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.

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.

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.

Epidemiology of hepatitis B in Canadian blood donors.

BACKGROUND: The residual risk of hepatitis B is higher than for other markers such as human immunodeficiency virus and hepatitis C virus in nonendemic countries. Evaluating the potential for further risk reduction requires a better understanding of the relationship between donor selection criteria, immigration from endemic countries, and public health vaccination strategies. STUDY DESIGN AND METHODS: Age and sex trends of hepatitis B surface antigen (HBsAg)-positive donors from 1997 to 2006 were analyzed using a Poisson model. All HBsAg-positive donors in 2005/2006 plus four matched control donors for every HBsAg-positive donor who participated were invited to participate in a risk factor interview and predictors of HBsAg positivity identified by logistic regression. A survey of 40,000 donors who did not react for all markers asked about vaccination history and country of birth. RESULTS: Most HBsAg-positive donations were from first-time donors (86%), have been decreasing in donors under the age of 30 (p < 0.01), and were correlated with geographic regions with more donors from higher-prevalence countries (p < 0001). Birth in a higher-prevalence country predicted HBsAg positivity (p < 0.01). Fifty-six percent of donors reported being vaccinated for hepatitis including approximately 80 percent of donors under age 30 who reported being vaccinated as part of regular school programs. CONCLUSION: HBsAg-positive donations are decreasing in donors under age 30, those most frequently vaccinated through provincial vaccination programs. HBsAg-positive donations largely reflect immigration from high-prevalence countries without other deferrable risk factors, mainly chronic cases that will be detected by current testing. Furthermore, risk of incident infections should decrease with increasing vaccination rates in donors, especially the younger cohort now receiving universal vaccination.

Risk of ruling out severe acute respiratory syndrome by ruling in another diagnosis: variable incidence of atypical bacteria coinfection based on diagnostic assays.

BACKGROUND: Severe acute respiratory syndrome (SARS) caused the first epidemic of the 21st century and continues to threaten the global community. OBJECTIVE: To assess the incidence of coinfection in patients confirmed to have SARS-associated coronavirus (SARS-CoV) infection, and thus, to determine the risk of ruling out SARS by ruling in another diagnosis. METHODS: The present report is a retrospective study evaluating the incidence and impact of laboratory-confirmed SARS-CoV and other pulmonary pathogens in 117 patients. These patients were evaluated in a Toronto, Ontario, community hospital identified as the epicentre for the second SARS outbreak. RESULTS: Coinfection with other pulmonary pathogens occurred in patients with SARS. Seventy-three per cent of the patient population evaluated had laboratory-confirmed SARS-CoV infection. Serology showing acute or recent Chlamydophila pneumoniae or Mycoplasma pneumoniae infection revealed an incidence of 30% and 9%, respectively, in those with SARS. These rates are similar to previously published studies on coinfection in pneumonia. All nucleic acid diagnostic assays were negative for C pneumoniae and M pneumoniae in respiratory samples from patients with SARS having serological evidence for these atypical pathogens. CONCLUSIONS: Diagnostic assays for well-recognized pulmonary pathogens have limitations, and ruling out SARS-CoV by ruling in another pulmonary pathogen carries significant risk. Despite positive serology for atypical pathogens, in a setting where clinical suspicion for SARS is high, specific tests for SARS should be performed to confirm or exclude a diagnosis.

Assessment of a travel question to identify donors with risk of Trypanosoma cruzi: operational validity and field testing.

BACKGROUND: Because Trypanosoma cruzi (T. cruzi) infection in Canada and the United States is largely contracted in endemic countries, targeted testing of blood donors with risk travel may improve safety. The operational validity of a travel question suitable for donor screening was tested, and it was field-tested. STUDY DESIGN AND METHODS: After 1331 donors completed a short travel question, operational validity was assessed by detailed travel histories in face-to-face interviews. Two nationwide donor surveys were carried out assessing donor responses to similar travel questions in 2001 (13,623 donors) and in 2006 (20,037 donors). All donors in Toronto, Ontario, answered a travel question in 1997 and those born in or who spent 6 months or more in Mexico, Central America, or South America were tested for antibody to T. cruzi. RESULTS: There was 97.3 percent agreement between the travel question and detailed interviews, with 15 donors (1.1%) failing to acknowledge risk travel (false-negative questioning responses). Of these, 6 donors were born there and 7 others had less than 1 year of cumulative travel. In 2001 and 2006, there were 2.1 and 2.0 percent of donors with risk travel, respectively, but 16.5 and 11.2 percent of these donors were identified only because they were born there (travel not acknowledge). There were 1337 (1.6%) donors in Toronto in 1997 with risk travel and none were positive for the presence of T. cruzi antibody. CONCLUSION: Donors can answer a short question about cumulative time in Latin America with similar accuracy to detailed questioning, but screening questions should also include country of birth.

Declining hepatitis C rates in first-time blood donors: insight from surveillance and case-control risk factor studies.

BACKGROUND: Hepatitis C virus (HCV) rates have decreased steadily in first-time donors in Canada since testing was implemented but reasons are unclear. A description of factors that may have played a role in this decline is reported. STUDY DESIGN AND METHODS: Descriptive analysis of first-time blood donors by HCV positivity status and year (1993--2006), sex, and age was carried out. HCV-positive first-time donors and matched controls participated in a confidential scripted telephone interview about risk factors in 1993 through 1994 and in 2005 through 2006, and risk factors independently predicting HCV positivity were determined with multiple logistic regression. RESULTS: HCV-positive donations occurred most frequently in donors born between 1945 and 1964 and decreased in this birth cohort over time (p < 0.01). At present, most first-time donors (74%) are born after 1964. History of intravenous drug use, sex with an intravenous drug user, blood transfusion, and tattoo independently predicted (p < 0.01) HCV positivity in both periods (1993--1994 and 2005--2006). CONCLUSION: Most HCV-positive donors were born between 1945 and 1964, and the decline in HCV rates is associated primarily with this birth cohort. The key risk factors predicting HCV positivity did not change over the 13 years of the study. With approximately two-thirds of HCV-positive Canadians in the general population having been tested for HCV, potential donors may be aware of their HCV status and be likely to self-defer. This, and an increasing proportion of first-time donors born after 1964, may contribute to declining HCV rates in first-time donors.

Hepatitis B virus DNA-positive, hepatitis B surface antigen-negative blood donations intercepted by anti-hepatitis B core antigen testing: the Canadian Blood Services experience.

BACKGROUND: The benefit of introducing anti-hepatitis B core antigen (HBc) screening for intercepting potentially infectious donations missed by hepatitis B surface antigen (HBsAg) screening in Canada was studied. STUDY DESIGN AND METHODS: Anti-HBc testing of all donations was implemented in April 2005, along with antibody to hepatitis B surface antigen (anti-HBs) and hepatitis B virus (HBV) DNA supplemental testing of anti-HBc repeat-reactive, HBsAg-negative donations. The proportion of potentially infectious donations intercepted by anti-HBc over the initial 18 months of testing was calculated based on three assumptions relating infectivity of HBV DNA-positive units to anti-HBs levels. Lookback was conducted for all DNA-positive donations. RESULTS: Of 493,344 donors, 5,585 (1.13%) were repeat-reactive for the presence of anti-HBc, with 29 (0.52%) being HBV DNA-positive and HBsAg-negative. The proportion of potentially infectious donations intercepted by anti-HBc screening was 1 in 17,800 if all HBV DNA-positive donations were infectious, 1 in 26,900 if infectivity was limited to donations with an anti-HBs level of not more than 100 mIU per mL, and 1 in 69,300 if only donations with undetectable anti-HBs were infectious. For 279 components in the lookback study, no traced recipients were HBsAg-positive and 7 recipients were anti-HBc-reactive in association with 4 donors, 3 of whom had an anti-HBs level of more than 100 mIU per mL and 1 of whom had a level of 61 mIU per mL. CONCLUSION: Implementation of anti-HBc screening reduced the risk of transfusing potentially infectious units by at least as much as had been expected based on the literature. The lookback did not provide proof of transfusion transmission of HBV from HBV DNA-positive, anti-HBc-reactive, HBsAg-negative donors but it did not establish lack of transmission either.