{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:42:13Z","timestamp":1791384133249,"version":"4.3.3"},"reference-count":70,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"5","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"unspecified","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":[[2026,5,6]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n                  <jats:p>Infants under 1 year of age are considered partially protected from malaria because of maternal antibodies and fetal hemoglobin. However, emerging evidence suggests that the malaria burden in this age group may be underestimated. A cohort of 855 infants in Busia District, Uganda, was enrolled in the present study to characterize malaria incidence and parasite prevalence during the first year of life and to identify risk factors for these outcomes. The study was conducted from 2021 to 2025, before the malaria vaccine roll-out. Infants born to HIV-uninfected women were enrolled at 4\u20138 weeks of age and followed by active and passive case detection to 1 year of age in a dedicated study clinic that is open 7 days\/week. Routine visits every 4 weeks included assessments for parasitemia via microscopy and quantitative polymerase chain reaction testing. Over 706.7 person-years of follow-up, 662 malaria episodes occurred. The overall prevalence of microscopic parasitemia was 7.9%, and the combined prevalence of microscopic and submicroscopic parasitemia was 21.8%. Sickle cell trait (Hemoglobin AS) conferred 39% protection against symptomatic malaria but was not associated with the risk of parasitemia. Modern housing construction and higher maternal education were independently associated with reduced malaria risk. District-wide distribution of long-lasting insecticide-treated nets containing alpha\u2013cypermethrin plus chlorfenapyr in October 2023 was followed by an 80% reduction in malaria incidence and significant declines in parasitemia prevalence. These findings underscore the urgent need for age-appropriate preventative interventions targeting young infants, such as earlier vaccine administration or treatment with monoclonal antibodies, alongside sustained investment in next-generation vector control and attention to socioeconomic determinants of malaria risk.<\/jats:p>","DOI":"10.4269\/ajtmh.25-0695","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T18:49:21Z","timestamp":1775155761000},"page":"905-912","source":"Crossref","is-referenced-by-count":3,"title":["Natural History and the Burden of Malaria During the First Year of Life in the High-Transmission Setting of Uganda"],"prefix":"10.4269","volume":"114","author":[{"given":"Miriam","family":"Aguti","sequence":"first","affiliation":[{"name":"Infectious Diseases Research Collaboration, Kampala, Uganda;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaniter I.","family":"Nankabirwa","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration, Kampala, Uganda;"},{"name":"School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimmy","family":"Kizza","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;"},{"name":"Department of Community and Public Health, Busitema University, Tororo, Uganda;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Ssemukuye","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration, Kampala, Uganda;"}],"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":"Peter","family":"Olwoch","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration, Kampala, Uganda;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bishop","family":"Opira","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration, Kampala, Uganda;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baker","family":"Odongo","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration, Kampala, Uganda;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylie","family":"Camanag","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University School of Medicine, Stanford, California, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Nakalembe","sequence":"additional","affiliation":[{"name":"School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant","family":"Dorsey","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasanna","family":"Jaganathan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University School of Medicine, Stanford, California, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moses R.","family":"Kamya","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration, Kampala, Uganda;"},{"name":"School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"b1","article-title":"World Malaria Report, 2024.","year":"2024"},{"key":"b2","series-title":"Malar J","first-page":"400","article-title":"Malaria in infants aged less than six months \u2013 Is it an area of unmet medical need?","volume":"11","author":"D\u2019Alessandro","year":"2012"},{"key":"b3","series-title":"Trop Med Int 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J","first-page":"310","article-title":"Malaria in infants below six months of age: Retrospective surveillance of hospital admission records in Blantyre, Malawi","volume":"8","author":"Larru","year":"2009"},{"key":"b8","series-title":"Clin Infect Dis","first-page":"1887","article-title":"Age-related changes in malaria clinical phenotypes during infancy are modified by sickle cell trait","volume":"73","author":"Zehner","year":"2021"},{"key":"b9","series-title":"Lancet","first-page":"1533","article-title":"Efficacy and safety of intermittent preventive treatment with sulfadoxine-pyrimethamine for malaria in African infants: A pooled analysis of six randomised, placebo-controlled trials","volume":"374","author":"Aponte","year":"2009"},{"key":"b10","series-title":"PLoS One","first-page":"e4569","article-title":"High resistance of Plasmodium falciparum to sulphadoxine\/pyrimethamine in northern Tanzania and the emergence of dhps resistance mutation at Codon 581","volume":"4","author":"Gesase","year":"2009"},{"key":"b11","series-title":"PLoS Med","first-page":"e1004582","article-title":"Dihydroartemisinin\u2013piperaquine plus sulfadoxine\u2013pyrimethamine versus either drug alone for intermittent preventive treatment of malaria in pregnancy: A double-blind, randomized, controlled trial","volume":"22","author":"Kakuru","year":"2025"},{"key":"b12","article-title":"Uganda Clinical Guidelines 2023: National Guidelines for Management of Common Health Conditions.","year":"2023"},{"key":"b13","series-title":"PLoS Med","first-page":"e1001788","article-title":"Ultra-sensitive detection of Plasmodium falciparum by amplification of multi-copy subtelomeric targets","volume":"12","author":"Hofmann","year":"2015"},{"key":"b14","series-title":"Malar J","first-page":"144","article-title":"Household and maternal risk factors for malaria in pregnancy in a highly endemic area of Uganda: A prospective cohort study","volume":"18","author":"Okiring","year":"2019"},{"key":"b15","series-title":"Expert Opin Pharmacother","first-page":"1711","article-title":"Antimalarial treatment in infants","volume":"23","author":"Kalkman","year":"2022"},{"key":"b16","series-title":"PLoS One","first-page":"e0123283","article-title":"Malaria care in infants aged under six months in Uganda: An area of unmet needs!","volume":"10","author":"Mbonye","year":"2015"},{"key":"b17","series-title":"Nat Commun","first-page":"7353","article-title":"Changes in susceptibility of Plasmodium falciparum to antimalarial drugs in Uganda over time: 2019\u20132024","volume":"16","author":"Okitwi","year":"2025"},{"key":"b18","series-title":"Front Immunol","first-page":"634749","article-title":"Malaria and early life immunity: Competence in context","volume":"12","author":"Callaway","year":"2021"},{"key":"b19","series-title":"N Engl J Med","first-page":"1833","article-title":"Safety and efficacy of a monoclonal antibody against malaria in Mali","volume":"387","author":"Kayentao","year":"2022"},{"key":"b20","series-title":"N Engl J Med","first-page":"1399","article-title":"Permethrin-treated baby wraps for the prevention of malaria","volume":"393","author":"Boyce","year":"2025"},{"key":"b21","article-title":"WHO Guidelines for Malaria.","year":"2025"},{"key":"b22","series-title":"Lancet Glob Health","first-page":"e195","article-title":"Burden of sickle cell trait and disease in the Uganda Sickle Surveillance Study (US3): A cross-sectional study","volume":"4","author":"Ndeezi","year":"2016"},{"key":"b23","series-title":"J Infect Dis","first-page":"178","article-title":"Sickle cell trait and the risk of Plasmodium falciparum malaria and other childhood diseases","volume":"192","author":"Williams","year":"2005"},{"key":"b24","series-title":"PLoS Med","first-page":"e128","article-title":"An immune basis for malaria protection by the sickle cell 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trial","volume":"391","author":"Protopopoff","year":"2018"},{"key":"b28","series-title":"Nat Med","first-page":"2813","article-title":"Extension of efficacy range for targeted malaria-elimination interventions due to spillover effects","volume":"30","author":"Benjamin-Chung","year":"2024"},{"key":"b29","series-title":"Trans R Soc Trop Med Hyg","first-page":"143","article-title":"Household and microeconomic factors associated with malaria in Mpumalanga, South Africa","volume":"104","author":"Coleman","year":"2010"},{"key":"b30","series-title":"Malar J","first-page":"370","article-title":"The mediating role of behavioural and socio-structural factors on the association between household wealth and childhood malaria in Ghana","volume":"23","author":"Habermann","year":"2024"},{"key":"b31","series-title":"Ecol Society","first-page":"33","article-title":"Independent associations of maternal education and household wealth with malaria risk in 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2024.","year":"2024"},{"key":"b2","series-title":"Malar J","first-page":"400","article-title":"Malaria in infants aged less than six months \u2013 Is it an area of unmet medical need?","volume":"11","author":"D\u2019Alessandro","year":"2012"},{"key":"b3","series-title":"Trop Med Int Health","first-page":"475","article-title":"Plasmodium falciparum malaria in the first year of life in an area of intense and perennial transmission","volume":"1","author":"Kitua","year":"1996"},{"key":"b4","series-title":"Infect Immun","first-page":"e0026823","article-title":"Associations between prenatal malaria exposure, maternal antibodies at birth, and malaria susceptibility during the first year of life in Burkina Faso","volume":"91","author":"Natama","year":"2023"},{"key":"b5","series-title":"Malar J","first-page":"132","article-title":"Varying efficacy of intermittent preventive treatment for malaria in infants in two similar trials: Public health implications","volume":"6","author":"Menendez","year":"2007"},{"key":"b6","series-title":"Parasitology","first-page":"129","article-title":"Plasmodium malaria and antimalarial antibodies in the first year of life","volume":"143","author":"Dobbs","year":"2016"},{"key":"b7","series-title":"Malar J","first-page":"310","article-title":"Malaria in infants below six months of age: Retrospective surveillance of hospital admission records in Blantyre, Malawi","volume":"8","author":"Larru","year":"2009"},{"key":"b8","series-title":"Clin Infect Dis","first-page":"1887","article-title":"Age-related changes in malaria clinical phenotypes during infancy are modified by sickle cell trait","volume":"73","author":"Zehner","year":"2021"},{"key":"b9","series-title":"Lancet","first-page":"1533","article-title":"Efficacy and safety of intermittent preventive treatment with sulfadoxine-pyrimethamine for malaria in African infants: A pooled analysis of six randomised, placebo-controlled trials","volume":"374","author":"Aponte","year":"2009"},{"key":"b10","series-title":"PLoS One","first-page":"e4569","article-title":"High resistance of Plasmodium falciparum to sulphadoxine\/pyrimethamine in northern Tanzania and the emergence of dhps resistance mutation at Codon 581","volume":"4","author":"Gesase","year":"2009"},{"key":"b11","series-title":"PLoS Med","first-page":"e1004582","article-title":"Dihydroartemisinin\u2013piperaquine plus sulfadoxine\u2013pyrimethamine versus either drug alone for intermittent preventive treatment of malaria in pregnancy: A double-blind, randomized, controlled trial","volume":"22","author":"Kakuru","year":"2025"},{"key":"b12","article-title":"Uganda Clinical Guidelines 2023: National Guidelines for Management of Common Health Conditions.","year":"2023"},{"key":"b13","series-title":"PLoS Med","first-page":"e1001788","article-title":"Ultra-sensitive detection of Plasmodium falciparum by amplification of multi-copy subtelomeric targets","volume":"12","author":"Hofmann","year":"2015"},{"key":"b14","series-title":"Malar J","first-page":"144","article-title":"Household and maternal risk factors for malaria in pregnancy in a highly endemic area of Uganda: A prospective cohort study","volume":"18","author":"Okiring","year":"2019"},{"key":"b15","series-title":"Expert Opin Pharmacother","first-page":"1711","article-title":"Antimalarial treatment in infants","volume":"23","author":"Kalkman","year":"2022"},{"key":"b16","series-title":"PLoS One","first-page":"e0123283","article-title":"Malaria care in infants aged under six months in Uganda: An area of unmet needs!","volume":"10","author":"Mbonye","year":"2015"},{"key":"b17","series-title":"Nat Commun","first-page":"7353","article-title":"Changes in susceptibility of Plasmodium falciparum to antimalarial drugs in Uganda over time: 2019\u20132024","volume":"16","author":"Okitwi","year":"2025"},{"key":"b18","series-title":"Front Immunol","first-page":"634749","article-title":"Malaria and early life immunity: Competence in context","volume":"12","author":"Callaway","year":"2021"},{"key":"b19","series-title":"N Engl J Med","first-page":"1833","article-title":"Safety and efficacy of a monoclonal antibody against malaria in Mali","volume":"387","author":"Kayentao","year":"2022"},{"key":"b20","series-title":"N Engl J Med","first-page":"1399","article-title":"Permethrin-treated baby wraps for the prevention of malaria","volume":"393","author":"Boyce","year":"2025"},{"key":"b21","article-title":"WHO Guidelines for Malaria.","year":"2025"},{"key":"b22","series-title":"Lancet Glob Health","first-page":"e195","article-title":"Burden of sickle cell trait and disease in the Uganda Sickle Surveillance Study (US3): A cross-sectional study","volume":"4","author":"Ndeezi","year":"2016"},{"key":"b23","series-title":"J Infect Dis","first-page":"178","article-title":"Sickle cell trait and the risk of Plasmodium falciparum malaria and other childhood diseases","volume":"192","author":"Williams","year":"2005"},{"key":"b24","series-title":"PLoS Med","first-page":"e128","article-title":"An immune basis for malaria protection by the sickle cell trait","volume":"2","author":"Williams","year":"2005"},{"key":"b25","series-title":"Blood","first-page":"3808","article-title":"Evidence for both innate and acquired mechanisms of protection from Plasmodium falciparum in children with sickle cell trait","volume":"119","author":"Gong","year":"2012"},{"key":"b26","series-title":"Lancet Infect Dis","first-page":"640","article-title":"Implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets: A WHO-coordinated, prospective, international, observational cohort study","volume":"18","author":"Kleinschmidt","year":"2018"},{"key":"b27","series-title":"Lancet","first-page":"1577","article-title":"Effectiveness of a long-lasting piperonyl butoxide-treated insecticidal net and indoor 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