Imperial College London
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Professor Thomas N Williams

Faculty of Medicine, Department of Surgery & Cancer

Chair in Haemoglobinopathy Research
 
 
 
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Contact

 

tom.williams Website

 
 
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Location

 

Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Abuga:2022:10.3324/haematol.2021.279316,
author = {Abuga, K and Muriuki, J and Uyoga, S and Mwai, K and Makale, J and Mogire, R and Macharia, A and Mohammed, S and Muthumbi, E and Mwarumba, S and Mturi, N and Bejon, P and Scott, A and Nairz, M and Williams, T and Atkinson, S},
doi = {10.3324/haematol.2021.279316},
journal = {Haematologica: the hematology journal},
pages = {1589--1598},
title = {Hepcidin regulation in Kenyan children with severe malaria and non-typhoidal Salmonella bacteremia},
url = {http://dx.doi.org/10.3324/haematol.2021.279316},
volume = {107},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Abuga,K
AU  - Muriuki,J
AU  - Uyoga,S
AU  - Mwai,K
AU  - Makale,J
AU  - Mogire,R
AU  - Macharia,A
AU  - Mohammed,S
AU  - Muthumbi,E
AU  - Mwarumba,S
AU  - Mturi,N
AU  - Bejon,P
AU  - Scott,A
AU  - Nairz,M
AU  - Williams,T
AU  - Atkinson,S
DO  - 10.3324/haematol.2021.279316
EP  - 1598
PY  - 2022///
SN  - 0390-6078
SP  - 1589
TI  - Hepcidin regulation in Kenyan children with severe malaria and non-typhoidal Salmonella bacteremia
T2  - Haematologica: the hematology journal
UR  - http://dx.doi.org/10.3324/haematol.2021.279316
UR  - https://haematologica.org/article/view/haematol.2021.279316
UR  - http://hdl.handle.net/10044/1/91298
VL  - 107
ER  -
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