Babesia microti Infection, Eastern Pennsylvania, USA
Marcela E. Perez Acosta, Peter T. Ender, Erin M. Smith, and Jeffrey A. Jahre
Author affiliations: St. Luke�s University Hospital and Health Network, Bethlehem, Pennsylvania, USA
Abstract
Infection with Babesia microti has not been well-described in eastern Pennsylvania, USA, despite the vector of this organism being prevalent. We report 3 cases of babesiosis in eastern Pennsylvania in persons without recent travel outside the region or history of blood transfusions, suggesting emergence of this infection.
Babesiosis is an intraerythrocytic infection caused by protozoan parasites of the genus Babesia. In the United States, Babesia microti is the most common species that causes human babesiosis. Disease-endemic areas include specific regions in the northeast and upper Midwest United States. Infection with this organism can be asymptomatic to life-threatening. Signs and symptoms include high fever, diaphoresis, chills, headaches, and anorexia. Patients can also have hemolytic anemia and thrombocytopenia (1).
B. microti is transmitted by the Ixodes scapularis tick, which is also the vector of Borrelia burgdorferi and Anaplasma phagocytophilum (2). Although B. burgdorferi is endemic to Pennsylvania (3), B. microti is not considered endemic to this region (4,5). We report 3 cases of human babesiosis in patients from Northampton County in eastern Pennsylvania, USA, who had not recently traveled outside the region or had blood transfusions. None of the patients had risk factors for severe babesiosis, such as asplenia.
The Patients
Patient 1 was a 68-year-old man who was hospitalized on August 18, 2011, because of 6 days of fever, arthralgias, generalized weakness, and confusion. He was given doxycycline for treatment of presumptive Lyme disease but showed no improvement. He had not traveled outside eastern Pennsylvania for >3 years. He had never received any blood transfusions. Although he did not recall any tick attachments, he enjoyed gardening and other outdoor activities.
Figure
Thumbnail of Wright-stained blood smear for patient 1 with babeosis on day 1 of hospitalization, eastern Pennsylvania, USA, showing an intraerythrocytic trophozoite of Babesia microti in a ring form (thin arrow) and a tetrad arranged in a cross-like pattern (thick arrow). Original magnification �1,000. Figure. . Wright-stained blood smear for patient 1 with babeosis on day 1 of hospitalization, eastern Pennsylvania, USA, showing an intraerythrocytic trophozoite of Babesia microti in a ring form (thin arrow) and...
Pertinent clinical and laboratory data are shown in the Table. During testing for thrombocytopenia, a peripheral blood smear was obtained on hospital day 1 and showed ring forms with tetrads (Figure) and a parasitemia level of 10%. A PCR result for the blood sample was positive for B. microti.
Despite treatment for 5 days with clindamycin and quinine, the treatment of choice for severe babesiosis, the fever persisted. Antimicrobial drug therapy was changed to atovaquone and azithromycin. The patient completed 10 days of treatment and showed resolution of symptoms and normalization of platelet count and total bilirubin level. Parasitemia level at the time of discharge was 1.2%. Laboratory data after discharge were not available.
Patient 2 was an 84-year-old woman with microcytic anemia who was hospitalized on June 8, 2012, because of 2 weeks of fever, diaphoresis, myalgias, progressive dyspnea, and fatigue. Originally from New Hampshire, she had been living in Northampton County, Pennsylvania, for >4 years. She had not traveled outside the region in the past 4 years. She received a blood transfusion for chronic anemia 1 year before onset of this illness. She recalled multiple tick bites in the recent past.
Because of pancytopenia (Table), a bone marrow biopsy was performed and showed intraerythrocytic ring forms with tetrads. Parasitemia level for a peripheral blood smear was 1.4%. A PCR result for B. microti was positive.
The patient was given atovaquone and azithromycin for 10 days and showed resolution of symptoms and improvement in abnormal laboratory values. A repeat blood smear on June 18 showed a parasitemia level of 0.1%, and a blood smear 1 month later showed no parasites.
Patient 3 was a 71-year-old man who was hospitalized on June 26, 2012, because of 2 weeks of fever and gradually worsening malaise and weakness. He had not traveled outside eastern Pennsylvania in the past 2 years and never received a blood transfusion. Two weeks before admission, he had an insect bite that developed into a larger, oval rash.
Initial testing for thrombocytopenia included a peripheral blood smear, which showed intraerythrocytic ring forms and tetrads and a parasitemia level of 0.4%. A PCR result was positive for B. microti. He was given atovaquone and azithromycin for 10 days. Because results of enzyme immunoassay and Western blot for B. burgdorferi were positive, he was also given doxycycline. Symptoms resolved, and the laboratory values improved. A repeat blood smear 1 week after starting antimicrobial drug therapy showed no parasites.
Conclusions
This report supports the hypothesis that babesiosis caused by B. microti is emerging in eastern Pennsylvania. As B. microti is spread by I. scapularis ticks, this infection might emerge in the range of the vector. Babesiosis is considered endemic to some states in which I. scapularis ticks are prevalent (6,7), but not in Pennsylvania.
All of these cases were confirmed by using robust laboratory methods. The 3 cases showed intraerythrocytic tetrad forms, an uncommon finding that is considered pathognomonic for Babesia infection (1). The strength of the diagnoses was further enhanced by PCR testing. Although PCR will amplify all Babesia species that are pathogenic in humans, the peak melting point temperature of amplicons for the 3 samples was nearly identical (difference ≤0.2�C) to that of the control B. microti amplicon, supporting B. microti as the causative agent (C.P. Cartwright, ViroMed Laboratories, Minnetonka, MN, USA, pers. comm.).
Two other persons with babesiosis have been treated at our institution since 2011. These case-patients were not included in this report because of inadequate laboratory confirmation for 1 patient and lack of a strict travel limitation for the other patient. One of these patients was given a diagnosis of babesiosis on the basis of serologic data obtained 2 months after the initial illness without blood smear confirmation. The second patient had traveled to western New Jersey, a babesiosis-endemic region, over a brief period before his illness.
The Pennsylvania Department of Health has received 39 voluntary reports of smear-positive babesiosis during 2005�2012 (K. Waller, Pennsylvania Department of Health, Harrisburg, PA, USA, pers. comm.). More than 60% of those reports were made after babesiosis became nationally reportable in 2011. Although many of these cases lacked detailed historical information to confirm that the cases were acquired in Pennsylvania, they further support the notion that B. microti is emerging in Pennsylvania.
Data on the prevalence of B. microti in I. scapularis ticks in eastern Pennsylvania are limited. However, 0.7% (3/443) of ticks collected from animals and humans in Monroe County in eastern Pennsylvania during 2004�2006 were infected with B. microti (3), supporting the plausibility of zoonotic transmission in the state.
Before these patients were identified, no cases of babesiosis had been diagnosed at our tertiary care center over the previous 10 years. Cases could have been missed because of the nonspecific nature of symptoms. However, this increase in the number of documented cases in 1 hospital is unlikely to be entirely explained by missed diagnoses. Furthermore, no other cases of babesiosis have been described at other institutions in this region.
This study had a few limitations. Recall bias could have played a role in obtaining a travel history. However, for each of these patients, family members were able to confirm the travel history, making recall bias unlikely. One of the patients had a blood transfusion 1 year before onset of systemic symptoms, making a transfusion-related infection unlikely. However, because this same patient was originally from New Hampshire, she might have been a chronic carrier.
These cases support the premise that babesiosis caused by B. microti infection is emerging in eastern Pennsylvania. Knowledge of the geographic distribution of B. microti is essential.
Diagnosis requires strong clinical suspicion and supportive laboratory data. Timely diagnosis and treatment for patients and testing of blood donors in areas in which B. microti is found might further prevent transfusion-related infection (8�10). Having this infection reportable in Pennsylvania and other states to which I. scapularis ticks are endemic might help identify the geographic region of this parasite.
Dr Perez Acosta is a second-year internal medicine resident at St. Luke�s University Hospital and Health Network in Bethlehem, Pennsylvania. Her research interests include vector-borne diseases and infectious diseases of the skin.
posted
I found it extremely interesting that patient 2 was found to have babesia sequestered in her bone marrow. Yes, this patient had received a blood transfusion, but she did report multiple tick bites as well.
Bea Seibert
Posts: 7306 | From Martinsville,VA,USA | Registered: Oct 2004
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posted
I sent a comment to the author of the journal article thanking them for publishing. Suggest that others do the same. There is a contact me link thru the original article.
I also briefly explained to the author that babesia can be chronic and resistant and in some cases relapsing and suggested follow-up of the patients.
Bea Seibert
Posts: 7306 | From Martinsville,VA,USA | Registered: Oct 2004
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lymednva
Frequent Contributor (1K+ posts)
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posted
Too bad they didn't explore Babesia Duncani.
-------------------- Lymednva Posts: 2407 | From over the river and through the woods | Registered: Apr 2006
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poppy
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posted
Seem like the bone marrow location should have been emphasized more in the article. Doesn't this show that babesia can exist in places other than red blood cells? Or am I missing something here? Does it mean stem cells can be infected? Can drugs get into bone marrow?
Posts: 2888 | From USA | Registered: Mar 2004
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Poppy -- Here is another medical journal abstact -- this one found babesia in the bone marrow, brain, spleen, heart, lung kidney and liver of mice.
Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2012 Dec 30;30(6):423-7.
[Establishment of the experimental animal model of Babesia microti].
[Article in Chinese]
Lu Y, Cai YC, Chen SH, Chen JX, Guo J, Chen MX, Ai L, Chu YH, Chen Z, Zhou XN.
Source
National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai 200025, China.
Abstract
OBJECTIVE:
To establish the experimental animal model for the study of Babesia mocroti.
METHODS:
BALB/c mice, immunosuppressive BALB/c mice, SCID mice and NOD-SCID mice were inoculated with B. mocroti-infected red blood cells (RBC) by intraperitoneal injection respectively. After inoculation, thin blood smears were prepared every day, stained with Giemsa staining and examined for the presence of parasitemia. Three mice were dissected to examine the infectiosity in bone marrow, brain, spleen, heart, lung, kidney and liver tissues. The infection rate of erythrocytes in different tissues was recorded, and the relationship between the infectiosity of tissues and infection rate in peripheral blood was analyzed. Blood samples infected with B. microti were preserved in liquid nitrogen with dimethyl sulfoxide (DMSO) for 2 months. The thawed parasitized blood was injected into the BALB/c mice by same route and the parasitemia was monitored.
RESULTS:
The four kinds of mice were all infected by B. microti with parasitemia. The percentage of parasitized red blood cells from peripheral blood were 82.4% (BALB/c mice, d7), 73.2% (immunosuppressive BALB/c mice, d5), 86.4% (SCID mice, d8) and 72.5% (NOD-SCID mice, d8) at the maximum, respectively. Parasitemia decreased rapidly in BALB/c mice, whereas decreased slowly in immunosuppressive BALB/c mice. Only the parasitemia in SCID mice and NOD-SCID mice decreased significantly and tended to picking up again. The parasites were observed in RBCs from bone marrow, brain, spleen, heart, lung, kidney and liver tissues. The infection rate of erythro- cytes in tissues increased with an increase of infection in peripheral blood. After cryopreservation, the parasites proliferated in BALB/c mice. Parasitemia appeared after inoculation with frozen infected blood two days later than that of fresh infected blood. The infection rate reached its peak after inoculation with frozen infected blood one day later than that of fresh infected blood.
CONCLUSION:
The experimental animal model of B. mictoti has been established. The infection rate of erythrocytes is related to the immune status of the host mice.
PMID: 23484250 [PubMed - in process]
Posts: 7306 | From Martinsville,VA,USA | Registered: Oct 2004
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posted
Do antimalarial meds get into the bone marrow and all of the other organs listed ?????????????????
That is a very good question. I don't think anyone has really tried to answer that that I am aware of.
I am having a discussion with the pathologists at Columbia University on Wednesday regarding Steve's brain and other tissues that were donated. Unfortunately they only have the brain and aorta and some nerve tissue.
Am also going to be talking to the hospital soon to see if they keep autopsy specimans and what would be required to get some other organs tested for babesia like organisms.
The abstract does say that the more infected red blood cells the more infected cells in the other organs. So maybe if you get rid of the infection in the bloodstream and continue treating long enough that eliminates the infection in other organs?
Bea Seibert
Posts: 7306 | From Martinsville,VA,USA | Registered: Oct 2004
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Don't know enough about research mice to know what the difference in the immune status of the 4 types listed in the abstract above are. That is something that seems like it needs lots more explanation.
What part of the immune system needs to be working to help eradicate a babesia infection?
Bea Seibert
Posts: 7306 | From Martinsville,VA,USA | Registered: Oct 2004
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GretaM
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posted
This is a wonderful article! Thank you for posting. Babesia in bone marrow... makes me sick to my stomach thinking about how 'thorough' Babesia is. argh.
Posts: 4358 | From British Columbia, Canada | Registered: Jun 2013
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