Sickle cell anaemia and severe P. falciparum malaria: a secondary analysis of the Transfusion and Treatment of African Children (TRACT) trial

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Title: Sickle cell anaemia and severe P. falciparum malaria: a secondary analysis of the Transfusion and Treatment of African Children (TRACT) trial
Authors: Uyoga, S
Olupot-Olupot, P
Connon, R
Kiguli, S
Opoka, R
Alaroker, F
Muhindo, R
Macharia, AW
Dondorp, A
Gibb, D
Walker, AS
George, E
Maitland, K
Williams, T
Item Type: Journal Article
Abstract: Background Sickle 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 anaemic crises, that would likely prove fatal without rapid access to blood transfusion services. Funding The TRACT trial was supported by a grant (MR/J012483/1) from the United Kingdom Medical Research Council (MRC) through a concordat with the Department for International Development. The MRC Clinical Trials Unit at University College London receives core support from the MRC (MC_UU_00004/05). ASW is a National Institutes of Health Research (NIHR) Senior Investigator. The views expressed do not represent those of the NIHR or Department of Health. SU was funded through the DELTAS Africa Initiative (DEL-15-003), an independent funding scheme of the African Academy of Sciences’ Alliance for Accelerating Excellence in Science in Africa that is supported by the New Partnership for Africa’s Development Planning and Coordinating Agency with funding from the Wellcome Trust (grant 203077/Z/16/Z) and the UK government. The research was funded in part by Wellcome (grant number 202800/Z/16/Z to TNW, grant no 209265/Z/17/Z to AMD and KM, and grant no 089275/Z/09/Z to AMD).
Issue Date: Sep-2022
Date of Acceptance: 29-Apr-2022
URI: http://hdl.handle.net/10044/1/97025
DOI: 10.1016/S2352-4642(22)00153-5
ISSN: 2352-4642
Publisher: Elsevier
Start Page: 606
End Page: 613
Journal / Book Title: The Lancet Child & Adolescent Health
Volume: 6
Issue: 9
Copyright Statement: © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
Sponsor/Funder: Wellcome Trust
Wellcome Trust
Wellcome Trust, MRC, UDAID, NIHR
Medical Research Council
Medical Research Council (MRC)
Medical Research Council
Wellcome Trust
Funder's Grant Number: 091758/B/10/Z
202800/Z/16/Z
MR/S004904/1
MR/JO12483
MR/J012483/1
MR/J012483/1
209265/Z/17/Z
Keywords: Anemia, Sickle Cell
Blood Transfusion
Child
Child, Preschool
Hemoglobins
Humans
Infant
Malaria
Malaria, Falciparum
Humans
Malaria
Malaria, Falciparum
Anemia, Sickle Cell
Hemoglobins
Blood Transfusion
Child
Child, Preschool
Infant
Publication Status: Published
Online Publication Date: 2022-07-02
Appears in Collections:Department of Surgery and Cancer
Department of Infectious Diseases
Faculty of Medicine



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