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Meningococcal infection is serious, often resulting in fulminant sepsis or meningitis. There are two main types of meningococcal conjugate vaccine currently available in Canada: serotype C meningococcal conjugate, and quadrivalent conjugate for serotypes A, C, Y, and W-135. The immunological characteristics that inform ongoing immunization policies, as well as some of the limits of current knowledge, are presented. All Canadian children should receive a conjugate meningococcal C vaccine (MCV-C) at 12 months of age, and either a booster dose of MCV-C or of quadrivalent meningococcal vaccine (MCV-4) in adolescence. Children at high risk of invasive meningococcal disease should start MCV-C at 2 months of age, and be given MCV-4 at two years of age.
Key Words: Adolescents, Children, Canada; MCV-4; Meningococcal infection; Meningococcal vaccine
In 2002, the Canadian Paediatric Society issued a statement on meningococcal vaccine for children  that made recommendations for the use of meningococcal serogroup C conjugate vaccine (MCV-C). As of December 2010, all provinces and territories have implemented publicly-funded, universal immunization programs in a wide range of age groups; some have also implemented catch-up programs . In 2009, the Canadian Paediatric Society issued a statement covering the use of a quadrivalent meningococcal conjugate vaccine for serogroups A, C, Y, and W-135 (MCV-4), providing recommendations on when it may be useful (Table 1). Since then, several provinces and territories have implemented publicly-funded programs -. The present statement replaces all previous statements on meningococcal vaccines and updates the present epidemiology of disease caused by this organism in Canada.
| TABLE 1|
Meningococcal vaccines in Canada
Polysaccharide A, C, Y, W-135
No longer useful in paediatrics
Neisseria meningitidis is a Gram-negative diplococcus that is usually associated with asymptomatic nasopharyngeal carriage. Sometimes, however, this organism causes septicemia, meningitis, septic arthritis, pneumonia and conjunctivitis. The severity of cases ranges from occult bacteremia to a fulminant and fatal disease. Mortality rates average 10% for invasive disease, with higher rates for septicemic disease (ie, meningococcemia) and serogroup C infection. The incidence of invasive disease varies widely throughout the world. In Canada, the rate of one per 100,000 people is in the intermediate range. Although the disease burden from invasive meningococcal disease in Canada is lower than for other invasive bacterial infections (eg, pneumococcal disease), cases of meningococcal infection generate great fear and anxiety in both physicians and parents. Media interest in this disease is unwavering.
Five serogroups (A, B, C, Y, and W-135, based on the polysaccharide capsule) cause virtually all meningococcal infections in Canada, with serogroups B and C predominating. Although the incidence of serogroup Y disease has increased in the United States among adolescents and adults, a similar increase has not occurred in Canada. Serogroup B disease occurs endemically in Canada, with a peak incidence in children younger than five years of age. Over 70% of cases in this age group are now due to serogroup B. Serogroup C disease often occurs in outbreaks, with a peak in adolescents from 15 to 19 years of age. Serogroup C disease is associated with a higher rate of septicemic disease and higher mortality than with other serogroups, particularly among adolescents. Since the introduction of publicly-funded MCV-C immunization programs for infants, there has been a substantial decrease in meningococcal serogroup C incidence, with no evidence of its replacement with other meningococcal serotypes -.
Before 2001, meningococcal vaccines available in Canada consisted of purified capsular polysaccharide against one or more serogroups. The most commonly used vaccine was the quadrivalent A, C, Y, W-135 vaccine. Although immunogenic and effective in older children and adults, the vaccine was poorly immunogenic in young infants and did not provide long-term protection at any age. First, conjugate meningococcal C vaccines became available, then the quadrivalent conjugated vaccine (MCV-4, Menactra) was licensed in Canada in 2007. A second MCV-4 vaccine (Menveo) was licensed in Canada in 2010. MCV-4 induces protective antibodies to serogroups A, C, Y, and W-135 in adults and in children two years of age or older. Studies on MCV-4 (Menveo) in infants are underway. It is unclear whether MCV-4 will protect children under 2 years of age against serogroup C, or against other serogroups in this age group, as effectively as MCV-C. Serious adverse events from MCV-4 are rare .
Meningococcal serogroup B organisms are now the most common cause of meningococcal infection in Canada. The challenge in developing a vaccine is that the polysaccharide of serogroup B is poorly immunogenic in humans. However, vaccines targeting non-polysaccharide surface antigens are under development and show considerable promise. Such a vaccine will be a major breakthrough, because serogroup B strains now cause the majority of invasive meningococcal infections in Canada.
Conjugate meningococcal vaccines induce strong antibody responses and prime the immune system for good memory responses. Universal vaccination programs may also reduce disease by conferring herd immunity. However, unlike many other infectious diseases, meningococcal disease has a very short incubation period (even as short as 48 hrs). It is thought that the anamnestic response cannot be relied upon to prevent disease and that circulating antibodies are needed at all times for protection. Thus, many experts believe lifetime protection cannot be achieved with a primary vaccination, and boosters will be needed. Many provinces and the three territories now have booster programs with MCV-C or MCV-4 for school-aged children. How often boosters will be required is, as yet, unknown.
Every province and territory offers publicly-funded, universal MCV-C vaccination programs for young children . All offer a dose at 12 months of age, with two provinces and two territories also providing doses at 2±4 months of age. Although immunization of infants less than 12 months of age may prevent a small number of additional cases, it requires considerable cost per case prevented . In addition, immunizing an infant less than 12 months of age fails to confer protection once the infant is over a year old. Thus, it is critical that at least one dose in a MCV-C vaccine program be given at or after 12 months of age for all infants.
Since serogroup trends differ between Canada and the United States, it will be critical to continue Canadian surveillance programs . The Canadian Immunization Monitoring Program ACTive (IMPACT) monitors all vaccine-preventable infections in Canada. Health care professionals who administer vaccines should assist in this process by reporting possible adverse events and vaccine failures. Strategies to protect the Canadian population against meningococcal infection will continue to evolve as serogroups shift, as newer and better vaccines become available, and as more becomes known about persistence of protective antibodies after immunization.
In view of the safety, immunogenicity and effectiveness of meningococcal vaccines, as well as the severity of some Neisseria meningitidis infections and public concern about the risk of severe meningococcal disease, the Canadian Paediatric Society recommends the following:
To report possible adverse events associated with vaccines, go to www.phac-aspc.gc.ca/im/aefi-form-eng.php.
Groups at increased risk of invasive meningococcal disease
Persons with anatomical or functional asplenia (eg, patients with sickle cell anemia)
Children with primary antibody deficiency disorders
Persons who have complement, properdin or factor D deficiency
Travellers to areas where meningococcal risk is high
Laboratory personnel with exposure to meningococcus
This position statement has been reviewed by the Canadian Paediatric Society’s Community Paediatrics Committee.
Members: Jane C Finlay MD; Susanna Martin MD (Board Representative); Jane C McDonald MD; Heather Onyett MD; Joan L Robinson MD (Chair)
Liaisons: Upton D Allen MD, Canadian Pediatrics AIDS Research Group; Janet Dollin MD, The College of Family Physicians of Canada; Charles PS Hui MD, Health Canada, Committee to Advise on Tropical Medicine and Travel); Nicole Le Saux MD, Canadian Immunization Monitoring Program ACTive); Larry Pickering MD, American Academy of Pediatrics, Committee on Infectious Diseases; Marina I Salvadori MD, National Advisory Committee on Immunization; John S Spika MD, Public Health Agency of Canada
Consultants: Robert Bortolussi MD; Noni E MacDonald MD; Dorothy L Moore MD
Principal authors: Marina I Salvadori MD; Robert Bortolussi MD
Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.