Mark Bigham

Elimination of acute hepatitis B among adolescents after one decade of an immunization program targeting Grade 6 students

Background. British Columbia introduced a preadolescent hepatitis B (HB) immunization program in 1992. This study documents trends in the reported rate of acute HB disease since 1992 and examines factors bearing on the rate of infection throughout the period of program implementation. Methods. All Grade 6 students were eligible for immunization. Vaccine uptake was reported annually for every school. Acute HB infections were reported by physicians and by biomedical laboratories. Year-to-year trends were analyzed overall and by age group using the electronic public health information system and S-plus. Likelihood ratio tests were used to establish whether a variable was associated with the rate of acute HB in a given cohort. Poisson regression was applied to determine which variables were independently associated with the rate of acute HB. Results. Immunization coverage ranged between 90 and 93% for each year between 1993 and 2001. The overall rate of reported acute HB declined from 7 per 100 000 to just more than 2 per 100 000, whereas that in 12- to 21-year-olds declined from 1.7 to 0 per 100 000 over this one decade period. In the final Poisson regression model, the rate of acute HB infection was significantly associated with year, urban region and lower vaccine uptake. There was an interaction between region and vaccine uptake such that higher vaccine uptake appeared more protective in rural than in urban regions. Conclusions. Acute HB has been eliminated in the immunized adolescent cohort. A higher carrier rate in urban regions most likely explains the apparent difference in program effectiveness between urban and rural regions.

Potential Capsule Switching from Serogroup Y to B: The Characterization of Three such Neisseria meningitidis Isolates Causing Invasive Meningococcal Disease in Canada

Three group B Neisseria meningitidis isolates, recovered from meningococcal disease cases in Canada and typed as B:2c:P1.5, were characterized. Multilocus sequence typing showed that all three isolates were related because of an identical sequence type (ST) 573. Isolates typed as 2c:P1.5 are common in serogroup Y meningococci but rare in isolates from serogroups B or C. Although no serogroup Y isolates have been typed as ST-573, eight isolates showed five to six housekeeping gene alleles that were identical to that of ST-573. This suggested that the B:2c:P1.5 isolates may have originated from serogroup Y organisms, possibly by capsule switching.

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.

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.

Routine nucleic acid testing of blood donations fails to detect all human immunodeficiency virus-positive blood donors.

The implementation of nucleic acid testing (NAT) was meant to shorten the window period and allow early detection of infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV). Canadian Blood Services (CBS) has routinely been screening donors with HCV and HIV NAT assays since 1999 and 2001, respectively, with HBV included with multiplex testing, Cobas TaqScreen MPX test (Roche Molecular Systems, Branchburg, NJ) in 2011. NAT-yield cases (NAT positive, antibody negative), however, have been rare at CBS, with approximately one HIV case per 7 million donations and one HCV case in 3 million donations. HIV antibody–positive donations are also rare with two to five positive donations per year and estimated incidence of 0.48 per 100,000 donations. However, we have recently had two cases in donors who tested negative on Cobas TaqScreen MPX test, but confirmed HIV-1 antibody positive. Donor 1 was a male donor who on further questioning admitted to being a known HIV case, on treatment and viral load undetectable, who came to donate to confirm test results from a diagnostic laboratory. Donor 2 was a female blood donor whose last donation was in 2007. She tested HIV-1/2 antibody repeat reactive (Abbott PRISM HIV O Plus, Abbott Diagnostics, Wiesbaden, Germany) and Cobas TaqScreen MPX negative (all markers). The GS HIV-1 Western blot (Bio-Rad Laboratories, Redmond, WA) was positive. The donor was interviewed and follow-up testing was performed by CBS, two Canadian Public Health Laboratories (using assays with a different primer and probe binding site from that used by Roche; Table 1) and Roche Diagnostics. When interviewed, the second donor revealed at least two possible sources of HIV infection—male sexual contacts. One occurred in 2010 (the donor was reported to have tested negative for HIV by a diagnostic testing lab, following this contact) and a more recent contact in the few months before donating, who had been subsequently implicated in several other cases of heterosexual HIV transmission. A lookback performed on the previous (2007) donation (as per CBS standard operating procedures) was negative. Genotyping and susceptibility testing was performed on the follow-up sample from Donor 2, at the British Columbia Center for Excellence in HIV/AIDS. The virus was HIV-1, Subtype B, with mutations found in Positions 41, 210, and 215 in the reverse transcriptase gene segment, with a predicted reduced response to stavudine and tenofovir. Follow-up testing on the original donation sample performed by Roche Diagnostics, using Cobas TaqScreen MPX, confirmed these findings. The mutations in the long terminal repeat sequence resulted in mismatches to the upstream primer and probe, compromising binding in regions of the COBAS TaqScreen MPX test, resulting in a “target not detected” result. A risk estimate was performed by CBS, to calculate the risk of infection with this mutation of the virus not detected by the single primer set in the Cobas TaqScreen MPX test and in the Cobas TaqScreen MPX test (Version 2.0, Roche Molecular Systems; now in use at CBS) in the window period of the antibody assay. The risk was found to be extremely low (approx. 1:203 million donations), based on the presumed prevalence of this mutation (0.017 per 100,000 donations), the incidence of HIV in CBS blood donors (0.48 per 100,000 donations), and the window period of the antibody assay (22 days rather than the 9.5 days for NAT). The risk was considered to be tolerable. However, given the high mutability of HIV, and increasing numbers of HIVinfected individuals now on antiretroviral treatment, it is possible that an HIV-infected donor in the antibody window period could evade detection and cause transfusion transmission of HIV. This has been previously reported in Europe. In Germany, five HIV-infected window period blood donors escaped detection by NAT assays, resulting in two cases of HIV transfusion transmission. In Italy, HIV RNA was undetectable in a repeat blood donor who had recently seroconverted. This was also described in a study of a group of 553 HIV patients (3.5% with absent or underestimates of viral load). In both reports, a variety of CE-marked assays were used. The Paul Ehrlich Institut subsequently requested that blood operators implement measures to address this risk, including the use of dual target NAT assays. Roche Diagnostics currently has a CE-marked MPX Version 3.0 assay which has a dual primer set. The assay is currently undergoing review by Health Canada for blood donor screening in Canada. These cases provide clear evidence of the presence of low or absent viral load, or viral variants, in the population which may evade detection by NAT assays and highlights the importance of both antibody testing and molecular surveillance of blood donors.

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.

The Prevalence of Hepatitis A in Children in British Columbia

BACKGROUND The risk of hepatitis A virus (HAV) infection during childhood is difficult to estimate without population serosurveys because HAV-related symptoms are often mild at this age. Few serosurveys have been conducted in Canada. The present study surveyed teenagers in two nonurban regions of British Columbia where the historical rate of reported HAV either exceeded (region A) or was less than (region B) the historical provincial rate. METHODS A point prevalence survey of salivary HAV-specific immunoglobulin G was conducted in high schools among grade 9 students in regions A and B. A questionnaire was used to gather sociodemographic data. The survey was extended to grade 1 and grade 5 students in community 1 of region B. Associations between risk factors and prior infection were evaluated by logistic regression. RESULTS Eight hundred eleven grade 9 students were tested. Antibody to HAV was detected in 4.7% of students in region A (95% CI 2.9% to 7.2%) and 9.6% of students in region B (95% CI 6.9% to 12.9%). The region B figure reflected HAV antibody prevalence rates of 19.5% in community 1 and 2.5% in the remainder of the region. Younger students in community 1 had low HAV antibody to HAV prevalence rates (3.9% for grade 1 and 3.1% for grade 5), and positive tests in this community were associated with a particular school, foreign travel and brief residence. The risk factors for HAV infection in grade 9 students were not determined. CONCLUSIONS Children in nonurban areas of British Columbia are generally at low risk of HAV infection during the first decade of life regardless of the reported population rates, thereby permitting the consideration of school-based HAV immunization programs.

Epidemiology, antibiotic susceptibility, and serotype distribution of Streptococcus pneumoniae associated with invasive pneumococcal disease in British Columbia - A call to strengthen public health pneumococcal immunization programs

BACKGROUND This study examined the epidemiology, antibiotic susceptibility and serotype distribution of Streptococcus pneumoniae associated with invasive pneumococcal disease (IPD) in British Columbia. METHODS Six hospitals and one private laboratory network participated in a prospective, sentinel laboratory based surveillance study of IPD, between October 1999 and October 2000. At each site, S pneumoniae isolates were collected and epidemiological data were gathered using a structured questionnaire, for all cases of IPD meeting the study case definition. Isolates were serotyped and tested for antimicrobial susceptibility. Bivariate associations were analyzed and multivariate logistic regression was used to identify independent risk factors associated with hospitalization or death. RESULTS One hundred three reports and isolates were collected. Seventy-nine per cent of cases were community-acquired, 64% required hospitalization and 5% died. Cases with one or more assessed risk factor for IPD and of female sex were independent variables associated with hospitalization or death. One-third of isolates had reduced penicillin susceptibility and 96% of these represented serotypes contained in the 23-valent pneumococcal polysaccharide vaccine (PPV-23). Overall, 89% of serotypes identified are included in the PPV-23 vaccine and 88% of isolates from children under five years of age are found in the 7-valent pneumococcal conjugate vaccine (PCV-7). Forty-one per cent of cases qualified for publicly funded pneumococcal vaccine and 34% of eligible persons were vaccinated. CONCLUSIONS Overall, pneumococcal serotypes associated with IPD in this study closely matched serotypes included in PPV-23 products currently licensed in Canada. Most serotypes associated with IPD in children under five years of age are included in a recently licenced PCV-7. One third of isolates demonstrated reduced penicillin susceptibility, most involving serotypes included in PPV-23. Effective delivery of current public health immunization programs using PPV-23 and extending protection to infants and young children using the PCV-7 will prevent many cases of IPD.