Short-Read Whole-Genome Sequencing for Laboratory-Based Surveillance of Bordetella pertussis.

Bordetella pertussis is a Gram-negative bacterium that causes respiratory infections in humans. Ongoing molecular surveillance of B. pertussis acellular vaccine (aP) antigens is critical for understanding the interaction between evolutionary pressures, disease pathogenesis, and vaccine effectiveness. Methods currently used to characterize aP components are relatively labor-intensive and low throughput. To address this challenge, we sought to derive aP antigen genotypes from minimally processed short-read whole-genome sequencing data generated from 40 clinical B. pertussis isolates and analyzed using the SRST2 bioinformatic package. SRST2 was able to identify aP antigen genotypes for all antigens with the exception of pertactin, possibly due to low read coverage in GC-rich low-complexity regions of variation. Two main genotypes were observed in addition to a singular third genotype that contained an 84-bp deletion that was identified by SRST2 despite the issues in allele calling. This method has the potential to generate large pools of B. pertussis molecular data that can be linked to clinical and epidemiological information to facilitate research of vaccine effectiveness and disease severity in the context of emerging vaccine antigen-deficient strains.

Rubella immunity among prenatal women in Ontario, 2006-2010.

BACKGROUND: Countries of the Americas have been working towards rubella elimination since 2003 and endemic rubella virus transmission appears to have been interrupted since 2009. To contribute towards monitoring of rubella elimination, we assessed rubella seroprevalence among prenatal screening tests performed in Ontario. METHODS: Specimens received for prenatal rubella serologic testing at the Public Health Ontario Laboratory, the provincial reference laboratory, between 2006 and 2010 were analyzed. A patient-based dataset was created using all tests occurring among 15-49 year-old females, where prenatal screening was indicated. Multiple tests were assigned to the same patient on the basis of health card number, name and date of birth. Only unique tests performed at least nine months apart were included. SAS version 9.2 was used for analysis. RESULTS: Between 2006 and 2010, we identified 459,963 women who underwent 551,160 unique prenatal screening tests for rubella. Of these, 81.6%, 17.1% and 1.4% had one, two and three or more tests respectively. CONCLUSION: Rubella susceptibility among prenatal women in Ontario supports elimination goals as population immunity in this group is relatively high. Higher susceptibility among young women and women living in the north highlights an opportunity for greater focus on identification and immunization of susceptible women in these groups.

An assessment of mumps vaccine effectiveness by dose during an outbreak in Canada.

BACKGROUND: This investigation was done to assess vaccine effectiveness of one and two doses of the measles, mumps and rubella (MMR) vaccine during an outbreak of mumps in Ontario. The level of coverage required to reach herd immunity and interrupt community transmission of mumps was also estimated. METHODS: Information on confirmed cases of mumps was retrieved from Ontario's integrated Public Health Information System. Cases that occurred between Sept. 1, 2009, and June 10, 2010, were included. Selected health units supplied coverage data from the Ontario Immunization Record Information System. Vaccine effectiveness by dose was calculated using the screening method. The basic reproductive number (R(0)) represents the average number of new infections per case in a fully susceptible population, and R(0) values of between 4 and 10 were considered for varying levels of vaccine effectiveness. RESULTS: A total of 134 confirmed cases of mumps were identified. Information on receipt of MMR vaccine was available for 114 (85.1%) cases, of whom 63 (55.3%) reported having received only one dose of vaccine; 32 (28.1%) reported having received two doses. Vaccine effectiveness of one dose of the MMR vaccine ranged from 49.2% to 81.6%, whereas vaccine effectiveness of two doses ranged from 66.3% to 88.0%. If we assume vaccine effectiveness of 85% for two doses of the vaccine, vaccine coverage of 88.2% and 98.0% would be needed to interrupt community transmission of mumps if the corresponding reproductive values were four and six. INTERPRETATION: Our estimates of vaccine effectiveness of one and two doses of mumps-containing vaccine were consistent with the estimates that have been reported in other outbreaks. Outbreaks occurring in Ontario and elsewhere serve as a warning against complacency over vaccination programs.

Estimating background rates of Guillain-Barré Syndrome in Ontario in order to respond to safety concerns during pandemic H1N1/09 immunization campaign.

BACKGROUND: The province of Ontario, Canada initiated mass immunization clinics with adjuvanted pandemic H1N1 influenza vaccine in October 2009. Due to the scale of the campaign, temporal associations with Guillain-Barré syndrome (GBS) and vaccination were expected. The objectives of this analysis were to estimate the number of background GBS cases expected to occur in the projected vaccinated population and to estimate the number of additional GBS cases which would be expected if an association with vaccination existed. The number of influenza-associated GBS cases was also determined. METHODS: Baseline incidence rates of GBS were determined from published Canadian studies and applied to projected vaccine coverage data to estimate the expected number of GBS cases in the vaccinated population. Assuming an association with vaccine existed, the number of additional cases of GBS expected was determined by applying the rates observed during the 1976 Swine Flu and 1992/1994 seasonal influenza campaigns in the United States. The number of influenza-associated GBS cases expected to occur during the vaccination campaign was determined based on risk estimates of GBS after influenza infection and provincial influenza infection rates using a combination of laboratory-confirmed cases and data from a seroprevalence study. RESULTS: The overall provincial vaccine coverage was estimated to be between 32% and 38%. Assuming 38% coverage, between 6 and 13 background cases of GBS were expected within this projected vaccinated cohort (assuming 32% coverage yielded between 5-11 background cases). An additional 6 or 42 cases would be expected if an association between GBS and influenza vaccine was observed (assuming 32% coverage yielded 5 or 35 additional cases); while up to 31 influenza-associated GBS cases could be expected to occur. In comparison, during the same period, only 7 cases of GBS were reported among vaccinated persons. CONCLUSIONS: Our analyses do not suggest an increased number of GBS cases due to the vaccine. Awareness of expected rates of GBS is crucial when assessing adverse events following influenza immunization. Furthermore, since individuals with influenza infection are also at risk of developing GBS, they must be considered in such analyses, particularly if the vaccine campaign and disease are occurring concurrently.

The shifting epidemiology and serotype distribution of invasive pneumococcal disease in Ontario, Canada, 2007-2017.

BACKGROUND: Ontario, Canada introduced a publicly-funded 13-valent pneumococcal conjugate vaccine (PCV13) for infants in 2010, replacing the 10-valent (PCV10, 2009-2010) and the 7-valent (PCV7, 2005-2009) conjugate vaccine programs; a 23-valent pneumococcal polysaccharide vaccine (PPV23) has been available for older adults since 1996. We examined the epidemiology and serotype distribution of invasive pneumococcal disease (IPD) in Ontario in the context of provincial immunization programs. METHODS: We included confirmed IPD cases reported in Ontario between 2007 and 2017. We grouped serotypes according to Ontario's current immunization program (PCV13, PPV23, and non-vaccine-preventable) and calculated incidence rates (per 100,000 population) using population data. RESULTS: Between 2007 and 2017, annual incidence of IPD in Ontario ranged between 7.3 and 9.7/100,000 per year. Measures of illness severity were high throughout the period of surveillance. After PCV13 program implementation in 2010, incidence due to PCV13 serotypes decreased significantly across all age groups, with the greatest reductions in children <5 years and adults ≥65 years. Conversely, incidence due to PPV23 unique serotypes increased significantly between 2007 and 2017, with the greatest increases observed in adults 50-64 years (1.4 to 3.5/100,000) and ≥65 years (2.3 to 7.2/100,000). Similar increases were observed in incidence due to non-vaccine-preventable serotypes among all age groups, except infants <1 year. Within specific serotypes, incidence due to serotypes 3 (0.42 to 0.98/100,000) and 22F (0.31 to 0.72/100,000) increased significantly between 2007 and 2017, while incidence due to serotypes 19A and 7F decreased significantly during the PCV13 period (2010-2017). CONCLUSIONS: Eight years after PCV13 implementation in Ontario, our data suggest both direct and indirect effects on serotype-specific incidence in young children and older adults. However, overall provincial rates have remained unchanged, and IPD continues to be a severe burden on the population. The rising incidence of IPD due to PPV23 unique and non-vaccine-preventable serotypes, and the growing burden of serotypes 3 and 22F, require further study.

Trends in medical and nonmedical immunization exemptions to measles-containing vaccine in Ontario: an annual cross-sectional assessment of students from school years 2002/03 to 2012/13.

BACKGROUND: Under Ontario legislation, for select vaccine-preventable diseases nonimmunized or under-immunized students must undergo vaccination or provide a statement of exemption, or risk suspension from school. At the time of this assessment, these diseases included measles, mumps, rubella, diphtheria, tetanus and polio. METHODS: Exemptions data for the school years 2002/03 to 2012/13 were obtained from the Immunization Records Information System used in Ontario. Temporal trends were expressed for 7- and 17-year-old students by exemption classification (medical, prior immunity, religious or conscientious belief, total) at the provincial level, by school year and by birth cohort. Regional analysis was conducted for the 2012/13 school year. A temporal trend analysis of exemptions for measles-containing vaccines was performed by using a Poisson distribution with a 2-sided test (α = 5%). RESULTS: For both 7- and 17-year-old students, religious or conscientious exemptions for measles-containing vaccines significantly increased over the study period (p < 0.001 in both age groups), whereas medical exemptions decreased (p < 0.001 in both age groups). The trends were reproduced when examined by birth cohort. The percentage of Ontario students with any exemption classification (total exemptions) remained low (< 2.5%) during the study period, although considerable geographic variation was noted. INTERPRETATION: Ontario data suggest that nonmedical exemptions have increased during the last 11 years, consistent with trends reported elsewhere. The trend toward increasing religious or conscientious exemptions coupled with declining medical exemptions explains why total exemptions have remained stable or decreased at the provincial level. The prominent geographic variability in exemptions suggests that targeted interventions may be suitable for consideration.

Have changing pneumococcal vaccination programmes impacted disease in Ontario?

BACKGROUND: Publicly funded infant 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in Ontario, Canada in 2005 and was replaced by 10- and 13-valent vaccines (PCV10, PCV13) in October 2009 and November 2010, respectively. Among adults ≥ 65 years, a 23-valent polysaccharide vaccine (PPV23) has been universally available since 1996. In January 2012, PCV13 was approved for adults ≥ 50 years. This study examines the impact of publicly funded vaccination programmes on invasive pneumococcal disease (IPD). METHODS: Laboratory data from population-based surveillance for IPD conducted at the Toronto Invasive Bacterial Disease Network and from Public Health Ontario Laboratories between January 1, 2008 and December 31, 2010 were analyzed. RESULTS: Between 2008 and 2010 there were 3259 cases of IPD; overall incidence was 7.4/9.3/8.3 per 100,000 in 2008/9/10, respectively. Incidence increased significantly among adults 65+ years during the period; this group had the highest incidence (21.5-25.6/100,000). The second highest incidence in 2008 and 2009 was in infants <1 year, whereas in 2010 it was in children 1-4 years. Among children <5 years, 68% and 19% of serotypes were covered by PCV13 and PCV10, respectively, between 2008 and 2010. In 2009, 6 cases with the 3 additional PCV10 serotypes were reported in infants compared with 2 in 2010. Among persons eligible for PCV7 (born≥2004), there was a 77% decrease in the rate of IPD due to PCV7 serotypes between 2008 and 2010 and a 60% decrease in PCV7 serotypes among persons not vaccine-eligible (born<2004). There was a 15% difference in serotype coverage between PCV13 and the 23-valent polysaccharide vaccine in adults≥50 years. CONCLUSIONS: During Ontario's PCV7 programme, serotype-specific decreases in IPD were observed, suggesting vaccine programme success, including herd immunity. Our results also suggest some early impact among infants from PCV10 introduction. A substantial burden of disease was also observed among older adults.