Canadian Blood Services traceback investigation of a suspected case of transfusion-transmitted malaria.

BACKGROUND: A 4-month-old infant hospitalized since birth received multiple blood transfusions. In March 2022, Plasmodium falciparum was confirmed with nucleic acid testing. As the mother was assessed as unlikely to be the source of infection, the blood operator initiated a traceback investigation for a potential blood donor source. The patient had received 13 red blood cell (RBC) transfusions (aliquoted from 11 donors), 4 apheresis platelet (PLT) transfusions and 16 buffy coat pooled PLT transfusions. The blood operator medical team developed a supplementary malaria infection risk questionnaire to identify donors at highest risk of life-time malaria infection, based on birthplace, residence, or travel in malaria-endemic regions. RESULTS: With 79 donors initially implicated, initial focus was on donors of RBC components. The 11 RBC donors were contacted and assessed using the supplementary questionnaire. Three donors, all of whom met current malaria-related donor eligibility criteria, were deemed high risk of prior malaria infection. These donors consented to P. falciparum serology and nucleic acid testing (NAT). One donor who was born and had resided in an endemic West African country for 14 years, was positive for P. falciparum by serology (indirect fluorescent antibody test) and NAT-(Ct ≥32). Lookback of this donor's transfused fresh co-components and prior donation identified no other malaria cases. CONCLUSION: This was a probable transfusion-transmitted malaria (TTM) case from an eligible donor who in retrospect was found to have unrecognized, asymptomatic, semi-immune malaria infection, and who was potentially infectious. Blood donor lack of recall of prior malaria infection does not negate the risk of TTM from those who have lived in malaria-endemic countries.

Babesia microti in a Canadian blood donor and lookback in a red blood cell recipient.

BACKGROUND AND OBJECTIVES: We describe the third documented case of autochthonous human babesiosis in Canada and the second in a Canadian blood donor. MATERIALS AND METHODS: Multiple laboratory investigations were carried out on the donor and the immunocompromised recipient of an associated, potentially infectious red blood cell product. RESULTS: The donor had not travelled except for outdoor exposure in south-eastern Manitoba, followed by illness and hospital admission. The donor had a notable parasitaemia, positive for Babesia microti using whole blood nucleic acid testing (NAT). The recipient was negative for B. microti by both serology and NAT. CONCLUSION: There was no evidence of transfusion-transmitted babesiosis.

Impacts of COVID-19 and elective surgery cancellations on platelet supply and utilization in the Canadian Province of British Columbia.

BACKGROUND AND OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic raised concerns about the vulnerability of platelet supply and the uncertain impact of the resumption of elective surgery on utilization. We report the impact of COVID-19 on platelet supply and utilization across a large, integrated healthcare system in the Canadian province of British Columbia (BC). MATERIALS AND METHODS: Historical platelet use in BC by indication was compiled for fiscal year 2010/2011-2019/2020. Platelet collections, initial daily inventory and disposition data were assessed pre-COVID-19 (1 April 2018-15 March 2020) and for two COVID-19 time periods in BC: a shutdown phase with elective surgeries halted (16 March-17 May, 2020) and a renewal phase when elective surgeries resumed (18 May-27 September 2020); comparisons were made provincially and for individual health authorities. RESULTS: Historically, elective surgeries accounted for 10% of platelets transfused in BC. Initial daily supplier inventory increased from baseline during both COVID-19 periods (93/90 units vs. 75 units pre-COVID-19). During the shutdown phase, platelet utilization decreased 10.4% (41 units/week; p < 0.0001), and remained significantly decreased during the ensuing renewal period. Decreased platelet utilization was attributed to fewer transfusions during the shutdown phase followed by a decreased discard/expiry rate during the renewal phase compared to pre-COVID-19 (15.2% vs. 18.9% pre-COVID-19; p < 0.0001). Differences in COVID-19 platelet utilization patterns were noted between health authorities. CONCLUSION: Decreased platelet utilization was observed in BC compared to pre-COVID-19, likely due to a transient reduction in elective surgery as well as practice and policy changes triggered by pandemic concerns.

De novo hepatitis B surface antigen (HBsAg)-positive, core antibody (anti-HBc)-negative, hepatitis B virus infection post-liver transplant from an anti-HBc, HBsAg-negative donor.

Liver transplant donors and recipients are routinely screened for hepatitis B virus (HBV) infection by measuring the levels of hepatitis B surface antigen (HBsAg) and hepatitis B core (anti-HBc) antibodies. Organs are accepted from donors who are HB-negative, and increased monitoring is required for organs from donors considered at increased risk. Transplant recipients are vaccinated if there is no sign of previous infection or immunity and monitored for reactivation in case of previous HBV infection. In cases where both the donor and the recipient are HBV-negative, no antiviral prophylaxis is used post transplant. This report describes a case of an HBV-immunized, anti-HBc-negative patient who underwent an orthotopic liver transplant from an anti-HBc-negative donor. The patient did not receive post-transplant antiviral prophylaxis due to mutual anti-HBc-seronegative status. However, the recipient developed HBV infection with isolated HBsAg and persistently negative anti-HBc. Mutations in the core/pre-core regions of the HBV gene were not implicated for unique serology in this case. Immunosuppression post liver transplant is the likely etiology for isolated HBsAg seroconversion despite significantly elevated HBV DNA. Our experience suggests that HBV DNA screening of liver transplant donors and recipients, in addition to HBV DNA monitoring of recipients, may reduce the risk of transplant-associated HBV.

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.

Stability of hepatitis B viral load during pregnancy and implications for antepartum prophylaxis: A prospective cohort study.

BACKGROUND: We examined changes in hepatitis B virus (HBV) viral loads (VLs) in pregnancy, their association with hepatitis B e antigen (HBeAg), and the associated infant outcomes. METHODS: We prospectively followed 132 mothers positive for hepatitis B surface antigen (HBsAg) and their 135 infants from 2011 to 2015 in Vancouver, British Columbia. Outcome measures included association between maternal HBeAg and high (>200,000 IU/mL) or low (≤200,000 IU/mL) HBV VL, changes in HBV VL through pregnancy, infant HBsAg status, and infant completion of the HBV vaccination series. RESULTS: f the 91 participants with an available HBV VL, 13 (14.3%) had an HBV VL of more than 200,000 IU/mL. Of 59 participants with paired HBeAg and HBV VL in pregnancy, 6 had an HBV VL of more than 200,000 IU/mL; of interest, 2 of the 6 (33.3%) were HBeAg-negative. Thirty-eight participants had HBV VL results at both mid-trimester and delivery. For these 38 participants, Wilcoxon signed-ranks test for paired data found that an HBV VL remained stable (p = .58). We observed no perinatal transmissions. However, 20.7% of infants did not have a documented complete HBV vaccination series, 20.0% did not have post-vaccination HBsAg testing completed, and 18% did not have anti-HBs titres measured by age 12 months. CONCLUSIONS: Our study demonstrates that HBeAg and HBV VL are not reliably predictive of each other. This supports the improved predictive value of VL measurement in pregnancy to risk stratify pregnant patients to offer antiviral treatment when indicated and further minimize the risk of perinatal transmission.

Duration of influenza outbreaks in long-term care facilities after antiviral prophylaxis initiation: Fraser Health, British Columbia, 2014-2017.

To assess the duration of antiviral prophylaxis (AP), we conducted a retrospective outbreak review over 3 seasons, looking for acute respiratory illness (ARI) onset after 5 days of AP. Of 114 facility-level outbreaks with 352 unit-level outbreaks, we found only 1 case of laboratory-confirmed influenza after 5 days of AP. New cases of ARI after 5 days of AP should be investigated, and recommendations for AP duration could be shortened to 7-8 days or less.

Estimated protective effectiveness of intramuscular immune serum globulin post-exposure prophylaxis during a measles outbreak in British Columbia, Canada, 2014.

INTRODUCTION: Intramuscular Immune Serum Globulin (IM ISG) is recommended as post-measles exposure prophylaxis (PEP) when administered within 6days of initial exposure, with variable effectiveness in preventing measles disease. Effectiveness of IM ISG PEP in preventing clinical measles was assessed during a 2014 measles outbreak among a religious-affiliated community in British Columbia, Canada. MATERIAL AND METHODS: Fifty-five self-reporting measles susceptible contacts were offered exclusively IM ISG PEP within an eligibility period best surmised to be within 6days of initial measles case exposure. Clinical outcome of IM ISG PEP recipients was determined by selective active surveillance and case self-reporting. IM ISG PEP failure was defined as onset of a measles-like rash 8-21days post-IM ISG PEP. Post-IM ISG PEP measles IgG antibody level was tested in 8 recipients. Factors associated with measles disease were analyzed. RESULTS: Seventeen of 55 IM ISG PEP recipients developed clinically consistent measles in the following 8-21days, corresponding to an estimated crude protective effectiveness of 69%. In school aged children 5-18years, among whom potential exposure intensity and immune status confounders were considered less likely, estimated IM ISG PEP protective effectiveness was 50%. Age <25years was significantly associated with breakthrough clinical measles in bivariate analysis (p=0.0217). Among 8 tested contacts of 17 considered IM ISG PEP failures, post-IM ISG PEP measles IgG antibody levels (mean 16.3days (range 16-17days) post-PEP) were all <150mIU/ml. CONCLUSIONS: The estimated crude IM ISG PEP protective effectiveness against measles disease within 8-21days post-ISG administration was 69%. Accuracy of this estimated protective effectiveness is vulnerable to assumptions and uncertainties in ascertaining exposure details and pre-exposure immune status. Increasing the Canadian recommended measles IM ISG PEP dose from 0.25 to 0.5ml/kg (up to 15ml maximum volume) may increase protective effectiveness.

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.

Missed opportunities for prevention of perinatal transmission of hepatitis B: a retrospective cohort study.

BACKGROUND: Perinatal transmission of hepatitis B virus (HBV) can occur despite postexposure prophylaxis (PEP). Recent literature suggests that antiviral treatment during pregnancy when maternal HBV DNA levels are elevated can further decrease vertical transmission. However, HBV DNA screening is not routinely performed antenatally. OBJECTIVE: To determine the rates of HBV prevalence and perinatal transmission in an antenatal cohort. METHODS: A retrospective review of public health records (December 2008 to December 2010) was performed for both mothers and newborns. RESULTS: A total of 725 mother-infant pairs were included. Of these, 574 of 715 (80%) women had antenatal hepatitis B e antigen (HBeAg) testing performed, and 127 of 574 (22%) were HBeAg positive (HBeAg+). Of babies born to hepatitis B surface antigen-positive (HBsAg+) mothers, only 573 of 725 (79%) received complete PEP. In addition, 172 of 725 (24%) infants did not receive post-PEP blood testing or were lost to follow-up. Of the 552 infants with results available, seven cases (1.3%) of mother-to-child HBV transmission were observed, six of which involved infants born to HBeAg+ women. CONCLUSIONS: Our findings suggest that routine HBeAg screening could identify a subset of mother-infant pairs among HBsAg+ pregnant women who are at higher risk for vertical HBV transmission. Determination of viral load in expectant HBeAg+ mothers may provide more precise insight into HBV transmission to their infants.

Low pertussis toxin antibody levels in two regional cohorts of Canadian pregnant women.

Infants under 6 months of age are at greatest risk of mortality and severe morbidity from pertussis disease. Interventions that increase pertussis protection in newborns are therefore a clear public health imperative. The objective of this study was to assess maternal pertussis toxin antibody (anti-PT) level as a potential source of mother-to-child transfer of pertussis-associated antibodies that may reduce neonatal risk of pertussis disease. Anti-PT level was assessed in a 2013 cohort of pregnant women from two regions in two Canadian provinces, British Columbia and Nova Scotia. Basic demographics, health, and pertussis immunization history were collected, along with blood specimens. Anti-PT levels were compared for self-reported vaccination status and prior pertussis disease. To assess secular trend, a parallel analysis was also undertaken, using anonymized residual sera from a 1996-1997 cohort of pregnant women in British Columbia. A total of 169 pregnant women participated in the study - 50 from Nova Scotia and 119 from British Columbia. The mean and median age of participants from both sites was 31 years of age (range 16-42 years). The lower limit of quantification of the anti-PT assay was 10 ELISA units per milliliter (EU/ml). Overall, 59% of women had anti-PT levels less than 10 EU/ml and anti-PT level did not differ with time since last self-reported pertussis vaccination (χ(2)(2)=3.166, p=0.205). Among a 1996-1997 cohort of pregnant women in British Columbia, 101 of 200 (51%) had anti-PT levels less than 10 EU/ml. Our study found that most pregnant women in two geographically disparate health regions in Canada have low residual anti-PT levels, may be vulnerable to pertussis infection themselves, and would unlikely be a source of passive ante- or postnatal transfer of anti-PT to their newborn.

Neutralization positive but apparent false-positive hepatitis B surface antigen in a blood donor following influenza vaccination.

We report a case of transient, confirmed positive hepatitis B surface antigen (HBsAg) in a 25 year old long term Canadian Blood Services (CBS) donor, who reported receiving 2011-2012 seasonal trivalent (A/H1N1, A/H3N2, Influenza B) inactivated influenza vaccine two days before donation. To our knowledge, this report is the first published case implicating influenza vaccine as a possible factor in false-positive HBsAg test results. Seasonal incidence of repeat-reactive HBsAg among CBS donors suggests a potential contributory role of influenza vaccine or community acquired infection. We speculate that influenza vaccine may rarely be associated with sporadic, transient, false-positive HBsAg results.

Adverse events following immunization: evaluating an enhanced nursing role for PHNs.

Maintaining confidence in vaccine safety is critical to successful public health immunization programs. Surveillance and assessment of adverse events following immunization (AEFIs) are important for maintaining vaccine safety. The authors describe the evaluation of an initiative at Fraser Health Authority designed to enhance the role of a communicable disease nurse coordinator (CDNC) in assessing AEFI reports, in collaboration with a designated medical health officer (MHO) as required, and providing recommendations to clients and immunization providers. Previously, only MHOs performed this role. This evaluation project demonstrates this initiative's feasibility and provides a roadmap for health authorities interested in pursuing a similar model. MHOs, public health nurses and public health management expressed satisfaction with the process and the quality of the CDNC's recommendations. There was no statistically significant difference in median turnaround time for AEFI reporting date and date of recommendation, indicating this work is completed in as timely a manner by the CDNC as by the MHO. This role provides opportunity for professional growth, facilitates nursing practice to full scope, enables acquisition of specialized knowledge and provides a platform to share nursing expertise at a provincial level.

Hepatitis C infection among pregnant women in British Columbia: reported prevalence and critical appraisal of current prenatal screening methods.

BACKGROUND: Despite the fact that hepatitis C virus (HCV) is a relatively common infection in Canada, particularly in British Columbia (BC), there is a paucity of information on actual HCV prevalence in pregnant women. At present, pregnant women are only screened if they fit risk criteria, which may result in under-identification of HCV in this population. The purpose of this study was to determine the overall prevalence rate, age and geographic distribution of reported HCV infection among pregnant women in BC, and compare results to a previously conducted anonymous seroprevalence survey. METHODS: Reported HCV prevalence was determined through a confidential database linkage of all prenatal screening results at the Canadian Blood Services (CBS) with all HCV test results at the Provincial Laboratory, from May 2000 to Oct 2002. Data were stratified by age group and geographic location, and subsequently compared to an anonymous prenatal seroprevalence survey conducted in 1994. RESULTS: The overall HCV prevalence rate was 50.3/10,000 (95% CI 46.3-54.6), or 0.5% of the cohort. Prevalence was highest in the northern BC region (66.2/10,000, 95% CI 51.4-85.3) and lowest in the populous suburban region southwest of Vancouver (38.0/10,000, 95% CI 32.3-44.8). Of note, the rate of reported HCV among pregnant women was significantly lower than the anonymous seroprevalence rate: 50.3/10,000 vs. 91.3/10,000 (p < 0.0001). CONCLUSION: Rates of reported HCV among pregnant women were approximately 50% lower than the rates determined by the anonymous seroprevalence survey. Further research is needed to determine the relative merits of the current selective screening policy versus universal prenatal HCV screening in pregnancy.

The approach taken to reducing the risk of transfusion related acute lung injury in Canada.

Transfusion related acute lung injury (TRALI) has become a major reported cause of severe transfusion reactions and mortality. Over the past four years significant changes have been taken in Canada in order both to improve the recognition of the risk and to decrease its incidence. An international meeting was held in April of 2004 entitled "Towards an Understanding of TRALI". As a result of the analysis and recommendations from this meeting, the Canadian Blood Services established an ongoing review committee and established a laboratory diagnostic facility to identify at risk donors and recipients. A system has been developed to identify implicated donors and exclude them from the blood donor pool. Other steps have been taken to exclude potentially high risk donors, such as previously pregnant females, from the plasma and platelet donor pool. A considerable amount of education also has been offered to clinical services in the country. This paper summarizes the definitions, categorizations of implicated donors, and the ongoing precautionary activities related to plasma products. Noted within the article are the methods used for locating and selecting data. These were primarily based on the international TRALI conference in 2004, and from ongoing discussions and information provided by the Canadian Blood Services TRALI Review Committee. No ethics referral or approval was requested, and a summary is included in the article.

Evaluating the impact of public health notification of suspected transfusion-transmissible hepatitis C virus infection and effectiveness of lookback and traceback investigations by Canadian Blood Services in British Columbia, Canada, August 2002 through February 2005.

BACKGROUND: Suspected transfusion-transmissible infections (TTIs) have been reported to public health (PH) in British Columbia (BC) since August 2002. The impact of PH notification of suspected transfusion-transmissible hepatitis C virus (TT-HCV) infection over the first 2.5 years and the effectiveness of HCV lookback (LB) and traceback (TB) investigations conducted by Canadian Blood Services (CBS) in BC were evaluated. STUDY DESIGN AND METHODS: Suspected TT-HCV cases reported to CBS in BC between August 28, 2002, and February 28, 2005, were analyzed. The incremental yield of plausible TTIs from PH-reported suspected TTIs was calculated. The effectiveness of LB and TB investigations was assessed with respect to the impact of improved anti-HCV donor screening, the number of newly recognized HCV infections, and the timeliness of initiating investigations. RESULTS: Nine of 553 (1.6%) investigations were initiated after PH reporting, yielding an additional 2 of 237 (i.e., 0.8%) plausible TTIs. Ninety-two percent of investigations with transfused units involved transfusions before implementing second-generation anti-HCV enzyme immunoassay (EIA) donor screening. Almost one-third of HCV-infected persons in linked investigations (i.e., LB triggered by a TB and vice versa) were newly identified. Recently tested, PH-reported cases incurred a mean delay exceeding 6 months until initiating a LB or TB investigation. CONCLUSION: PH reporting of TTIs and investigating transfusions after second-generation anti-HCV EIA donor screening identified few plausible TT-HCV infections. Many HCV-infected recipients or lapsed donors first became aware of their infection status as a result of CBS investigations. The current process of reporting suspected TTIs incurs significant time delay.

Participant-collected, mail-delivered oral fluid specimens can replace traditional serosurveys: a demonstration-of-feasibility survey of hepatitis A virus-specific antibodies in adults.

BACKGROUND: Although population-based serosurveys offer an optimal measure of cumulative infection rates, they are seldom performed due to high cost and complex logistics. Use of participant self-collected oral fluid as a diagnostic specimen and mail for specimen delivery has the potential of generating reliable, population-representative data at limited cost. METHODS: A survey of oral fluid HAV-specific immunoglobulin G (an indicator of past HAV infection) was undertaken in a provincially representative sample of 20-39 year olds as a pilot study. A provincial administrative database served as the sampling frame. Potential participants were invited by mail to collect oral fluid and complete a questionnaire at home and return both by mail. Additional telephone prompting was directed at slow responders. Oral fluid was tested using a validated ELISA. RESULTS: From among 2,448 potential participants, contact by mail or telephone was made with 1,009 eligible subjects; 59% (585) participated. Materials withstood mailing and the quality of self-collected specimens was excellent. A positive test result was found in 22.1% overall and in 15.7% of self-reported non-vaccinated subjects. Among Canadian-born, non-vaccinated individuals, the positive test rate increased progressively from 1.2% (95% CI: 0-6.3) in 20-24 year olds to 16.4% (95% CI: 9.5-23.3) in 35-39 year olds. Antibody prevalence was higher among Canadian-born non-immunized 20-29 year olds who reported travel to developing countries (33.3%, 95% CI: 11.6-55.1) than in non-travellers (2.5%, 95% CI: 0.7-6.2). CONCLUSIONS: Mail-based population surveys of infection markers in oral fluid are feasible provided an appropriate sampling frame is used. This survey revealed a high anti-HAV antibody prevalence in young Canadian adults, increasing with age and travel to developing countries.