Margaret Fearon

Measles Inclusion-Body Encephalitis Caused by the Vaccine Strain of Measles Virus

We report a case of measles inclusion-body encephalitis (MIBE) occurring in an apparently healthy 21-month-old boy 8.5 months after measles-mumps-rubella vaccination. He had no prior evidence of immune deficiency and no history of measles exposure or clinical disease. During hospitalization, a primary immunodeficiency characterized by a profoundly depressed CD8 cell count and dysgammaglobulinemia was demonstrated. A brain biopsy revealed histopathologic features consistent with MIBE, and measles antigens were detected by immunohistochemical staining. Electron microscopy revealed inclusions characteristic of paramyxovirus nucleocapsids within neurons, oligodendroglia, and astrocytes. The presence of measles virus in the brain tissue was confirmed by reverse transcription polymerase chain reaction. The nucleotide sequence in the nucleoprotein and fusion gene regions was identical to that of the Moraten and Schwarz vaccine strains; the fusion gene differed from known genotype A wild-type viruses.

Current incidence and residual risk of HIV, HBV and HCV at Canadian Blood Services

Estimates of the viral residual risk should be updated to reflect current incidence of infection in blood donors. Incidence rates were estimated for allogeneic whole‐blood donations made to Canadian Blood Services from 2006 to 2009 based on transmissible disease conversions of repeat donations within a 3‐year period. Residual risk was estimated as the incidence multiplied by the window period. The residual risk of HIV was 1 per 8 million donations, HCV 1 per 6·7 million donations and HBV 1 per 1·7 million donations. The residual risk remains low and has decreased for HCV since our previous estimates due to reduced incidence.

The epidemiology of human T‐cell lymphotropic virus types I and II in Canadian blood donors

Blood donors in Canada have been tested for Human T‐Cell Lymphotropic Virus (HTLV) since 1990. We report the epidemiology, risk factors and lookback/traceback of HTLV‐positive donors/recipients.

Blood-Borne Pathogens: A Canadian Blood Services Centre for Innovation Symposium

Abstract Testing donations for pathogens and deferring selected blood donors have reduced the risk of transmission of known pathogens by transfusion to extremely low levels in most developed countries. Protecting the blood supply from emerging infectious threats remains a serious concern in the transfusion medicine community. Transfusion services can employ indirect measures such as surveillance, hemovigilance, and donor questioning (defense), protein-, or nucleic acid based direct testing (detection), or pathogen inactivation of blood products (destruction) as strategies to mitigate the risk of transmission-transmitted infection. In the North American context, emerging threats currently include dengue, chikungunya, and hepatitis E viruses, and Babesia protozoan parasites. The 2003 SARS and 2014 Ebola outbreaks illustrate the potential of epidemics unlikely to be transmitted by blood transfusion but disruptive to blood systems. Donor-free blood products such as ex vivo generated red blood cells offer a theoretical way to avoid transmission-transmitted infection risk, although biological, engineering, and manufacturing challenges must be overcome before this approach becomes practical. Similarly, next generation sequencing of all nucleic acid in a blood sample is currently possible but impractical for generalized screening. Pathogen inactivation systems are in use in different jurisdictions around the world, and are starting to gain regulatory approval in North America. Cost concerns make it likely that pathogen inactivation will be contemplated by blood operators through the lens of health economics and risk-based decision making, rather than in zero-risk paradigms previously embraced for transfusable products. Defense of the blood supply from infectious disease risk will continue to require innovative combinations of surveillance, detection, and pathogen avoidance or inactivation.

Hepatitis E in Canadian blood donors

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.

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.

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.

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.