R Bortolussi, M Salvadori; Canadian Paediatric Society, Immunization and Infectious Diseases Committee.
A quadrivalent meningococcal conjugate vaccine for serogroups A, C, Y and W135 (MCV4 [Menactra, sanofi pasteur, Canada]) was introduced in Canada in 2007 for persons two years of age or older. MCV4 adds three serogroups to the meningococcal serogroup C conjugate vaccine, which has been used for several years. The rates of invasive meningococcal serogroup C infection have decreased over the past decade, attributable to the meningococcal C conjugate vaccine. However, the incidence of infection caused by serogroups A, B, Y and W135 have not changed substantially. MCV4 induces the production of protective antibodies to serogroups A, C, Y and W135 in adults and children older than two years of age. Serious adverse events from MCV4 are low. In view of the effectiveness of the meningococcal C conjugate vaccine for young infants and the historic high number of meningococcal serogroup C infections in Canada, physicians should encourage and promote publicly funded immunization programs for infants starting at two months of age. MCV4 should also be given to children aged two years who are at increased risk for meningococcal infection. MCV4 may also be considered for HIV-positive children two years of age or older. All adolescents should be offered a booster dose with MCV4 or a meningococcal C conjugate vaccine at approximately 12 years of age. Both vaccines are generally safe and well tolerated.
Key Words: Canada; MCV4; Meningococcal infection; Meningococcal vaccine
Several meningococcal conjugate vaccines are now authorized in Canada: three vaccines cover serogroup C (Menjugate [Novartis, Canada], Meningitec [Wyeth, Canada] and NeisVac-C [GlaxoSmithKline, Canada]) and a newly released vaccine covers serogroups A, C, Y and W135 (MCV4, Menactra [sanofi pasteur, Canada]). The National Advisory Committee on Immunization (NACI) published statements on MCV4 in 2007 and 2009 (1,2). NACI currently recommends the use of a monovalent meningococcal C conjugate vaccine for all infants, with at least one dose given after 12 months of age. MCV4 is recommended for children at increased risk of invasive meningococcal disease (Table 1) once they are older than two years of age. NACI also recommends that a booster dose with MCV4 or a meningococcal C conjugate vaccine be given routinely to all adolescents.
Previous position statements by the Canadian Paediatric Society have discussed the therapy of meningitis and the use of meningococcal C conjugate vaccines (3,4). The Canadian Paediatric Society continues to support these statements. The present statement adds to these by providing an update on the epidemiology of meningococcal disease in Canadian children and adolescents, by reviewing meningococcal vaccine safety and immunogenicity, and by addressing the question, 'What should physicians know and do?', now that the MCV4 vaccine is available.
WHAT IS THE INCIDENCE OF MENINGOCOCCAL DISEASE IN CHILDREN AND ADOLESCENTS?
Rates of invasive meningococcal infection have decreased in Canada over the past decade. However, mortality and morbidity remain high. Approximately 200 cases were reported annually in all age groups by Health Canada between 1995 and 2006 (2,5). The average annual incidence of infection over this period was 0.3 cases per 100,000 population for serogroup B, 0.25 for serogroup C, 0.09 for serogroup Y and 0.03 for serogroup W135. Cases caused by serogroup A were rare. An active surveillance program among 12 Canadian centres participating in the Immunization Monitoring Program, ACTive (IMPACT) is underway. IMPACT reported 33 cases annually between 2002 and 2006 among people younger than 20 years of age (6). More than one-half of the cases were caused by serogroup B, with serogroups C, W135 and Y causing the remaining cases. The incidence of infection caused by serogroups Y and W135 did not change significantly over these five years, while the incidence of serogroup C infection decreased significantly from 0.23 to 0.08 cases per 100,000 population (6). The authors attributed the decrease in serogroup C to the widespread use of a meningococcal C conjugate vaccine in infants.
DO MENINGOCOCCAL VACCINES WORK?
Meningococcal disease is a relatively rare infection, and thus, it is difficult to perform studies that demonstrate efficacy. Approval of meningococcal vaccines is based on the measurement of serum bactericidal antibody (SBA). In general, conjugate vaccines produce a higher and longer-lasting SBA titre than polysaccharide vaccines. MCV4 induces protective SBAs to serogroups A, C, Y and W135 in adults and children older than two years of age. The meningococcal C conjugate vaccines are immunogenic in children younger than two years of age; preliminary data indicate that provincial meningococcal C immunization programs have been effective at preventing infection. The incidence of serogroup C infection has declined since the introduction of meningococcal C conjugate vaccine, and only rare vaccine failures have been reported. MCV4 induces high SBA titres to serogroup C, but there are no head-to-head comparisons of MCV4 with the monovalent serogroup C conjugate vaccine.
IS MCV4 SAFE?
In prelicensure trials, MCV4 was well tolerated, and was associated with injection site reactions and mild systemic adverse events similar to many vaccines. Shortly after the introduction of MCV4 in the United States, several cases of Guillain-Barré syndrome (GBS) were identified in adolescents. Initial estimates suggested there was a larger number of cases than expected for adolescents who received the vaccine. However, since then, additional research has shown that the risk of GBS following MCV4 immunization has not increased in adolescents aged 11 to 19 years. Moreover, the rate of serious infection due to serogroups A, Y and W135 for individuals 10 to 24 years of age is 1.5 cases per million per year. This risk is greater than the estimated GBS risk following vaccination (0.5 to 1.0 cases per million doses) (2).
WHAT SHOULD PHYSICIANS DO?
Parents and families should be informed of the risks of meningococcal disease, and the benefits and risks of immunization. All provinces presently fund immunization programs that use monovalent meningococcal C conjugate vaccines (Menjugate, Meningitec or NeisVac-C) during infancy (administered as a single dose at one year of age or multiple doses before the first birthday with a booster dose at 12 months of age). MCV4 (Menactra) adds three serotypes to these programs. MCV4 can be offered to children older than two years of age previously immunized with a meningococcal C conjugate vaccine to reduce the risk of meningococcal infection due to other serogroups (A, Y or W135). MCV4 is currently covered by the Ministry of Health in some, but not all, provinces. Thus, parents should be aware that this booster vaccine may be an additional expense. The length of immunity is not known for either MCV4 or meningococcal C conjugate vaccines, and booster doses may be necessary in adulthood to achieve optimal protection.
- In view of the effectiveness of the conjugate meningococcal C vaccine for young infants and the historic high number of meningococcal serogroup C infections, physicians should encourage and promote publicly funded immunization programs for infants starting at two months of age.
- Children who are at increased risk for meningococcal infection (Table 1) should be given a meningococcal C conjugate vaccine during infancy and MCV4 when they reach two years of age. MCV4 may also be considered for HIV-positive children two years of age or older.
- All adolescents should be offered a booster dose with MCV4 or a meningococcal C conjugate vaccine at approximately 12 years of age. Both vaccines are generally safe and well tolerated.
- Public Health Agency of Canada, 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):1-23. <http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/07vol33/acs-03/index-eng.php> (Version current at August 19, 2009).
- Public Health Agency of Canada, National Advisory Committee on Immunization. Update on the invasive meningococcal disease and meningococcal vaccine conjugate recommendations. Can Commun Dis Rep 2009;36(ACS-3):1-39. <http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/09vol35/acs-dcc-3/index-eng.php> (Version current at August 19, 2009).
- Canadian Paediatric Society, Infectious Diseases and Immunization Committee. [Principal author: S Halperin]. Meningococcal vaccine for children and adolescents. Paediatr Child Health 2005;10:405-6.
- Canadian Paediatric Society, Infectious Diseases and Immunization Committee. [Principal author: R Bortolussi]. Therapy of suspected bacterial meningitis in Canadian children six weeks of age and older - summary. Paediatr Child Health 2008;13:309.
- Public Health Agency of Canada. Enhanced surveillance of invasive meningococcal disease in Canada: 1 January, 2004, through 31 December, 2005. Can Commun Dis Rep 2007;33:1-15. <http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/07vol33/dr3310a-eng.php> (Version current at August 19, 2009).
- Bettinger JA, Scheifele DW, Le Saux N, et al. The impact of childhood meningococcal serogroup C conjugate vaccine programs in Canada. Pediatr Infect Dis J 2009;28:220-4.
INFECTIOUS DISEASES AND IMMUNIZATION COMMITTEE
Members: Drs Robert Bortolussi, IWK Health Centre, Halifax, Nova Scotia (Chair); Jane Finlay, Richmond, British Columbia; Joan L Robinson, Edmonton, Alberta; Élisabeth Rousseau-Harsany, Sainte-Justine UHC, Montreal, Quebec (Board Representative); Lindy M Samson, Children's Hospital of Eastern Ontario, Ottawa, Ontario
Consultants: Drs James Kellner, Calgary, Alberta; Noni E MacDonald, IWK Health Centre, Halifax, Nova Scotia; Dorothy L Moore, The Montreal Children's Hospital, Montreal, Quebec
Liaisons: Drs Upton D Allen, The Hospital for Sick Children, Toronto, Ontario (Canadian Pediatric AIDS Research Group); Charles PS Hui, Children's Hospital of Eastern Ontario, Ottawa, Ontario (CPS Liaison to Health Canada, Committee to Advise on Tropical Medicine and Travel); Nicole Le Saux, Children's Hospital of Eastern Ontario, Ottawa, Ontario (Immunization Program, ACTive); Larry Pickering, Elk Grove, Illinois, USA (American Academy of Pediatrics); Marina I Salvadori, Children's Hospital of Western Ontario, Ottawa, Ontario (CPS Liaison to Health Canada, National Advisory Committee on Immunization)
Principal authors: Drs Robert Bortolussi, Halifax, Nova Scotia; Marina Salvadori, London, Ontario
Posted: October 2009