Susan Hollenberg, B.Sc., M.D., MCFP (biography and disclosures)
No disclosures.
What we had before
As a medical resident I feared missing a case of meningococcal meningitis in a pediatric patient. Equally dreaded was the hallmark rapidly progressing purpuric rash, visions of which seemed to leap out of the medical text and imprint in video on my brain. Now that I have some years of practice under my belt, I have relaxed a little, having thankfully not seen a clinical case of the same. Statistically, this is not unusual, given that between 2006 and 2011 there were on the average 196 cases of invasive meningococcal disease (IMD) diagnosed annually in Canada. However, what has not changed is the fact that this is a low incidence, very severe disease, with a case fatality rate of 10%. One third of survivors have sequellae such as hearing loss, neurologic disabilities and limb amputations.
Neisseria meningitides is an aerobic encapsulated diplococcus, classified according to the immunogenic reactivity of the polysaccharide capsule. It peaks in incidence in infants and again in the teenage and young adult years. When effective Meningitis serotype C (MenC) vaccines were developed and implemented in Canadian Public Health programs in 2003, rates of MenC disease plummeted. Public acceptance was favourable, given the spectre of a childhood illness that affects the brain. A decade later, the graphs illustrate another immunization success story, echoing the downward curves of previously dreaded, now vaccine- preventable illnesses such as measles and diphtheria.
The arrival of effective conjugate vaccines for not only type C, but, replacing polysaccharide vaccines for Men types A, Y and W, offered additional protection, especially for college-aged youth and travellers to meningitis endemic areas.
However, with a majority of cases of IMD in Canada, U.S. and Europe due to type B (MenB), the lack of an effective vaccine prevented us from making true inroads against the incidence of this disease. In B.C. in 2012, there were 16 cases of IMD: 10 B, 4 Y, 1 C and 1 non-typeable. In 2013, there were 11 cases of IMD in B.C.: 4 B, 5 Y and 2 C. The rates of serogroups A and W-135 have remained low over time, occurring as rare imported cases.
What changed my practice
In December, 2013, Health Canada approved a 4- component Meningitis type B (4CMenB) vaccine. This was good news, for although novel capsular MenB vaccines had been previously developed in countries like Cuba and New Zealand, they were of limited effectiveness outside of those narrow geographic regions due to large variations in the MenB capsule. They were also poorly immunogenic, due to similarities between the B capsular polysaccharides and human tissue.
The vaccine approved in Canada utilizes technology based on ‘outer membrane vesicles.’ These are unique capsular identifiers that comprise fingerprints for a serogroup B strain. The challenge has been that over 8000 MenB strains exist!
Four antigenic components were chosen to achieve broad, but not complete serotype B protection, and the 4CMenB vaccine has performed well in clinical trials. In Europe, this vaccine covers 78% of the MenB strains. However, in Canada, this vaccine covers an average of 66% of MenB strains. In addition, there is regionally variable MenB type and activity across Canada, ranging from 43-78% of strains covered by this 4CMenB vaccine. This vaccine will likely be more useful in Eastern Canada and less useful in B.C.
This vaccine is approved in Canada for individuals aged 2 months to 17 years. Clinical trials show it is safe and immunogenic when used in people up to 55 years of age. Side effects are typically mild and include local reactions of tenderness, erythema and induration at the site of injection. In adolescents, local side effects are reported along with myalgias, malaise and headache. 4CMenB vaccine can be administered at the same time as routine infant hexavalent and other vaccines, including MMR and Varicella without reducing immunogenicity, but we have observed higher rates of fever with this practice than with co-administration of these vaccines with Men-C vaccine. Given the number of vaccines already administered at these routine visits, and the increased potential for systemic side effects with the addition of 4CMenB, it might be prudent to give them at separate visits.
The schedule varies by age. Currently, the recommendation is for four doses for infants aged 2-5 months, three doses for infants 6-11 months, and 2 doses for those over 12 months – 55 years, according to schedules detailed in the product monograph. We currently have no data on administration to persons with chronic medical conditions, those who have had previous meningitis, pregnant or breast -feeding individuals.
We do not yet have data on effectiveness, NNV (number needed to vaccinate), impact on carriage, and duration of protection. The low incidence of IMD in Canada means that we cannot use clinical efficacy as an end point. During the time period 2006-2011 the Canadian incidence of MenB IMD was 0.33 cases per 100,000 population, with a case fatality rate of 5.5%. Pre-marketing studies have inferred efficacy by studying the immune response to the 4 antigenic components as a correlate of protection. One can also serotype meningococcal carriage in the nasopharynx to assess changes in prevalence in the community. We will only see the trend in IMD over time as the population is vaccinated, through protection against disease and herd immunity.
Carriers of meningococcal meningitis harbor the bacteria asymptomatically in the nose and throat. It is transmitted by mucosal contact with respiratory droplets. The risks for IMD include conditions that impair the integrity of the nasopharyngeal mucosa. These include recent influenza or upper respiratory infection, active and passive smoking. For this reason, we see most of our Canadian cases in the winter. Other high-risk groups include people with functional or surgical asplenia (who are susceptible to infection with encapsulated organisms), congenital or acquired complement deficiencies, and HIV-infected individuals, (especially congenitally acquired).
What we have now
At $125 a dose, this multiple dose vaccine can be a pricey investment! Until we have more complete information on the efficacy of this vaccine, it is not likely to be adopted into public health programs in the near future. Nevertheless, primary care providers have a duty to inform the public about this vaccine, and can utilize the information we do have to make some recommendations.
The National Advisory Committee on Immunization (NACI) recommends this MenB vaccine for persons with functional or anatomical asplenia, in addition to the conjugate MenACYW-125 vaccine. Conditions which contribute to functional asplenia include sickle cell disease, thalassemia major, thrombocytopenia, and even inflammatory bowel disease and celiac disease. Other indications include congenital complement, properdin, factor D or primary antibody deficiencies. It should be considered in anticipation of medically- induced complement deficiency prior to starting eculizumab, a drug used for atypical hemolytic uremic syndrome. Other high- risk persons include research and laboratory personnel who might be routinely exposed to MenB. Travellers to an area with an outbreak of MenB, or at high risk of a hyper endemic strain could consider this preparation.
Most frequently, I am seeing it being given to college or university aged students, especially those attending schools in Eastern Canada and the U.S. Outbreaks are reported in those living in dormitory- type situations. Similarly military recruits are at higher risk of this disease during their training in close living quarters. One should not neglect, however, in these situations, to discuss vaccination with the existing quadrivalent meningococcal vaccines, covering serotypes A, C, Y and W-125.
Vaccines are one of the most effective medical interventions we possess, both on a personal and population- wide basis. Undoubtedly, the new 4CMenB vaccine is a useful addition to our armamentarium. However, only with time will we be able to more fully evaluate its effectiveness in reducing deaths and disability from IMD. Until then, I remain on high alert for signs and symptoms of meningitis.
References and Resources:
- NACI Statement on Meningitis B Vaccine http://www.phac-aspc.gc.ca/naci-ccni/flu-grippe-eng.php Full Document: http://publications.gc.ca/collections/collection_2014/aspc-phac/HP40-104-2014-eng.pdf
- Canadian Immunization Guide http://www.phac-aspc.gc.ca/publicat/cig-gci/p04-meni-eng.php
- BCCDC Immunization Manual: Section VII–Biological Products http://www.bccdc.ca/NR/rdonlyres/528C4C20-F2F8-4333-9927-E8DC455A5E76/0/SectionVII_BiologicalProducts_October2014.pdf
- Robinson JL, Canadian Paediatric Society, Infectious Diseases and Immunization Committee. Immunization for meningococcal serogroup B: What does the practitioner need to know? Paediatrics & Child Health. 2014;19(2):91-94. Available from http://www.cps.ca/en/documents/position/immunization-for-meningococcal-serogroup-B
- Immunize.ca http://immunize.ca/en/default.aspx
- PHAC 2009 Statement on Invasive Meningococcal Disease and the use of Conjugate Vaccines http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/09vol35/acs-dcc-3/index-eng.php
- PHAC 2013 update on the use of quadrivalent Meningitis vaccines http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/13vol39/acs-dcc-1/index-eng.php
- Bettinger JA, Scheifele DW, Le Saux N, et al. The Disease Burden of Invasive Meningococcal Serogroup B Disease in Canada. Pediatr Infect Dis J. 2013; 2012;32:e20-e25. (View with UBC)
- Annual BCCDC summaries of Reportable Diseases 2013 http://www.bccdc.ca/NR/rdonlyres/D8C85F70-804C-48DB-8A64-6009C9FD49A3/0/2013CDAnnualReportFinal.pdf
- Annual BCCDC summaries of Reportable Diseases 2012 http://www.bccdc.ca/NR/rdonlyres/F30377E3-D33E-4755-B3F4-6844E01BD678/0/FinalAR2012.pdf
- Bexsero Product Monograph http://www.bexsero.ca/en/hcp/index.shtml
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I would like a cost analysis based on the very low incidence of the disease – 0.33 per 100,000 vs. the cost of the vaccine ( $125 x 3?). The fact that most post secondary students at BC schools have coverage for 150 per year for any vaccines I am much less likely to promote this vaccine over the HPV vaccine. which also is very expensive. Would love to hear your thoughts.
Good article. However, the comment that medical practitioners have a duty to advise patients about this vaccine is a bit over the top.
Thank you for this interesting update, but the statement “Nevertheless, primary care providers have a duty to inform the public about this vaccine” seems a bit strong when balanced with the previous statement “We do not yet have data on effectiveness, NNV (number needed to vaccinate), impact on carriage, and duration of protection.”
I think it is important to avoid words such as “duty” when the evidence is so tenuous.
The article states that the vaccine is approved in Canada for ages 2-17, however you see it most frequently being given to university aged students, who would be mainly over 17. Immunize BC website indicates use up to 55 years of age. Is it approved for adults in Canada?
As well, many children who are now in high school received Men C vaccine in grade 6, but are not eligible for a booster according to Immunize BC, even though CDC recommends a booster after 5 years in that age group. If they are going to university in eastern Canada, should they have the quadrivalent vaccine for better protection from A, C, Y and W, as well as the meningitis B vaccine?
Thank you for your excellent points. I would like to respond with some further comments.
The published resources on 4CMenB vaccine in Canada include the NACI recommendations and the BCCDC Immunization manual. There is not yet a Canadian Immunization Guide statement on this vaccine. The vaccine is approved in Canada for ages 2-17 based on manufacturer’s studies. The manufacturer does not list an adult schedule. However, clinical trials in ages 18-55 have shown this vaccine to be safe and immunogenic when used as a two dose schedule, 4 weeks or more apart.
I agree that the wording “duty” to inform patients is a little strong. However, it is based on CMPA guidelines on the physician’s obligations to inform patients of new and unfunded vaccine products https://www.cmpa-acpm.ca/-/new-vaccines-what-are-your-obligations. There are similar statements in the PHAC documents on Immunization Practice in Canada. I also agree that it is impossible to do in an evidence- based manner, given that there are no published trials yet on efficacy and effectiveness of this vaccine!
I do see it being given in conjunction with the MenACYW-135 as a booster for the MenC vaccine in students going to University. However, looking at the NACI data for incidence of MENB disease per 100,000 population for the years 2007-2011 in the university age group 20-24 years, the incidence in BC was 0.33, the incidence in Ontario was 0.29, and the highest incidences were in Que at 1.01, and New Brunswick at 0.43. During the same time period, the total of cases in Canada due to serogroups A,C, Y and W-135 was 0.19 per 100,000, or much lower than the total for MenB.
It is, at this time, a personal and financial-based decision, as we do not yet have cost effectiveness data or NNV statistics for this vaccine for a very low incidence, yet potentially fatal illness.
I agree that as this vaccine is not recommended by NACI for routine use, we are not legally mandated by CMPA to
discuss this vaccine with patients/parents. Why is this not funded for at risk patients in BC ?
Thanks Jane,
I just checked the BCCDC Immunization Manual again and this vaccine is currently provided free to:
“ Close contacts 2 months to 55 years of age of a case of serogroup B invasive meningococcal
disease who meet the public health criteria for chemoprophylaxis.
In consultation with BCCDC, individuals 2 months to 55 years of age at risk during IMD outbreaks caused by N. meningitidis serogroup B or the emergence of hyperendemic and/or hypervirulent N. meningitidis strains that are predicted to be susceptible to vaccine.”
These situations are unique public health decisions and not routinely delivered by primary care providers.
It would seem that high risk patients should receive this vaccine as they do quadrivalent Men vaccine. I would hope that this would be covered, on a case by case basis, for these rare patients on request from Public Health. Would like to hear if this is so.
Susan