Babesiosis in the Immediate Postoperative Period after Splenectomy for Trauma

Case Report

In August 2004, a 52-year-old woman from Martha's Vineyard presented to our institution hemodynamically unstable 13 days after a mechanical fall from standing. At the time, other than superficial abrasions over her right elbow and knee, she had no complaints and did not seek medical care. Four days before hospitalization, she had developed intermittent low-grade abdominal pain. This progressed to persistent severe pain in her left upper quadrant with radiation to her left shoulder. She developed dizziness that prompted her to seek medical care. She denied any history of recent fevers, chills, or sweats.

The patient initially presented to her local hospital where she was hypotensive and tachycardic, with evidence of hemorrhage from an enlarged spleen on a computed tomographic (CT) of her abdomen. She was resuscitated with two units of packed red blood cells and 4 L of crystalloid, then transferred to our institution. In our emergency department, she was afebrile but continued to be unstable hemodynamically. She was transferred directly to the operating room (OR) for an emergent laparotomy.

In the OR, the patient was found to have extensive hemoperitoneum originating from an enlarged and damaged spleen. She underwent an uncomplicated splenectomy and began oral intake on postoperative day (POD) 2. On POD 4, she developed a fever to 39.2°C and a white blood cell count (WBC) of 5270/microliter with a stable hematocrit. An evaluation of her fever was pursued.

Her vital signs were stable; she was otherwise asymptomatic; her abdominal examination was benign; the lower extremities were without edema or tenderness; and the wound was clean, dry, and intact, without erythema. Peripheral blood cultures, urinalysis, urine culture, and sputum culture were obtained and found to be negative. A chest radiograph was obtained and revealed small bilateral pleural effusions.

On POD 5, the patient was febrile to 40.2°C with a stable WBC. She now had episodes of shaking chills and profuse sweats. Laboratory values were notable for a high alanine aminotransferase (ALT) of 126 U/L (normal = 7–52 U/L), aspartate aminotransferase (AST) of 96 U/L (normal = 9–30U/L), and alkaline phosphatase (ALK) of 167 U/L (normal =36–118 U/L). An abdominal CT scan was negative for portal vein thrombosis or abscess.

Further questioning of the patient revealed a history of fatigue in the months before admission. Because of her time spent in an endemic area, we became concerned about the possibility of babesiosis. We obtained thin blood smears that revealed a parasitemia of 2.3%. No malarial parasites were seen on thin smear, and the patient denied a history of travel to areas where malaria is endemic. Pathology revealed an enlarged spleen, measuring 18.0 × 12.0 × 3.8 cm with a weight of 647 g. Giemsa staining of the spleen demonstrated intraerythrocytic Babesia confirming babesial infection pre-operatively (Fig. 1).

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FIG. 1.

Giemsa-stained sections of the spleen (1000x oil magnification). Intracellular organisms (white arrow head) were seen in the erythrocytes within the spleen and not within the spleen parenchyma itself. In the upper left corner, the arrow head points to a Maltese cross. (Photograph courtesy of Dr. Dan Milner, Department of Pathology, Brigham and Women's Hospital, Boston, MA.)

The patient was started on a regimen of atovaquone and azithromycin, with slow resolution of her constitutional symptoms. She was discharged on POD 12, without fever or detectable levels of parasitemia on repeat thin blood smear. She remained asymptomatic after completion of a 2-week course of antibiotics. Repeat blood smears in the following months remained negative for parasitemia, and the patient continues to be asymptomatic in follow-up.

Discussion

Babesiosis is an emerging tick-borne disease caused by infection with intraerythrocytic protozoan parasites of the genus Babesia [1]. Babesia is believed to have a worldwide distribution [2]. In the United States, Babesia was first recognized as a cause of human infection in New England during the 1960s [3,4]. Human babesiosis caused by Babesia microti is endemic to Martha's Vineyard, Nantucket, Shelter Island, and Long Island. Infections caused by Babesia microti have also been reported in Minnesota, Wisconsin, and Georgia, and other species have been recently described in Washington, California, and Missouri [5–9].

Babesia microti is transmitted to humans by Ixodes dammini (also known as Ixodes scapularis), the same tick responsible for the transmission of Lyme disease and ehrlichiosis [10]. The definitive host and most likely cause for the increasing incidence of babesiosis in the Northeast is the white-tailed deer; the primary reservoir for Babesia microti is the white-footed mouse [11–13]. Transmission usually occurs in the late spring and summer, when nymphs are more prevalent and humans are more likely to enter tick-infested areas [13]. There have been at least 40 documented cases of Babesia transmission by blood transfusion, and it is thought that Babesia microti is the most frequently transmitted parasitic agent in the blood supply of the U.S. [14,15].

The clinical severity of babesiosis, which is variable and probably reflects a host's level of parasitemia, ranges from asymptomatic infection to fulminant malaria-like illness resulting in death [16]. Latent infection, with an absence of signs or symptoms, may be present in up to one-third of infected individuals, as reported in an annual serosurvey of healthy individuals living on Block Island [17]. The most severe cases are more likely in immunocompromised hosts, who may develop acute respiratory failure, disseminated intravascular coagulation, congestive heart failure, renal failure, or hepatic failure [18]. One retrospective review of 139 patients hospitalized with babesiosis in New York State reported a mortality rate of 6.5% [19].

Symptoms of babesiosis result from lysis of the host's erythrocytes that occurs when the intraerythrocytic Babesia undergo asexual reproduction [16]. Approximately 25% to 30% of infected adults are asymptomatic or have only mild influenza-like symptoms [17,20]. Symptoms of babesiosis include high fever, fatigue and weakness, shaking chills, diaphoresis, and headaches. Patients may develop jaundice and dark urine as the disease progresses with hemolysis. Findings on physical examination may include hepatomegaly and splenomegaly but are usually limited to fever [13]. Laboratory abnormalities include high ALT, AST, ALK, indirect bilirubin, and lactate dehydrogenase. There may also be a normochromic, normocytic anemia, a high reticulocyte count, thrombocytopenia, and leukopenia.

Diagnosis of babesiosis may be made by identification of the organisms on thin or thick blood smears stained with Wright or Giemsa stain. A pathognomonic finding is the presence of a Maltese cross (Fig. 1), which consists of a tetrad of merozoites [18]. This finding is not seen in infection with Plasmodium falciparum. A further distinguishing feature is the absence of hemozoin pigment in cases of Babesia [18]. Confirmatory testing includes serologic testing for Babesia antibody using indirect immunofluorescent antibody (IFA) testing or detection of Babesia deoxyribonucleic acid using polymerase chain reaction (PCR). Both tests are highly sensitive (88–96% for IFA, 95% for PCR) and specific (90–100% for IFA, 100% for PCR) [21,22]. Because of the risk for concurrent infection with Lyme disease, testing for Borrelia burgdorferi should also be undertaken [23].

Treatment of babesiosis has traditionally been with a combination of clindamycin (600 mg every 6 h, intravenous or orally) and quinine (650 mg every 8 h) for 7 to 10 days [13]. A high frequency of adverse effects that, in approximately one-third of patients, leads to discontinuation of treatment or dosage reduction tends to limit this regimen [24]. In a randomized controlled trial, a 7-day course of combination atovaquone (750 mg every 12 h) and azithromycin (500 mg on day 1 and 250 mg/day thereafter) was compared with a regimen of clindamycin and quinine [24]. Both regimens were found to be equally effective, and the regimen of atovaquone and azithromycin had significantly fewer adverse effects (15%) than clindamycin and quinine (72%) [24]. The study excluded patients with life-threatening illness, so the authors recommended continued use of clindamycin and quinine in the most serious of cases. Because of the risk for concurrent infection with Lyme disease, consideration should be given to empirically treating for infection with Borrelia burgdorferi.

Severe cases of babesiosis, defined as organ failure or 10% or greater parasitemia, should have treatment initiated with clindamycin and quinine [18]. Failure of this regimen is an indication for whole-blood exchange transfusion, which serves to reduce a patient's parasitemia [25,26]. Additionally, plasmapheresis may be considered as a treatment option in severe cases [27].

Babesiosis in splenectomized individuals is a well-recognized occurrence. The first case of human babesiosis was reported in a splenectomized farmer, and most of the cases reported from Europe are in asplenic hosts [25–28]. Our case is most likely an example of a silent to mild infection that manifested in the early postoperative period after splenectomy in a previously immunocompetent host. Although this possibility has been suggested before, it is unique because the only other documented case of infection with Babesia microti in the immediate postoperative period after splenectomy was reported in a patient with acquired immune deficiency syndrome [29,30].

We hypothesize that our patient contracted babesiosis before or during the spring or early summer of 2004 and developed an enlarged spleen as a result of her babesiosis. This put her at higher risk for splenic rupture after a fall from standing. Aside from experiencing new onset of weakness and fatigue that lasted throughout the summer, she was otherwise asymptomatic until after her splenectomy. Because the incubation period for transfusion-transmitted babesiosis has been estimated at up to 9 weeks [13], and the patient had symptoms and evidence of an enlarged spleen before receiving a blood transfusion, we believe that it is an unlikely source of her babesiosis. Nonetheless, it cannot be excluded as a possible source of her infection.

Conclusion

Recognition of babesiosis by the surgeon is important for several reasons. It may lead to splenomegaly, increasing the risk of rupture from trivial or major trauma. Consideration must be given to babesiosis as a possible cause of postoperative fever in patients undergoing splenectomy who have lived or traveled in endemic areas. We believe that patients with splenic injury and splenomegaly who undergo splenectomy and live in endemic areas should be screened for babesiosis, even if asymptomatic, and treated appropriately to prevent recrudescence of symptomatic disease in the postoperative period. Patients who undergo splenectomy are at higher risk for developing babesiosis in the future and may benefit from active intervention to avoid tick exposure.