Abstract
Sickle cell disease (SCD) is a group of recessively inherited disorders of erythrocyte function that presents an ongoing threat to reducing childhood and adult morbidity and mortality around the world. While decades of research have led to improved survival for SCD patients in wealthy countries, survival remains dismal in low- and middle-income countries. Much of the early mortality associated with SCD is attributed to increased risk of infections due to early loss of splenic function. In the West, bacterial infections with encapsulated organisms are a primary concern. In sub-Saharan Africa, where the majority of infants with SCD are born, the same is true. However malaria presents an additional threat to survival. The search for factors that define variability in sickle cell phenotypes should include environmental modifiers, such as malaria. Further exploration of this relationship could lead to novel strategies to reduce morbidity and mortality attributable to infections. In this review, we explore the interactions between SCD, malaria and the spleen to better understand how splenomegaly and splenic (dys)function may co-exist in patients with SCD living in malaria-endemic areas.