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Published in: Malaria Journal 1/2007

Open Access 01-12-2007 | Research

Complement activation in Ghanaian children with severe Plasmodium falciparum malaria

Authors: Gideon K Helegbe, Bamenla Q Goka, Joergen AL Kurtzhals, Michael M Addae, Edwin Ollaga, John KA Tetteh, Daniel Dodoo, Michael F Ofori, George Obeng-Adjei, Kenji Hirayama, Gordon A Awandare, Bartholomew D Akanmori

Published in: Malaria Journal | Issue 1/2007

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Abstract

Background

Severe anaemia (SA), intravascular haemolysis (IVH) and respiratory distress (RD) are severe forms of Plasmodium falciparum malaria, with RD reported to be of prognostic importance in African children with malarial anaemia. Complement factors have been implicated in the mechanism leading to excess anaemia in acute P. falciparum infection.

Methods

The direct Coombs test (DCT) and flow cytometry were used to investigate the mean levels of RBC-bound complement fragments (C3d and C3bαβ) and the regulatory proteins [complement receptor 1 (CD35) and decay accelerating factor (CD55)] in children with discrete clinical forms of P. falciparum malaria. The relationship between the findings and clinical parameters including coma, haemoglobin (Hb) levels and RD were investigated.

Results

Of the 484 samples tested, 131(27%) were positive in DCT, out of which 115/131 (87.8%) were positive for C3d alone while 16/131 (12.2%) were positive for either IgG alone or both. 67.4% of the study population were below 5 years of age and DCT positivity was more common in this age group relative to children who were 5 years or older (Odds ratio, OR = 3.8; 95%CI, 2.2–6.7, p < 0.001). DCT correlated significantly with RD (β = -304, p = 0.006), but multiple regression analysis revealed that, Hb (β = -0.341, p = 0.012) and coma (β = -0.256, p = 0.034) were stronger predictors of RD than DCT (β = 0.228, p = 0.061). DCT was also not associated with IVH, p = 0.19, while spleen size was inversely correlated with Hb (r = -402, p = 0.001). Flow cytometry showed similar mean fluorescent intensity (MFI) values of CD35, CD55 and C3bαβ levels on the surfaces of RBC in patients and asymptomatic controls (AC). However, binding of C3bαβ correlated significantly with CD35 or CD55 (p < 0.001).

Conclusion

These results suggest that complement activation contributed to anaemia in acute childhood P. falciparum malaria, possibly through induction of erythrophagocytosis and haemolysis. In contrast to other studies, this study did not find association between levels of the complement regulatory proteins, CD35 and CD55 and malarial anaemia. These findings suggest that complement activation could also be involved in the pathogenesis of RD but larger studies are needed to confirm this finding.
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Metadata
Title
Complement activation in Ghanaian children with severe Plasmodium falciparum malaria
Authors
Gideon K Helegbe
Bamenla Q Goka
Joergen AL Kurtzhals
Michael M Addae
Edwin Ollaga
John KA Tetteh
Daniel Dodoo
Michael F Ofori
George Obeng-Adjei
Kenji Hirayama
Gordon A Awandare
Bartholomew D Akanmori
Publication date
01-12-2007
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2007
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-6-165

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