eMedicine Specialties > Infectious Diseases > Parasitic Infections

Babesiosis: Differential Diagnoses & Workup

Author: Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Contributor Information and Disclosures

Updated: Jul 28, 2008

Differential Diagnoses

Ehrlichiosis
Lyme Disease
Malaria
Rocky Mountain Spotted Fever
Typhoid Fever

Other Problems to Be Considered

Babesiosis usually manifests as an undifferentiated acute febrile illness that resembles malaria. Patients who previously had non– Plasmodium falciparum malaria may be experiencing a relapse of their previous malarial infection. A relapse of their malaria may be diagnosed based on prior exposure or infection as many as 40 years previously with a non-falciparum malaria. Diagnosis is based on demonstrated plasmodia in properly prepared Giemsa-stained or Wright-stained thick or thin blood smears. Patients with recrudescent malaria may have low levels of parasitemia and usually have increased malaria immunoglobulin G (IgG) titers.

Patients who present with a malarialike illness always should be questioned regarding potential for previous exposure to malaria.

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 Ixodidae tick vector associated with Lyme disease may also transmit Babesia organisms. Co-infections of Lyme disease and babesiosis are uncommon but can occur.

Ehrlichiosis (ie, "spotless" RMSF) also presents as an acute febrile infection that resembles RMSF. Because of the separate tick vectors, patients with ehrlichiosis are unlikely to be co-infected with Lyme disease or babesiosis. While seropositivity to Lyme disease and ehrlichiosis is common in endemic areas, clinical co-infection remains rare. Increased Ehrlichia titers with an IgG antibody titer equal to or greater than 1:64 or a 4-fold or greater change in antibody titers on immunofluorescent antibody (IFA) testing is diagnostic of ehrlichiosis.

Patients with ehrlichiosis often have leukopenia, anemia, and thrombocytopenia. The erythrocyte sedimentation rate (ESR) is minimally elevated in ehrlichiosis. Levels of serum transaminases may be mildly increased in ehrlichiosis, as with babesiosis, typhoid fever, and RMSF.

Typhoid fever, RMSF, and Lyme disease may be differentiated from babesiosis, ehrlichiosis, and malaria based on the presence or absence of hemolytic anemia. Hemolytic anemia is not a typical feature of typhoid fever, RMSF, or Lyme disease.

Except for Lyme disease and typhoid fever, thrombocytopenia is a feature of all of these infectious diseases. 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 feature of Lyme disease.

Arthropod-borne viral infections may be confused with babesiosis. However, arboviral illnesses are characterized by the extreme rapidity of onset and clinical severity, which is not the case in babesiosis unless the spleen is absent.

Relative bradycardia is a cardinal finding in many infectious diseases. Many arboviral infections (eg, yellow fever, dengue fever, African hemorrhagic fever [Ebola]) are characterized by relative bradycardia. Relative bradycardia is a common finding in patients with malaria, RMSF, and babesiosis but is not a feature of Lyme disease.

In rare cases, typhoidal Epstein-Barr virus (EBV) infections, mononucleosis, or typhoidal tularemia is confused with babesiosis. EBV-specific antibody testing and tube agglutination testing for tularemia can help exclude these diagnostic possibilities if they are considered in the differential diagnoses.

Typhoid fever is suggested by a severe headache and apathetic faces with few, if any, localizing signs. Splenomegaly may be present later in the course of the illness. A normal or slightly decreased peripheral WBC count is the characteristic hematologic finding in typhoid fever. The presence of eosinophilia or thrombocytopenia suggests an alternate diagnosis. Typhoid fever may be diagnosed based on staining or culturing the organism in RES tissues or body fluid, ie, blood, urine, or feces.

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

Headache is a prominent feature of malaria and typhoid fever but is less prominent with babesiosis and ehrlichiosis and is mild if present in Lyme disease.

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. These may also be diagnosed based on Wright stain on 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.

Babesiosis rarely affects the lungs. However, patients with babesiosis may develop noncardiogenic pulmonary edema, which may resemble pneumonia on chest radiography.

Workup

Laboratory Studies

Patients from areas endemic for babesiosis who present with a malarialike illness should undergo a workup for babesiosis with the following direct and indirect tests.

• Lactate dehydrogenase (LDH) and a properly stained peripheral blood smear offer the most important results in patients with suspected babesiosis who have a malarialike illness. Quantitatively stained buffy-coat smears concentrate 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.
  • Wright or Giemsa stain on thin blood smears reveals the ring forms of babesiosis. The ability to identify babesiosis depends on the expertise and experience of the microbiologist or physician and the degree of parasitemia.
  • 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.
  • Patients with Babesia infection, in addition to having intraerythrocytic ring forms, may also demonstrate merozoites arranged in a tetrad configuration that resembles a Maltese cross.
  • Tetrad forms are pathognomonic of babesiosis. Babesiosis may be differentiated from malaria based on the absence of pigment hemozoin, which is not present in babesiosis.
• Complete blood cell count and erythrocyte sedimentation rate
  • A CBC count should be obtained to look for the presence of hemolytic anemia, Howell-Jolly bodies indicative of splenic dysfunction, leukopenia, lymphopenia, thrombocytopenia, and an elevated ESR.
  • Hemolytic anemia, lymphopenia, and thrombocytopenia are the typical findings in babesiosis.
  • 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.
  • 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/severity of Babesia.
• Serum protein electrophoresis (SPEP): This test should be obtained, and results usually show a polyclonal gammopathy indicative of B-lymphocyte hyperreactivity SPEP (polyclonal gammopathy) in response to T-lymphocyte suppression by Babesia.
• Liver function tests
  • LFTs should be obtained to look for elevated transaminase 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. Increased serum transaminase levels are usually mildly and transiently elevated. A decreased haptoglobin level suggests a significant degree of intravascular hemolysis.
• Urinalysis
  • Urinalysis should be obtained to check for hemoglobinuria.
  • The degree of hemoglobinuria is related to the intensity of the Babesia infection.
• Serology
  • Immunoglobulin M (IgM) or IgG IFA B microti titers may be obtained in patients with suspected babesiosis who have negative findings on peripheral smears, eg, low levels of parasitemia.
  • A single IgM IFA titer of 1:64 or greater is diagnostic of babesiosis. Increased IgG IFA Babesia titers indicate past exposure rather than current infection.
  • 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.
• Polymerase chain reaction: This test may be used to help diagnose recrudescent Babesia infection in patients who have previously had babesiosis or in those whose treatment is of questionable effectiveness.

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