Aetiology

In the US, most cases of babesiosis are caused by Babesia microti. Less commonly, other Babesia types (B duncani in the US; B divergens in Europe; and B venatorum in Europe and East Asia) may also cause babesiosis.[13] Clinical infections are more common in asplenic patients, those with concurrent Lyme disease or human granulocytic anaplasmosis, patients with immunosuppression (either due to HIV infection or drug induced), or older patients.

Infection may result due to:

  • Tick bite: in the great majority of patients infection is transmitted through the bite of Ixodes ticks. Centers for Disease Control and Prevention: tick ID Opens in new windowThe vast majority of cases in the US occur in people who live in or have travelled to areas endemic for babesiosis, including coastal regions of the northeastern US and the northern midwest.[14][6] Residents of endemic areas can have seroprevalence rates as high as 10%.[15] Approximately one third of patients with evidence of babesiosis recall a preceding tick bite.[5] Thus, a history of preceding tick bite is helpful, but a history of no known preceding tick bite should not be used to rule out disease. Attached ticks should be removed promptly, as the risk of infection increases with the amount of time the tick remains attached.

  • Blood transfusion: infection has also been transmitted through blood transfusion, an uncommon but emerging route of disease transmission. The US Food and Drug Administration recommends regional testing for Babesia in blood donor samples.[16] The risk of transmission through transfusion in endemic areas has been estimated to be 0.17% per unit of packed cells.[17] Over 70 cases of transfusion-associated disease transmission have been reported over the past 30 years in the US, with most of the cases occurring in the past 10 years. Many of the donors and recipients were not residents of areas endemic for babesiosis, but donors had travelled to areas of endemicity in the weeks or months preceding donation.[18] Most donors are asymptomatic at the time of donation, and it is common for a single donor or donation to infect multiple patients.[19] This highlights the important impact of prolonged asymptomatic parasitaemia in many infected people.[20][21]

  • Vertical transmission: congenital infection has been reported, with data suggesting that transplacental infection can occur.[22]

Pathophysiology

Babesia parasites are deposited into the dermis of humans who are bitten by an Ixodes tick during the last hours of tick feeding, which may last for 48 to 72 hours or more. These parasites invade RBCs and reproduce asexually inside the cells. The incubation period for development of symptoms ranges from 5 to 30 days, but may be as long as 63 days in blood transfusion cases.[23] Haemolysis occurs when parasites burst from erythrocytes and through erythrophagocytosis by macrophages.[8] [24] It is not clear whether sequestration of infected RBCs plays a part in pathophysiology, as it does in malaria.

Clearance of parasites is likely to depend on both the innate and adaptive branches of the immune system. B microti infection in mice depleted of T cells leads to higher parasitaemia than in those with intact immune systems.[25] Additionally, studies in mice indicate that CD4+ T cells are critical for control and elimination of Babesia organisms. The production of the cytokine interferon (IFN)-gamma, which is associated with CD4+ T-cell activation (Th-1 cells), is key to a successful immune response. Babesia-immune mice depleted of the IFN-gamma gene became highly susceptible to re-challenge with B microti, indicating that IFN-gamma is important for protective immunity.[26] Additionally, killed, fixed B microti parasites given to mice with a glucan adjuvant (which stimulates granulocyte and macrophage production) controlled parasitaemia significantly more than killed, fixed parasites given alone.[27] Macrophages and natural killer cells play a role in control of parasitaemia and survival in infections with the WA-1 strain, but their role with B microti in humans is not well understood.[28]

Classification

Aetiological classification

Babesia microti

  • The most common species causing disease in the US, endemic in coastal regions of the northeast and the lakes region of the upper midwest, transmitted by the deer tick. Isolated cases of human babesiosis caused by B microti-like parasites have been reported in Germany, Japan, and Taiwan and uncharacterised babesias have also been detected in patients from South Africa, Brazil, India, and Egypt.[2]

B divergens

  • The most common species causing disease in Europe, but only 40 to 50 cases have been reported overall.

  • A related though quite distinct babesia, B venatorum (EU1), was incriminated in similar, though generally milder cases in Austria, Italy, and Germany.[3]

  • In the US, B divergens-like parasites (i.e., MO-1) have caused acute disease in 3 asplenic patients.

B duncani (CA-5, WA-1, CA-1)[4]

  • Other species of Babesia found to cause sporadic cases in California, Washington State, Missouri, and Kentucky.

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