Transfusion-associated babesiosis after heart transplant. (Dispatches).We describe a 54-year-old spleen-intact man with transfusion-associated Babesia microti infection after a heart transplant. Adult respiratory distress syndrome Adult Respiratory Distress Syndrome Definition
Adult respiratory distress syndrome (ARDS), also called acute respiratory distress syndrome, is a type of lung (pulmonary) failure that may result from any disease that causes large amounts of fluid to developed in the patient, and he required mechanical ventilation. Our experiences with this patient suggest that babesiosis babesiosis (bəbē'bēō`sĭs), tick-borne disease caused by a protozoan of the genus Babesia. Babesiosis most commonly affects domestic and wild animals and can be a serious problem in cattle. should be considered in the differential diagnosis of transplant patients who have fever and hemolytic anemia.
Babesiosis is a tick-borne protozoan protozoan (prō'təzō`ən), informal term for the unicellular heterotrophs of the kingdom Protista. Protozoans comprise a large, diverse assortment of microscopic or near-microscopic organisms that live as single cells or in simple illness caused by infection of erythrocytes with various species in the genus Babesia. In the United States, Babesia microti is the agent most commonly reported to cause human infection (1). More recently, the MOl-type, WA 1-type, and CA 1-type Babesia Babesia /Ba·be·sia/ (bah-be´ze-ah) a genus of protozoa found as parasites in red blood cells and transmitted by ticks; its numerous species include B. bige´mina, B. bo´vis, and B. species have been identified as causing clinical disease in the United States (2-5). Babesia infection can also be acquired by blood transfusion (2,6,7). More than 40 cases of transfusion-transmitted B. microti infection have been reported in the United States (R. Cable and B. Herwaldt, unpub, data). B. microti infection is often asymptomatic (8) but may cause a malaria-like illness characterized by fever and hemolytic anemia. Babesiosis can also be associated with severe complications that include renal failure (9,10), disseminated intravascular coagulation disseminated intravascular coagulation
Abbr. DIC A hemorrhagic disorder that occurs following the uncontrolled activation of clotting factors and fibrinolytic enzymes throughout small blood vessels, resulting in tissue necrosis and (9), and adult respiratory distress syndrome (1,9,10). The risk of developing this clinical infection is increased for elderly, asplenic, or immunosuppressed Immunosuppressed
A state in which the immune system is suppressed by medications during the treatment of other disorders, like cancer, or following an organ transplantation.
Mentioned in: Fifth Disease patients (11). Here we describe a case of B. microti infection in a 54-year-old spleen-intact man acquired by blood transfusion after cardiac transplantation.
Case Report of Blood Recipient
The patient, a 54-year-old resident of New Jersey, had a medical history of coronary artery disease coronary artery disease, condition that results when the coronary arteries are narrowed or occluded, most commonly by atherosclerotic deposits of fibrous and fatty tissue. and atrial fibrillation. Approximately 18 months before his transplant, a "bull's-eye" rash developed, and the patient was empirically treated for Lyme disease. He did not recall a tick bite.
On August 19, 2000, he had an anterior wall myocardial infarction and was hospitalized in his hometown. He required intubation intubation /in·tu·ba·tion/ (in?too-ba´shun) the insertion of a tube into a body canal or hollow organ, as into the trachea.
endotracheal intubation , placement of a coronary stent and an intra-aortic balloon pump intra-aortic balloon pump
A pump connected to a balloon device that is inserted into the descending aorta to provide temporary assistance to the heart in the management of left ventricular failure. , use of intravenous cardiac inotropes, and transfusion of 2 U of packed red blood cells Red blood cells
Cells that carry hemoglobin (the molecule that transports oxygen) and help remove wastes from tissues throughout the body.
Mentioned in: Bone Marrow Transplantation
red blood cells (PRBC PRBC Packed Red Blood Cells
PRBC Pay Rent, Build Credit
PRBC Pressure Ratio Bleed Controller ). When fever developed, he was empirically treated with vancomycin, ciprofloxacin, and metronidazole metronidazole /met·ro·ni·da·zole/ (-ni´dah-zol) an antiprotozoal and antibacterial effective against obligate anaerobes; used as the base or the hydrochloride salt. It is also used as a topical treatment for rosacea. without improvement. No source of infection was found. On September 6, he was transferred to a New York City New York City: see New York, city.
New York City
City (pop., 2000: 8,008,278), southeastern New York, at the mouth of the Hudson River. The largest city in the U.S. medical facility for placement of a left ventricular assist device left ventricular assist device Cardiology A mechanical device to ↑ force and volume of blood flowing through the heart. Cf CABG, Jarvik-7. . Staphylococcus epidermidis was isolated from two sets of blood cultures. He was then treated with vancomycin and trimethoprim-sulfamethoxazole for 4 weeks.
On September 26, the patient received an orthotopic cardiac transplant. He received 32 U of irradiated leukocyte-reduced PRBC, 23 U of fresh frozen plasma fresh frozen plasma
n. Abbr. FFP
Blood plasma frozen within 6 hours of collection.
fresh frozen plasma (FFP FFP - Formal FP. A language similar to FP, but with regular sugarless syntax, for machine execution.
See also FL.
["Can Programming be Liberated From the von Neumann Style? A Functional Style and Its Algebra of Programs", John Backus, 1977 Turing Award Lecture, CACM ), 6 U of irradiated platelets, and 4 U of cryoprecipitate cryoprecipitate /cryo·pre·cip·i·tate/ (-pre-sip´i-tat) any precipitate that results from cooling, sometimes specifically the one rich in coagulation factor VIII obtained from cooling of blood plasma. during his 5.5-week hospital stay. On October 16, he was discharged on an immunosuppression regimen of cyclosporine, mycophenolate, and prednisone prednisone (prĕd`nĭsōn): see corticosteroid drug. .
On November 5, the patient became febrile. He was evaluated by his cardiologist 3 days later. He had fever, chills, diaphoresis diaphoresis /di·a·pho·re·sis/ (-fah-re´sis) sweating, especially of a profuse type.
Perspiration, especially when copious and medically induced. , headache, and sore throat. Blood and throat cultures were obtained, as well as an endomyocardial biopsy specimen. No source of infection or evidence of cardiac rejection was found.
On November 9, he was hospitalized again for evaluation of continued fever. On admission, his temperature was 38.4xC. His surgical wound had healed well. Laboratory tests showed a leukocyte count of 4.3 x [10.sup.3]/[mm.sup.3] (83% neutrophils, 9% lymphocytes, 8% monocytes monocytes,
n.pl the largest of the white blood cells. They have one nucleus and a large amount of grayish-blue cytoplasm. Develop into macrophages and both consume foreign material and alert T cells to its presence. ), hemoglobin concentration of 11.4 g/dL, and a platelet count of 54,000/[mm.sup.3]. On November 10, the staff of the hospital parasitology laboratory identified intraerythrocytic ring forms and tetrads consistent with B. microti infection on a peripheral blood smear; these results were confirmed by the Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center. (CDC See Control Data, century date change and Back Orifice.
CDC - Control Data Corporation ). The parasitemia parasitemia /par·a·si·te·mia/ (par?ah-si-te´me-ah) the presence of parasites, especially malarial forms, in the blood.
The presence of parasites in the blood. level was 1.6%. Indirect fluorescent antibody (IFA Immunofluorescent assay (IFA)
A blood test sometimes used to confirm ELISA results instead of using the Western blotting. In an IFA test, HIV antigen is mixed with a fluorescent compound and then with a sample of the patient's blood. ) testing (12) of his serum at CDC showed that his IFA titers had risen from [less than or equal to] 1:8 (i.e., negative) pretransplant to 1:1024 posttransplant (Table). Nested polymerase chain reaction Nested polymerase chain reaction is a modification of polymerase chain reaction intended to reduce the contaminations in products due to the amplification of unexpected primer binding sites. (PCR PCR polymerase chain reaction.
polymerase chain reaction
Polymerase chain reaction (PCR) ) analysis of blood, using primers described previously (13), was positive for B. microti DNA DNA: see nucleic acid.
or deoxyribonucleic acid
One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. . Results of pre- and posttransplant serologic testing for antibodies to Borrelia burgdorferi, Ehrlichia chaffeensis, and the agent of human granulocytic ehrlichiosis human granulocytic ehrlichiosis: see ehrlichiosis. (14), performed at the New York State Department of Health, were negative (Table).
On November 10, therapy with quinine quinine (kwī`nīn', kwĭnēn`), white crystalline alkaloid with a bitter taste. Before the development of more effective synthetic drugs such as quinacrine, chloroquine, and primaquine, quinine was the specific agent in the treatment of (650 mg orally, 3 times a day) and clindamycin (400 mg intravenously, 4 times a day) was begun. His course was complicated by worsening parasitemia (maximum documented level was 3.1% on November 13), hemolytic anemia (hemoglobin concentration decreased from 11.4 g/dL on November 9 to a minimum value of 7.4 g/dL on November 15), acute renal failure acute renal failure Acute kidney failure Nephrology An abrupt decline in renal function, triggered by various processes–eg, sepsis, shock, trauma, kidney stones, drug toxicity-aspirin, lithium, substances of abuse, toxins, iodinated radiocontrast. (creatinine value rose from 1.4 mg/dL on November 9 to a maximum level of 3.3 mg/dL on November 15), and adult respiratory distress syndrome requiring mechanical ventilation.
On November 14, his therapy for babesiosis was changed to azithromycin (500 mg intravenously, once a day) and atovaquone (750 mg orally, 2 times a day) because of severe tinnitus, increased level of parasitemia (3.1% on November 13), and ongoing fever (maximum of 38.6[degrees]C). On November 21, he was afebrile afebrile /afe·brile/ (a-feb´ril) without fever.
afebrile adjective Feverless and had a negative blood smear. He was discharged on November 25. Therapy with azithromycin (250 mg orally, once a day) and atovaquone (750 mg orally, 2 times a day) was continued for a total of 2 weeks on these drugs. The patient remained well as of August 2001.
Investigation of Blood Donors
We traced the donors of the 32 PRBC units transfused during the patient's hospitalization in New York City. For two donors, the transfused units had associated frozen components (i.e., FFP) available that could be retrieved; for six donors, PRBC units from subsequent donations were available for testing. The blood products from these eight donors were negative for antibodies to B. microti by IFA testing.
The other 24 donors submitted blood for testing. On March 12, 2001, the New York State Department of Health laboratory reported that one donor had an IFA titer of 1:256, which was confirmed by CDC (Table). The other 23 donors had negative IFA titers. The blood specimen from the implicated donor had been obtained on February 28, 2001, 5 months after the original blood donation on September 22, 2000. The PRBC unit was transfused on October 1, 2000, and the patient first reported fever on November 5, 2000. Thus, the incubation period for the case of babesiosis was estimated to be 35 days. CDC performed additional diagnostic testing on the implicated donor's blood. PCR analysis was negative for B. microti DNA, and parasitemia did not develop in hamsters injected with his blood (Table). The donor was thus implicated on the basis of serologic rather than parasitologic data. Given that he was not treated for babesiosis, the negative results of the parasitologic testing suggest that the donor's infection cleared spontaneously. However, he could have had low-level or intermittent parasitemia not detected by the parasitologic testing.
After the donor was implicated, other components from the index donation were investigated. No other patients received blood components from the implicated donation. The only other component identified was one unused unit of FFP, which already had been destroyed. The donor's only previous donation was 1 year before the index donation. The lone recipient from that donation remained asymptomatic but was not tested for evidence of B. microti infection.
Investigation of Implicated Donor
The implicated donor, a 45-year-old spleen-intact man from Westchester County, New York '' Westchester County is a primarily suburban county located in the U.S. state of New York with about 950,000 residents. It is part of the New York Metropolitan Area. It was named after Chester, in England, and the county seat is White Plains. , had been asymptomatic the year before his blood donation. In 2000, he had visited New Haven County, Connecticut New Haven County is located in the south central part of the U.S. state of Connecticut. As of 2000 the population was 824,008. Two of the state's largest cities, New Haven and Waterbury are part of New Haven County. It is part of the New York Metropolitan Area. , in May; Long Island (Jones Beach), New York, in July and August; and Narragansett, Rhode Island Narragansett is a town in Washington County, Rhode Island, United States. The population was 16,361 at the 2000 census. The nickname for the town is 'Gansett.
For geographic and demographic information on the village of Narragansett Pier, which is part of Narragansett, see , in July. He worked outdoors and gardened as a hobby. He did not recall a tick bite.
Investigation of Heart Donor
The heart donor was a 54-year-old woman who died after a cerebrovascular accident. She had lived and worked in New York City and had had no symptoms consistent with babesiosis before the stroke. While hospitalized, she had remained afebrile with a normal complete blood count and renal function. No serum from her was available for B. microti IFA testing.
We conclude that our patient, who lived in New Jersey, acquired babesiosis through transfusion of PRBC in New York City after a cardiac transplant. The evidence consistent with this conclusion includes the following: he did not recall a tick bite (most patients with babesiosis do not [9-11]); he did not spend much time outdoors; he was seronegative seronegative /se·ro·neg·a·tive/ (-neg´ah-tiv) showing negative results on serological examination; showing a lack of antibody.
adj. by B. microti IFA 5 days before his heart transplant and markedly seropositive when babesiosis was diagnosed 45 days after his transplant; he received blood from a donor with a B. microti IFA titer of 1:256; and he became symptomatic during the typical two 8-week incubation periods for transfusion-transmitted B. microti infection (7).
Other possible modes of transmission seem much less likely. We doubt he became infected through a blood transfusion in New Jersey; he was seronegative by B. microti IFA 4.5 weeks after the New Jersey transfusions. We also doubt that he acquired his infection while recuperating after his heart transplant; his limited outdoor activities made tick exposure unlikely.
More than 40 cases of transfusion-transmitted babesiosis have been reported in the United States. Most infections have been acquired through PRBC transfusions, but cases have also resulted from transfusion of frozen-deglycerolized red cell units (15,16) and platelet units (6,7) (the latter have residual red cells). Two previous cases of B. microti infection have been reported in solid-organ transplant patients, although no cases acquired through transplantation per se have been reported (17,18).
We initially treated our patient with quinine and clindamycin but later changed the regimen to atovaquone and azithromycin. A recent clinical trial demonstrated that the combination of atovaquone and azithromycin is as effective as quinine and clindamycin for the treatment of babesiosis in patients without life-threatening disease (such patients were excluded from this trial) (19). In our patient, who was critically ill, immunosuppressed, and a solid-organ transplant recipient, the combination of atovaquone and azithromycin was effective therapy.
Babesiosis should be considered in the differential diagnosis of transplant patients who have fever and hemolytic anemia, and blood transfusion should be considered as one of the possible means of acquisition of infection. Solid-organ transplant recipients may receive many blood products, which necessitates an extensive investigation to implicate a donor.
Table. Results of serologic testing, polymerase chain reaction analyses, and hamster injection for specimens from the case-patient with babesiosis and the implicated blood donor (a) Date of specimen Timing of specimen Case-patient September 21,2000 Pretransplant November 14, 2000 Posttransplant November 14, 2000 Posttransplant September 21, 2000 Pretransplant November 14, 000 Posttransplant September 21, 2000 Pretransplant November 14, 2000 Posttransplant September 21, 2000 Pretransplant November 14, 2000 Posttransplant September 21,2000 Pretransplant November 14,2000 Posttransplant Implicated blood donor (tested approximately 5 months after donation) February 28, 2001 Postdonation February 28, 2001 Postdonation February 28, 2001 Postdonation Date of specimen Test Case-patient September 21,2000 Babesia microti IFA November 14, 2000 B. microti IFA November 14, 2000 B. microti PCR September 21, 2000 Agent of HGE, IgM (c) November 14, 000 Agent of HGE, IgM September 21, 2000 Agent of HGE, IgG November 14, 2000 Agent of HGE, IgG September 21, 2000 Ehrlichia chaffeensis IFA November 14, 2000 E. chaffeensis IFA September 21,2000 Lyme ELFA November 14,2000 Lyme ELFA Implicated blood donor (tested approximately 5 months after donation) February 28, 2001 Babesia microti IFA February 28, 2001 B. microti PCR February 28, 2001 Hamster inoculation (d) Date of specimen Result of testing Case-patient September 21,2000 [less than or equal to] 1:8 (b) November 14, 2000 1:1024 November 14, 2000 Positive September 21, 2000 Negative November 14, 000 Negative September 21, 2000 Negative November 14, 2000 Negative September 21, 2000 Negative November 14, 2000 Negative September 21,2000 Negative November 14,2000 Negative Implicated blood donor (tested approximately 5 months after donation) February 28, 2001 1:256 February 28, 2001 Negative February 28, 2001 Negative (a) IFA, indirect fluorescent antibody; PCR, polymerase chain reaction; HGE, human granulocytic ehrlichiosis; Ig, immunoglobulin; ELFA, enzyme-linked fluorescence assay. (b) Babesia microti IFA= 1:8=negative. (c) IgM and IgG immunoblots for HGE. (d) Two hamsters were each inoculated intraperitoneally on April 3 with 0.75 mL of blood obtained on February 28. Giemsa-stained smears were made from hamster blood obtained twice weekly, for 8 weeks, by tail snip. The hamsters did not become demonstrably parasitemic.
We thank the laboratory staff of the Division of Parasitic Diseases, Centers for Disease Control and Prevention; Adeleh Ebrahimzadeh from the New York City Public Health Laboratory; and Rich Gallo and staff from the New York State (Westchester County) Department of Health.
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pertaining to or emanating from serology.
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Address for correspondence: Brian E. Scully, Department of Medicine, Division of Infectious Diseases, Columbia University College of Physicians and Surgeons The Columbia University College of Physicians and Surgeons, abbreviated P&S, is a graduate school of Columbia University located on the health sciences campus in the Washington Heights neighborhood of Manhattan. , 630 West 168th Street, New York, NY 10032, USA; fax: 212-305-7290; e-mail: firstname.lastname@example.org
Joseph Z. Lux, * Don Weiss, ([dagger]) Jeanne V. Linden, ([double dagger]) Debra Kessler, ([section]) Barbara L. Herwaldt, ([paragraph]) Susan J. Wong, ([double dagger]) Jan Keithly, ([double dagger]) Phyllis Della-Latta, (#) and Brian E. Scully *
* Columbia University College of Physicians and Surgeons, New York, New York, USA; ([dagger]) New York City Department of Health, New York, New York, USA; ([double dagger]) Wadsworth Center, New York State Department of Health, Albany, New York For other uses, see Albany.
Albany is the capital of the State of New York and the county seat of Albany County. Albany lies 136 miles (219 km) north of New York City, and slightly to the south of the juncture of the Mohawk and Hudson Rivers. , USA; ([section]) New York Blood Center New York Blood Center bills itself as the "nation's largest, community-based, non-profit, independent blood center." Founded in 1964, it relies upon a staff of 2,000 volunteers and a much smaller permanent staff in order to supply over 200 hospitals in New York and New Jersey with , New York, New York, USA; ([paragraph]) Centers for Disease Control and Prevention, Atlanta, Georgia, USA; and (#) Columbia Presbyterian Medical Center, New York, New York, USA
Dr. Lux is an infectious diseases fellow at Columbia University College of Physicians and Surgeons.