Babesiosis Workup

Updated: May 22, 2017
  • Author: Burke A Cunha, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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Workup

Approach Considerations

Babesiosis should be considered in patients who have a malarialike illness in areas endemic for Babesia infection; however, it can be quite difficult to diagnose. Although the index of suspicion should be high in such areas, patients with babesiosis have few, if any, localizing signs to suggest the disease.

Various direct and indirect tests may be useful for diagnosis (see below), though the results of laboratory studies may be unremarkable in individuals who are asymptomatic. Confirmation of the diagnosis depends on the degree of parasitemia and on the expertise and experience of the laboratory personnel. All of the findings in babesiosis are nonspecific, and only the demonstration of Babesia in the peripheral smear can rapidly confirm the diagnosis.

Lactate dehydrogenase (LDH) measurement and a properly stained peripheral blood smear yield the most useful results in patients with suspected babesiosis who have a malarialike illness. Quantitatively stained buffy-coat smears concentrate white blood cells (WBCs) and increase the likelihood of demonstrating Babesia in the peripheral blood. As with malaria, multiple peripheral-stained thin smears or stained buffy-coat preparations may be necessary to detect low levels of Babesia parasitemia.

Consider the possibility of coinfection with Lyme disease because the 2 organisms share the same tick vector (I scapularis). Coinfection often results in increased duration and severity of illness.

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Serum Cellular Evaluation

A complete blood count (CBC) with differential should be performed. Mild-to-severe hemolytic anemia, lymphopenia, and thrombocytopenia are the typical findings in babesiosis. Decreased serum haptoglobin levels [1] and elevated reticulocyte counts are noted. Atypical lymphocytes may be present, as they are in malaria, and the number of atypical lymphocytes is not related to the degree of parasitemia or the severity of illness.

The following may be observed in patients with babesiosis:

  • The percentage of red blood cells (RBCs) parasitized in clinical cases is usually 1-10% but has ranged from less than 1% to 85%
  • The total leukocyte count may be within the reference range or mildly decreased
  • The erythrocyte sedimentation rate (ESR) may be elevated
  • Direct Coombs test results may or may not be positive
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Peripheral Blood Smears

Babesiosis is usually diagnosed by microscopic examination of Giemsa-stained or Wright-stained thin or thick blood smears (see the images below). The ability to identify babesiosis depends on the expertise and experience of the microbiologist or physician and the degree of parasitemia.

Blood smear showing Babesia species in erythrocyte Blood smear showing Babesia species in erythrocytes. Image courtesy of Centers for Disease Control and Prevention.
Peripheral smear showing babesiosis. Peripheral smear showing babesiosis.

Most patients with intact splenic function who are mildly to moderately ill with babesiosis have 10% or less of parasitemia in their peripheral blood; patients with asplenia usually have greater degrees of parasitemia (eg, >85%). However, the level of parasitemia does not directly correspond to the severity of disease.

Wright or Giemsa stain on thin blood smears reveals the ring forms of babesiosis.

Wright-stained or Giemsa-stained peripheral blood smears reveal intraerythrocytic ring forms with a central pallor. Stained smears from patients with Babesia infection, in addition to having these intraerythrocytic ring forms, may also demonstrate merozoites arranged in a tetrad configuration resembling a Maltese cross (see the image below). Tetrad forms are pathognomonic of babesiosis. In individuals with asymptomatic infection, smear results may be negative.


Babesia species, tetrad formation. Image courtesy Babesia species, tetrad formation. Image courtesy of Centers for Disease Control and Prevention.

Babesia may be mistaken for malarial parasites, particularly the ring forms of P falciparum. Helpful features that distinguish Babesia from Plasmodium include the following:

  • Absence of brownish pigment deposits (hemozoin)
  • Lack of synchronous stages (schizonts and gametocytes observed with Plasmodium species)
  • Occasional presence of tetrads (see above)

In addition, Babesia varies more in shape and in size and may be observed outside erythrocytes with heavier infestation.

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Serum Chemistry

Serum creatinine measurements should be obtained to assess potential renal insufficiency. Care must be taken to consider other causes of an increased serum creatinine level before ascribing these changes to Babesia infection. Both serum creatinine and blood urea nitrogen (BUN) levels may be elevated.

Liver function tests (LFTs) should be obtained to look for elevated hepatic transaminase (ie, aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) levels, an elevated alkaline phosphatase level, hyperbilirubinemia, and a decreased haptoglobin level. These abnormalities are variably present in patients with babesiosis.

Obviously, the total bilirubin and haptoglobin values reflect the intensity of the infection. Elevation of serum transaminase levels is usually mild and transient. A decreased haptoglobin level suggests a significant degree of intravascular hemolysis.

As with malaria, the diagnosis of babesiosis should be questioned if the serum LDH level is not elevated. Increased LDH levels reflect the degree of parasitemia, the severity of Babesia infection, or both.

Serum protein electrophoresis should be performed. Results usually show a polyclonal gammopathy indicative of B-cell hyperreactivity in response to T-cell suppression by Babesia.

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Serologic Testing

Indirect immunofluorescent antibody

Indirect immunofluorescent antibody (IFA) assay of immunoglobulin M (IgM) or immunoglobulin G (IgG) B microti titers can be used to make a serologic diagnosis of babesiosis. This test is considered the standard for serologic detection of B microti infection. An IgM titer of 1:64 or greater is considered positive; a titer of 1:32 or less indicates prior infection. Increased IgG Babesia titers indicate past exposure rather than current infection.

An IgM titer of 1:256 or higher or a greater than 4-fold increase in the titer is considered diagnostic of recent B microti infection (though the correlation between titer and symptom severity is poor). Most patients with an active infection develop serum titers of 1:1024 or higher within a few weeks. Antibody titers then decline slowly over a period of months to 1:256 or lower. Cross-reactions may occur in serum specimens from patients with malaria infections.

Serologic studies that test for B microti do not detect infections due to other strains of Babesia (eg, B divergens, B bovis, B duncani, and B gibsoni) .

Because of the antigenic differences, IFA testing for B microti infections does not detect the WA-1 (B duncani) and MO-1 strains. Accordingly, individuals whose exposure could have occurred on the West Coast of the United States should be tested for antibodies to WA-1 .

Immunoblot assay

For the diagnosis of babesiosis, immunoblot antibody testing has sensitivity and specificity comparable to those of IFA testing. Potential advantages of immunoblot assays over IFA assays include the lack of a need for concentrated serum samples and the relative ease of use (because they can be performed by generalist technicians as opposed to the trained microscopists required for IFA testing).

Enzyme-linked immunosorbent assay

The enzyme-linked immunosorbent assay (ELISA) IgM Lyme test is used in patients with suspected babesiosis because of the high (25%) incidence of coinfection with Lyme disease. Coinfection increases the severity of disease; therefore, it is important to diagnose and treat both infections.

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Hamster Inoculation

When peripheral blood smear and laboratory results are equivocal, the diagnosis may be facilitated by hamster (or gerbil) inoculation. Suspected B microti infection can be confirmed through intraperitoneal inoculation of 1 mL of ethylenediaminetetraacetic acid (EDTA) whole blood from the patient into the peritoneum of a golden hamster, then performing an antibody analysis of the animal’s blood. For suspected B divergens infection, a gerbil is used; this organism replicates readily in gerbils.

The main disadvantage of this test is that the animal must be checked periodically over a period of 6-8 weeks, which makes the test time- and labor-intensive and renders it impractical for rapid diagnosis.

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Polymerase Chain Reaction Assay

A polymerase chain reaction (PCR)–based diagnostic assay has been reported that appears to hold great promise for increasing the detection rate of very low-level parasitemia. Persistence of antibody titers for B microti has been shown to correlate with the detection of babesial DNA by PCR. [18] Krause et al reported the detection of babesial DNA by PCR for as long as 27 months after untreated infection. [19]

Compared with peripheral smear evaluation and hamster inoculation, PCR testing is more sensitive and equally specific. It may be useful in monitoring the infection, though it cannot differentiate between acute or active forms of babesiosis and chronic forms of the disease. In particular, PCR testing may be used to help diagnose recrudescent Babesia infection in patients who have previously had babesiosis or those whose treatment is of questionable effectiveness.

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Other Tests

Urinalysis

Urinalysis should be performed to check for hemoglobinuria. The degree of hemoglobinuria is related to the intensity of the Babesia infection. Urinalysis may also reveal proteinuria, and a dark color may be present.

Chest radiography

Chest radiography may be indicated for patients with respiratory complications, such as suspected pneumonia or acute respiratory distress syndrome (ARDS).

Bone marrow biopsy

Because of the possibility of hemophagocytic syndrome, bone marrow biopsy is indicated in patients whose laboratory studies reveal pancytopenia and whose physical examination reveals hepatosplenomegaly, fever, coagulopathy, or lymphadenopathy.

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