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PRIORITY PRESS - 10th Canadian Immunization Conference

Vancouver, BC / December 3-5, 2012

Vancouver - Asymptomatic nasopharyngeal (NP) colonization by typical colonizing bacteria, most notably Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae is a prerequisite for the development of local and invasive disease. Certain vaccines reduce vaccine-specific NP colonization, pathogen transmission and subsequent disease among vaccine recipients and among non-vaccine recipients through a herd effect. An evaluation of the impact of pneumococcal conjugate vaccines on NP colonization and invasive pneumococcal disease in Alberta provides one example of how these bacterial diseases can be attenuated. Catch-up pneumococcal disease vaccine programs can work but they are not without challenges, especially when trying to capture high-risk pediatric patients.

Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec

Vaccines and Decline in Nasopharyngeal Colonization

Asymptomatic nasopharyngeal (NP) colonization is a prerequisite for local and invasive disease caused by Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae. Reduction in NP colonization is thus the first step towards disease eradication. “When you have colonization, most of the time it leads to immunity against these pathogens but no apparent disease,” Dr. James Kellner, Professor of Paediatrics, University of Calgary, Alberta, told delegates. Protein polysaccharide vaccines reduce vaccine-specific NP colonization, subsequent transmission and ultimately, disease through the herd effect. For example, H. influenzae b (Hib) vaccines have reduced NP colonization rates to <1%, virtually eradicating invasive disease not only in vaccine recipients but in all ages, as Dr. Kellner observed.

Similarly, meningococcal disease caused by serogroup C has been virtually extinguished in Canada and elsewhere following widespread uptake of the conjugate C vaccine in the target population—“so there is an immediate effect to prevent disease but this also correlates with a significant decline in NP colonization,” Dr. Kellner observed. As is true of H. influenzae, virtual eradication of serogroup C invasive meningococcal disease (IMD) occurred when only a small proportion of the population received the vaccine.

A CASPER Survey

For pneumococcal disease, the prevalence of NP colonization is highest in children; higher in adults who have children, and lowest in adults with no exposure to children.

When pneumococcal serotypes do break past immune barriers, “you get local spread that causes otitis media or sinusitis,” he added. Invasive pneumococcal disease (IPD) may present as pneumonia, bacteremia or meningitis. The 7-valent (PCV7) vaccine was introduced into Alberta in 2002. In tracking the epidemiology of vaccine vs. non-vaccine serotypes following the introduction of PCV7, surveys done by the Calgary Area Streptococcus pneumoniae Epidemiology Research (CASPER) showed that the overall NP colonization rate did not change between 2003 and 2005.

However, colonization with vaccine serotypes declined by approximately two-thirds over the same time interval. “Thus, the decline in vaccine serotypes was offset by an increase in non-vaccine serotypes,” Dr. Kellner indicated. When CASPER resumed their survey of NP colonization in 2010, just before the 13-valent pneumococcal vaccine (PCV13) was introduced, “We saw there had been a significant decline in the overall NP colonization rates,” he added.

Specifically, between 2003 and 2005, the NP colonization rate was approximately 19% based on survey findings. Between 2010 and 2012, the rate declined to 13%—which clearly has important implications for disease incidence, as speakers here suggested. Importantly, as more and more children in Alberta receive PCV13, the decline in overall NP colonization rates has not been offset by colonization with non-vaccine serotypes, a finding that has been observed elsewhere.

At the same time, there’s been a dramatic change in serotype epidemiology such that in 2012, 94% of children swabbed in Calgary were colonized with non-vaccine serotypes. Some 5% were colonized with serotypes contained in PCV13, and only 1% by PCV7 serotypes. Also reported by CASPER here, 95 cases of IPD with available serotypes identified on later surveys indicated that the most common serotypes associated with IPD in 2011 were 19A, 7F, 4, 8 and 3; of these 19A, 7F, 4 and 3 are PCV13 serotypes.

A Positive Trend for the Herd Effect

Given that PCV13 was introduced into the province in 2010, these findings suggest that some PCV13 serotypes still cause IPD, especially in older patients, largely because there has not been enough time since its introduction for full herd immunity to develop. “With the 7-valent vaccine, it took about 6 years before we really eliminated colonization with the vaccine types,” Dr. Kellner said.

While survey data clearly indicate there has been a decline in IPD caused by the 6 additional serotypes in the 13-valent vaccine, “I think we’ll see the full effect of vaccine implementation over the next 2 to 4 years,” Dr. Kellner said, adding, “Our data clearly show that the vaccine has dramatically reduced the overall incidence of disease because we have reduced asymptomatic colonization. So, it’s tremendously effective.”

Catch-up Programs

The provinces and territories have largely adopted PCV13 as their preferred vaccine for IPD prevention but offering “catch-up” programs so as to provide protection against the additional 6 serotypes in PCV13 can be challenging. In Ontario, routine PCV13 schedules start at 2 months of age in healthy and high-risk infants, with 3 doses of PCV13 recommended at 2, 4 and 12 months of age for healthy children and 4 doses for high-risk children at 2, 4, 6 and 15 months of age. The Catch-Up PCV13 program for low-risk children who have either not completed or have not started their PCV13 series is variable and depends on the infants’ pneumococcal vaccination history.

As discussed by Dr. Marina Salvadori, Associate Professor of Paediatrics, University of Western Ontario, London, the decision to offer a PCV13 Catch-Up program in Ontario was based on several factors. Of the IPD cases reviewed prior to the introduction of PCV13 in the province, Dr. Salvadori indicated that 75 cases would have been covered by PCV13—“so clearly, if we wanted to cover most IPD, we would have to go to PCV13,” she observed.

A large proportion of Ontario children over the age of 12 months who developed IPD would also have been protected by PCV13, she added. Looking at the province’s IPD cases in 2009, “there was also large group of children between 24 to 35 months of age who had disease that would have been prevented by PCV13,” Dr. Salvadori noted. IPD would have been prevented by PCV13 in a fairly sizeable proportion of older children between 36 and 59 months as well.

“I think we had fairly good data upon which to base our Catch-Up program but we don’t have good coverage data,” Dr. Salvadori acknowledged. She also feels that a majority of health care providers likely missed the Catch-up directive as it was buried in lengthy government documents. Many high-risk children are actually cared for by subspecialists and they are less likely to be aware of PCV13 Catch-Up recommendations than family physicians, as Dr. Salvadori pointed out.

Lastly, many doctors will not vaccinate a child when they have an intercurrent illness and it’s usually the intercurrent illness that brings children to the doctor in the first place. All of these issues collectively suggest that there are still likely many children who are eligible for PCV13 who have yet to receive it.

Summary

NP colonization precedes invasive disease caused by H. influenzae, N. meningitidis and S. pneumoniae. Vaccines reduce or potentially eliminate vaccine-specific NP colonization and subsequent disease and protection is extended beyond vaccine recipients through the herd effect. CASPER findings from Calgary indicate that the introduction of PCV7 and more recently PCV13 has reduced colonization rates of vaccine-specific pneumococcal serotypes. Uncharacteristically, it does not appear that there is a corresponding increase in non-vaccine serotypes to offset this reduction. However, the full impact of PCV13 on NP colonization rates has yet to be realized and more time is needed to achieve optimal protection.  

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