Canada Communicable Disease Report

 

Volume: 34S2
March 2008

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Final Report of Outcomes from the National Consensus Conference for Vaccine-Preventable Diseases in Canada

June 2005

Disease Summaries

Invasive pneumococcal disease

Background

The purpose of this session was to update goals, recommendations and targets for the reduction of invasive pneumococcal disease (IPD) in Canada, based on a review of current evidence and the goals established at the 1998 Canadian Consensus Conference on Preventing Pneumococcal Disease. Below are highlights of presentations on IPD immunization and surveillance in Canada and the US.

Immunization in Alberta:

(Dr. James Kellner)

Following the product licensure for infants in mid-2001, Prevnar®, or heptavalent pneumococcal conjugate vaccine (Pneu-C-7) was provided to high-risk and Aboriginal children in Alberta. The Pneu-C-7 program joined an enhanced program for polyvalent pneumococcal vaccine or 23-valent vaccine (Pneu-P-23), which was introduced in 1998 for long-term care facility residents, adults > 65 years of age and high-risk persons > 5 years of age.

Uptake of Pneu-C-7, administered in three doses, approached 88% in children 2 years of age in Calgary and 92% in 12 month-olds in Edmonton. Uptake of Pneu-P-23 in adults ≥ 65 years of age, while below target, increased from 41% to 55% between 1999 and 2003. Following Pneu-C-7 licensure in Alberta, a 93% decline in vaccine serotype cases was observed. Incidence of invasive streptococcal pneumococcal (lSP) in 0 to 23 month-olds dropped from the 1998-2001 average of 53.0 cases per 100,000 to 3.9 cases per 100,000 in 2004, with significant declines observed across all serotypes. During the same period, a 67% decrease in Pneu-C-7 serotype cases was also observed in adults ≥ 65 years of age; a decline which began with introduction of Pneu-P-23 programs. This experience shows that Pneu-C-7 is effective in preventing IPD and suggests evidence of herd immunity in children and adults > 65 years of age.

Immunization in Canada:

(Christine Navarro, MSc)

The following summary of statistics of pneumococcal immunization programs in Canada was provided:

  • As of July 2005, 12 of 13 jurisdictions in Canada will have implemented universal infant immunization programs. Still, the National Immunization Coverage Survey (NICS) revealed that, from 2002 to 2004, following the introduction of programs in Alberta, British Columbia and Nunavut, the coverage rate in the 2-year-old cohort had increased only slightly from 11% to 13%. There is speculation that the increase may have been minimized due to errors in reporting by parents, sampling errors, and/or incomplete program rollout at the time of the survey.
  • A 1999 cross-sectional survey of provincial long-term care facilities showed an overall immunization rate of 71% among residents. However, immunizations were not routinely offered in 17% of facilities and overall coverage was low relative to influenza.
  • The 2001 NICS national telephone survey revealed low coverage in other groups, with immunization administered to 40% of non-institutionalized adults ≥ 65 years of age and 15% of high-risk persons 18 to 64 years of age.
  • Immunization coverage in provinces and territories has generally fallen short of targets for all age groups.
Immunization in the US:

(Dr. Pekka Nuorti, CDC)

In the US in 2003, 87% of children had received at least one dose of vaccine by 2 years of age, with about one-third receiving a booster dose by the same age. Immunization programmers were faced with unprecedented rapid uptake of the vaccine which resulted in vaccine shortages. However, post-Pneu-C-7 data show dramatic reductions (48% to 83% depending on age group) in IPD incidence in children < 5 years of age. Indirect effects (herd immunity) in children and infants outside the targeted age groups have also been observed, along with significant declines in IPD incidence in black and Alaskan native children, basically eliminating racial health disparities for IPD. A 63% drop in IPD cases caused by penicillin-resistant strains was observed. A substantial herd protection has been seen in adults, suggesting that an effective IPD prevention approach is to vaccinate children. This effect is unlikely to be due to immunization with Pneu-P-23. Finally, preliminary data from population-based studies point to the effectiveness of Pneu-C-7 in reducing rates of otitis media and all-cause clinical pneumonia in young children, as well as the need for tympanostomy tubes.

Pneumococcal replacement disease has been observed in non-target age groups after the introduction of Pneu-C-7; increases were found in 24 to 59 month-olds compared to baseline data and in the working-age HIV-AIDS population as compared to the non HIV-AIDS population. However, the absolute rates of replacement disease are low. Serotype 19A is emerging as a problem vaccine serotype, and serotypes 15 and 33-F as problematic non-vaccine serotypes, underscoring the importance of serotype analysis for IPD surveillance.

Surveillance in Canada:

(Dr. David Scheifele, BC Children's Hospital)

Serotype data from IMPACT between 1991-1998 showed an 86% correlation between isolates and vaccine serotypes in children 6 months to 5 years of age. Lower match rates were found in older children and Aboriginal children, with higher penicillin non-susceptibility also seen in the latter group. From 1998 to 2003, a modest decrease in serotype matches was seen in main target groups, with serotype matches in the Aboriginal population remaining low and penicillin non-susceptibility high by comparison. In all cases, match rates varied from year to year and between centres, impeding analysis. The possible role of clonal serotypes in match rate variation was acknowledged, as was the need for increased epidemiological study and standardized reporting across provinces and territories.

Surveillance in Canada and Alberta:

(Dr. Greg Tyrrell)

The National Centre for Streptococcus (NCS) has seen 58 different serotypes in Canada between 1998 and 2004, with Pneu-C-7 covering seven of the eight most common serotypes. Blood and cerebral spinal fluid account for 97% of submitted specimens, most of which come from Alberta. Within Alberta, children ≤ 2 years of age have shown the most dramatic decline in pneumococcal cases caused by serotypes covered by the Pneu-C-7 vaccine. A similar decline was observed in isolates from the rest of Canada for this age group although it was not as dramatic. In the elderly (> 65 years), both Pneu-C-7 and non-Pneu-C-7 isolates are common, with only a slight drop in the number of Pneu-C-7 isolates submitted over the same time period. The overall penicillin non-susceptible rate for both Pneu-C-7 and non-Pneu-C-7 serotypes submitted for this age group is about 11%, with a noted decrease in the number of penicillin non-susceptible Pneu-C-7 isolates.

Discussion

Taking into account the evidence presented, participants identified the following issues related to updating the IPD reduction goals established at the 1998 Consensus Conference. The discussion guide used by participants is attached in Appendix B.

Immunization coverage: It was suggested that the original target of 40% for all vaccine-eligible groups should be revised upward, given the post-Pneu-C-7 declines in observed incidence in infants, even though immunization coverage targets for IPD prevention generally have not been met.

Hospitalization targets: It was recommended that hospitalization targets should not be set for IPD, given the difficulties in monitoring hospital data and the projected decline in hospitalization rates associated with the attainment of disease reduction targets.

High-risk groups: It was recommended that disease reduction targets should follow the attainment of immunization coverage targets, however should not be set for high-risk groups due to a lack of surveillance data.

Serotyping: To establish disease reduction targets for IPD, it is important to be able to monitor the serotype of the causative strain to accurately determine the incidence of vaccine-preventable cases of IPD. This is particularly important with regard to replacement disease. Therefore, it was agreed that a recommendation be made to flag the need for serotype surveillance or to set a target for serotyping IPD isolates (e.g., all isolates, a constant percentage of isolates, all isolates from children < 2 years of age).

Setting goals and recommendations

Participants revisited the disease reduction goals and targets proposed at the 1998 Consensus Conference, and came to the following recommended updates and comments.

Goal

Reduce illness and death due to pneumococcal disease through immunization.

Rationale: The 1998 overarching goal to "reduce the incidence/impact of pneumonia disease by immunization across all ages" should be revised to focus on illness and death.

Disease incidence

Recommendation 1

Achieve a sustained reduction of 80% in the incidence of IPD in children < 2 years of age compared with pre-conjugate vaccine incidence by 2010.

Rationale: Given the experience in the US, an 80% reduction in all serotype disease relative to pre-vaccine incidence rates should be attainable in children < 2 years of age. Spin-off benefits in other age groups are also anticipated. A target date of 2010 reflects the current state of surveillance in Canada and allows for the extension of government interest should targets be attained sooner than planned.

Recommendation 2

Achieve a sustained reduction of 40% in the incidence of IPD in adults ≥ 65 years of age compared with 1998 incidence by 2010.

Rationale: The original disease reduction target of 40% in this age group is realistic based on the evidence that shows a 20% reduction can be achieved with Pneu-C-7 coverage and the balance with existing polysaccharide vaccines. Further evidence demonstrated reductions in IPD incidence in this age group of 25% in Calgary between 1998 and 2004 and 31% in the US between 1998 and 2003.

Issues: The role of Pneu-P-23 in the attainment of disease reduction targets was debated. It was generally agreed that the impact of the polysaccharide vaccine is likely modest, with uptake and effectiveness cited as issues. Questions regarding the value of continuing with Pneu-P-23 for high-risk groups and the elderly gave rise to the need for program reevaluation.

Immunization coverage

Recommendation 3

Achieve and maintain age-appropriate immunization coverage with pneumococcal conjugate vaccine in 90% of children by their 2nd birthday by 2008.

Rationale: The target of 90% coverage by the end of 2008, a reduction of 5% from the previously proposed national target(6) reflects the fact that all provinces and territories (exception Northwest Territories) have initiated or are in the process of initiating immunization programs; Ontario and Quebec have established coverage targets of 97% and 90% respectively. With respect to programming issues, Pneu-C-7 is administered with DTaP and should approach the 95% infant coverage target established for pertussis.

Issues: The original 95% coverage target was discussed, as this has yet to be achieved with existing infant immunization programs (e.g., in Alberta and US programs, 88% and 67% of children, respectively, received three doses by their 2nd birthday). In contrast, it was noted that Pneu-C-7 is administered with DTaP and therefore should approach the 95% infant coverage target established for pertussis. The ability to achieve national coverage targets is negatively influenced by the varied schedules and delivery programs among provinces and territories.

Recommendation 4

Achieve and maintain age-appropriate immunization coverage with a single dose of pneumococcal polysaccharide vaccine in 80% of adults ≥ 65 years of age by 2010.

Rationale: As seen with influenza, rapid increases in coverage can be achieved once a vaccine has gained acceptance. On this basis, a target of 80% is recommended despite the current 40% coverage rate for non-institutionalized adults ≥ 65 years of age. The extended timeframe acknowledges the potential for vaccine supply shortages.

Recommendation 5

Achieve and maintain age-appropriate immunization coverage with pneumococcal polysaccharide vaccine in 95% of residents of long-term care facilities by 2008.

Rationale: The recommended target is based on the current 80% coverage rate for residents of long-term care facilities, up from 71% in 1999, and the likelihood of continued incremental increases in coverage is consistent with the influenza example.

Other

Recommendation 6

Achieve a sustained reduction of 20% in mortality rates due to IPD in adults ≥ 65 years of age compared with 1998 baseline rates by 2010.

Rationale: Mortality rates are an important indicator, given the potential impact on society, cost to the health care systems and the significance of death as a disease outcome and performance driver in the medical system.

The proposed disease reduction target is achievable considering, a pre-vaccine mortality rate of 4.1 per 100,000 reported for this age group. However, the original recommendation should be revised to read "mortality rates" instead of "deaths".

Recommendation 7 (Statement)

All provinces and territories should continue to optimize their pneumococcal immunization programs for individuals at high risk for IPD as defined by NACI guidelines.

Rationale: A numeric target is not recommended for high-risk groups, as disease reduction and immunization coverage in these populations will become less of an issue the longer universal immunization programs are in place. However, a statement is appropriate, given the need to generate increased surveillance data and improve coverage across provincial/territorial programs targeting high risk groups. Further, rather than focus on persons with conditions which significantly increase the risk of IPD (e.g., asplenia, asthma), the statement should cover high-risk groups as defined by NACI guidelines.

Issues: Questions were raised about the focus on Pneu-C-7 despite the availability of Pneu-P-23. Consideration was given to lowering the age for universal Pneu-P-23 immunization to capture more high-risk persons; however, experience in the US suggests there is little to be gained by this strategy. In addition, issues arise related to re-immunization, duration of the vaccine effect, and shortage of vaccine supply.

Recommendation 8 (Statement)

Serotype determination should be made on a representative sample of invasive Streptococcus pneumoniae isolates starting in 2006.

Rationale: Comprehensive population-based surveillance is needed to support accurate rate calculations and to monitor replacement disease. Recommended areas of focus include IPD, which has the greatest impact and can be readily diagnosed; serotyping of isolates; high-incidence and high-risk populations including ethnic groups. The working group also supported the creation of a national network of linked provincial/territorial immunization registries to support comprehensive surveillance.

Issues: Consideration was given to limiting representative sample collection to serotypes responsible for severe outcomes; however, the decision was made to promote comprehensive surveillance and confirmation by serotyping all isolates.

Vote

Participants achieved consensus on the following recommendations for IPD reduction, with statements provided in lieu of targets for high-risk groups and surveillance. For all recommendations, it was agreed that the National Case Definition for IPD should apply. The impact of replacement strains on achieving disease reduction targets was also noted, however no offsetting increases in immunization coverage targets were proposed.

Table 3 - Invasive pneumococcal disease votes
Recommendations Agree Agree with reservations Disagree
Goal
Reduce illness and death due to pneumococcal disease through immunization. 97% 3% 0%
Disease reduction
Recommendation 1
Achieve a sustained reduction of 80% in the incidence of IPD in children < 2 years of age compared with pre conjugate vaccine incidence by 2010.
88% 10% 2%
Recommendation 2
Achieve a sustained reduction of 40% in the incidence of IPD in adults ≥ 65 years of age compared with 1998 incidence by 2010.
78% 22% 0%
Immunization coverage
Recommendation 3
Achieve and maintain age-appropriate immunization coverage with pneumococcal conjugate vaccine in 90% of children by their 2nd birthday by 2008.
76% 24% 0%
Recommendation 4
Achieve and maintain age-appropriate immunization coverage with a single dose of pneumococcal polysaccharide vaccine in 80% of adults ≥ 65 years of age by 2010.
78% 22% 0%
Recommendation 5
Achieve and maintain age-appropriate immunization coverage with pneumococcal polysaccharide vaccine in 95% of residents of long-term care facilities by 2008.
79% 21% 0%
Other
Recommendation 6
Achieve a sustained reduction of 20% in mortality rates due to IPD in adults ≥ 65 years of age compared with 1998 baseline rates by 2010.
69% 27% 3%
Recommendation 7 (Statement)
All province/territories should continue to optimize their pneumococcal immunization programs for individuals at high risk for IPD as defined by NACI guidelines.
81% 12% 7%
Recommendation 8 (Statement)
Serotype determination should be made on a representative sample of invasive Streptococcus pneumoniae isolates starting in 2006.
84% 9% 7%

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