Pathways Case Record: A Case of Severe Babesiosis

A 68-year-old woman with a history notable for alcohol use disorder presented with malaise, body aches and labored breathing upon exertion. Upon admission, the patient was diagnosed with severe babesiosis with a parasite load of 5.4% and was subsequently treated with atovaquone and azithromycin. Initial labs showed elevated liver enzymes and mild pancytopenia (low blood cell and platelet count). Her clinical status worsened over the course of three days as seen by the development of severe mixed anion gap and non-anion gap metabolic acidosis complicated by significant respiratory distress and a new requirement for blood pressure support.

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She was intubated and transferred to Massachusetts General Hospital for further management. Upon arrival, her parasite load had increased to 6.3% and she was treated with a regimen of three antibiotics: clindamycin, azithromycin and atovaquone (Open Forum Infect Dis). She did not require an exchange transfusion.

The patient was extubated approximately one week later and subsequently, her parasite load resolved with concurrent decreased oxygen requirement.

The Pathways Consult Service in the Department of Medicine was consulted and focused on the question: why did this patient develop such a severe case of babesiosis?

Background and Diagnosis

Babesia microti, the most common species of Babesia in the northeastern U.S., enters the body through the bite of Ixodes ticks (CDC). These ticks typically transmit B. microti to humans during their nymph and adult stages. Babesia exist as intraerythrocytic parasites and replicate asexually via budding (Clin Microbiol Rev). The white-footed mouse, which can serve as a pathogen reservoir, and white-tailed deer, are the primary hosts of the Ixodes ticks. Following a tick bite in humans, B. microti sporozoites enter the bloodstream to infect red blood cells. Common risk factors for severe Babesia infection include immunocompromised status, advanced age and splenectomy (CDC).

Our immune system responds to infection by B. microti through phagocytosis of infected red blood cells by macrophages and presentation of Babesia protein fragments (antigens) on the major histocompatibility complex (MHC) class I and II. This antigen presentation triggers activation of T helper 1 (Th1) cells, which release interferon gamma (IFNγ) (Front Microbiol). IFNγ subsequently activates splenic macrophage to promote the clearance of B. microti-infected red blood cells. In addition to the activity of macrophages and Th1 cells, B cells play a small, but important, role in the host response to B. microti as evidenced by difficulty clearing the infection in patients on rituximab (Diagn Microbiol Infect Dis). The underlying mechanism remains understudied.

Aging inherently impacts immune system function. Older people have reduced production of adaptive immune cells (i.e., B and T cells). Memory T cells predominate as people age with an increased proportion of regulatory T cells. Researchers have hypothesized that this change contributes to the decreased ability of the adaptive immune system to respond against new targets. Additionally, a process termed "inflammaging," which is described as a consistently low level of inflammation driven by chronically activated macrophages, is hypothesized to occur in older adults (Clin Infect Dis; J Immunol). It is possible that the underlying inflammatory state of our patient prior to infection may have contributed to her susceptibility to babesiosis and disease severity.

While her age increases her risk for a more severe course of babesiosis, there are other factors that may have contributed to her disease progression. The strain of B. microti may have been more virulent, therefore making it more difficult for her immune system to clear the parasite. A delayed presentation to the hospital or inadequate absorption of antimicrobials may provide the opportunity for B. microti to replicate and cause more extreme symptoms. Pre-existing factors within the patient may also contribute such as red blood cell susceptibility, abnormal macrophage function, or abnormal splenic or reticuloendothelial system function. Her red blood cells could have upregulated Babesia-binding domains (Transfusion), which could enable B. microti entry into the cells at a greater rate. This could be easily explored by measuring B. microti uptake by our patient's cells compared to a control over time. Alternatively, her disease may have resulted from abnormal macrophage functions such as the impaired ability to phagocytose the infected cells or properly respond to IFNγ stimulation. Lastly, alcohol use over an extended period of time could have contributed to splenic or reticuloendothelial system dysfunction (e.g., portal hypertension or splenic hyperfiltration). Changes in splenic filtration may predispose individuals to a more severe course of infection. Thus, the Pathways service hypothesized that one or more predisposing factors enabled B. microti to infiltrate our patient and cause severe babesiosis.

Summary and Future Steps

Key information regarding susceptibility and response to B. microti have not yet been fully elucidated. Further investigation into the underlying risk factors of babesiosis and development of severe disease is needed. Currently, no randomized controlled trials studying the efficacy of triple antimicrobial therapy compared to the more standard regimen (e.g., azithromycin and atovaquone) have been performed. As cases of Babesia infection in the U.S. increase, a better understanding of the risk factors for severe disease and optimal treatment strategies will be important.

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