{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T18:50:26Z","timestamp":1775328626176,"version":"3.50.1"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T00:00:00Z","timestamp":1681344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Sensitive molecular assays, such as quantitative reverse-transcription polymerase chain reaction (qRT-PCR) of Plasmodium 18S ribosomal RNA (rRNA), are increasingly the primary method of detecting infections in controlled human malaria infection (CHMI) trials. However, thick blood smears (TBSs) remain the main method for confirming clearance of parasites after curative treatment, in part owing to uncertainty regarding biomarker clearance rates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>For this analysis, 18S rRNA qRT-PCR data were compiled from 127 Plasmodium falciparum\u2013infected participants treated with chloroquine or atovaquone-proguanil in 6 CHMI studies conducted in Seattle, Washington, over the past decade. A survival analysis approach was used to compare biomarker and TBS clearance times among studies. The effect of the parasite density at which treatment was initiated on clearance time was estimated using linear regression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The median time to biomarker clearance was 3 days (interquartile range, 3\u20135 days), while the median time to TBS clearance was 1 day (1\u20132 days). Time to biomarker clearance increased with the parasite density at which treatment was initiated. Parasite density did not have a significant effect on TBS clearance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The Plasmodium 18S rRNA biomarker clears quickly and can be relied on to confirm the adequacy of Food and Drug Administration\u2013approved treatments in CHMI studies at nonendemic sites.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ofid\/ofad202","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T11:58:19Z","timestamp":1681387099000},"source":"Crossref","is-referenced-by-count":4,"title":["<i>Plasmodium<\/i> 18S Ribosomal RNA Biomarker Clearance After Food and Drug Administration\u2013Approved Antimalarial Treatment in Controlled Human Malaria Infection Trials"],"prefix":"10.1093","volume":"10","author":[{"given":"Chris","family":"Chavtur","sequence":"first","affiliation":[{"name":"Malaria Molecular Diagnostic Laboratory, Department of Laboratory Medicine and Pathology and Center for Emerging and Re-emerging Infectious Diseases, University of Washington , Seattle, Washington , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weston J","family":"Staubus","sequence":"additional","affiliation":[{"name":"Malaria Molecular Diagnostic Laboratory, Department of Laboratory Medicine and Pathology and Center for Emerging and Re-emerging Infectious Diseases, University of Washington , Seattle, Washington , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mabel","family":"Ho","sequence":"additional","affiliation":[{"name":"Malaria Molecular Diagnostic Laboratory, Department of Laboratory Medicine and Pathology and Center for Emerging and Re-emerging Infectious Diseases, University of Washington , Seattle, Washington , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dianna E B","family":"Hergott","sequence":"additional","affiliation":[{"name":"Malaria Molecular Diagnostic Laboratory, Department of Laboratory Medicine and Pathology and Center for Emerging and Re-emerging Infectious Diseases, University of Washington , Seattle, Washington , USA"},{"name":"Department of Epidemiology, School of Public Health, University of Washington , Seattle, Washington , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annette M","family":"Seilie","sequence":"additional","affiliation":[{"name":"Malaria Molecular Diagnostic Laboratory, Department of Laboratory Medicine and Pathology and Center for Emerging and Re-emerging Infectious Diseases, University of Washington , Seattle, Washington , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Healy","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases , Bethesda, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Duffy","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases , Bethesda, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Jackson","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Washington Health Research Institute , Seattle, Washington , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Talley","sequence":"additional","affiliation":[{"name":"Spero Therapeutics , Cambridge, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan H I","family":"Kappe","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children's Research Institute , Seattle, Washington , USA"},{"name":"Department of Pediatrics, University of Washington , Seattle, Washington , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen L","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Sanaria , Rockville, Maryland , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas L","family":"Richie","sequence":"additional","affiliation":[{"name":"Sanaria , Rockville, Maryland , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James G","family":"Kublin","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center , Seattle, Washington , USA"},{"name":"Seattle Malaria Clinical Trials Center, Fred Hutchinson Cancer Research Center , Seattle, Washington , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Chang","sequence":"additional","affiliation":[{"name":"Malaria Molecular Diagnostic Laboratory, Department of Laboratory Medicine and Pathology and Center for Emerging and Re-emerging Infectious Diseases, University of Washington , Seattle, Washington , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean C","family":"Murphy","sequence":"additional","affiliation":[{"name":"Malaria Molecular Diagnostic Laboratory, Department of Laboratory Medicine and Pathology and Center for Emerging and Re-emerging Infectious Diseases, University of Washington , Seattle, Washington , USA"},{"name":"Seattle Malaria Clinical Trials Center, Fred Hutchinson Cancer Research Center , Seattle, Washington , USA"},{"name":"Department of Microbiology, University of Washington , Seattle, Washington , USA"},{"name":"Department of Laboratories, Seattle Children's Hospital , Seattle, Washington , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,4,13]]},"reference":[{"key":"2024021700134170900_ofad202-B1","doi-asserted-by":"crossref","DOI":"10.30875\/6c551ba0-en","volume-title":"World Malaria Report 2021","author":"World Health Organization","year":"2021"},{"key":"2024021700134170900_ofad202-B2","doi-asserted-by":"crossref","first-page":"e00479","DOI":"10.1128\/IAI.00479-17","article-title":"Controlled human malaria infection: applications, advances, and challenges","volume":"86","author":"Stanisic","year":"2018","journal-title":"Infect Immun"},{"key":"2024021700134170900_ofad202-B3","doi-asserted-by":"crossref","first-page":"824","DOI":"10.4269\/ajtmh.12-0675","article-title":"Malaria diagnostics in clinical trials","volume":"89","author":"Murphy","year":"2013","journal-title":"Am J Trop Med Hyg"},{"key":"2024021700134170900_ofad202-B4","first-page":"621","article-title":"Use and limitations of light microscopy 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