Transfusion-related Epstein-Barr virus (EBV) infection: A multicenter prospective cohort study among pediatric recipients of hematopoietic stem cell transplants (TREASuRE study).

BACKGROUND: Epstein-Barr virus (EBV) is carried in the blood of most adults, and transfusion-related infections have been reported. EBV is particularly deleterious in immunosuppressed transplant patients. The aim was to determine if EBV transmission occurred through leukodepleted blood product transfusion in pediatric recipients of hematopoietic stem cell transplants (HSCT). STUDY DESIGN AND METHODS: This prospective Canadian multi-center cohort study includes 156 allogeneic HSCT pediatric recipients. The association between EBV and transfusion was analyzed using Cox regressions. EBV infection, defined by a PCR+ test in the blood of seronegative recipients of an EBV-negative graft, was monitored in order to correlate the recipient EBV strain with that of the blood donors. EBV genotypes were determined by PCR amplification followed by DNA sequencing at two loci (EBNA3b and LMP1). RESULTS: No statistically significant associations were found between transfusions and EBV. One case of post-transplant EBV infection was identified among the 21 EBV-seronegative recipients receiving an EBV-negative graft. A total of 22 blood donors were retraced to determine whether the recipient's EBV strain matched that of a donor. One donor strain showed 100% sequence homology at the EBNA3b locus, but differed by one or two point mutations and by a 132-bp deletion at the LMP1 locus. The blood donor in question was alone among the 22 donors to show amplifiable virus in plasma. Blood from this donor readily produced an immortalized lymphoblastoid cell line in culture. CONCLUSION: While considered a rare event, EBV transmission through transfusion may occur in the context of severe immunosuppression.

A case series of inactivated Japanese encephalitis virus vaccination associated with positive West Nile virus blood donor screening nucleic acid tests.

BACKGROUND: West Nile Virus (WNV) is a member of the Japanese Encephalitis (JE) serocomplex within the Flaviviridae family. We report four whole blood donors and one plasma donor with WNV nucleic acid test (NAT)-reactive donations between September 2018 and November 2019, following recent Japanese Encephalitis virus (JEV) vaccination. CASE SERIES: Cases 1 and 4 had reactive WNV NAT donations 1 day after receiving the JEV vaccine. Case 2 had a reactive WNV donation 3 days after receiving the JEV vaccine. Case 3 had a reactive WNV NAT donation 3 days after returning from Arizona and 1 day after receiving the JEV vaccine. Case 5 had a reactive WNV donation the same day as receiving the JEV vaccine. STUDY DESIGN AND METHODS: WNV screening used the Roche cobas WNV nucleic acid test (NAT) (Roche Molecular Systems). Reference testing on WNV-reactive donations was carried out by the National Microbiology Laboratory (NML). JEV vaccine dilutions were also analyzed. RESULTS: Supplemental NAT was negative for WNV and JEV for Cases 1, 3, and 5. Case 2 had a weak amplification curve for one of two JEV NAT targets. Case 4 was JEV NAT-positive, WNV NAT-negative. Serologic testing on donation specimens for Cases 2, 4, and 5 did not support recent or remote WNV infection. JEV vaccine dilutions were detected by both cobas and supplemental NAT. CONCLUSIONS: We recommend implementing a temporary blood donor deferral following a JEV vaccination, if screening utilizes a WNV assay with the capability of detecting other members of the JE serocomplex.

Prevalence of Babesia in Canadian blood donors: June-October 2018.

BACKGROUND: The erythrocytic protozoan parasite Babesia microti, the cause of human babesiosis, is transmitted not only by tick bites but also via blood transfusion. B. microti is endemic in the northeastern/upper midwestern United States, where partial screening of blood donations has been implemented. In Canada, a 2013 study of approximately 14,000 donors found no B. microti antibody-positive samples, suggesting low risk at that time. METHODS: Between June and October 2018, 50,752 Canadian donations collected from sites near the US border were tested for Babesia nucleic acid by transcription-mediated amplification (TMA). Reactive donations were tested for B. microti by IgG immunofluorescence assay and polymerase chain reaction. A subset of 14,758 TMA nonreactive samples was also screened for B. microti antibody. Donors who tested reactive/positive were deferred, asked about risk factors, and were requested to provide a follow-up sample for supplemental testing. RESULTS: One sample from Winnipeg, Manitoba, was TMA and antibody reactive. Of the 14,758 TMA-nonreactive donations tested for antibody, four reactive donations were identified from southwestern Ontario near Lake Erie. None of the interviewed donors remembered any symptoms, likely tick exposure, or relevant travel within Canada or the United States. CONCLUSIONS: This is the largest B. microti prevalence study performed in Canada. The results indicate very low prevalence, with only one TMA-confirmed-positive donation of 50,752 tested. This donor was from the only region in Canada where autochthonous infection has been reported. Seropositive donations in southwestern Ontario suggest low prevalence; travel should not be ruled out given the proximity to the US border.

Risk of Exposure to Zika Virus and Impact on Cord Blood Banking and Adult Unrelated Donors in Hematopoietic Cell Transplantation: The Canadian Blood Services Experience.

Zika virus has emerged as a potential threat to the Canadian blood supply system. Stem cell donors within Canadian Blood Services' Cord Blood Bank (CBB) and OneMatch Stem Cell and Marrow Network (OM) now undergo screening measures designed to reduce the risk of Zika virus transmission. The impact these screening measures have on cord blood and unrelated adult stem cell donations is currently unknown. Among 146 donor workups initiated by OM between July 2016 and May 2017, 102 were completed and 44 workups were canceled. There were 17 potential donors (11.6%) with a risk of Zika virus exposure identified by the donor questionnaire (13 completed, 4 canceled workups). None of the workups involved a donor diagnosed with confirmed Zika virus within the past 6 months. Only 1 of the 44 canceled workups (and only 1 of 4 cases with a risk of Zika transmission) was canceled because of the risk of Zika transmission, and a backup donor was selected. Canadian Blood Services' CBB identified 25 of 875 cord blood units (2.9%) from women who donated their infants' cord blood and underwent screening that otherwise met the initial cell number thresholds for banking and had at least 1 risk factor for exposure to Zika virus. No women were diagnosed with Zika virus at any point of their pregnancy. All 25 units were discarded. Unrelated donors at OM have a higher incidence of a risk of exposure to Zika virus compared with cord blood donors. Only rarely did transplant centers cancel donor workups due to potential Zika virus exposure. The impact of screening for Zika virus exposure risk on cord blood banking was minor. Continued vigilance and surveillance is recommended.

Assignment of cytomegalovirus infection status in infants awaiting solid organ transplant: Viral detection methods as adjuncts to serology.

Assignment of CMV infection status in infants awaiting SOT is challenging as passive maternal antibody can lead to false-positive serology. Since 2000, our protocol has recommended sending throat and urine samples for CMV viral detection, culture, or NAAT, for CMV-seropositive infants <18 months awaiting SOT. We reviewed pretransplant CMV serology for 152 infants and, for CMV seropositives, examined relationships between CMV IgG OD values, age, and CMV viral detection to explore time to clearance of maternal CMV IgG and evaluate viral detection in assignment of pretransplant CMV infection status. The proportion of CMV-seropositive infants decreased from 52% in infants 0-6 months of age to 28% in those 12-18 months. Among CMV-seropositive infants, median OD was significantly higher in the 6- to 12- and 12- to 18-month groups compared to the 0- to 6-month group. Distribution of OD by age group suggested that maternal antibody cleared before 12 months. Of 59 eligible CMV-seropositive infants, 49 (83%) had CMV viral detection studies and 18 of 49 (36.7%) had detectable CMV: 9 of 30 (30.0%) infants 0-6 months, 7 of 15 (46.7%) infants 6-12 months, and 2 of 4 (50.0%) infants 12-18 months. CMV viral detection studies are useful to confirm positive CMV infection status in CMV-seropositive infants awaiting SOT. Maternal CMV IgG likely clears before 12 months.

Mitigation of the threat posed to transfusion by donors traveling to Zika-affected areas: a Canadian risk-based approach.

BACKGROUND: The recent spread of the Zika virus to the Americas and the recognition that it can cause severe disease in the developing fetus has prompted the adoption of measures to mitigate the risk that this virus might pose to transfusion safety. In nonendemic countries, the risk to transfusion results from donors traveling to an endemic region. Canada implemented a 21-day temporary deferral for prospective donors who traveled to such regions. We present the rationale for this policy, including a quantitative risk assessment supported by a Monte Carlo simulation. STUDY DESIGN AND METHODS: The model considered the following parameters, each with specified values and ranges: the probability that a donor recently returned from a Zika-endemic region, the duration of travel to this region, the daily risk of acquiring Zika while in an endemic region, and the incubation and viremic periods. We ran the simulation 20 times, each with 10 million iterations. RESULTS: In the absence of any travel deferral, 32 donors (range, 20-46 donors) would be able to donate while still being at risk of transmitting Zika, corresponding to a rate of 1:312,500 (range, 1:217,000 to 1:500,000). None of these donors would be viremic beyond 21 days after returning from their travel, with a risk estimated at less than 1:200,000,000. CONCLUSIONS: A 21-day temporary travel deferral offers an extremely wide margin of safety for the possible transmission of Zika by a donation obtained from someone who recently returned from a country where the virus is circulating.

Hepatitis E in Canadian blood donors.

BACKGROUND: Hepatitis E virus (HEV) is a virus of emerging importance to transfusion medicine as studies on blood donors and other populations demonstrate that the prevalence of endemic cases is higher than previously recognized and the risk to vulnerable transfusion recipients is not insignificant. STUDY DESIGN AND METHODS: We carried out an HEV prevalence study on 13,993 Canadian blood donors with polymerase chain reaction (PCR) testing on all donors and antibody testing on a subset of 4102 donors. HEV antibody-positive and age- and sex-matched antibody-negative donors were invited to participate in a scripted telephone interview about risk factors. RESULTS: There were no PCR-positive samples found (95% confidence interval [CI], 0%-0.026%). The seroprevalence of HEV in our tested population was 5.9% (95% CI, 5.16%-6.59%). HEV antibody positivity was associated with male sex and increasing age. In case-control analysis history of living outside Canada (odds ratio [OR], 2.9; 95% CI, 1.56-5.32) and contact with farm animals (OR, 1.5; 95% CI, 1.01-2.28) were associated with HEV seropositivity. CONCLUSION: This is the largest data set to date on HEV infection in Canada. Results suggest low lifetime exposure to HEV and that infectious donations are rare.

Residual risk of HIV, HCV and HBV in Canada.

BACKGROUND: Residual risk is estimated as the product of the incidence and the infectious window period, the time during which a blood donation could be infectious but the assay may not detect it. In 2011 nucleic acid multiplex testing (MPX) was implemented in 6 unit minipools (previously 24 unit minipools). MPX also included hepatitis B (HBV) NAT for the first time (complementing HBsAg screening) in addition to HIV-1 and hepatitis C (HCV) as before. We aimed to estimate window period risk-day equivalents for MPX, and the residual risk of viral infections in blood donations updated to reflect current incidence and testing. METHODS: Transmissible disease conversions of repeat donations to Canadian Blood Services within the three-year period 2012-2014 divided by person-years estimated incidence for HIV, HCV and HBV (adjusted for transient viremia). Window period risk-day equivalents for MPX were estimated using a published method. Residual risk was the product of incidence and window period risk-day equivalents. 95% confidence intervals were estimated using Monte Carlo simulation of the window period risk-day equivalents and the incidence density 95% confidence intervals. RESULTS: The incidence rate per 100,000 person years for HIV was 0.28, HCV 1.0 and HBV 0.26. The residual risk of HIV was 1 per 21.4 million donations, HCV 1 per 12.6 million donations and HBV 1 per 7.5 million donations. CONCLUSION: The residual risk of infection is very low, similar to 2006-2009. The safety benefit of further shortening of the infectious window period is below the threshold to quantify.

Seroprevalence of Babesia microti infection in Canadian blood donors.

BACKGROUND: Human babesiosis, caused by the intraerythrocytic protozoan parasite Babesia microti, is primarily transmitted by tick bites and is also transmitted by transfusion. Infections have been identified in U.S. blood donors close to Canadian borders. We aimed to assess the risk of transfusion-transmitted babesiosis in Canada by examining infections in ticks and seroprevalence in blood donors. STUDY DESIGN AND METHODS: Passive surveillance (receipt of ticks submitted by the public) was used to identify regions for tick drag sampling (active surveillance, 2009-2014). All ticks were tested for B. microti using an indirect immunofluorescent antibody assay (Imugen, Inc.). Between July and December 2013, blood donations from selected sites (southern Manitoba, Ontario, Québec, New Brunswick, and Nova Scotia) near endemic U.S. regions were tested for antibody to B. microti. Donors completed a questionnaire about risk travel and possible tick exposure. RESULTS: Of approximately 12,000 ticks submitted, 14 were B. microti positive (10 in Manitoba, one in Ontario, one in Québec, two in New Brunswick). From active tick surveillance, six of 361 ticks in Manitoba were positive (1.7%), three of 641 (0.5%) in Québec, and none elsewhere. There were 26,260 donors at the selected sites of whom 13,993 (53%) were tested. None were positive for antibody to B. microti. In 2013, 47% of donors visited forested areas in Canada, and 41% traveled to the United States. CONCLUSION: The data do not suggest that laboratory-based testing is warranted at this time. However, there are indicators that B. microti may be advancing into Canada and ongoing monitoring of tick populations and donor seroprevalence is indicated.

Evaluation of selective screening of donors for antibody to Trypanosoma cruzi: seroprevalence of donors who answer "no" to risk questions.

BACKGROUND: Selective testing of donors for Trypanosoma cruzi infection relies on identification of at-risk donors with screening questions. Using risk modeling and a seroprevalence study, we evaluated the risk of questions failing to identify T. cruzi antibody-positive donors. STUDY DESIGN AND METHODS: The rate of donors with unreported risk was estimated by a telephone survey of 2677 donors who answered "no" to risk questions. The number of T. cruzi antibody-positive donors missed by risk questions was estimated from the product of this rate and the selective testing T. cruzi antibody-positive rate. The 95% confidence interval (CI) was estimated by Monte Carlo simulation. To test the model, 60,132 donors were tested for T. cruzi antibody (26% of donors in selected regions, Phase I). In Winnipeg, Manitoba, the highest-risk region, 26,915 donors were tested (92.5% of donors, Phase II). RESULTS: In the telephone survey, 21 (0.8%) donors reported risk factors that would have identified them for selective testing. Seven were born in Mexico or Central or South America, five had travel risk, and nine had mother or maternal grandmother risk. The 95% CI for predicted number of T. cruzi antibody-positive donors answering "no" to risk questions was 0.71 to 4.38. In Phase I, one Winnipeg donor confirmed positive but had answered risk questions correctly. No other positive donations were identified. CONCLUSION: The estimated risk of T. cruzi-positive donors who answer "no" to risk questions is low and is confirmed by the seroprevalence among these donors.

Selective testing for Trypanosoma cruzi: the first year after implementation at Canadian Blood Services.

BACKGROUND: Various testing strategies may reduce the risk of Chagas disease transmission in nonendemic, low-prevalence countries. Results of the first year of selective testing of at-risk donors at Canadian Blood Services are reported. STUDY DESIGN AND METHODS: Since February 2009, platelets were not produced from at-risk donors. Since May 2010, at-risk donors were tested for Trypanosoma cruzi antibodies. Donors testing positive were interviewed about risk factors, and lookback studies were initiated. RESULTS: There were 7255 at-risk donors of 421,979 donors screened (1.72%). Risk factors were born in Latin America (50.6%), mother or maternal grandmother born in Latin America (28%), and 6 months or more travel history or residence in Latin America (19%). Sixteen (16) at-risk donors had T. cruzi repeat-reactive test results of whom 13 confirmed positive. Eleven of 13 were born in Latin America (nine in Paraguay and two in Argentina), and the other two were born in Canada but had short-term travel history and mothers who had been born in Latin America. Ten of the donors spoke German as their first language (all of those born in Paraguay and one born in Canada). There were 148 previous donations (176 components transfused) evaluated by lookback, of which 28% of recipients could be tested. None were positive. CONCLUSION: Selective testing has mitigated a small risk to the blood supply with very few false-positive results. Most positive donors were born in a risk country, with a concentration of German-speaking immigrants from Paraguay. Residency or travel alone were not clear risk factors.

A case of vertical transmission of Chagas disease contracted via blood transfusion in Canada.

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and is endemic in many countries in Latin America, where infected bugs of the Triatominea subfamily carry the parasite in the gut and transmit it to humans through fecal contamination of a bite. However, vertical transmission and transmission through blood transfusion and organ transplantation is well documented. Increasing immigration from endemic countries to North America has prompted blood operators, including Canadian Blood Services and Hema Quebec, to initiate blood donor testing for Chagas antibody. In the present report, an unusual case of vertical transmission from a mother, most likely infected through blood transfusion, and detected as part of a concurrent seroprevalence study in blood donors is described.

La maladie de Chagas est causée par le parasite protozoaire Trypanosoma cruzi. Elle est endémique dans de nombreux pays d'Amérique latine, où des insectes infectés de la sous-famille des Triatominea sont porteurs du parasite dans leur intestin et le transmettent aux humains par contamination fécale secondaire à une morsure. Cependant, la transmission verticale, par transfusion sanguine et par transplantation d'organe, est bien étayée. L'immigration croissante de pays endémiques en Amérique du Nord a incité les organismes transfusionnels, y compris la Société canadienne du sang et Héma-Quebec, à amorcer le dépistage de l'anticorps de la maladie de Chagas dans le sang des donneurs. Dans le présent rapport, les chercheurs décrivent un cas inhabituel de transmission verticale par la mère, probablement infectée par une transfusion sanguine, dépistée dans le cadre d'une étude concomitante sur la séroprévalence chez les donneurs de sang.

Trypanosoma cruzi infection in North America and Spain: evidence in support of transfusion transmission.

BACKGROUND: The United States, Canada, and Spain perform selective testing of blood donors for Trypanosoma cruzi infection (Chagas disease) to prevent transfusion transmission. The donor, product, and patient characteristics associated with transfusion-transmitted infections are reviewed and the infectivity of components from donors with serologic evidence of infection is estimated. STUDY DESIGN AND METHODS: A systematic review of transfusion-transmitted T. cruzi cases and recipient tracing undertaken in North America and Spain is described. Cases were assessed for the imputability of the evidence for transfusion transmission. RESULTS: T. cruzi infection in 20 transfusion recipients was linked to 18 serologically confirmed donors between 1987 and 2011, including 11 identified only by recipient tracing. Cases were geographically widely distributed and were not associated with incident or autochthonous infections. Index clinical cases were described only in immunocompromised patients. All definite transmissions (n = 11) implicated apheresis or whole blood-derived platelets (PLTs), including leukoreduced and irradiated products. There is no evidence of transmission by red blood cells (RBCs) or frozen products, while transmission by whole blood transfusion remains a possibility. Recipient tracing reveals low component infectivity from serologically confirmed, infected donors of 1.7% (95% confidence interval [CI], 0.7%-3.5%) overall: 13.3% (95% CI, 5.6%-25.7%) for PLTs, 0.0% (95% CI, 0.0%-1.5%) for RBCs, and 0.0% (95% CI, 0%-3.7%) for plasma and cryoprecipitate. CONCLUSIONS: T. cruzi is transmitted by PLT components from some donors with serologic evidence of infection. Evidence of transmission before the implementation of widespread testing in the countries studied is sparse, and selective testing of only PLT and fresh whole blood donations should be considered.

West Nile virus in 2006 and 2007: the Canadian Blood Services' experience.

BACKGROUND: The Canadian blood supply has been screened for West Nile virus (WNV) since 2003. A strategy for targeted individual-donation nucleic acid testing (ID-NAT) was implemented in 2004 to identify potentially infectious donations that may be missed by minipool (MP) testing. In 2007, Canada experienced a larger epidemic than in previous years providing an opportunity to evaluate the ID-NAT triggering algorithm in higher-risk areas. STUDY DESIGN AND METHODS: A specially created database and internal-external communication identified regions for targeted ID-NAT using MP and community triggers. WNV-positive donations identified by ID-NAT were reexamined in MP to assess the efficacy of targeted ID-NAT in identifying potentially infectious donations that may have been missed by MP testing. WNV-positive donation data from 2006 and 2007 were analyzed to examine temporal and geographic trends. A telephone survey about symptoms was carried out after the 2007 season. RESULTS: In total 78 WNV-positive donations were identified (66 true-positives and four false-positives being in 2007). Most positive donations were in the late summer, concentrated in the same western provinces as community cases. Fifty-two donations were identified by ID-NAT and 46% were consistently positive in MP. Of the other 54%, 74% were immunoglobulin (Ig)M- and/or IgG-positive. Fifty-six percent of donors experienced mostly mild symptoms before or after donation (but all said they were well at the time of donation). CONCLUSION: WNV-positive donations correspond geographically with the epidemic. MP testing identifies most potentially infectious donations with a smaller potential benefit from targeted ID-NAT. Mild symptoms are common but may not deter donation.

Impact of a policy to permit the return of donors repeat-reactive to the Abbott PRISM antibody to hepatitis B core antigen assay.

BACKGROUND: The expected donor loss from recent implementation of antibody to hepatitis B core antigen (anti-HBc) testing in Canada was uncertain but potentially significant based on US experience. To reduce donor loss from false-reactive tests, repeat-reactive donors without other evidence of infection were eligible to return. The aim was to evaluate the impact of anti-HBc testing on donor loss and to evaluate the effectiveness of this policy. STUDY DESIGN AND METHODS: For each donor in the first year of implementation (April 9, 2005-April 8, 2006) repeat-reactive for the presence of anti-HBc only but eligible to return (screening test for hepatitis B surface antigen-negative, plus not reactive to antibody to hepatitis B surface antigen [anti-HBs] and hepatitis B virus [HBV] DNA supplemental tests), 10 matched donors not reactive to the anti-HBc assay were selected. Return rates over 2 years were compared using conditional logistic regression. Testing outcomes were tabulated. RESULTS: Over the first year of testing, 412,236 donors (951,423 donations) were tested for anti-HBc, and 4,489 donors were repeat-reactive (1.3% of first-time donors, 1.0% of repeat donors). Of these 85.6 percent were also reactive for the presence of anti-HBs and/or HBV DNA supplemental tests leaving less than 15 percent eligible to return, of whom 73 percent returned (vs. 90% of controls, p < 0.001). Of the 300 anti-HBc repeat-reactive returning donors, 74 percent were anti-HBc repeat-reactive again (thus permanently deferred), 19 percent were deferred for other reasons versus 14 percent of controls (p < 0.05), and 7 percent (21 donors) did not react and were eligible to continue donating. CONCLUSION: Most donors repeat-reactive for the presence of anti-HBc likely have past exposure to HBV. If eligible, most are willing to return, but likely to test anti-HBc repeat-reactive again.

Prognosis after West Nile virus infection.

BACKGROUND: The long-term prognosis of patients infected with West Nile virus is not well understood. OBJECTIVE: To describe the patterns of physical and mental function after infection with West Nile virus and to determine factors associated with recovery. DESIGN: Longitudinal cohort study. SETTING: Data were collected during home visits and from ambulatory clinics in 4 Canadian provinces. PARTICIPANTS: 156 persons with West Nile virus infection. MEASUREMENTS: Scores on the Physical Component Summary and Mental Component Summary of the Short Form-36, Depression Anxiety Stress Scale, and Fatigue Severity Scale. RESULTS: Physical and mental function, as well as mood and fatigue, seemed to return to normal within 1 year of symptom onset. Participants with neuroinvasive disease took slightly longer to recover. Maximum predicted recovery or rate of recovery in any domain did not differ between participants with meningoencephalitis and those with encephalitis. Lack of preexisting comorbid conditions was associated with faster recovery of physical function, whereas lack of comorbid conditions and male sex were associated with faster recovery of mental function. LIMITATIONS: The analysis excluded 7 patients who died shortly after diagnosis, so the study's estimates of prognosis may be overoptimistic. The authors did not formally assess neuropsychological difficulties. The estimates of recovery are relative to the U.S. population, not to participants' function levels before West Nile virus infection. CONCLUSION: Physical and mental outcome measures seem to normalize within approximately 1 year in patients with West Nile virus. The presence of preexisting comorbid conditions is associated with longer recovery.