The genus Babesia belongs to the subphylum Apicomplexa, which includes Toxoplasma and the malaria parasite Plasmodium. Ninety-nine species of Babesia have been identified. B. microti (reservoir in mice), B. divergens (reservoir in cattle), and the recently identified species WA-1 and MO-1 (reservoir unknown) are implicated in human disease in the United States. B. divergens is the major pathogen in Europe.

Microscopically, Babesia organisms are small (1 to 5 mm long), round, oval, or pear shaped. Because Babesia produces an illness similar to that produced by Plasmodium, the distinguishing laboratory features used to differentiate the two include Babesia‘s inability to produce pigments in red blood cells (RBCs) in the latter stages of its life cycle, the presence of extracellular merozoites, and the rare formation of tetrads of merozoites resembling a Maltese cross.

In the United States, the Ixodidae family of small, hard-bodied ticks is the primary vector for B. microti. This tick infects the northeastern United States from Wisconsin and Minnesota to Maryland. Infections due to variants of B. microti have also been reported in Missouri and on the coast of the United States in Washington and California. Ixodes scapularis is the species predominantly incriminated and is the same species of the tick implicated in Lyme disease and human granulocytic ehrlichiosis. Transmission through blood transfusion and from transplanted organs as well as perinatal transplacental transmission have also occurred.

The tick’s life cycle spans approximately 2 years and comprises three stages: larval, nymphal, and adult. The most common host for the larval form is the white-footed mouse, Peromyscus leucopus. The transformation of the larval form to the nymphal form occurs transtadial. The white-tailed deer is the major reservoir for the adult tick, allowing mating to occur. The deer reservoir has allowed an expansion of the scope of babesiosis due to an increase deer population allowing an associated rise in the tick population. Babesia is transmitted to humans predominantly by the nymphal form of the tick.

Babesiosis occurs most often in the United States during late summer and fall, which is the nymph’s major feeding period. Most cases have been confined to the northeastern states, coinciding with the tick vector epidemiology.

Although the exact mechanisms that allow Babesia to enter the red cell are unknown, the complement C3b receptor has been shown to be involved in the parasite’s entry into the RBC in mice infected with B. rodhani. Once inside the RBC, the organism reproduces asexually by budding into two to four merozoites, which are released from the RBCs at varying times, in contrast to malaria-causing plasmodia, which are released synchronously from RBCs. Thus, Babesia generally is marked by milder symptoms of RBC lysis. The actual mechanisms that lead to hemolysis are unknown. Acute renal failure can occur with massive hemolysis.

The spleen is intimately involved in the disease process. Splenic dysfunction generally causes a more severe case of babesiosis. Owing to the spleen’s reticuloendothelial cell capacity to remove deformed (parasitized) RBCs, removal of the spleen can lead to a relapse of disease in treated patients.

Cell-mediated immunity appears critical to control infections, although a humoral immune response is manifested.