Hepcidin regulation in Kenyan children with severe malaria and non-typhoidal Salmonella bacteremia
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Malaria and invasive non-typhoidal Salmonella (NTS) are life-threatening infections that often co-exist in African children. The iron-regulatory hormone hepcidin is highly upregulated during malaria and controls the availability of iron, a critical nutrient for bacterial growth. We investigated the relationship between Plasmodium falciparum malaria and NTS bacteremia in all pediatric admissions aged ≤5 years between August 1998 and October 2019 (n=75,034). We then assayed hepcidin and measures of iron status in five groups: (1) children with concomitant severe malarial anemia (SMA) and NTS (SMA+NTS, n=16); and in matched children with (2) SMA (n=33); (3) NTS (n=33); (4) cerebral malaria (CM, n=34); and (5) community-based children. SMA and severe anemia without malaria were associated with a two-fold or more increased risk of NTS bacteremia, while other malaria phenotypes were not associated with increased NTS risk. Children with SMA had lower hepcidin/ferritin ratios (0.10 [IQR 0.03, 0.19]) than those with CM (0.24 [0.14, 0.69]; P=0.006) or asymptomatic malaria (0.19 [0.09, 0.46]; P=0.01) indicating suppressed hepcidin levels. Children with SMA+NTS had lower hepcidin levels (9.3 ng/mL [4.7, 49.8]) and hepcidin/ferritin ratios (0.03 [0.01, 0.22]) than those with NTS alone (105.8 ng/mL [17.3, 233.3]; P=0.02 and 0.31 [0.06, 0.66]; P=0.007, respectively). Since hepcidin degrades ferroportin on the Salmonella-containing vacuole (SCV), we hypothesize that reduced hepcidin in children with SMA might contribute to NTS growth by modulating iron availability for bacterial growth. Further studies are needed to understand how the hepcidin-ferroportin axis might mediate susceptibility to NTS in severely anemic children.
Date Issued
2022-07
Date Acceptance
2021-08-18
Citation
Haematologica: the hematology journal, 2022, 107 (7), pp.1589-1598
ISSN
0390-6078
Publisher
Ferrata Storti Foundation
Start Page
1589
End Page
1598
Journal / Book Title
Haematologica: the hematology journal
Volume
107
Issue
7
Copyright Statement
©2022 Ferrata Storti Foundation
Haematologica material is published under a CC
BY-NC license.
Haematologica material is published under a CC
BY-NC license.
License URL
Sponsor
Wellcome Trust
Wellcome Trust
Wellcome Trust
Identifier
https://haematologica.org/article/view/haematol.2021.279316
Grant Number
091758/B/10/Z
202800/Z/16/Z
203077/C/16/Z
Subjects
Anemia
Bacteremia
Child
Ferritins
Hepcidins
Humans
Iron
Kenya
Malaria
Malaria, Falciparum
Salmonella
Humans
Salmonella
Bacteremia
Malaria
Malaria, Falciparum
Anemia
Iron
Child
Kenya
Ferritins
Hepcidins
1102 Cardiorespiratory Medicine and Haematology
Immunology
Publication Status
Published
Date Publish Online
2022-07