Invasive bacterial diseases in northern Canada

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Published by: The Public Health Agency of Canada
Issue: Volume 47 No. 11, November 2021: Multisystem Inflammatory Syndrome in Children
Date published: November 2021
ISSN: 1481-8531

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All ICS regions had implemented the PCV13 vaccine schedule by January 1, 2011. Thirty-four cases that occurred after PCV13 implementation were age-appropriately vaccinated with at least one dose and serotyped. Individuals were age-appropriately vaccinated based on the minimum three-dose national recommendation. Of these 34 cases, three cases (9%) had vaccine-breakthrough disease. Breakthrough disease occurs if the serotype of the case is any of the serotypes covered by the vaccine administered. Two of these cases were serotype 19A and one was serotype 3. Of the 55 PPV23-vaccinated and serotyped cases, 46 cases (84%) had vaccine-breakthrough disease.

Of the 670 cases with information on clinical manifestation, bacteremia (n=577; 86.1%) and pneumonia (n=442; 66.0%) were the most commonly reported manifestations. Of the 692 IPD cases, 585 (85%) were hospitalized.

Of the 649 cases with information on fatality, 59 were fatal (9.1%).The majority of the fatal cases were 60 years and older (n=24; 41%), followed by those aged 40 to 59 years (n=20; 34%). Individuals in these two age groups had significantly higher risk of fatality than those in younger age groups (case fatality ratio [CFR] =14.2% vs. 4.4%; p<0.0001). The CFR did not vary between Indigenous and non-Indigenous people (9.5% vs. 6.1%; p=0.31). Of the 53 fatal cases with serotype information, 45% were PPV23-specific serotypes not covered by PCV13. The top six reported serotypes were 20, 10A, 15C, 22F, 15A and 3.
When fatality and hospitalization rates were compared for males and females, hospitalization was significantly higher for males (Table 1).
Antimicrobial susceptibility was examined for the IPD isolates with available data (Table 3).

Invasive group A streptococcal disease

The incidence rate (β=0.08; p<0.0001) of iGAS (per 100,000 population) increased significantly from 2000 to 2018. The age-standardized incidence rates for males (16.07; CI: 13.65–18.84) and females (11.83; CI: 9.58–14.52) did not differ significantly. The incidence rate (per 100,000 population) was highest for infants younger than one year old (51.25; CI: 34.90–75.27) and adults 60 years and older (36.64; CI: 30.00–44.75). The difference in the average annual incidence rates between those of Indigenous and non-Indigenous origin was significant in northern regions (Table 1). The age-standardized incidence rate of iGAS in northern regions was 3.2 times higher than the rest of Canada (Table 2).

Of the 311 iGAS cases, 249 were serotyped. The most common emm types were emm1 with 28 cases (11.2%), emm83 with 17 cases (6.8%), emm3 with 15 cases (6.0%) and emm11 and emm59 with 14 cases each (5.6%) (Figure 3). The predominant emm type varied across the years, and while emm1 was circulating most years, it was not always the most common strain in a given year. The most common strain in 2017 and 2018 was emm11.

Of the 307 cases with information on clinical manifestation, bacteremia (n=196; 63.8%) and cellulitis (n=96; 31.3%) were the most commonly reported manifestations, and 273 (88.9%) cases were hospitalized. Of the 296 cases with outcome information, 30 deaths (CFR: 10%) were reported. When fatality and hospitalization rates were compared for males and females, hospitalization was significantly higher for males (Table 1). The emm types with the highest fatality ratios were emm87 (50.0%) and emm2 (50.0%), followed by emm3 (33.3%) and emm75 (33.3%).

Antimicrobial susceptibility was examined for the iGAS isolates with available data (Table 3).

Invasive Haemophilus influenzae disease

There was no significant change in the (β=0.02; p=0.06) incidence rate of Hi (per 100,000 population) from 2000 to 2018. The age-standardized incidence rates for males (7.84; CI: 6.44–9.54) and females (6.85; CI: 5.44–8.63) did not differ significantly. The incidence rate (per 100,000 population) was highest among infants younger than one year old (195.15; CI: 160.29–237.59), children one to four years old (39.90; CI: 23.05–49.67) and adults 60 years and older (9.54; CI: 6.45–14.12). The difference in the average annual incidence rates between those of Indigenous and non-Indigenous origin was significant in northern regions (Table 1).

Hi serotype a (Hia) accounted for 60.5% of cases (n=156), non-typeable strains accounted for 17.8% (n=46), Hib accounted for 11.2% (n=29), serotype f accounted for 4.7% (n=12), serotype c and d accounted for 1.6% each (n=4), serotype e accounted for 0.4% (n=1) and 2.7% (n=6) had unknown serotype (Figure 4). Rates of Hia increased significantly from 2000 to 2018 (β=0.04; p=0.01), and 69.2% (n=108) of Hia cases were in children up to two years old. The age-standardized incidence rate of Hib in northern regions was 8.8 times higher than the rest of Canada (Table 2).

There were no significant changes in Hib rates from 2000 to 2018 (β=−0.01; p=0.7). Of the 29 Hib cases, three were adults and 26 children aged three years and younger. Of the 29 Hib cases, 14 (48%) were age-appropriately vaccinated, 10 (35%) were either unvaccinated or not up-to-date with their vaccinations, three (10%) were age ineligible for vaccination and two (7%) had unknown vaccine history.

Of the 246 cases with information on clinical manifestation, bacteremia (n=201; 81.7%) and pneumonia (n=87; 35.4%) were the most commonly reported manifestations. Of the 258 cases of Hi, 222 (86.0%) were hospitalized. Of the 226 cases with outcome information, 19 deaths (8.4%) were reported. Of these 19 cases, 11 were serotype a, five were non-typeable, two were serotype f and one was serotype b.

No significant difference was observed in the hospitalization and fatality rates of males and females (Table 1).

Invasive meningococcal disease

There was no significant change in the incidence rate of IMD (per 100,000 population) from 2000 to 2018 (β=0.03; p=0.3). The incidence rate (per 100,000 population) was the highest for infants younger than one year old (29.57; CI: 17.83–49.04) and children one to four years old (3.99; CI: 2.00–7.98).

Of the 31 cases of IMD, 16 cases (52%) were serogroup B, seven (23%) were serogroup W, four (13%) were serogroup C, one (3%) was serogroup Y and three (10%) were of unknown serogroup (Figure 5). The seven serogroup W cases all occurred between 2012 to 2018, constituting 47% of all IMD cases during that period. No serogroup W cases were reported prior to 2012.

The median age of the serogroup B cases was younger than one year, with a range of 0–30 years; the median age of the serogroup W cases was younger than one year, with a range of 0–28 years; and the median age of the serogroup C cases was 29.5 years, with a range of 0–56 years.

The difference in the average annual incidence rates between those of Indigenous and non-Indigenous origin was not significant (Table 1). Of the 30 cases with information on clinical manifestation, meningitis (n=21; 70%) and bacteremia (n=13; 43%) were most commonly reported and 90% were hospitalized. Of the 30 cases with fatality information, four deaths (CFR: 13%) were reported.

No significant difference was observed in the hospitalization and fatality rates of males and females (Table 1).

Invasive group B streptococcal disease

There was no significant change in the incidence rate of GBS from 2000 to 2018 (β=−0.01; p=0.6). The incidence rate (per 100,000 population) was highest for infants younger than one year (46.16; CI: 29.09–73.26) and adults 60 years and older (3.97; CI: 2.07–7.64). The difference in the average annual incidence rates between those of Indigenous and non-Indigenous origin was not significant (Table 1).

Of the 44 GBS cases, 16 cases (36%) were neonatal and 28 cases (64%) were non-neonatal. Of the 16 neonatal cases, 10 were early onset disease, five were late onset disease and one was unknown. Of the seven neonatal cases with serotype information, four cases were serotype III and the remaining three were serotype Ia, Ib and V. Of the 15 neonatal cases with information on clinical manifestation, bacteremia (n=10) and meningitis (n=6) were most commonly reported.

Of the 28 non-neonatal cases, the median age was 55.5 years (range 0–88 years). Of the 25 non-neonatal cases with serotype information, 6 (24%) were serotypes III and V each, three (12%) were serotypes Ia, Ib and VI each, two (8%) were serotype IV, and one was serotype II and one serotype VI (4% each). Of the 27 non-neonatal cases with information on clinical manifestation, bacteremia (n=21; 78%), septic arthritis (n=6, 22%) and cellulitis (n=5, 19%) were most commonly reported. Of all the non-neonatal cases, 93% were hospitalized; no deaths were reported.

No significant difference was observed in the hospitalization and fatality rates between males and females (Table 1).

Discussion

In this report, we describe the epidemiology of invasive bacterial diseases in northern Canada from 1999 to 2018 and compared the incidence rates there to those in the rest of Canada. The rates of most of the invasive disease remained stable over time with the exception of IPD, which trended down, and iGAS, which trended up over time. The incidence of IPD, iGAS and Hib were 2.8, 3.2 and 8.8 times higher, respectively, in northern Canada than in the rest of the country. The average annual incidence rates for IPD, iGAS and Hi in northern Canada were significantly higher for those who identified as Indigenous than those of non-Indigenous origin. The highest incidence rates were among the very young and older people.

Similar to the Alaskan ICS population (personal communication, T. Zulz, Jan 19, 2021), in northern Canada, IPD presented the highest burden of disease and accounted for over half of the total reported cases during the study period. The incidence of iGAS in northern regions has been increasing, a trend that has also been observed nationally, where the incidence rate has increased three-fold from 2000 to 2018^{Footnote 34}, with outbreaks in the community, military bases and in shelters^{Footnote 35Footnote 36Footnote 37Footnote 38}. Hia accounted for over 60% of cases and has been increasing significantly over the years. There is also a high prevalence of Hia in the Alaskan population (personal communication, T. Zulz, Jan 19, 2021). According to data collected from the US Active Bacterial Core surveillance sites, between 2002–2008 and 2009–2015, the prevalence of Hia disease increased by 13% annually with an overall increase of 148%^{Footnote 39}.

The burden of disease for IMD and GBS is much lower than the other three diseases, and IMD and GBS rates did not significantly change during the study period. The results also indicate that there was no statistical difference between the age-standardized incidence rates of IMD for the rest of Canada and northern Canada.

The rates of IPD have significantly decreased over the years due to a significant decrease in PCV7 and PCV10-specific vaccine serotypes, indicating that the conjugate vaccine programs have been successful at reducing the circulation of the serotypes these vaccines protect against. There were no significant decreases of PCV13-specific serotypes over the years. Further study is required to monitor the impact of the PCV13 vaccine versus the PCV10 vaccine, especially following the recent switch from the PCV13 vaccine schedule to a mixed PCV10 and PCV13 vaccine schedule in the Québec regions.

Non-vaccine serotypes have significantly increased following the introduction of the conjugate vaccine programs. PPV23-specific serotypes have also increased and the high percentage of breakthrough disease indicates that the PPV23 vaccine is not as effective at preventing disease in the 65-year-and-older ICS population compared to the conjugate vaccines in the younger ICS population.

Rates of Hib have not significantly changed in northern Canada during this study period. No IMD serogroup C cases have been reported since 2010 and this may be due to the implementation of the Men-C-C vaccine in routine childhood vaccine programs by the mid-2000s^{Footnote 40}. Within the last seven years, serogroup B and W have been reported exclusively and the highest burden has been in infants younger than one year.

Strengths and limitations

The ICS program is an important source of epidemiological and laboratory-linked information. It is the only enhanced invasive bacterial disease surveillance system that provides information on ethnicity in Canada, which means that it can be used to monitor the epidemiology of invasive bacterial diseases among the Indigenous peoples of northern Canada.

ICS is a passive surveillance system and some cases may be missed. In some communities, antibiotics may have been started prior to the collection of cultures. Results are unstable due to the small number of cases and small population sizes; therefore, caution should be used when interpreting the results. Because of incomplete reporting of clinical manifestation, vaccine history and underlying conditions and risk factors, these results may be under or overestimated. In addition, not all cases had further serotyping done.

Conclusion

The burden of invasive bacterial diseases is higher in the northern ICS population than the rest of Canada, especially in the Indigenous population. We have limited health information for the large Indigenous population in northern Canada, but existing health disparities need to be monitored and addressed. Ongoing surveillance is needed to continue monitoring disease trends, support prevention and control strategies, and inform immunization recommendations.

Authors' statement

• GH — Methodology, software, formal analysis, investigation, data curation, writing-original draft, writing–review and editing, visualization
• IM — Methodology, formal analysis, writing–original draft, writing–review and editing
• RST — Methodology, formal analysis, writing–original draft, writing–review and editing
• WHD — Methodology, formal analysis, writing–original draft, writing–review and editing
• GJT — Methodology, formal analysis, writing–original draft, writing–review and editing
• YAL — Methodology, formal analysis, writing–review, editing and project administration
• CD — Conceptualization, writing–review and editing
• FR-D — Methodology and writing–review and editing
• SGS — Conceptualization, methodology, writing–review and editing, project administration

Competing interests

None.

Acknowledgements

We would like to thank all members of the Canadian International Circumpolar Surveillance Invasive Bacterial Diseases Working Group for their invaluable contribution to the International Circumpolar Surveillance.

Funding

Canada's participation in the International Circumpolar surveillance was paid for by the Public Health Agency of Canada.

This work is licensed under a Creative Commons Attribution 4.0 International License