Elevated uric acid levels, mortality and cognitive impairment in children with severe malaria

Caitlin Bond; Olivia J. Bednarski; Dibyadyuti Datta; Ruth Namazzi; Robert O. Opoka; Giselle Lima-Cooper; Anthony Batte; Keerthi Udumula; Deepali Balasubramani; Marilyn Vasquez; Ana Rodriguez; Claire Liepmann; Paul Bangirana; Marco Abreu; Tae Hwi Schwantes-An; Yi Zhao; Tarek M. El-Achkar; Nathan W. Schmidt; Chandy C. John; Andrea L. Conroy

doi:10.1038/s41591-024-03430-8

Elevated uric acid levels, mortality and cognitive impairment in children with severe malaria

Caitlin Bond, Olivia J. Bednarski, Dibyadyuti Datta, Ruth Namazzi, Robert O. Opoka, Giselle Lima-Cooper, Anthony Batte, Keerthi Udumula, Deepali Balasubramani, Marilyn Vasquez, Ana Rodriguez, Claire Liepmann, Paul Bangirana, Marco Abreu, Tae Hwi Schwantes-An, Yi Zhao, Tarek M. El-Achkar, Nathan W. Schmidt, Chandy C. John, Andrea L. Conroy

Research output: Contribution to journal › Article › peer-review

Abstract

We investigated the role of uric acid in the pathogenesis of severe malaria (SM) in two independent cohorts of children with SM. Hyperuricemia (blood uric acid ≥ 7 mg dl⁻¹) was present in 25% of children with SM and was associated with increased in-hospital mortality and postdischarge mortality in both cohorts. Increased blood uric acid levels were also associated with worse scores in overall cognition in children with SM < 5 years old in both cohorts. Hemolysis of infected red blood cells and impaired renal excretion of uric acid were the primary drivers of hyperuricemia in SM. Hyperuricemia was associated with multiple complications of SM, including acute kidney injury, acidosis, impaired perfusion, coma and intestinal injury with increases in the abundance of Gram-negative uricase-producing pathobionts (Escherichia and Shigella) in the stool. Clinical trials evaluating uric acid-lowering medications as adjunctive therapy for children with SM should be considered to improve survival and protect neurodevelopment.

Original language	English
Article number	36
Journal	Nature Medicine
DOIs	https://doi.org/10.1038/s41591-024-03430-8
Publication status	Accepted/In press - 2025
Externally published	Yes

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10.1038/s41591-024-03430-8

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Bond, C., Bednarski, O. J., Datta, D., Namazzi, R., Opoka, R. O., Lima-Cooper, G., Batte, A., Udumula, K., Balasubramani, D., Vasquez, M., Rodriguez, A., Liepmann, C., Bangirana, P., Abreu, M., Schwantes-An, T. H., Zhao, Y., El-Achkar, T. M., Schmidt, N. W., John, C. C., & Conroy, A. L. (Accepted/In press). Elevated uric acid levels, mortality and cognitive impairment in children with severe malaria. Nature Medicine, Article 36. https://doi.org/10.1038/s41591-024-03430-8

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title = "Elevated uric acid levels, mortality and cognitive impairment in children with severe malaria",

abstract = "We investigated the role of uric acid in the pathogenesis of severe malaria (SM) in two independent cohorts of children with SM. Hyperuricemia (blood uric acid ≥ 7 mg dl−1) was present in 25% of children with SM and was associated with increased in-hospital mortality and postdischarge mortality in both cohorts. Increased blood uric acid levels were also associated with worse scores in overall cognition in children with SM < 5 years old in both cohorts. Hemolysis of infected red blood cells and impaired renal excretion of uric acid were the primary drivers of hyperuricemia in SM. Hyperuricemia was associated with multiple complications of SM, including acute kidney injury, acidosis, impaired perfusion, coma and intestinal injury with increases in the abundance of Gram-negative uricase-producing pathobionts (Escherichia and Shigella) in the stool. Clinical trials evaluating uric acid-lowering medications as adjunctive therapy for children with SM should be considered to improve survival and protect neurodevelopment.",

author = "Caitlin Bond and Bednarski, {Olivia J.} and Dibyadyuti Datta and Ruth Namazzi and Opoka, {Robert O.} and Giselle Lima-Cooper and Anthony Batte and Keerthi Udumula and Deepali Balasubramani and Marilyn Vasquez and Ana Rodriguez and Claire Liepmann and Paul Bangirana and Marco Abreu and Schwantes-An, {Tae Hwi} and Yi Zhao and El-Achkar, {Tarek M.} and Schmidt, {Nathan W.} and John, {Chandy C.} and Conroy, {Andrea L.}",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature America, Inc. 2025.",

year = "2025",

doi = "10.1038/s41591-024-03430-8",

language = "English",

journal = "Nature Medicine",

issn = "1078-8956",

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Bond, C, Bednarski, OJ, Datta, D, Namazzi, R, Opoka, RO, Lima-Cooper, G, Batte, A, Udumula, K, Balasubramani, D, Vasquez, M, Rodriguez, A, Liepmann, C, Bangirana, P, Abreu, M, Schwantes-An, TH, Zhao, Y, El-Achkar, TM, Schmidt, NW, John, CC & Conroy, AL 2025, 'Elevated uric acid levels, mortality and cognitive impairment in children with severe malaria', Nature Medicine. https://doi.org/10.1038/s41591-024-03430-8

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AU - Bond, Caitlin

AU - Bednarski, Olivia J.

AU - Datta, Dibyadyuti

AU - Namazzi, Ruth

AU - Opoka, Robert O.

AU - Lima-Cooper, Giselle

AU - Batte, Anthony

AU - Udumula, Keerthi

AU - Balasubramani, Deepali

AU - Vasquez, Marilyn

AU - Rodriguez, Ana

AU - Liepmann, Claire

AU - Bangirana, Paul

AU - Abreu, Marco

AU - Schwantes-An, Tae Hwi

AU - Zhao, Yi

AU - El-Achkar, Tarek M.

AU - Schmidt, Nathan W.

AU - John, Chandy C.

AU - Conroy, Andrea L.

PY - 2025

Y1 - 2025

N2 - We investigated the role of uric acid in the pathogenesis of severe malaria (SM) in two independent cohorts of children with SM. Hyperuricemia (blood uric acid ≥ 7 mg dl−1) was present in 25% of children with SM and was associated with increased in-hospital mortality and postdischarge mortality in both cohorts. Increased blood uric acid levels were also associated with worse scores in overall cognition in children with SM < 5 years old in both cohorts. Hemolysis of infected red blood cells and impaired renal excretion of uric acid were the primary drivers of hyperuricemia in SM. Hyperuricemia was associated with multiple complications of SM, including acute kidney injury, acidosis, impaired perfusion, coma and intestinal injury with increases in the abundance of Gram-negative uricase-producing pathobionts (Escherichia and Shigella) in the stool. Clinical trials evaluating uric acid-lowering medications as adjunctive therapy for children with SM should be considered to improve survival and protect neurodevelopment.

AB - We investigated the role of uric acid in the pathogenesis of severe malaria (SM) in two independent cohorts of children with SM. Hyperuricemia (blood uric acid ≥ 7 mg dl−1) was present in 25% of children with SM and was associated with increased in-hospital mortality and postdischarge mortality in both cohorts. Increased blood uric acid levels were also associated with worse scores in overall cognition in children with SM < 5 years old in both cohorts. Hemolysis of infected red blood cells and impaired renal excretion of uric acid were the primary drivers of hyperuricemia in SM. Hyperuricemia was associated with multiple complications of SM, including acute kidney injury, acidosis, impaired perfusion, coma and intestinal injury with increases in the abundance of Gram-negative uricase-producing pathobionts (Escherichia and Shigella) in the stool. Clinical trials evaluating uric acid-lowering medications as adjunctive therapy for children with SM should be considered to improve survival and protect neurodevelopment.

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SN - 1078-8956

JO - Nature Medicine

JF - Nature Medicine

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ER -

Elevated uric acid levels, mortality and cognitive impairment in children with severe malaria

Abstract

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