Approach
Diagnosis of babesiosis is based on epidemiologic, clinical, and laboratory information. Diagnostic criteria include the presence of viral infection-like symptoms and identification of babesial parasites in blood by smear evaluation, or by polymerase chain reaction (PCR) amplification of babesial DNA.
Babesiosis is a nationally notifiable disease in the US and should be reported by local and state health departments through the National Notifiable Disease Surveillance System to the Centers for Disease Control and Prevention.
History
Disease occurs mainly in those who live in or travel to endemic areas, or who have received a blood transfusion containing the parasite within the previous 9 weeks.[31] Peak transmission occurs from May to September in upper midwestern and northeastern US; however, transfusion-related transmission can occur anywhere and at any time of year.[6] The disease is rare in other countries. Because unengorged Ixodes scapularis nymphs are quite small (2 mm), most patients do not always recall receiving a tick bite.
Most infections of Babesia microti in young healthy people are subclinical or mild and are likely to often go undiagnosed. A full history should be taken to include recognized conditions (e.g., asplenia/previous splenectomy, malignancy, and HIV infection), as clinical infections are more common in asplenic patients, those with concurrent Lyme disease, patients with immunosuppression (either due to HIV or drug induced), or older patients. Symptoms may appear 1 to 4 weeks after the tick bite, with a gradual onset of malaise, fatigue, myalgias, sweats, arthralgias, shaking, and chills.[5] A sustained or intermittent fever may develop within 1 week of symptom onset.
Less frequent symptoms include anorexia, vomiting, cough, abdominal pain, photophobia, conjunctival injection, and a sore throat. Manifestations such as hemolytic anemia or thrombocytopenia may be severe or life threatening, and disease can (rarely) also be fatal.[6]
Infection with B divergens, which is more commonly found in Europe, occurs mostly in asplenic patients and is always fulminant and hemolytic.[8] Infections with rarer species such as B duncani, MO-1, and CA-1 also tend to be fulminant.[4]
Physical exam
Physical exam findings are nonspecific and may include fever, splenomegaly, hepatomegaly, or jaundice.[6] Pyrexia is one of the most common findings on physical exam. Petechiae, splinter hemorrhages, or ecchymoses are infrequently found and, if present, indicate disseminated intravascular coagulation.
Investigations
Because the clinical findings are nonspecific, laboratory testing is required to confirm the diagnosis. Those who require testing include:
Any patient with influenza-like symptoms who reports a history of a tick bite and who lives in or has traveled to an endemic area over the previous 5 weeks. Endemic areas include coastal areas of the northeastern US and the lakes region of the upper midwest.
Persistent influenza-like symptoms in a patient with no history of tick bite residing in an endemic area, as two-thirds of those diagnosed with babesiosis report no history of a tick bite.
Patients who have received a recent blood transfusion and have viral illness-type symptoms and/or laboratory evidence of hemolysis.
Patients with evidence of Lyme disease who do not respond adequately to antibiotic treatment for Lyme disease (persistence of high fever after >48 hours of appropriate antibiotics, persistence of viral illness-type symptoms after resolution of erythema migrans with antibiotics).
Initial laboratory investigations include:[6]
CBC: may reveal decreased hematocrit (due to hemolytic anemia), leukopenia, or thrombocytopenia.
LFTs: transaminases may be elevated.
Serum creatinine and blood urea nitrogen: may be elevated in severe cases.
Urinalysis may reveal the presence of dark urine with urobilinogen and conjugated bilirubin indicating hemolysis.
The Infectious Diseases Society of America (IDSA) recommends peripheral blood smear examination or PCR for diagnostic confirmation of acute babesiosis, rather than antibody testing.[31]
Peripheral blood smear
Light-microscopic identification of the parasite on Giemsa- or Wright-stained thin blood smears is recommended for diagnostic confirmation.[6][31]
Manual review of blood smears should be requested explicitly. Multiple smears should be examined, as only a few RBCs may be infected during the initial stages of infection.[6]
Babesia may be confused with malarial parasites on blood smear (both appear as intraerythrocytic rings). Therefore, additional laboratory testing may be considered to confirm the diagnosis and identify the specific babesial pathogen.[6] Babesiosis and malaria have no geographic overlap, so the epidemiologic history of the patient is extremely important.
B microti may form tetrads (Maltese cross) within RBC.
Molecular testing
PCR amplification of blood for babesial DNA is another diagnostic confirmation option, when available.[6][31]
PCR may be considered in patients with intraerythrocytic ring-like structures on blood smear, to differentiate from malaria, and for patients with negative smears for whom clinical suspicion is high.[32][33]
Serologic testing
Serologic testing can provide supportive evidence for the diagnosis, but does not reliably distinguish between active and prior infection.[6]
A single positive antibody test is not sufficient to establish a diagnosis as Babesia antibodies can persist in the blood for a year or more following apparent clearance of infection (with or without treatment). Therefore, in patients who have a positive antibody test only, IDSA recommends confirmation with peripheral blood smear or PCR before treatment is considered.[31]
ELISA and/or immunofluorescence assay for Lyme disease should be included in the differential diagnosis of any patient who develops fever or clinical illness after tick bite. It is transmitted through the bite of the deer tick (Ixodes scapularis), the same vector as for B microti.
PCR and/or immunofluorescence assay or buffy coat smear for human granulocytic anaplasmosis should be included in the differential diagnosis of any patient who develops fever or clinical illness after tick bite. It is transmitted through the bite of the deer tick (I scapularis), the same vector as for B microti.
Follow-up laboratory testing
Once started on treatment, patients with moderate to severe disease should have the hematocrit and peripheral blood smear monitored daily or every other day until parasitemia falls below 5% of erythrocytes parasitized.[34] Quantitative PCR can be used to monitor B microti parasitemia, even at submicroscopic levels, during and after treatment.[32][33]
Testing for Borrelia burgdorferi (Lyme disease) antibodies and Anaplasma phagocytophilum (HGA or ehrlichiosis) coinfection in patients with severe or persistent symptoms despite receipt of appropriate antibabesial therapy should be considered.
Additionally, testing for HIV infection and for other causes of immunodeficiency (such as malignancy or asplenia) should be considered in patients with severe or prolonged disease.[35]
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