Babesiosis As A Rare Cause of Fever in The Immunocompromised Patient: A Case Report
Babesiosis As A Rare Cause of Fever in The Immunocompromised Patient: A Case Report
Babesiosis As A Rare Cause of Fever in The Immunocompromised Patient: A Case Report
Case report
Babesiosis as a rare cause of fever in the immunocompromised
patient: a case report
Daniel A Nelson, Joanna K Bradley, Rajiv Arya, Monica Ianosi-Irimie,
Andreia Marques-Baptista and Mark A Merlin*
Address: Department of Emergency Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School,
1 Robert Wood Johnson Place, MEB Room 104, New Brunswick, NJ, USA
Email: DAN - nelsond1@umdnj.edu; JKB - bradlejk@umdnj.edu; RA - aryara@umdnj.edu; MII - ianosimo@umdnj.edu;
AMB - marqueao@umdnj.edu; MAM* - merlinma@umdnj.edu
* Corresponding author
Abstract
Introduction: This is the case of a rare and regional disease not often considered in the
immunocompromised patient presenting with a chief complaint of fever.
Case presentation: A 37-year-old immunocompromised Indian woman presented with a chief
complaint of fever, in the absence of localizing signs and symptoms, from an area endemic to Babesia
microti.
Conclusions: Our patient’s case is instructive in that Babesiosis and other arthropod born illnesses
should be considered in immunocompromised patients presenting with fever in the absence of
localizing signs or symptoms. This is especially true when he or she presents from an area with
known endemic disease. While the management of fever in immunocompromised patients is largely
standardized, considering Babesiosis from the beginning may prompt early investigation of a blood
smear, which has the potential to alert the emergency department physician to Babesiosis. In
addition, considering the disease from the outset has the potential to accelerate administration of the
appropriate antimicrobial therapy and thus prevent unnecessary morbidity and possible mortality.
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The patient’s initial chest radiograph was negative for etiologic agent of Lyme disease, and Anaplasma phagocyto-
any acute disease process. A blood smear was obtained phila, the etiologic agent of human granulocytic anaplas-
(Figure 1). Numerous ring trophozites measuring approxi- mosis. Humans most often acquire the disease through the
mately 2.0 microns were seen and estimated to involve 3.8 bite of the deer tick and infrequently through contami-
percent of the erythrocytes. The infected erythrocytes nated blood transfusions [3].
appeared the same size as the surrounding, non-infected
cells. No other inclusions, with the exception of the According to the Centers for Disease Control, Babesia is
pyroplasms, were seen in the erythrocytes. A rapid malaria endemic to the Northeastern United States, more specifi-
antigen test was performed and found to be negative. cally New York, Massachusetts, Connecticut, and Rhode
Island. There is also a considerable focus of disease in
At this point, the patient was admitted with a presumptive Wisconsin and Minnesota. In 2003, New Jersey was added
diagnosis of Babesiosis. The patient was started on to the list of states Babesia calls home. All reported and
azithromycin 250 milligrams daily, doxycycline 100 confirmed cases of Babesiosis in New Jersey have occurred
milligrams twice daily, and atovaquone 750 milligrams in the central portion of the state with most being reported
twice daily. On hospital day two, additional data was in Burlington and Ocean Counties [4]. Peak transmission
obtained about the patient’s hematologic status. The occurs from May to September, with July being the most
patient was found to have a reticulocyte count of 1.32 common month of infection. Children and adults are
(an inadequate bone marrow response most likely affected equally; however, adults tend to have a greater
secondary to chronic renal failure), a haptoglobin level proportion of symptomatic infections [5].
less than 7, and a falling hemoglobin level. In the setting of
increased red cell destruction and decreased red cell Clinically, Babesiosis most often presents in a flu-like
production, the patient was transfused two units of packed manner with fever, chills, diaphoresis, malaise, myalgias,
red blood cells. The patient responded well to the and arthralgias. Patients have also reported headache, neck
transfusions and her hemoglobin subsequently stabilized stiffness, sore throat, cough, shortness of breath, anorexia,
while her lactate dehydrogenase and haptoglobin nausea, vomiting, and hepatosplenomegaly. Patients can
improved only marginally. also be completely asymptomatic. In a study by Hatcher et al
of thirty-four cases of Babesiosis in an endemic area of New
While the patient’s hemoglobin initially dropped, the York, it was found that patients presented on average 15.4
patient’s renal function steadily improved with treatment days after the onset of symptoms. In addition, only thirty-
of her underlying infection. By the end of the patient’s one- two percent of patients were able to recount a tick bite [3].
week hospital stay, her creatinine had returned to baseline.
In addition, her bilirubin, electrolytes, white blood cell Objectively, patients often present with hemolytic anemia
count, and platelet count improved over the week. as evidenced by an elevated indirect bilirubin, elevated
lactate dehydrogenase, and depleted haptoglobin levels. If
The diagnosis of Babesiosis was eventually confirmed by hemolysis is present, urine analysis often reveals hemo-
polymerase chain reaction (PCR) performed by Focus globinuria and proteinuria without the concomitant
Diagnostics Incorporated in Cypress, California. In addi- presence of microscopic red cells. Leucopenia and
tion, a diagnosis of Lyme disease was presumed secondary thrombocytopenia may also be present secondary to a
to elevated Lyme titers and high rate of concurrent Tumor necrosis factor (TNF)-mediated immune response.
infection of Babesiosis with Lyme disease. Our patient Patients may also have elevated liver enzymes including
did extremely well and was discharged home with no aspartate aminotransferase, alanine aminotransferase, and
residual symptoms. alkaline phosphatase [5].
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Differentiating Plasmodium, the etiologic agent of Malaria, transfusion which may be curative in those situations.
from Babesia, the etiologic agent of Babesiosis, can be Interestingly, Babesia infections in immunocompromised
achieved in a number of ways. The simplest is through individuals can persist despite treatment. These patients
giemsa-stained thin blood smears revealing intra-erythro- are more likely to relapse or continue to remain subclinical
cyte ring forms, also known as pyriform inclusions, with hosts for the parasite. In 2008, Krause et al found that
light blue cytoplasm. A smear of Babesia infected immunocompromised patients required treatment for at
erythrocytes is characteristically very similar to that of least two weeks after the blood smear no longer shows
erythrocytes infected with Plasmodium; however, they can trophozites in erythrocytes in order for a cure to have been
be differentiated by the greater degree of pleomorphisms achieved [9-11].
as well as the presence of the pathognomonic finding of
trophozites in the form of Maltese crosses in Babesia Conclusions
smears. Diagnosis is confirmed through serologic testing Our patient’s case is instructive in that Babesiosis and
or PCR. PCR targeting of the 18S rDNA portion of the other arthropod born illnesses should be considered in
genome is more sensitive than, and equally specific as, immunocompromised patients presenting with fever in
serologic testing in the detection of acute Babesia spp. the absence of localizing signs or symptoms. This is
Infections with as few as three parasites in 100 microliters especially true when he or she presents from an area with
of blood can yield a positive result with PCR [5,6]. endemic disease. While the management of fever in
immunocompromised patients is largely standardized
Microscopically, Babesia invades erythrocytes and causes from an emergency department perspective, considering
damage through parasite directed alterations of the Babesiosis from the beginning may prompt early investi-
erythrocyte membrane [9]. These changes cause erythro- gation of a blood smear, which has the potential to alert
cytes to adhere to the endothelium of the microvasculature the emergency department physician to Babesiosis. In
resulting in excessive pro-inflammatory cytokine release addition, considering the disease from the outset has the
and tissue hypoxia [5]. In addition, the finding of anemia potential to accelerate administration of the appropriate
is a result of the lysis of erythrocytes [10]. The severity of antimicrobial therapy and thus prevent unnecessary
disease is proportional to the parasite load with complica- morbidity and possible mortality.
tions most commonly occurring in those individuals with
a parasitemia level greater than 10.0 percent or hemoglo- List of abbreviations
bin less than 10.0 grams/deciliter on admission [3]. PCR, Polymerase Chain Reaction; pg/cell, Picograms/cell;
Complications of Babesiosis include acute respiratory RMSF, Rocky Mountain Spotted Fever; SLE, Systemic
failure (20.6%), disseminated intravascular coagulation Lupus Erythematosis; TNF, Tumor Necrosis Factor.
(17.6%), non-cardiogenic pulmonary edema (11.8%),
and renal failure (5.9%) [3]. Consent
Written informed consent was obtained from the patient
Immunocompromised hosts are more susceptible to for publication of this case report and accompanying
Babesiosis than the immunocompetent population. images. A copy of the written consent is available for
More specifically, those patients treated with prednisone review by the Editor-in-Chief of this journal.
and tacrolimus are at risk of symptomatic infection
because these drugs suppress T-cell activation and Competing interests
calcineuron/interleukin-2 production needed to fight an The authors declare that they have no competing interests.
intracellular pathogen. Because of this decreased immune
response, an immunocompromised patient is more likely Authors’ contributions
to have a high peak parasitemia level and thus more likely DN was integral in the care of the patient in the emergency
to suffer from severe disease and complications [3,7,9]. department, developed the concept for the paper,
assembled the appropriate resources for writing the
The rate of mortality has been estimated to be approxi- paper, and was the primary researcher and author on the
mately five percent in patients with clinically evident paper. JB helped gather information about the patient on
disease and thus treatment is indicated for all patients the inpatient unit, and helped research, write, and review
presenting for medical care. Prior to 2000, the treatment of the paper. RA was the physician of note and responsible
Babesiosis had classically entailed a combination of for the care of the patient in the emergency department,
quinine and clindamycin. In 2000, Krause et al showed helped develop the concept, and critically reviewed the
that the combination of atovaquone and azithromycin paper. MI reviewed the patient’s blood smear and
was as efficacious as the standard treatment and consider- contributed to the writing of the pathology portions of
ably more tolerable. Patients with severe disease and those the paper. AM helped write the introduction and critically
at risk for complications may also require exchange reviewed the paper. MM helped develop the concept for
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the paper and helped write and critically review the paper.
All authors read and approved the final manuscript.
Acknowledgements
The authors of this case report have no acknowledgements.
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