Decreased parasite burden and altered host response in children with sickle cell anemia and severe anemia with malaria.

Abstract

Plasmodium falciparum malaria causes morbidity and mortality in African children with sickle cell anemia (SCA), but comparisons of host responses to P falciparum between children with SCA (homozygous sickle cell disease/hemoglobin SS [HbSS]) and normal hemoglobin genotype/hemoglobin AA (HbAA) are limited. We assessed parasite biomass and plasma markers of inflammation and endothelial activation in children with HbAA (n = 208) or HbSS (n = 22) who presented with severe anemia and P falciparum parasitemia to Mulago Hospital in Kampala, Uganda. Genotyping was performed at study completion. No child had known SCA at enrollment. Children with HbSS did not differ from children with HbAA in peripheral parasite density, but had significantly lower sequestered parasite biomass. Children with HbSS had greater leukocytosis but significantly lower concentrations of several plasma inflammatory cytokines, including tumor necrosis factor α (TNF-α). In contrast, children with HbSS had threefold greater concentrations of angiopoietin-2 (Angpt-2), a marker of endothelial dysregulation associated with mortality in severe malaria. Lower TNF-α concentrations were associated with increased risk of postdischarge mortality or readmission, whereas higher Angpt-2 concentrations were associated with increased risk of recurrent clinical malaria. Children with SCA have decreased parasite sequestration and inflammation but increased endothelial dysregulation during severe anemia with P falciparum parasitemia, which may ameliorate acute infectious complications but predispose to harmful long-term sequelae.

• Authors: Ryan C Henrici, Casey L Sautter, Caitlin Bond, Robert O Opoka, Ruth Namazzi, Dibyadyuti Datta, Russell E Ware, Andrea L Conroy, Chandy C John
• Journal: Blood advances (Blood Adv) Vol. 5 Issue 22 Pg. 4710-4720 (11 23 2021) ISSN: 2473-9537 [Electronic] United States
• PMID: 34470050 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Topics

• Aftercare
• Anemia, Sickle Cell (complications)
• Animals
• Child
• Humans
• Malaria
• Parasites
• Patient Discharge
• Uganda (epidemiology)