indian Council of Medical Research-National Institute of Research in Tribal Health , Jabalpur, 482002 Madhya Pradesh , India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0296-8296","authenticated-orcid":false,"given":"Shrikant","family":"Nema","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research-National Institute of Malaria Research , Dwarka, 110077 New Delhi , India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4138-1180","authenticated-orcid":false,"given":"Kristan A","family":"Schneider","sequence":"additional","affiliation":[{"name":"University of Applied Sciences , 09648 Mittweida , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sri","family":"Krishna","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research-National Institute of Research in Tribal Health , Jabalpur, 482002 Madhya Pradesh , India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3105-4138","authenticated-orcid":false,"given":"Anil Kumar","family":"Verma","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research-National Institute of Research in Tribal Health , Jabalpur, 482002 Madhya Pradesh , India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4081-5816","authenticated-orcid":false,"given":"Aparup","family":"Das","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research-National Institute of Research in Tribal Health , Jabalpur, 482002 Madhya Pradesh , India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2548-4884","authenticated-orcid":false,"given":"Praveen Kumar","family":"Bharti","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research-National Institute of Malaria Research , Dwarka, 110077 New Delhi , India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,12,2]]},"reference":[{"key":"2024051515163526700_jiad553-B1","author":"World Health Organization"},{"key":"2024051515163526700_jiad553-B2","first-page":"205","article-title":"Antimalarial drug policy in India: past, present & future","volume":"139","author":"Anvikar","year":"2014","journal-title":"Indian J Med Res"},{"key":"2024051515163526700_jiad553-B3","author":"Government of India"},{"key":"2024051515163526700_jiad553-B4","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S1473-3099(17)30048-8","article-title":"The spread of artemisinin-resistant Plasmodium falciparum in the Greater Mekong subregion: a molecular epidemiology observational study","volume":"17","author":"Imwong","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"2024051515163526700_jiad553-B5","doi-asserted-by":"crossref","first-page":"16690","DOI":"10.1038\/s41598-017-16866-5","article-title":"Prevalence of mutations linked to antimalarial resistance in Plasmodium falciparum from Chhattisgarh, central India: a malaria elimination point of view","volume":"7","author":"Patel","year":"2017","journal-title":"Sci Rep"},{"key":"2024051515163526700_jiad553-B6","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1128\/AAC.48.3.879-889.2004","article-title":"Plasmodium falciparum isolates in India exhibit a progressive increase in mutations associated with sulfadoxine-pyrimethamine resistance","volume":"48","author":"Ahmed","year":"2004","journal-title":"Antimicrob Agents Chemother"},{"key":"2024051515163526700_jiad553-B7","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s13312-020-1888-5","article-title":"Malaria elimination in India: bridging the gap between control and elimination","volume":"57","author":"Nema","year":"2020","journal-title":"Indian Pediatr"},{"key":"2024051515163526700_jiad553-B8","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1186\/s12936-016-1555-4","article-title":"Therapeutic efficacy of artemether\u2013lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria from three highly malarious states in India","volume":"15","author":"Bharti","year":"2016","journal-title":"Malar J"},{"key":"2024051515163526700_jiad553-B9","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1186\/s12936-021-03762-7","article-title":"Therapeutic efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in four malaria endemic states of India","volume":"20","author":"Krishna","year":"2021","journal-title":"Malar J"},{"key":"2024051515163526700_jiad553-B10","author":"World Health Organization"},{"key":"2024051515163526700_jiad553-B11","doi-asserted-by":"crossref","first-page":"e0157949","DOI":"10.1371\/journal.pone.0157949","article-title":"Prevalence of pfhrp2 and\/or pfhrp3 gene deletion in Plasmodium falciparum population in eight highly endemic states in India","volume":"11","author":"Bharti","year":"2016","journal-title":"PLoS One"},{"key":"2024051515163526700_jiad553-B12","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.3201\/eid2110.150678","article-title":"Detection of mixed infections with Plasmodium spp. by PCR, India, 2014","volume":"21","author":"Krishna","year":"2015","journal-title":"Emerg Infect Dis"},{"key":"2024051515163526700_jiad553-B13","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1093\/trstmh\/trac007","article-title":"Unreported mixed Plasmodium species infection may increase vivax malaria in India: a challenge for malaria elimination","volume":"116","author":"Nema","year":"2022","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"2024051515163526700_jiad553-B14","first-page":"102","article-title":"Rapid staining of malarial parasites by a water soluble stain","volume":"79","author":"Singh","year":"1944","journal-title":"Ind Med Gaz"},{"key":"2024051515163526700_jiad553-B15","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0166-6851(93)90050-8","article-title":"Identification of the four human malaria parasite species in field samples by the polymerase chain reaction and detection of a high prevalence of mixed infections","volume":"58","author":"Snounou","year":"1993","journal-title":"Mol Biochem Parasitol"},{"key":"2024051515163526700_jiad553-B16","author":"R Core Team"},{"key":"2024051515163526700_jiad553-B17","doi-asserted-by":"crossref","first-page":"943625","DOI":"10.3389\/fepid.2022.943625","article-title":"A maximum-likelihood method to estimate haplotype frequencies and prevalence alongside multiplicity of infection from SNP data","volume":"2","author":"Tsoungui Obama","year":"2022","journal-title":"Front Epidemiol"},{"key":"2024051515163526700_jiad553-B18","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1534\/genetics.114.165266","article-title":"Conditional asymmetric linkage disequilibrium (ALD): extending the biallelic r2 measure","volume":"198","author":"Thomson","year":"2014","journal-title":"Genetics"},{"key":"2024051515163526700_jiad553-B19","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.3390\/microorganisms10102021","article-title":"Molecular profiles of multiple antimalarial drug resistance markers in Plasmodium falciparum and Plasmodium vivax in the Mandalay region, Myanmar","volume":"10","author":"L\u00ea","year":"2022","journal-title":"Microorganisms"},{"key":"2024051515163526700_jiad553-B20","doi-asserted-by":"crossref","first-page":"e105562","DOI":"10.1371\/journal.pone.0105562","article-title":"Molecular evidence of increased resistance to anti-folate drugs in Plasmodium falciparum in north-east India: a signal for potential failure of artemisinin plus sulphadoxine-pyrimethamine combination therapy","volume":"9","author":"Mohapatra","year":"2014","journal-title":"PLoS One"},{"key":"2024051515163526700_jiad553-B21","doi-asserted-by":"crossref","first-page":"286","DOI":"10.4103\/0976-9668.116970","article-title":"Antimicrobial resistance in India: a review","volume":"4","author":"Kumar","year":"2013","journal-title":"J Nat Sci Biol Med"},{"key":"2024051515163526700_jiad553-B22","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1186\/s12936-016-1636-4","article-title":"Emerging polymorphisms in falciparum Kelch 13 gene in northeastern region of India","volume":"15","author":"Mishra","year":"2016","journal-title":"Malar J"},{"key":"2024051515163526700_jiad553-B23","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1080\/20477724.2017.1331875","article-title":"Clinical and molecular monitoring of Plasmodium falciparum resistance to antimalarial drug (artesunate + sulphadoxine-pyrimethamine) in two highly malarious district of Madhya Pradesh, central India from 2012\u20132014","volume":"111","author":"Mishra","year":"2017","journal-title":"Pathog Glob Health"},{"key":"2024051515163526700_jiad553-B24","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1056\/NEJMc1713777","article-title":"Evidence of artemisinin-resistant Plasmodium falciparum malaria in eastern India","volume":"379","author":"Das","year":"2018","journal-title":"N Engl J Med"},{"key":"2024051515163526700_jiad553-B25","doi-asserted-by":"crossref","first-page":"e0278928","DOI":"10.1371\/journal.pone.0278928","article-title":"Ten-year persistence and evolution of Plasmodium falciparum antifolate and anti-sulfonamide resistance markers pfdhfr and pfdhps in three Asian countries","volume":"17","author":"Srisutham","year":"2022","journal-title":"PLoS One"},{"key":"2024051515163526700_jiad553-B26","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1186\/s12936-018-2620-y","article-title":"Prevalence of molecular markers of sulfadoxine\u2013pyrimethamine and artemisinin resistance in Plasmodium falciparum from Pakistan","volume":"17","author":"Yaqoob","year":"2018","journal-title":"Malar J"},{"key":"2024051515163526700_jiad553-B27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/1995-7645.368016","article-title":"Time to stimulate Plasmodium vivax research in India: a way forward","volume":"16","author":"Gupta","year":"2023","journal-title":"Asian Pac J Trop Med"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiad553\/54450199\/jiad553.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/229\/5\/1574\/57674688\/jiad553.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/229\/5\/1574\/57674688\/jiad553.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T15:17:19Z","timestamp":1715786239000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/229\/5\/1574\/7458043"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,2]]},"references-count":27,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,12,2]]},"published-print":{"date-parts":[[2024,5,15]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiad553","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,5,15]]},"published":{"date-parts":[[2023,12,2]]}}}