easily be misdiagnosed as Plasmodium. Human patients with repeat babesiosis infection may exhibit premunity. Cause Babesia species are in the phylum Apicomplexa, which also has the protozoan parasites that cause malaria, toxoplasmosis, and cryptosporidiosis. Four clades of Babesia species infect humans. The main species in each clade are: B. microti (<3 µm) B. duncani B. divergens (cattle parasite seen mostly in Europe) and B. venatorum (roe deer parasite, formerly called EU1), most closely related to the large Babesia clade Large Babesia (>3 µm) mostly infects ungulates, but also includes K01 strain (an isolated case observed in South Korea, see isolated cases) Pathophysiology Babesia parasites reproduce in red blood cells, where they can be seen as cross-shaped inclusions (four merozoites asexually budding, but attached together forming a structure looking like a "Maltese cross") and cause hemolytic anemia, quite similar to malaria. Unlike the Plasmodium parasites that cause malaria, Babesia species lack an exoerythrocytic phase, so the liver is usually not affected. In nonhuman animals, Babesia canis rossi, Babesia bigemina, and Babesia bovis cause particularly severe forms of the disease, including a severe haemolytic anaemia, with positive erythrocyte-in-saline-agglutination test indicating an immune-mediated component to the haemolysis. Common sequelae include haemoglobinuria "red-water", disseminated intravascular coagulation, and "cerebral babesiosis" caused by sludging of erythrocytes in cerebral capillaries. In bovine species, the organism causes hemolytic anemia, so an infected animal shows pale mucous membranes initially. As the levels of bilirubin (a byproduct of red blood cell lysis) continue to increase, the visible mucous membranes become yellow in color (icterus) due to the failure of the liver to metabolize the excess bilirubin. Hemoglobinuria is seen due to excretion of red-blood-cell lysis byproducts via the kidneys. Fever of 40.5 °C (105 °F) develops due to release of inflammatory byproducts. Diagnosis Only specialized laboratories can adequately diagnose Babesia infection in humans, so Babesia infections are considered highly under-reported. It develops in patients who live in or travel to an endemic area or receive a contaminated blood transfusion within the preceding 9 weeks, so this aspect of the medical history is vital. Babesiosis may be suspected when a person with such an exposure history develops persistent fevers and hemolytic anemia. The definitive diagnostic test is the identification of parasites on a Giemsa-stained thin-film blood smear. So-called "Maltese cross formations" on the blood film are diagnostic (pathognomonic) of babesiosis, since they are not seen in malaria, the primary differential diagnosis.