Reports

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 - 10th Canadian Immunization Conference

Vancouver, BC / December 3-5, 2012

Vancouver - Each year in Canada, approximately 200 individuals are affected by invasive meningococcal disease (IMD), and about half of them are children. Mortality from IMD has remained essentially unchanged since the 1950s with a case-fatality rate of 5 to 10%. Further, approximately 20% of patients will have significant-long term disability as a result of IMD. Vaccines are already available against most serogroups that cause IMD except serogroup B. A novel multi-component serogroup B candidate vaccine is expected to be protective against the majority of circulating B strains in Canada. Results from the clinical development program of the novel candidate vaccine showed the vaccine to be immunogenic in infants, children, adolescents and adults and has a manageable reactogenicity profile. There is mounting evidence to suggest that parental acceptance of this vaccine for their children will be high. An evidence-based document addressing gaps in knowledge about meningococcal B has been developed to serve as a bridge to guidelines governing immunization against serogroup B disease.

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

Looking at the outcomes of children and adults who developed invasive meningococcal disease (IMD) in Canada between 2002 and 2010, Sadarangani et al. reported that mortality rates in a cohort of 851 such patients was 4% in children and 12% in adults (Abstract P008). The sequelae rate was 21% in children and 15% in adults. However, in children <1 year of age, some 75% of the sequelae were neurological in nature, higher than for any other age group, as the authors pointed out. By far the greatest risk factor for mortality in the Canadian cohort was the presence of shock with an odds ratio of 25 vs. no shock.

The most significant risk factors for sequelae were shock and seizures. In contrast, getting patients into the ICU was protective. “When meningitis strikes, it is extremely sudden and unpredictable and it can be fatal within 24 to 48 hours,” Dr. Tajdin Jadavji, Professor of Microbiology, Immunology, Infectious Disease and Paediatrics, University of Calgary, Alberta confirmed. This is why it is important to have high levels of circulating antibodies so that the immune system can deal with the invading serogroup quickly. When an effective vaccine such as the conjugate meningococcal C vaccine was introduced, widespread uptake dramatically reduced the burden of meningococcal C disease in Canada, to the point where in some provinces, serogroup C has caused virtually no IMD over the past few years.

IMPACT Evaluation

The epidemiology of the 5 main serogroups that cause IMD is unpredictable and varies geographically and over time. IMPACT investigators showed that distribution of serogroup B disease between 2002 and 2009, for example, was highest in Quebec at 73% and lowest in B.C. at 39%. In a presentation by Dr. Julie Bettinger, Assistant Professor, Vaccine Evaluation Center, Infectious and Immunological Disease, University of British Columbia, Vancouver, IMPACT evaluated how well the new multi-component meningococcal disease against serogroup B disease (4CMenB) vaccine would protect against circulating strains of serogroup B.

Across the years 2006 to 2009, “the overall strain coverage rate of the 4CMenB vaccine [would have been] 66% for Canada overall with a high of 72% in 2006 to a low of 58% in 2008,” she reported. Again, the degree to which the new vaccine might protect against serogroup B disease varied across the country. The majority of serogroup B isolates from the Prairies Provinces, Ontario, Quebec, Nova Scotia and Newfoundland would potentially be covered by the vaccine, so for these provinces, “the vaccine looks promising,” Dr. Bettinger stated. On the other hand, “you really need to look at the epidemiology of IMD in each province because there are regional variations so you have to decide how well the vaccine is going to work in your own province,” she added.

Clinical Development Program

The clinical development program evaluating the 4CMenB vaccine includes 12 studies involving more than 7000 subjects starting at 2 months of age. In infants, post-primary and post-booster doses of the 4CMenB vaccine produced protective antibody responses against the 4 vaccine components in 84-100% and 95-100% of subjects, respectively. In adolescents between 11 and 18 years of age, the 4CMenB vaccine produced protective antibody responses to all components of the vaccine in virtually 100% of recipients.

“No clinically relevant immunological interference was seen when the 4CMenB was given concomitantly with other routine vaccines,” Dr. Marc Lebel, Professor of Medicine, University of Montreal, Quebec, reported here. At 40 months of age, 88-100% of young children achieved seroprotective bactericidal titers ≥4 to each of the 4 components of the vaccine. Fever does occur within about 6 hours of giving the 4CMenB vaccine either alone or concomitantly with routine infant vaccines, as Dr. Lebel indicated.

Prophylactic acetaminophen given at the same time as the vaccine reduces fever risk in half. When fever is discussed with parents, they also know what to expect and it does not seem to be an issue in real practice, Dr. Lebel added.

Parental Acceptance

Parental acceptance of the new meningococcal B vaccine is an expected issue of discussion. An interim analysis from a pan-Canadian research study led by William Fisher, PhD, Professor of Psychology, University of Western Ontario, London (e-poster P019), suggests that parental acceptance will be high. Parents of infants aged 2 to 6 months (n=115), presenting for scheduled “healthy-baby visits,” were interviewed before and after physician interaction during which information about IMD and MenB vaccine was provided. Parents responded to measures of spontaneously elicited beliefs concerning positive and negative aspects of infant immunization, and the new MenB vaccine, sources of social support for vaccinating their infants with MenB vaccine, knowledge about IMD and MenB vaccine, and direct measures of attitudes, social and physician support, and intention to vaccinate their infant with MenB vaccine.

Over 80% agreed strongly with the statement that their doctor would want them to have their baby immunized against meningococcal B disease and 80% moderately or strongly agreed that most people would want their infant immunized against B disease. Approximately 60% indicated that they strongly intended to vaccinate their infant when the meningococcal B disease vaccine becomes available.

Following the physician interaction, the majority of parents (76.5%) intend to vaccinate their infant with the MenB vaccine. The cost of the vaccine had an impact on acceptability with higher price leading to less intention to vaccinate. However, neither the number of shots nor the safety and tolerability profile of the MenB vaccine influenced parental intention to vaccinate. “With minimal physician interaction, parents’ attitudes towards meningococcal B vaccine, their perceptions of support for vaccination from significant others and their perceptions of physician recommendation, strongly predict their acceptance of the vaccine when available,” Dr. Fisher concluded.

Evidence-Based Reference

As pointed out in a poster (P077) by Jadavji et al., understanding the vaccine and recommendations for its use need to be addressed in order to facilitate the introduction and use of the candidate MenB vaccine. A Steering Committee of experts in IMD, infectious diseases and vaccinology was established to provide oversight and governance for the development of an evidence-based reference document to address the need for answers to commonly asked questions by health care practionners. Questions were collected from accredited continuing medical education (CME) events and through the Novartis Medical Information Centre support line. A Scientific Advisory Committee was convened to obtain consensus on reference based responses and their relevance from an immunisation perspective. Consensus was obtained on Frequently Asked Questions (FAQs) and evidence based answers, generating an open source document.

What emerged from 8 different CME events as well as questions sent through the Medical Information Center was a series of 16 prioritized questions which Dr. Jadavji discussed. The FAQs range from the epidemiology and burden of IMD; coverage of MenB and how it compares to other vaccines; risk for IMD in Canada; effectiveness data on and experience with the MenB vaccine; how many vaccines can be given in a single visit to infants; how the new MenB vaccine would fit into the current immunization schedule and how do physicians overcome parent hesitancy towards another new vaccine?

“This evidence-based reference document will…address the immediate need for answers to commonly asked questions from a scientific, clinical and practical perspective,” the authors write.

Summary

Effective vaccines already exist for IMD caused by serogroups A, C, Y and W-135. Now, a candidate vaccine against the serogroup B disease has been evaluated in clinical trials. It is expected to be effective against the majority of circulating B strains in Canada. Recent data suggests that parental acceptance of this vaccine for their infants will be strong. In order to facilitate introduction and use of the candidate MenB vaccine, an evidence-based reference document has been developed to address any knowledge gaps or concerns physicians may have in counseling parents about the new meningococcal B vaccine. 

Mednet reports which have been accredited by McGill University under the MedPoint Accredited Conference Report Series are eligible for Mainpro-M1 and MOC Program credits.

© 2012 Mednet Inc. All rights reserved. Priority Press™ is an independent medical news reporting service providing educational updates reflecting peer opinion from accredited scientific medical meetings worldwide and/or published peer-reviewed medical literature. Distribution of this educational publication is made possible through the support of industry under written agreement that ensures independence. Views expressed are those of the participants and do not necessarily reflect those of the publisher, McGill University or the sponsor. No claims or endorsements are made for any products, uses or doses. Specific medicines or treatment strategies discussed in this publication may not yet be approved in Canada. Prior to prescribing any medication, the complete prescribing information in Canada, including indications, contraindications, warnings, precautions, and adverse effects should be consulted. No part of this publication may be reproduced in any form or distributed without written consent of the publisher. Information provided herein is not intended to serve as the sole basis for individual care. Our objective is to facilitate physicians’ and allied health care providers’ understanding of current trends in medicine. Your comments are encouraged.