TRANSFUSION-TRANSMITTED BABESIOSIS IN ONTARIO: FIRST REPORTED CASE IN CANADA

Introduction

Human babesiosis is a tick-borne zoonosis caused by protozoa of the genus Babesia. While the genus comprises over one hundred species, most cases of human babesiosis in North America are caused by Babesia microti^(1-4). The great majority of these cases are transmitted by the bite of the deer or blacklegged tick, Ixodes scapularis^(2-4). The clinical manifestations of babesiosis range from asymptomatic to severe and occasionally fatal disease characterized by fever, intravascular hemolysis, hemoglobinuria, and renal failure. Severe disease is more common in asplenic individuals, elderly patients, and those with underlying immunodeficiency states including the acquired immunodeficiency syndrome^(5,6).

Babesia parasites invade and survive within erythrocytes. They remain viable under blood bank conditions and there have been several well documented cases of babesiosis acquired from blood transfusion in the United States^(7-11). We report the first transfusion-transmitted case of babesiosis in Canada.

Methods

Whole blood samples from the blood donors and the recipient were examined using Giemsa-stained thick and thin films and by the polymerase chain reaction (PCR) for parasite DNA. At least 400 thick smear fields were examined at a magnification of 1,000 times. In addition, at least 400 thin smear fields were examined at a magnification of 1,000 times. Genomic DNA was extracted from whole blood using Qiagen columns and Babesia DNA was amplified as previously described^(1,12).

Serum specimens were also tested at the United States Centers for Disease Control and Prevention by indirect immunofluorescent antibody (IFA) assay for reactivity to B. microti and for human monocytic and human granulocytic ehrlichiosis, and Lyme disease (by enzyme-linked immunosorbant assay [ELISA] and Western blot) by the Ontario Provincial Ministry of Health laboratory.

Case report of the blood recipient

The recipient was a 53-year-old immunocompetent spleen-intact woman who had emigrated from Pakistan to Canada in 1988. One year previously she had returned to visit Pakistan for 4 weeks. Her past medical history included asthma and ß-thalassemia. She initially presented on 23 October 1998 with a history of dyspepsia and melena stools. Her hemoglobin was 69 g/L and on 6 November 1998 she was transfused with three units of packed red blood cells (PRBCs). Her post-transfusion hemoglobin was 106 g/L. Endoscopy of her upper gastrointestinal tract and abdominal computed tomography scans performed at that time were normal. She was readmitted on 25 February 1999 for colonoscopy. She was noted to have a hemoglobin of 70 g/L and was transfused with two additional units of PRBCs. Her post-transfusion hemoglobin was 104 g/L. Her colonoscopy was normal but a small bowel follow-through examination revealed an annular tumor of her small intestine. On 9 March 1999 she underwent laproscopic resection of the tumor without complication. However, she was readmitted on 11 April 1999 following a 7-day history of high fever, chills, diaphoresis, nausea, and weakness.

Her physical examination on admission was unremarkable with the exception of a temperature of 40° C. Laboratory investigations on this admission demonstrated a hemoglobin of 66 g/L (normal 120 g/L to 140 g/L), a white blood cell count of 4.2 x 10⁹/L, an elevated total bilirubin of 31 µmol/L (normal < 17 µmol/L). Her lactate dehydrogenase level was elevated at 161 U/L (normal 45 U/L to 90 U/L) and her aspartate aminotransferase level was elevated at 63 U/L (normal < 35 U/L). Examination of peripheral blood smears revealed intraerythrocytic ring forms initially attributed to Plasmodium falciparum infection at a parasitemia of 2.5%. However, smears were reviewed at the Tropical Disease Unit of the Toronto Hospital; a diagnosis of babesiosis was confirmed by the presence of typical intraerythrocytic forms of babesiosis and by PCR results which were positive for B. microti DNA. The recipient was treated with quinine (600 mgs TID for 7 days) and clindamycin (600 mgs TID for 7 days). She responded promptly and was asymptomatic 3 months later at follow up. Follow-up blood smears were negative for Babesia.

Investigation of blood donors

The recipient received a total of five units of PRBCs from five donors during hospitalizations in November 1998 and February 1999.

During the November 1998 admission, the recipient received three units of PRBCs from three donors. The first donor was a 46-year-old male who had donated blood nine times previously. He had travelled to Pennsylvania in March of 1998 and had camped in a rural area in Ontario. He did not remember any tick bites and remained well in follow up. He returned for follow-up serologic and PCR testing for babesiosis. His Giemsa-stained thick and thin films, Babesia serology, and PCR for Babesia DNA were all negative.

The second donor was a 43-year-old female who had donated blood products eight times previously. She had not travelled outside Canada in the last year and had undertaken no camping or rural travel within Canada. She also remained well. Her Giemsa-stained thick and thin films, Babesia serology, and PCR for Babesia DNA were also negative.

The third donor was a 22-year-old male, first-time donor who had traveled to Taiwan in January 1998 and to urban areas in the United States in August 1998 (Chicago and West Lafayette). This individual remained well during and after travel. This donor did not return to provide a follow-up blood sample.

During the February 1999 admission, the recipient received two units of PRBCs from two donors. One was a 48-year-old male who had donated blood nine times previously. He donated a unit of PRBCs on 6 February 1999, which was transfused into the recipient on 26 February. He provided a recent history of travel to South America but no travel on the continental United States in the last 3 years. He remained well and submitted a follow-up blood sample. His thick and thin films, Babesia serology, and PCR for Babesia DNA were negative.

The last donor was a 40-year-old male who had donated blood twice previously. He gave a history of camping in rural and forested areas in Cape Cod in August 1998. He did not remember receiving any tick bites and he denied any febrile illnesses during or after his return from Cape Cod. He donated a unit of blood on 6 February 1999 which was transfused into the recipient on 25 February 1999. He also gave a travel history of visiting the United States (Arizona, St. Louis, New York City, and Michigan) in the previous year. He provided a follow-up blood sample. His blood sample was positive for B. microti by blood smear and by PCR. His Babesia serology was also positive at a titer of 1:1024 by IFA. He was negative for erlichiosis and Lyme disease by serologic testing. He received treatment with clindamycin (600 mgs TID for 7 days) and quinine (600 mgs TID for 7 days) and remained well in follow up. Repeat blood smears at 1 month post therapy were negative.

Discussion

This is the first report of transfusion-transmitted babesiosis in Canada and only the third and fourth cases of B. microti infection recognized in this country.

As was the case for the donor in this report, individuals infected with babesiosis may remain asymptomatic but parasitemic for months to years following tick-transmitted disease⁽¹³⁾. Since the parasite remains infective under blood-banking conditions, transfusion associated babesiosis is a risk of transfusion with blood components including platelet concentrates, PRBCs, and frozen, thawed, and deglycerolized erythrocytes^(7-11). The risk of acquiring babesiosis from a blood transfusion in Canada is unknown but would be expected to be very low. A study of transfusion recipients in Connecticut, an area endemic for babesiosis, reported a risk of 0.17% per unit of transfused PRBCs⁽¹¹⁾.

In Canada, blood banks do not routinely inquire of donors about travel to Babesia-endemic areas (e.g. Cape Cod, Martha's Vineyard, Connecticut), tick bites, or a past history of babesiosis. However, since most immunocompetent individuals who acquire babesiosis do not remember a tick bite and since most will have either minimal or no symptoms, this deferral practice would be unlikely to identify most Babesia-infected donors. The great majority of cases of babesiosis in the northeastern United States are acquired during peak deer tick activity (June-September)(3). Consequently, the greatest risk of transfusion-transmitted babesiosis would be expected to occur during the summer season(11). However, since infected individuals may remain parasitemic for up to years and since PRBCs are stored for up to 42 days, even seasonal deferral of potential high-risk donors would not be expected to prevent transfusion-associated babesiosis.

Similar to previously reported cases of transfusion-associated babesiosis in the United States, the recipient of Babesia-infected blood products in this case developed moderate to severe manifestations of infection⁽⁷⁾. Severe and occasionally fatal disease may occur in certain risk groups especially those who are elderly, splenectomized, or otherwise immunocompromised. Both the donor and recipient in this series were treated with a combination of quinine and clindamycin, and both had a satisfactory clinical and or parasitologic response. However, there have been a number of recent reports including a case of imported babesiosis in our own experience that have not responded optimally to this traditional therapy. These patients have however generally responded to the combination of azithromycin and atovaquone^(14,15).

Babesiosis is a significant public health problem in several regions of the northeastern United States. As the tick vector increases in geographic distribution^(2,16,17), an increase in the incidence of babesiosis and subsequent transfusion-transmitted infections may occur. In addition to B. microti, tick-borne and transfusion-associated infection with related parasites including WA1 and MO1 have recently been reported^(18,19).

Given the millions of Canadians who visit Babesia-endemic regions of the United States each year, we must anticipate an increase in the number of cases of imported babesiosis and the potential for transfusion-transmitted disease in this country. Our own anecdotal experience with five documented cases of babesiosis in Toronto residents within the last 2 years supports this contention. Canadian physicians must consider babesiosis in the differential diagnosis of a patient who developing fever or a hemolytic reaction after a recent blood transfusion. Prompt recognition and an accurate diagnosis are important since Babesia infections respond to therapy and may be severe or fatal in certain risk groups. Improved strategies to prevent transfusion-associated babesiosis are required.

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Source: S Bu Jassoum, MD, I W Fong, MD, Department of Medicine, St. Michael's Hospital; B Hannach, MD, Canadian Blood Services, Toronto Centre; KC Kain, MD, Tropical Diseases Unit, Division of Infectious Diseases, Toronto General Hospital, University of Toronto, Toronto, Ont.