Cases Of Transfusion-transmitted Babesiosis Research Articles

Babesia blood testing: the first-year experience.

Babesia is an intraerythrocytic parasite responsible for hundreds of cases of transfusion-transmitted babesiosis in the past 50 years. In May of 2020, blood testing for Babesia was implemented at the American Red Cross (ARC) for all donations in endemic areas of the northeastern and midwestern regions of the United States. Between May 2020 and May 2021, 1,816,669 donations from 13 states and DC were tested for Babesia by the ARC. Testing was performed in pools of 16 whole blood lysates using a licensed nucleic acid test (NAT) targeting Babesia 18S rRNA. Reactive donations were tested for B. microti antibody by immunoglobulin G immunofluorescence. Suspected cases of transfusion-transmitted babesiosis (TTB) were investigated if reported. The first 13 months of Babesia screening identified 365 NAT-reactive donations. Antibodies for B. microti were detected in 79% (287) of reactive donations; negative serology samples were prevalent between May and July. Follow-up donations were collected from 142 donors, and 86% (122), collected up to 74 days after index, remained NAT reactive. Reactive donations were mainly collected in MA (77), CT (68), NY (49), NJ (47), and PA (44), but were identified in all states except Delaware. Most reactive blood donors were male (65%) aged between 40 and 80 years. Since the beginning of Babesia testing, no case of TTB was identified. The absence of TTB cases since implementation of Babesia screening for blood donations collected in endemic areas suggests testing is an effective strategy to eliminate TTB.

Risk of transfusion-transmitted Babesia microti in Canada.

Babesia microti has gained a foothold in Canada as tick vectors become established in broader geographic areas. B. microti infection is associated with mild or no symptoms in healthy individuals but is transfusion-transmissible and can be fatal in immunocompromised individuals. This is the first estimate of clinically significant transfusion-transmitted babesiosis (TTB) risk in Canada. The proportion of B. microti-antibody (AB)/nucleic acid amplification test (NAT)-positive whole blood donations was estimated at 5.5% of the proportion of the general population with reported Lyme Disease (also tick-borne) based on US data. Monte Carlo simulation estimated the number and proportion of infectious red cell units for three scenarios: base, localized incidence (risk in Manitoba only), and donor study informed (prevalence from donor data). The model simulated 1,029,800 donations repeated 100,000 times for each. In the base scenario 0.5 (0.01, 1.75), B. microti-NAT-positive donations would be expected per year, with 0.08 (0, 0.38) recipients suffering clinically significant TTB (1 every 12.5 years). In the localized incidence scenario, there were 0.21(0, 0.7) B. microti-NAT-positive donations, with 0.04 (0, 0.14) recipient infections (about 1 every 25 years). In the donor study informed scenario, there were 4.6 (0.3, 15.8) B. microti-NAT-positive donations expected, and 0.81 (0.05, 3.14) clinically significant TTB cases per year. The likelihood of clinically relevant TTB is low. Testing would have very little utility in Canada at this time. Ongoing pathogen surveillance in tick vectors is important as B. microti prevalence appears to be slowly increasing in Canada.

Educational Case: A Case of Transfusion-Transmitted Babesiosis: Diagnostic Perspectives Across the Clinical Laboratory

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1

2247 Transfusion Associated Babesiosis: An Uncommon Cause of Acute Liver Failure

INTRODUCTION: Babesiosis is a zoonotic disease caused by obligate intracellular protozoa that reproduce in erythrocytes. We present a case of transfusion-transmitted babesiosis (TTB) leading to acute liver failure (ALF). Whereas mild liver chemistry abnormalities are common in babesiosis, to the authors’ knowledge this is the first case of TTB directly leading to ALF. CASE DESCRIPTION/METHODS: A 79-year-old man from New Jersey with end stage renal disease presented with two weeks of flu-like illness and was found to have profound liver function abnormalities consistent with ALF. Six weeks prior the patient was hospitalized for a diverticular bleed at which time he received multiple packed red blood cell transfusions and recovered to his baseline health. At that time, liver chemistries were normal. On arrival, he was afebrile and normotensive. He was oriented but lethargic. Skin exam notable for pallor. His abdomen was benign. Initial investigations revealed AST 3497 IU/L, ALT 2719 IU/L, ALP 259 IU/L, TB 5.2mg/dl, DB 3.6mg/dl. INR was 4.1, Hgb 8.7g/dL, and fibrinogen 252mg/dl. LDH 2003 IU/L with haptoglobin < 8.0mg/dl. Peripheral smear revealed ring-shaped intra-erythrocytic trophozoites (Figure 1). Babesia microti PCR was positive. Atovaquone and azithromycin were started and exchange transfusion performed. Fevers and worsening encephalopathy progressed despite directed treatment. Multi-system organ failure developed and care was withdrawn. Further testing determined our patient was a recipient of babesia microti contaminated transfusion. DISCUSSION: Babesiosis is a world-wide emerging disease caused by intra-erythrocytic protozoa that are transmitted primarily through Ixodes ticks but also through blood transfusion. TTB is often severe in presentation with a mortality rate of approximately 20%. Marked hemolytic anemia, disseminated intravascular coagulation, and adult respiratory distress syndrome may develop. Case series have established that patients with babesiosis exhibit abnormal liver chemistries with median values notable for ALT of 59 IU/L and AST 79 IU/L. A literature review reveals just one published case of babesiosis presenting as ALF, and no such cases when babesia is transmitted through transfusion. Babesiosis should be considered in the differential diagnosis of ALF in patients living in or having recently travelled to an endemic area or who have recently received transfusions. In such patients, we recommend performing blood smear to prevent delay in treatment.

Babesia: Prevention for the Blood Supply

Exposure to blood, whether through blood transfusion, organ transplantation, or even pregnancy (mother to fetus), can transmit infectious disease. Blood suppliers routinely test donated blood for a variety of infectious pathogens and screening for Babesia spp. occurs in endemic areas of the United States. People living in areas of endemicity are not allowed to donate blood if they have a history of babesiosis. Transmission of Babesia microti through red blood cell blood transfusion is a serious, although rare, public health threat for which these preventive measures are necessary. The first case of transfusion-transmitted babesiosis in the United States occurred in 1979, and the incidence has increased. The National Healthcare Safety Network Hemovigilance Module tracks transfusion-transmitted infections (TTI). In a reporting period ending December, 2016, the most frequently reported TTI involving red blood cell units was for Babesia spp. in 16 of 24 reported infections.

Characteristics of transfusion-transmitted Babesia microti, American Red Cross 2010-2017.

Babesia microti, a red blood cell (RBC) parasite transmitted naturally to vertebrate hosts by ixodid ticks, is endemic to the northeastern and upper midwestern United States, with the geographic range of infected ticks expanding. B. microti is a blood safety issue with >200 transfusion-transmissions reported. The American Red Cross's Hemovigilance program investigated hospital-reported transfusion-transmitted babesiosis (TTB) cases. Follow-up samples from involved donors were tested for B. microti antibodies and parasite DNA, the latter by real-time polymerase chain reaction (PCR). Test-positive donors were permanently deferred from future donations. B. microti-positive donors were implicated in 77 of 143 suspect TTB cases investigated from 2010 through 2017. In four cases, two positive donors were identified for a total of 81 positive donors. In three cases, a RBC unit was split and components transfused multiple times to the same pediatric recipient. RBCs were the transmitting product in all cases. At follow-up, all involved donors were antibody positive; 25 donors were also PCR positive. Positive donations were collected throughout the year, peaking in the summer. Most donors (78) were resident of, or traveled to (2), an endemic state. One donor resided in a non-endemic state without relevant travel history. One fatality listed babesia as a contributing factor. No implicated donation was screened by an investigational protocol. Babesiosis remains a blood safety issue. Prior to FDA-licensed screening test availability and final FDA Guidance, blood collectors in endemic states investigationally tested none, a portion, or all collections. Future expanded testing will reduce the frequency of TTB cases.

Transfusion-Transmitted Babesiosis.

Babesiosis is most commonly caused by Babesia microti and is transmitted via the bite of an infected Ixodes spp tick. However, Babesia is also transmitted via blood transfusion. In the United States, the first case of transfusion-transmitted babesiosis was recognized in 1979, and in recent years, the incidence has rapidly increased. Because most of the infected blood donors do not experience any symptoms, they pose a significant risk to the blood supply. Donor deferral for a history of babesiosis is currently performed but is ineffective. In March 2018, the FDA licensed a DNA PCR and antibody assay that were used in tandem in pivotal trials for screening blood donors for B microti; with other assays still being evaluated under investigational new drug protocols. Blood donation screening is essential to reducing the risk of transfusion-transmitted babesiosis, which is why blood centers collecting in geographic regions of highest risk have been testing since approximately 2010. Investigational NAT assays of higher sensitivity are pending FDA review. Further, in July 2018, the FDA issued a draft guidance for reducing the risk of transfusion-transmitted babesiosis. Release of the final guidance may be postponed until sensitivities and specificities of all current and potential strategies have been properly evaluated.

Transfusion‐transmitted babesiosis: one state's experience

The risk for tickborne exposure to Babesia microti infection exists statewide in Massachusetts. Broad exposure complicates investigations of transfusion-transmitted babesiosis (TTB). We summarize 8 years of the epidemiology of TTB and highlight the role of public health in prevention and control. Cases of babesiosis are routinely reported to the Massachusetts Department of Public Health. These are investigated to determine whether they meet the surveillance case definition and to identify whether they were potentially transfusion transmitted. Frequencies from 2009 to 2016 are described and incidence rates calculated using population denominators from the US census. Changes over time were analyzed using simple linear regression. From 2009 to 2016, there were 2578 cases of babesiosis reported; of these, 45 (1.7%) were transfusion transmitted. Of the 45 cases of TTB, 15 (33%) received blood products from two or more suppliers. In 11 TTB cases, the Department of Public Health was notified first, who in turn notified the appropriate blood provider. In 2009, the crude rate of reported babesiosis was 1.2 per 100,000 population and increased significantly through 2016 to 7.8 per 100,000 population (p = 0.006). The number of blood donors reported with laboratory evidence of B. microti infection increased from 19 in 2012 to 78 in 2016; at the same time, the number of TTB cases decreased from six to three. TTB remains a major challenge, and blood donor screening strategies are currently in the process of implementation. While population and environmental changes facilitate increases in babesiosis, donor screening has the potential to eliminate TTB.

Transfusion-transmitted and community-acquired babesiosis in New York, 2004 to 2015.

Babesiosis is a potentially life-threatening zoonotic infection most frequently caused by the intraerythrocytic parasite Babesia microti. The pathogen is usually tickborne, but may also be transfusion or vertically transmitted. Healthy persons, including blood donors, may be asymptomatic and unaware they are infected. Immunocompromised patients are at increased risk for symptomatic disease. All reported community-acquired babesiosis cases in New York from 2004 to 2015 were evaluated, enumerated, and characterized. All potential transfusion-transmitted babesiosis (TTB) cases reported through one or more of three public health surveillance systems were investigated to determine the likelihood of transfusion transmission. In addition, host-seeking ticks were actively collected in public parks and other likely sites of human exposure to B.microti. From 2004 to 2015, a total of 3799 cases of babesiosis were found; 55 (1.4%) of these were linked to transfusion. The incidence of both community-acquired babesiosis and TTB increased significantly during the 12-year study period. The geographic range of both ticks and tickborne infections also expanded. Among TTB cases, 95% of recipients had at least one risk factor for symptomatic disease. Implicated donors resided in five states, including in 10 New York counties. More than half of implicated donors resided in counties known to be B.microti endemic. The increasing incidence of TTB correlated with increases in community-acquired babesiosis and infection of ticks with B.microti. Surveillance of ticks and community-acquired cases may aid identification of emerging areas at risk for Babesia transfusion transmission.

Transfusion-Transmitted Babesia microti.

Because testing of donors for Babesia microti has become available, it is important to determine the kinds of patients who should receive B microti-tested blood. We searched PubMed, AABB abstracts, and FDA Web site to identify all cases of transfusion-transmitted babesiosis (TTB). Cases were analyzed for underlying medical condition, age, presence of spleen, and reason for transfusion in relation to 5 classes of recipient outcome severity. Sixty-seven reports included 256 transfusion cases where donor tested positive for B microti, 165 of which resulted in TTB. Sixty recipients did not develop disease or become test positive, and test results were not known for 31 more. The 165 cases of TTB involved hematologic (19%), neonate (10%), cardiovascular (8%), and gastrointestinal (6%) patients. Thirty-two (19%) of the 165 infected patients died with death attributed to babesiosis in 25 of the cases. Nine (5%) were asymptomatic, 27 (16%) were symptomatic but had uncomplicated disease, and 16 (10%) had complicated disease. The severity of disease was mixed among many disease categories. Patients >65 years of age included the largest number of recipients (59/165, 36%) and deaths (11/32, 34%), although deaths occurred in other age groups as well. TTB cases were predominantly due to red cells (133 of 140 specified units), with red blood cell units processed in a variety of ways and at all storage duration. TTB with complicated babesiosis and/or death occurred in patients of all age groups and with a variety of underlying medical conditions.

Cost-effectiveness of Babesia microti antibody and nucleic acid blood donation screening using results from prospective investigational studies.

Babesia microti causes transfusion-transmitted babesiosis (TTB); currently, blood donor screening assays are unlicensed but used investigationally. We developed a decision tree model assessing the comparative- and cost-effectiveness of B. microti blood donation screening strategies in endemic areas compared to the status quo (question regarding a history of babesiosis), including testing by: (1) universal antibody (Ab), (2) universal polymerase chain reaction (PCR), (3) universal Ab/PCR, and (4) recipient risk-targeted Ab/PCR. The model predicted the number of TTB cases, complicated TTB cases, cases averted, and quality-adjusted life years (QALYs). Economic outcomes included each strategy's per-donation cost, waste (number of infection-free units incorrectly discarded), and waste index (number wasted units/number true positives). Sensitivity analyses examined uncertainty in transmission probabilities, prevalence rates, and other key model inputs. Universal PCR in four endemic states would prevent 24 to 31 TTB cases/100,000 units transfused (pht) at an incremental cost-effectiveness ratio (ICER) of $26,000 to $44,000/QALY (transmission probability dependent) and waste index of zero. Universal Ab/PCR would prevent 33 to 42 TTB cases pht at an ICER of $54,000 to $83,000/QALY and waste index of 0.05. The questionnaire is most wasteful (99.62 units wasted pht; 208.62 waste index), followed by the risk-targeted strategy (76.27 units wasted pht; 0.68 waste index). The model predicted zero cases of TTB or complicated TTB with universal Ab/PCR (versus [33, 42] and [13, 18] pht, respectively [no screening]). Results are highly sensitive to transmission probabilities. Universal PCR in endemic states is an effective blood donation screening strategy at a threshold of $50,000/QALY. Using a higher cost-effectiveness ratio, universal Ab/PCR is the most effective strategy.

Blood donation screening for Babesia microti: feasibility and results

Background and ObjectivesBabesia microti, an intraerythrocytic parasite, causes babesiosis; transfusion‐transmitted babesiosis (TTB) is reported primarily in the United States where no licensed screening tests are available.Materials and MethodsBabesia microti donor screening results using investigational antibody and DNA tests in six US states are reviewed from both repository testing and prospective screening. Testing results performed in endemic counties from June 2012 to April 2014 were combined to update prevalence and marker duration in infected donors and estimate testing efficacy (i.e. the reduction of reported TTB cases).ResultsA total of 84 209 donations were tested and 331 were reactive by either antibody and/or DNA for a total prevalence of 0·39%. Of those that were DNA positive, the retrieved red cell units from nearly one‐third caused infection in hamsters. In addition, eight units were identified that were PCR positive but antibody negative (window‐period donors).ConclusionsScreening is feasible, removing likely infectious donations. Followed donors retained PCR positivity over several months but antibody reactivity for over 3 years.

A longitudinal study of Babesia microti infection in seropositive blood donors

Babesia infection is caused by intraerythrocytic tick-borne parasites. Cases of transfusion-transmitted babesiosis have been increasingly recognized. To date, no Babesia test has been licensed for screening US blood donors. We conducted a longitudinal study to assess the course and markers of Babesia infection among seropositive donors identified in a seroprevalence study. Eligible donors had B. microti indirect fluorescent antibody (IFA) titers of 64 or greater. Enrollees were monitored up to 3 years, by IFA and three methods for evidence of parasitemia: B. microti nested polymerase chain reaction (PCR) analysis (at two laboratories), hamster inoculation, and blood-smear examination. Among 115 eligible donors, 84 (73%) enrolled. Eighteen enrollees (21%) had evidence of parasitemia for 30 total specimens (17% of 181), which were collected in 9 different months and tested positive by various approaches: PCR (25 specimens/16 persons), hamster inoculation (13 specimens/8 persons), and blood smear (one specimen positive by all three approaches). Overall, 14 persons had one or more specimen with positive PCR results at both laboratories (12 persons) and/or had parasitologically confirmed infection (eight persons). Three of nine persons who had more than one specimen with evidence of parasitemia had nonconsecutive positives. Several enrollees likely had been infected at least 1 year when their last positive specimen was collected. The final three specimens for seven persons tested negative by all study methods, including IFA. Seropositive blood donors can have protracted low-level parasitemia that is variably and intermittently detected by parasitologic and molecular methods. Donor-screening algorithms should include serologic testing and not solely rely on molecular testing.

Cost-effectiveness of blood donor screening for Babesia microti in endemic regions of the United States.

Babesia microti is the leading reported cause of red blood cell (RBC) transfusion-transmitted infection in the United States. Donor screening assays are in development. A decision analytic model estimated the cost-effectiveness of screening strategies for preventing transfusion-transmitted babesiosis (TTB) in a hypothetical cohort of transfusion recipients in Babesia-endemic areas of the United States. Strategies included: 1) no screening; 2) Uniform Donor Health History Questionnaire (UDHQ), "status quo"; 3) recipient risk targeting using donor antibody and polymerase chain reaction (PCR) screening; 4) universal endemic donor antibody screening; and 5) universal endemic donor antibody and PCR screening. Outcome measures were TTB cases averted, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs; $/QALY). We assumed a societal willingness to pay of $1 million/QALY based on screening for other transfusion-transmitted infections. Compared to no screening, the UDHQ avoids 0.02 TTB cases per 100,000 RBC transfusions at an ICER of $160,000/QALY whereas recipient risk-targeted strategy using antibody/PCR avoids 1.62 TTB cases per 100,000 RBC transfusions at an ICER of $713,000/QALY compared to the UDHQ. Universal endemic antibody screening avoids 3.39 cases at an ICER of $760,000/QALY compared to the recipient risk-targeted strategy. Universal endemic antibody/PCR screening avoids 3.60 cases and has an ICER of $8.8 million/QALY compared to universal endemic antibody screening. Results are sensitive to blood donor Babesia prevalence, TTB transmission probability, screening test costs, risk and severity of TTB complications, and impact of babesiosis diagnosis on donor quality of life. Antibody screening for Babesia in endemic regions is appropriate from an economic perspective based on the societal willingness to pay for preventing infectious threats to blood safety.

Preventing transfusion‐transmitted babesiosis: preliminary experience of the first laboratory‐based blood donor screening program

Babesiosis is the most common transfusion-transmitted infection reported to the Food and Drug Administration (FDA). We developed and implemented the first laboratory-based blood donor screening program for Babesia microti to help reduce and prevent transfusion-transmitted babesiosis (TTB) and report results for the initial year. Selective B. microti donor screening was performed using real-time polymerase chain reaction (PCR) and indirect immunofluorescence assay (IFA) to reduce the incidence of TTB in neonates and pediatric sickle cell and thalassemia patients under an FDA-approved investigational new drug application. We compared the reports of TTB in these patients in the first 12 months of the study with those of patients who received unscreened blood from 2005 to 2010. There were 2113 units tested with 2086 negative results, 26 positive IFA results (1.23%), and one indeterminate PCR result (0.05%). No reported case of TTB occurred with any B. microti-screened unit transfused to the targeted patients (0/787 units) or to any patient who received the screened units (0/2086 units). Before screening, there were seven cases of TTB in neonates, sickle cell, and thalassemia patients from 6500 unscreened units (one case/929 units) and 24 cases in the total transfused population from 496,545 units distributed (one case/20,686 units). Implementation of B. microti IFA and PCR screening is compatible with blood center operations to provide tested units. While the results after 1 year are not powered to demonstrate a change in the rate of TTB after testing, they are encouraging.

TRANSFUSION COMPLICATIONS: Transfusion‐transmitted babesiosis in Rhode Island

BACKGROUND: Babesiosis is caused by an intraerythrocytic protozoan transmitted by ticks. Blood transfusion is another mode of transmission.STUDY DESIGN AND METHODS: This was a retrospective study based on babesiosis cases reported to the Rhode Island Department of Health between 1999 and 2007. Additional cases were also identified.RESULTS: Twenty‐one cases of transfusion‐transmitted babesiosis (TTB) were identified from 1999 through 2007. From 2005 through 2007, the incidence approached one case per 9000 units of blood transfused. One of 21 (5%) TTB cases was diagnosed in July, in sharp contrast to 65 of 152 (43%) of the total babesiosis cases diagnosed during July in Rhode Island. Many cases were identified when a complete blood count with a differential was routinely requested and parasites were noted by laboratory technologists. Most patients with TTB had underlying conditions known to predispose to symptomatic infection.CONCLUSION: Blood transfusion is an important mode of Babesia transmission. The current screening method of omitting donors with a history of babesiosis may be effective in preventing some, but not all, cases of TTB and current processing of blood products does not eradicate this parasite. Thus, a better screening test is needed. Alternatively, pathogen reduction technology could be utilized to prevent this mode of transmission.

EDITORIAL: The problem of transfusion‐transmitted babesiosis

EDITORIAL: The problem of transfusion‐transmitted babesiosis

Transfusion‐transmitted babesiosis: a case report from a new endemic area

The seventh documented case of babesiosis transmitted by transfusion is reported. Both the donor and the recipient are residents of Connecticut, where the presence of endemic babesiosis has only recently been established. As the range of Babesia microti, and its vector the Ixodes dammini tick, continues to expand, clinicians and blood bank directors should be aware that cases of transfusion-transmitted babesiosis may occur in newly endemic areas.