Complement binding to erythrocytes is associated with macrophage activation and reduced haemoglobin in Plasmodium falciparum malaria

We have examined IgG and complement factor C3d deposition on erythrocytes b y means of the direct Coombs' test (DAT) and looked for an association with the anaemia seen in falciparum malaria in children living in an area of hy perendemic malaria transmission (in Ghana). In one study (in 1997), 53 out of 199 patients had a positive DAT. Of these, 45 samples reacted with anti- C3d antibodies, 2 with anti-IgG and 6 with both reagents. There were signif icantly lower haemoglobin (Hb)-levels and higher prevalence of spleen enlar gement in DAT-positive than in DAT-negative patients. Hb-levels were indepe ndently associated with DAT and age. This initial study was designed to inv estigate the role of intravascular haemolysis (IVH), but we found no associ ation between IVH and either DAT result or anaemia. Because of the risk of selection bias we repeated the study using consecutive enrolment of malaria patients and were able to confirm the results in a total of 49 DAT-positiv e and 183 DAT-negative patients. This second study (in 1998) was designed t o look at the importance of erythrophagocytosis through measurement of plas ma neopterin levels and total nitrite and nitrate as markers of NO-release. Both parameters were significantly higher in DAT-positive than in DAT-nega tive patients (P < 0.001), indicating that complement binding to erythrocyt es was associated with macrophage activation. Plasma levels of haptoglobin, interleukin-10 and tumour necrosis factor-alpha did not vary between the g roups. The studies support the role of complement activation and erythropha gocytosis in the pathogenesis of anaemia in falciparum malaria in African c hildren.