Babesiosis Differential Diagnoses

Updated: Apr 01, 2021
  • Author: Rachel E Strength, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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Diagnostic Considerations

Babesiosis usually manifests as an undifferentiated acute febrile illness resembling malaria. Patients may have fever, myalgias, fatigue, and anemia. [30] Patients who present with a malaria-like illness should be questioned regarding the possibility of previous exposure to malaria.

Patients who previously had malaria could be experiencing a relapse. Plasmodium vivax and P. ovale are well-known to recrudesce, though there have been case reports of recurrence with P. falciparum and P. malariae. [31, 32] Such a relapse may be diagnosed on the basis of prior malaria exposure or infection up to 40 years previously. Diagnosis requires demonstration of plasmodia in properly prepared and stained thick or thin blood smears. [33] Patients with recrudescent malaria may have low levels of parasitemia and usually have increased malaria immunoglobulin G (IgG) titers.

Patients should also be questioned about a previous history of Lyme disease. Although the signs and symptoms of Lyme disease differ from those of babesiosis, the tick vector associated with Lyme disease (I. scapularis) may also transmit Babesia organisms. Coinfections of babesiosis and Lyme disease are not uncommon, though the clinical significance is unclear. [29]

Ehrlichiosis is an acute febrile infection resembling Rocky Mountain spotted fever (RMSF); it is often called “spotless” RMSF due to the lack of a rash. [30]  Coinfections of babesiosis with RMSF or ehrlichiosis are rare because RMSF and ehrlichiosis are transmitted by Dermacentor ticks rather than Ixodes ticks. Increased Ehrlichia titers with an IgG titer of 1:64 or greater is suggestive of Ehrlichia infection, and a four-fold or greater change in antibody titers on immunofluorescent antibody (IFA) testing measured two to four weeks apart is diagnostic of ehrlichiosis. [34]

Human monocytic ehrlichiosis (HME), human granulocytic anaplasmosis (HGA), and human granulocytic ehrlichiosis (HGE) may be diagnosed serologically in patients with a nonspecific febrile illness in endemic areas. [34] These may also be diagnosed through Wright stain of peripheral blood smears or buffy-coat preparations that demonstrate regularly-stained cytoplasmic inclusions in monocytes or, less commonly, lymphocytes, which are mulberry-shaped and are called morulae. Morulae are seen more frequently in HME than in HGE.

Patients with ehrlichiosis often have leukopenia, anemia, and thrombocytopenia. [30] The erythrocyte sedimentation rate (ESR) is minimally elevated. Levels of serum transaminases may be mildly increased in ehrlichiosis, as in babesiosis, typhoid fever, and RMSF. Typhoid fever, RMSF, and Lyme disease may be differentiated from babesiosis, ehrlichiosis, and malaria on the basis of the presence or absence of hemolytic anemia, which is not a typical feature of the first three conditions.

Except for Lyme disease and typhoid fever, thrombocytopenia is a feature of all of these infectious diseases. [34] Leukopenia is a common finding in typhoid fever, RMSF, babesiosis, and ehrlichiosis but is not a characteristic finding in Lyme disease.

Splenomegaly may be present in patients with typhoid fever, malaria, babesiosis, ehrlichiosis, and RMSF but is not a common feature of Lyme disease. [30]

Arthropod-borne viral infections may be confused with babesiosis. However, arboviral illnesses are characterized by their extreme rapidity of onset and their clinical severity, neither of which is typical of babesiosis unless the spleen is absent. [30]

Relative bradycardia is a cardinal finding in many infectious diseases, including many arboviral infections (e.g., yellow feverdengue fever, and Ebola). Likewise, it can be seen in patients with malaria, RMSF, and babesiosis. [35]

In rare cases, typhoidal Epstein-Barr virus (EBV) infection, mononucleosis, or typhoidal tularemia may be confused with babesiosis. [30]  If these illnesses are being considered in the differential diagnosis, EBV-specific antibody testing, serum antibody titers or culture for tularemia, and multiple other tests can help exclude these possibilities. [36]

Typhoid fever may resemble babesiosis in its clinical presentation. As with babesiosis, physical signs are usually absent in patients. Patients with typhoid fever often present with constipation rather than diarrhea, which may be helpful because neither constipation nor diarrhea is a common feature of babesiosis.

Differential Diagnoses