Babesiosis is a parasitic infection caused by protozoa of the genus Babesia. Babesia species have been subdivided into four categories, known as clades. Babesia microti is the most prevalent and well-described species and is a classified as a Clade 1 organism. Babesiosis is typically acquired by bites from ticks carrying the protozoa. As the parasite infects erythrocytes (red blood cells), the infection can be acquired through blood transfusion and therefore can occur in persons who have not traveled to endemic areas. Transplacental transmission has also been reported.
Of the more than 100 Babesia species known to infect vertebrate animals, only a few have been documented to cause infection in humans. Ixodes ticks are the vector, and the primary reservoirs are typically small vertebrates such as rodents (particularly the white-foot mouse in the U.S.) and birds and the interaction between the vector and primary reservoir is required to complete the organism's life cycle. Larger mammals, particularly deer, sustain the adult population by providing a source of blood meal but are not reservoir hosts. Humans are accidental and dead-end hosts, and infections tend to occur in late spring through the fall in areas where humans are in proximity to ticks and their reservoirs. The majority of cases of Babesiosis in the United States occur in the Northeast (CT, MA, NJ, NY, RI) and upper Midwest (MN, WI) and are due to Babesia microti, transmitted by the Ixodes scapularis tick. The incidence of infection in this geographic area has been increasing. Babesiosis occurs sporadically in the Pacific Northwest, due to the Ixodes pacificus tick, and caused by the species Babesia duncani. In Europe, babesiosis is typically caused by Babesia divergens.
The nymphal stage of the Ixodes is the primary vector and typically requires attachment to a host for at least 36 to 72 hours to complete a blood meal. If the tick is carrying the protozoa, the second or third day of attachment is typically when the babesia infection occurs with the transmission of sporozoite forms. These sporozoites attach and enter erythrocytes where they mature and divide via binary fission to form merozoites. These merozoites then leave the host erythrocyte, rupturing the cell, and go on to infect other erythrocytes, repeating the cycle above. The spleen is essential in the host's ability to control this infection. Erythrocytes infected with Babesia are recognized as abnormal as they pass through the spleen and are targeted for destruction by macrophages. People with a history of splenectomy are at high risk for severe infection with high-level parasitemia. Other high-risk populations include those with HIV, older than 50 years, neonates, and immunosuppressed patients (particularly TNF inhibitors or CD20 antibody).
The clinical presentation of babesiosis can range from asymptomatic to severe infection causing multi-organ failure. The severity of infection is often dependent on the immunocompetence of the host. The asymptomatic infection has been reported in up to 20% of adults and 50% of children. The incubation period has been reported to be typically between one to six weeks. Symptomatic illness in patients without immunodeficiencies usually consists of a febrile, flu-like illness often with a chill, sweats, malaise, fatigue, and headache. Other less common symptoms include a cough, arthralgia, sore throat, abdominal pain, nausea, emotional lability, and depression. On exam, apart from fever, patients may have hepatosplenomegaly, jaundice, retinopathy, or pharyngeal erythema. A rash is not a common symptom and may indicate co-infection with Lyme disease. Severe disease typically occurs only in high-risk populations mentioned above, particularly in those with a history of asplenia. These patients may have multi-organ dysfunction, including respiratory distress, congestive heart failure, renal failure, splenic rupture, disseminated intravascular coagulation (DIC), hepatitis, or coma.
The diagnosis of babesiosis is typically made by identifying the organism on a thin smear of peripheral blood, using Giemsa or Wright staining, and the severity of parasitemia can be assessed. In early infection, it is recommended that multiple thin smears be examined as parasite burden may be low initially. Ring forms are most commonly seen and can have multiple rings per cell. Tetrad formations, also known as Maltese cross, are occasionally seen. PCR testing is also available at reference laboratories and is more sensitive than peripheral smears. Serology is performed via indirect immunofluorescent antibody testing and can be useful for confirming the diagnosis. A single positive serology cannot distinguish between acute and previous infection, but a four-fold rise in acute and convalescent titers confirms a recent infection. Lab abnormalities that may be seen in babesiosis include anemia, elevated LDH, thrombocytopenia, transaminitis, proteinuria and elevated BUN and creatinine. 
Treatment is indicated in symptomatic cases or in asymptomatic patients who have a positive blood smear or PCR for more than three months. There are two regimens used for treatment in mild to moderate disease. The first and most commonly used regimen is atovaquone plus azithromycin. The other option is quinine plus clindamycin which has much higher rates of adverse drug reactions compared to atovaquone/azithromycin (72% versus 15% respectively). A 7- to 10-day course of either regimen is recommended. Severe disease, requiring hospitalization or causing organ failure, typically occurs in high-risk populations or in those infected with the B. divergens species. These patients require treatment with clindamycin plus quinine (IV quinidine may also be used, but patient require monitoring for QT prolongation). The duration of treatment is at least 7 to 10 days but is based on clinical and laboratory response. Some of these patients with immunocompromising conditions will have a persistent or relapsing disease, in which case, a course of at least six weeks is recommended, with treatment continued for at least two weeks after parasites are no longer detected on blood smears. For patients who fail to respond to standard therapy, other regimens have been used including atovaquone plus azithromycin plus clindamycin; atovaquone plus azithromycin plus doxycycline; and atovaquone plus clindamycin plus doxycycline. No particular anti-parasitic combination therapeutic drug regimen has demonstrated superiority. If possible, it is also recommended to reduce underlying immunosuppression.
Partial or complete red blood cell (RBC) exchange transfusion is indicated in patients presenting with parasitemia of at least 10% and anemia with hemoglobin of <10 g/dL. Consideration for exchange transfusion should be strongly given in those with infection due to B. divergens pulmonary, renal or hepatic dysfunction, regardless of parasitemia level.
Babesiosis became a reportable disease in the United States in January 2011, and its incidence has been increasing, due in part to a geographic expansion of the vector. Because Ixodes scapularis is also the vector for Borrelia burgdorferi and Anaplasma phagocytophilum, coinfections do occur and should especially be considered in patients failing to improve on therapy.
Babesiosis is a rare tick-borne infection with a varied presentation. The organism can affect many organ systems and is best managed by a multidisciplinary team. As soon as the infection is diagnosed, it has to be reported to the local public health authority and the infectious disease expert should be consulted on management. Delayed diagnosis can lead to a high morbidity and mortality.