Sickle Cell Anemia and Babesia Infection

Abstract

Babesia is an intraerythrocytic, obligate Apicomplexan parasite that has, in the last century, been implicated in human infections via zoonosis and is now widespread, especially in parts of the USA and Europe. It is naturally transmitted by the bite of a tick, but transfused blood from infected donors has also proven to be a major source of transmission. When infected, most humans are clinically asymptomatic, but the parasite can prove to be lethal when it infects immunocompromised individuals. Hemolysis and anemia are two common symptoms that accompany many infectious diseases, and this is particularly true of parasitic diseases that target red cells. Clinically, this becomes an acute problem for subjects who are prone to hemolysis and depend on frequent transfusions, like patients with sickle cell anemia or thalassemia. Little is known about Babesia’s pathogenesis in these hemoglobinopathies, and most parallels are drawn from its evolutionarily related Plasmodium parasite which shares the same environmental niche, the RBCs, in the human host. In vitro as well as in vivo Babesia-infected mouse sickle cell disease (SCD) models support the inhibition of intra-erythrocytic parasite proliferation, but mechanisms driving the protection of such hemoglobinopathies against infection are not fully studied. This review provides an overview of our current knowledge of Babesia infection and hemoglobinopathies, focusing on possible mechanisms behind this parasite resistance and the clinical repercussions faced by Babesia-infected human hosts harboring mutations in their globin gene.

Elucidating parasite and host-cell factors enabling Babesia infection in sickle red cells under hypoxic/hyperoxic conditions

“…For blood-borne parasites, the environment within the host RBC together with its membrane proteins and hemoglobin (Hb), the primary O 2 carrier, are important determinants of parasite success. 5 Pathogenesis of the 2 major human intraerythrocytic parasites, Plasmodium and Babesia , is intrinsically tied to parasite replication within the RBC followed by the lytic destruction of these cells, leading to anemia and organ damage. 6 , 7 , 8 , 9 , 10 …”

“… 11 , 12 , 13 Of the 4 Babesia species that can infect humans, B microti, B divergens, B duncani , and B venatorum , only B divergens and B duncani can be propagated continuously in vitro culture in human RBCs. 14 , 15 , 16 We have focused on B divergens to dissect the relationship between this parasitic infection and SCD 5 , 17 and to understand the mechanisms and pathology that compromise parasite growth in sickle (SS) cells. The single point genetic mutation in the beta chain of globin (Glu6Val) causes the production of abnormal Hb (HbS) in sickle RBCs.…”

Identification and characterization of extracellular vesicles from red cells infected with Babesia divergens and Babesia microti

“…Like the others, Babesia parasites present a complex life cycle spanning two hosts-a tick vector and a mammalian host. Of the five species that cause human disease, B. divergens and B. microti have received the most attention because of their growing infection rate in humans via transfer from animal reservoirs, and as asymptomatic infections in man are common, these can be life threatening in certain blood transfusion recipients like hemoglobinopathic individuals (Lobo et al, 2013;Schmidt et al, 2014;Beri et al, 2021).…”

Transfusion‐transmitted babesiosis in a patient with sickle cell disease undergoing chronic red cell exchange

“…Prompt recognition is critical to prevent the progression of infection with the development of associated complications. Second, patients with SCD are disproportionately at risk of TTB— and specifically—of severe or even fatal sequelae 8,9 . There are both intrinsic and extrinsic factors that account for this vulnerability.…”