Complement activation in Ghanaian children with severe Plasmodium falciparum malaria.
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 C3balphabeta) 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 (beta = -304, p = 0.006), but multiple regression analysis revealed that, Hb (beta = -0.341, p = 0.012) and coma (beta = -0.256, p = 0.034) were stronger predictors of RD than DCT (beta = 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 C3balphabeta levels on the surfaces of RBC in patients and asymptomatic controls (AC). However, binding of C3balphabeta correlated significantly with CD35 or CD55 (p < 0.001).


CONCLUSIONS
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.
Helegbe
Gideon K
GK
Department of Biochemistry and Molecular Medicine, SMHS, UDS, Tamale, Ghana. kofigidi@yahoo.com
Goka
Bamenla Q
BQ
Kurtzhals
Joergen A L
JA
Addae
Michael M
MM
Ollaga
Edwin
E
Tetteh
John K A
JK
Dodoo
Daniel
D
Ofori
Michael F
MF
Obeng-Adjei
George
G
Hirayama
Kenji
K
Awandare
Gordon A
GA
Akanmori
Bartholomew D
BD
D000367:Age Factors; D000740:Anemia / Q000209:etiology* / Q000276:immunology; D018958:CD55 Antigens / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003167:Complement Activation / Q000276:immunology / Q000502:physiology*; D003179:Complement C3b / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D015933:Complement C3d / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D003298:Coombs Test; D004912:Erythrocytes / Q000276:immunology; D005434:Flow Cytometry; D005869:Ghana; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007223:Infant; D016779:Malaria, Cerebral / Q000209:etiology* / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology*; D011237:Predictive Value of Tests; D017463:Receptors, Complement 3b / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D012140:Respiratory Tract Diseases / Q000209:etiology* / Q000276:immunology; D013223:Statistics as Topic
D018958:CD55 Antigens; C509991:CR1 protein, human; D006454:Hemoglobins; D017463:Receptors, Complement 3b; D003179:Complement C3b; D015933:Complement C3d