{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:42:12Z","timestamp":1791384132960,"version":"4.3.3"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T00:00:00Z","timestamp":1616112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["P01 HD059454"],"award-info":[{"award-number":["P01 HD059454"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1141549"],"award-info":[{"award-number":["OPP1141549"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Infants are protected against Plasmodium falciparum malaria. Mechanisms that drive this protection remain unclear due to a poor understanding of malaria clinical phenotypes during infancy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We enrolled a birth cohort of 678 infants in Busia, Uganda, an area of high malaria transmission. We followed infants through 12 months of age and quantified protection against parasitemia and clinical disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Symptomatic malaria incidence increased from 1.2 to 2.6 episodes per person-year between 0 and &amp;lt;6 months and between 6 and 12 months of age, while the monthly probability of asymptomatic parasitemia given infection decreased from 32% to 21%. Sickle cell trait (HbAS) was protective against symptomatic malaria (incidence rate ratio \u2005=\u20050.57 comparing HbAS vs hemoglobin AA (HbAA); 95% confidence interval, 0.44\u20130.74; P\u2005&amp;lt;\u2005.001), but age modified this relationship (Pint\u2005=\u2005&amp;lt;0.001), with nonlinear protection that waned between 0 and 9 months of age before increasing. Increasing age was associated with higher parasite densities at the time of infection and, in infants with HbAS, a reduced ability to tolerate high parasite densities without fever.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Age-dependent changes in HbAS protective efficacy in infancy were accompanied by differential loss of antiparasite and antidisease protection among HbAS and HbAA infants. This provides a framework for investigating the mechanisms that underlie infant protection against malaria.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT02793622.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciab245","type":"journal-article","created":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T04:14:19Z","timestamp":1615954459000},"page":"1887-1895","source":"Crossref","is-referenced-by-count":16,"title":["Age-Related Changes in Malaria Clinical Phenotypes During Infancy Are Modified by Sickle Cell Trait"],"prefix":"10.1093","volume":"73","author":[{"given":"Nicholas","family":"Zehner","sequence":"first","affiliation":[{"name":"Department of Medicine, Stanford University, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harriet","family":"Adrama","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abel","family":"Kakuru","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teddy","family":"Andra","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Kajubi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Conrad","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San 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