Meningococcal meningitis and septicaemia is globally endemic with periodic epidemics. Five serotypes (A, B, C, W135, Y) of Neisseria meningitidis' 13 serogroups account for virtually all disease.¹

• In the UK and other European countries, serotypes B and C are responsible for most of the endemic disease.¹ Serotype C's contribution has fallen since the introduction of childhood vaccination against the disease.²
• Serogroup A causes the majority of epidemic meningococcal infection in the African meningitis belt. Serogroup W135 has also been associated with Hajj outbreaks and a large epidemic in Burkina Faso in 2002/2003.^1,2 In 2006, a new serotype A strain was responsible for increased meningitis attack rates across the African meningitis belt but also extending down into the Great Lakes area (Burundi, Rwanda and Tanzania).³
• Incidence of meningococcal disease is highest in the under 1s, followed by 1-5 year olds with a second peak of risk occurring in 15 to19 year-olds (particularly in those living in crowded or closed communities, e.g. barracks and student halls).¹
• Although meningococcal disease occurs more commonly in young children, the mortality rate amongst young adults is actually higher.¹ However, immunisation is not generally recommended after the age of 25 years.⁴

Meningitis immunisation

• A conjugate vaccination - meningococcal Group C (MenC) - has been adopted in the UK's routine immunisation schedule since November 1999, having demonstrated protective immunity in children under two.¹
• Polysaccharide vaccines are less effective at protecting this age group due to their immature response to this source of antigen.⁵
• Providing early immunity is important since preschool children are particularly vulnerable to infection from encapsulated bacteria.
• In addition to direct immunity, MenC has also been shown to have a significant protective effect on herd immunity.^6,7
• Conjugate vaccines are expensive which can preclude their use in developing countries.⁸
• Currently no widely effective or safe vaccine exists against serotype B. B-polysaccharide is similar structurally to human neural surface antigens and improving its immunogenicity risks autoantibody induction.²

Available vaccines

1. Meningococcal Group C (MenC) conjugate vaccine
2. Meningococcal polysaccharides A, C, W135 and Y vaccine (ACWY Vax®)
3. Quadrivalent meningococcal diphtheria-conjugate vaccine (MCV-4); In March 2010, a conjugated quadrivalent (A, C, W135,Y) meningococcal meningitis vaccine (Menveo®) was made available in the UK. Menveo® has been approved for use in Europe for immunisation of those aged 11 years of age or older at risk of exposure to Neisseria meningitidis (A, C, W135, Y).⁹

Previously to the MenC conjugate vaccine, the only vaccine available against meningococcal disease had been a heat stable polysaccharide vaccine covering serotypes A and C and now W135 and Y. The response to serotype C in unconjugated vaccine in those younger than 18 months is not as good or as long-lasting as in adults and its use in infants aged between 2 months and 2 years is unlicensed.

The MCV-4 vaccine is active against subtypes A, C, W135 and Y also and has been licensed in the United States, where it is recommended for the routine immunisation of adolescents and other high-risk groups.¹⁰ Safety of the polysaccharide and conjugate vaccines are thought to be similar but with improved antibody response with the conjugate vaccine.^10,7

Indications

• Childhood immunisation (see also separate article Immunisation Schedule UK):
  • Meningococcal Group C (MenC) conjugate vaccine is now part of the primary course of childhood immunisation with 2 doses at 3 and 4 months of age, and the combined Hib and MenC conjugate vaccine is given as a booster at 12 months.¹¹
  • The routine booster dose should be given one month before the booster dose of pneumococcal conjugate vaccine.
  • Those aged 5-12 months not previously vaccinated should receive 2 doses, a month apart, and anyone aged less than 25 (but over a year) not previously vaccinated should receive a single dose.
• Asplenia or dysfunctional spleen:
  • MenC is recommended for patients with asplenia or splenic dysfunction.
  • Children under 1 year should be vaccinated according to the Immunisation Schedule (section 14.1).
  • Unimmunised adults and children over 1 year should be given 2 doses of MenC vaccine (usually combined with Haemophilus influenzae type b vaccine) with an interval of 2 months between doses.
  • Immunised adults and children who develop splenic dysfunction should be given 1 additional dose of MenC (usually combined with Haemophilus influenzae type b vaccine).
• Travel immunisation:¹²
  • Individuals travelling to countries of risk (in particular Sub-Saharan Africa, the Middle East and the Indian subcontinent - but, consult up-to-date travel information) should be immunised with a meningococcal polysaccharide vaccine that covers serotypes A, C, W135 and Y, even if they have previously received MenC.¹³
  • Country-by-country information is available from the National Travel Health Network and Centre (www.nathnac.org).
  • If the person has recently received MenC, an interval of at least 2 weeks should be allowed before administration of the A, C, W135 and Y vaccine..
  • The risk for meningococcal meningitis is extremely low for tourists but higher for those living or working with local areas in endemic or outbreak areas.²
  • Proof of vaccination is required for those travelling on the Hajj or Umrah pilgrimages to Saudi Arabia.
  • The antibody response to serotype C in unconjugated meningococcal polysaccharide vaccines in children under 18 months may be suboptimal.
  • Vaccination is particularly important for those living or working with local people or visiting an area of risk during outbreaks.
• Contacts of infected individuals:
  • Follow the advice of the local Health Protection Team.
  • Family members and very close contacts of individuals with meningococcal A or C disease are usually vaccinated in addition to receiving chemoprophylaxis.
  • Similarly, outbreaks of A or C within closed or semi-closed communities may be controlled by vaccination.
• Laboratory workers handling N.meningitidis should also receive vaccination.

Contra-indications

• Acute febrile illness does not preclude vaccination.
• In pregnancy there is no evidence that either vaccine is unsafe but the usual advice is to avoid unless the mother is at high risk of disease.
• Individuals with a previous hypersensitivity reaction to any component of the vaccine including tetanus toxoid or variant diphtheria toxin should not receive vaccination.

Adverse reactions^1,14

For MenC conjugate vaccine:

• Common:
  • Local reactions include redness and swelling at the injection site. They increase with age at vaccination.
  • Systemic reactions include mild fever, irritability, and headache. Systemic reactions are in the same order as those associated with other routinely administered vaccines - approximately 4% of infants develop redness around injection site, 2-4% develop fever but 50% are said to display irritability in the 24-48 hours following vaccination.
• Serious:
  • Hypersensitivity reactions (including anaphylaxis, bronchospasm and angioedema) are rare.
  • Symptoms of meningism have been reported rarely but there is no evidence that the vaccine can cause meningitis.
  • Convulsions and purpura had been linked to MenC vaccination¹⁵ but post-license safety data show no causal relationship.¹⁶

The Committee on Safety of Medicines (CSM) review of safety data (2000) concluded that the vaccine appeared safe and that the balance of risks to benefits was overwhelmingly favourable.¹⁵ All suspected adverse reactions should continue to be reported via the Yellow Card system.

For meningococcal polysaccharide A, C, W135 and Y vaccine:

• Approximately 10% develop local injection-site reactions.
• More generalised fever, headache and fatigue are much rarer, with children more likely to be affected.
• Hypersensitivity and anaphylaxis have been reported.

For quadrivalent capsular group A, C, Y and W135 meningococcal conjugate (MCV4) vaccine:

• Cases of Guillain-Barré syndrome have been reported to occur following vaccination. Currently, evidence is insufficient to prove or disprove a causal relationship so research and surveillance continue.¹⁷
• Other studies have shown MCV4 to be as safe and effective as the currently available polysaccharide vaccine, and seems to provide longer-lasting protection against meningococcal disease.¹⁸

Giving the vaccines^1,14

• Store vaccine at 2-8°C. Do not freeze vaccine or diluent.¹
• Giving injection IM or with deep subcutaneous injection is recommended for MenC, with the subcutaneous route for patients with thrombocytopenia or haemophilia. Deep subcutaneous injection is recommended for ACWY Vax®. In infants, the anterolateral aspect of the thigh and a 25G needle are advised. For older children and adults, the anterolateral thigh, upper arm or buttocks and a 23G needle.¹⁴
• Immunisation with AXWY Vax® should be at least 2-3 weeks prior to travel.¹⁴
• Booster intervals:
  • A booster is currently not recommended for MenC conjugate vaccine because immunity is thought to be long-lasting.
  • However although antibody responses and vaccine effectiveness are sustained in adolescents, there is a rapid waning in young children immunised. It has therefore been suggested that a booster may be appropriate for those initially immunised during the pre-school years.¹⁹
  • For ACWY Vax®: a booster dose given after 5 years is recommended for those at continued risk (children who were under 5 years of age when first vaccinated should be given a booster dose after 2-3 years).²⁰

Patient advice¹⁴

• Seek urgent medical advice if the patient becomes short of breath, has swelling of the mouth or throat or has a rash within a few days of immunisation.
• Parents should give a dose of paracetamol or ibuprofen if their child develops a fever post-immunisation, keeping the child cool and seeking medical advice if the fever persists after a second dose.
• Travel immunisation for meningococcal meningitis is not routinely available on the NHS and payment is at the discretion of the practice.

Document references

1. Immunisation against infectious disease - 'The Green Book'; Dept of Health (various dates)
2. Segal S, Pollard AJ; Vaccines against bacterial meningitis.; Br Med Bull. 2005 Mar 31;72:65-81. Print 2004. [abstract]
3. Wilder-Smith A; Meningococcal vaccine in travelers. Curr Opin Infect Dis. 2007 Oct;20(5):454-60. [abstract]
4. British National Formulary; 58th Edition (September 2009) British Medical Association and Royal Pharmaceutical Society of Great Britain, London.
5. Makwana N, Riordan FA; Bacterial meningitis: the impact of vaccination. CNS Drugs. 2007;21(5):355-66. [abstract]
6. Ramsay ME, Andrews NJ, Trotter CL, et al; Herd immunity from meningococcal serogroup C conjugate vaccination in England: database analysis. BMJ. 2003 Feb 15;326(7385):365-6.
7. Pichichero M, Casey J, Blatter M, et al; Comparative trial of the safety and immunogenicity of quadrivalent (A, C, Y, W-135) meningococcal polysaccharide-diphtheria conjugate vaccine versus quadrivalent polysaccharide vaccine in two- to ten-year-old children. Pediatr Infect Dis J. 2005 Jan;24(1):57-62. [abstract]
8. Prasad K, Karlupia N; Prevention of bacterial meningitis: An overview of Cochrane systematic reviews. Respir Med. 2007 Oct;101(10):2037-43. Epub 2007 Aug 13. [abstract]
9. Menveo Group A, C, W135 and Y conjugate vaccine; The electronic Medicines Compendium (eMC)
10. Harrison LH; Prospects for vaccine prevention of meningococcal infection. Clin Microbiol Rev. 2006 Jan;19(1):142-64. [abstract]
11. Men C article from Immunisation information website, NHS
12. Meningococcal meningitis, National Travel Health Network and Centre; Health Professional Information Sheet
13. No authors listed; Hajj 2007: vaccination requirements and travel advice issued. Euro Surveill. 2006 Nov 30;11(11):E061130.1.
14. Immunizations - travel vaccinations, Clinical Knowledge Summaries (2007)
15. CMO Update 27 A communication to all doctors from the Chief Medical Officer, Dept of Health; Meningococcal C immunisation Update (August 2000)
16. Andrews N, Stowe J, Miller E, et al; Post-licensure safety of the meningococcal group C conjugate vaccine. Hum Vaccin. 2007 Mar-Apr;3(2):59-63. Epub 2007 Mar 17. [abstract]
17. No authors listed; Update: Guillain-Barre syndrome among recipients of Menactra meningococcal conjugate vaccine--United States, October 2005-February 2006. MMWR Morb Mortal Wkly Rep. 2006 Apr 7;55(13):364-6. [abstract]
18. Smith MJ; Meningococcal tetravalent conjugate vaccine. Expert Opin Biol Ther. 2008 Dec;8(12):1941-6. [abstract]
19. Perrett KP, Winter AP, Kibwana E, et al; Antibody Persistence after Serogroup C Meningococcal Conjugate Immunization of Clin Infect Dis. 2010 May 11. [abstract]
20. British National Formulary; 59th Edition (March 2010) British Medical Association and Royal Pharmaceutical Society of Great Britain, London (link to current BNF)

Internet and further reading

• National Travel Health Network and Centre

Acknowledgements