Age-Related Changes in Malaria Clinical Phenotypes During Infancy Are Modified by Sickle Cell Trait
Copyright policy )Age-Related Changes in Malaria Clinical Phenotypes During Infancy Are Modified by Sickle Cell Trait
Abstract Background 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. Methods 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. Results Symptomatic malaria incidence increased from 1.2 to 2.6 episodes per person-year between 0 and <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 = 0.57 comparing HbAS vs hemoglobin AA (HbAA); 95% confidence interval, 0.44–0.74; P < .001), but age modified this relationship (Pint = <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. Conclusions 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. Clinical Trials Registration NCT02793622.
Malaria (rcdc), 2.2 Factors relating to the physical environment (hrcs-rac), 11 Medical and Health Sciences (for), Parasitemia, Medical and Health Sciences, Pediatrics, Clinical Research (rcdc), malaria in infancy, 2.2 Factors relating to the physical environment, Disease, Malaria, Falciparum, 32 Biomedical and Clinical Sciences (for-2020), Genetic and Clinical Aspects of Hemoglobin Disorders, Internal medicine, Pediatric, Humans (mesh), 3 Good Health and Well Being (sdg), Incidence (geometry), Physics, Cohort, Hematology, Biological Sciences, Malaria (mesh), Phenotype (mesh), 06 Biological Sciences (for), Asymptomatic, Infection (hrcs-hc), Infectious Diseases, Phenotype, Medical Microbiology, Plasmodium falciparum (mesh), Medicine, Infection, Falciparum, Sickle cell trait, 570, Malaria Parasite, Clinical Sciences, Plasmodium falciparum, Immunology, Falciparum (mesh), 610, Sickle Cell Disease (rcdc), Microbiology, Sickle Cell Trait (mesh), Sickle Cell Trait, Rare Diseases (rcdc), Rare Diseases, Clinical Research, Health Sciences, Genetics, Humans, 3207 Medical Microbiology (for-2020), Global Impact of Arboviral Diseases, Pediatric (rcdc), 3202 Clinical Sciences (for-2020), Sickle Cell Disease, Hematology (rcdc), Biomedical and Clinical Sciences, FOS: Clinical medicine, Confidence interval, Public Health, Environmental and Occupational Health, Infant, Rate ratio, Vector-Borne Diseases (rcdc), Infant (mesh), Optics, 3202 Clinical sciences (for-2020), asymptomatic parasitemia, Malaria, Vector-Borne Diseases, Major Articles and Commentaries, Good Health and Well Being, Infectious Diseases (rcdc), Microbiology (science-metrix), FOS: Biological sciences, sickle cell trait, Parasitemia (mesh)
Malaria (rcdc), 2.2 Factors relating to the physical environment (hrcs-rac), 11 Medical and Health Sciences (for), Parasitemia, Medical and Health Sciences, Pediatrics, Clinical Research (rcdc), malaria in infancy, 2.2 Factors relating to the physical environment, Disease, Malaria, Falciparum, 32 Biomedical and Clinical Sciences (for-2020), Genetic and Clinical Aspects of Hemoglobin Disorders, Internal medicine, Pediatric, Humans (mesh), 3 Good Health and Well Being (sdg), Incidence (geometry), Physics, Cohort, Hematology, Biological Sciences, Malaria (mesh), Phenotype (mesh), 06 Biological Sciences (for), Asymptomatic, Infection (hrcs-hc), Infectious Diseases, Phenotype, Medical Microbiology, Plasmodium falciparum (mesh), Medicine, Infection, Falciparum, Sickle cell trait, 570, Malaria Parasite, Clinical Sciences, Plasmodium falciparum, Immunology, Falciparum (mesh), 610, Sickle Cell Disease (rcdc), Microbiology, Sickle Cell Trait (mesh), Sickle Cell Trait, Rare Diseases (rcdc), Rare Diseases, Clinical Research, Health Sciences, Genetics, Humans, 3207 Medical Microbiology (for-2020), Global Impact of Arboviral Diseases, Pediatric (rcdc), 3202 Clinical Sciences (for-2020), Sickle Cell Disease, Hematology (rcdc), Biomedical and Clinical Sciences, FOS: Clinical medicine, Confidence interval, Public Health, Environmental and Occupational Health, Infant, Rate ratio, Vector-Borne Diseases (rcdc), Infant (mesh), Optics, 3202 Clinical sciences (for-2020), asymptomatic parasitemia, Malaria, Vector-Borne Diseases, Major Articles and Commentaries, Good Health and Well Being, Infectious Diseases (rcdc), Microbiology (science-metrix), FOS: Biological sciences, sickle cell trait, Parasitemia (mesh)
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