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Canadian Immunization Guide

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Part 4
Active Vaccines

Meningococcal Vaccine

Key Information (Refer to text for details)

What

  • The majority of invasive meningococcal disease (IMD) is associated with Neisseria meningitidis serogroups A, B, C, Y and W-135
  • IMD is endemic in Canada but occurs at low rates, with the incidence being highest in infants
  • Persons at higher risk of IMD include:
    • persons with functional or anatomic asplenia
    • persons with congenital complement, properdin, factor D or primary antibody deficiencies
    • persons with acquired complement deficiency due to receipt of the terminal complement inhibitor eculizumab (Soliris™)
    • travellers to areas with high rates of endemic meningococcal disease or transmission, including travellers to the meningitis belt of sub-Saharan Africa and pilgrims to the Hajj in Mecca, Saudi Arabia
    • research, industrial and clinical laboratory personnel who may be at risk of exposure to N. meningitidis
    • military personnel who are at increased risk of meningococcal disease
    • HIV positive individuals should be considered for vaccination, especially if HIV is congenitally acquired
  • Meningococcal vaccines are initially highly effective but effectiveness wanes over time
  • There may be redness, swelling and soreness at the injection site

Who

  • Healthy children: should be immunized with a monovalent conjugate C meningococcal (Men-C-C) vaccine routinely at 12 months of age; however, they may begin meningococcal immunization earlier, depending on provincial and territorial schedules. If not previously immunized as infants or toddlers, children less than 5 years of age should receive Men-C-C vaccine. It should also be considered for children 5 to 11 years of age. Additionally, the multicomponent meningococcal (4CMenB) vaccine may be considered on an individual basis for children two months of age and older to protect against serogroup B strains expressing antigens covered by the vaccine.
  • Adolescents and young adults: either a Men-C-C or a quadrivalent conjugate meningococcal (Men-C-ACYW) vaccine, depending on local epidemiology and programmatic considerations, is recommended for adolescents routinely at 12 years of age, and young adults, even if they have previously been vaccinated as an infant or toddler. In addition, 4CMenB may be considered on an individual basis for those wishing to protect against IMD caused by relevant serogroup B strains.
  • High risk individuals: Men-C-ACYW and 4CMenB vaccine are recommended for children and adults with increased risk of IMD. The choice of vaccine and recommended schedule vary with age. Periodic booster doses with Men-C-ACYW vaccine are recommended.
  • Post-exposure management: in addition to chemoprophylaxis that is recommended for close contacts, if the serogroup is vaccine-preventable, immunoprophylaxis should also be considered, depending on the exposure history.

How

  • Routine infant immunization: give Men-C-C vaccine to healthy infants according to provincial and territorial schedules.
  • 12 months to 11 years of age: give one dose of Men-C-C vaccine at 12 to 23 months of age, routinely at 12 months, whether the child has been immunized as an infant or not. For previously unimmunized children less than 5 years of age, give one dose of Men-C-C vaccine. Consider one dose of Men-C-C vaccine in children aged 5 to 11 years who were previously unimmunized.
  • 12 to 24 years of age: give adolescents, routinely at 12 years of age, and young adults one dose of either Men-C-C or Men-C-ACYW vaccine, even if previously they have been vaccinated as an infant or toddler.
  • Men-C-C and Men-C-ACYW-CRM vaccine may be administered concomitantly with routine childhood vaccines, and Men-C-ACYW vaccine may be administered concomitantly with adolescent and adult age-appropriate vaccines at different injection sites, using separate needles and syringes.

Why

  • IMD mortality is approximately 10%.
  • Of IMD survivors, 10% to 20% have long term sequelae which include hearing loss, neurologic disabilities, and digit or limb amputations.

Significant revisions since the last chapter update are highlighted in the Canadian Immunization Guide (CIG) Table of Updates.

For additional information, refer to previously published National Advisory Committee on Immunization (NACI) Statements and Statement Updates.

Epidemiology

Disease description

Infectious agent
Meningococcal disease is caused by an aerobic encapsulated diplococcus, N. meningitidis (meningococcus). Meningococcal serogroups are classified according to the immunologic reactivity of the polysaccharide capsule. Almost all invasive meningococcal disease (IMD) is associated with serogroups A, B, C, Y, and W-135. Meningococcal serogroups A, B, and C cause the majority of disease worldwide and are responsible for most sporadic cases and outbreaks. For further information about Neisseria meningitidis, refer to the Public Health Agency of Canada (PHAC) website.

Reservoir
Humans are the only reservoir for N. meningitidis.

Transmission
Meningococci are transmitted person-to-person by mucosal contact with respiratory droplets from the nose and throat of infected persons. Most people who are colonized with meningococci are asymptomatic carriers.

Risk factors
Risk factors for the development of IMD include: complement, properdin or factor D deficiencies; functional or anatomic asplenia, including sickle cell disease; certain genetic risk factors (e.g. polymorphisms in the genes for mannose-binding lectin and tumor necrosis factor); household exposure to an infected person; concurrent respiratory tract infection; recent infection with influenza; household crowding; and active and passive smoking. Persons with HIV infection may be at increased risk for meningococcal disease, especially if HIV is congenitally acquired.

Seasonal and temporal patterns
Although disease occurs year-round, there is seasonal variation, with the majority of cases occurring in the winter and spring period in temperate climates, and in the dry season in tropical climates. Most noteworthy is the "meningitis belt" of sub-Saharan Africa where the majority of cases occur from December to June. For further information, refer to the Committee to Advise on Tropical Medicine and Travel (CATMAT) website.

Spectrum of clinical illness
IMD is characterized by a short incubation period (2 to 10 days, usually 3 to 4 days) and usually presents as an acute febrile illness with rapid onset and features of meningitis or septicemia (meningococcemia), or both, and a characteristic non-blanching petechial or purpuric rash. Symptoms of meningitis include intense headache, fever, nausea, vomiting, photophobia and stiff neck. Meningococcemia is characterized by circulatory collapse, hemorrhagic skin rash and a high fatality rate. Overall mortality is approximately 10%, and 10% to 20% of survivors have long term sequelae which include hearing loss, neurologic disabilities, and digit or limb amputations.

Disease distribution

IMD occurs sporadically worldwide and in focal epidemics. In Canada, IMD is endemic and reported year round with peaks in winter. Although people at any age can develop IMD, children younger than 5 are at the greatest risk, followed by people aged 15-19 years and 60 years and up. Serogroups B, C, W-135 and Y are most commonly reported types in the country.

With the introduction of childhood immunization programs against serogroup C IMD in 2002, not unexpectedly, the incidence of serogroup C has decreased significantly over the years. While the incidence of serogroup B remains predominant, disease caused by serogroup W-135 and Y have stabilized at relatively lower incidence rates.

For more information about IMD distribution in Canada, refer to the PHAC website. Comprehensive updates on the epidemiology of IMD in Canada are published periodically in the Canada Communicable Disease Report (CCDR).

Preparations Authorized for Use in Canada

Meningococcal vaccines

Monovalent conjugate meningococcal vaccines (Men-C-C)

  • Meningitec® (meningococcal group C oligosaccharide conjugated to CRM197 protein), Berna Biotech, AG (manufacturer), Pfizer Canada Inc. (distributor). (Men-C-C-CRM)
  • Menjugate® (meningococcal group C oligosaccharide conjugated to CRM197 protein), Novartis Vaccines and Diagnostics (sponsor), Novartis Pharmaceuticals Canada Ltd. (distributor). (Men-C-C-CRM)
  • NeisVac-C® (meningococcal group C polysaccharide conjugated to tetanus toxoids), Baxter (manufacturer), GlaxoSmithKline Inc. (distributor). (Men-C-C-TT)

Quadrivalent conjugate meningococcal vaccines (Men-C-ACYW)

  • Menactra® (meningococcal groups A, C, Y, and W-135 polysaccharides conjugated to diphtheria toxoid protein), Sanofi Pasteur Ltd. (Men-C-ACYW-DT)
  • Menveo (meningococcal groups A, C, Y and W-135 oligosaccharides conjugated to CRM197 protein), Novartis Vaccines and Diagnostics Inc. (Men-C-ACYW-CRM)
  • Nimenrix® (meningococcal groups A, C, Y, and W-135 polysaccharides conjugated to tetanus toxoid protein), GlaxoSmithKline Inc. (Men-C-ACYW-TT)

Quadrivalent polysaccharide meningococcal vaccine (Men-P-ACYW-135)

  • MENOMUNE® A/C/Y/W-135 (meningococcal groups A, C, Y and W-135 polysaccharide antigens), Sanofi Pasteur Inc. (manufacturer), Sanofi Pasteur Ltd. (distributor). (Men-P-ACYW-135).

Multicomponent meningococcal vaccine (4CMenB)

  • Bexsero® (meningococcal porin A [PorA], factor H binding protein [fHbp], neisserial antigen 2091 [GNA2091], heparin binding antigen [NHBA], neisserial antigen 1030 [GNA1030], and Neisserial adhesion A [NadA] surface proteins), Novartis Vaccines and Diagnostics Inc. (4CMenB)

For complete prescribing information, consult the product leaflet or information contained within the product monograph available through the Health Canada's Drug Product DatabaseExternal Link. Refer to Contents of Immunizing Agents Available for Use in Canada in Part 1 for a list of all vaccines available for use in Canada and their contents.

Efficacy, Effectiveness and Immunogenicity

Efficacy and effectiveness

A study of Men-C-C vaccine demonstrated effectiveness in infants of 97% within one year of vaccination, decreasing to 68% after 1 year. Longer term vaccine effectiveness requires receipt of a booster dose in the second year of life for those immunized in infancy. Vaccine effectiveness of Men-C-ACYW-DT within 3 to 4 years of vaccination in adolescence is 80% to 85%; however, effectiveness wanes over time. There is no efficacy or effectiveness data available for Men-C-ACYW-CRM, Men-C-ACYW-TT or 4CMenB. Vaccine effectiveness measured at the individual level may under-estimate the impact of the immunization programs on the burden of meningococcal disease in the community, due to the additional benefit conferred by herd immunity.

Immunogenicity

Men-C-C and Men-C-ACYW vaccines are immunogenic in infants and toddlers but those vaccinated in infancy show a waning immune response over time. Vaccination with conjugate meningococcal vaccine primes the immune system for memory and induces good anamnestic responses; however, anamnestic response may not be sufficient to prevent disease after exposure and circulating antibodies are thought to be essential. In comparison to polysaccharide meningococcal vaccine, conjugate meningococcal vaccines demonstrate greater immunogenicity and induce better immunologic memory. Conjugate meningococcal vaccines do not result in hyporesponsiveness and have been shown to overcome the hyporesponsiveness evident with polysaccharide meningococcal vaccine usage. In clinical trials, the 4CMenB vaccine has shown to be immunogenic in toddlers and children after at least two doses, and in adolescents and adults after one dose.

Recommendations for Use

Healthy infants and children (2 months to 11 years of age)

Infants may receive Men-C-C vaccine beginning at 2 months of age, depending on the provincial and territorial schedule and the incidence of meningococcal serogroup C disease in their jurisdiction. Men-C-C vaccine is recommended for all children at 12 to 23 months of age, regardless of any doses given during the first year of life. It is routinely given at 12 months and is recommended in unimmunized children less than 5 years of age. Men-C-C vaccine may be considered for children 5 to 11 years of age if they have not previously been immunized as infants or toddlers. In addition, immunization with 4CMenB vaccine may be considered on an individual basis, for children two months of age and older, to protect against IMD caused by serogroup B strains expressing antigens covered by the vaccine.

Healthy adolescents and young adults (12 to 24 years of age)

Either Men-C-C or Men-C-ACYW vaccine, depending on local epidemiology and programmatic considerations, is recommended for adolescents, routinely at 12 years of age and young adults, even if they have previously been vaccinated as an infant or toddler. In addition, 4CMenB vaccine may be considered on an individual basis, depending on the preferences of the vaccine recipient, regional serogroup B IMD incidence and strain susceptibility to 4CMenB vaccine, for protection against serogroup B strains expressing antigens covered by the vaccine.

High risk groups
Underlying medical conditions

Individuals with increased risk of meningococcal disease because of underlying medical conditions are as follows:

  • persons with functional or anatomic asplenia, including sickle cell disease
  • persons with congenital complement, properdin, factor D or primary antibody deficiencies
  • persons with acquired complement deficiency due to receipt of the terminal complement inhibitor eculizumab (Soliris™)
  • individuals with HIV, especially if it is congenitally acquired

Table 3 outlines the recommended schedule for vaccination of individuals who are at high risk due to underlying medical conditions. Refer to Booster doses and re-immunization section for additional information.

Increased risk of exposure

Either Men-C-ACYW, 4CMenB, or both vaccines are recommended for individuals at increased risk of exposure to meningococcal disease as follows:

  • travellers when meningococcal vaccine is recommended. Refer to Travellers section for additional information.
  • laboratory personnel who are potentially routinely exposed to N. meningitides. Refer to Workers section for additional information.
  • military personnel during recruit training and on certain deployments.

Meningococcal vaccine is also recommended for most close contacts of a case of IMD and for outbreak control, if the disease is caused by a serogroup contained in the vaccine. Refer to Post-exposure management and Outbreak control for additional information.

Age considerations for choice of vaccine for high risk groups

2 to 23 months of age
Based on available published data in this age group, Men-C-ACWY-CRM should be used because it has been found to be safe and immunogenic. Routine meningococcal C conjugate vaccine does not need to be administered in addition to Men-C-ACWY-CRM. For toddlers and children who may be at increased high risk of IMD caused by serogroup B, 4CMenB vaccine should also be considered.

24 months to 55 years of age
Any of the Men-C-ACYW vaccines may be used. For individuals who are at high risk of IMD caused by serogroup B, 4CMenB vaccine should also be considered.

56 years of age and older
Any of the Men-C-ACYW vaccines should be considered. For individuals who are at high risk of IMD caused by serogroup B, 4CMenB vaccine should also be considered.

Refer to Schedule for additional information, Table 1 for recommended vaccination for certain travellers and Table 3 for recommended vaccination of high risk individuals with underlying medical conditions.

Persons with inadequate immunization records

Children and adults lacking adequate documentation of immunization should be considered unimmunized and started on an immunization schedule appropriate for their age and risk factors. Conjugate meningococcal vaccine, as appropriate for age, may be given regardless of possible previous receipt of the vaccine, as adverse events associated with repeated immunization have not been demonstrated. Refer to Immunization of Children and Adults with Inadequate Immunization Records in Part 3 for additional general information.

Pregnancy and breastfeeding

Conjugate meningococcal vaccines have not been studied in pregnancy; however, there is no theoretical reason to suspect that adverse events will occur and, in circumstances in which the benefits outweigh the risks, the use of conjugate meningococcal vaccines in pregnancy may be considered. Inactivated vaccines, such as conjugate or multicomponent meningococcal vaccines, may be administered to women who are breastfeeding. Refer to Immunization in Pregnancy and Breastfeeding in Part 3 for additional general information.

Infants born prematurely

Premature infants in stable clinical condition should be immunized with conjugate meningococcal vaccine at the same chronological age and according to the same schedule as full-term infants. Infants born prematurely, especially those weighing less than 1,500 grams at birth are at higher risk of apnea and bradycardia following vaccination. Hospitalized premature infants should have continuous cardiac and respiratory monitoring for 48 hours after their first immunization. Refer to Immunization of Infants Born Prematurely in Part 3 for additional general information.

Persons/residents in health care institutions

Residents of long-term care facilities should receive meningococcal vaccine as appropriate for their risk factors. Refer to Immunization of Patients in Health Care Institutions in Part 3 for additional general information.

Immunocompromised persons

Quadrivalent conjugate meningococcal vaccine is recommended for certain high risk individuals as outlined under High risk groups above. 4CMenB vaccine should also be considered for individuals who are at high risk of IMD caused by serogroup B strains expressing antigens covered by the vaccine. When considering immunization of an immunocompromised person, consultation with the individual's attending physician may be of assistance in addition to the guidance provided below. For complex cases, referral to a physician with expertise in immunization or immunodeficiency is advised.

Congenital (primary) immunodeficiency

Persons with complement, properdin, factor D or primary antibody deficiencies should be vaccinated with Men-C-ACYW vaccine. Refer to Table 3 for additional information.

Acquired (secondary) immunodeficiency

Hematopoietic stem cell transplantation (HSCT- autologous or allogeneic)
For children and adults, the effect of any previous meningococcal vaccine will be diminished following HSCT; therefore, HSCT recipients should be vaccinated as per recommendations for the previously unvaccinated based on their age or risk factors for IMD. If routinely indicated based on age or other risk factors, conjugate meningococcal vaccine can be given as early as 6 months after transplantation, unless needed earlier for management of a close contact or outbreak. However, if it is given earlier than 6 months after transplant the response may not be optimal and consideration should be given to repeating the dose at least 6 months after transplant (and at least 8 weeks after the previous dose) if ongoing protection is needed.

Solid organ transplantation
Conjugate meningococcal vaccine (type of vaccine as appropriate for age) is recommended to be given at least two weeks before transplantation if it is routinely indicated based on age or risk factors for IMD. If not given prior to transplant and routinely indicated based on age or other risk factors, meningococcal vaccine can be given any time after 6 months post-transplant and at least one month after discontinuation of treatment for acute rejection unless needed earlier for management of a close contact or outbreak. However, if it is given earlier than 6 months after transplant or earlier than 1 month after discontinuing treatment for acute rejection, the response may not be optimal and consideration should be given to repeating the dose at least 6 months after transplant and at least 1 month after discontinuing treatment for acute rejection (and at least 8 weeks after the previous dose) if ongoing protection is needed.

HIV-infected
Two doses of Men-C-ACYW vaccine should be considered for individuals with HIV infection. Refer to Table 3 for additional information.

Acquired complement deficiency
People with conditions such as paroxysmal nocturnal hemoglobinuria who are receiving the terminal complement inhibitor eculizumab (Soliris™) should receive two doses of Men-C-ACYW vaccine. They must be vaccinated at least two weeks prior to receiving the first dose of eculizumab, if possible, and every 5 years thereafter if they continue to use the drug. Refer to Table 3 for additional information.

Refer to Booster doses and re-immunization for additional information and Immunization of Immunocompromised Persons in Part 3 for additional general information.

Persons with chronic diseases

Asplenia
Two doses of Men-C-ACYW vaccine are recommended for persons with anatomic or functional asplenia, including sickle cell disease. When elective splenectomy is planned, all recommended vaccines should ideally be completed at least 2 weeks before surgery; if only one dose can be given before surgery, the second dose should be given 8 weeks after the first dose, with a minimum interval of 4 weeks. In the case of an emergency splenectomy, two doses of vaccine should ideally be given beginning 2 weeks after surgery but can be given earlier, before discharge, if the person might not return for vaccination after discharge. Persons one year of age and older with asplenia who have not received Men-C-ACYW vaccine should receive two doses administered 8 weeks apart, with a minimum interval of 4 weeks. Periodic booster doses with Men-C-ACYW vaccine are also recommended. In addition, 4CMenB vaccine should be considered for individuals who are at high risk of IMD caused by serogroup B.

Refer to Table 3 for vaccination recommendations of high risk individuals due to underlying conditions based on age. Refer to Booster doses and re-immunization for additional information and Immunization of Persons with Chronic Diseases in Part 3 for additional general information.

Travellers

Travellers should be vaccinated with Men-C-ACYW, 4CMenB or both vaccines, depending on the risk of meningococcal disease in the area of travel. Men-C-C vaccine alone is not appropriate for protection of travellers, as it does not protect against serogroup A, which is endemic in selected regions of the world (e.g. sub-Saharan Africa), or serogroup W-135 disease. 4CMenB vaccine is recommended for individuals travelling to an area with a hyperenedemic strain or an outbreak that is known to be caused by a serotype B that can be prevented by the vaccine. Current meningococcal disease outbreak information is available from the WHO at: http://www.who.int/csr/don/archive/disease/meningococcal_disease/en/.

Refer to Table 1 for recommended immunization for travellers to destinations where risk of meningococcal transmission is high.

Proof of meningococcal immunization may be required by certain countries. For example, Saudi Arabia requires proof of immunization with a quadrivalent vaccine for pilgrims to the Hajj in Mecca (refer to http://www.moh.gov.sa/en/Hajj/Pages/default.aspx). For travel to the Hajj, re-immunization at an interval of less than 5 years from the last dose may be required. Refer to Immunization of Travellers in Part 3 for additional general information.

Refer to the CATMAT information on assessing a traveller's need for pre-travel vaccination.

Table 1: Recommended immunization schedule for travellers to destinations where risk of meningococcal transmission is high, not previously immunized with Men-C-ACYW or 4CMenB vaccine.
Age Recommended vaccine(s) ScheduleTable 1 - Footnote 1, Table 1 - Footnote 2
Table 1 - Footnote 1
Travellers to the Hajj should check recommendations for re-vaccination at: http://www.moh.gov.sa/en/Hajj/Pages/default.aspx as more frequent re-vaccination may be required.
Table 1 - Footnote 2
A booster dose of Men-C-ACYW should be given every 3 to 5 years if vaccinated at 6 years of age or younger and every 5 years for those vaccinated at 7 years of age and older.
Table 1 - Footnote 3
Depending on the age at which immunization is initiated, the manufacturer of 4CMenB recommends three doses for infants who begin primary immunization between the ages of 2 and 5 months, and two doses when the first dose is received between ages of 6 and 11 months.
Table 1 - Footnote 4
Men-C-ACYW-CRM may be given a minimum of 4 weeks apart if accelerated immunization is needed.
Table 1 - Footnote 5
Men-C-ACYW and 4CMenB are not authorized for use in those 56 years of age and older; however, based on limited evidence and expert opinion its use is considered appropriate.
2 to 11 months of age Men-C-ACYW-CRM or 4CMenB 2 or 3 dosesTable 1 - Footnote 3 given 8 weeks apart (with another dose between 12-23 months of age that is at least 8 weeks from the previous dose)Table 1 - Footnote 4
12 to 23 months of age Men-C-ACYW-CRM or 4CMenB 2 doses at least 8 weeks apartTable 1 - Footnote 4
24 months to 10 years of age Men-C-ACYW or 4CMenB 1 dose of Men-C-ACYW; 2 doses of 4CMenB given at least 8 weeks apart
11 years of age and olderTable 1 - Footnote 5 Men-C-ACYW or 4CMenB 1 dose of Men-C-ACYW; 2 doses of 4CMenB given at least 4 weeks apart
Persons new to Canada

Health care providers who see persons newly arrived in Canada should review the immunization status and update immunization for these individuals. Review of meningococcal vaccination status is particularly important for persons from areas of the world where sickle cell disease is present as persons with sickle cell disease are at risk of serious meningococcal infections. In many countries outside of Canada, conjugate meningococcal vaccines are in limited use. Information on vaccination schedules in other countries can be found on the following website:
http://www.who.int/vaccines/GlobalSummary/Immunization/ScheduleSelect.cfm.
Refer to Immunization of Persons New to Canada in Part 3 for additional general information.

Workers

Laboratory workers
Research, industrial and clinical laboratory personnel who are potentially routinely exposed to N. meningitidis should be offered one dose of either Men-C-ACYW, 4CMenB or both vaccines. Re-vaccination is generally recommended every 5 years for Men-C-ACYW. Routine infection control precautions should be practiced at all times to minimize the risk of exposure in laboratory workers and post-exposure prophylaxis should be offered after recognized exposures. Refer to Booster doses and re-immunization for additional information.

Health care workers (HCW)
Nosocomial transmission of IMD is very uncommon. HCW are considered as close contacts only if they have had intensive, unprotected contact (without wearing a mask) with infected patients (e.g., intubating, resuscitating or closely examining the oropharynx). It is recommended that HCW use barrier precautions to avoid direct contact with respiratory secretions of patients with meningococcal disease until the patient has completed 24 hours of effective antibiotic therapy, according to provincial and territorial communicable disease control guidelines.

There is no evidence to recommend routine meningococcal immunization of HCW since the risk period for acquisition ends when contact with an untreated patient terminates, and antibiotic chemoprophyalxis should be sufficient in the high-risk situation described above.

Military personnel
Military personnel may be at increased risk when accommodated in close quarters or through deployment to endemic or epidemic countries.

Refer to Immunization of Workers in Part 3 for additional general information.

Post-exposure management

Contacts of cases
Close contacts of individuals with meningococcal infections have an increased risk of developing IMD; this risk is greatest for household contacts. The increased risk of disease for household contacts persists for up to 1 year after disease in the index case and beyond any protection from antibiotic chemoprophylaxis. In general, this prolonged risk is not seen in contacts who do not have ongoing exposure.

Chemoprophylaxis should be offered to all persons having close contact with a case of IMD from 7 days before onset of symptoms in the case to 24 hours after onset of effective treatment in the case, regardless of their immunization status. Refer to the PHAC Guidelines for the Prevention and Control of Meningococcal Disease for information about chemoprophylaxis in the management of close contacts of individuals with meningococcal infection.

Vaccination or re-vaccination of certain close contacts should be considered in addition to chemoprophylaxis when the serogroup is vaccine preventable, as it may further reduce the risk of subsequent meningococcal disease.

Close contacts requiring chemoprophylaxis and consideration for immunoprophylaxis
The following individuals (regardless of immunization status) should receive chemoprophylaxis and, if the meningococcal serogroup identified in the case of IMD is vaccine preventable, should also be considered for immunoprophylaxis:

  • Household contacts of a case of IMD
  • Persons who share sleeping arrangements with a case of IMD
  • Persons who have direct nose or mouth contamination with oral or nasal secretions of a case of IMD (e.g., kissing on the mouth, shared cigarettes, sharing bottles)
  • Children and staff in contact with a case of IMD in child care or nursery school facilities

Refer to Table 2 for specific recommendations for immunoprophylaxis of close contacts of IMD cases according to the serogroup in the index case and the age and underlying conditions of the contact.

Re-vaccination criteria for those previously vaccinated against IMD
The following provides criteria for the re-vaccination of previously vaccinated close contacts when the index case has a vaccine preventable IMD serogroup or there is a vaccine preventable outbreak of IMD:

  • Those previously vaccinated with a serogroup that differs from the index case or outbreak strain should be vaccinated immediately with the appropriate vaccine (as outlined in Table 2);
  • Those previously vaccinated with a serogroup that is the same as the index case or outbreak strain should be re-vaccinated with the appropriate vaccine (as outlined in Table 2);
    • If they were less than 1 year of age at last meningococcal vaccination and more than 4 weeks has passed since their last meningococcal vaccine;
    • If they have an underlying medical condition that puts them at risk for meningococcal disease and more than 4 weeks has passed since their last meningococcal vaccine;
    • If more than a year has passed since their last meningococcal vaccine, if they were not less than 1 year of age at the time of their last meningococcal vaccination and if they have no underlying medical condition that puts them at risk for meningococcal disease.

Close contacts requiring chemoprophylaxis only
The following individuals should receive chemoprophylaxis only, immunoprophylaxis is not necessary:

  • Health care workers who have had intensive unprotected contact (without wearing a mask) with infected patients (i.e., intubating, resuscitating or closely examining the oropharynx).
  • Airline passengers sitting immediately on either side of the case (but not across the aisle) when the total time spent aboard the aircraft was at least 8 hours.
  • Close contacts of a case of IMD due to serogroups not present in meningococcal vaccines, or when the serogroup in the index case has not been determined.
  • Previously vaccinated close contacts who do not meet the criteria for re-vaccination as outline above.
Outbreak control

Outbreaks of meningococcal disease
Consultation with public health officials, experts in communicable disease, or both is important in the assessment and control of meningococcal disease outbreaks. Outbreaks may be controlled by the use of a conjugate meningococcal vaccine. The type of vaccine to use in an outbreak is dependent on the serogroup causing the outbreak and the age of those being vaccinated as outlined in Table 2. Re-vaccination criteria of previously vaccinated individuals are outlined above in Re-vaccination criteria for those previously vaccinated against IMD.

Table 2: Recommended vaccination of close contacts for post-exposure management and for outbreak control
Group Recommended vaccine(s) Schedule
Table 2 - Footnote 1
At high risk due to underlying medical conditions - refer to Underlying medical conditions
Table 2 - Footnote 2
In general, a minimum four week interval is recommended between doses of conjugate meningococcal vaccines; however, in an outbreak or to manage a close contact of a case of IMD, the second dose of conjugate meningococcal vaccine may be given as soon as indicated to provide protection to a close contact who is unvaccinated for the implicated serogroup.
Table 2 - Footnote 3
Individuals at high risk due to underlying medical conditions routinely need two doses of Men-C-ACYW
Table 2 - Footnote 4
Only for outbreak control of IMD caused by serogroup B strains that are predicted to be susceptible to the vaccine based on Meningococcal Antigen Typing System (MATS) testing. Consultation with public health officials, experts in communicable disease or both is required for optimal management of meningococcal disease outbreaks.
Table 2 - Footnote 5
During an outbreak, the vaccine should be provided as soon as possible after the identification of a serogroup B strain that is predicted to be susceptible to the vaccine.

Close contacts and outbreak control of serogroup C invasive meningococcal disease

2 months to less than 12 months of age

Men-C-C

Unvaccinated: 1 dose immediately after exposure then complete the routine series of Men-C-C

Previously vaccinated: If previously vaccinated then re-vaccinate with Men-C-C if at least 4 weeks have elapsed since last dose, then complete the routine series of Men-C-C if necessary

12 months - 10 years of age

Men-C-C

Unvaccinated: 1 dose immediately after exposure

Previously vaccinated: If previously vaccinated at less than 1 year of age OR person is at high risk for IMD due to underlying medical conditionsTable 2 - Footnote 1, then re-vaccinate with one dose of Men-C-C if at least 4 weeks since last dose; otherwise re-vaccinate if at least 1 year since last dose

11 years of age and older

Men-C-C

OR

Men-C-ACYW

Unvaccinated: 1 dose immediately after exposure

Previously vaccinated: If previously vaccinated at less than 1 year of age OR person is at high risk for IMD due to underlying medical conditionsTable 2 - Footnote 1, then re-vaccinate with one dose of vaccine of choice if at least 4 weeks since last dose; otherwise re-vaccinate if at least 1 year since last dose

Close contacts and outbreak control of serogroup A, Y, or W-135 invasive meningococcal disease

2 months to less than 12 months of age

Men-C-ACYW-CRM

Unvaccinated: 2 or 3 doses given 8 weeks apart with another dose between 12 and 23 months and at least 8 weeks from the previous dose

Previously vaccinated:

  • If previously vaccinated with only Men C-C, give Men-C-ACYW-CRM as for unvaccinated persons, regardless of when Men-C-C was previously givenTable 2 - Footnote 2
  • If previously vaccinated with Men-C-ACYW, then re-vaccinate with one dose of Men-C-ACYW-CRM if at least 4 weeks since last dose of Men-C-ACYW vaccine; then complete series

12 to 23 months of age

Men-C-ACYW-CRM

Unvaccinated: 2 doses at least 8 weeks apart

Previously vaccinated:

  • If previously vaccinated with only Men C-C, give Men-C-ACYW-CRM as for unvaccinated persons, regardless of when Men-C-C was previously givenTable 2 - Footnote 2
  • If previously vaccinated with Men-C-ACYW at less than 1 year of age OR person is at high risk for IMD due to underlying medical conditionsTable 2 - Footnote 1, then re-vaccinate with one dose of Men-C-ACYW-CRM if at least 4 weeks since last dose of Men-C-ACYW; otherwise re-vaccinate with one dose of Men-C-ACYW-CRM if at least 1 year since last dose of Men-C-ACYW

2 years and older

Men-C-ACYW

Unvaccinated: 1 dose immediately after exposureTable 2 - Footnote 3

Previously vaccinated:

  • If previously vaccinated with only Men C-C, give Men-C-ACYW as for unvaccinated persons, regardless of when Men-C-C was previously givenTable 2 - Footnote 2
  • If previously vaccinated with Men-C-ACYW at less than 1 year of age OR person is at high risk for IMD due to underlying medical conditionsTable 2 - Footnote 1, then re-vaccinate with one dose of Men-C-ACYW if at least 4 weeks since last dose of Men-C-ACYW; otherwise re-vaccinate if at least 1 year since last dose

Close contacts and outbreak control of serogroup B invasive meningococcal diseaseTable 2 - Footnote 4

2 months to less than 6 months 4CMenB

Unvaccinated: 1 dose immediately after exposureTable 2 - Footnote 5; then re-vaccinate with 2 more doses with at least a 4 week interval between doses.

Previously vaccinated: 1 dose immediately after exposureTable 2 - Footnote 5

6 months to less than 11 years 4CMenB

Unvaccinated: 1 dose immediately after exposureTable 2 - Footnote 5; then re-vaccinate with a single dose after at least 8 weeks.

Previously vaccinated: 1 dose immediately after exposureTable 2 - Footnote 5

11 years and older 4CMenB

Unvaccinated: 1 dose immediately after exposureTable 2 - Footnote 5; then re-vaccinate with a single dose after at least 4 weeks.

Previously vaccinated: 1 dose immediately after exposureTable 2 - Footnote 5

Vaccine Administration

Dose, route of administration, and schedule

Dose
Each dose of meningococcal vaccine is 0.5 mL.

Route of administration
Conjugate meningococcal vaccine should be administered intramuscularly (IM). Refer to Vaccine Administration Practices in Part 1 for additional information.

Schedule

Recommended meningococcal immunization schedules and products vary across provinces and territories, depending upon the epidemiology of meningococcal disease in the jurisdiction and other programmatic factors.

Healthy infants and children (2 to 23 months of age)
Men-C-C vaccine should be provided to healthy infants according to provincial and territorial schedules. If Men-C-C vaccine is given to infants less than 12 months of age, a booster dose should be given between 12 to 23 months of age. If the booster dose is missed, it can be given at the next vaccination opportunity.

Healthy children, adolescents and young adults
One dose of Men-C-C vaccine is recommended for previously unimmunized children 12 months to less than 5 years of age and may be considered for children 5 to 11 years of age. In addition to routine Men-C-C vaccine for infants, and young children, adolescents and young adults (12 to 24 years of age) should receive one dose of either Men-C-C or Men-C-ACYW vaccine, based on local epidemiology and programmatic considerations, with around 12 years being the preferred age for the routine dose.

High risk individuals due to underlying medical conditions
High risk individuals are those with underlying conditions that make them more likely to develop IMD. Schedule options for high risk individuals who have not previously received a quadrivalent conjugate or multicomponent meningococcal vaccine are included in Table 3. As noted in Table 3, previously unimmunized high risk persons 12 months of age and older should receive a two dose primary series administered 8 weeks apart, with a minimum interval of 4 weeks.

Table 3: Recommended immunization for high risk groups because of underlying medical conditionsTable 3 - Footnote 1 not previously immunized with Men-C-ACYW or 4CMenBTable 3 - Footnote 2 vaccine
Age Recommended vaccine(s) ScheduleTable 3 - Footnote 3
Table 3 - Footnote 1
At high risk due to underlying medical conditions: refer to Underlying medical conditions
Table 3 - Footnote 2
Although not recommended for routine immunization, 4CMenB vaccine should be considered for immunization of high risk individuals greater than or equal to two months of age against invasive meningococcal disease caused by serogroup B strains expressing antigen covered by the vaccine
Table 3 - Footnote 3
A booster dose should be given every 3 to 5 years if vaccinated at 6 years of age or younger and every 5 years for those vaccinated at 7 years of age and older.
Table 3 - Footnote 4
Depending on the age at which immunization is initiated, the manufacturer of 4CMenB recommends three doses for infants who begin primary immunization between the ages of 2 and 5 months, and two doses when the first dose is received between ages of 6 and 11 months.
Table 3 - Footnote 5
Men-C-ACYW vaccines may be given a minimum of 4 weeks apart if accelerated immunization needed.
Table 3 - Footnote 6
Men-C-ACYW vaccines are not authorized for use in those 56 years of age and older and 4CMenB vaccine is not authorized for use in those 17 years of age and older; however, based on limited evidence and expert opinion its use is considered appropriate.
2 to 11 months of age Men-C-ACYW-CRM and 4CMenB 2 or 3 dosesTable 3 - Footnote 4 given 8 weeks apart (with another dose between 12-23 months of age that is at least 8 weeks from the previous dose)Table 3 - Footnote 3
12 to 23 months of age Men-C-ACYW-CRMTable 3 - Footnote 2 and 4CMenB 2 doses at least 8 weeks apartTable 3 - Footnote 5
24 months to 10 years of age Men-C-ACYW and 4CMenB 2 doses at least 8 weeks apartTable 3 - Footnote 5
11 years of age and olderTable 3 - Footnote 6 Men-C-ACYWTable 3 - Footnote 5 and 4CMenB 2 doses of Men-C-ACYW-CRM 8 weeks apartTable 3 - Footnote 5; 2 doses of 4CMenB given at least 4 weeks apart
Booster doses and re-immunization

Circulating antibodies are considered necessary to protect an individual against IMD. Re-vaccination is recommended as follows:

  • Individuals at high risk of developing meningococcal disease due to underlying conditions as outlined in Underlying medical conditions. Re-vaccination with Men-C-ACYW is recommended every 3 to 5 years for those vaccinated at 6 years of age and younger and every 5 years for those vaccinated at 7 years of age and older.
  • When travelling to areas where meningococcal vaccine is recommended or required. Re-vaccination with Men-C-ACYW is recommended every 3 to 5 years of age for those vaccinated at 6 years of age and younger, and every 5 years for those vaccinated at 7 years of age and older. Previously vaccinated travellers are advised to check requirements for re-vaccination with meningococcal vaccines prior to travel to the Hajj as more frequent vaccination may be required (refer to http://www.moh.gov.sa/en/Hajj/Pages/default.aspx and Travellers).
  • Military personnel who remain at risk due to travel or overcrowded conditions. A booster dose of Men-C-ACYW is recommended every 5 years if at ongoing risk.
  • At the time of exposure for contacts of a case of IMD in some circumstances. Refer to Post-exposure management.
  • During a community outbreak of IMD in some circumstances. Refer to Post-exposure management.
  • All laboratory personnel who are potentially routinely exposed to N. meningitidis. Booster doses of Men-C-ACYW should be given at routine 5 year intervals for those laboratory workers who remain at ongoing risk of exposure. Refer to Workers.

People previously vaccinated with a polysaccharide meningococcal vaccine should be re-vaccinated with the appropriate conjugate or multicomponent meningococcal vaccine if they remain at ongoing risk for meningococcal disease, with at least a 6 month interval following vaccination with polysaccharide meningococcal vaccine. The need for and timing of 4CMenB booster doses has not yet been determined.

Serologic Testing

Serologic testing is not recommended before or after receiving meningococcal vaccine.

Storage Requirements

Menactra®, Meningitec®, NeisVac-C®: Store in a refrigerator at +2°C to +8°C. Do not freeze.

Bexsero®, Menjugate®, Menveo, Nimenrix®: Store in a refrigerator at +2°C to +8°C. Do not freeze. Protect from light.

Refer to Storage and Handling of Immunizing Agents in Part 1 for additional general information.

Simultaneous Administration with Other Vaccines

Men-C-C vaccine may be administered concomitantly with routine childhood vaccines, and Men-C-ACYW vaccine may be administered concomitantly with adolescent and adult age appropriate vaccines at different injection sites using separate needles and syringes. The immune response to routine infant vaccines and the 4CMenB vaccine does not appear to be affected when these vaccines are administered simultaneously.

Men-C-ACYW-CRM can be administered with routine paediatric vaccines; however, further studies are needed with regard to concomitant administration with pneumococcal 13-valent conjugate vaccine. Co-administration of Men-C-ACYW-CRM and combined tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) may result in a lower immune response to the pertussis antigens than when Tdap vaccine is given alone; however, the clinical significance of this is unknown. Tdap vaccine given one month after Men-C-ACYW-CRM induces the strongest immunologic response to pertussis antigens. Refer to Timing of Vaccine Administration in Part 1 for additional general information.

Vaccine Safety and Adverse Events

Refer to Vaccine Safety in Part 2 for additional general information. Refer to the PHAC website for Adverse Events Following Immunization (AEFI) Quarterly Reports.

Common and local adverse events
Conjugate meningococcal vaccines

Men-C-ACYW vaccines
Injection site reactions occur in up to 59% of vaccinees. Fever is reported in up to 5% of recipients and systemic reactions, such as headache and malaise, are reported in up to 60% of recipients.

Men-C-C vaccines
Mild reactions, including injection site reactions (redness, tenderness, and swelling), occur in up to 50% of vaccine recipients. Irritability occurs in up to 80% of infants and fever in up to 9% when other vaccines were administered. Headaches and malaise occur in up to 10% of older children and adults. These reactions last no more than a few days.

Multicomponent meningococcal vaccine

4CMenB vaccine
Solicited local and systemic reactions have been commonly reported in clinical trials and include tenderness, induration, sleepiness and irritability. Higher rates of fever have been observed with simultaneous administration of 4CMenB vaccine and routine infant vaccines; therefore, routine prophylactic administration of acetaminophen or separating 4CMenB vaccination from routine vaccination schedule has been proposed for preventing fever in infants and children up to three years of age.

Less common and serious or severe adverse events

Serious adverse events are rare following immunization and, in most cases, data are insufficient to determine a causal association.

Guidance on reporting Adverse Events Following Immunization (AEFI)

Vaccine providers are asked to report, through local public health officials, any serious or unexpected adverse event felt to be temporally related to vaccination. An unexpected AEFI is an event that is not listed in available product information but may be due to the immunization, or a change in the frequency of a known AEFI. Refer to Box 1 in Vaccine Safety in Part 2 and Reporting Adverse Events Following Immunization (AEFI) in Canada for additional information about AEFI reporting.

Contraindications and precautions

Meningococcal vaccine is contraindicated in persons with a history of anaphylaxis after previous administration of the vaccine and in persons with proven immediate or anaphylactic hypersensitivity to any component of the vaccine or its container. Refer to Table 1 in Contents of immunizing agents available for use in Canada in Part 1 for lists of all vaccines available for use in Canada and their contents. For meningococcal vaccines, potential allergens include:

  • Bexsero®: latex in tip cap of syringe, Neisseria meningitidis group B proteins (NHBA, NadA, fHbp, OMV)
  • Menactra®: diphtheria toxoid protein
  • Meningitec®: latex in vial stopper, diphtheria CRM toxoid carrier protein
  • Menjugate®: latex in tip cap of syringe, diphtheria CRM toxoid carrier protein
  • Menomune®: thimerosal, latex
  • Menveo: diphtheria CRM toxoid carrier protein
  • NeisVac-C®: tetanus toxoid protein
  • Nimenrix®: tetanus toxoid protein

There are very few individuals who cannot receive meningococcal vaccines. In situations of suspected hypersensitivity or non-anaphylactic allergy to vaccine components, investigation is indicated, which may involve immunization in a controlled setting. Consultation with an allergist is advised. Men-P-ACYW-135 may be considered in the rare circumstance that someone is allergic to components other than latex in the conjugate meningococcal vaccines.

Administration of meningococcal vaccine should be postponed in persons with moderate or severe acute illness. Persons with minor acute illness, with or without fever, may be vaccinated.

Refer to Contraindications and Precautions in Part 2 for additional general information.

Interchangeability of vaccines

There are no published data regarding the interchangeability of Men-C-C vaccines, but the vaccines have been safely interchanged without a noticeable decrease in efficacy. When possible, the infant series should be completed with the same vaccine. Either Men-C-ACYW vaccine may be used for re-vaccination, regardless of which meningococcal vaccine was used for initial vaccination. Refer to Principles of Vaccine Interchangeability in Part 1 for additional general information.

Selected References

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  • Borrow R, Fox AJ, Richmond PC et al. Induction of immunological memory in UK infants by a meningococcal A/C conjugate vaccine. Epidemiol Infect 2000;124(3):427-32.
  • Borrow R, Southern J, Andrews N et al. Comparison of antibody kinetics following meningococcal serogroup C conjugate vaccine between healthy adults previously vaccinated with meningococcal A/C polysaccharide vaccine and vaccine-naive controls. Vaccine 2001;19(23-24):3043-50.
  • Canadian Immunization Committee. Supplement: Advice for Consideration of Quadrivalent (A, C, Y, W135) Meningococcal Conjugate Vaccine, for use by Provinces and Territories. Can Commun Dis Rep 2010;36(S2):1-35.
  • Centers for Disease Control and Prevention. Laboratory-acquired meningococcemia - California and Massachusetts. MMWR Morb Mortal Wkly Rep 1991;40(3):46-7, 55.
  • Centers for Disease Control and Prevention. Prevention and control of meningococcal disease: rec-ommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2005;54(RR-7):1-21.
  • Centers for Disease Control and Prevention. Updated Recommendations for Use of Meningococcal Conjugate Vaccines - Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Morb Mortal Wkly Rep 2011;60(03):72-76.
  • Choo S, Zuckerman J, Goilav C et al. Immunogenicity and reactogenicity of a group C meningococcal conjugate vaccine compared with a group A+C meningococcal poly-saccharide vaccine in adolescents in a randomised observer-blind controlled trial. Vaccine 2000;18(24):2686-92.
  • Committee to Advise on Tropical Medicine and Travel (CATMAT). Statement on meningococcal vaccination for travellers. Can Commun Dis Rep 2009;35(ASC4):1-22.
  • Cooke RP, Riordan T, Jones DM et al. Secondary cases of meningococcal infection among close family and household contacts in England and Wales, 1984-7. BMJ 1989;298(6673):555-58.
  • De Wals P, De Serres G, Niyonsenga T. Effectiveness of a mass immunization campaign against serogroup C meningococcal disease in Quebec. JAMA 2001;285(2):177-81.
  • English M, MacLennan JM, Bowen-Morris JM et al. A randomised, double-blind, controlled trial of the immunogenicity and tolerability of a meningococcal group C conjugate vac-cine in young British infants. Vaccine 2000;19(9-10):1232-38.
  • Erickson L, De Wals P. Complications and sequelae of meningococcal disease in Quebec, Canada, 1990-1994. Clin Infect Dis 1998;26(5):1159-64.
  • Fairley CK, Begg N, Borrow R et al. Conjugate meningococcal serogroup A and C vaccine: reactogenicity and immunogenicity in United Kingdom infants. J Infect Dis 1996;174:1360-63.
  • Gilmore A, Stuart J, Andrews N. Risk of secondary meningococcal disease in health-care workers. Lancet 2000;356(9242):1654-55.
  • GlaxoSmithKline Inc. Product Monograph - NeisVac-C®. June 2010.
  • Gold R, Lepow ML, Goldschneider I et al. Immune response of human infants of polysaccharide vaccines of group A and C Neisseria meningitidis. J Infect Dis 1977;136:S31-5.
  • Hastings L, Stuart J, Andrews N. A retrospective survey of clusters of meningococcal disease in England and Wales, 1993 to 1995: estimated risks of further cases in household and educational settings. Commun Dis Rep CDR Rev 1997;7(13):R195-200.
  • MacDonald NE, Halperin SA, Law BJ et al. Induction of immunologic memory by conjugated vs plain meningococcal C polysaccharide vaccine in toddlers: a randomized controlled trial. JAMA 1998;280(19):1685-9.
  • MacLennan J, Obaro S, Deeks J et al. Immune response to revaccination with meningococcal A and C polysaccharides in Gambian children following repeated immunisation during early childhood. Vaccine 1999;17(23-24):3086-93.
  • MacLennan J, Obaro S, Deeks J et al. Immunologic memory 5 years after meningococcal A/C conjugate vaccination in infancy. J Infect Dis 2001;183(1):97-104.
  • MacLennan JM, Shackley F, Heath PT et al. Safety, immunogenicity, and induction of immunologic memory by a serogroup C meningococcal conjugate vaccine in infants: a randomized controlled trial [see comments]. JAMA 2000;283(21):2795-801.
  • Meningococcal B Pilot Project Task Group. The Recommended Use of the Multicomponent Meningococcal B (4CMenB) Vaccine in Canada: Common Guidance Statement. Public Health Agency of Canada. March 2014 (Catalogue no. HP40-103/2014E-PDF).

  • National Advisory Committee on Immunization. Statement on conjugate meningococcal vaccine for serogroups A, C, Y and W135. Can Commun Dis Rep 2007;33(ACS-3):1-24.
  • National Advisory Committee on Immunization. Update on the Use of Quadrivalent Conjugate Meningococcal Vaccines. Can Commun Dis Rep 2013;39(ACS-1)
  • National Advisory Committee on Immunization. Update on the Invasive Meningococcal Disease and Meningococcal Vaccine Conjugate Recommendations. Can Commun Dis Rep 2009;36(ACS-3):1-40.
  • National Advisory Committee on Immunization (NACI).Update on quadrivalent meningococcal vaccines available in Canada. Public Health Agency of Canada. October 2014 (Catalogue no. HP40-125/2014E-PDF).

  • Neal KR, Nguyen-Van-Tam J, Monk P et al. Invasive meningococcal disease among university undergraduates: association with universities providing relatively large amounts of catered hall accommodation. Epidemiol Infect 1999;122(3):351-57.
  • Novartis Pharmaceuticals Canada Ltd. Product Monograph - MENJUGATE®. February 2011.
  • Novartis Vaccines and Diagnostics Inc. Product Monograph - Menveo. June 2011.
  • Pfizer Canada Inc. Product Monograph - MENINGITEC®. October 2010.
  • PHLS Meningococcal Infections Working Group and Public Health Medicine Environmental Group. Control of meningococcal disease: guidance for consultants in communicable disease control. Commune Dis Rep CDR Rev 1995;5(13):R189-95.
  • Public Health Agency of Canada. Guidelines for the prevention and control of meningococcal disease. Can Commun Dis Rep 2005;31(S1):1-26.
  • Ramsay ME, Andrews N, Kaczmarski EB et al. Efficacy of meningococcal serogroup C conjugate vaccine in teenagers and toddlers in England. Lancet 2001;357(9251):195-96.
  • Richmond P, Borrow R, Goldblatt D et al. Ability of 3 different meningococcal C conjugate vaccines to induce immunologic memory after a single dose in UK toddlers. J Infect Dis 2001;183(1):160-63.
  • Richmond P, Borrow R, Miller E et al. Meningococcal serogroup C conjugate vaccine is immunogenic in infancy and primes for memory. J Infect Dis 1999;179(6):1569-72.
  • Richmond P, Goldblatt D, Fusco PC et al. Safety and immunogenicity of a new Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine in healthy adults. Vaccine 1999;18(7-8):641-46.
  • Richmond P, Kaczmarski E, Borrow R et al. Meningococcal C polysaccharide vaccine induces immunologic hyporesponsiveness in adults that is overcome by meningococcal C conjugate vaccine. J Infect Dis 2000;181(2):761-64.
  • Sanofi Pasteur Ltd. Product Monograph - MENOMUNE® - A/C/Y/W-135. October 2005.
  • Sanofi Pasteur Ltd. Product Monograph - Menactra®. April 2011.
  • Trotter CL, Andrews NJ, Kaczmarski EB et al. Effectiveness of meningococcal serogroup C conjugate vaccine 4 years after introduction. Lancet 2004;364(9431):365-67.
  • United Kingdom Health Protection Agency. UK Immunization Guide Chapter 22 Meningococcal. accessed March 2012 at: http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digitalasset/dh_125942.pdf

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