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Babesia spp. (True Pathogen –Babesiosis)

Organism:
This organism belongs to the phylum Apicomplexa, is a true pathogen, and causes babesiosis.  All forms of the human life cycle will appear in the thick and thin blood films. 

Babesia spp. ring forms
NOTE:     The Maltese Cross forms do not appear in every species of Babesia; without these forms and in cases of low parasitemia, it may be very difficult to differentiate Plasmodium falciparum from Babesia.
 
Life Cycle:
Infection is transmitted by several species of ticks in which the sexual multiplication cycle occurs. When a tick takes a blood meal, the infective forms are introduced into the human host. The organisms infect the RBCs, in which they appear as pleomorphic, ring-like structures. They resemble the early trophozoite (ring) forms of malarial parasites, particularly P. falciparum. The organisms measure 1.0 to 5.0 µm, the RBCs are not enlarged or pale, and the cells do not contain stippling. Malarial pigment is never seen. The early form contains very little cytoplasm and has a very small nucleus. In mature forms, two or more chromatin dots may be seen. Occasionally a tetrad formation, referred to as a Maltese cross, may be seen.
Babesia are grouped into the small Babesia (1.0 to 2.5 µm) and include B. gibsoni, B. microti, and B. rodhaini.  The large Babesia (2.5 to 5.0 µm) include B. bovis, B. caballi, and B. canis.  These phenotypic classifications are, for the most part, consistent with genetic characterization based on nuclear small subunit-ribosomal DNA sequences.  The small babesias are more closely related to Theileria spp. than are the larger organisms.  The one exception is B. divergens, which appears small on blood smears, but is genetically related to the large babesias.  The two primary pathogens of humans are B. microti and B. divergens, along with the WA1 (Washington) (now called Babesia duncani), CA 1 (California), and MO1 (Missouri).

Acquired:
Bite:  various ticks; blood, shared needles, congenital infections

Epidemiology:
Sporadic distribution; tick to human, human to human transmission

Clinical Features:
Early InfectionBabesia infections described in California and in other parts of the world are quite different from those seen in the northeast United States, where the infection is most often subclinical. Infections in California and Europe tend to present as a fulminate, febrile, hemolytic disease affecting splenectomized or immunosuppressed individuals.
In those patients from Nantucket Island, Massachusetts, who were not splenectomized, symptoms began 10 to 20 days after a tick bite and continued for several weeks. There was general malaise, followed by fever, shaking chills, profuse sweating, arthralgias, myalgias, fatigue, and weakness. Hepatosplenomegaly was present, and five patients had slightly elevated serum bilirubin and transaminase levels due to hemolytic anemia.          
Complications:  Babesiosis is usually a self-limiting disease; also there are probably asymptomatic and undiagnosed carriers; the mortality rate has been reported at about 5%.  However, infections in Europe caused by B. divergens are far more serious with a mortality rate of 42%.  Fatal cases of B. divergens have been reported in France, Britain, Ireland, Spain, Sweden, Switzerland, the former Yugoslavia, and the former USSR.

Clinical Specimen:
Blood:  Multiple draws (EDTA).  Many patients have a low parasitemia; thus multiple blood draws might be required to make the diagnosis.

Laboratory Diagnosis:
Both thick and thin blood films should be prepared on admission of the patient (clinic, emergency room, in-house), and at least 300 oil immersion fields should be examined on the thick and thin films before a negative report is issued.  Since one set of negative films will not rule out babesiosis, additional blood specimens should be examined over a 36 h time frame.  Although Giemsa stain is usually recommended for all parasitic blood work; the organisms can also be seen with other blood stains such as Wright’s stain, Wright/Giemsa combination stain, and the rapid blood stains.  Blood collected with EDTA anticoagulant is recommended.  Also, it is important to remember that the proper ratio between blood and anticoagulant is necessary for good organism morphology.
            Potential diagnostic problems with use of automated differential instruments have been reported. A case of babesiosis and two cases of malaria were completely missed when blood smears were examined by these methods. The number of fields scanned by a technologist on instrument‑read smears is quite low; thus, a light parasitemia will almost surely be missed. Failure to make the diagnosis resulted in delayed therapy for a number of days. Although these instruments are not designed to detect intracellular blood parasites, routine use of the automated systems may pose serious diagnostic problems, particularly if the suspect diagnosis is not conveyed to the laboratory. 
Note: Most documented human cases have a low parasitemia; thus, both thick and thin blood films stained with any of the blood stains must be examined.
Unusual parasites may be detectable by blood film examination, but not by serologic or molecular testing for B. microti or WA1-type parasites.  This is important to remember, since new organisms similar to, but not identical to, a number of the well-known Babesia spp. may be identified in patients in different parts of the world.  Without the manual examination of blood films, these organisms may be missed.  Note:  The third documented transfusion case caused by B. duncani underscores the fact that babesiosis can be caused by agents not detected by molecular or serologic analyses for B. microti.

Organism Description:
Babesia spp. ring forms resemble the early trophozoite (ring) forms of malarial parasites, particularly P. falciparum. The organisms measure 1.0 to 5.0 µm, the RBCs are not enlarged or pale, and the cells do not contain stippling. Malarial pigment is never seen. The early form contains very little cytoplasm and has a very small nucleus. In mature forms, two or more chromatin dots may be seen. Occasionally a tetrad formation, referred to as a Maltese cross, may be seen.

Laboratory Report:
A number of reports can be relevant – remember to add the appropriate report comments.
Report 1:  No Parasites Seen:  The submission of a single blood specimen will not rule out malaria; submit additional bloods every 4-6 hours for 3 days if malaria remains a consideration.
Report 2Plasmodium spp. Seen:  Unable to rule out Plasmodium falciparum or Plasmodium knowlesi
Report 3Plasmodium spp., possible mixed infection:  Unable to rule out Plasmodium falciparum or Plasmodium knowlesi
Report 4:  Babesia spp. forms seen: Unable to identify to the species level.
Report 5:  Negative for parasites using automated hematology instruments.  Automated Hematology instruments will not detect low parasitemias seen in immunologically naïve patients (travelers)

Treatment: 
Garcia, L.S. 2007.  Diagnostic Medical Parasitology, 5th ed., ASM Press, Washington, D.C.

Control:
Improved tick control; no use of shared needles, checking blood supply