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ARCHIVED - ENHANCED SURVEILLANCE OF INVASIVE MENINGOCOCCAL DISEASE IN CANADA: 1 JANUARY, 1999, THROUGH 31 DECEMBER, 2001

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Invasive meningococcal disease (IMD) has been a nationally reportable disease in Canada since 1924(1). The Immunization and Respiratory Infections Division, Centre for Infectious Disease Prevention and Control, has published enhanced IMD surveillance reports since 1995(2-4). This surveillance report provides information on IMD from 1 January, 1999, through 31 December, 2001.

Methods

The national case definition of IMD was revised throughout the period covered by this surveillance report. In 1999, the case definitions used for surveillance of IMD at the national level were as follows(5):

Confirmed case: clinically compatible symptoms with the identification of meningococcus (Neisseria meningitidis) or its antigen from any normally sterile site or skin lesion.

Clinical case: symptoms clinically compatible with purpura fulminans even if there is failure to identify an organism in the blood or cerebrospinal fluid (CSF) either by isolation or antigen detection.

As of 1 January, 2000, clinical cases of IMD were excluded from national reporting. As of this date, the case definition has been(6)

Confirmed case: invasive diseasea with laboratory confirmation of infection:

  • isolation of N. meningitidis from a normally sterile site (blood, CSF, joint, pleural or pericardial fluid) OR
  • demonstration of N. meningitidis antigen in CSF.

Provincial and territorial departments of health report non-nominal epidemiologic data to Health Canada on all IMD meeting the national case definition. Provincial and territorial public health and/or hospital laboratories send most N. meningitidis isolates to the National Microbiology Laboratory (NML) in Winnipeg for confirmation of serogroup and further bacteriologic studies (serotyping and subtyping for all isolates and multilocus enzyme electrophoresis for all serogroup C isolates). Probabilistic matching is conducted to link epidemiologic and laboratory data. Matching is done using the following variables: province, date of birth (or age), sex, onset date, and serogroup (when available). In 2001, three provinces (British Columbia, Alberta, and Quebec) provided case-by case data pre-linked to laboratory data. Data are entered into spreadsheets and analyzed using Epi Info version 6.04c.

Statistics Canada supplies denominator data(7). All incidence rates are per 100,000 population per year. Chi-square tests, t tests, or the non-parametric Kruskal-Wallis H test were used to test for associations between variables.

Health Canada does not have a systematic method of surveying IMD outbreaks in Canada. In order to describe the number of IMD outbreaks during this surveillance period, an e-mail survey was conducted in July 2002. The survey was sent to IMD representatives in all provinces and territories.

Results

Number of Cases

In 1999, the provinces and territories reported 205 cases of IMD to Health Canada; 196 (95.6%) met the confirmed case definition and nine (4.4%) met the clinical case definition. Of the 196 confirmed cases, 159 (81.1%) were successfully matched to laboratory data. The NML reported an additional nine cases that could not be matched to those reported by the provinces and territories (three from Quebec, two from Ontario and one from each of Manitoba, Saskatchewan, Alberta, and British Columbia). Therefore, the total number of cases considered during 1999 is 214.

In 2000 and 2001, 232 and 333 cases of IMD respectively were reported by the provinces and territories. Clinical cases were not reported. In 2000, 187 (80.6%) were successfully matched to laboratory data; in 2001, 269 (80.8%) were successfully matched. The NML reported an additional nine cases in 2000 and 17 cases in 2001 that could not be matched to those reported by the provinces and territories (in 2000, Alberta two, New Brunswick one, Ontario four, and Quebec two; in 2001, Alberta one, British Columbia two, Manitoba one, New Brunswick one, Ontario four, Quebec eight). Therefore, the total number of cases considered in 2000 is 241 and during 2001 is 350.

Tables 1 to 3 provide detailed incidence, case fatality, and serogroup data by age group.

Table 1. Incidence, case fatality and serogroup data for IMD by age group, Canada, 1999

Age group, years

< 1

1-4

5-9

10-14

15-19

20-24

25-64

65+

Age unknown

Total

# cases

38

36

13

10

31

16

52

16

2

214

Incidence rate per 100 000 population

11.26

2.42

0.63

0.49

1.50

0.78

0.31

0.42

N/A

0.70

# deaths

1

3

2

2

2

2

8

3

0

23

Case fatality ratio

2.60%

8.30%

15.40%

20.00%

6.50%

12.50%

15.40%

18.70%

N/A

10.70%

Mortality rate per 100 000 population

0.30

0.20

0.10

0.10

0.10

0.10

0.05

0.08

N/A

0.08

# serogroup B cases

31

16

2

3

8

8

21

1

2

92

# serogroup C cases

1

11

8

6

15

3

16

3

0

63

# serogroup Y cases

2

0

0

1

2

0

6

7

0

18

# cases with other serogroups (e.g. 29E, W135)

2

1

1

0

2

2

3

1

0

12

# cases with serogroup unknown

2

7

3

0

4

3

6

4

0

29


Table 2. Incidence, case fatality and serogroup data for IMD by age group, Canada, 2000

Age group, years

< 1

1-4

5-9

10-14

15-19

20-24

25-64

65+

Age unknown

Total

# cases

38

25

17

10

50

26

57

18

0

241

Incidence rate per 100 000 population

11.30

1.73

0.83

0.49

2.41

1.25

0.34

0.47

N/A

0.78

# deaths

4

1

2

1

3

1

7

2

0

21

Case fatality ratio

10.50%

4.00%

11.80%

10.00%

6.00%

3.80%

12.30%

11.10%

N/A

8.70%

Mortality rate per 100 000 population

1.19

0.07

0.10

0.05

0.14

0.05

0.04

0.05

N/A

0.07

# serogroup B cases

26

7

5

2

7

4

12

4

0

67

# serogroup C cases

5

12

9

5

31

15

24

5

0

106

# serogroup Y cases

2

1

1

1

3

1

9

7

0

25

# cases with other serogroups (e.g. 29E, W135)

1

0

0

0

2

2

2

1

0

8

# cases with serogroup unknown

4

5

2

2

7

4

10

1

0

35


Table 3. Incidence, case fatality and serogroup data for IMD by age group, Canada, 2001

Age group, years

< 1

1-4

5-9

10-14

15-19

20-24

25-64

65+

Age unknown

Total

# cases

30

33

22

32

77

31

92

33

0

350

Incidence rate per 100 000 population

9.21

2.35

1.08

1.54

3.69

1.46

0.54

0.84

N/A

1.13

# deaths

3

3

2

2

2

2

14

5

0

33

Case fatality ratio

10.00%

9.10%

9.10%

6.20%

2.60%

6.50%

15.20%

15.20%

N/A

9.40%

Mortality rate per 100 000 population

0.92

0.21

0.10

0.10

0.10

0.09

0.08

0.13

N/A

0.11

# serogroup B cases

19

12

3

3

20

8

12

8

0

85

# serogroup C cases

8

14

14

22

40

18

52

14

0

182

# serogroup Y cases

1

0

3

5

8

1

8

4

0

30

# cases with other serogroups (e.g. 29E, W135)

1

3

0

0

0

0

3

2

0

9

# cases with serogroup unknown

1

4

2

2

9

4

17

5

0

44


Incidence

The incidence rates of IMD in 1999, 2000, and 2001 were 0.70, 0.78, and 1.13 per 100 000 population respectively. Figure 1 shows the annual number of cases and incidence rates since 1986.


Figure 1. Number of cases and incidence rate of IMD in Canada, 1986-2001

Figure 1. Number of cases and incidence rate of IMD in Canada, 1986-2001


Figures 2 and 3 show the annual number of cases and rates by province and territory for 1999 to 2001. These rates may be unstable because of small numbers.


Figure 2. Number of cases of IMD by province/territory by year

Figure 2. Number of cases of IMD by province/territory by year


Figure 3. Incidence rate of IMD by province/territory by year

Figure 3. Incidence rate of IMD by province/territory by year



Sex

Females accounted for 50.9%, 54.5%, and 47.9% of IMD cases in 1999, 2000 and 2001 respectively.

Age Distribution

In 1999, the median age of IMD cases was 16 years (range 0-93), 25% of cases being <= 2 years of age. The highest incidence rates were seen among children: infants <= 1 year of age and children 1 to 4 years of age had rates of 11.26 and 2.42 cases per 100 000 population respectively. People 15 to 19 years of age had the third highest rate, of 1.50 cases per 100 000 population. Interestingly, age distribution varied by sex: the median age of females was 19 years and of males was 9 years (p= 0.002).

In 2000, the median age of IMD cases was 18 years (range 0-86), 25% of cases being < 4 years of age. The highest incidence rates were among infants and teenagers: infants <= 1 year of age had a rate of 11.3 and people 15 to 19 years of age had a rate of 2.41 cases per 100 000 population. Children 1 to 4 years of age had the third highest rate, of 1.73 cases per 100 000 population.

In 2001, the median age of IMD cases was 18 years (range 0-94), 25% of cases being <= 10 years of age. The highest incidence rates were seen among children: infants <= 1 year of age had a rate of 9.21 and people 15 to 19 years of age had a rate of 3.69 cases per 100 000 population. Children 1 to 4 years of age had the third highest rate, of 2.35 cases per 100 000 population. Age distribution did not vary by sex in 2000 and 2001.

Seasonal Distribution

As expected, IMD cases peaked in the winter months, from December to April. The lowest number of cases was seen in the summer months. Figure 4 shows the seasonal distribution of IMD cases.


Figure 4. Distribution of IMD cases by month, 1999-2001

Figure 4. Distribution of IMD cases by month, 1999-2001



Case Fatality and Mortality

IMD is associated with a relatively high case fatality. Case fatality ratios were 10.7%, 8.7%, and 9.4% in 1999, 2000, and 2001 respectively. The median age of fatal cases was 22, 19, and 35 years in 1999, 2000, and 2001 respectively. In 1999, people >= 65 years of age had the highest case fatality at 18.7%, whereas in 2000, adults aged 25 to 64 years had the highest fatality, at 12.3%. In 2001, both age groups - adults aged 25 to 64 years and those aged >= 65 years of age - had the highest case fatalities, at 15.2%.

Mortality rates for IMD were 0.08, 0.07, and 0.11 per 100 000 population in 1999, 2000, and 2001 respectively. However, in all years, infants < 1 year of age had the highest mortality rate, which ranged between 0.30 and 1.2 deaths per 100 000 population. The lowest mortality rate in all years occurred among adults aged 25 to 64 years, from 0.04 to 0.08 deaths per 100 000 population. Case-fatality and mortality rates are unstable because of small numbers.

Serogroups

In 1999, serogroup information was available for 90.2% (185/205) of confirmed cases. The serogroup distribution was as follows: 92 were serogroup B, 63 were serogroup C, 18 were serogroup Y, 11 were serogroup W135, and 1 was serogroup 29E. The median ages were statistically different for IMD cases caused by serogroups B, C and Y: the ages were 4, 17, and 56 years respectively (p< 0.0001). Serogroup C had the highest case-fatality ratio of 15.9%; serogroups B and Y had the lowest case-fatality ratios of 7.6% and 5.6% respectively.

In 2000, serogroup information was available for 85.5% (206/241) of cases. The serogroup distribution was as follows: 67 were serogroup B, 106 were serogroup C, 25 were serogroup Y, and 8 were serogroup W135. The median ages were statistically different for cases caused by serogroups B, C and Y: the ages were 5, 18, and 52 years respectively (p< 0.0001). Serogroup C had the highest case-fatality ratio of 9.3%; serogroup W135 had the lowest case-fatality with 0 deaths.

In 2001, serogroup information was available for 87.4% (306/350) of cases. The serogroup distribution was as follows: 85 were serogroup B, 182 were serogroup C, 30 were serogroup Y, and 9 were serogroup W135. The median ages were not statistically different for IMD cases caused by serogroups B, C and Y; the ages were 17, 19, and 17 years respectively (p= 0.20). Serogroups C and Y had the highest case-fatality ratios of 11.0% and 10.0% respectively; serogroup B had the lowest case-fatality ratio of 2.4%.

Figures 5 to 7 compare the serogroup distribution by year.


Figure 5. Serogroup distribution of IMD cases, 1999 (n = 185)*

Figure 5. Serogroup distribution of IMD cases, 1999 (n = 185)*

* excludes cases with unknown serogroups


Figure 6. Serogroup distribution of IMD cases, 2000 (n = 206)*

Figure 6. Serogroup distribution of IMD cases, 2000 (n = 206)*

* excludes cases with unknown serogroups


Figure 7. Serogroup distribution of IMD cases, 2001 (n = 306)*

Figure 7. Serogroup distribution of IMD cases, 2001 (n = 306)*

* excludes cases with unknown serogroups


Serotypes and Serosubtypes

In 1999, 39% (32/83) of serogroup B cases were non-serotypeable; 24% (20/83) were serotype 4 and 20% (17/83) were serotype 15. The most common serotype and subtype combinations for serogroup B cases were B:NT:P1. (19/83) and B:4:P1. (8/83). Of serogroup C cases, 68% (41/60) were serotype 2a, and 27% (16/60) were non-serotypeable. The most common combinations for serogroup C cases were C:2a:P1.2 (15/60) and C:2a:P1. (9/60). Of serogroup Y cases, 59% (10/17) were non-serotypeable, and 41% (7/17) were serotype 14. The most common Y combinations were Y:NT:P1.2,5 (5/17) and Y:14:P1. (4/17).

In 2000, 45% (29/64) of serogroup B cases were non-serotypeable; 31% (20/64) were serotype 4. The most common combinations were B:NT:P1.15 (7/64) and B:4.P1.14 (6/64). Of serogroup C cases, 88% (86/98) were serotype 2a; the remaining 12% (12/98) were non-serotypeable. The most common combinations were C:2a:P1.2,5 (33/98) and C:2a:P1.2 (32/98). Of serogroup Y cases, 70% (16/23) were non-serotypeable, 26% were serotype 14, and 4% were serotype 1. The most common Y combinations were Y:NT:P1.5 (9/23), Y:NT:P1.2,5 (5/23), and Y:14:P1.2,5 (4/23).

In 2001, 45% (35/78) of serogroup B cases were non-serotypeable; 23% (18/78) were serotype 4, 13% (10/78) were serotype 14, and 12% (9/78) were serotype 15. The most common B combinations were B:NT:P1. (11/78) and B:15:P1.7,16 (6/78). Of serogroup C cases, 87% (150/173) were serotype 2a, and 13% (22/173) were non-serotypeable. The most common combinations were C:2a:P1.2,(5) (73/182) and C:2a:P1.1,7 (42/182 ) Of serogroup Y cases, 31% (9/29) were serotype 14. The most common Y combination was Y:14:P1. (5/29).

Multilocus Enzyme Electorphoretic Typing

The NML conducts multilocus enzyme electrophoretic typing on serogroup C isolates received from the provinces and territories. In 1999, 91.7% (55/60) of serogroup C strains from IMD cases were found to belong to the hypervirulent clone of ET-37, 94.5% (52/55) of these being the ET-15 variant. Only three strains (5%) belonged to neither ET-15 nor other members of the ET-37 clonal complex; two strains (3.3%) did not have ET profile data. In 2000, 97.0% (96/99) of serogroup C strains were ET-37, 97.9% (94/96) of these being the ET-15 variant. Three strains (3.0%) were neither ET-15 nor ET-37. In 2001, 98.3% (170/173) of serogroup C isolates were ET-37, 96% (166/170) being the ET-15 variant. Only three strains (1.7%) were neither ET-15 nor ET-37.

Outbreaks

Twelve of the 13 provinces and territories (92%) responded to the e-mail survey. Survey results indicated that eight IMD outbreaks occurred in Canada between 1999 and 2001: one in Alberta, three in Ontario, two in Quebec, one in British Columbia and one in Manitoba. All were community outbreaks of serogroup C meningococcus.

The outbreak in Edmonton, Alberta, was the largest, affecting children and young adults and consisting of 61 IMD cases, including two deaths. It occurred between December 1999 and April 2001. Three mass vaccination campaigns, using polysaccharide quadrivalent meningococcal vaccine, were initiated and 87% of target individuals immunized (over 200 000 individuals vaccinated). The most common strains identified in this outbreak were characterized as C:2a:P1.2,(5)(8).

In Ontario, there were three IMD outbreaks between 1999 and 2001. The first occurred in February and March 1999 among elementary and high school students in Windsor Essex county; there were three cases, including one death. A mass immunization campaign was initiated using quadrivalent meningococcal vaccine and targeting day-care centres and elementary and high school students in a confined geographic area. Approximately 5000 doses of vaccine were distributed and an estimated 80% of targeted individuals immunized. The strain associated with this outbreak was C:2a:P1.2,5. A second outbreak occurred in London-Middlesex county between February and May 2001 among individuals 2 to 24 years of age. A total of six cases were identified, and no deaths occurred. A mass immunization campaign was initiated using quadrivalent and bivalent polysaccharide meningococcal vaccine for those aged 2 to 24 years of age (100 000 doses distributed) and MenC conjugate vaccine for children <= 2 years of age (10 000 doses distributed); an estimated 93% of targeted individuals were immunized. The strain associated with the London-Middlesex outbreak was C:2a:P1.1,7. The third IMD outbreak occurred in Toronto between May and August 2001 among men who have sex with men (MSM) in the 20 to 44 year age group. Six cases were identified, including two deaths. A mass immunization campaign was initiated that targeted all MSM in Toronto; 3850 doses of polysaccharide vaccine were distributed. The strain associated with the MSM outbreak was C:NT:P1.2(9).

In Quebec, two clusters were reported between 1999 and 2001. The first occurred in a secondary school in the Montérégie region (three cases) and the second in the general community in Quebec City (10 cases) in February and March 2001. Mass immunization programs targeting people 12 to 17 years of age in high incidence regions and using quadrivalent polysaccharide vaccines were implemented in March to May 2001; 50,000 doses were distributed. Additional IMD cases were observed in younger children in Quebec City, and so a second immunization campaign was initiated using MenC conjugate vaccine, targeting children 2 months to 11 years of age; 95,000 doses were distributed. A third mass immunization campaign was initiated in September 2001 as IMD cases continued to occur in other regions; this campaign used MenC conjugate vaccine exclusively and targeted all individuals in the province 2 months to 20 years of age. Approximately 81% of the targeted population were fully immunized (Dr. Philippe DeWals: personal communication, November 2003). The strain associated with these clusters was C:2a:P1.1,7.

In Abbotsford, British Columbia, an IMD outbreak affecting people 15 to 29 years of age occurred between December 2000 and July 2001; eight cases were identified, including two deaths. A mass immunization campaign (40 000 doses) was initiated with both polysaccharide quadrivalent vaccine (15 000 doses) and MenC conjugate vaccine (25 000 doses); an estimated 90% of targeted high school students and 70% of other targeted groups were immunized. The strain associated with the Abbotsford outbreak was C:2a:P1.5(10).

In Winnipeg, Manitoba, an IMD outbreak occurred among teenagers aged 13 to 19 years between January 2001 and June 2002; 12 cases were identified, none were fatal. A mass immunization campaign was initiated targeting everyone aged 13 to 19 years living in Winnipeg. Approximately 44 000 doses of polysaccharide quadrivalent vaccine were distributed and an estimated 83% of targeted individuals immunized.

Discussion

Polymerase Chain Reaction

Increasingly, polymerase chain reaction (PCR) technology is being used as an alternative laboratory method of detecting N. meningitidis when bacterial culture and antigen detection fail. PCR is not currently part of the national case definition for IMD. In 2001, an additional 16 IMD cases were detected by PCR (not included in this report), of which three (19%) were fatal. Health Canada is considering revising the national IMD case definition to include cases detected by PCR.

Serogroups

An interesting observation occurred in 2001, when the median ages of cases with serogroup B and serogroup Y disease (both serogroup B and Y had a median age of 17 years) were both statistically and epidemiologically different from those observed in 1999 (medians of 4 years for serogroup B and 56 years for serogroup Y) and 2000 (medians of 5 years for serogroup B and 52 years for serogroup Y). Future surveillance data will determine whether this is an anomaly or whether a true change in the age distribution of serogroups B and Y exists.

Further detailed antigenic characterization of serogroup Y meningococci have revealed that many of the non-serotypeable strains were found to belong to serotype 2c (which is not a common serotype in other serogroups of meningococci)(11). Using these results, the two most common serotypes found in serogroup Y strains between 1999 and 2001 were 2c and 14, and these serotypes were frequently associated with the serosubtype antigens P1.5 or P1.2,5.

Underreporting

The scope of underreporting is unknown. However, in 1999, 2000, and 2001, 4.2%, 3.7%, and 4.9% respectively of cases of invasive disease were reported by the NML and could not be matched to epidemiologic reports from the provinces/territories. The epidemiologic information on these cases was either taken from the laboratory requisition or is missing.

Limitations

Because of the instability of results based on small numbers, caution should be used when interpreting these results. Additionally, as the case definition changed during the interval covered in this report, caution should also be used when comparing the two periods.

Acknowledgements

We would like to thank our colleagues from the provincial and territorial ministries of health for providing epidemiologic data and the public health and hospital laboratories from across Canada for submitting isolates to the National Microbiology Laboratory for further studies. We would also like to thank François Collins and Jan Stoltz for their technical expertise in conducting laboratory testing of isolates submitted to the National Microbiology Laboratory.

References

  1. Health Canada. Notifiable diseases on-line. URL: <http://dsol-smed.phac-aspc.gc.ca/dsol-smed/ndis/index_e.html>.

  2. Whalen CM, Hockin JC, Ryan A et al. The changing epidemiology of invasive meningococcal disease in Canada, 1985 through 1992. Emergence of a virulent clone of Neisseria meningitidis. JAMA 1995;273(5):390-94.

  3. Deeks S, Kertesz D, Ryan A et al. Surveillance of invasive meningococcal disease in Canada, 1995-1996. CCDR 1997;23(16):121-25.

  4. Squires SG, Pelletier L, Mungai M et al. Invasive meningococcal disease in Canada, 1 January, 1997, to 31 December, 1998. CCDR 2000;26(21):177-82.

  5. Health and Welfare Canada. Canadian communicable disease surveillance system. Disease-specific case definitions and surveillance methods. CCWR 1991;17(S3):24.

  6. Health Canada. Case definitions for diseases under national surveillance. CCDR 2000;26S3:49.

  7. Statistics Canada. Population estimates, 1999 final post-censal, 2000-2001 revised post-censal. Ottawa: Demography Division, Statistics Canada.

  8. Tyrrell GJ, Chui L, Johnson M et al. and the Edmonton Meningococcal Study Group. Outbreak of Neisseria meningitidis in Edmonton, Alberta, Canada. Emerg Infect Dis 2002;8(5):519-21.

  9. Tsang RSW, Kiefer L, Law DKS et al. Outbreak of serogroup C meningococcal disease caused by a variant of Neisseria meningitidis serotype 2a ET-15 in a community of men who have sex with men. J Clin Microbiol 2003;41(9):4411-14.

  10. Patrick DM, Champagne S, Goh SH et al.Neisseria meningitidis carriage during an outbreak of serogroup C disease. Clin Infect Dis 2003;37:1183-88.

  11. Tsang RSW, Squires SG, Zollinger WD et al. Distribution of serogroups of Neisseria meningitidis and antigenic characterization of serogroup Y meningococci in Canada, January 1, 1999 to June 30, 2001. Can J Infect Dis 2002;13:391-39

Source: SG Squires, MSc, SL Deeks, MD, MHSc, Immunization and Respiratory Infections Division, Centre for Infectious Disease Prevention and Control, Health Canada, Ottawa, Ontario. RSW Tsang, MMedSc, PhD, CNS Infection Division, National Microbiology Laboratory, Winnipeg, Manitoba.


a Invasive meningococcal disease usually manifests itself as meningitis and/or septicemia, although other manifestations may be observed. Invasive disease may progress rapidly to purpura fulminans, shock, and death.


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