TY - JOUR

T1 - Complement activation in Ghanaian children with severe Plasmodium falciparum malaria

AU - Helegbe, Gideon K

AU - Goka, Bamenla Q

AU - Kurtzhals, Jørgen

AU - Addae, Michael M

AU - Ollaga, Edwin

AU - Tetteh, John K A

AU - Dodoo, Daniel

AU - Ofori, Michael F

AU - Obeng-Adjei, George

AU - Hirayama, Kenji

AU - Awandare, Gordon A

AU - Akanmori, Bartholomew D

N1 - Keywords: Age Factors; Anemia; Antigens, CD55; Child; Child, Preschool; Complement Activation; Complement C3b; Complement C3d; Coombs' Test; Erythrocytes; Flow Cytometry; Ghana; Hemoglobins; Humans; Infant; Malaria, Cerebral; Malaria, Falciparum; Predictive Value of Tests; Receptors, Complement 3b; Respiratory Tract Diseases; Statistics as Topic

PY - 2007

Y1 - 2007

N2 - 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). 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.

AB - 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). 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.

U2 - 10.1186/1475-2875-6-165

DO - 10.1186/1475-2875-6-165

M3 - Journal article

C2 - 18086298

VL - 6

SP - 165

JO - Malaria Journal

JF - Malaria Journal

SN - 1475-2875

ER -