More than malaria: Exploring Babesia, Leishmania and Trypanosoma in sickle cell disease

Vector-borne parasites, such as species of Babesia, Trypanosoma, and Leishmania, are emerging and re-emerging causes of infectious diseases that contribute substantially to global morbidity and mortality. Epidemiological shifts, such as expansion of arthropod vector ranges, increased international travel, and transfusion-associated transmission, have amplified their public health impact. A key distinction among these parasites is their localization within the host. Babesia spp. infect erythrocytes, Leishmania spp. reside within macrophages, and Trypanosoma cruzi invades muscle cells, whereas Trypanosoma brucei remains extracellular within the bloodstream and lymphatics. These differences influence immune evasion, disease progression, and treatment response. Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by abnormal erythrocytes, chronic hemolysis, vaso-occlusion, and progressive organ damage, which may significantly alter host susceptibility to parasitic infections. While interactions between SCD and malaria-causing Plasmodium spp. are well established, less is known about its impact on infections caused by Babesia spp., Trypanosoma spp., and Leishmania spp. This narrative review synthesizes current evidence on the relationship between SCD and these parasites, focusing on pathophysiology, immune responses, clinical manifestations, and management strategies. Differences in intracellular versus extracellular localization are examined to better understand their effects on disease severity and treatment outcomes. Improved understanding of these interactions may inform targeted screening, novel therapeutic/management approaches, and transfusion safety strategies (especially those at increased risk for transfusion-transmitted infections), while highlighting critical gaps for future research.