{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T00:51:44Z","timestamp":1793235104001,"version":"4.5.0"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"US Department of Defense Health Program","award":["WUN D1430"],"award-info":[{"award-number":["WUN D1430"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,9,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The emergence and spread of chloroquine-resistant\n              <jats:italic>Plasmodium vivax<\/jats:italic>\n              have necessitated the assessment of alternative blood schizonticidal drugs. In Vietnam, chloroquine-resistant\n              <jats:italic>P. vivax<\/jats:italic>\n              malaria has been reported. In an open-label, single-arm trial, the safety, tolerability, and efficacy of pyronaridine-artesunate (Pyramax, PA) was evaluated in Dak Nong province, Vietnam. A 3-day course of PA was administered to adults and children (\u226520 kg) infected with\n              <jats:italic>P. vivax<\/jats:italic>\n              . Patients also received primaquine (0.25 mg\/kg daily for 14 days). PA was well tolerated with transient asymptomatic increases in liver transaminases. The per-protocol proportion of patients with day 42 PCR-unadjusted adequate clinical and parasitological response was 96.0% (95% CI, 84.9%\u201399.0%,\n              <jats:italic>n<\/jats:italic>\n              = 48\/50). The median parasite clearance time was 12 h (range, 12\u201336 h), with a median fever clearance time of 24 h (range, 12\u201360 h). Single nucleotide polymorphisms (SNPs) as potential genetic markers of reduced drug susceptibility were analyzed in three putative drug resistance markers,\n              <jats:italic>Pvcrt-o<\/jats:italic>\n              ,\n              <jats:italic>Pvmdr1<\/jats:italic>\n              , and\n              <jats:italic>PvK12<\/jats:italic>\n              . Insertion at position K10 of the\n              <jats:italic>Pvcrt-o<\/jats:italic>\n              gene was found in 74.6% (44\/59) of isolates.\n              <jats:italic>Pvmdr1<\/jats:italic>\n              SNPs at Y976F and F1076L were present in 61% (36\/59) and 78% (46\/59), respectively. Amplification of\n              <jats:italic>Pvmdr1<\/jats:italic>\n              gene (two copies) was found in 5.1% (3\/59) of parasite samples. Only 5.1% (3\/59) of isolates had mutation 552I of the\n              <jats:italic>PvK12<\/jats:italic>\n              gene. Overall, PA rapidly cleared\n              <jats:italic>P. vivax<\/jats:italic>\n              blood asexual stages and was highly efficacious in treating vivax malaria, with no evidence of artemisinin resistance found. PA provides an alternative to chloroquine treatment for vivax malaria in Vietnam.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CLINICAL TRIALS<\/jats:title>\n            <jats:p>\n              This study is registered with the\n              <jats:related-object xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"pre-results\" document-id=\"ACTRN12618001429246\" document-id-type=\"clinical-trial-number\" source-id=\"https:\/\/www.anzctr.org.au\/\" source-id-type=\"registry-nameov\" source-type=\"clinical-trials-registry\" xlink:href=\"https:\/\/anzctr.org.au\/Trial\/Registration\/TrialReview.aspx?ACTRN=ACTRN12618001429246\">\n                <jats:ext-link ext-link-type=\"uri\" xlink:href=\"https:\/\/www.anzctr.org.au\/\" xlink:type=\"simple\">Australian New Zealand Clinical Trials Registry<\/jats:ext-link>\n                as\n                <jats:ext-link ext-link-type=\"uri\" xlink:href=\"https:\/\/anzctr.org.au\/Trial\/Registration\/TrialReview.aspx?ACTRN=ACTRN12618001429246\" xlink:type=\"simple\">ACTRN12618001429246<\/jats:ext-link>\n              <\/jats:related-object>\n              .\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00044-24","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T13:02:02Z","timestamp":1721826122000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Therapeutic efficacy of pyronaridine-artesunate (Pyramax) in treating\n            <i>Plasmodium vivax<\/i>\n            malaria in the central highlands of Vietnam"],"prefix":"10.1128","volume":"68","author":[{"given":"Nguyen Duc","family":"Manh","sequence":"first","affiliation":[{"name":"Vietnam People\u2019s Army Military Institute of Preventive Medicine, Hanoi, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Van","family":"Thanh","sequence":"additional","affiliation":[{"name":"Vietnam People\u2019s Army Military Institute of Preventive Medicine, Hanoi, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huynh Hong","family":"Quang","sequence":"additional","affiliation":[{"name":"Vietnam Ministry of Health Institute of Malariology, Parasitology and Entomology, Qui Nhon, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thi Thanh","family":"Van","sequence":"additional","affiliation":[{"name":"Vietnam People\u2019s Army Military Institute of Preventive Medicine, Hanoi, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Ngoc","family":"San","sequence":"additional","affiliation":[{"name":"Vietnam People\u2019s Army Military Institute of Preventive Medicine, Hanoi, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguen Chinh","family":"Phong","sequence":"additional","affiliation":[{"name":"Vietnam People\u2019s Army Military Institute of Preventive Medicine, Hanoi, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey W.","family":"Birrell","sequence":"additional","affiliation":[{"name":"Australian Defense Force Malaria and Infectious Disease Institute, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly A.","family":"Edgel","sequence":"additional","affiliation":[{"name":"U.S. Naval Medical Research Unit INDO PACIFIC, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Martin","sequence":"additional","affiliation":[{"name":"U.S. Naval Medical Research Unit INDO PACIFIC, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Edstein","sequence":"additional","affiliation":[{"name":"Australian Defense Force Malaria and Infectious Disease Institute, 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