Review Hemoglobinopathies: Slicing the Gordian Knot of Plasmodium falciparum Malaria Pathogenesis

Abstract: Plasmodium falciparum malaria kills over 500,000 children every year and has been a scourge of humans for millennia. Owing to the co-evolution of humans and P. falciparum parasites, the human genome is imprinted with polymorphisms that not only confer innate resistance to falciparum malaria, but also cause hemoglobinopathies. These genetic traits—including he-moglobin S (HbS), hemoglobin C (HbC), and a-thalasse-mia—are the most common monogenic human disorders and can confer remarkable degrees of protection from severe, life-threatening falciparum malaria in African children: the risk is reduced 70 % by homozygous HbC and 90 % by heterozygous HbS (sickle-cell trait). Impor-tantly, this protection is principally present for severe disease and largely absent for P. falciparum infection