Canada Communicable Disease Report

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

June 2005

Disease Summaries

Pertussis

Background

The purpose of this session was to develop updated recommendations and targets for pertussis immunization in Canada, based on a review of current evidence and the recommendations and targets set at the 2002 Pertussis Consensus Conference. Below are highlights of presentations on pertussis surveillance, epidemiology and immunization.

Epidemiology:

(Drs. Scott Halperin and Shelley Deeks)

The incidence of pertussis in Canada has risen since the 1990s, with the highest incident rates occurring in infants < 1 year of age. Further, the disease is cyclical (every 4 to 5 years) and has undergone a shift in age distribution since 2000, with pre-adolescents (10 to 14 years) replacing preschool children as the age group with the second highest incidence rate. Increases in incidence may be artifact (e.g., due to increases in reporting, use of newer diagnostic methods such as polymerase chain reaction [PCR], changes in case definition) or real (e.g., due to low efficacy of whole-cell vaccines, decreases in coverage, waning immunity, changes in strains) or a combination of both.

Immunization:

(Dr. Shelley Deeks)

Pertussis vaccine was first introduced in Canada in 1943. From 1958-1996, a series of combined whole-cell pertussis vaccines were licensed and used throughout the country. Pertussis vaccines are most commonly given in combination with other immunizing agents such as in combination with inactivated polio (IPV) as a quadravalent (DTaP-IPV) or pentavalent and Haemophilus influenzae Type b (Hib) (DTaP-IPV-Hib) vaccine. Because of the frequency of local and systemic adverse events following immunization with a whole-cell pertussis containing vaccine, acelluar pertussis vaccines, previously used in Japan since the early 70's, were licensed for use in the mid 90's. The benefits of acellular vaccine are that it boasts fewer side-effects and higher efficacy than the whole-cell vaccine and is safe to use in adolescents and adults. Currently, NACI recommends that pertussis vaccines be given at 2, 4, 6, and 18 months, followed by a preschool vaccine at 4 to 6 years and a booster for adolescents (14 to 16 years). An adult booster is recommended for adults who have not been previously immunized with acellular pertussis vaccine. As of September 2004, all provinces/territories had implemented universal adolescent acellular pertussis programs with Tdap.

Age related controls: While disease elimination across the age spectrum is desirable, it is not likely achievable at this time given the high prevalence of pertussis in the population and the time-limited immunity afforded by immunization. As an alternative, age-related controls for infants, children, adolescents and adults, focusing on the following prevention gaps were recommended.

• Infants: Infants < 1 year of age have the highest morbidity and account for virtually all of the mortality among pertussis cases. Infants < 2 months of age are not being effectively protected (i.e. current immunization programs begin at 2 months of age). Questions for participants to consider include: 1) Would immunizing parents effectively decrease pertussis among infants 2) Would post-partum immunization produce protective levels quickly enough and 3) Would maternal immunization provide passive protection to infants in the first 2 months of life?
• Adolescents: Immunization coverage for adolescents will improve over time, given the recent implementation of adolescent immunization programs in all provinces and territories. Questions for participants to consider include: 1) Will adolescents who received all preschool doses with acellular need a Tdap booster 2) What is the duration of protection after the five-dose acellular preschool series 3) What is the duration of protection for the acellular adolescent pertussis vaccine and 4) What is the optimal time for a booster?
• Adults: Adult immunization is impeded by a lack of awareness among health care professionals regarding the importance of adult immunizations and generally held concerns about adult immunization and immunization during pregnancy. Suggested strategies include immunizing the entire adult population. (It was noted that no country has implemented a universal adult immunization program) or targeting adults who are in close contact with children. Questions for participants to consider include: 1) Is there an age-related burden of illness among adults 2) Are there special populations at higher risk of contracting pertussis 3) What is the appropriate interval for adult immunization and 4) What are the costs versus benefits of various strategies for adult immunization?

Immunization costs/benefits:

(Dr. Gaston De Serres)

Economic analyses in Ontario and Quebec suggest a high cost of pertussis immunization per case averted. However, had societal costs been considered in these studies (e.g., homecare costs, lost work days), the pertussis immunization cost-benefit ratio might have been slightly better.

Surveillance:

(Dr. Shelley Deeks)

Pertussis is a nationally notifiable disease and voluntary reporting to the national level occurs however, age-based data analysis is impeded by non standardized reporting practices (i.e. aggregate versus case-based). Surveillance activities are further challenged by problems relating to under-diagnosis of pertussis in adolescents and adults, assessment of immunization coverage in adults, the lack of a national network of immunization registries to collect data on immunization and disease status, and the impact of improvements in diagnostics or diagnosis on reported cases.

Laboratory diagnostics:

(Dr. Mark Peppler)

Goals for laboratory diagnostics put forward at the 2002 Pertussis Consensus Conference were reviewed. This includes: 1) PCR should be established as a gold standard for diagnosis within 3 years; 2) a system should be established for selective performance of culture strain typing and identification of new strains; 3) there should be support for the development of criteria for serologic diagnosis; 4) international reference sera and reference antigens should be available; and 5) an international consensus conference on diagnostic methods should be held.

In the absence of a national framework, initiatives have been undertaken in support of these goals on a random and voluntary basis. It was suggested that the 2002 goals for laboratory diagnostics be incorporated into the updated pertussis reduction goals, with the added recommendation that quality assurance programs be put in place.

Discussion

Taking into account the evidence presented, participants identified the following issues related to the development of updated recommendations and targets for pertussis control. The discussion guide used by participants is attached in Appendix B.

Laboratory diagnostics: It was concluded that laboratory issues had not been targeted for discussion and therefore should not be addressed as part of the recommendations arising from the 2005 Consensus Conference. However, given the importance of the issues identified, participants agreed to draft a statement to the CIC and Canadian Public Health Laboratory Network (CPHLN) recommending that laboratory diagnostics for pertussis be examined as soon as possible, and a national strategy developed.

Equity of coverage: Questions were raised regarding the relationship between socio-economic status, the incidence of pertussis and access to prevention and vaccine programs in Canada. The prospect of targeting activities to better reach populations with lower than average immunization coverage (e.g., First Nations) was raised. Participants agreed that a goal of all pertussis recommendations should be to provide equitable access across all age and socio-economic groups. Also noted was the importance of collecting more and improved (i.e. case by case versus aggregated) data on pertussis outbreaks, to assist in identifying and reaching high-need populations.

Hospitalization: It was agreed that increased immunization coverage should result in decreased hospitalizations, eliminating the need to set hospitalization reduction targets.

Defining goals: Participants determined that, while desirable, elimination of pertussis was not a realistic recommendation at this time. Rather, in all age categories, recommendations should focus on disease reduction. It was further agreed that relative targets, as opposed to proportional targets, would be appropriate for all pertussis recommendations, given current issues with diagnosis and surveillance.

Setting Goals and Recommendations

Based on the recommendations and targets outlined in the pertussis discussion guide (Appendix B), participants recommended the following goal and recommendations for pertussis control in Canada.

Goal (proposed):

Reduction of disease incidence through routine immunization and increased access to immunization in populations with low coverage.

Rationale: Disease elimination is not a realistic goal at this time. Awareness of adult immunizations must be increased as protection conferred by pertussis immunization is not life-long. Cost to benefit ratio of immunization remains high.

Disease incidence

Recommendation 1

Achieve a sustained reduction in the reported incidence of pertussis among persons 10 to 19 years of age to at least the levels present in persons 1 to 4 years of age by 2010.

Rationale: The 10 to 14 year of age group has the second highest rate of pertussis in Canada and therefore warrants targeting. The recommended goal is achievable given the introduction of universal adolescent immunization programs in all province/territories.

Recommendation 2

Reduce the reported incidence of pertussis in persons 30 to 39 years of age to the same levels as in persons 20 to 29 and 40 to 59 years of age by 2015.

Rationale: Elevated incidence rates exist among adults of parenting age (i.e. 30 to 39 years). Targeting this age group is expected to decrease incidence in adults overall, after which other subpopulations of adults can be targeted. Decreased incidence may occur in younger populations (i.e. offspring) as a result; however, adults should be immunized for their own sake. 2015 is a more realistic timeframe for achieving the proposed goal, although considerable reductions are expected by the end of 2010.

Issues: Concerns were expressed at the working group and plenary level about the appropriateness and necessity of targeting a subpopulation of adults, with some participants suggesting that the recommendation should target adults of all ages. Questions were also raised about the existence of a secondary rationale related to the protection of children, an approach which has not been validated as well as the feasibility of implementing the proposed recommendation at the provincial/territorial level.

Immunization coverage

Recommendation 3

Achieve and maintain age-appropriate immunization coverage with acellular pertussis vaccine in 95% of infants by 3 months of age (first dose) by 2010.

Rationale: Timely administration of a first dose of acellular pertussis vaccine is critical to reducing illness and death in infants.

Issues: It will be difficult to assess immunization status in this age group. Further, 3 months is not a routine age milestone for measuring coverage.

Recommendation 4

Achieve and maintain age-appropriate immunization coverage with acellular pertussis vaccine in 95% of infants by 7 months of age (3 doses) by 2010.

Rationale: The first three doses of acellular pertussis vaccine are the most critical in reducing infant mortality and hospitalization rates. Focusing on delivery of the first three doses should produce better results than the typical coverage target of 2 years of age.

Issues: Questions were raised about the appropriateness of eliminating the 2-year-old coverage target from the recommendations for pertussis. While coverage is already measured by the second birthday (i.e. the age at which diphtheria, tetanus and polio coverage are measured) regardless of when immunization occurs, participants agreed to add a recommendation reinforcing the 2-year-old coverage target for pertussis.

Recommendation 5

Achieve and maintain age-appropriate immunization coverage with acellular pertussis vaccine in 95% of children by their 2^nd birthday (4 doses) by 2010.

Rationale: Further to the discussion on recommendation 5, the 2-year-old coverage target is appropriate for pertussis as coverage is routinely measured by the second birthday. However, focus should still be placed on monitoring uptake of the first three doses.

Recommendation 6

Achieve and maintain age-appropriate immunization coverage with acellular pertussis vaccine in 95% of children by their 7^th birthday (5 doses) by 2010.

Rationale: The target builds on the proposal to give the first three doses and fourth dose of acellular pertussis vaccine by the ages of 7 months and 2 years, respectively.

Recommendation 7

Achieve and maintain age-appropriate immunization coverage with Tdap vaccine in 85% of adolescents by their 18th birthday by 2010.

Rationale: It is important to capture primary series and boosters. As the age limit of school monitoring programs and the cut-off age between adolescence and adulthood, 18 years is a reasonable age for ensuring immunization in adolescents. The target of 85% recognizes that adolescents are more difficult to monitor than their younger counterparts.

Recommendation 8

Provinces/territories should replace Td with Tdap for the adult population by 2010.

Rationale: The absence of provincial/territorial programs for adults renders the establishment of adult coverage targets unrealistic. Switching adult immunization boosters from Td to Tdap is a more feasible way of addressing adult immunization needs.

Issues: Concern was expressed that the proposed change may result in adults receiving more antigen than they require; although NACI recommendations allow one dose of Tdap for adults, offering more than one vaccine could cause confusion. The appropriateness and feasibility of targeting adults (versus children and adolescents) was also challenged, notwithstanding the 2002 Consensus Conference conclusion that adults should be immunized for their own sake.

Other

Recommendation 9

Decrease the number of deaths from pertussis to zero in the target population of ≤ 3 months of age by 2010.

Rationale: Most deaths currently occur in infants too young to receive immunizations (i.e. < 3 months). A focus on timely first dose, as well as subsequent doses and boosters in older populations, was seen as essential to achieving the proposed goal.

Issues: It will be difficult to assess mortality rates in this age group. Further, 3 months of age is not a routine milestone for measuring immunization coverage.

Recommendation 10

The Canadian Public Health Laboratory Network should reaffirm the laboratory recommendations from the 2002 Pertussis Consensus Conference.

Rationale: Standardization is needed to address differences in provincial/territorial diagnostic tests and enable advances in Canadian diagnostic methods.

Vote

Participants considered a total of 10 recommendations for pertussis control, achieving consensus on eight recommendations including the newly added Recommendation 5. Consensus was not reached on Recommendations 2 and 8, following extensive discussion and second votes (see votes 1 and 2). It was agreed that issues raised in the working group and at the plenary level regarding Recommendations 2 and 8 should be considered by the CIC during its review of the consensus conference recommendations.