{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T13:12:55Z","timestamp":1776258775663,"version":"3.50.1"},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:00:00Z","timestamp":1689724800000},"content-version":"vor","delay-in-days":18,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The location of Plasmodium falciparum within the body is determined by the life cycle of the parasite; young rings are in the peripheral blood, whereas mature parasites are sequestered in deep tissues. We can calculate a \u201cring ratio,\u201d the proportion of parasites in the periphery to the total number of parasites in the body. Artesunate acts on all parasite life stages, whereas quinine is effective only on sequestered parasites. Children with cerebral malaria (CM) treated with artesunate clear parasites faster than those treated with quinine. In this study, we established the relationship between ring ratio and parasite clearance rate and used the ring ratio to determine if the benefit derived from artesunate treatment could be attributed to its broader effect on life cycle stages.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Ring ratios were calculated for 400 hospitalized children with CM in Blantyre, Malawi between 2010 and 2019 (quinine: 2010\u20132013, artesunate: 2014\u20132019).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In both treatment groups, parasite clearance rates were positively associated with the ring ratios, with a stronger association in the artesunate era than the quinine era. In the quinine era, an increase of 1-unit log10 difference between parasitemia and plasma P falciparum histidine-rich protein 2 (a proxy for ring ratio) resulted in a 0.27-unit increase in the parasite clearance rate, whereas in the artesunate era an equal increase resulted in a 0.41-unit increase (P = .04 for the difference).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This analysis provides in vivo evidence supporting the hypothesis that more rapid parasite clearance rates in artesunate recipients are due to its superiority over quinine in killing ring-stage parasites.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ofid\/ofad380","type":"journal-article","created":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T00:57:29Z","timestamp":1689814649000},"source":"Crossref","is-referenced-by-count":1,"title":["Differential Effects of Antimalarial Drugs on Parasite Clearance Rates Are Reflected by <i>Plasmodium falciparum<\/i> Ring Ratio"],"prefix":"10.1093","volume":"10","author":[{"given":"Alexuse M","family":"Saidi","sequence":"first","affiliation":[{"name":"Blantyre Malaria Project, Kamuzu University of Health Sciences , Blantyre , Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4381-1124","authenticated-orcid":false,"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center , Seattle, Washington , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melody","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Statistics, University of Washington , Seattle, Washington , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kondwani","family":"Kawaza","sequence":"additional","affiliation":[{"name":"Departments of Paediatrics and Child Health, Queen Elizabeth Central Hospital, Kamuzu University of Health Sciences , Blantyre , Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janelisa","family":"Musaya","sequence":"additional","affiliation":[{"name":"The Malawi Liverpool Wellcome Trust Clinical Research Program, Queen Elizabeth Central Hospital, Kamuzu University of Health Sciences , Blantyre , Malawi"},{"name":"Department of Microbiology, Kamuzu University of Health Sciences , Blantyre , Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terrie","family":"Taylor","sequence":"additional","affiliation":[{"name":"Blantyre Malaria Project, Kamuzu University of Health Sciences , Blantyre , Malawi"},{"name":"Department of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University , East Lansing, Michigan , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9859-9549","authenticated-orcid":false,"given":"Karl","family":"Seydel","sequence":"additional","affiliation":[{"name":"Blantyre Malaria Project, Kamuzu University of Health Sciences , Blantyre , Malawi"},{"name":"Department of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University , East Lansing, Michigan , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,7,19]]},"reference":[{"key":"2023072809340919200_ofad380-B1","volume-title":"World malaria report 2022","author":"World Health Organization (WHO)","year":"2022"},{"key":"2023072809340919200_ofad380-B2","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.30875\/6c551ba0-en","volume-title":"World malaria report 2021","author":"World Health Organization (WHO)","year":"2021"},{"key":"2023072809340919200_ofad380-B3","first-page":"0788","article-title":"Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2","volume":"2","author":"Dondorp","year":"2005","journal-title":"PLoS Med"},{"key":"2023072809340919200_ofad380-B4","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1001297","article-title":"Diagnosing severe falciparum malaria in parasitaemic African children: a prospective evaluation of plasma PfHRP2 measurement","volume":"9","author":"Hendriksen","year":"2012","journal-title":"PLoS Med"},{"key":"2023072809340919200_ofad380-B5","article-title":"Improving the diagnosis of severe malaria in African children using platelet counts and plasma Pf HRP2 concentrations","volume":"14","author":"Watson","year":"2021","journal-title":"Sci Transl Med"},{"key":"2023072809340919200_ofad380-B6","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0140-6736(05)67176-0","article-title":"Artesunate 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of the sequestered parasite load in severe malaria patients using both host and parasite markers","volume":"131","author":"Ochola","year":"2005","journal-title":"Parasitology"},{"key":"2023072809340919200_ofad380-B13","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.1038\/s41467-022-30990-5","article-title":"The impact of malaria-protective red blood cell polymorphisms on parasite biomass in children with severe Plasmodium falciparum malaria","volume":"13","author":"Uyoga","year":"2022","journal-title":"Nat Commun"},{"key":"2023072809340919200_ofad380-B14","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1006\/expr.1993.1010","article-title":"Plasmodium falciparum in vitro studies of the pharmacodynamic properties of drugs used for the treatment of severe malaria","volume":"76","author":"ter Kuile","year":"1993","journal-title":"Exp Parasitol"}],"container-title":["Open Forum Infectious 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