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This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - 9th Canadian Immunization Conference (CIC)

Quebec City, Quebec / December 5-8, 2010

The 13-valent pneumococcal conjugate vaccine (PCV13) is replacing the 10-valent PCV previously offered to infants in Quebec and Ontario, starting at 2 months of age. In a letter dated November 9, 2010, the Ontario Ministry of Health and Long-Term Care (MHLTC) informed health care providers (HCPs) that the PCV13 is now available as part of the province’s publicly-funded childhood vaccination program as a result of the changing epidemiology of invasive pneumococcal disease (IPD). A similar announcement was made by Quebec health authorities during the opening ceremonies at the Canadian Immunization Conference (CIC).

The 13-valent vaccine provides protection against 6 additional serotypes than the earlier PCV7 version and 3 more serotypes than the 10-valent vaccine. The unique 3, 6A and 19A serotypes not contained in either the PCV7 or the PCV10 could increase risk of IPD in otherwise healthy infants with no medical condition. Therefore, public health officials recommend a 3-dose schedule of PCV13, the first to be given at 2 months, the second at 4 months and the final one at 12 months of age. After careful review of case-controlled studies in the US, which showed no differences in clinical outcomes in children who received 3 doses of the vaccine from those who received 4 doses, the 2 + 1 PCV13 schedule was chosen for low-risk children rather than the 3 + 1 schedule initially recommended for the PCV7.

However, for infants who are at high risk for IPD (e.g. infants with chronic renal disease, asplenia, chronic respiratory disease, etc.), a 4-dose schedule is still recommended, starting at 2 months, the second and third doses at 4 and 6 months of age and the final dose at 15 months of age. Ontario health officials also recommend a catch-up PCV13 program for infants and children with varying histories of PCV. More information is available at http://www.health.gov.on.ca/english/providers/program/immun/pdf/schedule.pdf.

Not a Uniform Pathogen

As discussed here at the CIC by Dr. Jim Kellner, Professor and Head, Department of Paediatrics, Microbiology & Infectious Diseases, University of Calgary, Alberta, Streptococcus pneumoniae is typically thought of as a uniform pathogen; yet with 91 different serotypes known to cause disease in humans, “it is not really a single pathogen but many individual species that can cause disease,” he observed. Indeed, the different serotypes tend to cause different diseases—pneumonia, meningitis, bacteremia, otitis media—in different geographic regions and in different age groups, he added. Since the introduction of the publicly-funded PCV7 immunization program, the epidemiology of S. pneumoniae has shifted dramatically.

Regarding IPD rates in the US in 2007 compared with 1998-1999, there has been a 76% reduction in the overall incidence of IPD in children <5 years of age and a 100% reduction in the incidence of disease caused by serotypes covered by PCV7. While there has been an increase of 324% in serotype 19A and 51% in other non-vaccine serotypes, Dr. Kellner noted that “the increase in non-vaccine serotype disease has been small compared to the significant decrease in disease overall.” For all ages combined, the same dataset shows that there has been a 45% decline in the overall incidence of IPD, “so by giving the vaccine to infants, we are having a big impact on disease in all ages,” Dr. Kellner told delegates.

Serotype 19A has now become the predominant serotype causing IPD, accounting for 42% of all IPD in children <5 years old, according to IMPACT data presented at the CIC by Bettinger et al. (It was for this reason that the Ontario MHLTC announced the switch to PCV13 from the 10-valent vaccine, noting that the incidence of IPD caused by non-vaccine serotypes, notably 3 and 19A covered by PCV13, has increased, particularly for 1- and 2-year-old children).

Dr. Kellner stressed that the emergence of 19A as the predominant serotype took a few years after the introduction of the PCV7 vaccine and it has subsequently levelled off.

Surveillance data from Calgary corroborate the same prompt decline in IPD in children <2 years old and a “really significant” decline in PCV7 serotype disease, with zero cases of IPD reported in 2008 and 2009 and no cases as of November 2010. Dr. Kellner suggested that any replacement disease due to serotypes not contained in the 13-valent vaccine that may emerge with widespread uptake of PCV13 is also likely to level off, as has been seen with 19A disease. PCV13 covers approximately 60% of IPD due to all 91 serotypes.

Immunization Schedules

With most (if not all) provinces and territories expected to adopt PCV13 as part of their publicly-funded childhood vaccination program, the immunization schedule for the vaccine should be reasonably uniform across the country. The same cannot be said for other childhood vaccines, as many inter-provincial and territorial differences in immunization schedules exist for childhood vaccines.

As of 2010, for example, the National Advisory Committee on Immunization (NACI) recommended that the hepatitis B vaccine be given either in infancy or in pre-teen years. Hence, British Columbia (BC) immunizes infants against hepatitis B at 2, 4 and 6 months; Prince Edward Island delivers it at 2, 4 and 15 months; Ontario and Nova Scotia immunize grade 7 students; and Quebec immunizes students in grade 4. (BC was the first province to have a school-based hepatitis B program which was initiated in 1992 but from 2001 onward, the infant schedule was adopted because a very sizeable proportion of the BC population are foreign born, at least half of whom are from endemic areas including Asia and the Middle East.) Quebec was the first province to offer the dual hepatitis A/B vaccine to grade 4 students, at an age when the immune response to the vaccine is most robust. Children receive 2 doses of the hepatitis A/B vaccine instead of the recommended 3, as the 2-dose schedule has been shown to protect over 96% of recipients.

Provinces are less likely to deviate from the NACI recommendation for measles-mumps-rubella (MMR) vaccination at 12 and 18 months or at 4 to 6 years, with most giving the MMR vaccine at 12 and 18 months, although Nova Scotia gives the second dose at 6 years and Prince Edward Island offers the first dose at 15 months.

Vaccination against the human papillomavirus (HPV) also differs considerably from province to province and in the number of doses given. In BC, girls receive 2 doses of the vaccine in grade 6, and there is a plan for a third dose at 60 months pending data on longer-term protection. Quebec provides the HPV vaccine to girls in grade 4, but similarly plans for a third dose at 60 months when the girls are in grade 9, pending data on longer-term protection. Ontario offers the HPV vaccine to girls in grade 8.

Summary

S. pneumoniae is the leading cause of bacteremia, meningitis, bacterial pneumonia and acute otitis media in children. The publicly-funded PCV7 has been available for all childhood immunization programs for a number of years. Now, it would appear that most provinces are replacing the PCV7 with the PCV13 as a result of the changing epidemiology of pneumococcal disease, largely due to the emergence of serotype 19A disease. With broader coverage against important serotypes, the incidence of IPD will likely continue to decline, an important public health goal for the benefit of all.