Factor H-related protein 1 deficiency and risk of severe falciparum malaria in Ghanaian children: a cohort analysis.

Malaria caused by Plasmodium falciparum remains a leading cause of childhood mortality in sub-Saharan Africa. The intraerythrocytic parasite can evade complement-mediated destruction through recruitment of human Factor H (FH). In vitro, Factor H-related protein 1 (FHR-1) competes with FH for binding sites, suggesting a potential role in modulating complement activation during infection. Because one-third of Africans carry a CFHR3/1 deletion, we examined the impact of FHR-1 deficiency on malaria severity. We analyzed plasma from 500 Ghanaian children presenting with different clinical manifestations. One-third of plasma samples lacked detectable FHR-1 protein, but logistic regression analysis revealed no association between FHR-1 deficiency and risk of severe malaria. In contrast, FHR-1 deficiency was overrepresented among children presenting with anemia and multiple syndromes and affected children exhibited markedly lower hemoglobin levels. These findings indicate that FHR-1 deficiency does not affect overall progression of severe falciparum malaria, but correlates with severe malarial anemia.