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{Uyoga:2022:10.1016/S2352-4642(22)00153-5,
author = {Uyoga, S and Olupot-Olupot, P and Connon, R and Kiguli, S and Opoka, R and Alaroker, F and Muhindo, R and Macharia, AW and Dondorp, A and Gibb, D and Walker, AS and George, E and Maitland, K and Williams, T},
doi = {10.1016/S2352-4642(22)00153-5},
journal = {The Lancet Child & Adolescent Health},
pages = {606--613},
title = {Sickle cell anaemia and severe P. falciparum malaria: a secondary analysis of the Transfusion and Treatment of African Children (TRACT) trial},
url = {http://dx.doi.org/10.1016/S2352-4642(22)00153-5},
volume = {6},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundSickle cell anaemia (SCA; HbSS) has historically been associated with high levels of childhood mortality in Africa. While malaria plays a major contribution to this mortality to date, the clinical pathology of malaria among children with SCA has been poorly described. Methods We investigated the burden and severity of malaria infections among children recruited with severe anaemia to the TRACT trial of blood transfusion in Africa. This secondary analysis, conducted after trial completion, is restricted to Uganda, where the birth prevalence of SCA is approximately 1% and malaria transmission is high. Children were classified as normal (HbAA), heterozygous (HbAS) or homozygous (HbSS; SCA) for the rs334 A>T sickle mutation in HBB following batch-genotyping by PCR at the end of trial. To avoid confounding from SCA-specific medical interventions, we considered children with an existing diagnosis of SCA (known-SCA) separately from those diagnosed at the end of the trial (unknown-SCA). Findings Overall, 1,038 of 3,483 (30%) of the Ugandan children recruited to TRACT had SCA. While 1,815/2,321 (78%) of the non-SCA (HbAA) children tested positive for P. falciparum malaria, the prevalence was significantly lower in children with SCA (347/1,038; 33%; p<0.001). Concentrations of plasma P. falciparum Histidine Rich Protein 2 (PfHRP2), a marker of the total burden of malaria parasites within an individual, were significantly lower in children with either known-SCA (median 8 ng/mL; IQR 0-57) or unknown-SCA (7 ng/mL (0-50 ng/mL) than in HbAA children (346 ng/mL; 21-2,121; p<0.001). By contrast to HbAA children, few HbSS children presented with classic features of severe and complicated malaria, but both the frequency and severity of anaemia were higher in HbSS children.Interpretation The current study suggests that children with SCA are innately protected against classic severe malaria. However, it also shows that even low-level infections can precipitate severe
AU  - Uyoga,S
AU  - Olupot-Olupot,P
AU  - Connon,R
AU  - Kiguli,S
AU  - Opoka,R
AU  - Alaroker,F
AU  - Muhindo,R
AU  - Macharia,AW
AU  - Dondorp,A
AU  - Gibb,D
AU  - Walker,AS
AU  - George,E
AU  - Maitland,K
AU  - Williams,T
DO  - 10.1016/S2352-4642(22)00153-5
EP  - 613
PY  - 2022///
SN  - 2352-4642
SP  - 606
TI  - Sickle cell anaemia and severe P. falciparum malaria: a secondary analysis of the Transfusion and Treatment of African Children (TRACT) trial
T2  - The Lancet Child & Adolescent Health
UR  - http://dx.doi.org/10.1016/S2352-4642(22)00153-5
UR  - https://www.sciencedirect.com/science/article/pii/S2352464222001535?via%3Dihub
UR  - http://hdl.handle.net/10044/1/97025
VL  - 6
ER  -
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