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8th Canadian Immunization Conference

Toronto, Ontario / November 30-December 3, 2008

Surveillance data provided by IMPACT (Immunization Monitoring Program ACTive), an active sentential surveillance system, provides valuable insight into how meningococcal disease has changed since meningococcal conjugate C vaccine programs were introduced. As discussed by Dr. Julie Bettinger, Vaccine Evaluation Centre and Assistant Professor of Pediatrics, University of British Columbia, Vancouver, IMPACT showed that there was an overall decrease in the incidence of meningococcal disease between 2002 and 2006 as well as a significant decrease in serogroup C disease. Serogroup B disease is not preventable by currently available vaccines, Dr. Bettinger reminded delegates. But of that disease which is preventable, the distribution of serogroup-preventable disease suggests that broader-spectrum vaccine coverage could reduce a significant proportion of the disease that is still occurring.

For example, in children between 10 and 19 years of age, surveillance data indicate that 21% of meningococcal disease is caused by serogroups Y and W-135. Similarly, with the exception of Quebec, a significant proportion of disease in most provinces is caused by serogroups Y and W-135; 16% in Halifax and St. John’s; 35% in Ontario; 29% in Manitoba and Saskatchewan; and 20% in Alberta and BC. In other words, only about half of serogroup-preventable disease is being prevented by the current meningococcal C vaccine program, at least in high-risk age groups.

Given that immunity against meningococcal disease is serogroup-specific, noted Dr. Scott Halperin, Head, Division of Infectious Disease, Dalhousie University, Halifax, Nova Scotia, the quadrivalent conjugate vaccine offers greater protection against vaccine-preventable disease than the monovalent conjugate C vaccine.

While meningococcal disease from serogroup Y has remained relatively stable in Canada, the same cannot be said of other regions of the world. In the US, only 9% of meningococcal disease was caused by serogroup Y between 1990 and 1992. Between 1997 and 2003, the proportion of Y-attributable disease increased to 28%. While the epidemiology of disease in the US does not necessarily reflect the situation in Canada, Y disease may well be capable of making it across the border, as Dr. Halperin suggested in an interview. Indeed, in anticipation that disease from both serogroup Y and W-135 may increase here, Prince Edward Island, New Brunswick and the Northwest Territories are offering “catch-up” programs for adolescents using the new multivalent conjugate vaccine. Dr. Halperin also reported that the estimates of excess cases of the Guillain-Barré syndrome derived from the passive adverse event reporting system in the US have been declining, despite increased use of the quadrivalent conjugate vaccine.

Furthermore, with some 20 million doses now having been distributed, the Advisory Committee on Immunization Practices (ACIP) has also not seen any safety signal from widespread uptake of the quadrivalent conjugate vaccine to warrant changing its current recommendations. “The optimal approach to control of meningococcal disease depends on the objective of the control strategy,” Dr. Halperin stated. Nevertheless, when polled, well over half of the delegates at the session here indicated that they would favour the quadrivalent over the monovalent vaccine presumably out of concern that non-C-serotype disease is occurring in most parts of Canada.

“If parents want to maximize protection against meningococcal disease, to me, [the multivalent conjugate vaccine] is a worthwhile investment,” Dr. Halperin confirmed.

Influenza-attributable Mortality

Delegates were also reminded that influenza-attributable mortality has steadily decreased over the past three decades, a decline that is “directly attributable to vaccination,” noted Dr. Allison McGeer, Professor of Laboratory Medicine, Pathobiology and Public Health Sciences, University of Toronto, Ontario. Nevertheless, influenza continues to take a steady toll on the population, especially among the elderly. For example, in Ontario, deaths and hospitalizations from influenza are also occurring among older adults, despite the fact that approximately 85% of healthy older adults receive their annual flu shot.

Whether or not the annual flu shot provides adequate protection against influenza in the elderly is the subject of debate right now, remarked Dr. Arnold Monto, Professor of Epidemiology, University of Michigan School of Public Health, Ann Arbor. Some researchers have reported that the influenza vaccine reduces winter mortality by 30% to 50% while others maintain the vaccine does not appreciably reduce winter hospitalizations attributable to influenza.

Pneumonia and influenza deaths have also not decreased among the elderly even while rates of vaccination have increased, Dr. Monto added. “The vaccine is still preventing 70% of laboratory-confirmed influenza in healthy adults but in older individuals, it is working at a reduced efficacy,” he informed delegates. “We need to work towards improved vaccines for all populations, even though we should continue to vaccinate older patients for whatever protection the vaccine can give.”

More Immunogenic Vaccines

Dr. Fred Ruben, former Professor of Medicine, University of Pittsburgh, Pennsylvania, agreed that more immunogenic vaccines for the aged and the immunosuppressed are needed. It would also help if patient acceptance of vaccines were enhanced to improve overall coverage rates, he added. New intranasal influenza vaccines appear to work well in children, especially those over the age of 2, and represent a “good non-needle” alternative to standard intramuscular (i.m.) vaccines.

Boosting immunogenic responses through the use of adjuvanted vaccines that “rev up” the immune system may help ensure individuals are better primed to recognize potentially pandemic viruses such as the H5N1 virus. Increasing the vaccine dose may also help fortify the immune system.

In a study by Keitel et al., patients 65 years of age and older mounted a significantly higher immunogenic response to the highest dose of an i.m. influenza vaccine (60 mcg) compared to those who received the standard dose (15 mcg), a signal that high doses of the influenza vaccine may improve overall protection among the elderly (Arch Intern Med 2006;166(10):1121-7).

Another promising approach is the use of a new intradermal influenza vaccine. Using the skin’s rich immunopotential, researchers devised an intradermal influenza vaccine with a needle not much larger than the proboscis of a mosquito, Dr. Ruben also noted. Researchers recently reported that healthy adults between 18 and 57 years of age who received a single dose of the intradermal trivalent inactivated influenza vaccine mounted similar humoral immune responses against all three strains and more efficacious responses against both A strains in the vaccine than subjects given a conventional i.m. dose (Leroux-Roels et al. Vaccine 2008;26(51):6614-9).

Dr. Ruben also cited a trial involving 1107 individuals over the age of 60 that compared the intradermal vaccine against a control i.m. vaccine, but this time the intradermal vaccine was formulated to be more immunogenic (Holland et al. J Infect Dis 2008;198(5):650-8). All geometric mean titres with the microinjection intradermal system were higher than those seen following i.m. vaccination, as were seroprotection rates and mean titre increases for the intradermally administered vaccine in most analyses.

“For the first time, the intradermal vaccination route has been used to elicit immune responses significantly superior to those noted in association with the conventional i.m. vaccination route… using an easy-to use, reliable microinjection system,” the authors concluded. “This superior response is expected to enhance annual protection against influenza in this vulnerable population.”

Summary

The epidemiology of vaccine-preventable meningococcal disease is changing in most parts of Canada, especially that due to serotypes Y and W-135 in older children and adolescents. By providing protection against four major meningococcal serotypes, the quadrivalent vaccine could expand protection beyond serogroup C disease, as is currently offered by the monovalent vaccine. Novel strategies including high-dose vaccination and a new microdermal injection system have both been shown to offer improved protection against influenza in older recipients than standard i.m. vaccination. The virtually needle-free microdermal injection system should also prove highly acceptable to patients.