Risk of transfusion-transmitted Babesia microti in Canada.

BACKGROUND: 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. STUDY DESIGN AND METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Transfusion-transmitted babesiosis: is it time to screen the blood supply?

PURPOSE OF REVIEW: This review summarizes the current status of blood screening to prevent transfusion-transmitted babesiosis (TTB). RECENT FINDINGS: Babesia microti has recently been determined to be the most common transfusion-transmitted pathogen in the United States. Patients who acquire TTB often experience severe illness with an associated mortality rate of about 20%. Recent studies have demonstrated that laboratory screening using B. microti antibody and/or PCR assays can effectively identify infectious blood donors and that this approach may offer a cost- effective means of intervention. Pathogen inactivation methods may offer an alternative solution. None of these methods has yet been licensed by US Food and Drug Administration, however, and current efforts to prevent TTB rely on excluding blood donors who report having had babesiosis. SUMMARY: TTB imposes a significant health burden on the United States population. Further research is needed to better inform decisions on optimal screening strategies and reentry criteria, but given the acute need and the currently available screening tools, initiation of blood donor screening to prevent TTB should be given high priority.

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

BACKGROUND: Babesia microti causes transfusion-transmitted babesiosis (TTB); currently, blood donor screening assays are unlicensed but used investigationally. STUDY DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Costs, consequences, and cost-effectiveness of strategies for Babesia microti donor screening of the US blood supply.

BACKGROUND: Babesia microti is regarded as the foremost infectious risk to the US blood supply for which a regulatory-approved screening test is unavailable. More than 160 cases of transfusion-transmitted Babesia microti (TTB) have been reported to date, yet there is little consensus regarding a mitigation strategy. STUDY DESIGN AND METHODS: This study sought to assess the cost-utility of donation screening by mode of testing (immunofluorescence assay, enzyme-linked immunosorbent assay [ELISA], polymerase chain reaction [PCR], and combinations thereof) as well as extent of geographic inclusion (4-state, 7-state, 20-state, or national screening). A discrete-time Markov cohort model to simulate the outcomes of B. microti infection and survival of the transfused population was developed. Seroprevalence was estimated by extrapolating babesiosis claims from the Centers for Medicaid and Medicare Services and reports to the Centers for Disease Control and Prevention. Test performance was estimated from clinical diagnostics and limited donor screening studies, while transmissibility was estimated as a weighted average of three studies. Results are reported as the cost per quality-adjusted life-year (QALY) for each strategy compared to no screening. RESULTS: Given model inputs, 4-state and 7-state ELISA in combination with PCR would cost $5.2 million and $6.6 million/QALY, respectively. Cost-effectiveness for 20-state and national screening strategies were less favorable. CONCLUSION: Targeted screening in states with the highest seroprevalence of infection is likely to exceed an implicit threshold of $1 million/QALY often used in blood safety. However, the proportion of donor-seronegative parasitemia, transmissibility, and clinical outcomes resulting from TTB are uncertain.

Detection of Borrelia burgdorferi, Anaplasma phagocytophilum and Babesia microti, with two different multiplex PCR assays.

We have developed 2 real-time multiplex PCR assays for detection of Borrelia burgdorferi, Anaplasma phagocytophilum, and Babesia microti. The efficiency and sensitivity of each multiplex PCR assay was evaluated using field-collected Ixodes scapularis ticks that were positive for each of the pathogens, cloned plasmids harboring each of the PCR targets, and laboratory I. scapularis infected with B. burgdorferi B31. There was no difference in efficiency or sensitivity when comparing the multiplex PCR with the individual PCR reactions. If the 2 multiplex PCR assays are used in the same analysis, field-collected ticks that only harbor B. miyamotoi can also be identified. The multiplex assays are fast and cost-effective methods for screening and detecting pathogens in ticks, when compared to single-target PCR.

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

BACKGROUND: 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. STUDY DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Assessment of polymicrobial infections in ticks in New York state.

Ixodes scapularis ticks are clinically important hematophagous vectors. A single tick bite can lead to a polymicrobial infection. We determined the prevalence of polymicrobial infection with Borrelia burgdorferi, Anaplasma phagocytophilum, Babesia microti, Borrelia miyamotoi, and Powassan virus in 286 adult ticks from the two counties in New York State where Lyme disease is endemic, utilizing a MassTag multiplex polymerase chain reaction assay. Seventy-one percent of the ticks harbored at least one organism; 30% had a polymicrobial infection. Infections with three microbes were detected in 5% of the ticks. One tick was infected with four organisms. Our results show that coinfection is a frequent occurrence in ticks in the two counties surveyed.

Odour learning and immunity costs in mice.

There is accumulating evidence that learning is metabolically costly. One way in which this may manifest itself is in trade-offs between learning effort and immune function, with learning increasing susceptibility to infection. We tested this idea in the context of odour learning using outbred (BKW) male laboratory mice. Mice were exposed to three experimental treatments in which they were required to learn different numbers of urinary odours. While treatment affected the extent to which mice habituated to test odours during training, differences were not a simple function of the number of odours. The fact that there was also no significant effect of treatment on the degree of preference for novel over familiar odours in subsequent tests suggests mice retained learned odour profiles equally well regardless of the number of odours. That subsequent infection with Babesia microti increased with the number of odours mice had to learn is then consistent with an increased cost to learning effort when more odours were presented. Analysis within treatments, and relationships with the change in corticosterone concentration over the period of the experiment, suggested that it was a failure to learn, rather than maintaining learning performance, in more difficult learning tasks that led to greater infection. As in a previous study of maze learning in the strain, there was no direct relationship between infection and measures of peripheral antibody (total IgG) titre. The results are discussed in relation to studies in other learning contexts and reported relationships between glucocorticoid hormones and learning outcomes.