The Traveling Farm Wife
Article Outline
Presentation
In late summer, a 77-year-old woman was hospitalized after 9 days of chills, low-grade fever, fatigue, and generalized weakness. She did not have abdominal pain, coughing, diarrhea, dyspnea, jaundice, nausea, rashes, sore throat, vomiting, or weight loss. Her medical history was significant for well-controlled type 2 diabetes mellitus, dyslipidemia, hypertension, hypothyroidism, osteoarthritis, and osteoporosis. She took alendronate, calcium, levothyroxine, lisinopril, metformin, naproxen, and simvastatin. None of these had been initiated in the weeks prior to onset of symptoms.
The patient and her husband resided on a farm in eastern Pennsylvania. She had horses, dogs, and cats but did not tend to farm animals directly. Although she had traveled extensively outside of the United States, including excursions to Brazil, Europe, and South Africa, she had not traveled internationally in over 15 years. When symptoms began in July, she was vacationing in Florida. Prior to this trip, she had spent time at a home in Nantucket, Massachusetts. She did not recall any animal or tick bites, but her family noted a possible insect bite 4 weeks prior to the onset of symptoms. She had no history of alcohol, illicit drug use, or smoking.
Upon examination, the patient’s temperature ranged from 98.6°F (37.0°C) to 102.7°F (39.3°C), and her heart rate, respiratory rate, blood pressure, and oxygen saturation were all normal. Her scleras were icteric, and her conjunctivae were pale. A lung examination revealed bibasilar rales; cardiac and neurologic examinations were normal. Her abdomen was tender on the left side and in the right upper quadrant, but the liver and spleen were not palpable. Multiple ecchymoses were visible on the lower extremities, and symmetric bilateral edema was noted in the knees. There were no joint effusions.
Initial laboratory evaluation showed a hemoglobin level of 9.1 g/dL, platelet count of 33 x 103 per mm3, and white blood cell count of 4.9 × 103 cells/mm3. Her blood urea nitrogen level was 54 mg/dL, serum creatinine was 2.0 mg/dL, total bilirubin was 5.9 mg/dL, and direct bilirubin was 5.0 mg/dL. The patient was treated with azithromycin and atovaquone. Over the next 5 days her renal function continued to deteriorate so that hemodialysis was required. She was then transferred to our hospital.
Assessment
On transfer, the patient had an apparent worsening of her pallor and jaundice, and her oxygen saturation was mildly decreased. Laboratory data showed a hemoglobin of 8.7 g/dL; platelets, 79 × 103 per mm3; and white blood cells, 10.8 × 103 cells/mm3 with 68% neutrophils, 3% bands, 12% lymphocytes, and 16% monocytes. Additional results were as follows: serum creatinine, 3.9 mg/dL; total bilirubin, 20 mg/dL with direct bilirubin, 16.5 mg/dL; aspartate aminotransferase, 118 U/L; alanine aminotransferase, 65 U/L; alkaline phosphatase, 118 U/L; lactate dehydrogenase, 914 U/L; and haptoglobin less than 6 mg/dL. A urine dipstick revealed a pH of 6.5, bilirubin, hemoglobin pigments, and a 2+ protein. No cells or casts were visible upon microscopic evaluation.
A peripheral smear revealed intraerythrocytic parasites consistent with Babesia species with 5%-8% parasitemia (Figure 1). Borrelia burgdorferi serologies were negative, as were polymerase chain reaction tests for Erlichia chaffeensis and Streptococcus equi.
Figure 1.
Intraerythrocytic parasites with 5%-8% parasitemia were evident on a peripheral blood smear obtained on admission before treatment began (left). By day 4 of treatment parasitemia was reduced (right).
Diagnosis
Babesiosis, a zoonotic illness caused by a protozoan parasite, infects red blood cells. This organism is carried by the deer tick Ixodes scapularis, also the vector for the organisms that cause Lyme disease and human granulocytic ehrlichiosis. In the United States, the disease occurs in the summer and is almost always caused by the species Babesia microti, which is endemic in northeastern coastal areas. The incidence in some endemic areas is rising, with seroprevalence reported to be as high as 10%.1 Clinical presentation varies from asymptomatic infection to massive hemolysis, but classically includes flu-like symptoms such as arthralgias, chills, fatigue, fever, headache, hemolytic anemia, malaise, and myalgias. Diagnosis is confirmed by Geimsa- or Wright-stained thick and thin peripheral blood smears that demonstrate round or oval intraerythrocytic ring forms.2 The structures are distinguished from Plasmodium falciparum by the absence of pigment granules or the presence of the classic “Maltese cross” tetrads.
While most patients exhibit asymptomatic to mild clinical illness, approximately 40% of patients who are hospitalized for Babesia infection develop severe complications, namely respiratory failure, disseminated intravascular coagulation, congestive heart failure, renal failure, and shock.3, 4 Mortality among those needing hospitalization is 5%-9%.3, 4, 5 Of these, 52% had an underlying chronic disease, 12% had a prior splenectomy, and 27% were older than 55 years.3 Renal failure is among the least common complications, occurring in 4%-6% of inpatients with babesiosis, with only 2% requiring hemodialysis.3, 4
The mechanism of acute renal failure in babesiosis is yet to be elucidated. Studies in mice infected with B. microti parasites suggest that tumor necrosis factor and other pro-inflammatory cytokines trigger red blood cell destruction and leukocyte accumulation in blood vessels with subsequent hemolysis, renal hypoperfusion, and acute tubular necrosis.6 Similar pathogenesis may account for other uncommon sequelae, such as acute respiratory distress syndrome, disseminated intravascular coagulation, and shock.
Kidney failure occurring with related parasitic infections, such as Plasmodium falciparum malaria in humans and Babesia canis in dogs, may share a common mechanism. B. canis infection causes acute renal failure in 2% of cases, particularly in dogs with marked icterus or underlying renal insufficiency.7 Histologic examination of infected kidneys shows shrunken glomeruli, tubular necrosis, and hemoglobin granules. Similarly, in P. falciparum malaria, acute tubular necrosis is the predominant renal pathology.8 The reported prevalence of renal failure in malaria is highly variable—ranging from less than 1% to 30%—and is associated with high rates of parasitemia, hemolysis, multi-organ failure, and death.9, 10
Management
Standard treatment of babesiosis is a 7- to 14-day course of clindamycin and quinine, though the combination is associated with intolerable side effects in up to 72% of patients, and treatment failures have been reported.11 When this traditional regimen was compared to atovaquone and azithromycin in patients without life-threatening disease, the newer regimen had equivalent efficacy with a far lower frequency of adverse reactions (15% versus 72%).12
In severe cases, disease may rapidly progress despite appropriate antimicrobial treatment. Exchange transfusions with whole blood or red blood cells, intended to clear parasites and remove pro-inflammatory cytokines, may be life-saving and is generally initiated for parasitemia of 5% or higher.13 Plasmapheresis has also been reported as a successful method for reducing parasitemia and resulting hemolysis in severely ill and immunosuppressed patients who fail antimicrobials and/or exchange transfusion.14 Anecdotal evidence supports the use of hemodialysis early in the disease course for patients with acute renal failure with P. falciparum malaria.15 Although hemodialysis in treatment of babesiosis has not been similarly described, it should be initiated if clinically indicated just as it is for patients with acute renal failure of other etiologies.
Our patient was elderly, immunocompetent, and non-splenectomized with severe babesiosis complicated by renal failure. She did not experience shock, disseminated intravascular coagulation, or acute respiratory distress syndrome. Underlying hypertension and diabetes, along with regular use of potentially nephrotoxic drugs (eg, angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs) might have made her more susceptible to renal failure, particularly in the setting of ongoing hemolysis. In addition, intravenous contrast was inadvertently administered on hospital day 7 during a computed tomography scan. She was hemodynamically stable with parasitemia less than 10%, so antimicrobial treatment with atovaquone and azithromycin was maintained for 14 days.
Disease progressed despite antibiotic therapy, with ongoing parasitemia, increased hemolysis, and renal failure. This prompted exchange transfusion on hospital day 3, with subsequent clinical improvement and successful clearance of infection by day 4. The patient’s renal function initially worsened with a peak creatinine of 5.1 mg/dL so that hemodialysis was necessary on hospital day 5, but it gradually improved with no further need for hemodialysis by discharge (Figure 2). A subsequent peripheral blood smear showed reticulocytosis with intracellular parasitemia of less than 1% (Figure 1, right panel). By hospital day 8, intraerythrocytic parasites were not seen on peripheral thick and thin blood smears. Her bilirubin level also trended down, and she was discharged in good condition 11 days after the initial hospitalization.
Figure 2.
Renal function and parasitemia over hospital course.
References
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- . Human babesiosis in New York State: review of 139 hospitalized cases and analysis of prognostic factors. Arch Intern Med. 1998;158:2149–2154
- . Severe babesiosis in Long Island: review of 34 cases and their complications. Clin Infect Dis. 2001;32:1117–1125
- . Human babesiosis in New York State: an epidemiologic description of 136 cases. Clin Infect Dis. 1992;15:1019–1023
- . Role of cytokines in the pathogenesis of human Babesia isolates in mice. Am J Trop Med Hyg. 1996;55(S2):40
- . The pathophysiology of canine babesiosis: new approaches to an old puzzle. J S Afr Vet Assoc. 1994;65:134–145
- . The pathophysiology of severe falciparum malaria. Parasitol Today. 1986;2:271–282
- . A case series of falciparum malaria-induced acute renal failure. Ann Acad Med Singapore. 1999;28:578–582
- . Acute renal failure due to falciparum malaria. Ren Fail. 1990;12:15–19
- . Babesiosis in patients with AIDS: a chronic infection presenting as fever of unknown origin. Clin Infect Dis. 1996;22:809–812
- Atovaquone and azithromycin for the treatment of babesiosis. N Engl J Med. 2000;343:1454–1458
- . Fulminant babesiosis treated with clindamycin, quinine, and whole-blood exchange transfusion. Transfusion. 2000;40:375–380
- . Therapeutic apheresis for babesiosis. J Clin Apher. 1998;13:32–36
- Treatment of malarial acute renal failure by hemodialysis. Am J Trop Med Hyg. 1999;60:233–237
Charles M. Wiener, MD, Section Editor
Requests for reprints should be addressed to Charles M. Wiener, MD.
E-mail address: cwiener@jhmi.edu
PII: S0002-9343(06)01357-X
doi:10.1016/j.amjmed.2006.11.009
© 2007 Elsevier Inc. All rights reserved.
