Babesia Treatment at the Mayo Clinic: A Review of 38 Cases
Nearly half did not recall a tick bite
More than two-thirds required hospitalization
Most initially received atovaquone plus azithromycin
How were patients with babesiosis treated at the Mayo Clinic? In a retrospective review of 38 cases, most patients initially received atovaquone plus azithromycin. More than two-thirds required hospitalization, and several severely ill patients required intensive care or exchange transfusion.
Fida and colleagues reviewed 38 adults diagnosed with and treated for babesiosis at three Mayo Clinic sites—two in Minnesota and one in Wisconsin—between January 1, 2005, and December 31, 2017. The average age was 63.1
The study illustrates the wide range of babesiosis presentations—from nonspecific symptoms to severe illness requiring intensive care. The average follow-up was four years, and none of the patients died from babesiosis.
For a broader discussion of current treatment options, including approaches considered when initial therapy is unsuccessful, see Babesiosis Treatment: Options When Standard Therapy Fails.
Nearly half did not recall a tick bite
Only 55% of the patients recalled a tick bite. This means that 45% had no known history of being bitten.
The nonspecific nature of their symptoms also contributed to delays in diagnosis. The average duration of illness before diagnosis was 15.6 days.
A patient’s inability to recall a tick bite should not automatically exclude babesiosis. Blacklegged ticks can be extremely small, and their bites may go unnoticed.
What were the most common Babesia symptoms?
The most frequently reported symptoms included:
- Malaise: 84%
- Subjective fever: 71%
- Chills: 52%
- Joint pain: 32%
These findings demonstrate why babesiosis may initially be mistaken for another infection or a nonspecific viral illness. Malaise, fever, chills, and joint pain are not unique to Babesia infection.
Babesiosis can also cause laboratory abnormalities associated with the destruction of red blood cells, including hemolytic anemia. Thrombocytopenia and elevated liver enzymes may also occur.
Most patients required hospitalization
Sixty-eight percent of the patients required hospitalization, while 21% of the entire 38-patient cohort required intensive care.
Indications for intensive care included:
- Severe hemolytic anemia in five patients
- Shock requiring vasopressor support in two patients
- Acute respiratory distress syndrome in one patient
Patients requiring intensive care had more severe anemia and higher levels of parasitemia—the percentage of red blood cells infected with the parasite—than patients admitted to a regular hospital floor.
The mean hemoglobin level was 7.5 g/dL among patients requiring intensive care, compared with 10.9 g/dL among patients admitted to a regular hospital floor. Mean parasitemia was 10.1% in the intensive care group, compared with 1.4% among patients admitted to the medical floor.
All five patients without a functioning spleen required hospitalization, and three required intensive care. People without a spleen are at increased risk of severe or prolonged babesiosis.
Babesia blood smears were sometimes negative
Diagnosis was made using polymerase chain reaction (PCR) testing and examination of peripheral blood smears.
Half of the patients were diagnosed using both PCR and a blood smear, while the other half were diagnosed by PCR alone. Among patients with a positive PCR result, 27% had a negative peripheral blood smear.
In a symptomatic patient with suspected acute babesiosis, a negative initial blood smear may not exclude infection, particularly when parasitemia is low. PCR testing may provide additional evidence.
Smear-positive disease was associated with more severe illness in this case series. Sixteen of the 17 patients with a positive blood smear were hospitalized.
Coinfections were common
Twenty-four percent of the patients had evidence of Lyme disease coinfection, 5% had an Anaplasma coinfection, and 8% had evidence of both Lyme disease and Anaplasma.
When the overlapping categories were combined, 28.9% had Lyme disease and 10.5% had an Anaplasma coinfection.
The authors reported that coinfection with Borrelia or Anaplasma was associated with more severe symptoms and a greater likelihood of hospitalization.
Because Lyme disease, babesiosis, and anaplasmosis can be transmitted by the same blacklegged tick, more than one tick-borne infection may need to be considered when a patient is unusually ill or does not respond as expected.
The authors specifically advised considering babesiosis when a patient diagnosed with Lyme disease or anaplasmosis does not improve after treatment begins.
How were the Babesia patients treated?
The two principal treatment combinations used in the study were:
- Atovaquone plus azithromycin
- Clindamycin plus quinine or quinidine
Sixty-eight percent of the patients were initially treated with atovaquone plus azithromycin. Atovaquone is the active ingredient in Mepron and is also included with proguanil in Malarone.
The remaining 32% initially received clindamycin plus quinine or quinidine. Among the patients started on clindamycin plus quinine, 75% required a treatment change after an average of four days because of adverse effects associated with quinine.
Reported adverse effects included hearing problems, QT prolongation, cardiac arrhythmias, hemolysis, and hypoglycemia.
Current CDC guidance lists atovaquone plus azithromycin as the preferred combination for most ill patients and clindamycin plus quinine as an alternative.2 Treatment must be individualized according to illness severity, immune status, the infecting Babesia species, medication tolerance, and clinical response.
How long were the patients treated?
Treatment duration varied according to the patient’s clinical response. The average treatment duration was 18.6 days, while the median duration was 10 days. The difference between these figures reflects the substantially longer treatment required by a small number of patients.
One patient was treated for 210 days because blood smears remained persistently positive. That patient had undergone a splenectomy for leukemia, was coinfected with Lyme disease, and had a peak parasitemia of 11%.
Treatment was discontinued after the patient’s blood smears remained negative for approximately one month.
Current CDC guidance describes a 7- to 10-day course as standard for ill patients with competent immune systems. Most asymptomatic patients do not require treatment. Patients who are highly immunocompromised or have persistent or relapsing infection may require substantially longer treatment and close clinical and laboratory monitoring.2
The duration reported in this retrospective study should not be interpreted as the appropriate duration for every patient. Treatment decisions should be based on the individual clinical circumstances.
Three patients required exchange transfusion
Three severely ill patients underwent exchange transfusion. Their parasitemia levels ranged from 12.3% to 28.5%.
During a red blood cell exchange transfusion, infected red blood cells are removed and replaced with donor cells. This procedure is considered for selected patients with life-threatening babesiosis and is used in addition to antimicrobial treatment.
The CDC notes that exchange transfusion may be considered in patients with high-grade parasitemia or moderate-to-high parasitemia accompanied by severe hemolytic anemia or declining pulmonary, renal, or hepatic function.2
Most patients were not immunocompromised
Approximately two-thirds of the patients in this Mayo Clinic series were not immunocompromised.
Although immunosuppression, older age, and the absence of a functioning spleen can increase the risk of severe babesiosis, significant illness can also occur in individuals without recognized immune compromise.
My clinical perspective
This Mayo Clinic study primarily describes patients with laboratory-confirmed babesiosis, many of whom were sick enough to require hospitalization. The findings are valuable, but they do not represent every patient with Babesia infection.
Most of the patients with Babesia infection whom I evaluate in my New York practice have never been hospitalized. They may instead report less dramatic but persistent symptoms, such as fatigue, night sweats, cognitive difficulties, dizziness, exercise intolerance, and air hunger.
Findings such as severe anemia, marked thrombocytopenia, high parasitemia, shock, or respiratory failure are more likely to be recognized in hospitalized populations. Their absence in an outpatient does not, by itself, answer whether Babesia should remain in the differential diagnosis.
Additional research is needed to determine the most effective treatment approaches for patients with persistent symptoms, medication intolerance, immune compromise, or concurrent tick-borne infections.
Study limitations
This was a retrospective review of only 38 patients from three Mayo Clinic sites in the Upper Midwest. Treatment was not randomized, and patients differed in illness severity, immune status, coinfections, and treatment duration.
The high hospitalization rate may also reflect referral bias, since patients with more severe illness were more likely to be evaluated at a tertiary medical center.
The study describes how these patients presented and were managed, but it cannot determine which treatment regimen is best for every patient with babesiosis.
Frequently Asked Questions
What is the preferred treatment for babesiosis?
For most ill immunocompetent patients, current CDC guidance lists atovaquone plus azithromycin as the preferred combination. Clindamycin plus quinine is an alternative. The appropriate regimen depends on illness severity, immune status, the infecting Babesia species, and medication tolerance.
Do asymptomatic Babesia infections require treatment?
Most asymptomatic patients do not require treatment, according to current CDC guidance. Treatment decisions should be individualized, particularly for patients at risk of severe or relapsing infection.
How long is Babesia treatment?
A 7- to 10-day course is commonly used for ill patients with competent immune systems. Longer treatment may be necessary for highly immunocompromised patients or those with persistent or relapsing infection.
Can a Babesia blood smear be negative?
Yes. In the Mayo Clinic series, 27% of patients with a positive PCR test had a negative peripheral blood smear. In a symptomatic patient with suspected acute babesiosis, a negative initial smear may not exclude infection, particularly when parasitemia is low.
When is exchange transfusion used for babesiosis?
Exchange transfusion may be considered for selected patients with severe babesiosis, particularly those with high parasitemia, severe hemolytic anemia, or declining pulmonary, renal, or hepatic function. It is used with antimicrobial therapy rather than as a replacement for it.
Can Babesia occur with Lyme disease?
Yes. The same blacklegged ticks can transmit both infections. In this study, 24% of patients had Lyme disease alone, while another 8% had evidence of Lyme disease and Anaplasma coinfection.
Clinical Takeaway
This Mayo Clinic review shows that babesiosis can range from nonspecific illness to severe disease requiring intensive care or exchange transfusion. Nearly half of the patients did not recall a tick bite, more than one-fourth of the PCR-positive patients had a negative blood smear, and coinfections were associated with greater illness severity.
The findings should be interpreted in the context of a small retrospective series that included many hospitalized patients. Outpatient presentations may be less dramatic, and treatment decisions must account for clinical severity, immune status, coinfections, medication tolerance, and response.
Babesiosis should remain a diagnostic consideration when compatible symptoms and exposure risks are present—even when no tick bite was recalled or an initial blood smear is negative.
Related Articles
Babesia and Lyme Disease
When Should Babesia Be Suspected in Lyme Disease? An Early Coinfection Case
Various Clinical Presentations of Babesia
Babesia Symptoms Can Vary Widely: What a Case Series Found
References
- Fida M, Challener D, Hamdi A, O’Horo J, Abu Saleh O. Babesiosis: A retrospective review of 38 cases in the Upper Midwest. Open Forum Infect Dis. 2019;6(7):ofz311.
- Centers for Disease Control and Prevention. Clinical care of babesiosis. 2024.
Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.
Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention
