Brief Case | December 20, 2023 | FREE
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An older patient with multiple comorbidities presented with headaches, fevers, myalgias, arthralgias, and some loss of balance.

The patient

A 69-year-old man with hypertension, type 2 diabetes, and stage IIIa chronic kidney disease presented with one week of headaches, fevers, myalgias and arthralgias, and some loss of balance. He did not report focal weakness, dyspnea, nausea, or dysuria. The patient was febrile and tachycardic. Physical examination was significant for mild photophobia, mild neck tenderness with flexion, soft systolic heart murmur, a normal neurological examination, and no skin rash or lesions.

Image by Getty Images
Image by Getty Images

Laboratory findings were notable for mild leukopenia with bandemia (white blood cell count, 3.7 × 109 cells/L [reference range, 4.0 to 10.5 × 109 cells/L] with 14 bands and otherwise normal differential), acute normocytic anemia (hemoglobin level, 8.4 g/dL; reference range, 12.5 to 17 g/dL), rare schistocytes and teardrop cells, acute moderate thrombocytopenia (platelet count, 77 × 109 cells/L; reference range, 140 to 350 × 109 cells/L), and acute kidney injury (creatinine level, 1.76 mg/dL [reference range, 0.53 to 1.30 mg/dL]; baseline value, 1.40 mg/dL). A lumbar puncture was performed, but traumatic tap precluded direct analysis. Chest X-ray, urinalysis, and respiratory panel were unremarkable.

The patient was started on vancomycin, ceftriaxone, and ampicillin for empiric coverage of possible bacterial meningitis. Additional studies included meningitis/encephalitis panels, lactate dehydrogenase (LDH)/reticulocyte count/haptoglobin to exclude hemolysis, a disseminated intravascular coagulation (DIC) panel, an ADAMTS13 activity to exclude thrombotic thrombocytopenic purpura, and testing for Lyme disease, Babesia, and Anaplasma. Pertinent positive findings included high LDH and low haptoglobin levels suggestive of hemolysis, but normal reticulocyte count and normal bilirubin level. Babesiosis was confirmed with peripheral blood smear showing erythrocytic parasites. The patient was treated with atovaquone and azithromycin for 10 days and gradually improved, with discharge to home.

The diagnosis

The diagnosis is babesiosis. Babesiosis is a tick-borne zoonotic illness typically characterized by flu-like symptoms, but it also often causes hemolysis and hemoglobinuria. In the U.S., it is most commonly due to the intraerythrocytic parasite Babesia microti. Babesia divergens is most common in Europe, and Babesia duncani causes sporadic cases around the U.S. Babesia is transmitted through the blood meal of Ixodes ticks with peak transmission from May to September in the upper midwestern and northeastern U.S. Transfusion-related transmission has also rarely occurred, with 162 cases documented from 1979 to 2009. The infection itself is considered rare, with fewer than 3,000 cases reported per year, but it is increasing in frequency.

Babesiosis usually causes asymptomatic or a mild viral-like illness in younger and healthy populations, but it may cause more serious disease in patients who have asplenia, are immunocompromised, or are older. Typically recognized presentations after one to four weeks of incubation include fever, chills, fatigue, myalgias, arthralgias, headache, and nausea, as well as hemolysis and hemoglobinuria. Unlike other tick-borne illnesses, it usually does not cause a rash. Complications of babesiosis commonly include hypotension, severe hemolytic anemia, and thrombocytopenia. More rare, with rates ranging from 1% to 20%, are DIC, organ failure, and death.

Diagnosis in symptomatic patients is usually made by a peripheral blood smear demonstrating the parasite within red blood cells. Polymerase chain reaction testing for Babesia microti DNA is a more sensitive and specific, but also more expensive, option. Patients with confirmed babesiosis who remain symptomatic (other than fatigue) for more than one week despite appropriate therapy should be tested for human granulocytic anaplasmosis (HGA), as co-infection can occur, can worsen symptoms of babesiosis, and has no hallmark signs other than severe or prolonged disease. Patients should also be tested for Lyme disease, as there is a 6% to 23% incidence of co-infection.

Patients who are immunocompetent, have mild to moderate symptoms, have parasitemia less than 4%, and are ambulatory do not require hospitalization. Treatment is azithromycin plus atovaquone and is well tolerated. According to guidelines of the Infectious Diseases Society of America, clindamycin plus quinine is an alternative option when the primary regimen is not tolerated or available. Typical treatment lasts seven to 10 days but may need to be extended to at least six weeks in patients who are immunocompromised. Blood transfusion and/or exchange transfusion may be necessary with severe disease (parasitemia >10%, or moderate- to high-grade parasitemia with severe hemolytic anemia and/or severe pulmonary/renal/hepatic compromise).

Fever and parasites on blood smear usually clear within a week. Monitoring parasitemia is recommended until symptoms resolve in all patients. Immunocompromised patients should be monitored daily until parasitemia is less than 4%, then weekly until the parasite is not detected. Fatigue may persist for months to a year, but there are no indications for continued monitoring or follow-up.


  • Babesiosis should be considered in patients presenting with a flu-like illness and evidence of hemolysis, especially in the upper midwestern and northeastern U.S. from May to September.
  • Although babesiosis is typically mild, severe disease can occur in asplenic or immunocompromised patients and in older individuals.